Amsterdam Neuroscience - Self-Evaluation Report 2016-2021

Amsterdam Neuroscience

Self-Evaluation Report 2016-2021

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Board of directors Arjen Brussaard – director (2016-2022) Diederik van de Beek – co-director (2016–2021) Guus Smit – co-director (as of 2021) Yolande Pijnenburg – co-director (as of 2022) Marten Smidt – co-director (as of 2022)

Authors: Arjen Brussaard, Guus Smit, Yolande Pijnenburg, Marten Smidt, Lara Martin Sanchez, Naomi Vorstermans Contributors: Diederik van de Beek, Paul Lucassen, Brenda Penninx, Susanne la Fleur, Taco de Vries, Guido van Wingen, program leaders and taskforce members Data mining: Arjen Brussaard, Lisette Kuijper, Lara Martin Sanchez, Rhanna Haantjes Support: Anita Osinga Layout and design: Michella Dijkinga Copy editing & proofreading: Julia Gorodecky Photography & infographics: i.a. Karen Folkertsma, Anita Edridge, Bas Uterwijk, DigiDaan, Marieke de Lorijn, Mark van den Brink, Michella Dijkinga

© 2022 Amsterdam Neuroscience research institute www.amsterdamneuroscience.com neuroscience@amsterdamumc.nl

Amsterdam UMC in collaboration with Vrije Universiteit Amsterdam & University of Amsterdam

Table of Contents List of abbreviations 04 Word from the directors

05 Chapter 1 Introduction 06 Chapter 2 Mission, vision, core values, and strategic aims 07

of the past six years – 2016-2021 Chapter 3 Strategy 09 Chapter 4 Evidence - research quality and societal relevance 17 Chapter 5 Accomplishments – research quality and societal relevance 20 Chapter 6 Strategy for the next six years 25 Summary

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Appendices Appendix 1 Appendix 2 Appendix 3 Appendix 4 Appendix Appendix Appendix Appendix

5 6 7 8

32 Governance 33 Research programs 37 Research input, output and funding 56 CWTS bibliometric analyses: open access, collaboration 66 profile, science mapping & societal impact Addendum Amsterdam Neuroscience co-author analyses 79 Use cases Amsterdam Neuroscience 2016-2021 83 Proof-of-Concept & alliance projects 102 Open Science, PhD policy & training academic culture, 103 Human Resource policy & ethical review

List of abbreviations Research programs BI BM CIA CMM CTG MAP

Brain Imaging (2016 to present day) Brain Mechanisms (2016-2018) Compulsivity, Impulsivity & Attention (2016 to present day) Cellular & Molecular Mechanisms (2019 to present day) Complex Trait Genetics (2016 to present day) Mood, Anxiety & Psychosis (2016-2018)

MAPSS ND NDIS NII NT SNN

Mood, Anxiety, Psychosis, Stress & Sleep (2019 to present day) Neurodegeneration (2016 to present day) Neurovascular Disorders (2016 to present day) Neuroinfection & -inflammation (2016 to present day) Neurotechnology (2016-2018) System & Network Neuroscience (2019 to present day)

Amsterdam Brain & Mind Project A personalized Medicine Approach for Alzheimer’s Disease ADORE Clinical Research Unit Alzheimer’s Disease Amsterdam Oncology and Neuroscience Research Academic Medical Center Amsterdam Amsterdam Neuroscience Amsterdam Research Board Association of Amsterdam UMC PhD Candidates Advanced Therapy Medicinal Product Center for Neurogenomics and Cognitive Research Centre for Science and Technology Studies Deep Brain Stimulation Electronic Health Record European Medicines Agency Enhancing Neuroimaging Genetics through Meta-Analysis European Research Council Frontotemporal Disorders General Data Protection Regulation Industry Alliance Office Induced Pluripotent Stem Cells Innovation Exchange Amsterdam Knowledge and Innovation Covenant Royal Netherlands Academy of Arts and Sciences Medical Doctor Medical Research Ethics Committee

MNCS MNJS MS NBB NFU NIN NWA NWO OA ONWAR PD PoC ProPark SEP SILS SWOT SynGO TKI TN2 UBVU UNL UvA VU Amsterdam VUmc WMO ZonMw

Mean Normalized Citation Score Mean Normalized Journal Score Multiple Sclerosis Netherlands Brain Bank The Netherlands Federation of University Medical Centres Netherlands Institute for Neuroscience Dutch Research Agenda Dutch Research Council Open Access Graduate School Neurosciences Amsterdam Rotterdam Parkinson’s Disease Proof of Concept Profiling Parkinson’s Disease Strategy Evaluation Protocol Swammerdam Institute for Life Sciences Strengths, Weaknesses, Opportunities and Threats Synaptic Gene Ontologies Top Consortia for Knowledge and Innovation Translational Neuroscience Network University Library – Vrije Universiteit Amsterdam Universities of the Netherlands (former VSNU) University of Amsterdam Vrije Universiteit Amsterdam Vrije Universiteit Medical Center Medical Research Involving Human Subjects Act The Netherlands Organization for Health Research and Development

Other ABMP ABOARD ACRU AD ADORE AMC AN ARB ASAP ATMP CNCR CWTS DBS EHR EMA ENIGMA ERC FTD GDPR IAO IPS IXA KIC KNAW MD METC

Amsterdam Neuroscience

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Word from the directors Amsterdam Neuroscience provides common ground for clinicians and basic scientists in the field of neuroscience in the Amsterdam area in the Netherlands. The institute helps to support excellent and outstanding neuroscience research and showcases its outcome and societal impact. In the six years under review in this self-evaluation report (2016-2021), researchers of the Amsterdam Neuroscience community have published approximately 7,995 peer-reviewed papers and have acquired more than €346 million research funding.

This has led to groundbreaking translational research and clinical trials all within the field of neuroscience. Researchers from all disciplines within our research institute have contributed to major, world-leading innovation addressing the brain in both health and disease. We have also provided an excellent graduate training environment for the 523 PhD candidates that were embedded in Amsterdam Neuroscience and that graduated between 2016-2021.

However, the past few years have been challenging. In February 2020, Diederik van de Beek was on the phone with several biotech companies, drawing attention and alerting them to the new SARS-CoV-2 virus (what we now call COVID-19) and asking them to consider repurposing their work and innovations in the fight against it. Around the same time, in the Amsterdam Neuroscience office, we chose the research institute’s central theme for 2020 to

Self-Evaluation Report 2016-2021

be ‘Team Science’, which is one of the pillars of Amsterdam UMC. We had no way of knowing just how spot-on that concept – and just how great the need for it – would be within a short matter of months. Around March 13, 2020, the first wave of COVID-19 patients hit our hospitals and all research units were brought to a halt by the lockdown of our labs and offices, while several of us kept on wholeheartedly fighting for the lives of patients in the hospital. This was something that not only hit our hospital and research units, but society as a whole, on a global level.

As 2020 drew to a close, we looked back at, what had proved to be, an incredibly intense year. A year of numerous team efforts. This contemplation on the year we had left behind also brought an optimistic outlook for the near future. It was, without a doubt, a year of team science for our institute. That year also showed our ability to be resilient. And with that in mind, we picked ‘Resilience’ as the central theme for 2021. A theme that addresses plenty of specialisms within the neuroscience field: from the psyche and the capability to adjust to new and stressful situations to the fundamental science and the adaptive brain cells.

With the COVID-19 pandemic continuing through 2021, our leaders in the academia participated intensely in the public debate, but at the same time, they worried about the social isolation in

which the younger generation had to endure the semi-lockdown. It meant another year in which we studied, worked and met each other online, during webinars. Fortunately, in October 2021 we were able to organize the Amsterdam Neuroscience Annual Meeting as a hybrid event in which we celebrated the accomplishments within Amsterdam Neuroscience and benchmark the tradition of our open academic culture.

The central motto of Amsterdam Neuroscience is: ‘Connecting the people, the science and the brain’. The good-spirited way in which teams of neuroscientists kept presenting themselves in interviews, in webinars and at our Annual Meetings reflects both the resilience and the ‘can-do’ attitude that became an increasingly driving force in how neuroscience is done!

Arjen Brussaard current executive director Diederik van de Beek former co-director Guus Smit current co-director and future executive director Yolande Pijnenburg current co-director Marten Smidt current co-director

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1. Introduction Amsterdam Neuroscience was founded in 2016 by a team of two directors, a management team with seven members from all faculties involved, and a team of eighteen program leaders, with equal representation of clinicians and laboratory-based scientists. It is an interdisciplinary collaboration of Amsterdam UMC and the science faculties of the Vrije Universiteit Amsterdam and the University of Amsterdam (UvA).

The institute is one of Amsterdam UMC’s eight research institutes, and has close to 800 participants, with approximately 75% appointed at Amsterdam UMC and 25% affiliated with either of the science faculties of Vrije Universiteit Amsterdam and UvA. Amsterdam Neuroscience encompasses a diverse array of expertise, strengthens scientific excellence and clinical translation, and forms one of the largest neuroscience communities in Europe.

Bridging the gap At Amsterdam Neuroscience we aim to bridge the gap between basic research and clinical medicine by gaining a deep understanding of various brain disease mechanisms. Our institute employs a spectrum of technologies and disciplines and covers almost all research methods used nowadays in neuroscience.

We take advantage of our proven expertise in brain disease and clinical innovation in the fields of neurology and psychiatry. We do this by initiating new research strategies and proof-of-concept (PoC) studies for new approaches in the diagnosis and treatment of brain diseases and by enabling interactions between all generations of investigators from (under-)graduate trainees up to full professors working in teams. Through monthly webinars, via the publication of news items, our annual magazines, annual reports and Annual Meetings (see see Annual Meeting 2021), 2021 we try to unite the community of neuroscientists in the Amsterdam area and pave the path for future generations. What’s more, thanks to our position within Amsterdam UMC and our Amsterdam Neuroscience

connections with the GGZ inGeest we have access to patient groups that are essential in bridging the gap between fundamental research and clinical practices.

Research programs and funding At Amsterdam Neuroscience we have organized our research in a focused way along nine translational research programs, each around a specific brain and nervous system disease, disease mechanism or technology innovation. In 2019, halfway through our six-year accreditation period, we renewed the leadership in seven out of the nine research programs. Over the past six years, four dozen outstanding PoC and alliance projects were funded for a total of €6.75 million by the central administration of the institute, in addition to an additional €3 million for 10 postdoc projects in the collaboration between the science faculties. Additional cooperation, use of datasets, contract research and industry-sponsored clinical trials, set up by the Industry Alliance Office (IAO) and sponsored by societal parties and by the biotech and

pharma industries in this period, tally up to €57.2 million in total.

Seven priorities for the organization After the establishment of Amsterdam Neuroscience during the period 2016-2018, the management of Amsterdam Neuroscience has focused on seven priorities: i) placing more emphasis on the establishment of an accessible infrastructure through internal key funding (in addition to alliance- and PoC-funding); ii) organizing more webinars; iii) bringing staff recruitment decisions in the different departments in line with the overall strategy of the institute; iv) bringing the issue of ‘dedicated research’ time to the attention of heads of department, in particular in the hospital; v) aiming for external national key funding programs; vi) risk mitigation to keep talent on board by the proper embedding and awarding of new initiatives, both at a personal and team level; and vii) the branding of Amsterdam Neuroscience via an integrated communication strategy and professional support via the central executive office.

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2. Mission, vision, core values, and strategic aims of the past six years – 2016-2021 Mission The overall mission of Amsterdam Neuroscience is to broaden the fundamental knowledge around the (central) nervous system and to translate this into effective therapies and treatments for the individual patient with a neurological or psychiatric disorder.

Vision Amsterdam Neuroscience is an interdisciplinary research institute that makes a powerful impact in the field of basic neuroscience and Translational Neuroscience. We aim to be a fertile breeding ground for the next generation of neuroscientists. Armed with outstanding scientific knowledge, the highest clinical standards and pioneering innovations, we play a pivotal role in the battle against brain diseases.

For the patient of today and the future.

focused research programs; a strong strategic and complementary research agenda; a shared, excellent graduate- and medicaltraining program; shared infrastructure; and service facilities (including a clinical trial unit) for large-scale (investigator-initiated and sponsored) investigations. What’s more, the idea of a strong embedded business development strategy aimed at adding new industry alliance programs was embraced in order to reach our translational goals. Best practice models of how to organize Amsterdam Neuroscience were available in each of the participating institutes. Working from a shared vision towards a shared implementation plan, outlined below, we created an appropriate follow-up action plan in the program of the new network organization.

Strategic aims at the start of Amsterdam Neuroscience When we launched Amsterdam Neuroscience in 2016, we did so with a strategic plan that was the result of an internal SWOT analysis and discussions with program leaders. Although there was no simple recipe for success at the time, this bottom-up approach made it possible to define major characteristics for building a strong partner organization, irrespective of laboratory or clinical housing. These included a consensus on shared leadership in various

The overall strategy Amsterdam Neuroscience focuses on scientific excellence, young talent and innovation in four cross-disciplinary research programs. In addition, there are five more clinical-oriented research programs that focus on both existing and new treatments for a number of brain and nervous system diseases, including neurological, neurovascular and psychiatric disorders.

Amsterdam Neuroscience’s overall mission is to broaden the fundamental knowledge base to improve our understanding of the human brain

Self-Evaluation Report 2016-2021

and nervous system in health and disease, and to translate this into effective therapies and treatments for the individual patient.

With a focus on both fundamental and Translational Neuroscience, we work on aspects of the primary function of the brain and the underlying cellular and molecular mechanisms.

In addition, however, we also identify relevant biomarkers, drug targets and new molecular structures for interventions for brain disorders. Through clinical trials on patients, we validate new diagnostic tests, therapies and interventions. Our clinical research often focuses on the prevention of brain disorders, or the recovery thereof. We do this both by investigator-initiated research and through collaborations with external parties such as biotech or pharma companies. Cooperation with industrial partners can, in turn, help accelerate clinical development and validation of new methods and interventions. And all while putting the interests of the patient first.

Through scientific excellence and high clinical standards, we provide the best breeding 07

ground for the next-generation professionals working in the neuroscience field. Team science and communication are important core values that make Amsterdam Neuroscience the connecting research institute, where investigators contribute to a good infrastructure with partnerships, suitable financing and valorization opportunities.

Strategic aims set out in 2016 •

•

•

Build a strong research network organization Amsterdam Neuroscience aimed to strengthen collaborations between investigators from various disciplines by focusing its research strategy on nine research programs. Five research programs focusing on specific brain and nervous system disease mechanisms were complemented by four programs focusing on innovation and technology that would provide PoC for causal relationships in brain and nervous system function mechanisms. This would be applied in translational research, and linked these two groups of research programs. At Amsterdam Neuroscience, innovation took place (and still does to this day) at all levels of research, from molecular, to cellular studies, to circuitry and intact brain and behavior, both at the individual as well as population level.

Provide instruments to facilitate collaboration A ‘network’ research organization with collaborations between different departments was preferred at this stage. There was consensus on the sense of urgency to focus on a limited number of experimental approaches, brain functions and disease mechanisms. A condition sine qua non was that each of the research programs should have substantial internal (seed) funding to initiate novel PoC projects. The projects within each of the nine research programs were to strengthen the link between different disciplines and collaboration between different partners (irrespective of their campus location).

Specify focus and strategy in each of the nine research programs A total of nine research programs were defined, and the number of investigators per research program and specific goals, ambitions, assets, translational links and priorities of each research program were outlined by the program leaders. The participating departments

Amsterdam Neuroscience

and Principal Investigators and their research teams were categorized accordingly.

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Identify - and collaborate with - strategic partners at regional, national and international levels The research being executed in Amsterdam Neuroscience relied on excellent research in major neuroscience areas. Investigators at Amsterdam Neuroscience were to coordinate, or participate in, major European research programs. In addition, major patient and human subject cohorts and major research infrastructures were already available (or were in the process of being set up). An alliance between Amsterdam UMC and the Netherlands Institute for Neuroscience (NIN; of the Royal Netherlands Academy of Arts and Sciences, KNAW) had already been formed via the Netherlands Brain Bank (NBB) and via dual appointments of several Principal Investigators.

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Facilitate talent development, provide quality promotion, control and monitoring of the regulations, and connect with (institute-specific) core facilities and infrastructure

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Facilitate valorization via dedicated business development Translational Neuroscience is at the core of the collaboration between university labs and clinical practice. This was exemplified by our proposal to involve an embedded business development office to bridge the gap between academia/clinic and biotech and pharma industries (i.e., through the IAO) and, if possible, through an embedded Clinical Trial Unit (to facilitate the execution of investigator- and industry-initiated clinical trials).

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3. Strategy (including the strategic process) Start of Amsterdam Neuroscience (2016-2018) When Amsterdam Neuroscience began in 2016, there was a solid balance between basic neuroscience and clinical research. The idea behind this strategy was that basic neuroscience provides a deep understanding of molecular and cellular mechanisms, the neuronal systems involved and disease-associated pathology.

Using an integrative approach, new insights in neuroscience can find the basis in, or may be linked to, research using complex trait genetics and structural or functional brain imaging.

In parallel, we prioritized clinical research, intending to answer burning clinical questions.

We identified ‘translational medicine’, a developing research field that fosters the integration of basic research and patientoriented research, as the potential stronghold of Amsterdam Neuroscience.

This implied that Amsterdam Neuroscience aimed explicitly at transforming the fundamental understanding of the biology of the brain into effective health measures. With this aim in mind, we stimulated collaborative research between the science faculties of both universities of Amsterdam UMC, and of external stakeholders from the biotech and pharma industries. Our goal at the time was to accelerate early detection and discovery of disease mechanisms, the identification of novel (drug) targets for intervention and paving the way towards drugs discovery and novel Advanced Therapy Medicinal Product (ATMP) interventions, all in clinical trials.

Self-Evaluation Report 2016-2021

Figure 1 Infographic of the research organization of Amsterdam Neuroscience in the period 2016-2018.

At the time, Amsterdam Neuroscience introduced an IAO team of business developers.

The purpose of the team is to facilitate this research strategy by initiating, supporting and structuring the scientific discussions leading towards the project definition and execution of Translational Neuroscience and clinically oriented contracts, which are sponsored by external stakeholders from the biotech and pharma industries in the fields of Translational Neuroscience, neurology and psychiatry.

Organization of research (2016-2018) Amsterdam Neuroscience started with nine research programs (see Figure 1). Five of these research programs focused on specific brain and nervous system diseases, and four programs focused on innovation and technology. The programs were organized in a matrix in order to underscore the fact that innovation takes place at all levels of study: from molecular to cellular studies, to circuitry and intact brain and behavior, both at the individual as well as population level.

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Strengths Translational Neuroscience & Medicine Ambitious (young) Principal Investigator Community Largest Neuroscience community in The Netherlands Strong links with biotech & pharma-industry

Weaknesses Lack of leadership in some Research Programs Principal Investigators lacking internal drive to reach out beyond borders of their own labs or institutes Lack of cohesive strategy within and between Research Programs

Opportunities Lateralisation in Amsterdam ADORE Investment opportunities in ADORE Clinical trial opportunities via IAO Better patient stratification Translation medicine infrastructure

Threats Diversification of focus and attention of Principal Investigators Lack of funding for high end core facilities such as biocomputation & bioinformatics Lack of dedicated research time for young MD, PhDs

Figure 2 Infographic summarizing the SWOT (Strengths, Weaknesses, Opportunities & Threats) highlights of Amsterdam Neuroscience.

The analysis is based on the institute’s 2016-2018 metrics and the trend-watching by Amsterdam Neuroscience’s management team in communication with the program leaders.

Amsterdam Neuroscience

The nine research programs had dedicated steering committees and included, on average, 25 Principal Investigators and additional talent.

Shared infrastructure and translational efforts were being realized. Graduate training and the involvement of medical residents in research were implemented with the aim of guiding the younger generations through an integrative approach within each of the research programs.

Midterm evaluation Halfway into the six years of our accreditation period as an institute (i.e., in 2019, for the period 2016-2018) we performed an internal inspection of the research organization with the help of an independent ad hoc scientific advisory committee. While we were able to reflect on many strengths, opportunities and weaknesses, we also saw a trend of three major threats (see Figure 2). First, the conditional grant system in the Netherlands and Europe had become increasingly competitive and reflected a worldwide trend that led to a diversification of the attention span of our investigators. Second, the central administration of Amsterdam UMC needed to make confirmative and positive decisions towards (central funding of) core facilities required for top-line research. Third, there appeared to be a structural lack of dedicated research time allocated to young MD-PhD investigators and team leaders.

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Restructuring the organization in 2019 As part of the internal SWOT analysis at the beginning of 2019 by the directors and the management team of Amsterdam Neuroscience (see Figure 2, p. 10), we made changes in the positioning and focus of two of the nine research programs. First, the former Neurotechnology program was changed into a new Systems and Network Neuroscience program. Secondly, the former Brain Mechanisms program was changed into a new Cellular and Molecular Mechanisms program. While the collaboration within the former Neurotechnology domain was fruitful, it turned out to be primarily strategic. Further internal discussions and development of insights had meanwhile led to the realization that a wider perspective on the higher dimensional levels of brain organization is needed in the coming years.

What’s more, the former Brain Mechanisms program in essence had too large a core group of founders working on very different – but interconnected – levels, from molecular and cellular mechanisms up to neural networks and systems. Hence to create a better balance, a select number of co-workers from the former Brain Mechanisms program were regrouped under the newly established Systems and Network Neuroscience program together with the founding group of former Neurotechnology investigators, while a second subgroup of the former Brain Mechanism program regrouped under the new Cellular and Molecular Mechanisms program.

Self-Evaluation Report 2016-2021

Figure 3 Infographic of the research organization of Amsterdam Neuroscience in the period 2019-2021.

In line with this internal SWOT analysis, the infographic of Amsterdam Neuroscience’s strategy was changed accordingly (please compare Figure 1 (p. 09) and Figure 3 to appreciate how this affects the organization).

In addition, separate SWOT analyses of the research programs are attached to this report to provide further rationale on these changes.

The program leaders of the restructured organization (see Appendix 1, p. 33)

have performed a SWOT analysis based on the perspective of the past three years of the research programs’ existences (2019-2021) and given their vision on the future up to 2024 (see Appendix 2, p. 37).

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Furthermore, a total of sixteen new full professorship appointments were achieved between 2016 and 2021 in line with Amsterdam Neuroscience’s overall research program strategy, and an additional lineup of four similarly-positioned appointments will be made in 2022 (see Figure 4).

2016 Odile vd Heuvel

Camiel Boon

Rob de Bie

Charlotte Teunissen

Claudi Bockting

Joep Killestein

Helmut Kessels

Christiaan Lohmann

2017

2018 Ysbrand vd Werf

Guido van Wingen

Karin Verweij

2019

Central government

Health funds 2020 Hilgo Bruining

Yolande Pijnenburg

Martijn vd Heuvel

Neurologists 2021 Christiaan Vinkers

Neuro scientists Psychologists

Media

Companies

Nicole Wolf

Psychiatrists

Expertise centers 2022 Matthijs Brouwer

Ronald v Kesteren

Ingo Willuhn

Leon de Bruin

Politics

Figure 4 New appointments of full professorships in various departments in line with the research program strategy of Amsterdam Neuroscience over the period 2016-2022.

New leadership in 2019: research program leaders and full professorships At the same time as restructuring the organization, we also appointed new program leaders in seven out of the nine research programs. Individual program leader appointments were made for Cellular & Molecular Mechanisms (CMM), Complex Trait Genetics (CTG), Neuroinfection & -inflammation (NII), Compulsivity, Impulsivity & Attention (CIA) and Mood, Anxiety, Psychosis, Stress & Sleep (MAPSS), while two new program leaders (and task force members) were appointed for both Systems & Network Neuroscience (SNN) and Neurovascular Disorders (NDIS). Leadership for Neurodegeneration (ND) and Brain Imaging (BI) has been firmly in place since 2016 but may need revision in 2022-2023.

Amsterdam Neuroscience

Students

Patients

Investors

Staff

Supporters care, research & education Regional government

Science Parks

Figure 5 From 2019 onwards, Amsterdam Neuroscience has been aiming for a more widespread community of stakeholders. In addition to addressing the question of how to organize the external stakeholder network and how to organize patient recruitment for clinical trials (i.e., Hersenonderzoek.nl), we have also been strategically positioning the teams of investigators at international level (such as in ENIGMA, the Human Brain Project and the SynGO consortium).

Furthermore, we have been firmly addressing our (social) media strategy and focusing on involving complementary fields of research (through the Amsterdam Research Board and the Amsterdam Valorisation Board).

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The strategy of the institute (2019-2021) In the fall of 2019 Amsterdam Neuroscience adopted the slogan: ‘Connecting the people, the science and the brain.’ To direct Amsterdam Neuroscience’s activities during the second half of its accreditation period, it was decided the institute should focus on the following seven major strategic points of attention for the years 2019-2021 with regards to investments, activities and efforts from the research institute and its directors in order to bring the new strategy in line with its campaign to reach a wider community of stakeholders (see Figure 5, p. 12).

I. More emphasis on the establishment of infrastructure by means of key funding (in addition to alliance & PoC funding) Over €80 million (Vrije Universiteit Amsterdam) funding was secured to build a new research center housing the research facilities of the Center for Neurogenomics and Cognitive Research (CNCR) at the Vrije Universiteit Amsterdam and over €160 million (Amsterdam UMC and ADORE) funding was secured to build an innovative research and diagnostics center for ADORE (Amsterdam Oncology and Neuroscience Research). This will include a new IPS center facility, an integrated proteomics and genomics center, a total body PET facility and a biocomputation and bioinformatics center.

II. Organize webinars: bring more cohesion across the Amsterdam Neuroscience community and support the branding of Amsterdam Neuroscience We have been organizing webinars more than ever. In the fall of 2020, Amsterdam Neuroscience and Amsterdam UMC teams joined forces and organized the online Amsterdam UMC & COVID-19 research event. It featured an interview with Dr. Anthony Fauci and several young clinical residents who are busy in the fight against COVID-19. We had more than 1,000 active attendants and another 10,000 participants who streamed the content later on. In addition to this, the Amsterdam Neuroscience Annual Meeting 2020 was also completely online (with 500 active attendants). And the 2021 edition of the Annual Meeting consisted of a hybrid event (with 200 visitors on-site and 400 online). Moreover, all Translational Neuroscience Network (TN2) events were online webinars, currently visited by around 100 participants per webinar each month.

Self-Evaluation Report 2016-2021

III. Work on staff recruitment: more emphasis on how they fit in the strategy of Amsterdam Neuroscience See Figure 4 (p. 12) for new appointments made to date.

IV. Protected research time for Principal Investigators and staff is an important and sine que non condition for translational research Key opinion leaders of Amsterdam UMC joined a national initiative around Recognition & Rewards – Room for Everyone’s Talent and directors have been reiterating this issue with heads of departments since 2019. Many heads of departments respond positively to this request but prefer tailormade career planning via shared decision-making rather than through formalized top-down rules.

V. Work on national funding programs There were major efforts made by current directors and program leaders in initiating national funding opportunities.

These include Brainscapes, ABOARD, Brainmodel (see use cases in Appendix 6, p. 83), in addition to MedTech, Biotech Booster, Knowledge Transfer Organization-NL and more.

VI. Work on risk mitigation Leadership needs to have a strategy in place to respond to possible scenarios of successful Principal Investigators being offered a tempting position elsewhere. This is currently done by the proper embedding and awarding of new initiatives both at the level of personalized funding for excellent Principal Investigators (for instance through ERC funding) as well as by awarding (large) team science (as is becoming very evident in so-called large scale (inter) national consortia funding).

VII. Increase Amsterdam Neuroscience’s PR relations, branding and identity There was major and new professional support for this part of our strategy. We published annual magazines, produced professional video material, sent out monthly newsletters, and posted more than 200 news items on a renewed research website, around 500 tweets and >200 LinkedIn posts. We are currently receiving more than 20,000 views every month (see use cases in Appendix 6, p. 83).

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The Industry Alliance Office is a one-stop-shop for biotech and pharma industry, for fast contracting of basic and translational neuroscience and clinical trials.

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Figure 6 The essence of how the IAO is positioned as a business development organization of Amsterdam Neuroscience. For more information, see the Industry Alliance Office website. The IAO team support both Translational Neuroscience contract research and clinical trials. For a quick overview, see the IAO introduction video.

Facilitating valorization through the concept of an Industry Alliance Office Translational Neuroscience is at the core of the collaboration between university labs, clinical practice and the biotech and pharma industries In Amsterdam Neuroscience this is facilitated and supported by an embedded business development office – the so-called ‘Industry Alliance Office’ (IAO) – to bridge the gap between academia, medical faculty, hospitals and the biotech and pharma industries.

Amsterdam Neuroscience

The IAO acts on behalf of the entire Amsterdam Neuroscience organization and is a full-service shop (from scouting to contracting) for the biotech and pharma industries for basic and Translational Neuroscience, but also for clinical trials up to Phase III. Since 2013 the IAO has turned parts of scientific excellence into commercial value, research assets, access to patient cohorts and material, and infrastructure based on a disease-orientated approach. In 2018 we upscaled this embedded

business development activity to include the entire Amsterdam Neuroscience area, including location AMC and, in 2022, the UvA. The essence of how the IAO is positioned in the organization of Amsterdam UMC is illustrated in Figure 6. Cumulative categories of contracts and deal flow are illustrated in Figures 7 (p. 15) and 8 (p. 16), respectively.

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Contracting Values (€k) of Amsterdam Neuroscience | Industry Alliance Office

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@C@ ;A;>;

CONTRACTS;A9B< - Location DBL

CONTRACTS - Location MBD

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12,000 10,000 8,000 6,000 4,000 2,000 0 2013

2014

2015

2016

2017

2018

2019

2020

2021

Year

Figure 7 Cumulative contracting value of IAO-initiated research at Amsterdam Neuroscience (pooled for Amsterdam UMC, location De Boelelaan – DBL and the Neuroscience department of the Vrije Universiteit Amsterdam in green; Amsterdam UMC location Meibergdreef – MBD in orange. More dissemination of the IAO strategy for the Neuroscience department of the UvA is aimed for the coming years).

The figure shows an increasing trend over the years 2013 to 2021, reaching a substantial value of €57.2 million, as part of the institute’s valorization strategy.

Self-Evaluation Report 2016-2021

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Figure 8 Deal flow through the years at Amsterdam UMC, location De Boelelaan pooled with the Neuroscience department of the Vrije Universiteit Amsterdam for preclinical, translational and clinical research and trials contracted via the IAO under supervision of the directors of Amsterdam Neuroscience. Left: contract research categorized per disease area (AD: Alzheimer’s Disease, FTD: Frontotemporal Disorders, PD: Parkinson’s Disease, MS: Multiple Sclerosis, Psych: Psychiatry). Right: distribution of the different domains of contract research (preclinical, translational and clinical research and trials). The relative contribution of the three domains varies through the years. An equal contribution from each domain is the ideal goal.

Amsterdam Neuroscience

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4. Evidence - research quality and societal relevance As described above, achievements have been realized by following the original strategic aims we set up in 2016 (see Section 2, p. 08) and the institute’s subsequent strategy (i.e., 2019-2021, see Section 3, p. 13). In this section, ‘Evidence’, the Strategy Evaluation Protocol (SEP) is strictly followed by discussing research quality and relevance to society. The narratives in this domain are evidence-based and supported by so-called matrix analyses, as shown in Appendices 3 (p. 57), 4 (p. 66) and 5 (p. 79), and further showcased by a selection of ‘use cases’ collected in Appendix 6 (p. 83).

Research Quality Research products for peers

Use of research products by peers

Marks of recognition from peers

The research output of Amsterdam Neuroscience is summarized in Table 3.2.1 and Table 3.2.2 (p. 57); our work includes 7,995 peer-reviewed articles in addition to book chapters and conference proceedings.

The institute’s research output is the result of an increasing number of co-authorships between Amsterdam Neuroscience’s Principal Investigators (see Appendix 5, p. 79). We established a research infrastructure with several new corefacilities in a new research initiative called ADORE, co-founded Hersenonderzoek.nl and we organize various scientific conferences such as our Amsterdam Neuroscience Annual Meetings and TN2 conferences. In addition, we advertise the research we do through our website, at conferences and symposia, and in (social) media (see Appendix 6, p. 98).

Over the years we have published numerous excellent reviews (see Table 3.2.1 and Table 3.2.2, p. 57). Overall our work is well cited as is clear from our Annual Reports (see Annual Reports 2016-2021) and also summarized in Appendix 3 (p. 64) and analyzed by an external agency in Appendix 4 (p. 66). Over the years, we have established several expertise centers (see Figure 12, p. 22) and also built data-platforms that are made available to our peers (i.e., Hersenonderzoek.nl and RCT-Alert). Appendix 4 (p. 66) includes tables listing the number of papers co-authored with other academic institutes, with non-academic private hospitals and with industrial partners.

The Veni-Vidi-Vici grants received by investigators affiliated with Amsterdam Neuroscience are listed on our website, as are our ERC recipients. In addition, key opinion leaders of Amsterdam Neuroscience coordinate several major grant-awarded collaborative projects, including a Gravity Project (Brainscapes), several Dutch Research Agenda (NWA) projects, a Knowledge and Innovation Covenant (KIC) center grant, a National Public-Private Partnership grant (ABOARD), and a Neurotech grant (see Appendix 6, p. 83). Many of the program leaders and taskforce members listed in Appendix 1 (p. 33) have affiliated appointments in scientific councils, advisory committees and international organizations (such the Alzheimer’s Association International Conference, the European Committee for Treatment and Research in Multiple Sclerosis, the European Congress of Clinical Microbiology and Infectious Diseases, and the European College of Neuropsychopharmacology Congress).

Self-Evaluation Report 2016-2021

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Relevance to society Metrics analysis

Evidence-based narratives (research products for societal target groups)

For the purpose of this evaluation, the analysis of the relevance of our research to society was pursued in several ways. As indicated in Appendix 4 (p. 66), so-called ‘term map’ visualizations (networks) were produced based on keywords, extracted from textual data of titles and abstracts of all research publications reported by Amsterdam Neuroscience in the period 2016-2021. The term map visualizations were created with VOSviewer (Van Eck and Waltman, 2010; see Figure 4.2.1, p. 72). Next, so-called ‘societal heatmaps’ were produced by color-coding the relative uptake of these terms – as compared to a worldwide reference database (generated by the Centre for Science and Technology Studies (CWTS) at Leiden University) - in policy documents, clinical guidelines, the media, citations in patents, and the relative number of co-authors in industry and non-academic hospitals (see Figures 4.2.2-4.2.7, p. 73).

In addition to the estimated metrics of societal relevance, we have also produced an overview in which we provide evidence-based narratives by presenting a selection of use cases which, in our view, are most relevant both in terms of scientific excellence as well as in terms of societal relevance (see Appendix 6, p. 83). These include a number of books authored by Amsterdam Neuroscience affiliates (including Cyriel Pennartz, Damiaan Denys, Odile van den Heuvel, Annemieke Dols and Christiaan Vinkers) that have been published. And a number of patents have been filed by CNCR and UvA-Swammerdam Institute for Life Sciences (SILS) investigators (Guus Smit, Matthijs Verhage, Marten Smidt and Lars van der Heide).

In each of these figures, the three or four most prominent contributing research programs of Amsterdam Neuroscience were overlaid on these societal heatmaps. This showed, for instance, that MAPSS, CIA and NII publish research on topics and terms most often used in policy documents worldwide (Figure 4.2.2, p. 73); that MAPSS, CIA and NDIS publish on topics and terms most often used in clinical guidelines worldwide (Figure 4.2.3, p. 74); that ND, BI and CTG publish on topics and terms often used in the media worldwide (Figure 4.2.4, p. 75); that BI, CMM, CTG and ND publish using key terms of relevance to industry (Figure 4.2.5 p. 76); that CMM, BI, CTG and ND also publish using terms often used in patent citations worldwide (Figure 4.2.6, p. 77); and NDIS, NII and ND are the programs that most often publish reports with experts from non-academic hospitals as co-authors (Figure 4.2.7, p. 78). The relevance of the SNN research program to society is not limited to one specific research topic area in the term map, which explains why this program did not appear to be prominent in Figures 4.2.1-4.2.7. Their research areas are more spread and overlap with other programs (mainly BI, CMM and ND) in the network).

Amsterdam Neuroscience

We have published several video-films and online conference material (i.e., the Amsterdam UMC & COVID-19 event, and IAO film) and we have posted several news items in particular over the past three years through our website and LinkedIn. The visitor statistics for the Amsterdam Neuroscience website are vastly rising, as are the numbers of visitors to the more than 500 posts on LinkedIn and Twitter (see Appendix 6, Figure 6.1, p. 98). In addition, the Alzheimer Center Amsterdam, the MS Center Amsterdam and the CNCR organize public meeting days on an annual basis in which patients and carers are informed about the latest insights in the field (see Figure 10, p. 20). And last but not least, we have been publishing the Amsterdam Neuroscience MAGAZINE every year since 2019 (see Figure 9, p. 19) as an integral result of our renewed communication strategy (see Figure 5, p. 12).

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Relevance to society Use of products by societal target groups Here we want to showcase two projects in particular: ABOARD, coordinated by Wiesje van der Flier, and Don’t be late, coordinated

by Hanneke Hulst. We perform contract research and execute clinical trials through our IAO. As indicated in the previous section, the IAO has generated major contract deal flow through the years and is serving many global biotech and pharma parties.

Amsterdam Neuroscience’s investigators also organize the Graduate School Neurosciences Amsterdam Rotterdam (ONWAR) (also see Appendix 8, p. 103).

Amsterdam Neuroscience

MAGAZINE

We care about the brain

Magazine 2019

Magazine 2020

Magazine 2021 (online only) Figure 9 Team science is a prominent element being featured in our Amsterdam Neuroscience MAGAZINE, the annual publication that celebrates the achievements and hard work of the investigators and colleagues in the neuroscience field. The three editions of the magazine already published contain in-depth interviews and short profiles of prominent junior and senior investigators. A must-read for anyone interested in the neuroscience research community in Amsterdam. See Amsterdam Neuroscience MAGAZINE.

Amsterdam Neuroscience

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5. Accomplishments – research quality and societal relevance Open Science At any given year the Amsterdam Neuroscience community, as a network institute, publishes more than 1,250 peer-reviewed papers, with more than 55% open access labels (see Appendix 4, p. 66). The policy on Open Science is described in Appendix 8 (p. 103).

Academic culture We have an open academic culture where the strategic aims of reaching scientific excellence, Translational Neuroscience and creating societal impact are supplemented and supported by a series of network institute initiatives, including Annual Meetings, TN2 webinar series, the publication of the Amsterdam Neuroscience MAGAZINE, ad hoc hybrid conference organizations (such as the Amsterdam UMC & COVID-19 research event), and the Young Amsterdam Neuroscience intervision (online) meetings. At all events, in which we celebrate the academic dialogue, we strive for a culture of being the resource-based teaching-research nexus.

Keynote lectures, clinical case discussions on stage (with patients being interviewed by their treating physician, see Figure 10), and young talent award competitions are deliberate instruments to create an all-inclusive culture and dialogue across the different generations of neuroscientists of Amsterdam Neuroscience.

Over the past six years, the executive office of Amsterdam Neuroscience has been very active in helping and letting this academic culture flourish.

Self-Evaluation Report 2016-2021

The Amsterdam UMC Doctoral School ensures a good education and development of PhD candidates by offering support to the candidates and their supervisors. Its training platform provides PhD candidates with a wide variety of courses to develop their skills, and the PhD advisers provide coaching, advice and support so that PhD candidates can safely and efficiently carry out their research. Within our

institute, we support young talent in becoming excellent researchers. As stated in our set of PhD regulations, the Amsterdam Neuroscience PhD education commission stimulates PhD candidates to develop both their technical and transferable skills by following courses, by attending national and international conferences or by gaining experience in teaching, among others.

Figure 10 Bringing patients on stage as we do during our Annual Meetings and at other events benchmarks the fact that our institute serves both as a teaching-research nexus as well as an organization that reaches out to our respected stakeholders. From left to right (top): Jens Neumann (a blind patient who had a neurotechnical device implanted) on stage in 2017; Job Hoff (a patient with extreme tremors, implanted with a DBS electrode) on stage in 2017; Sophie van Nuis meeting Larry Steinman and Joep Killestein (Sophie van Nuis is an MS patient in her thirties, Steinman is the inventor of Natalizumab, and Killestein is an MS neurologist) on stage in 2018; Jetske van der Schaar (a PSEN1 gene carrier with healthy cognition) on stage in 2019; Wim van Vollenhoven (born in 1921 and participant of the 100-plus study) on stage in 2021. From left to right (bottom): the STXBP1 public day at CNCR (autism spectrum patients and their carers brought on stage by CNCR, 2019); an MS patient (being interviewed by MS Center Amsterdam in recent years).

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Facilitate team science A second element of the academic culture is that we strive to facilitate team science. This was our theme for 2020, and it was one that we had selected even before the outbreak of the COVID-19 pandemic. Team science is of great importance, for example, in translational research and it is imperative for the mission and vision of our research institute. This is why we aim to build teams around important topics in neuroscience, to enhance our knowledge, develop new treatments and make a difference for patients. In the past few years during the COVID-19 pandemic, the team science theme turned out to be spot-on.

Not only was it an essential state of affairs for many of our colleagues within Amsterdam Neuroscience, but it was also a prerequisite to continue and strive for meaningful and curiosity-driven academic endeavors and translational medicine research. In essence, it was essential for keeping up the work within the neuroscience field. Team science at Amsterdam Neuroscience has been an essential achievement from the start as is proved from our co-author’s analysis in Appendix 5, Figure 5.1 and Figure 5.2 (p. 80). These network plots indicate that researchers from Amsterdam Neuroscience collaborate with researchers from both in and

outside the research institute. In both figures, the first three years (2016-2018) are compared to the second three-year period (2019-2021).

It appears that, in the second period, the extent of collaborations is more granulated.

Team science has also been showcased in various ways in our Amsterdam Neuroscience MAGAZINEs over the past three years, and played the central theme of the 2020 edition (see Figure 11).

Figure 11 The numbers of established teams working across disciplines on important issues at Amsterdam Neuroscience are staggering, and these pictures illustrate the team science within the institute.

Team science was a central theme of the 2020 edition of Amsterdam Neuroscience MAGAZINE, thereby underscoring the fact that, these days, it is hard to imagine working at the frontier and creating opportunities for breakthrough science without working in a team.

Self-Evaluation Report 2016-2021

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Centers that combine patient care and research A third major driving source of innovation in Amsterdam Neuroscience’s endeavors is our focus on scientific excellence and patientcentered Translational Neuroscience, which go hand in hand. This is manifested in the way in which we structured our research

organization along the research programs (see Figures 1, p. 09 and 3, p. 11). It is also the latest incentive behind our plans to establish and start branding our expertise centers (see Figure 12). And it is confirmed by the citation analysis (see Appendix 4, p. 66); by the recognition of international collaborators (such as is well established through our

Figure 12 Expertise centers affiliated with Amsterdam Neuroscience. The research efforts of SILS, CNCR and the collaborative partner institute Netherlands Institute of Neuroscience are aligned with the Amsterdam UMC-based (expertise) centers for clinical research. Some centers have been well-established for decades; these include the Alzheimer Center Amsterdam, MS Center Amsterdam and Amsterdam Leukodystrophy Center. Others have been active for several years but could improve their branding; these include the Parkinson’s Disease & Movement Disorder Center Amsterdam, Deep Brain Stimulation Center Amsterdam, Neuroinfection Center Amsterdam and Neurovascular Disorder Center Amsterdam. Other centers were established more recently or are yet to be set up, for example, the N = You Neurodevelopmental Precision Center, and the Anxiety & Depression Center Amsterdam. Criteria for their foundation often include a) a unique longitudinal patient cohort in which retrospective and prospective research about the disease etiology is made possible, b) a major scientific track record underscored by the ambition to establish new appointments and secure funding for infrastructure, c) being an international hub in the neuroscience community, and d) being a major hub in the matrix of the research organization chart of Amsterdam UMC.

Amsterdam Neuroscience

participation in the Human Brain Project, and the SynGO project in collaboration with MIT Harvard and the Simons Foundation); and by the recognition of our societal impact consortia (the ABOARD project under the supervision of Alzheimer Center Amsterdam, the Don’t be late project established under the supervision of MS Center Amsterdam, and the N=You Neurodevelopmental Precision Center activities for autism patients with epileptogenic phenotypes). See several use cases in Appendix 6, p. 83).

Support in the COVID-19 period A fourth and timely incentive in getting organized during the COVID-19 pandemic was the deeply-felt motivation of several groups of investigators and supportive staff at Amsterdam Neuroscience to participate in the COVID-19 Taskforce. There was the active participation of co-director Diederik van de Beek in both a COVID-19 clinical trial on the ICU of Amsterdam and his efforts together with Matthijs Brouwer (and many others) in organizing the COVID-19 biobank initiative (see COVID-19 biobank and here). Secondly, the teams headed up by both Brenda Penninx and Guido van Wingen were involved in applying artificial intelligence (AI) algorithms to all kinds of data (including imaging, epidemiology and blood biomarkers). Thirdly, the business development team under the supervision of Pieter van Bokhoven performed a biweekly market watch from 2019 to 2022 to identify novel interventions both relevant for the ICU protocols and in search of a proper vaccine.

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And last but not least, Arjen Brussaard and Naomi Vorstermans organized an online Amsterdam UMC & COVID-19 research event that was held on December 3, 2020, and was attended by more than 1,000 participants and watched more than 10,000 times afterwards.

PhD candidates Amsterdam Neuroscience has a vibrant PhD community with, on average, 450 PhD candidates working in active projects each year.

The PhD candidates are enrolled in the doctoral school program of either the Vrije Universiteit Amsterdam or the UvA, which recently merged to become the Amsterdam UMC Doctoral School for the medical faculties. Mandatory and eligible courses for PhD candidates are organized by the universities’ science faculties, in collaboration with NIN and in ONWAR (see Appendix 8, p. 103).

The standard evaluation protocol audit of the Amsterdam UMC Doctoral School will be executed in 2024 and is separated from the Amsterdam Neuroscience audit in 2022.

As outlined previously we have an open academic culture in which PhD candidates are actively involved in the research strategy being undertaken in the departments and being executed in collaborative projects of the research programs (see Appendix 7, p. 102). We facilitate dialogues with the younger generations of researchers at the Annual Meetings, in which we organize poster- and story slamcompetitions across the research programs every year; at TN2 symposia biannually; and in our monthly TN2 webinars (2020-2021).

Moreover, we reach out to them via our social media channels and through our newsletters

Figure 13 Young Amsterdam Neuroscience meetings started in 2016 by bringing a group of selected high-potential junior faculty members together in dialogue with the directors of Amsterdam Neuroscience. The meetings include discussions about their careers, invited guests (for instance ERC recipients and those alike), and coaching by professionals to guide them through the project interviews at grant agencies (such as their Vidi, Vici or ERC starting grant application).

Self-Evaluation Report 2016-2021

(watch a recap of our two-day hybrid Annual Meeting of 2021).

Furthermore, Amsterdam UMC has an active PhD association called the Association of Amsterdam UMC PHD Candidates (ASAP). ASAP offers a professional and social network for PhD candidates at Amsterdam UMC by organizing symposia, workshops and networking events.

Furthermore, ASAP is involved in the training for PhD candidates. They also represent Amsterdam UMC PhD candidates in the employee’s council, in the Amsterdam UMC Research Board and national PhD student associations.

Apart from that, both universities have a PhD council. The energetic VU PhD council advocates for the interests of internal and external Vrije Universiteit Amsterdam PhD candidates. They work on social and professional interplay within the PhD trajectory of Vrije Universiteit Amsterdam PhD candidates and are concerned with organizational developments affecting PhDs. The Central PhD Council of the UvA serves the interests of all UvA PhD candidates at an administrative level, and is a sounding board for organizational developments concerning PhD candidates within the university. The Central PhD Council has monthly meetings to exchange information between the PhD candidates of each facility and quarterly meetings with the University’s Rector Magnificus, a representative of the department of academic affairs and a representative of the faculty deans. And each half year, they monitor the experiences of PhD candidates via a survey.

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Human Resource policy Amsterdam Neuroscience gives consent to the Human Resource policy of its universities and the affiliated university medical centers (see Appendix 8, p. 103). This includes participation in the Principal Investigator system, which challenges individual scientists to take up leadership, develop their own research lines and gain visibility. The criteria are: Publications during the past six years as first or last author that demonstrate one’s line of research; active research funding of ≥ €200,000 as the main applicant; and supervision of ≥ 1 PhD candidate as co-promotor. Principal Investigators are appointed annually by the executive board.

The Principal Investigator system originated at location AMC, was adopted at location VUmc in 2017, and has been harmonized at both locations of Amsterdam UMC since 2019.

Amsterdam Neuroscience

The Principal Investigator system at Amsterdam UMC aligns with the policy of the universities’ science faculties (CNCR and SILS) to become an assistant professor. As such, Principal Investigators, assistant professors and associate professors form the core of the faculty of the research programs of Amsterdam Neuroscience. The guidance of their careers is primarily carried out at department level, however there is a secondary setting across generation intervision in Amsterdam Neuroscience’s research programs by which guidance is offered. In addition, the directors of Amsterdam Neuroscience are active and in frequent dialogue with the junior faculty via the Young Amsterdam Neuroscience (online) meetings (see Figure 13, p. 23).

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6. Strategy for the next six years In the fall of 2019 Amsterdam Neuroscience adopted the slogan, ‘Connecting the people, the science and the brain.’ To direct Amsterdam Neuroscience’s activities during the second half of its accreditation period, it was decided the institute should focus on seven points of attention for the years 2019-2021 (see Section 3: Strategy, p. 13). Investments, activities and efforts from the research institute were mainly geared towards these points in order to bring the new strategy in line with its campaign to reach a wider community of stakeholders (see Figure 5, p. 12). With this strategy, Amsterdam Neuroscience has created a solid foundation for its researchers and has established itself as an important connector between the Amsterdam UMC, Vrije Universiteit Amsterdam and UvA knowledge institutes, and their strategic plans for the coming years (see VU Amsterdam Strategy 2020-2025; see UvA Strategy 2021-2026; and Amsterdam UMC Strategy 2021-2026 is available on request).

Steps going forward When the 2016-2021 period under review here came to an end last year, the new board of directors continued with these achievements, taking them into 2022 with a fresh perspective: that of the next six-year period and on the grand challenges in our field.

As a first step, and as a follow-up of the 2019 evaluation, we performed an internal SWOT analysis in dialogue with the directors, management team and program leaders. Figure 14 (p. 26) shows that both internal and external factors are likely to contribute to what can be seen as strongholds and points on which the organization needs to improve.

Self-Evaluation Report 2016-2021

As a second step, we asked all program leaders (see Appendix 1, p. 33) to perform a SWOT analysis for their respective research programs (as shown in Appendix 2, p. 37). Strongholds, focus areas for research for the coming years, and points of specific focus are addressed for each of the nine research programs.

Thirdly, the new board of directors of Amsterdam Neuroscience – in dialogue with the management team – proposes to focus on seven Grand Challenges, three internal operational organization objectives and four external strategic goals.

In doing so, Amsterdam Neuroscience wants to become a ‘future-proof’ institute, with an entrepreneurial mind, with the aim of providing a healthy and fruitful academic world for the neuroscientists of today and tomorrow. A network organization in Amsterdam where young talents can flourish, with sustainable research programs and projects, and where collaborations are formed to improve our understanding of the human brain and nervous system in health and disease.

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Grand Challenges:

Helpful Harmful Strengths Translational neuroscience Research program strategy Evidence-based connections between genetics, neuroscience, psychiatry, and neurology Forging ahead with the precision medicine approach Connecting with external stakeholders, including patients The largest community of neuroscientists in the Netherlands New leadership team of three directors with different backgrounds Industry Alliance Office strategy Strong track record in communication, branding, and webinar

Opportunities National funding programs (AI & Health, MedTech, Biotech Booster, and Urban Diagnostics) New research buildings (O2, W&N-CNCR, and ADORE-RDC) Bioinformatics and Biocomputing Center and Clinical Trial Unit (funded by ADORE) New expertise centers to connect health care and research Use core facilities as assets in public-private partnerships Provide networking opportunities for graduate students

Weaknesses Some research programs lack a cohesive and dedicated funding strategy Link between science facilities and clinic is suboptimal Difficulty securing commitment on the dedicated research time for Principal Investigators and staff Lack of external funding in some preclinical domains Downside of being (too) large as an institute and the risk of losing talent Risk of losing leadership in neuroradiology and neuropathology

Threats Negative effects of COVID-19 lockdown measures, particularly for (under) graduate investigators The (highly) competitive world of funding for fundamental research, and a system where application procedures are inefficient and not sustainable Top-down decisions in science policy and lack of bottom-up approaches harm cohesive funding strategy Relocation of animal facilities and VU neuroscience to a new building will negatively impact research Possible negative implications that (i) necessary expenditure to combat climate change and (ii) geopolitical issues will have on large-scale science funding opportunities

Figure 14 Infographic summarizing the SWOT (Strengths, Weaknesses, Opportunities and Threats) highlights of Amsterdam Neuroscience. The analysis is based on the institute’s 2019-2021 metrics and the trend-watching by Amsterdam Neuroscience’s directory board in dialogue with the management team and the program leaders of the nine research programs.

Amsterdam Neuroscience

I. From ‘precision science’ to ‘precision medicine’ to acknowledge ‘individuality in biology, diagnosis and treatments’ In our quest for the best diagnosis and treatment of each patient, individuality has become a point of interest in all research fields, including neuroscience.

Personalized or precision medicine is high on the scientific agenda. Complementary to studying groups with similar symptoms, disentangling the heterogeneity in underlying disease mechanisms will bring customized diagnostics, individual treatment solutions and prognoses, and care a step closer to the patients. It is a prospective approach in order to achieve optimal individual health decisions. This needs further investment in the research field of individuality and brings with it the challenge to adequately value individual differences in fundamental and clinical studies.

II. Application of data-driven research to shape the field of genetics, neuroscience, neurology and psychiatry The rise of Electronic Health Records (EHRs) and robust information technology (IT) systems supporting both research and health care delivery has placed patients and research participants who agree to provide biospecimens and share their clinical and research data at the epicenter of precision medicine research.

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In parallel, novel computational methods in fundamental science have already yielded results, e.g., new insights in genetics and genomics data, molecular modeling and information processing in the brain.

Big data-driven science will be a major component of future studies and Amsterdam Neuroscience will accommodate these developments.

III. Translate breakthrough innovations in fundamental science into clinical use CRISPR gene editing is considered highly significant in biotech and medicine as it allows for the genomes to be edited in vivo with extremely high precision, cheaply and with ease. New sequencing technologies provide unprecedented insight into cellular processes, and stem cell technologies have changed the way we can work with patient-derived materials. In extension of this, the European Medicines Agency (EMA) has defined ATMPs as medicines for human use that are based on gene therapy, somatic-cell therapy, vectorized antibodies or tissue-engineered medicines. For most new technologies, the implementation into clinical use will be an exciting challenge.

In line with this, in the new Research & Diagnostics facilities of ADORE on the Vrije Universiteit Amsterdam campus, integrated research efforts and core facilities will be available to facilitate this ambition.

Self-Evaluation Report 2016-2021

IV. From first-in-kind to best-in-kind: prioritize investigator-initiated and industry-sponsored clinical research In extension of the ambition to focus, investigators will be able to participate in the newly established ADORE Clinical Research Unit (ACRU), where we will integrate several trial groups from different therapeutic areas within the Neuroscience and Oncology departments into a newly formed structure. ACRU will design, conduct and report in early and later phase clinical trials and cohort studies in neuroscience and oncology, and secure Amsterdam UMC’s leading position in breakthrough clinical research by optimizing the synergistic collaboration of translational and clinical oncology and neuroscience research. ACRU will provide a high-quality infrastructure for both investigator-initiated and industrysponsored clinical research.

V. Participate and lead national and international team science projects and large consortia Taking initiatives to join national and international team science efforts are important to create breakthrough opportunities; for example, the CNCR and SILS participate in the Human Brain Project, a formally European Commission Future and Emerging Technologies flagship project that was awarded €1 billion in 2013. Other examples of international team science in which Amsterdam Neuroscience researchers

participate (and often take the lead), include the Psychiatry Genomics Consortium, ENIGMA, and SynGo 1.0 and 2.0. And more recently, Amsterdam Neuroscience’s Principal Investigators initiated the NWO gravitation program, Brainscapes. Another important collaboration is when Amsterdam Neuroscience joined the lead-team of, and successfully launched, the Biotech Booster campaign, which focuses on extending the development of knowledge into business. In addition to application in health care, the proposal also focuses on other sectors such as the chemical industry and agriculture.

The maximum investment from the National Growth Fund is €246 million, with €50 million set aside for the first phase along with a conditional allocation of €196 million.

As such, the Biotech Booster has great potential for Amsterdam Neuroscience.

VI. Organize a proper ‘bedside-to-bench’ translational strategy and stimulate ‘predictive, personalized, preventive and participatory medicine’ One of the Grand Challenges for the coming years is to improve the inclusion of ‘value-based health care’ principles and patient participation in our translational neuroscientific strategy. Only then will we be able to ask pressing health care questions and translate these into relevant scientific ones. In other words, Translational Neuroscience is not only ‘bench-tobedside’, but also ‘bedside-to-bench’.

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In doing so, this may bring a) predictive medicine based on companion diagnostics and may be applied to a substratified patient that has been selected on the basis of predictive biomarkers. This may result in b) personalized medicine for each individual patient, which leads to c) preventive medicine aimed at preventing or delaying the onset of diseases. This can be done with predictive and precise diagnoses and adequate treatments on people who are in an asymptomatic state in which clinical symptoms or severe tissue damage have not yet occurred. And it will stimulate d) participatory medicine, where participation of (distinct) patient populations, innovation and the application of AI technology (and wearables) are changing business-as-usual in health care: this will lead to high(er) patient expectations, technology-enabled care, new treatments and increase efficacy of existing treatments, more effective focus on quality and costs, and big data use at point of care.

VII. Public-private partnerships as accelerators to achieve value for society Amsterdam Neuroscience’s overall aim is to transform the fundamental understanding of human well-being and human diseases into effective, peoplecentered and affordable health measures.

Working in public-private partnerships supports this aim by accelerating opportunities for prevention, the Amsterdam Neuroscience

discovery of disease mechanisms, the identification of novel (drug) targets for intervention and facilitating the discovery of drugs. It also accelerates opportunities for the development of ATMPs, diagnostic instruments, biomarkers, algorithms, medical devices and treatment strategies, which in turn need validation in clinical trials, supported by AI, data science and participatory medicine. As a dedicated business development office, Amsterdam Neuroscience’s IAO will be facilitating the strategy of our investigators.

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of Amsterdam Neuroscience is instrumental to the programs.

The board will take this dialogue and use the insights/input in the strategy of the coming years, with the notion that sustainable basic science is a cornerstone of innovative translational programs. Here, the connection between clinicians and basic scientists in team science is crucial and can be developed even further. (3) Reshuffling or re-organizing (a) program(s) will be considered if necessary to increase success.

Internal organization: In addition to the Grand Challenges, the new directors will take the following operational steps as far as internal organization is concerned:

b. Building on continued funding and accessibility of core facilities, including those for animal research, imaging, IPS facilities, proteomics and genomics, drug screening and AI- and computational infrastructure

a. Improving on cross-links between the research programs of Amsterdam Neuroscience, taking into account that basic science is the foundation of the innovative translational programs

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The board foresees difficulties that come with large investments and high access fees due to depreciation costs. Amsterdam Neuroscience co-funding might aid in the use of facilities with high costs, which might benefit the use of high-end technologies in the research programs.

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The board will carefully monitor the impact of the move of animal research into a new facility which may experience delays or setbacks.

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Feedback from the Amsterdam Neuroscience community is required to explore this model and to identify whether and how new shared technology infrastructure

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The directory board will (1) start a dialogue with the program leaders concerning the program’s needs, potential, and synergy with the other programs.

Taking this input, we will (2) bring together program leaders to outline a strategy that is aimed at further enhancing science, promoting translational research and new funding options. The board will explore whether (or not) distributed seed funding

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will benefit the research output of the programs.

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The board will improve the visibility of the core facilities for potential users.

c. Providing more network opportunities for young researchers and students •

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For undergraduate students there is a growing need to find their way and work in the labs of researchers within Amsterdam Neuroscience. The board will address this by generating a web-based platform to connect students to ongoing projects.

Amsterdam Neuroscience has a large body of MSc and PhD candidates. The board will strive to improve the alignment of the teaching portfolio offered by the ONWAR graduate school as well as the Amsterdam UMC Doctoral School.

Amsterdam Neuroscience will be aligning with the strategic plans of Vrije Universiteit Amsterdam, UvA and Amsterdam UMC – this relates to acknowledging team science, to open and transparent reporting and to recognizing the development of young talents and diversity in personnel, given the international setting in which we operate nowadays (see Appendix 8, p. 103).

External strategy: The new directors – in collaboration with the program leaders - will aim for the following strategics goals as far as external opportunities are concerned:

Researcher-driven initiatives that need internal assembly and eventually sponsoring from external partners. The latter can be accommodated to a large extent by the Amsterdam Neuroscience IAO (see also below, under item ‘d’).

a. Building on more external funding commitment with the aim of providing sufficient support for innovation and collaboration between Amsterdam Neuroscience’s investigators

c. Align strategy of valorization and working towards societal impact as an integral part of the translational and clinical research strategy

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The Amsterdam Neuroscience board sees that large differences exist between Amsterdam Neuroscience researchers with respect to the strategies they use to obtain external funding. This may need exchange of practices and insights between Principal Investigators.

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The board wishes to explore the potential to increase, in particular, the external funding component where this is felt difficult to obtain. This may also need exchange of ideas and insights between Principal Investigators.

b. Aim for (and take the lead in) national and international consortia and funding opportunities for research infrastructure, research and innovation •

Self-Evaluation Report 2016-2021

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The board aims to further explore the potential to lead national consortia and research infrastructures, funded by NWO, ZonMw and ministries-sponsored programs.

The Amsterdam UMC has appointed a vice-dean Valorisation of Research. We will increase the expertise of Principal Investigators regarding this topic by individual courses, bringing them in touch with our IAO, and stimulating contacts with the relevant patient organizations and knowledge institutes.

d. Building on the success of the IAO •

The board has identified that the partner scouting and contract-making capacity of the IAO has not penetrated equally well into all partner groups/institutes.

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We aim to advertise the work of the IAO for those that have not yet been in contact with it and explored possibilities for projects and collaborative project funding.

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The IAO can also be instrumental in bringing researchers together within Amsterdam Neuroscience by assembling science teams that optimally match internal expertise and external demand.

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Summary Founded in 2016 by a team of directors, management and program leaders (with equal representation of clinicians and laboratory-based scientists), Amsterdam Neuroscience is an interdisciplinary collaboration of the Amsterdam UMC and the science faculties of the Vrije Universiteit Amsterdam and University of Amsterdam (UvA). As one of Amsterdam UMC’s eight research institutes, Amsterdam Neuroscience has close to 800 participants and encompasses a diverse array of expertise, strengthens scientific excellence and clinical translation, and forms one of the largest neuroscience communities in Europe.

Amsterdam Neuroscience’s overall mission is to broaden the fundamental knowledge base around the brain and (central) nervous system, and to translate this into effective therapies and treatments for the individual patient.

Our work is organized along nine translational research programs, each around a specific brain and nervous system disease, disease mechanism or technology innovation. With a focus on both fundamental and Translational Neuroscience, we work on aspects of understanding the primary function of the brain and its underlying cellular and molecular mechanisms. Furthermore, we also identify relevant biomarkers and drug targets, and explore avenues for targeted interventions for brain disorders. We do all this by employing a spectrum of technologies and disciplines and encompassing almost all research methods used nowadays in neuroscience.

Our clinical trials on patients focus on the prevention of brain and nerve disorders

Amsterdam Neuroscience

or the recovery thereof, and enable us to validate new diagnostic tests, therapies and interventions. Our research is carried out both by investigator-initiated studies and through collaborations with external parties such as biotech or pharma companies. Cooperation with industrial partners can, in turn, help accelerate clinical development and the validation of new methods and interventions.

And all while putting the interests of the patient first.

As well as initiating new research strategies and proof-of-concept studies for new approaches in the understanding, diagnosis and treatment of brain diseases, Amsterdam Neuroscience also provides the optimal breeding ground for future neuroscientists, neurologists and psychiatrists.

This is done by enabling interactions between all generations of investigators from (under-) graduate trainees up to full professors working in teams, and has resulted in an excellent graduate training environment. In the period

2016-2021, a total of 523 PhD candidates were embedded in Amsterdam Neuroscience and successfully graduated during that time.

Team science and communication are important core values that make Amsterdam Neuroscience the connecting research institute, with an infrastructure that hosts Amsterdam Neuroscience-private partnerships, suitable financing and valorization opportunities. Providing common ground for clinicians and basic scientists in the neuroscience field in the Amsterdam area, Amsterdam Neuroscience helps to support excellent and outstanding neuroscience research and showcases the research outcome and societal impact.

In the six years under review in our 2016-2021 self-evaluation report, researchers of the Amsterdam Neuroscience community of investigators published approximately 7,995 peer-reviewed papers and acquired more

30

Amsterdam Neuroscience: Connecting the people, the science and the brain.

than €346 million in research funding. This has led to groundbreaking translational research and clinical trials all within the field of neuroscience. Furthermore, we contributed to major, world-leading innovations within our nine research programs.

When it comes to communication, we also unite our community of neuroscientists via monthly webinars, the publication of news items, and through our annual magazines, reports and Annual Meetings.

With a successful six years behind us, we look forward to a future that is just as fruitful.

But, far from resting on our laurels, we are determined to continue our efforts and become an entrepreneurial ‘future-proof’ institute, with the aim of providing a healthy and fertile academic world for the neuroscientists of today and tomorrow. Our path to this will see us performing precision medicine by incorporating multilevel data-driven research; bringing results of fundamental research to the

Self-Evaluation Report 2016-2021

clinic; leading in global research in the form of team science; and optimizing valorization through public-private partnerships.

There may be challenges ahead, but we are ready to take them on and create a network organization in Amsterdam where young talents can flourish, with sustainable research programs and projects, and where collaborations are formed to improve our understanding of the human brain and nervous system in health and disease.

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Appendices Appendix 1 Appendix 2 Appendix 3 Appendix 4 Appendix Appendix Appendix Appendix

Appendices

5 6 7 8

Governance 33 Research programs 37 Research input, output and funding 56 CWTS bibliometric analyses: open access, collaboration 66 profile, science mapping & societal impact Addendum Amsterdam Neuroscience co-author analyses 79 Use cases Amsterdam Neuroscience 2016-2021 83 Proof-of-Concept & alliance projects 102 Open Science, PhD policy & training academic culture, 103 Human Resource policy & ethical review

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Appendix 1 |

Governance

Board of directors Arjen Brussaard (director) Guus Smit (co-director) Yolande Pijnenburg (co-director) Marten Smidt (co-director) Diederik van de Beek (co-director)

2016-present Amsterdam UMC – location VUmc 2021-present Vrije Universiteit Amsterdam 2022-present Amsterdam UMC – location VUmc 2022-present University of Amsterdam 2016-2021 Amsterdam UMC – location AMC

Management team Diederik van de Beek 2021-present Amsterdam UMC – location AMC Paul Lucassen 2017-present University of Amsterdam Susanne la Fleur 2017-present Amsterdam UMC – location AMC Brenda Penninx 2019-present Amsterdam UMC – location VUmc Taco de Vries 2019-present Amsterdam UMC – location VUmc Guido van Wingen 2019-present Amsterdam UMC – location AMC Guus Smit 2016-2021 Vrije Universiteit Amsterdam Yolande Pijnenburg 2018-2021 Amsterdam UMC – location VUmc Damiaan Denys 2016-2019 Amsterdam UMC – location AMC Jeroen Geurts 2016-2018 Amsterdam UMC – location VUmc Cyriel Pennartz 2016-2017 University of Amsterdam Philip Scheltens 2016-2018 Amsterdam UMC – location VUmc Board of deans Chris Polman (chair) 2016-present Hans van Goudoever 2022-present Guus Schreiber 2016-present Peter van Tienderen 2016-present Hans Romijn 2016-2021

Appendix 1

Amsterdam UMC – location VUmc Amsterdam UMC – location AMC Faculty of Science, Vrije Universiteit Amsterdam Faculty of Science, University of Amsterdam Amsterdam UMC - location AMC

33

Program leaders & taskforce members Brain Imaging Program leaders Dick Veltman Liesbeth Reneman

2016-present 2016-present

Amsterdam UMC – location VUmc Amsterdam UMC – location AMC

Taskforce members Fleur van Rootselaar Bart van Berckel

2016-present 2016-present

Amsterdam UMC – location AMC Amsterdam UMC – location VUmc

System & Network Neuroscience (former Neurotechnology program) Program leaders Huibert Mansvelder 2019-present Vrije Universiteit Amsterdam Helmut Kessels 2019-present University of Amsterdam Johannes de Boer 2016-2018 Vrije Universiteit Amsterdam Rick Schuurman 2016-2018 Amsterdam UMC – location AMC Taskforce members Johannes de Boer Rick Schuurman Huibert Mansvelder Wytse Wadman

2019-present 2019-present 2016-2018 2016-2018

Vrije Universiteit Amsterdam Amsterdam UMC – location AMC Vrije Universiteit Amsterdam University of Amsterdam

Cellular & Molecular Mechanisms (former Brain Mechanisms program) Program leaders Matthijs Verhage 2016-present Vrije Universiteit Amsterdam Susanne la Fleur 2017-present Amsterdam UMC – location AMC Marten Smidt 2016-2018 University of Amsterdam

Appendix 1

Taskforce members Marjo van der Knaap Eric Reits

2016-present 2016-present

Amsterdam UMC – location VUmc Amsterdam UMC – location AMC

Complex Trait Genetics Program leaders Danielle Posthuma Frank Jacobs Hanne Meijers

2016-present 2019-present 2016-2018

Vrije Universiteit Amsterdam University of Amsterdam Amsterdam UMC – location AMC

Taskforce members Tinca Polderman Karin Verweij Frank Jacobs Matthijs Verhage

2016-present 2019-present 2017-2018 2016-2017

Vrije Universiteit Amsterdam Amsterdam UMC – location AMC University of Amsterdam Vrije Universiteit Amsterdam 34

Appendix 1

Neurodegeneration Program leaders Wiesje van der Flier Rob de Bie

2016-present 2016-present

Amsterdam UMC – location VUmc Amsterdam UMC – location AMC

Taskforce members Charlotte Teunissen Lars van der Heide Wilma van de Berg Paul Lucassen

2016-present 2016-present 2019-present 2016-2017

Amsterdam UMC – location VUmc University of Amsterdam Amsterdam UMC – location VUmc University of Amsterdam

Neuroinfection & -Inflammation Program leaders Joep Killestein 2016-present Matthijs Brouwer 2017-present Diederik van de Beek 2016-2017

Amsterdam UMC – location VUmc Amsterdam UMC – location AMC Amsterdam UMC – location AMC

Taskforce members Elga de Vries Filip Eftimov Ivo van Schaik

2016-present 2017-present 2017-2017

Amsterdam UMC – location VUmc Amsterdam UMC – location AMC Amsterdam UMC – location AMC

Neurovascular Disorders Program leaders Jonathan Coutinho Dagmar Verbaan Peter Vandertop Yvo Roos

2017-present 2020-present 2016-2019 2016-2017

Amsterdam UMC – location AMC Amsterdam UMC – location AMC Amsterdam UMC – location VUmc Amsterdam UMC – location AMC

Taskforce members Gert Kwakkel Charles Majoie

2016-present 2016-present

Amsterdam UMC – location VUmc Amsterdam UMC – location AMC

Compulsivity, Impulsivity & Attention Program leaders Odile van den Heuvel 2016-present Dirk Jan Smit 2020-present Judy Luigjes 2019-2020 Wim van den Brink 2016-2018

Amsterdam UMC – location VUmc Amsterdam UMC – location AMC Amsterdam UMC – location AMC Amsterdam UMC – location AMC

Taskforce members Taco de Vries Conrado Bosman

Amsterdam UMC – location VUmc University of Amsterdam

2016-present 2016-present

35

Amsterdam Neuroscience

Appendix 1

Mood, Anxiety, Psychosis, Stress & Sleep Program leaders Sabine Spijker 2016-present Christiaan Vinkers 2019-present Brenda Penninx 2016-2018

Vrije Universiteit Amsterdam Amsterdam UMC – location VUmc Amsterdam UMC – location VUmc

Taskforce members Lieuwe de Haan Aniko Korosi Mirjam van Zuiden

Amsterdam UMC – location AMC University of Amsterdam Amsterdam UMC – location AMC

2016-present 2017-present 2022-present

Amsterdam Neuroscience executive office Anita Osinga 2016-present Naomi Vorstermans 2019-present Lisette Kuijper 2021-present Rhanna Haantjes 2021-present Lara Martin Sanchez 2022-present Michella Dijkinga 2022-present Thea Laan 2016-2021 Sabira Noerkhan 2017-2021 Noa Ijdo 2021-2022

Management assistant & event coordinator Communication advisor Staff advisor Staff advisor assistant Staff advisor Communication officer Policy officer & secretary Management assistant Communication assistant

TN2 organization committee Matthijs Brouwer Jeroen Hoozemans Menno Schoonheim Micha Wilhelmus Hugo Vrenken Arjen Brussaard

Amsterdam Amsterdam Amsterdam Amsterdam Amsterdam Amsterdam

UMC UMC UMC UMC UMC UMC

– – – – – –

location AMC location VUmc location VUmc location VUmc location VUmc location VUmc

36

Appendix 2 | 2.1

Research programs

Brain Imaging

Inventory of the 2016-2021 period: • The essence of our research program is the development and clinical application of advanced brain imaging techniques focused on multi-modal imaging, precision medicine and minimally invasive brain imaging.

• In 2016-2021 we adhered to the goals set out in the ‘Project plan Amsterdam Neuroscience’ (2015), namely to focus on fully translational (from bench to bedside via micro EEG/PET/SPECT/ MRI) via institutional funding, multimodal imaging technologies, with minimally invasive programs suitable for ‘personalized medicine’ and drug-targeting strategies (via defining new physiological parameters such as pharmacoMRI, dynamic fMRI-MRS, MEG, amyloid and tau PET, and other innovative receptor imaging strategies, like synaptic vesicle glycoprotein (SV2A) imaging and EEG/neuropsychological data).

• More recently, with the advent of big data approaches and AI methods such as radiomics and machine learning, we added the organization of core facilities and engagement in data processing and analysis initiatives to our agenda via intensified integration with physics and mathematics (via PoC and Amsterdam Neuroscience funding), as well as institutional funding for building a basic neuroimaging infrastructure and AI databases.

• We impact patient well-being by providing potential prognostic and diagnostic neuroimaging biomarkers that can be used for precision medicine in patients with MS, AD, depression, ADHD, OCD, movement disorders, post-anoxic coma, etc. For example, machine learning analysis of clinical and neuroimaging data enabled early confirmation of the diagnosis of frontotemporal dementia (J Alzheimer’s Dis 2019).

Also, with machine learning of EEG data we obtained faster and more accurate predictions of good and poor outcome in patients in coma after a cardiac arrest (Ann Neurology 2019). For more information see Amsterdam Neuroscience - Brain Imaging.

Appendix 2

Strengths: • The Brain Imaging program has a strong distinctive profile, which is the application of advanced imaging tools and techniques primarily to advance drug-targeting strategies. This is where the available expertise of the Principal Investigators lies and where we can make a difference.

• We are a medium sized program with respect to budget and full-time equivalent (FTE). With relatively little funding, our program was highly productive over the past six years: on average 2.99 publications/PI/year were published, whereas this was 2.29 for other technical programs.

These publications were also of high quality (average no. of impact papers between IF 5-10 was 0.52 /PI/year, whereas 0.44 for other technical programs). Nevertheless, we lack real high impact (IF >10) papers: this was only 0.12 paper/PI/year versus 0.33 for the rest, likely reflecting the lack of really high impact brain imaging journals.

Our thesis production was on average for the technical programs; namely 0.15 PhD thesis/PI/year. In sum, a highly efficient and productive program. Several prestigious grants have been obtained, including Veni, Vidi (2), Memorable, TOP, Abipat, DATA2PERSON, ENBIT, Eurostars (4), COVID-19 (2), Alzheimer Nederland, STW (NWO), NWA-ORC and an ERC Consolidator grant.

• Over the past period, we have been working on improving our weak points, such as getting preclinical studies going as well as studies at 7T, in addition to building a basic research infrastructure.

• Another strength is the enormous amount of talent and expertise that is available within our program. We engage in big data approach, for instance, by setting up an Amsterdam Neuroscience Neuroimaging database and analysis pipeline. D. Veltman is a driving force behind several ENIGMA programs. We also have a decent amount of AI knowledge within our program, which is strengthened with the close collaboration of the department of Biomedical Engineering and Physics. Since brain imaging is a fast-evolving field, we want to

37

put young enthusiastic researchers in the spotlight more; they have organized the TN2 meeting on Brain Imaging in the fall of 2019 as well as 2022. Of note, several young talents (Vriend, Mutsaerts, Schrantee, Golla) were appointed fixed positions. Interestingly, their postgraduate careers took a fly after receiving a proof-of-concept (PoC) or regular grant from Amsterdam Neuroscience, illustrating the success of this program.

Weaknesses: • The enormous amount of talent and expertise is at the same time a weakness of our program, because the available expertise is scattered on small islands all over Amsterdam Neuroscience. There is still (too) little collaboration with other departments (e.g., Mathematics and Computer Science, and Biomedical Engineering and Physics / Medical Physics).

• We do not have the infrastructure to host all these AI and big data approaches. We are currently working on expanding the existing research infrastructure with existing initiatives (AI infrastructure, ADORE, as well as the Imaging Core Facility of the departments of Radiology and Nuclear Medicine). For this purpose, we need to embed the newly established neuroimaging infrastructure. In addition, the available technical knowledge on both sides of the Amstel (physicists, engineers, ICT specialists, etc.) will have to become more involved in the Brain Imaging program. Another weakness is that for transparency regarding pricing of PET and MRI scans, we are relying on the Imaging Core Facility.

Opportunities: • The strong AI focus, by appointing four professors in AI at the UvA (of which one on AI and Medical Image Analysis at the departments of Radiology and Nuclear Medicine and Medical Physics location AMC), the huge amounts of imaging data that are already available, which is like a goldmine for AI, as well a number of initiatives that are taking place for building a large infrastructure, such as the RICC/Imaging Core Facility, ADORE, AI infrastructure, and the enormous amount Appendix 2

•

of talent and expertise that is available within our program are all opportunities we need to grasp.

Quick wins: research with large international patient cohorts (e.g., ENIGMA, human connectome project, MS imaging data), joining the AI course that has been started, and joining in / further developing research infrastructure within Informatieplan Onderzoek 2019-2022, as well as the HPC facility, Imaging Core Facility, and the newly build Imaging Center at location VUmc. The Imaging Center at location VUmc is a unique building where MRI, PET including whole body PET-CT, CT, optical imaging, radionuclide synthesis facilities and cyclotrons are united, making it highly suitable for true multimodal imaging.

Threats: • Currently, the technical input in the Brain Imaging program is still limited, as it is too scattered and present on several islands within Amsterdam Neuroscience. We will strengthen this by the activities indicated above.

• Staff positions are scarce, which makes it extremely difficult to keep highly talented PhD and post docs. We need more structural support in the form of fixed positions for young talent.

• Costs of dynamic PET scans, tracer production, arterial sampling and data analysis are (very) high.

• Availability of PET and MRI slots for brain research.

Research strategy for the coming 6 years: • Although our strategy for 2019-2021 was to (1) fully embed the newly established research infrastructure within the goals set out by the Brain Imaging program)(see above) and (2) provide centralized support, especially optimize opportunities in the field of AI and big data analysis, we only partly achieved this goal, partly also due to COVID related issues, as well as the fact that the Imaging Core Facility (within the department of Radiology and Nuclear Medicine) is still under construction. For the coming 3 years, we want to finalize these goals by executing the following: (1) the basic research neuroimaging infrastructure that has been set up should be 38

embedded within Amsterdam Neuroscience via a grant(s), possibly sponsored via the Amsterdam Biocomputation Center (ACB) and/or ADORE fund, in addition to the Imaging Core Facility (that is still under construction). And (2) our strategy for centralized support is to involve technical experts (e.g., Hugo Vrenken, Alle Meije Wink, Matthan Caan, Henk Marquering, Ivana Išgum, Paul Groot, Ronald van Schijndel, Martijn Steenwijk, Ronald Boellaard, Maqsood Yaqub, Sandeep Golla and others) more in our program; although this has been actualized, we want to involve a technical expert(s) also in steering committee of the Brain Imaging program. In addition, we want to organize several method-specific subgroups within the Brain Imaging program. For instance, through Amsterdam Neuroscience calls for grants with a specific topic like we did in 2020 on AI, which was a huge success. Moreover, we want to organize regular methodspecific meetings within our program. In conclusion, in the coming years, the Brain Imaging program will focus on infrastructure, gluing the islands together and joining forces!

For the Top 5 publications, see Appendix 3 – Output (p. 59).

2.2

Systems & Network Neurosciences

Inventory of period 2019-2021 (outcomes, process and integration): • The goal of the research program Systems & Network Neuroscience is to understand how networks of neurons and brain areas give rise to brain function and behavior. In addition, studying the interaction of the central nervous system with peripheral organs offers new avenues to improve health. The research program of Systems & Network Neuroscience brings together research groups using invasive and non-invasive approaches in the living brain to study and manipulate brain networks in health and disease.

• This research program relates to the fundamental as well as the clinical themes in Amsterdam Neuroscience, with good connections with the industry, facilitating novel technological developments.

Applying these technologies to study and manipulate neuronal and brain networks in the living brain and actively apply it to the treatment of pathological conditions will not only increase understanding of how brain networks give rise to function, but also have direct impact on health prospects of patients.

Strengths: • The program promotes the implementation of technological advances in neuroscience such as: MEG, EEG, deep brain stimulation (DBS), TMS/TDCS, brain surgery, in vivo nerve stimulation, in vivo neuronal and network recordings, opto-and chemogenetic manipulations, Optical Coherence Tomography (OCT) of the human retina, miniscope and 2P imaging, functional magnetic resonance imaging (fMRI), PET scans, computational approaches and others.

• A major focus of the program is on understanding brain networks for sensory processing, motor control, cognition, mood, reward and harnessing collaborations on cross-discipline functional studies of brain function in relation to health.

Appendix 2

39

Weaknesses: • The fact that research groups are scattered in different locations limits the ability to share facilities and resources, and the opportunity for interactions among researchers.

• Lack of an efficient communication platform to share progress with participating Principal Investigators.

Opportunities: • Key indicators of the program: ◦ Study of network function and pathophysiological mechanisms of disease at the systems level. ◦ A mechanistic understanding of how networks of neurons give rise to brain function and behavior. ◦ Use of cell-type and network specific manipulations of brain function in health and disease ◦ Examine how neural activity in the central nervous system coordinates the activity between the brain and body. ◦ Design and engineering of electrophysiological or mechanical systems that control sensory feedback and information processing in the brain. ◦ Improvement of clinical applications of technologies developed within and outside Neuroscience Amsterdam.

• Excellent research groups with top publications.

• Strong complementary expertise at both universities and Amsterdam UMC on neurotechnology.

• Strong ties with clinical departments with large patient cohorts for current and future applications of technologies.

• Strong links with industry to facilitate technological developments.

• •

Time-consuming bureaucracy for obtaining ethical permits for animal and human.

Pandemics.

Research strategy for the coming 3 years: • Our goal is to understand how networks of neurons and brain areas give rise to brain function and behavior. In addition, studying the interaction of the central nervous system with peripheral organs offers new avenues to improve health. The research program of Systems & Network Neuroscience will continue to bring together research groups using invasive and non-invasive approaches in the living brain to study and manipulate brain networks in health and disease. The program will keep on promoting the implementation of technological advances in the neuroscience field such as described in the strengths above.

For the Top 5 publications, see Appendix 3 – Output (p. 59).

Threats: • Lack of opportunities for research funding (particularly for individual grants).

• Excessive demand for valorization and collaborations with non-academic sectors.

• Excessive teaching load.

Appendix 2

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2.3

Cellular & Molecular Mechanisms

Strengths: • Strong link with Amsterdam Neuroscience clinical programs, strong translational profile.

• Coordination of SYNGO consortium (CNCR leads international consortium of expert labs, Koopmans et al. Neuron, top 5% best cited papers, excellent funding by Broad, SFARI).

• Key opinion leaders in monogenic neurodevelopmental disorders of the synapse (SNAREopathies, white paper in Neuron 2019, coordinate international consortium, organize patient family days) and technology to tag, isolate, sort, harvest and probe cell-type/circuitspecific synaptic populations at a molecular level.

• New assays for functional analysis of disease mutations in neurodevelopmental disorders, novel cellular model to quantitatively assess synaptic parameters in iPSC-derived human neurons at a single-cell level (Meijer et al., 2019).

• Expertise in iPSC derived neural cells: a biobank to store cells for the generation of patient iPSC, expertise on generating neural cell structures from patient cells to answer research questions in disease-relevant tissue, optimizing culture for iPSC derived inhibitory neurons to create E/I balanced human networks in vitro.

• Key expertise and infrastructure for functional imaging in neuronal cells and organoids, screening platforms, advanced data management and AI-driven data analysis (coordination NWO Roadmap NL-BioImaging).

• Unique expertise in molecular pathways in neurodegenerative diseases (proteostasis, stress, protein misfolding (e.g., Alzheimer’s, Parkinson’s, Huntington’s Disease).

• Expertise groups on alterations in proteomics and metabolomics in neurodegenerative diseases.

• Expertise on the blood-retinal and blood-brain barrier (BBB) and the neurovascular unit (NVU), based on human retinal and brain tissue and animal models.

• Expertise in analysis and targeting of metabolic processes in the brain (mitochondria, microglia-neuron interactions, lipid droplets, circadian clock machinery, gene and protein profiling with postmortem human brain tissues) and link this to behavior and peripheral metabolism.

Appendix 2

•

PoC funding has strengthened the collaboration between the collaborating CMM teams.

Weaknesses: • Diversity of topics, expertise and lab locations.

• Bioinformatic support/expertise is limited (especially for analysis and integration of -omics datasets).

• While collaborations between CMM members at the CNCR of the Vrije Universiteit Amsterdam are established, collaborations with CMM members outside this campus are more difficult.

• Throughput of our analysis is rate limiting.

• Limited access to genomic profiles of patients with neurodegenerative disease in Amsterdam and the Netherlands limits the establishment of cohorts.

• Progress is currently slowed by the labor-intensive nature of patch-clamp electrophysiology. A more high-throughput technology to assess synapse function, such as cutting-edge optical methods, could be beneficial if proper resolution can be obtained.

• • Individual approaches to use (patient-derived) iPSC cell lines for validation.

Opportunities: • Increasing interest from industry for our assays, tools and expertise.

• Opportunities to combine different life science & enabling technologies e.g., visual omics by combining microscopy and omics data of the same sample will translate next-generation life science technologies to applications and scientific breakthroughs.

• Share CMM expertise in different biomedical technologies, methodologies and analysis to connect single molecule research to their analysis in intact organisms in different (disease) models.

• Team science: CMM members lead or are part of many leading consortia worldwide (Human Brain Project, SYNGO, ESCO, Brainmodel, Brainscapes).

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• • •

• • • •

Mathematical modeling to describe/understand how cellular phenotypes translate to network/disease phenotypes and to predict druggable targets.

Data management/data access mechanisms for sensitive data to organize stem cell research.

Cellular Imaging (LCAM-AMC) and O2Flow facility MCBI at the UMC location VUmc have state-of-the-art techniques available for (correlative light and) electron microscopy, functional imaging of cells, organoids and tissues, light sheet and super resolution imaging, and flow cytometry.

The research line on the molecular mechanisms of synaptic inhibition could be better integrated at the biophysical level to strengthen the mechanistic interpretation, as well as at a higher systems level.

Better integration, collaboration and exchange of techniques between CNCR at Vrije Universiteit Amsterdam and SILS and AMC location.

Accelerate development of innovative medicines by understanding the relation between (disease-related) proteins, molecular pathways, neuronal cell phenotypes and small animal models.

Established infrastructure and expertise will be used for a more prominent role in national consortia including NWO Roadmap GWI, NWA and Gravitation.

Threats: • The locations: Vrije Universiteit Amsterdam / Amsterdam UMC location VUmc will move to new building which result in a discontinuation of animal research.

• PhD candidates that encountered delays due to COVID lab closing are reaching the end of their contracts in 2022-2024 but failed to catch up experimentally.

• Reduction in the acceptance of animal experimentation (yet partly covered by proposed patient-derived iPSC activities).

• Comparatively less funding opportunities for non-disease related, fundamental neuroscience research.

Appendix 2

• • •

Excessive bureaucracy and delays for obtaining ethical permits for animal and human experiments.

Increasing costs for lab reagents.

Reagents are on back order causing delays for PhD candidates.

Strategy for 2022-2027: • Develop new dimensions for the SYNGO knowledgebase (proteinprotein interactions, causality modeling).

• Promote international collaboration on monogenic neurodevelopmental disorders of the synapse (SNAREopathies) and promote trial readiness.

• Identify cellular mechanisms which regulate synaptic strength and explore the physiological relevance on synaptic computation and brain function.

• Team up with computational neuroscientists for modelling our in vitro human networks.

• Continue developing technology to probe the molecular framework of sparsely distributed memory encoding ensembles, including cell-state dependent proteomics (e.g., protein turnover in the face of neuronal activity). This technology will be available for others within CMM who would like to apply it to their own research.

• Further development of proteomics / imaging methods to study glia-synapse interaction, which may be of interest / compatible to the research of many in the CMM program.

• Continue developing models (BBB, NVU, iPSC, neuron-glia co-culture) to understand the correlation between metabolic disease and brain function and pathology (i.e., dementia, depression, diabetes, obesity).

• Development of a zebrafish model for studying pathophysiological effects on the BBB. For the Top 5 publications, see Appendix 3 – Output (p. 60).

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2.4

Complex Trait Genetics

The CTG program investigates the genetic, epigenetic and environmental causes of individual differences in brain function and dysfunction related to cognitive, mental and physical health. CTG has approximately 30 members, from several departments of the Vrije Universiteit Amsterdam, Amsterdam UMC (location VUmc & AMC) and University of Amsterdam.

Strengths: • Establishment of a biobank to store cells for the generation of patient iPSC (VU Amsterdam).

• Establishments of platforms for generating neural (UvA, VU Amsterdam) and retinal (Amsterdam UMC) cell structures from patient cells, including 3D organoid structures, to address research questions in disease-relevant tissues.

• Development of a 3D-bioprinting platform for analyzing genetically modified stem cell lines for studying age-related macular degeneration (Amsterdam UMC).

• Establishment of a (pre-)clinical translational genetics AUMC pipeline for gene therapy, small molecule therapy, and stem cell replacement therapy of genetic retinal disorders (Amsterdam UMC).

• Deepening links between psychiatry and complex trait genetics and vice versa (GGZ inGeest AUMC/VUmc).

• Newly established collaborations with national and international consortia, such as between AMC and NESDA, between UvA and the ‘Collaborative Center for XDP (CCXDP) @ Massachusetts General Hospital, NWA-consortia, NWO Zwaartekracht, etc.

• Founding of new expertise centers: Eye and Brain Platform, Emma Precision Medicine Center (Amsterdam UMC).

• Funding and completion of six successful research programs through the Amsterdam Neuroscience PoC /Alliance grant system.

• Many prestigious grants and awards, including ERC starting/advanced, NWO ZonMw TOP, Vidi, Vici.

• High quality and quantity of research output.

Appendix 2

Weaknesses: • There is not yet enough connection and collaboration between different CTG research groups regarding shared research disciplines and shared technical expertise, such as the iPSC labs at the VU Amsterdam/UvA/ Amsterdam UMC, methodology, strategies and knowledge on complex genetics analysis (VU Amsterdam/UvA/Amsterdam UMC).

• There is not yet enough connection and collaboration between different CTG research groups regarding unique research disciplines and research-group-specific expertise: such as integrating knowledge on complex genetic loci/repetitive DNA with GWAS-associated studies (UvA/VU Amsterdam), linking genetics with neuro-psychiatric and neurological disease phenotypes (UvA/VU Amsterdam/Amsterdam UMC), 3D bioprinting technologies (Amsterdam UMC/UvA/VU Amsterdam), Genetics and the penetrance of neurological disease associated phenotypes (Amsterdam UMC/UvA/VU Amsterdam).

• Growing need for expertise to perform multi-modal analysis (e.g., multi-omics).

• Continuing and growing need for funds to support research projects to connect the different research groups and share expertise within CTG. Opportunities: • We should have regular meetings within CTG, focusing on knowledge exchange and stimulating collaborations between different groups.

• Increased knowledge exchange can lead individual CTG members to write new grant proposals on projects that bridge different research programs.

• Improvement of data management and data access mechanisms for patient-derived sensitive data.

• Communicate and share expertise and knowledge regarding computational modeling and specific technical expertise that could be applied to other research questions (3D organoid model-systems, 3D bioprinting, etc.).

43

Threats: • A continuing threat to the CTG program is how to fund research that would strengthen the collaborations between individual researchers, research programs and institutes, which is the main goal of Amsterdam Neuroscience. In times when most researchers are hired on specific projects with little time to explore additional research interests, great ideas and ambitions for collaborations within CTG can only be realized if there are funds available.

• There are significant worries about the continued availability and cost increases of certain specialized lab reagents as a result of COVID-related shortages and recent geopolitical issues.

Future perspectives for the next 6 years: • The ambition for the next six years is for CTG to invest more in translational genetics: Studying genetic disorders and specific sub-phenotypes of psychiatric disorders using CRISPR/Cas9 genetic engineering, multi-omics approaches, 3D organoid modeling and 3D bioprinting.

• We further aim to develop and apply novel statistical tools for the analyses of genetic data, and increasingly apply bioinformatics tools to integrate the outcomes from genetic studies into neurobiological and functional follow-up studies.

For the Top 5 publications, see Appendix 3 – Output (p. 60).

Appendix 2

2.5

Neurodegeneration

Strengths: • Within the program the main focus is Alzheimer’s disease (AD), Parkinson’s disease (PD), Frontotemporal dementia (FTD), and Dementia with Lewy bodies (DLB). Amsterdam Neuroscience holds strong expertise in clinical phenotyping, neuroanatomy/ neuropathology and molecular profiling of neurodegenerative disorders and conduct of clinical trials. In the past year, translational research and team science was stimulated by various local (i.e., seminars, PoCs, TKI-PPP) and national (e.g., ZonMw Memorabel PAGE-AD, NWA BioClock application SILS-NIN, Parkinson Alliance Netherlands) initiatives. This has led to novel collaborations between basic and clinical researchers on campus and initiatives to integrate patient care and research.

• For AD, the main focus in the past years was to study the origin of disease using biological markers and genetics, to improve diagnosis and prognosis by identifying and applying robust and disease-specific biomarkers (Teunissen, Lancet Neurol 2021) and identify meaningful subtypes to improve patient stratification (Tijms, Brain 2020) e.g., in clinical trials. Substantial advances have been made in PET, MRI and biofluid biomarker measurements for AD early diagnosis and predicting progression (van Maurik, Lancet Neurol 2019). A major strength of the Alzheimer program has been the large Amsterdam Dementia Biobank infrastructure with biofluids combined with large datasets of the Amsterdam Dementia cohort (n>6000 patients; e.g., Verberk Ann, Neurol 2018). Expertise in genetic, molecular, pathological, high-end microscopy and (in vivo and postmortem) MRI has contributed to novel insights into disease mechanisms underlying early age-at-onset and/ or atypical (non-amnestic) AD and FTD. Amsterdam took the lead in large consortia (e.g., Netherlands Consortium of Dementia Cohorts, NCDC; A Personalized Medicine Approach for Alzheimer’s Disease, ABOARD; www.aboard-project.nl) to move toward a personalized approach in patient care and treatment strategies.

• The main focus in Parkinson’s research is to improve the treatment of PD by (1) identifying tissue, biofluid and imaging biomarkers for diagnosis and prediction of disease progression, (2) understanding 44

psychiatric and cognitive symptoms, and (3) advancing treatments of motor symptoms. Preclinical PD research focused on unraveling disease mechanisms showed that disturbed lipid metabolism plays a central role in Lewy body formation (Shahmoradian et al. Nature Neurosci 2019). To guide the development of novel biomarkers, a multicenter longitudinal cohort study named ‘Profiling Parkinson’s’ (ProPark), has been formed in close collaboration with academic, private and industry partners. After showing that deep brain stimulation (DBS) surgery is equally efficacious when performed under general anesthesia as opposed to awake surgery for PD (Holewijn et al. JAMA 2021), the focus is now on the development of adaptive DBS and automated DBS programming. In 2017, Professor Marten Smidt and dr. Lars van der Heide founded Macrobian Biotech to work towards novel treatments for PD (macrobianbiotech.com).

Weaknesses: • It has been difficult to obtain funding for research across diseases. It has been difficult to recruit or hold onto postdocs/young researchers willing to dedicate their time to basic or clinical research. Talent policy in general is hampered by a CAO that makes it difficult to keep personnel on temporary contracts. The lack of legal support in Amsterdam UMC is an important weakness. Compute, clusters, infrastructural support for large datasets, particularly imaging is insufficiently accounted for. Neuroscience cluster is down, but access to surfSARA is not yet organized. Also, with growing datasets and an increasing emphasis on making data available, an increasing demand is made on the time of research personnel that is in fact not hired to prepare, query and archive data sets.

Opportunities: • The search for biomarker panels (tissue, CSF and blood) can be continued using the biological samples in combination with the comprehensive and uniformly acquired longitudinal clinical data, imaging data of the clinical cohorts. For AD, we will further strengthen our position for clinical trials by a firm link with IAO, ACRU in the Appendix 2

•

context of ADORE, and knowledge that can be applied to improve trial design (e.g., outcome measures, particularly Amsterdam IADL-Q, proteomics-based subtypes, genetic or molecular profiles, responder analyses).

In 2022, the Amsterdam UMC Parkinson and Movement Disorders Center will be launched, and programs will be developed to further integrate care and research, develop a PD and movement disorders biobank and stimulate team science. We will also stimulate research across parkinsonian disorders to identify common and disease-specific pathogenetic mechanisms.

Threats: • The research is financed largely by external funding which makes the program vulnerable. To secure successful continuation of the important research lines of Alzheimer Center Amsterdam and Parkinson and Movement Disorders center, it is of the utmost importance that the external funding is matched, and a mature infrastructure of senior research staff can be accommodated within the first cash flow.

Continuity of external funding is crucial because a considerable part of the research team depends on these funds. Constant and high-quality staff and services in all departments are essential for our multidisciplinary research (e.g., imaging infrastructure/pipelines; genetics/ genomics/clinical research and bioinformatics facilities).

Research strategy, research process and innovation - 2022- 2027: We will continue to grow as an attractive partner for basic research and clinical trials, via recruitment, stratification of participants for next clinical phase 1 to phase 4 trials (in collaboration with the Industry Alliance Office and Brain Research Center). With hersenonderzoek.nl we facilitate recruitment of participants for brain research. To achieve a future of individualized prevention of neurodegenerative diseases, we will further optimize (molecular) diagnosis and identify (poly)genic risk factors that contribute to early age-at-onset, more severe disease progression or resilience in well-defined AD/PD/FTD/DLB cohorts. In addition to our clinical cohorts, we will continue to build cohorts of cognitively normal 45

individuals (e.g., twins, 100+). To overcome the heterogeneity dilemma that hampers drug development and to identify molecular profiles and (novel) drug targets for personalized treatment strategies, we will set up an induced pluripotent stem cells (iPSC) biobank of the brain donors (TKI-PPP TKI CONCERT, Van de Berg/Pijnenburg). We will continue to search for novel tissue, blood and PET biomarkers for improving early diagnosis and predicting disease progression for AD, PD and related disorders. For PD, we will embark on clinical personalized and pharmacogenomics research, amongst others via the Levodopa in early Parkinson’s disease cohort (Leap study), the Parkinson Personalized Therapeutics Initiative (www.proparkinson.nl), adaptive DBS and automated DBS programming.

For the Top 5 publications, see Appendix 3 – Output (p. 61).

2.6

Neuroinfection & -Inflammation

The neuroinfection & -inflammation program has a strong track record in preclinical models, cohort studies and clinical randomized controlled trials leading to high profile output. The theme’s clinical research addresses burning clinical questions with direct relevance to patient care resulting in high societal impact.

Period 2019-2022 The neuroinfection & -immunity program has focused on two disease areas: multiple sclerosis (MS; location VUmc) and neurological infections (location AMC), but also includes research on the blood-brain barrier and immune-mediated neuromuscular disorders.

Strengths: • Several prestigious research grants have been obtained including ERC Consolidator, ZonMw Vidi, ZonMw Vici, Topconsortia for Knowledge and Innovation (TKI), Prinses Beatrix Spierfonds (PBF), Marie Curie International Trainings network (ITN) and MS Research Foundation Center Grant.

• Twenty-six PhD theses have been successfully defended and the number of publications was >450.

• Nationwide MS projects have been initiated on extended dosing of natalizumab (NEXT-MS trial, Dutch Brain Foundation and MS Research Foundation), on feasibility of stopping immunomodulatory therapy in stable patients (DOT-MS trial, funded by ZonMw and MS Research Foundation) and extended dosing of Ocrelizumab, BLOOMS-trail, funded by ZonMw and Treatmeds).

• Two investigator initiated randomized controlled trials in chronic inflammatory demyelinating polyneuropathy (CIDP) and myositis have started (funded by ZonMw and PBF).

• A multicenter study has been initiated aimed at improving prognosis by using innovative methods to diagnose causes of encephalitis (the IPACE study funded by ZonMw Vidi and ERC Consolidator grant).

Appendix 2

46

•

• •

An institutional PoC grant started a nationwide cohort study and biobank of neonatal bacterial meningitis has been established.

Recent grants from the European and Developing Countries Clinical Trials Partnership (Horizon 2020) and Gates Foundation sustained this project.

TN2 meetings were transformed into a successful webinar series including sessions on neuroinfection &-inflammation.

During the COVID pandemics the investigators from the neuroinfection & -inflammation program initiated several high profile COVID19 related projects: ◦ The Amsterdam UMC COVID19 biobank was set up by Diederik van de Beek and Matthijs Brouwer and resulted in a biobank with over 5,000 patients and >80,000 samples. These samples could be used for multiple local, national and international projects that have been published in Nature, Science (3), Science immunology, PNAS and many other journals. Funding was acquired from the Amsterdam UMC COVID19 fund (150k€) to perform a baseline set of measurements that could be used by all Amsterdam UMC researchers. 2) As member of the ‘Target to B consortium’ for B-cell mediated autoimmune disease Filip Eftimov acquired ZonMw funding (3.5M€) to assess the efficacy of COVID19 vaccination in patients using immunosuppressive medication so far resulting in publications in Lancet Rheumatology, BMC Medicine, MS Related Disorders and several others submitted papers. The COVID-related national infrastructure that was set up for this study will be used for the ImmuneHealth XL, a developing collaboration between the different consortia on autoimmunity (including CIDP and MS). ◦ After prior cooperation between the neuro-infections research group (Diederik van de Beek) and InflaRx, a pharmaceutical company producing a C5a complement inhibitor (Vilobelimab), a phase II RCT in severe COVID-19 patients was set up in early 2020 in a collaboration of InflaRX and the departments of Internal medicine, Neurology and ICU of Amsterdam UMC. The phase II RCT showed potential benefit of the drug (publication Lancet Rheumatology) after which a phase III RCT with 360 patients was performed, of which the results are expected in April 2022.

Appendix 2

Weaknesses: • Interaction between NII members is suboptimal because of different lab locations, expertise and topics. No routinely scheduled meetings have been set up to improve interaction. However, the balance between having more meetings and keeping time for research is challenging.

• Continuity of external funding remains important to consolidate the successes of the past.

• Dependence on external funding for core research structures such as biobanking.

Opportunities: • Sharing of new diagnostic methods to speed up diagnostics or monitor disease activities through biomarkers research. To optimize innovative developments within Amsterdam Neuroscience, increased interaction between research groups is paramount. So far, this has mostly been done at the research institute level, whereas cooperation on the research program level has not been optimally explored.

• Regular meetings (e.g., biannual) with the research program leaders and task force members to identify opportunities for cooperation, and shared scientific presentations. An example of successful interaction has been the MS/CIDP joint research project, enabled by an Amsterdam Neuroscience seeding grant.

• Learning from each other’s research strategies, which already resulted in a shift in focus from industry driven to investigator-initiated research in MS research and a reciprocal shift towards industry projects in the neuro-infection research.

• There is a sense of urgency to create a clinical trial unit, which will be incorporated in the ADORE Concept. This unit will be elemental for future multicenter studies, using a hubs and spokes model with Amsterdam UMC and regional hospitals.

• Both locations of Amsterdam UMC are well known tertiary referral centers in the Netherlands for autoimmune neurological diseases, including multiple sclerosis, immune-mediated neuropathies and myopathies and neurosarcoidosis, and neurologic infections such as bacterial meningitis and neuroborreliosis, both for diagnosis and (advanced) treatments.

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• •

•

The close interaction between clinicians and basic researchers stimulates research to solve major clinical problems. Clinicians and researchers take part in several national and international bodies (e.g., guideline committees, advisory boards of patient and government organizations), write for the lay-press and are active in national media. Researchers are involved in active dissemination e.g., website, Twitter, Facebook and organization patient/participant days.

We actively seek collaboration with the industry, both for diagnostics, disease monitoring and treatment.

The national RIVM booster vaccination program affecting hundreds of thousands of patients with auto-immune diseases in the Netherlands was tailored based on results of the Target to B-COVID study emphasizing the societal impact of our studies.

The vitality of the research program is high. Two MS fellow neurologists and one MS research fellow have been appointed for at least another two years, who were involved in recent successful grant applications. A recent 2021 ERC Consolidator grant has further boosted the neuro-infections research line. Combined with 2019 Vici grant, there is substantial room to invest in new research opportunities. Structural funding has been acquired to consolidate the neuro-sarcoidosis research. A nationwide research network has been established for a neonatal meningitis and sepsis cohort (NO-GBS study). Furthermore, a worldwide database (INCbase) for CIDP has been set up which will put us at the front of inflammatory neuropathies research. At this moment, alternative trial designs such as Trials within Cohorts (TwiCs) is being explored within INCbase as funding for investigator-initiated trails in rare disease remains cumbersome. Renewal of leadership and acknowledgment of talent is an important theme in Neuroinfection & -inflammation.

Threats: • The merge of AMC and VUmc may lead to increased management tasks and meeting frequencies, which inevitably leads to reduced time for research.

• Increasing use of healthcare by an aging population will increase clinical tasks whereas educational tasks are not expected to decrease.

• The high workload for partners in MSCA due to either increased bureaucracy, clinical tasks and/or teaching duties limiting time investment into research (and grant writing).

• A cutting-edge genetic core facility and biocomputational support will be vital for the near future. At this moment it remains difficult to attract knowledgeable biocomputational experts.

• Continuity of external funding remains important to consolidate the successes of the past.

• Availability of neuroimaging is currently an important threat in the field of MS research, both in the clinical setting and for research.

• Finally, legal support is too often an important delaying factor in setting up research collaborations, multicenter studies and randomized clinical trials.

Strategy 2022-2024: We will continue with clinical and translational research by combining large nationwide prospective cohorts and randomized controlled clinical trials with extensive bio-banking to facilitate patient stratification and basic and translational research. Innovative research methods that have recently been implemented in Amsterdam Neuroscience such as single cell sequencing, single cell immune profiling, single molecule arrays, platelet sequencing, multiparameter flow cytometry, lipidomics, high-end microscopical imaging (Nikon center of excellence) and pathogen discovery sequencing will spark further high-resolution studies using our human samples. Biomarker research will be one of the more directly clinically applicable techniques that can change clinical practice in the next 5-10 years. With the unique cohorts, we will remain an attractive partner for industrial partners for development of new diagnostic tools, but also for randomized controlled trials.

For the op 5 publications, see Appendix 3 – Output (p. 62).

Appendix 2

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2.7

Neurovascular Disorders

Strengths: • Translational research/AI: several research groups seek to improve treatment of acute stroke. ◦ RADISH: platelet RNA as biomarker for delayed cerebral ischemia in subarachnoid hemorrhage. ◦ INSIST (In Silico Trials for treatment of Acute Ischemic Stroke) consortium. ◦ The role of pericyte contraction and specialized pro-resolving lipid mediators in microvascular reperfusion after acute ischemic stroke. ◦ AI-STROKE, ELECTRA-STROKE: EEG for the detection and triage of acute stroke patients, using in-depth signal analysis and AI. • Improvement of treatment for acute stroke, both ischemic and hemorrhagic, cerebral venous thrombosis and subdural hematomas (CONTRAST collaboration: MR CLEAN NO-IV, published in NEJM; MR CLEAN MED, published in Lancet; MR CLEAN LATE, final analysis ongoing; MR ASAP, final analysis ongoing]; ULTRA, published in Lancet; ISCHEMIA, inclusion ongoing; DIST, submitted for publication; TORCH, inclusion ongoing; ELIMINATE, pilot study ongoing; TO-ACT, published in JAMA Neurology).

• Chair of Stroke Recovery and Rehabilitation Task force aimed to achieve consensus on outcomes and improve trials in neurorehabilitation.

• Research strategy: Maintaining leading role in prospective registries and clinical trials Maximum focus on following research lines: ◦ Diagnosis and acute treatment of acute ischemic stroke including prehospital triage and early rehabilitation. ◦ Subarachnoid and intracerebral hemorrhage. ◦ Cerebral venous thrombosis. ◦ Subdural hematoma.

All research lines collaborate on (inter)national basis.

• Societal impact: Endovascular treatment (MR CLEAN) has become the standard of care worldwide for patients with acute ischemic stroke. The department

Appendix 2

of neurorehabilitation has been recognized as center of excellence in the field worldwide.

Weaknesses: • For some conditions: small population of patients, usually with severe deficits.

• Collaboration on a national basis can be challenging because there are many partners involved.

• Increasing bureaucracy, both internally and externally, delays research and increases costs.

• Insufficient collaboration with neurologists in acute stroke care settings with respect to research.

Opportunities: • Proof-of-Concepts/Collaborations: ◦ CINTICS trial: Circulating Nanotraces to Identify the Cause of Stroke. This is a collaboration with LUMC, to improve pre-hospital triage of stroke patients. ◦ CONTRAST-2 consortium: New funding opportunities for stroke research Dutch Heart Foundation, Dutch Brain Foundation and industry. Aimed for 2023. In collaboration with Erasmus MC and Maastricht UMC. Studies focused on acute stroke treatment, pre-hospital triage and intracerebral hemorrhage. ◦ CLEOPATRA: Cost-Effectiveness of CT Perfusion for Patients suffering from Acute ischemic stroke. ◦ PROFITS: Identifying biomarkers of spontaneous neurological recovery and improving patient-specific prognostic modeling of outcome at 3 months post-stroke. ◦ Vaccine induced immune thrombotic thrombocytopenia (VITT): International collaboration. ◦ IRIS: Improving Reperfusion Strategies In acute Stroke: international collaboration.

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•

•

•

IRIS-pooling: Initiated pooling of six trials comparing EVT alone versus IV alteplase and EVT. ◦ DSHR/iCORIC: Dutch chronic Subdural Hematoma Research group/The international COllaborative Research Initiative on Chronic subdural hematoma.

‘Quick wins’/sense of urgency/societal impact: ◦ For ischemic stroke: Impact by improving pre-hospital triage (CINTICS, ELECTRA-STROKE, AI-STROKE). ◦ For hemorrhagic stroke: the DIST-RCT study (CONTRAST consortium) will show whether minimally-invasive endoscopy-guided surgery will be effective. ISCHEMIA aims at paradigm shift in treatment of DCI in SAH. National and international collaboration in the field of cSDH will hopefully lead to treatment guidelines.

External stakeholders: Funding has been received from several industry partners such as Stryker, Medtronic, Penumbra, Bayer, etc. Need for nationwide funding, especially for translational research in stroke recovery and rehabilitation.

Vitality/worldwide trends/funding highlights: ◦ MR CLEAN Registry (national database for endovascular treatment for patients with acute ischemic stroke). ◦ Supervision of MRCLEAN NO-IV replica trial in China (DIRECT-MT), data-pooling. ◦ International cerebral venous thrombosis consortium. ◦ Nationwide Quality Registration Neurological Surgery for subarachnoid hemorrhage. ◦ Dutch Chronic subdural hematoma registry. ◦ IRIS Program leaders include new, young and ambitious research leaders.

Appendix 2

Threats: • Capacity of Amsterdam UMC to admit patients.

• General Data Protection Regulation.

• Lack of structural research funding.

• Lack of core facilities that support research.

• Focus on outcomes such as mRS limits understanding of stroke recovery in terms of behavioral restitution.

Strategy for the coming years: The overarching aim of our research theme for the coming 6 years is on improving diagnosis and treatment of acute stroke. Within this context, we have a special focus on clinical research (clinical trials), phenotyping and translational research (including AI). To attain our goals, we need to consolidate and strengthen our (inter)national collaboration. Funding must come from NWO/ZonMw and ERC grants, charity organizations and industry. We need to attract new young talent, both physicians (investigator-clinicians) and researchers.

For the Top 5 publications, see Appendix 3 – Output (p. 62).

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2.8

Compulsivity, Impulsivity & Attention

Strengths: • Strong in experimental and translational research.

• Strong group of mid-career scientists (with huge grants).

• CIA is well organized.

• CIA meetings were attractive to multiple Principal Investigators from different fields of expertise, leading to multiple collaborative projects led by Principal Investigators from the various institutes.

Due to COVID-19 the meetings disappeared from the agenda. At this moment it is possible again to re-introduce these regular brainstorm meetings.

• Functional analysis of disease mutations involved in neurodevelopment disorders. Development of IPSC derived networks of inhibitory and excitatory neurons to study E/I balance in neurodevelopment disorders in vitro.

Summary: The CIA has continuously been an active program with a high level of Principal Investigator participation and others, regularly attending meetings and actively seeking collaborations across the institutions (although we were severely hindered by COVID in this respect). Because of the representation across many levels of science (animal work, in vitro work, clinical work, neuroscience, and genetics) this has led to cross-fertilization and links across the scientific levels from basic/fundamental to applied. The program is still on par for obtaining funding (but see below at threats). The high level of funding and functioning has resulted in an ability to attract and keep high quality students and PhD candidates who become talented early career postdocs.

Weaknesses: • We need to increase throughput of our analysis and better access to genomic profiles of patients with neurodevelopmental disorders in Amsterdam and the Netherlands to create cohorts.

• No solid longitudinal cohorts, apart from pre-post treatment study designs.

Appendix 2

• •

We should try bringing together more closely the pre-clinical and clinical research.

We should benefit more from the multidisciplinary collaborations (as initiated by institute seed money) in getting external funding for these translational projects.

Summary: The lack of cohort studies may be seen as a hiatus in the consolidation of the CIA work across institutes. This includes the lack of longitudinal assessments of patients and systematic assessment of genetics/neuroscience, in patient cohorts as well as population-based ones. Collaborative projects (i.e., across Amsterdam UMC/UvA/VU Amsterdam) for translational research, bench to bedside, may have lacked external funding.

Opportunities: • Translation between preclinical and clinical research.

• Studying disease phenotypes at different scales in the brain in the same patient. Collaboration between neuroscientists and clinicians.

• Expected merge of the 2 departments of Psychiatry in 2022/2023.

• Group funding.

• More collaboration with industrial parties in valorization projects, by building new consortia with help of the Industry Alliance Office.

Summary: Some of the novel opportunities for CIA may arise with the upcoming integration of the Psychiatry departments of the VUmc and AMC (both strong on OCD/compulsivity research), providing new opportunities in integrating the research performed at different levels, in-depth at the neuronal level (depth recordings, mouse models, and in vitro IPSC recordings) or systems level (EEG, fMRI) and their translation into the clinic (neuromodulatory techniques such as DBS and TMS). There are opportunities for creating grant proposals across the participating institutions.

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Threats: • Slow merging process departments of Psychiatry.

• Interdisciplinary and preclinical research in psychiatry is hard to get funded.

• COVID-19.

• Temporary closure of the animal lab facilities at the campus of the Vrije Universiteit Amsterdam, delaying projects and hampering the attraction of young talent.

Summary: Funding is perceived as one of the major threats to continuing our CIA program successfully. Although our relatively small program has proven to be able to attract grants, soft money is never guaranteed in the competitive scientific world and therefore a continuously present threat. COVID has been disruptive for some (not all) research, especially animal and patient research. This may re-emerge in the fall of 2022.

Strategy for the coming years: • A continuation of the translational neuroscientific work. CIA is at the forefront of deepening our knowledge of deep-brain stimulation research (OCD) with direct usability of that knowledge for optimizing treatment. CIA is also at the forefront in studies of non-invasive neuromodulation (rTMS) in OCD, using personalized (task-)fMRI-based targeting. These topics in DBS/TMS will be expanded for optimal treatment outcome, prediction of response and the study of the short- and long-term neuroplastic effects.

• A continuation of research into treatment prediction models, by integrative modeling of neuroscience and genetics data. Future continuation of this work will focus on multi-omics by integrating the various levels of genetic variants, transcriptomics and imaging genetics (at meso- and systems level).

• Continuation and strengthening of consortium work that is making Amsterdam a hub for large-scale international neuroscience and genetics. Our aim is to obtain and/or maintain prominent positions in the ENIGMA consortium, and in the Psychiatric Genomics Consortium.

• The merger of Psychiatry departments of Amsterdam UMC will give the opportunity to integrate research work for topics in which there Appendix 2

•

•

•

•

is little collaboration presently. OCD and OCD spectrum disorders are strongly represented across both sides of Amsterdam UMC. Likewise, the merger may also be an opportunity for research in the impulsive disorders.

We seek to strengthen computational modeling in various forms in our research programs. We seek an expansion of Artificial Intelligence approaches (Artificial Neural Networks) to a wider range of fields, such as (Psychiatric) Genetics. A further integration of departments will aid. There are further opportunities for the integration of neuronal modeling (as performed in various labs: UvA Human Brain Project and VU Neural Biomarker Toolbox). We will continue these approaches to inform clinical treatment of OCD (TMS and DBS) and Autism/sensory sensitivity.

We have the ambition to integrate research topics across ages (child and adult), especially for typical childhood neuropsychiatric disorders of CIA (OCD, ASD, ADHD) a lifespan perspective is consistent with the early onset and recognizes the protracted course these disorders often take.

Recent developments in genetic methodology–including the availability of large scale genetically informative datasets, mouse and human brain transcriptome datasets, and more–allows the integration of human psychiatric genetics research with animal research. Results from genetic studies are increasingly powerful and consistently point to specific neurotransmitters and/or brain structures involved in disease etiology, as well as neuroinflammatory involvement.

This knowledge can be used to inform mouse studies (e.g., with chemogenetic drivers), which in turn may inform the localization of neural circuits that can be targeted in TMS or DBS approaches.

Our aim is to start leveraging the integration of the large available genetic datasets and translate them into treatment, thus integrating the many specialized CIA groups.

Disorders investigated in CIA show prevalence differences in the sexes, as well as qualitative differences in disease expression. We aim to consequently investigate these sex differences.

For the Top 5 publications, see Appendix 3 – Output (p. 62).

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2.9

Mood, Anxiety, Psychosis, Stress & Sleep

Depression, anxiety, and psychosis constitute the majority of the most prevalent mental disorders, accounting for two-thirds of all affected people. These disorders share several risk factors with, and hence the biological underpinning of less prevalent, but possibly even more burdening– chronic psychiatric disorders like psychotic disorders and post-traumatic stress disorder. Our research program therefore aims for a transdiagnostic understanding of these disorders. We take a life span perspective (from early vulnerability to late disease chronicity) and integrate cross-disorder translational, preclinical and clinical studies to improve treatment and prevention possibilities for these disorders in an evidence-based way.

Strengths: Amsterdam Neuroscience has been a leader in research on depression, anxiety disorders, and psychosis for decades, and recently acquired international leadership in insomnia research. Hitherto, the MAPSS program has been very successful with regard to grant acquisition, and publication- and societal output as generated by outstanding scientists and science teams.

•

• •

Strong collaboration and integration of our scientific research program with Mental Health Care Organizations (MHCO) in the area of Amsterdam (e.g., GGZ inGeest and Arkin). There are collaborative academic workplaces in the areas of depression, anxiety, bipolar disorder, PTSD and psychosis in these MHCOs. There are long-term observational cohorts such as the Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands Sleep Registry that provide new knowledge.

There are many innovative clinical trials within depression, anxiety, and psychosis that focus on topics as childhood trauma, inflammation, suicidality, and sleep. These include large randomized clinical trials aiming to reverse childhood trauma (RESET trial), anti-inflammatory treatment for immunometabolic depression (INFLAMED trial), antidepressant discontinuation, adulthood trauma and trials

Appendix 2

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• •

• •

using rTMS for bipolar depression. These examples illustrate the innovative approach to look beyond ‘classical’ psychiatric diagnoses and to develop approaches that are more transdiagnostic. Single cell proteomics and transcriptomics in animal models (at risk) for psychiatric disorders can be used to find pathways used for hypothesis-driven interventions. Stress and sleep are modifiable risk factors for the onset and a poorer course across mood and anxiety and psychotic disorders that can be disentangled.

The key role of insomnia in the risk, severity, treatment resistance and relapse of mood and anxiety disorders has been demonstrated across our studies using epidemiology, GWAS, experimental EEG and brain imaging, and intervention and prevention RCTs. MAPSS currently runs a worldwide unique study on the value of integrating insomnia intervention in the treatment of anxiety- and stress-related disorders.

MAPSS is involved in many EU projects, such as EarlyCause and A-Tuition, the IMI-project PRISM2 and personal ERC grants.

MAPSS-based researchers lead several multi-center RCTs on antidepressant discontinuation (TEMPO and OPERA) that involve psychiatrists, GPs, pharmacists across five Dutch university medical centers (next to Amsterdam, also Groningen, Nijmegen, Rotterdam and Leiden).

The MARIO project (Mood And Resilience In Offspring) is an Amsterdam-based multicenter study to understand intergenerational transmission of MDD. New collaborations formed over the last two years, with roots in several funded PoC grants– in terms of a large Gravitation application (submitted 2022) on sleep and memory processing led by Eus van Someren, under the name ‘Nightwatch’, and an NWA grant on stress and burn-out by Christiaan Vinkers under the name ‘DESTRESS’ (submitted 2022).

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Weaknesses: • The breadth of activities of individual researchers within MAPSS spans the entire fundamental-translational chain from molecule to patient. This makes it difficult to integrate all research activities.

Yet, this might not be necessary, as small-scale collaborative efforts have proven worthwhile as well.

• The different locations make it challenging to convene regularly.

A future merger of the Departments of Psychiatry at the locations VUmc and AMC could be a facilitator of more integration, with better exchange between departments and specializations within the MAPSS program.

Opportunities: • The multidisciplinary research infrastructure within MAPSS opens up possibilities for national and international collaborations as well as providing opportunities for young talent. EU-based funding is generally well geared for this, and individual research teams have been successful with this in the past. For example, stress researchers from molecule to patient from over all of the Netherlands have united in the STRESS-NL consortium to foster new translational collaborations (www.stress-nl.nl) and have now expanded into Europe with the STRESS-EU database that combines and unites existing data and researchers (www.stressdatabase.eu).

• When it comes to uniting all these research activities within MAPSS, knowledge centers could overcome fragmentation to a certain extent by integrating facilitating research themes centered around depression, anxiety disorders, and psychosis, covering the entire chain from fundamental to translational research; from molecular biology to applied clinical research, with tracking of patient cohorts and clinical trials.

• As the research within MAPSS integrates both fundamental research (animal models, molecular and cellular level), as well as innovative treatments for patients, another opportunity for MAPSS is to be an important regional partner for innovative research activities, building and consolidating network structures with top clinical university

Appendix 2

•

•

hospitals, universities (VU Amsterdam and UvA), and mental health institutions in the Amsterdam/North Holland region. Within large mental health institutions such as Arkin and GGZ inGeest, scientists and clinicians can come together to create innovative scientific patient-related outcomes.

Being active in the full breadth of the scientific field of mood, anxiety, and psychosis, MAPSS can be clearly recognizable to the general public, other Dutch and international scientists, and funding agencies to shape and implement innovative patient-related research.

Another relatively quick win is that several existing large databases can be used to augment the transdiagnostic and translational MAPSS strategy. We have ongoing collaborations for this with e.g., innovative small-scaled companies (e.g., Metabolon) as well as with large pharma companies (Jansen, Boehringer Ingelheim), which can be further exploited for future studies.

Threats: We identified several general and some MAPSS-specific threats: • A major threat for MAPSS and research in general is the increased bureaucracy with respect to preclinical research that depends on animals (CCD, DEC, IvD), and clinical research with respect to patients (extensive legal contracts required for even relatively elementary collaborations, ethical approval, data storage, monitoring, particularly for investigator-initiated studies) which impedes progress related to innovative approaches and team science, and makes research more costly than it should be, and which is not reflected in the project duration and budgets of national and international funding agencies.

• Another major threat for (MAPSS-related) fundamental research is the sentiment of research without animals as articulated by our own minister, as discussed in the media roughly a year ago. In addition, costs of rebuilding and exploitation of a new animal facility are left for individual researchers to pay, as prices have increased >40%, whereas grant money is not sufficient. Lastly, the move to a new building and facility while our current building/facility is partially shut down impact current research lines.

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It is more and more difficult to share some of our MAPSS cohort/study data and biosamples with (academic) partners within and outside of Europe through stricter laws. Contracts for this take more and more energy and time, which limits adequate collaboration.

Financial support for large-scale studies (infrastructure) from funding agencies and within the institute is limited which makes it hard to maintain such useful infrastructures for the future and further build on them.

Overhead rates within the Amsterdam UMC, Vrije Universiteit Amsterdam and UvA are such that it makes it rather unattractive for private entities to collaborate.

Mental Health research is embedded in two research institutes: next to Amsterdam Neuroscience, there is also participation in Amsterdam Public Health. This requires division of attention of clinical researchers involved, but also limits visibility of the entire range of research activities. Establishing integrative research centers around certain strong and central themes (e.g., through an Amsterdam Center of Depression and Anxiety, ADA) could help reduce this threat.

Future Strategy: Priority on: • Integration of fundamental and clinical research.

• Expanding on transdiagnostic approaches.

• Unite for external funding.

• Prevention research for mood, anxiety and psychotic disorders.

For the Top 5 publications, see Appendix 3 – Output (p. 63).

Appendix 2

55

Appendix 3 |

Research input (personnel)

About the metrics To collect the metrics of our research institute we followed the Strategy Evaluation Protocol of the Universities of the Netherlands (UNL, former VSNU), the Netherlands Organization for Scientific Research (NWO), and the Royal Netherlands Academy of Arts and Sciences (KNAW). As for funding categorization for the university medical centers, we used the Netherlands Federation of University Medical Centers (NFU) criteria. In the ratio-conversion from personnel to the full-time-equivalent (FTE) spent on research the default guidelines (HRM-SAP instructed) can be applied: full professor: 0.1-0.2 FTE; strategic professor: 0.1-0.2 FTE; associate professor: 0.2-0.4 FTE; assistant professor: 0.4; investigator: 0.6-0.8 FTE; postdoc: 0.85 FTE; PhD candidate: 0.75 FTE. Amsterdam Neuroscience – Research institute (unique personnel counts) The collective ‘community’ of the Amsterdam Neuroscience research institute over the years ranged from 784-1025 investigators.

This included over 150 Principal Investigators, around 100 faculty members & residents, more than 200 postdocs and research associates, and between 376-479 PhD candidates per year.

Appendix 3

Amsterdam Neuroscience – Research program affiliations Shown here are also the research program affiliations of all personnel as well as the affiliations of PhD candidates only. Double affiliations were allowed, in particular for Principal Investigators.

Table 3.1 Personnel of the Amsterdam Neuroscience research institute over the years 2016-2021, divided per research program. The first table shows all personnel, followed by Phd candidates only.

Affiliations subtotals bi nt bm 89 48 201 114 62 261 118 51 244 bi snn cmm 122 61 252 111 58 225 95 61 216

ctg 50 80 83 ctg 73 73 78

nd 137 182 177 nd 190 179 150

nii 119 149 137 nii 147 142 106

ndis 40 64 74 ndis 84 76 71

cia 100 128 132 cia 145 120 102

map 96 114 109 mapss 98 90 88

PhD candidates only Affiliations subtotals Year Total bi nt bm 2016 416 43 23 97 2017 479 53 25 117 2018 439 40 18 108 Year Total bi snn cmm 2019 453 58 20 145 2020 427 55 19 137 2021 376 47 23 128

ctg 24 37 32 ctg 33 32 31

nd 66 85 82 nd 81 70 60

nii 57 70 67 nii 86 72 52

ndis 19 30 32 ndis 50 37 36

cia 48 60 54 cia 84 70 54

map 46 53 39 mapss 44 35 35

All personnel Year 2016 2017 2018 Year 2019 2020 2021

Total 863 1025 877 Total 888 877 784

* The column Total indicates the total number of affiliations to Amsterdam Neuroscience over the years. It is not equivalent to the sum of the research program affiliation subtotals, since double affiliations to research programs are also taken into account (for example, one Principal Investigator can be affiliated to two different research programs).

56

Appendix 3 |

Research output

Table 3.2.1 Publications of the Amsterdam Neuroscience research institute in the period 2016-2018, divided per research program.

2016 Refereed article Non-Refereed article (1) Books Book chapters PhD theses Conference papers Professional publication (2) Publications aimed at the general public (3) Other research output (4) Total publications With impact > 10 Refereed articles (selected output) With impact > 5 < 10 Refereed articles (selected output)

Total 1242 15 1 10 105 8 35 5 13 1434 Subtotal 143 Subtotal 313

bi 123 2 0 0 10 3 1 0 0 139 bi 4 bi 27

nt 52 1 1 0 6 0 4 0 0 64 nt 7 nt 16

bm 221 2 0 6 42 0 4 1 1 277 bm 25 bm 53

ctg 91 2 0 0 5 0 0 0 0 98 ctg 29 ctg 21

nd 194 3 0 2 14 0 13 0 0 226 nd 22 nd 60

nii 149 0 0 0 7 0 2 2 2 162 nii 16 nii 35

ndis 123 0 0 0 5 1 2 0 1 132 ndis 6 ndis 33

cia 105 2 0 0 13 2 2 1 4 129 cia 5 cia 14

map 184 3 0 2 3 2 7 1 5 207 map 29 map 54

2017 Refereed article Non-Refereed article (1) Books Book chapters PhD theses Conference papers Professional publication (2) Publications aimed at the general public (3) Other research output (4) Total publications With impact > 10 Refereed articles (selected output) With impact > 5 < 10 Refereed articles (selected output)

Total 1264 4 2 15 60 3 27 4 30 1409 Subtotal 130 Subtotal 316

bi 123 0 0 3 11 3 1 0 1 142 bi 2 bi 20

nt 19 0 0 0 1 0 0 0 0 20 nt 3 nt 6

bm 295 0 0 2 17 0 2 0 2 318 bm 27 bm 90

ctg 99 0 0 1 2 0 1 0 3 106 ctg 26 ctg 17

nd 161 1 2 1 5 0 3 0 3 176 nd 17 nd 46

nii 191 0 0 0 5 0 5 0 6 207 nii 16 nii 61

ndis 96 0 0 3 5 0 1 0 9 114 ndis 10 ndis 24

cia 76 1 0 0 9 0 6 2 4 98 cia 9 cia 9

map 204 2 0 5 5 0 8 2 2 228 map 20 map 43

2018 Refereed article Non-Refereed article (1) Books Book chapters PhD theses Conference papers Professional publication (2) Publications aimed at the general public (3) Other research output (4) Total publications With impact > 10 Refereed articles (selected output) With impact > 5 < 10 Refereed articles (selected output)

Total 1239 25 1 6 99 8 24 1 4 1407 Subtotal 160 Subtotal 284

bi 121 2 0 0 10 3 1 0 0 137 bi 2 bi 19

nt 46 2 1 0 6 0 0 0 0 55 nt 2 nt 4

bm 235 0 0 2 41 0 2 1 1 282 bm 30 bm 64

ctg 67 2 0 0 4 0 0 0 0 73 ctg 23 ctg 10

nd 191 4 0 0 11 0 2 0 0 208 nd 28 nd 65

nii 158 4 0 0 6 0 3 0 2 173 nii 21 nii 49

ndis 99 6 0 0 5 1 3 0 1 115 ndis 12 ndis 33

cia 95 4 0 0 13 2 8 0 0 122 cia 13 cia 10

map 227 1 0 4 3 2 5 0 0 242 map 29 map 30

Appendix 3

Amsterdam Neuroscience – Research output Shown here are the metrics for all types of publications. Double affiliations are not shown, i.e., each publication in this table is a unique product, only affiliated with one research program.

57

Table 3.2.2 Publications of the Amsterdam Neuroscience research institute in the period 2019-2021, divided per research program.

2019 Refereed article Non-Refereed article (1) Books Book chapters PhD theses Conference papers Professional publication (2) Publications aimed at the general public (3) Other research output (4) Total publications With impact > 10 Refereed articles (selected output) With impact > 5 < 10 Refereed articles (selected output)

Total 1338 50 0 23 83 13 71 2 11 1591 Subtotal 175 Subtotal 317

bi 157 3 0 4 8 7 1 0 1 181 bi 7 bi 27

snn 33 0 0 0 7 0 2 0 1 43 snn 6 snn 10

cmm 205 9 0 10 9 0 4 0 1 238 cmm 32 cmm 61

ctg 92 2 0 3 4 0 1 0 0 102 ctg 27 ctg 24

nd 234 9 0 2 15 3 15 1 5 284 nd 41 nd 53

nii 190 10 0 0 18 0 7 0 1 226 nii 20 nii 62

ndis 127 5 0 1 6 1 4 0 0 144 ndis 7 ndis 25

cia 101 6 0 1 6 2 17 0 1 134 cia 15 cia 21

mapss 199 6 0 2 10 0 20 1 1 239 mapss 20 mapss 34

2020 Refereed article Non-Refereed article (1) Books Book chapters PhD theses Conference papers Professional publication (2) Publications aimed at the general public (3) Other research output (4) Total publications With impact > 10 Refereed articles (selected output) With impact > 5 < 10) Refereed articles (selected output)

Total 1315 61 0 15 86 9 64 0 24 1574 Subtotal 175 Subtotal 354

bi 125 5 0 1 8 7 3 0 6 155 bi 7 bi 33

snn 31 2 0 2 4 0 1 0 0 40 snn 2 snn 4

cmm 207 10 0 1 14 0 5 0 2 239 cmm 33 cmm 61

ctg 86 6 0 0 7 0 2 0 0 101 ctg 34 ctg 14

nd 238 9 0 3 14 1 10 0 3 278 nd 32 nd 63

nii 184 5 0 2 19 0 3 0 1 214 nii 15 nii 72

ndis 119 7 0 2 8 1 5 0 1 143 ndis 14 ndis 38

cia 95 7 0 2 4 0 15 0 3 126 cia 10 cia 11

mapss 230 10 0 2 8 0 20 0 8 278 mapss 28 mapss 58

2021 Refereed article Non-Refereed article (1) Books Book chapters PhD theses Conference papers Professional publication (2) Publications aimed at the general public (3) Other research output (4) Total publications With impact > 10 Refereed articles (selected output) With impact > 5 < 10) Refereed articles (selected output)

Total 1597 74 2 17 90 26 40 3 48 1897 Subtotal 276 Subtotal 256

bi 187 7 0 4 5 25 0 0 9 237 bi 16 bi 42

snn 41 2 0 0 1 1 0 1 11 57 snn 17 snn 4

cmm 203 11 0 9 23 0 3 0 3 252 cmm 34 cmm 42

ctg 105 9 0 0 1 0 1 0 3 119 ctg 32 ctg 17

nd 258 15 0 1 16 0 5 0 2 297 nd 70 nd 39

nii 229 13 0 0 9 0 3 0 8 262 nii 41 nii 47

ndis 176 7 0 1 12 0 2 1 3 202 ndis 20 ndis 10

cia 132 6 1 1 6 0 10 0 3 159 cia 12 cia 13

mapss 266 4 1 1 17 0 16 1 6 312 mapss 34 mapss 42

Appendix 3

Notes on the distinct categories (according to the latest SEP protocol): 1. Articles in journals that are non-refereed, yet deemed important for the field; 2. Publications aimed at professionals in the public and private sector (professional publications), including patents and annotations (e.g., law); 3. Also known as ‘populariserende artikelen’; 4. Other types of research output (if applicable), such as abstracts, patents, editorships, inaugural lectures, designs and prototypes (e.g., engineering) and media appearances.

58

TOP 5 Publications Brain Imaging • van den Heuvel MP, Sporns O. A cross-disorder connectome landscape of brain dysconnectivity. Nat Rev Neurosci. 2019 Jul;20(7):435-446.

• de Ruiter MB, Reneman L, Kieffer JM, Oldenburg HSA, Schagen SB. Brain White Matter Microstructure as a Risk Factor for Cognitive Decline After Chemotherapy for Breast Cancer. J Clin Oncol. 2021 Dec 10;39(35):3908-3917.

• Schrantee A, Tamminga HG, Bouziane C, Bottelier MA, Bron EE, Mutsaerts HJ, Zwinderman AH, Groote IR, Rombouts SA, Lindauer RJ, Klein S, Niessen WJ, Opmeer BC, Boer F, Lucassen PJ, Andersen SL, Geurts HM, Reneman L. Age-Dependent Effects of Methylphenidate on the Human Dopaminergic System in Young vs Adult Patients With Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2016 Sep 1;73(9):955-62.

• Chard DT, Alahmadi AAS, Audoin B, Charalambous T, Enzinger C, Hulst HE, Rocca MA, Rovira À, Sastre-Garriga J, Schoonheim MM, Tijms B, Tur C, Gandini Wheeler- Kingshott CAM, Wink AM, Ciccarelli O, Barkhof F; MAGNIMS Study Group. Mind the gap: from neurons to networks to outcomes in multiple sclerosis. Nat Rev Neurol. 2021 Mar;17(3):173-184.

• Filippi M, Rocca MA, Ciccarelli O, De Stefano N, Evangelou N, Kappos L, Rovira A, Sastre-Garriga J, Tintorè M, Frederiksen JL, Gasperini C, Palace J, Reich DS, Banwell B, Montalban X, Barkhof F; MAGNIMS Study Group. MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol. 2016 Mar;15(3):292-303.

Appendix 3

Systems & Network Neuroscience • Chen X, Wang F, Fernandez E, Roelfsema PR. Shape perception via a high-channel-count neuroprosthesis in monkey visual cortex.

Science. 2020 Dec 4;370(6521):1191-1196. doi: 10.1126/science. abd7435.

• Dore K, Carrico Z, Alfonso S, Marino M, Koymans K, Kessels HW, Malinow R. PSD-95 protects synapses from beta-amyloid.

Cell Reports 2021. 2021 Jun 1; 35 (9): doi: 10.1016/j. celrep.2021.109194.

• de Kloet SF, Bruinsma B, Terra H, Heistek TS, Passchier EMJ, van den Berg AR, Luchicchi A, Min R, Pattij T, Mansvelder HD. Bi-directional regulation of cognitive control by distinct prefrontal cortical output neurons to thalamus and striatum. Nature Commun. 2021 Mar 31;12(1):1994. doi: 10.1038/s41467-021-22260-7.

• Blanken TF, Benjamins JS, Borsboom D, Vermunt JK, Paquola C, Ramautar J, Dekker K, Stoffers D, Wassing R, Wei Y, van Someren EJW. Insomnia disorder subtypes derived from life history and traits of affect and personality. The Lancet Psychiatry 2019 6(2): 151-163.

• Zimmer TS, David B, Broekaart DWM, Schidlowski M, Ruffolo G, Korotkov A, van der Wel NN, van Rijen PC, Mühlebner A, van Hecke W, Baayen JC, Idema S, François L, van Eyll J, Dedeurwaerdere S, Kessels HW, Surges R, Rüber T, Gorter JA, Mills JD, van Vliet EA, Aronica E. Seizure-mediated iron accumulation and dysregulated iron metabolism after status epilepticus and in temporal lobe epilepsy. Acta Neuropathol. 2021 142 (4), 729-759.

59

Cellular & Molecular Mechanisms • Koopmans F, van Nierop P, Andres-Alonso M, Byrnes A, Cijsouw T, Coba MP, Cornelisse LN, Farrell RJ, Goldschmidt HL, Howrigan DP, Hussain NK, Imig C, de Jong APH, Jung H, Kohansalnodehi M, Kramarz B, Lipstein N, Lovering RC, MacGillavry H, Mariano V, Mi H, Ninov M, Osumi-Sutherland D, Pielot R, Smalla KH, Tang H, Tashman K, Toonen RFG, Verpelli C, Reig-Viader R, Watanabe K, van Weering J, Achsel T, Ashrafi G, Asi N, Brown TC, De Camilli P, Feuermann M, Foulger RE, Gaudet P, Joglekar A, Kanellopoulos A, Malenka R, Nicoll RA, Pulido C, de Juan-Sanz J, Sheng M, Südhof TC, Tilgner HU, Bagni C, Bayés À, Biederer T, Brose N, Chua JJE, Dieterich DC, Gundelfinger ED, Hoogenraad C, Huganir RL, Jahn R, Kaeser PS, Kim E, Kreutz MR, McPherson PS, Neale BM, O’Connor V, Posthuma D, Ryan TA, Sala C, Feng G, Hyman SE, Thomas PD, Smit AB, Verhage M. SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse. Neuron. 2019 Jul 17;103(2):217-234.e4. doi: 10.1016/j. neuron.2019.05.002. Epub 2019 Jun 3.

• Persoon CM, Hoogstraaten RI, Nassal JP, van Weering JRT, Kaeser PS, Toonen RF, Verhage M. The RAB3-RIM Pathway Is Essential for the Release of Neuromodulators. Neuron. 2019 Dec 18;104(6):1065-1080.e12. doi:10.1016/j.neuron.2019.09.015. Epub 2019 Oct 31.

• Rosato M, Stringer S, Gebuis T, Paliukhovich I, Li KW, Posthuma D, Sullivan PF, Smit AB, van Kesteren RE. Combined cellomics and proteomics analysis reveals shared neuronal morphology and molecular pathway phenotypes for multiple schizophrenia risk genes. Mol Psychiatry. 2021 Mar;26(3):784-799. doi:10.1038/s41380019-0436-y. Epub 2019 May 29.

• Wang XL, Kooijman S, Gao Y, Tzeplaeff L, Cosquer B, Milanova I, Wolff SEC, Korpel N, Champy MF, Petit-Demoulière B, Goncalves Da Cruz I, Sorg-Guss T, Rensen PCN, Cassel JC, Kalsbeek A, Boutillier AL, Yi CX. Microglia-specific knock-down of Bmal1 improves memory and protects mice from high fat diet-induced obesity. Mol Psychiatry.

2021 Nov;26(11):6336-6349.

Appendix 3

•

Zimmer TS, David B, Broekaart DWM, Schidlowski M, Ruffolo G, Korotkov A, van der Wel NN, van Rijen PC, Mühlebner A, van Hecke W, Baayen JC, Idema S, François L, van Eyll J, Dedeurwaerdere S, Kessels HW, Surges R, Rüber T, Gorter JA, Mills JD, van Vliet EA, Aronica E. Seizure-mediated iron accumulation and dysregulated iron metabolism after status epilepticus and in temporal lobe epilepsy. Acta Neuropathol. 2021 Oct;142(4):729-759.

Complex Trait Genetics • Ian Fiddes, Gerrald Lodewijk, Meghan Mooring, Colleen M. Bosworth, Adam Ewing, Gary Mantalas, Adam Novak, Anouk van den Bout, Alex Bishara, Jimi L. Rosenkrantz, Ryan Lorig-Roach, Andrew R. Field, Maximilian Haeussler, Lotte Russo, Aparna Bhaduri, Tomasz Nowakowski, Alex Pollen, Max Dougherty, Xander Nuttle, Marie Claude Addor, Simon Zwolinski, Sol Katzman, Arnold Kriegstein, Evan E. Eichler, Sofie R. Salama, Frank M.J. Jacobs #, David Haussler #. Human-specific NOTCH2NL genes affect Notch signaling and cortical neurogenesis. Cell, 173(6):1356-1369. (2018) (#Shared Last/ corresponding authors).

• Wightman DP, Jansen IE, Savage JE, Shadrin AA, Bahrami S, Holland D, Rongve A, Børte S, Winsvold BS, Drange OK, Martinsen AE, Skogholt AH, Willer C, Bråthen G, Bosnes I, Nielsen JB, Fritsche LG, Thomas LF, Pedersen LM, Gabrielsen ME, Johnsen MB, Meisingset TW, Zhou W, Proitsi P, Hodges A, Dobson R, Velayudhan L; 23andMe Research Team, Sealock JM, Davis LK, Pedersen NL, Reynolds CA, Karlsson IK, Magnusson S, Stefansson H, Thordardottir S, Jonsson PV, Snaedal J, Zettergren A, Skoog I, Kern S, Waern M, Zetterberg H, Blennow K, Stordal E, Hveem K, Zwart JA, Athanasiu L, Selnes P, Saltvedt I, Sando SB, Ulstein I, Djurovic S, Fladby T, Aarsland D, Selbæk G, Ripke S, Stefansson K, Andreassen OA, Posthuma D. A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease. Nat Genet. 2021 Sep;53(9):1276-1282.

60

•

•

•

Jansen IE, Savage JE, Watanabe K, Bryois J, Williams DM, Steinberg S, Sealock J, Karlsson IK, Hägg S, Athanasiu L, Voyle N, Proitsi P, Witoelar A, Stringer S, Aarsland D, Almdahl IS, Fred Andersen F, Bergh S, Bettella F, Bjornsson S, Brækhus A, Bråthen G, de Leeuw CA, Desikan RS, Djurovic S, Dumitrescu L, Fladby T, Homan T, Jonsson PV, Kiddle SJ, Rongve KA, Saltvedt I, Sando SB, Selbæk G, Shoai M, Skene N, Snaedal J, Stordal E, Ulstein ID, Wang Y, White LR, Hardy J, Hjerling-Leffler J, Sullivan PF, van der Flier WM, Dobson R, Davis LK, Stefansson H, Stefansson K, Pedersen NL, Stephan Ripke S, Andreassen OA, Posthuma D. Genetic meta-analysis identifies 9 novel loci and functional pathways for Alzheimer’s disease risk.

Nature Genetics. 2019 Mar;51(3):404-413.

Jansen PR, Watanabe K, Stringer S, Skene N, Bryois J, Hammerschlag AR, de Leeuw CA, Benjamins J, Muñoz-Manchado AB, Nagel M, Savage JE, Tiemeier H, White T, The 23andMe Research Team, JY, Hinds DA. Vacic V, Sullivan PF, van der Sluis S, Polderman TJ, Smit AB, Hjerling-Leffler J, Van Someren EJW, Posthuma D. Genome-wide Study of Insomnia (N=1,331,010) Identifies Novel Genetic Loci and Functional Pathways. Nature Genetics. 2019 Mar;51(3):394-4032019.

Werme J, van der Sluis S, Posthuma D, de Leeuw CA. An integrated framework for local genetic correlation analysis. Nat Genet. 2022 Mar;54(3):274-282. doi: 10.1038/s41588-022-01017-y. Epub 2022 Mar 14. PMID: 35288712.

Appendix 3

Neurodegeneration • van Maurik IS, Vos SJ, Bos I, Bouwman FH, Teunissen CE, Scheltens P, Barkhof F, Frolich L, Kornhuber J, Wiltfang J, Maier W, Peters O, Rüther E, Nobili F, Frisoni GB, Spiru L, Freund-Levi Y, Wallin AK, Hampel H, Soininen H, Tsolaki M, Verhey F, Kłoszewska I, Mecocci P, Vellas B, Lovestone S, Galluzzi S, Herukka SK, Santana I, Baldeiras I, de Mendonça A, Silva D, Chetelat G, Egret S, Palmqvist S, Hansson O, Visser PJ, Berkhof J, van der Flier WM; Alzheimer’s Disease Neuroimaging Initiative. Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): a modelling study. Lancet Neurol. 2019 Nov;18(11):1034-1044. doi: 10.1016/ S1474-4422(19)30283-2.

• Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, Cummings J, van der Flier WM. Alzheimer’s disease. Lancet. 2021 Apr 24;397(10284):1577-1590. doi: 10.1016/ S0140-6736(20)32205-4.

• Holewijn RA, Verbaan D, van den Munckhof PM, Bot M, Geurtsen GJ, Dijk JM, Odekerken VJ, Beudel M, de Bie RMA, Schuurman PR. General Anesthesia vs Local Anesthesia in Microelectrode RecordingGuided Deep-Brain Stimulation for Parkinson Disease: The GALAXY Randomized Clinical Trial. JAMA Neurol 2021;78(10):1212-1219.

• Shahmoradian SH, Lewis AJ, Genoud C, Hench J, Moors TE, Navarro PP, Castaño-Díez D, Schweighauser G, Graff-Meyer A, Goldie KN, Sütterlin R, Huisman E, Ingrassia A, Gier Y, Rozemuller AJM, Wang J, Paepe A, Erny J, Staempfli A, Hoernschemeyer J, Großerüschkamp F, Niedieker D, El-Mashtoly SF, Quadri M, Van IJcken WFJ, Bonifati V, Gerwert K, Bohrmann B, Frank S, Britschgi M, Stahlberg H, Van de Berg WDJ, Lauer ME. Nat Neurosci. 2019 Jul;22(7):1099-1109.

• Verschuur CVM, Suwijn SR, Boel JA, Post B, Bloem BR, van Hilten JJ, van Laar T, Tissingh G, Munts AG, Deuschl G, Lang AE, Dijkgraaf MGW, de Haan RJ, de Bie RMA; LEAP Study Group. Randomized Delayed-Start Trial of Levodopa in Parkinson’s Disease. N Eng J Med, 2019.

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Neuroinfection & -Inflammation • van de Beek D, Brouwer MC, Koedel U, Wall EC. Communityacquired bacterial meningitis. Lancet. 2021;398:1171-1183.

• Lees JA, (…) Brouwer MC, Barrett JC, Bentley SD, van de Beek D. Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis. Nat Commun. 2019;10:217.

• Adrichem, ME, Lucke IM (…) de Haan RIJ, van Schaik IN, Eftimov F. Withdrawal of intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy. Brain 2022 Epub.

• Wattjes MP, Ciccarelli O, Reich DS, (…), Rovira À; Magnetic Resonance Imaging in Multiple Sclerosis study group; Consortium of Multiple Sclerosis Centres; North American Imaging in Multiple Sclerosis Cooperative MRI guidelines working group. 2021 MAGNIMSCMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis. Lancet Neurol. 2021;20:653-670.

• van Olst L, Rodriguez-Mogeda C, (…) de Vries HE, Reynolds R, Witte ME. Meningeal inflammation in multiple sclerosis induces phenotypic changes in cortical microglia that differentially associate with neurodegeneration. Acta Neuropathol 2021;141:881-899.

Neurovascular Disorders • Van den Berg, et al. Two-Year Outcome after Endovascular Treatment for Acute Ischemic Stroke. N Engl J Med, 2017.

• LeCouffe, et al. A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke. N Engl J Med, 2021.

• Post et al. Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial. Lancet 2021.

• Sanchez van Kammen et al. Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic. JAMA 2021.

• Coutinho et al. Effect of Endovascular Treatment With Medical Management vs Standard Care on Severe Cerebral Venous Thrombosis: The TO-ACT Trial. JAMA Neurology 2020.

Appendix 3

Compulsivity, Impulsivity & Attention • Shephard, E, Stern, ER, van den Heuvel, OA, Costa, DLC, Batistuzzo, MC, Godoy, PBG, Lopes, AC, Brunoni, AR, Hoexter, MQ, Shavitt, RG, Reddy, YCJ, Lochner, C, Stein, DJ, Simpson, HB & Miguel, EC 2021, ‘Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder’, Molecular Psychiatry, vol. 26, no. 9, pp. 4583-4604.

• Vezoli, J, Vinck, M, Bosman, CA, Bastos, AM, Lewis, CM, Kennedy, H & Fries, P 2021, ‘Brain rhythms define distinct interaction networks with differential dependence on anatomy’, Neuron, vol. 109, no.

23, pp. 3862-3878.e5.

• Graat, I, Mocking, R, Figee, M, Vulink, N, de Koning, P, Ooms, P, Mantione, M, van den Munckhof, P, Schuurman, R & Denys, D 2021, ‘Long-term Outcome of Deep Brain Stimulation of the Ventral Part of the Anterior Limb of the Internal Capsule in a Cohort of 50 Patients With Treatment-Refractory Obsessive-Compulsive Disorder’, Biological psychiatry, vol. 90, no. 10, pp. 714-720.

• Mistarz, N, Andersen, K, Nielsen, ASG, Goudriaan, AE, Michel, TM, Skøt, L, Nielsen, DG & Mellentin, AI 2021, ‘Pharmacological enhancing agents targeting cognition in patients with alcoholinduced neurocognitive disorders: A systematic review’, Neuroscience and biobehavioral reviews, vol. 125, pp. 608-626.

• Weeland, CJ, White, T, Vriend, C, Muetzel, RL, Starreveld, J, Hillegers, MHJ, Tiemeier, H & van den Heuvel, OA 2021, ‘Brain Morphology Associated With Obsessive-Compulsive Symptoms in 2,551 Children From the General Population’, Journal of the American Academy of Child and Adolescent Psychiatry, vol. 60, no.

4, pp. 470-478.

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Mood, Anxiety, Psychosis, Stress & Sleep • Jansen, R., Han, Laura KM, Verhoeven, Josine E, Aberg, Karolina A, van den Oord, Edwin CGJ, Milaneschi, Yuri, Penninx, Brenda WJH. An integrative study of five biological clocks in somatic and mental health. eLife 2021;10:e59479 DOI: 10.7554/eLife.59479.

• Milaneschi Y, Lamers F, Berk M, Penninx BWJH. Depression Heterogeneity and Its Biological Underpinnings: Toward Immunometabolic Depression. Biol Psychiatry. 2020 Sep 1;88(5):369-380. doi: 10.1016/j.biopsych.2020.01.014. Epub 2020 Jan 28. PMID: 32247527.

• Spijker S, Koskinen MK, Riga D. Incubation of depression: ECM assembly and parvalbumin interneurons after stress.

Neurosci Biobehav Rev. 2020 Nov;118:65-79. doi: 10.1016/j. neubiorev.2020.07.015.

• Rao-Ruiz P, Couey JJ, Marcelo IM, Bouwkamp CG, Slump DE, Matos MR, van der Loo RJ, Martins GJ, van den Hout M, van IJcken WF, Costa RM, van den Oever MC, Kushner SA. Engram-specific transcriptome profiling of contextual memory consolidation. Nat Commun. 2019 May 20;10(1):2232. doi: 10.1038/ s41467-019-09960-x.

• Matos MR, Visser E, Kramvis I, van der Loo RJ, Gebuis T, Zalm R, Rao-Ruiz P, Mansvelder HD, Smit AB, van den Oever MC. Memory strength gates the involvement of a CREB-dependent cortical fear engram in remote memory. Nat Commun. 2019 May 24;10(1):2315. doi: 10.1038/s41467-019-10266-1.

Appendix 3

63

Appendix 3 |

Funding

Amsterdam Neuroscience – Research funding Shown here is the grand total and the subtotals per type of funding and per research program of newly acquired funding for the institute.

In this table funding that is unique to each particular research program is shown.

Table 3.3 Funding acquired in the period 2016-2021, divided per research program.

2016 Total €

1st cash flow 2nd cash flow 3rd cash flow 4th cash flow

€ € € €

2017 Total €

1st cash flow 2nd cash flow 3rd cash flow 4th cash flow

€ € € €

2018 Total €

1st cash flow 2nd cash flow 3rd cash flow 4th cash flow

€ € € €

Grand total 41,978,650 € Total 1,450,000 26,347,126 4,041,767 10,139,757

€ € € €

Grand total 49,405,912 € Total 3,546,691 27,725,790 10,514,423 7,619,008

€ € € €

Grand total 46,898,432 € Total 2,080,235 23,627,387 11,118,757 10,072,053

€ € € €

bi 1,877,855 Subtotal bi 100,000 545,167 350,000 882,688 bi 2,221,590 Subtotal bi 520,493 1,534,227 166,870 bi 4,362,519 Subtotal bi 558,729 2,918,855 88,347 796,588

€

€ € € €

nt bm 1,023,783 € 10,039,266 € nt 50,000 546,875 426,908

€ € € €

bm 530,000 8,237,389 511,000 760,877

€ € € €

ctg 2,854,634 €

nd 9,117,952 €

nii 4,537,160 €

ndis 1,233,638 €

cia 4,571,232 €

map 6,773,131

ctg 320,000 2,330,946 203,688 -

nd 200,000 2,432,321 1,766,079 4,719,552

nii 100,000 1,665,719 1,161,000 1,560,441

ndis 50,000 1,183,638 -

cia 50,000 4,421,232 100,000

€ € € €

map 50,000 4,983,839 50,000 1,689,292

€ € € €

€ € € €

€ € € €

€ € € €

€

nt bm 2,267,967 € 13,910,948 €

ctg nd 3,002,456 € 11,926,221 €

nii 5,564,970 €

ndis 5,240,768 €

cia 1,621,742 €

map 3,649,251

€ € € €

nt 249,081 2,000,140 18,746

ctg 55,556 2,433,400 513,500 -

nii 737,684 1,797,643 1,161,511 1,868,132

ndis 940,520 2,947,309 1,337,939 15,000

cia 132,742 1,489,000 -

€ € € €

map 291,738 2,993,127 149,111 215,276

€

nt 2,789,366 €

bm 9,843,349 €

€ € € €

nt 50,000 2,489,366 250,000 -

bm 606,444 4,403,671 3,635,224 1,198,010

€ € € €

€ € € €

bm 545,556 6,411,959 3,475,306 3,478,128

€ € € €

€ € € €

€ € € €

nd 73,325 6,118,984 3,877,056 1,856,855

€ € € €

ctg nd 1,779,000 € 14,404,356 € ctg 909,000 870,000 -

€ € € €

nd 6,415,353 2,058,902 5,930,100

€ € € €

€ € € €

€ € € €

nii 3,570,396 €

ndis 3,411,563 €

cia 2,746,192 €

map 3,991,691

nii 144,618 497,536 914,082 2,014,160

ndis 649,444 636,242 1,992,682 133,195

cia 1,596,619 1,149,573 -

map 71,000 3,760,745 159,946 -

€ € € €

€ € € €

€ € € €

Table 3.3 continues on the next page

Appendix 3

64

NFU definition • 1st cash flow: Shown is internal so-called alliance funding (i.e., 2,475 k€) only; the unconditional internal funding for tenured and other personnel is estimated to be > 50 M€ per year in the period 2016-2021; • 2nd cash flow: conditional funding by intermediary public bodies and agencies (ZonMw, NWO, KNAW and the EU); • 3rd cash flow: private funding by non-profit organizations; • 4th cash flow: private funding from commercial sources: contract-research and clinical trial research funded by biotech and pharma industry and acquired by the Industry Alliance Office (IAO).

2019 Total €

1st cash flow 2nd cash flow 3rd cash flow 4th cash flow

€ € € €

2020 Total €

1st cash flow 2nd cash flow € 3rd cash flow € 4th cash flow € 2021 Total €

1st cash flow 2nd cash flow 3rd cash flow 4th cash flow

Appendix 3

€ € € €

Grand total 76,429,394 € Total 2,475,000 33,050,876 20,617,131 20,286,387

€ € € €

Grand total 55,337,353 € Total 18,449,232 23,774,947 13,113,174

€ € € €

Grand total 75,838,309 € Total 415,921 32,088,842 29,435,643 13,897,903

€ € € €

bi 9,152,036 Subtotal bi 275,000 1,954,261 607,957 6,314,818 bi 4,609,550 Subtotal bi 343,072 3,687,765 578,713 bi 3,168,770 Subtotal bi 1,237,715 746,305 1,184,750

€

snn cmm 5,122,629 € 10,134,647 €

ctg nd nii 6,908,639 € 16,026,305 € 16,822,569 €

ndis 2,833,940 €

cia 4,130,124 €

mapss 5,298,505

€ € € €

snn 275,000 4,552,594 235,598 59,436

ctg 275,000 6,047,038 355,159 231,442

ndis 275,000 1,116,100 521,858 920,982

cia 275,000 3,255,691 584,133 15,300

€ € € €

mapss 275,000 2,452,669 1,773,493 797,344

€

snn 1,614,398 €

cia 1,855,320 €

mapss 7,439,428

€ € € €

snn 446,652 854,828 312,918

€ € € €

€ € € €

cmm 275,000 6,104,601 1,813,915 1,941,132

€ € € €

€ € € €

nd 275,000 2,615,253 8,946,905 4,189,147

€ € € €

nii 275,000 4,952,669 5,778,114 5,816,787

€ € € €

€ € € €

cmm 5,894,371 €

ctg nd 3,842,748 € 18,151,277 €

nii 8,811,804 €

ndis 3,118,457 €

cmm 1,695,704 3,679,355 519,312

ctg 1,287,843 2,213,021 341,884

nii 2,606,456 3,377,525 2,827,823

ndis 259,000 1,620,607 1,238,850

€ € € €

€ € € €

nd 6,431,234 5,020,705 6,699,338

€ € € €

€ € € €

€ € € €

cia 636,706 624,278 594,336

€ € € €

mapss 4,742,565 2,696,863 -

€

snn cmm 7,581,991 € 11,789,080 €

ctg nd 2,566,374 € 22,442,323 €

nii 9,827,684 €

ndis cia 1,595,841 € 13,127,942 €

mapss 3,738,304

€ € € €

snn 855,000 6,691,397 35,594

ctg 1,939,192 528,072 99,110

nii 25,000 5,964,102 3,087,634 750,948

ndis 406,491 1,164,000 25,350

mapss 25,000 3,628,404 13,900 71,000

€ € € €

cmm 365,921 3,745,032 2,844,817 4,833,310

€ € € €

nd € - € € 5,636,753 € € 10,828,814 € € 5,976,756 €

€ € € €

€ € € €

cia 8,676,153 3,530,704 921,085

€ € € €

65

Appendix 4 |

CWTS bibliometric analyses: open access, collaboration profile, science mapping & societal impact

Publication performance To analyze the publication performance of Amsterdam Neuroscience, the Centre for Science and Technology Studies (CWTS) has performed bibliometric analyses using different indicators; publication output (number of publications) citation impact, Open Access, performance in collaboration and societal impact. These indicators provide information on the position of Amsterdam Neuroscience in terms of publication performance, above or below the worldwide average of its own research fields.

Amsterdam Neuroscience researchers publish most of their work in collaboration, and with international partners, papers are well cited and recognized by peers and they publish in high impact journals. The percentage of publications in collaboration with the industry is expected to increase in the next years thanks to the current strategy of the institute. Regarding open access publications, the tendency is an increase in the number of open access publications, as seen in the last three years (2019-2021).

Appendix 4

Figure 4.1 Amsterdam Neuroscience publication performance (2016-2021) Amsterdam Neuroscience Research Institute

P [full] P [fract] P OA PP [OA] PP [collab] PP [industry] PP [int. collab] TCS MCS P [top10%] PP [top10%] MNCS MNJS

Primary Author Yes No 4,557 2,511 1,728 422 3,372 1,974 74% 79% 88% 99% 7% 16% 49% 82% 47,627 51,834 10.45 20.64 774 688 15% 21% 1.31 1.88 1.31 1.68

Overall 7,068 2,151 5,346 76% 92% 10% 61% 99,461 14.07 1,463 16% 1.42 1.38

Research Programs

Research Program bi snn cmm ctg nd nii ndis cia mapss

P [full] 779 190 1,205 474 1,095 967 672 535 1,173

MNCS 1.32 1.59 1.27 1.72 1.40 1.40 1.44 1.45 1.58

MNJS 1.15 1.36 1.35 1.59 1.38 1.46 1.40 1.32 1.48

Figure 4.1.1 Overall publication statistics at the institute level and per Research Program in the six years period.

P[full], total number of publications; P[fract], normalized number of publications, indicating the contribution of the institute to the total number of publications. This value is calculated by dividing each publication by the number of co-author organizations involved; P [OA] and PP [OA], number and proportion of Open Access publications; PP[collab], proportion of publications involving collaborations; PP[industry], proportion of publications involving co-authoring with industry; PP[int collab], proportion of publications involving international co-authors; TCS and MCS, the total and mean citation score; P(top 10%) and PP(top 10%), the number and the proportion of publications in the top 10% of most frequently cited publications, compared with others in the same field and year; MNCS and MNJS, the mean normalized citation score and journal score, normalized for field and publication year.

66

Trend overall statistics P[full]

2016 1,035 340 17% 1.56 1.54

P [full] P [fract] PP [top10%] MNCS MNJS

P[fract]

2017 1,123 370 16% 1.37 1.30

Trend graph by PP[OA]

2016

2017

2018

2019

2020

2021

1,035

1,123

1,146

1,204

1,195

1,365

340

370

369

353

344

374

2018 2019 17% 1,146PP[top10%] 1,204 369 353 1.56 14%MNCS 16% 1.38 1.35 1.54 1.34MNJS 1.32

2020 16% 1,19514% 344 1.3716% 1.38 1.40 1.30 1.391.34

2021 16% 1,36516% 374 1.35 17%1.40 1.47 1.32 1.401.39

Single institution

Trend graph (PP[OA]) 0.8 0.6

17%

0.4 1.47

National

0.2 0.0

1.40

2016-2018

2019-2021

Figure 4.1.2 Trend over the years in the period 2016-2021. Left, publication statistics over the years. Right, trend graph of the proportion of Collaboration profile open access publications in the two periods, 2016-2018 and 2019-2021.

P[fract] 0

2,000

MNCS 4,000

0.50

1.00

International

1.50

1.00

Single institution

0 P[fract] 0

50

100

150

200

MNCS 250

300

350

0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80

National

MNCS MNJS PP[top10%] P[fract] 10% P[full]

1.00

International institution FigureSingle 4.1.2 Trend over the years in the period 2016-2021

0

2,000

4,000

0.50

P[full]

1.00

Profile legend MNCS 50 100 150 200 MNJS P[full] PP[top10%] P[fract] P[full]

250

300

350

0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80 MNJS

1.50 0% 5% 10% 15%

MNJS

PP[top10%]

National

International

10% 0

50

100

150

200

P[full]

250

300

350

0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80 MNJS

0%

5%

10%

15%

20%

PP[top10%]

MNCS MNJS PP[top10%] P[fract] P[full]

Figure 4.1.3 Collaboration Profile. Publication performance in internal, national and international collaboration; number of publications (P), citation and journal scores and proportion of publications with a top 10% number of citations are shown.

Appendix 4

67

0%

5%

Table 4.1 – Co authoring institutions: universities, university medical centers and hospitals Co-authoring institutions Co-authoring institutions Universities, university medical centers and hospitals with a minimum of three publications shared with Amsterdam Neuroscience researchers

(# co-publications >= 2) (# co-publications >= 2) are shown.

MNCS

Short Name

Coun.. # co-pu..

MNCS

Short Name

Coun.. # co-pu..

Univ

Utrecht

NL

207

1.61

Utrecht Univ

NL

207

1.61

Erasmus Univ Rotterdam

NL

183

1.60

Erasmus Univ Rotterdam

NL

183

1.60

Univ

Leiden

NL

158

1.61

Leiden Univ

NL

158

1.61

Univ Groningen

NL

147

1.78

Univ Groningen

NL

147

1.78

Radboud Univ

NL

132

1.49

Univ Radboud

NL

132

1.49

Univ

Maastricht

NL

106

1.52

Maastricht Univ ­

NL

106

1.52

Univ Coll London

GB

46

2.09

­ Univ Coll London

GB

46

2.09

Univ

Harvard

US

42

3.07

Harvard Univ

US

42

3.07

Univ Leuven

Katholieke

BE

34

1.90

Katholieke Univ Leuven

BE

34

1.90

Univ

Lund

SE

27

2.09

Lund Univ

SE

27

2.09

Karolinska Inst

SE

26

3.55

Inst

Karolinska

SE

26

3.55

Univ British Columbia

CA

26

2.29

British Columbia Univ

CA

26

2.29

Univ Melbourne

AU

26

2.73

Univ Melbourne

AU

26

2.73

Coll London King's

GB

24

2.38

King's Coll London

GB

24

2.38

Univ Toronto ­

CA

24

3.33

Univ Toronto

CA

24

3.33

Delft Technol

Univ ­

NL

23

0.90

Delft Univ Technol

NL

23

0.90

Univ Copenhagen

DK

21

2.49

Univ Copenhagen

DK

21

2.49

NL Netherlands Cancer Inst Antoni

van Leeuwenhoek ..

20

1.69

Cancer Inst Antoni van Leeuwenhoek ..

NL Netherlands

20

1.69

Univ Oxford

GB

19

2.47

Univ Oxford

GB

19

2.47

Med Univ Vienna

AT ­

19

2.52

Univ Vienna Med

­ AT

19

2.52

Univ California - San Francisco

US

18

4.94

- Univ California San Francisco

­ US

18

4.94

Univ Gothenburg

SE

18

4.26

­

Univ Gothenburg

SE

18

4.26

Heidelberg

Univ

DE

17

2.41

Univ Basel

CH

17

2.41

Univ

Heidelberg

Basel

Univ

­

17 DE

CH 17

16 NL

2.41

2.41

Univ Twente ­

NL

16

1.30

Univ Calgary

CA

Ludwig-Maximilians Univ München

2.16

2.39

Univ Twente

Univ Calgary

Ludwig-Maximilians Univ München

Univ Oslo

Univ Geneva

DE

NO

CH

16

16

15

15

2.35

2.51

Icahn Sch Med

- Mt Sinai

Univ Queensland

US

AU

14

14

Univ Cambridge

McGill Univ

GB

CA

Massachusetts Gen Hosp

Univ Edinburgh

CA

DE

16

16

Univ Oslo

Univ Geneva

NO

CH

15

15

2.79

2.99

- Mt Sinai Icahn Sch Med

Univ Queensland

US

AU

14

14

14

13

2.82

2.71

Univ Cambridge ­ Univ

McGill

GB

CA

14

13

US

GB

13

13

3.02

2.35

Gen Hosp Massachusetts

Univ Edinburgh

US

GB

13

13

Ghent Univ

Commonwealth Virginia

Univ

BE

US

13

13

1.46

1.60

Univ Lausanne

Johns Hopkins

Univ

CH

US

13

12

2.34

2.77

Univ

Ghent

Univ Virginia Commonwealth

BE

US

13

13

Univ Antwerp

Univ Helsinki

BE

FI

12

12

1.52

3.26

Lausanne

Univ Hopkins

Johns Univ

CH

US

13

12

Univ Zurich

CH

DE

12

12

US

CH

2.29

2.60

4.07

BE

FI

Univ California - San Diego

Univ Bern

12

12

11

Univ Antwerp

Univ Helsinki

CH

DE

¡ 12 ¡ 12

11

1.85

Univ Zurich

Univ Bonn ff

- San Diego Univ California

US

¡ 11

Appendix Univ Bonn 4

1.30

2.16 2.39

2.35 ¡

2.51 2.79 ¡

2.99

2.82 2.71

¡ 3.02

2.35

1.46 ¢ 1.60

¢ 2.34 ¢¡ 2.77 ¡ 1.52 3.26

2.29

¢¡ 2.60 4.07

Table 4.1 continues on the next page

68

¢

Co-authoring institutions

(# co-publications >= 2)

Short Name

Coun.. # co-pu..

MNCS

¢

¢

¢¡

Coun.. # co-pu..

MNCS ¡

Co-authoring institutions

(# co-publications >= 2)

Short Name

Utrecht Univ

NL

207

1.61

Utrecht Univ

NL

207

1.61

Erasmus Univ Rotterdam

NL

183 ¡

1.60

Erasmus Univ Rotterdam

NL

183

1.60 ¡

ff Leiden Univ

NL

158 ¡

1.61 ¢¡

Univ

Leiden

NL

158

1.61 ¡

Univ Groningen

NL

147 ¡

1.78

Groningen

Univ

NL 147

1.78

Radboud Univ

NL

132 ¡

1.49

Radboud Univ

NL

132

1.49

Maastricht Univ

NL

¡ 106

¡ 1.52

ff Univ Maastricht

NL

106

¡ 1.52

Coll London

Univ

GB

¡ 46

2.09

Univ Coll London

GB

46

2.09 ¢¢

Harvard Univ

US

¡ 42

3.07

Univ

Harvard

US

42

£ ¡¤ 3.07

­ Katholieke Univ Leuven

BE

¡ 34

¢ 1.90

Univ Leuven Katholieke

BE

34

1.90

Lund Univ

SE

¡ 27

2.09

Lund Univ ­

SE

27

£ ¢ 2.09

Karolinska Inst

SE

¡ 26

3.55

Karolinska Inst

SE

26

3.55 ¡¤

Univ British Columbia

CA

¡ 26

2.29 ¡

Columbia Univ British

CA

26

£ ¥ 2.29

Univ Melbourne

AU

¡ 26

2.73

Univ Melbourne

AU

26

¦ 2.73

Coll London King's

GB

24

¢ 2.38

Coll London

King's

GB

24

2.38 ¤

Univ Toronto

CA

24

3.33

­ Univ Toronto

CA

24

¤ 3.33

Delft Univ Technol

NL

23

¡ 0.90

Delft Univ Technol

NL

23

0.90 ¦

Copenhagen

Univ

DK

21

2.49 ¡

ff

Univ Copenhagen

DK

21

£ ¤ 2.49

Cancer Inst Antoni van Leeuwenhoek .. NL Netherlands

20

1.69 ¢¡

Cancer

NL Netherlands Inst Antoni van Leeuwenhoek ..

20

£ ££ 1.69

Univ Oxford

GB

19

¡ 2.47

Univ Oxford

GB

19

2.47 ¤¦

Med Univ Vienna

AT

19

2.52 ¡

Univ

Med Vienna

AT

19

£ £ 2.52

California - San Francisco Univ

US

18

4.94

­ - San Francisco Univ California

US

18

£

4.94

Univ Gothenburg

SE

18

4.26

Gothenburg

Univ

SE

18

¦ 4.26

Univ

Heidelberg

DE

17

2.41

Heidelberg Univ

DE

17

¢ 2.41

Basel

Univ

CH

17

2.41 ¢

Univ Basel

CH

17

¤ ¢£ 2.41

Univ Twente

NL

16

¡ 1.30

Univ Twente

NL

16

1.30 ¤

Univ Calgary

CA

16

2.16

Calgary

Univ

CA

16

2.16

Ludwig-Maximilians Univ München

DE

16

2.39 ¢¡

Ludwig-Maximilians Univ München

DE

16

2.39

Univ Oslo

NO

15

2.35

Oslo

Univ

NO

15

¡ 2.35

Univ Geneva

CH

15

¡ 2.51

Univ Geneva

CH

15

£ ¥¤ 2.51

Icahn Sch Med - Mt Sinai

US

14

2.79

Sch

Sinai Icahn Med - Mt

US

14

¤ ¡ 2.79

Queensland

Univ

AU

14

¡ 2.99

­ Univ Queensland

AU

14

2.99 ¥

Cambridge

Univ

GB

14

¢ 2.82

Univ Cambridge

GB

14

£

2.82

Univ

McGill

CA

13

2.71

Univ

McGill

CA

13

£ £¦ 2.71

Gen Hosp

Massachusetts

US

13

3.02

Massachusetts Gen Hosp

US

13

3.02 ¢¢

Univ Edinburgh

GB

13

2.35

Edinburgh

Univ

GB

13

£ £¡ 2.35

Ghent Univ

BE

13

¡ 1.46

Ghent Univ

BE

13

£

1.46

Univ Virginia Commonwealth

US

13

1.60

Virginia Commonwealth Univ

US

13

¡ 1.60

Univ Lausanne

CH

13

¢ 2.34

Univ Lausanne

CH

13

£ ¦¥ 2.34

Hopkins Univ Johns

US

12

2.77

Hopkins ­ Univ Johns

US

12

£ ¤ 2.77

Antwerp

Univ

BE

12

¢ 1.52

Univ Antwerp

BE

12

£ ¦¦ 1.52

Univ Helsinki

FI

12

3.26

Univ Helsinki

FI

12

¡ 3.26

Univ Zurich

CH

12

2.29

Univ Zurich

CH

12

£ £ 2.29

Univ Bonn

DE

12

2.60

Univ Bonn

DE

12

£

2.60

Univ California - San Diego

US

11

4.07

- Univ California San Diego

US

11

¥£ 4.07

Univ Bern

CH

11

1.85

Bern

Univ

CH

11

1.85 ¥

Eberhard Karls Univ Tübingen

DE

11

¡ 2.00

Eberhard Karls Univ Tübingen

DE

11

£ ¤¢ 2.00

RWTH Aachen Univ

DE

11

¡

1.47

Univ

RWTH Aachen

DE

11

¡

1.47

Penn

Univ

US

11

3.93

Penn

Univ

US

11

3.93

Appendix 4

Table 4.1 continues on the next page

69

­

£ ¤

£ ¦¦

¡

£ £

Short Name

Coun.. # co-pu..

£ MNCS

Co-authoring institutions

(# co-publications >= 2)

Co-authoring institutions

(# co-publications >= 2)

Short Name

¦

¤

¢

Coun.. # co-pu..

¡¡ MNCS

Utrecht Univ

NL

207

¥£ 1.61

Univ

Utrecht

NL

207

¤ 1.61

Univ Rotterdam Erasmus

NL

183

1.60 ¥

Univ Rotterdam Erasmus

NL

183

¤¤ 1.60

Univ

Leiden

NL

158

£ ¤¢ 1.61

Univ

Leiden

NL

158

¤¡ 1.61

Univ Groningen

NL

147

¡

1.78

Univ Groningen

NL

147

¥ 1.78

Radboud Univ

NL

132

1.49

Univ

Radboud

NL

132

£ 1.49

Univ Maastricht

NL

106

1.52 £

­

Maastricht Univ

NL

106

¥ 1.52

London Univ Coll

GB

46

2.09 ¡¤

ff Univ Coll London

GB

46

¢ 2.09

Univ

Harvard

US

42

¦ ¤ 3.07

Harvard Univ

US

42

£¥ 3.07

­ Katholieke Univ Leuven

BE

34

£ ¢ 1.90

Katholieke Univ Leuven

BE

34

¦¢ 1.90

Lund Univ

SE

27

£ ¡ 2.09

Lund Univ

SE

27

¡£ 2.09

Inst

Karolinska

SE

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King's London

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Univ Oslo ­

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Univ Antwerp

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Univ Zurich

Univ Bonn

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Univ Tübingen Eberhard Karls

Appendix 4

Aachen Univ RWTH

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70

­ ff

Table 4.2 – Co authoring institutions: companies

Companies with at least one publication shared with Amsterdam Neuroscience researchers are shown.

­

­

­

­

­ ff

­

­ ff

Appendix 4

­

71

Societal Impact of Amsterdam Neuroscience To monitor how Amsterdam Neuroscience research is relevant to society, CWTS has performed so-called area-based connectedness (ABC) analyses. This method assesses the potential contribution of different research areas to society. To do that they first create a so-called term map with the keywords most used in Amsterdam Neuroscience publications, which shows the research landscape of Amsterdam Neuroscience, i.e., the different research areas of Amsterdam Neuroscience publications. Then, they assess how often those terms are being used in different societal areas to estimate the relation between the research performed at the Institute and society.

Figure 4.2 Societal heatmaps of Amsterdam Neuroscience research (landscape) The next series of figures show the potential societal impact of Amsterdam Neuroscience. The heatmaps are based on a term map analysis of all publications from 2016-2021, the colors indicate the relative uptake of these terms in policy documents, clinical guidelines, the media, citations in patents, or the relative number of co-authors in industry and non-academic hospitals. The three or four most prominent research programs per figure are indicated by ovals.

The following figures show the potential societal impact of Amsterdam Neuroscience regarding several aspects: policy, clinical guidelines, industry, media, patents and collaboration with non-academic hospitals.

Figure 4.2.1 Amsterdam Neuroscience research landscape. This term network provides a keyword based structure of Amsterdam Neuroscience research output and indicates the main research topics of the institute. The colors indicate clusters of terms that co-occur in publications.

Appendix 4

72

CTG MAPSS CIA

ND

CMM

NII NDIS

BI

Figure 4.2.2 Potential relevance to policy. The colors indicate the relative uptake of the terms in policy documents (red, higher frequency; blue, lower frequency) compared to the average of a reference database (=1). A value above 1 means that a keyword is more cited in policy documents than average.

Appendix 4

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CTG MAPSS CIA

ND

CMM

NII NDIS

BI

Figure 4.2.3 Potential relevance to clinical guidelines. The colors indicate the relative uptake of the terms in clinical guidelines (red, higher frequency; blue, lower frequency) compared to the average of a reference database (=1). A value above 1 means that a keyword is more cited in clinical guidelines than average.

Appendix 4

74

MAPSS CIA

CTG

ND

CMM

NII NDIS

BI

Figure 4.2.4 Estimated appearance in the media. The colors indicate the relative uptake of the terms in the media (red, higher frequency; blue, lower frequency) compared to the average of a reference database (=1). A value above 1 means that a keyword is more cited in the media than average.

Appendix 4

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MAPSS CIA

CTG

ND

CMM

NII NDIS

BI

Figure 4.2.5 Potential relevance to industry. The colors indicate the relative number of industrial co-authors (red, higher number; blue, lower number of industry co-authors) compared to the average of a reference database (=1). A value above 1 means that the keywords appear more in publications with industrial partners.

Appendix 4

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MAPSS CIA

CTG

ND

CMM

NII NDIS

BI

Figure 4.2.6 Estimated citations in patents. The colors indicate the relative uptake of the terms in patent citations (red, higher frequency; blue, lower frequency) compared to the average of a reference database (=1). A value above 1 means that the keywords appear more in patent citations.

Appendix 4

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CTG MAPSS CIA

ND

CMM

NII NDIS

BI

Figure 4.2.7 Potential relevance to hospitals. The colors indicate the relative number of non-academic hospitals as co-authors, suggesting their interest in collaboration (red, higher number; blue, lower number of hospital co-authors) compared to the average of a reference database (=1). A value above 1 means that the keywords appear more in publications with hospitals.

Appendix 4

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Appendix 5 | Addendum Amsterdam Neuroscience co-author analyses These analyses, made by the CWTS in Leiden, show the internal cooperation within the Amsterdam Neuroscience research institute and map out the connections between the research programs of the institute. Three analyses were made: a network analysis to map out cooperation, a network of Principal Investigators from the nine different research programs and a keyword analysis to visualize the research focus.

Explanation and background of the network analyses Based on the metadata of publications from sources such as Web of Science, Scopus or Pubmed, networks can be visualized on the basis of co-author relationships. For these analyses, the publication set of Amsterdam Neuroscience over the years 2016-2021 was used. For this purpose, the institute has provided an overview of publications with corresponding digital object identifiers (doi’s). Due to a reorganization of the research programs in 2019, which lead to the disappearance of two programs and the creation of two new ones, two different datasets were provided, one corresponding to publications from 2016-2018 and a second one corresponding to 2019-2021. Network analyses were performed separately for both periods. A CWTS enhanced version of the Web of Science core collection has been used in this project. This bibliographic data source provides a clear view of the international scholarly communication, though it does not capture all scholarly output.

Appendix 5

In the visualizations, the sphere size is a measure of the number of publications of an author compared to other authors. The lines between the spheres reflect co-author relationships within the analysis period. The colors reflect groups of authors who often publish together and are a proxy for research groups.

An interactive presentation of these networks can be found online in the URLs located below the figures, which link to the VOSviewer software. The left side panel of VOSviewer allows for different possibilities in visualizing the data, such as adjusting the sphere size, the amounts of links between spheres or the colors of the clusters.

To correct for author name variants, a thesaurus was constructed. Next, a number of choices have to be made in the visualization of the network, such as the threshold for the number of publications per author to appear in the network and whether or not to include publications with large author lists in the network. The visualizations have limitations.

For example, not all spheres in the network can be displayed by name. This means that in the network visualizations sometimes names that might have been expected are not shown.

In the various visualizations over time, an attempt was made to show as many different researchers as possible.

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2016-2018

Interactive map in VOSviewer 2016-2018

2019-2021

Interactive map in VOSviewer 2019-2021

Figure 5.1 Amsterdam Neuroscience network in the two periods 2016-2018 and 2019-2021. Network of Amsterdam Neuroscience researchers and how they collaborate.

The network shows authors from Amsterdam Neuroscience, but also includes the most frequent co-authors from outside the institute (authors with minimal 15 publications are shown, publications with more than 50 authors excluded, color coding is cluster based and arbitrary).

Appendix 5

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2016-2018

2019-2021

BI SNN CMM CTG ND NII NDIS CIA MAPSS

Brain Imaging | Systems & Network Neuroscience | Cellular & Molecular Mechanisms | Complex Trait Genetics | Neurodegeneration | Neuroinfection & Inflamation | Neurovascular Disorders | Compulsivity, Impulsivity & Attention | Mood, Anxiety, Psychosis, Stress & Sleep

Interactive map in VOSviewer 2016-2018

Interactive map in VOSviewer 2019-2021

Figure 5.2 Amsterdam Neuroscience Principal Investigators network in the two periods 2016-2018 and 2019-2021. The network plot shows that 97,5% of all Principal Investigators of Amsterdam Neuroscience have substantial co-authorships and that there are many co-authors affiliated with different research programs of the institute. The color coding is based on the classification by research program.

Appendix 5

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Interactive map in VOSviewer 2016-2021 Figure 5.3 Amsterdam Neuroscience keywords network for the whole period 2016-2021. This network gives an impression of the most important research topics within the institute.

Appendix 5

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Appendix 6 | Use cases Amsterdam Neuroscience 2016-2021 1.

Consortia • ABOARD • Brainscapes • Brainmodel • ProPark • ENIGMA • Don’t be late

2.

Research projects • Genetics & epilepsy • I-pace • Brain networks on cognition • Novel dimensionality-reduction to predictive of behavior • Visual cortical prosthesis to restore vision • Imagine genetics • Deep Brain Stimulation in Obsessive Compulsive Disorders • Causality studies in substance use • EEG controlled triage in the ambulance for acute ischemic stroke

3.

Research facilities & support • SynGO • ADORE • Hersenonderzoek.nl • MeMo lab

Appendix 6

4.

Cohorts • NESDA cohort • The Netherlands sleep registry • MS cohort • MeninGene cohort • Amsterdam dementia cohort • COVID-19 biobank • 100-plus study • INCbase

5.

Clinical trials • MR clean study • TETRO trial • Blood test for Alzheimers’ disease • Vanishing White Matter Trial

6.

Companies • Macrobian Biotech • NBT Analytics

7.

Communication & society • Amsterdam Neuroscience MAGAZINE • Communication channnels • Online & hybrid events • Books

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1.

Consortia

Consortia help us to stay connected, broaden our network and showcase our research and expertise internationally, to show what we can do when we work together. Researchers from the Amsterdam Neuroscience research institute have been participating in or leading many consortia that include partners from all over the world and in various fields.

ABOARD: Stopping Alzheimer’s together before it starts ABOARD, in full ‘A personalized Medicine Approach for Alzheimer’s Disease’, is a large-scale research project carried out by a national, multidisciplinary consortium. This consortium of more than thirty partners works towards a future with personalized diagnoses, prediction and prevention of AD. Personalized medicine ABOARD’s mission is to make a start with personalized medicine for AD by making all the preparations for effective patient-directed diagnosis, prediction, and prevention.

The goal is to pave the way for tailor-made treatment for Alzheimer’s so better strategies for diagnosing, predicting, and preventing Alzheimer’s can be created. In this way, patients and relatives feel supported and more in control.

Collaborations The ABOARD consortium launched in April 2021. The project brings over thirty partners together, among which five Dutch Alzheimer centers, including the Alzheimer Center Amsterdam, a center of expertise of Amsterdam Appendix 6

Neuroscience, and patients’ organizations like Alzheimer Nederland. Public and private parties across the entire knowledge chain work together in this consortium, from universities to care and knowledge institutions, civil society organizations and businesses. An overview of all involved partners and more information about ABOARD can be found on the project website.

Support by the Dutch government ABOARD is the first research project to be launched as part of the National Dementia Strategy 2021-2030 of the Ministry of Health, Welfare and Sport. It also contributes to the Knowledge and Innovation Agenda 2020-2023 of Health~Holland, in which public and private partners collaborate to improve the quality of life of people (Mission IV).

BRAINSCAPES: A roadmap from neurogenetics to neurobiology The Brainscapes consortium aims to map the biological mechanisms underlying multiple brain disorders. Recent genetic discovery studies have provided more insight into the genes involved in brain disorders. The next step is to use this knowledge for gaining mechanistic disease insight, although this is an extremely complex task to fulfill due to the involvement of many different research fields that all speak their own language. The research group that is coordinated by Professor Danielle Posthuma will develop novel analytic and experimental tools to study the functional consequences of risk genes on the function of specific cells, their circuits and functional output. These insights into the molecular and cellular basis of complex brain disorders can be used to design novel treatments.

Long term funding On August 30, 2019, the Dutch Research Council (NWO) announced that the Brainscapes consortium was awarded a Gravitation grant to the value of €20 million. The Ministry of Education, Culture and Science provides

84

this type of funding for long-term (10-year) multidisciplinary projects, with the ambition to stimulate world-leading Dutch research that could potentially lead to international breakthroughs.

Research findings In May 2020, the Brainscapes consortium published their first review in the journal Biological Psychiatry. In their paper, Emil Uffelmann and Danielle Posthuma reviewed resources and methods used by geneticists to point to the most-likely biological mechanism underlying a psychiatric condition. Their review includes a detailed overview of tools and resources that aid in interpreting GWAS results.

In October 2021, two co-leaders of Brainscapes, Amsterdam Neuroscience Professor Huib Mansvelder and Professor Boudewijn Lelieveldt from Leiden University Medical Centrum, have contributed to successfully map the different cell types of the motor cortex and other cortical areas in the brain. They take part in a major NIH-funded international study called the BRAIN initiative Cell Census Network, worth more than 4 billion dollars, of which the goal is to map all brain cells of several species including humans. Nature has devoted a special 17-paper issue to describe the first BICCN’s findings covering the motor cortex, including two papers to which Mansvelder and Lelieveldt contributed with their specific functional and informatics expertise, respectively.

Appendix 6

BRAINMODEL: Precision medicine for brain disorders A team of researchers from six Dutch knowledge institutions (including Vrije Universiteit Amsterdam as coordinator) is introducing new research methods to improve treatment for developmental disorders of the brain. The scientific team will work together with societal partners, clinical associations, and companies in the BRAINMODEL consortium and will implement new stem cell-based methods to improve diagnostics and therapy decisions and to develop new therapies.

ZonMw has allocated a grant of €4 million for this work.

BRAINMODEL project. The main objective of this project is to use iPSC-based analyses to detect abnormal cellular functions in material from patients with brain disorders and link these to clinical outcome measures, such as EEG biomarkers. The N=You center combines EEG analyses with genetic and cellular diagnostics. Linking the genetic material to the EEG results can show the effect on information processing and brain development. The use of stem cell cultures opens a new framework for rational, mechanism-based treatment. The N=You center of Amsterdam UMC collaborates with the Radboudumc expert center for rare genetic disorders in Nijmegen.

Living nerve cells in a dish BRAINMODEL’s new approach is based on patient-derived cells with which networks of living nerve cells are produced in a culture dish.

These closely resemble the neural networks in our brains. This is known as ‘pluripotent stem cell technology (iPSC)’ and offers new opportunities in terms of understanding human diseases and finding personalized treatments. iPSC-based strategies are particularly promising for understanding developmental brain disorders because they overcome the problem of not having access to brain tissue to study underlying causes.

N=You center N=You neurodevelopmental precision center, led by Professor Hilgo Bruining, is part of the

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ProPark: Project Profiling Parkinson’s Disease ProPark stands for ‘Profiling Parkinson’s Disease’ and is a collaboration of Parkinson’s disease (PD) researchers over a timeframe of five years starting in 2019. Wilma van de Berg, Senior Associate Professor at the Department of Anatomy & Neurosciences at Amsterdam UMC, is involved in this national consortium.

The overall aim of ProPark is to (1) evaluate the role of existing and novel quantitative biomarkers in understanding the heterogeneity in the Parkinson’s phenotype (i.e., rate of progression, motor dysfunction, and cognitive and neuropsychiatric impairment), predicting treatment response, and assess the occurrence of adverse drug reactions over a three-year period; (2) develop a ProPark biobank containing comprehensive and uniformly acquired longitudinal clinical data, imaging data and biological samples for identification and validation of biomarker panels and data-driven approaches to unravel heterogeneity in PD phenotype. Together with LUMC, ErasmusMC, and nearby community hospitals, Amsterdam UMC recruits 1,250 PD patients in two years and follows them up for at least three years.

Appendix 6

ENIGMA Researchers from all over the world, including several Principal Investigators and staff of Amsterdam Neuroscience, are part of the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium. This global consortium of over 1,400 scientists across 43 countries, studies the human brain in health and disease and brings together researchers from the fields of imaging genomics, neurology and psychiatry.

Collaboration for more than a decade In March 2020, a review in Translational Psychiatry was published on the last decade of large-scale studies of the brain by the ENIGMA consortium and in parallel an update on the genetic basis of corticavl structures studied by ENIGMA was published in Science.

ENIGMA on obsessive-compulsive disorders This worldwide imaging consortium is led from Amsterdam, by Professor Odile van den Heuvel, and appears very strong in connecting OCD imaging experts from the whole world to perform well powered metaand mega-analyses. In this consortium, the first steps are made towards the link with genetics. The ENIGMA-OCD consortium now also develops task-based functional MRI metaand mega-analyses.

A group of MS researchers and supportive organizations, known as the ‘Don’t be late’ consortium, has been awarded €1.6 million in funding within the second round of the Dutch Research Agenda (NWA), called Research along Routes by Consortia (NWA-ORC). Their mission is to postpone cognitive decline and prevent unemployment in patients with MS. Cognitive decline is one of the symptoms of MS, affecting up to 70% of the (young) people with MS. When patients with MS report cognitive and work-related problems, these problems are often too advanced for treatment.

Intervening sooner rather than later is crucial, which requires a paradigm shift from symptom management to prevention of symptoms. By focusing on prevention, quality of life and participation in society will be enhanced.

ENIGMA Parkinson’s disease Another ENIGMA group led by an Amsterdam Neuroscience researcher is the worldwide working group on Parkinson’s disease led

by Professor Ysbrand van der Werf. This Parkinson’s project consists of three major studies, including: A) A meta-analysis of volumetric changes in Parkinsonian versus healthy brains, using previously developed FreeSurfer protocols; B) A shape meta-analysis of deep gray matter structures; and C) A meta-analysis of white matter differences, based on the ENIGMA-DTI protocol.

Don’t be late consortium on multiple sclerosis

‘Don’t be late’ is led by neuroscientist Hanneke Hulst, who has worked for the MS Center Amsterdam of Amsterdam UMC for many years.

Researchers from different organizations throughout The Netherlands are involved, such as: Vrije Universiteit Amsterdam, 86

Leiden University, Sanofi Genzyme, Merck bv, Personal Fitness Nederland, MS vereniging Nederland, St. Anthonius Hospital Nieuwegein, Hospital Rivierenland Tiel, Medisch Spectrum Twente Enschede, Stichting MS Research, Nationaal MS Fonds, Nederlandse Vereniging voor Verzekeringsgeneeskunde, Nederlandse Vereniging voor Arbeids- en bedrijfsgeneeskunde, MSweb.nl.

2.

Research Projects

Our research projects are directed to fulfill the Amsterdam Neuroscience mission (to broaden the fundamental knowledge of the nervous system and to translate this into effective therapies and treatments for the individual patient with a neurological disorder) with an interdisciplinary approach.

Physiological and genetic fingerprints of seizure freedom after epilepsy surgery The current leading treatment for intractable drug-resistant epilepsy is surgical resection of the responsible brain tissue, but seizures remain in 30% of patients after surgery.

Amsterdam Neuroscience researchers Ilse van Straaten, Natalia Goriounova and Linda Douw are looking for ways to better predict the surgery outcome of epilepsy patients.

This project’s long-term goal is to improve the selection of epilepsy patients for surgery candidates and to improve neurosurgical resection plans.

First, these women in science aimed to identify morphological and neurophysiological biomarkers related to seizure freedom after surgery. Training random forest algorithms on presurgical neurophysiological and MRI data showed that machine learning outperformed logistic regression models. Neuronal electrophysiological and morphological features in the resected non-pathological tissue from a limited number of eligible patients (n=14) revealed no differences between seizure free and non-seizure free patients after surgery. The next step is to build an individual prediction tool based on the data to better inform patients on the surgery outcome and therefore to better tailor patient selection.

Appendix 6

Improving Prognosis by using innovative methods to diagnose Causes of Encephalitis (I-PACE) Meningitis can be caused by bacteria, viruses, or other microorganisms, but also excessive activation of the immune system as seen in auto-immune diseases can be identified as the cause. During the last two decades, the spectrum of bacteria causing meningitis during childhood has substantially changed due to the introduction of vaccinations. Furthermore, diagnostic methods have improved and new viruses were discovered that can cause meningitis. Because of these changes, we are currently able to identify the cause of meningitis in the majority of cases. However, in a substantial number of the patients (~30%) the cause is still unknown.

I-PACE study Amsterdam Neuroscience Principal Investigators Matthijs Brouwer and Diederik van de Beek are involved in the I-PACE study whose primary aim is to determine the causes of meningitis and/or encephalitis. Furthermore, the study aims to evaluate the clinical signs and symptoms and cerebrospinal fluid (CSF) laboratory characteristics of patients with a diagnosis of meningitis and/or encephalitis.

All patients in whom meningitis is suspected who receive a lumbar puncture can be 87

included. After informed consent is given by the patient or his/her representative/ caregivers the leftover CSF derived from the diagnostic puncture will be stored and later tested for an extensive panel of known and unknown viruses. Furthermore, additional material (feces, blood and throat swab) will be stored and later tested for the presence of (new) viruses. Clinical data will be stored in an online clinical database.

From single neurons to brain networks of cognition Temporal lobe epilepsy (TLE) patients are at risk of memory deficits, which have been linked to functional network disturbances, particularly of integration of the default mode network (DMN). However, the cellular substrates of functional network integration are unknown.

Researchers Natalia Goriounova (Vrije Universiteit Amsterdam) and Linda Douw (Amsterdam UMC) leverage a unique cross-scale dataset of drug-resistant TLE patients (n = 31), who underwent pseudo resting-state functional magnetic resonance imaging (fMRI), resting-state magnetoencephalography (MEG) and/or neuropsychological testing before neurosurgery. fMRI and MEG underwent atlas-based connectivity analyses.

Functional network centrality of the lateral middle temporal gyrus, part of the DMN, was used as a measure of local network integration. Subsequently, non-pathological cortical tissue from this region was used Appendix 6

for single cell morphological and electrophysiological patch-clamp analysis, assessing integration in terms of total dendritic length and action potential rise speed. As hypothesized, greater network centrality is related to better memory performance.

Moreover, greater network centrality correlated with more integrative properties at the cellular level across patients. Goriounova and Douw concluded that individual differences in cognitively relevant functional network integration of a DMN region are mirrored by differences in cellular integrative properties of this region in TLE patients.

teams used a novel dimensionality reduction method on both optical (n = 5 rats) and electrophysiological data (n = 3 rats) recorded from simultaneously rat medial PFC ensembles to predict the animal’s performance during an action control task. They decoded the animal’s behavior from the ensemble activity, which enabled them to predict errors in the task performance up to 1s before the animal failed to engage in the task successfully. This project allowed these researchers to forge a collaboration between AMC and VU Amsterdam researchers and provides a novel data-analysis platform that can be used in both labs.

A novel dimensionality-reduction method for optical and electrophysiological data to identify neural population code predictive of behavior

Shape perception via a high-channel-count neuroprosthesis in monkey visual cortex

A collaboration between researchers from Vrije Universiteit Amsterdam and Amsterdam UMC resulted in a study to find out which intricate neural mechanisms drive the cognitive process involved in attention.

Aishwarya Parthasarathy, Christiaan de Kock, and Ingo Willuhn join forces in this project.

Attention refers to the process of allocating sufficient cognitive resources to complete a task successfully. While the overall role of the prefrontal cortex (PFC) in attention is well established through fMRI and lesion studies, knowledge about the intricate neural mechanisms driving specific cognitive processes involved in attention (engagement) is lacking.

Parthasarathy, de Kock and Willuhn and their

Blindness affects 40 million people across the world. One day, a neuroprosthesis could restore functional vision in the blind. Pieter Roelfsema of Vrije Universiteit Amsterdam and his team implanted a 1024-channel prosthesis in areas V1 and V4 of the visual cortex of monkeys and used electrical stimulation to elicit percepts of dots of light (called phosphenes) on hundreds of electrodes, the locations of which matched the receptive fields of the stimulated neurons.

Activity in area V4 predicted phosphene percepts that were elicited in V1. Roelfsema simultaneously stimulated multiple electrodes to impose visible patterns composed of several phosphenes. The monkeys immediately recognized them as simple shapes, motions, or letters. These results demonstrate the potential of electrical stimulation to restore functional, life-enhancing vision in the blind.

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Imaging Genetics

Causality studies in substance use

Several initiatives for imaging genetics substantiate the target expressed in the midterm evaluation of Amsterdam Neuroscience institute. Two and a half years ago, Shu Liu started his PhD project in imaging genetics supervised by Amsterdam Neuroscience Principal Investigators Guido van Wingen (Compulsivity, Impulsivity & Attention) and Karin Verweij (Complex Trait Genetics). He combines information from imaging measures (sMRI and fMRI) with genome-wide genetic data to investigate the underlying biological mechanisms of a broad range of mental health outcomes (including psychiatric disorders and substance use phenotypes). This PhD project is funded by a personal fellowship from a Chinese governmental institute.

A new line of research is to use a genetic instrumental variable approach (Mendelian Randomization) to investigate causal associations between traits. Over the last years, this method has been successfully applied to investigate (bidirectional) causal associations of substance use with brain volumes, insomnia, ADHD, and loneliness, resulting in four publications. In 2021, a systematic review was performed by Amsterdam UMC researchers Jorien Treur and Karin Verweij, summarizing the findings of all existing Mendelian Randomization studies on the association between substance use and mental health outcomes.

Deep Brain Stimulation in Obsessive Compulsive Disorders A retrospective study showed that individual differences in white matter anatomy could explain differences in deep brain stimulation (DBS) response in patients with OCD (Liebrand et al., 2019). This has resulted in a change in the DBS targeting procedure, which is now done using individual white matter tractography. The initial evaluation of this procedure showed that it did not result in better treatment response, but it had a large effect on reducing side-effects (Graat et al., submitted). This work fits the general aim of Amsterdam Neuroscience to translate neuroscientific knowledge into clinical practice.

Appendix 6

EEG controlled triage in the ambulance for acute ischemic stroke

neurologist Jonathan Coutinho and technical physician Wouter Potters examine whether electroencephalography (EEG) is suitable for this purpose.

ELECTRA-STROKE is an ongoing diagnostic pilot study that consists of four phases that started in October 2018. In phases 1 and 2, technical and logistical feasibility of performing dry electrode EEGs were tested in the outpatient clinic and Neurology ward of the Amsterdam UMC. In phase 3, EEGs were performed on 250 patients wo were presented to the emergency room of Amsterdam UMC with a suspected stroke. In phase 4 of the study, ambulance paramedics will perform EEGs in a pre-hospital setting in 222 suspected stroke patients. The primary goal of the study is to develop an EEG algorithm for prehospital LVO-detection. Phase 4 started in August 2020; the first patient was enrolled on August 25, 2020.

Endovascular stroke treatment (EVT) is highly effective but can be performed in selected hospitals only. Pre-hospital identification of stroke patients who are eligible for this therapy would allow paramedics to bring patients straight to the right hospital, thus saving valuable time. In ELECTRA-STROKE

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3.

Research facilities & support

Amsterdam Neuroscience has scientific knowledge, infrastructure, and state-of-the-art facilities to perform preclinical and clinical studies, often working toward end-to-end research solutions and always in a multidisciplinary setting. These research facilities or support centers help to accelerate scientific developments and share knowledge with research colleagues.

Syngo: Defining the synapse The Synaptic Gene Ontologies (SynGO) consortium is coordinated by the Center for Neurogenomics and Cognitive Research (CNCR) (Frank Koopmans, Loek van der Kallen, Guus Smit, and Matthijs Verhage) and brings together leading experts in synapse biology on a worldwide level to establish a knowledgebase of the synapse. The CNCR works together with the Stanley Center at the Broad institute in Cambridge, MA, USA on this international gene annotation effort for preand postsynaptic genes. SynGO builds on prior initiatives generated in European consortia on synapse research EU-Synapse, EuroSpin, and SynSys. The aim of SynGO is to provide evidence-based annotation of synaptic gene products as a universal reference for synapse research and to facilitate enrichment studies in large scale -omics data.

In previous years, the consortium has built a new ontology for the synapse and annotated more than 1,000 synaptic proteins based exclusively on published experimental evidence. Since launching the SynGO portal and publication of the first analyses by the consortium in Neuron in 2019, the knowledgebase and portal have served many scientists worldwide, with many Appendix 6

daily users of the portal and the Neuron paper being in the top 5% of most cited papers in the field (March 1, 2022: 195 citations in <2 years; Google Scholar).

Amsterdam UMC, the dream and ambition is to find a solution for cancer and brain diseases.

Why do cells in one person grow explosively but in the other person die, as happens in diseases such as multiple scleroses?

ADORE: Amsterdam Oncology and Neuroscience Research

Location The city of Amsterdam is providing a subsidy of more than 600.000 euros for the ADORE Research and Diagnostic Center to be built at Amsterdam UMC. The start of the new building of this Research and Diagnostics center will be in spring 2022. ADORE will be a center with offices and laboratories between VU Amsterdam campus and Amsterdam UMC. It will be the biggest neuro-onco campus in the world, where researchers, doctors and patients can come together. The arrival of ADORE attracts companies from the Netherlands and abroad and strengthens the Life Sciences and Health sector in the region.

ADORE, short for Amsterdam Oncology and Neuroscience research, is a new form of medical-scientific research.

Their goal is to develop and apply new medicine and treatments for patients with cancer and brain diseases by doing research based on the parallels between oncology and neurology.

Ambitions Cross-fertilization between cancer researchers and neuroscientists should lead to new diagnostics and therapies. There are differences between these diseases, but also similarities. Therefore, Amsterdam UMC decided to combine cancer and neuroscience research within ADORE to boost breakthroughs. Professor Philip Scheltens, director of Alzheimer Center Amsterdam, is involved in the foundation of this unique concept.

Together with doctors and researchers from

Vision ADORE will guarantee a research infrastructure of at least ten years, to ensure that the best of the best researchers and clinicians can work for a longer period on unique and groundbreaking research. Within ADORE, the focus for the next years will be on immunotherapy, imaging, and artificial intelligence.

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Hersenonderzoek.nl: Accelerating research into brain diseases Hersenonderzoek.nl is an online platform that helps researchers find the right participants for their studies. It is a platform where healthy people and patients can register their interest in participating in brain research.

Neuroscientists can call on this registry and indicate their search for participants for a specific research project. The platform brings researchers into contact with people who want to participate in their studies.

Renewed funding Hersenonderzoek.nl received renewed funding in January 2022 from ZonMw, Alzheimer Nederland, Dutch Brain Foundation, and Amsterdam Neuroscience. With this renewed funding they will be able to continue their work, which aims to accelerate research into brain diseases. More research is needed to cure brain diseases such as AD, other forms of dementia, Parkinson’s, or MS. Globally, there is a severe shortage of healthy controls and patients to participate in brain research, which results in research delays.

Appendix 6

MeMo lab The Memory Modification platform for the development of novel smoking cessation methods based on recent insights in the field of neuroscience and psychology. This is an initiative by Taco de Vries and Ysbrand van der Werf in the Department of Anatomy and Neurosciences.

The professors De Vries and Van der Werf are currently testing a novel protocol that is based on both Eye Movement Desensitization and Reprocessing (EMDR) and recent insights from animal studies. It is known that deep memory paths in the brain strongly affect the persistence of addictive behavior. By keeping those memory paths preoccupied with other tasks, while simultaneously triggering memories associated with nicotine addiction in a virtual 3D environment, they try to rewire the paths that trigger smoking behavior.

nicotine addiction, Nathan Marchant in the team of De Vries found strong evidence for a role of the anterior insula in relapse to nicotine seeking using chemogenetic intervention and in vivo calcium imaging techniques in rats. His studies also suggest opposing roles of left and right insula in reward seeking, in line with observations in humans. Based on these findings the researchers will now start a clinical trial in smokers and apply deep rTMS to either the left or right insula using a newly designed H-coil in combination with cue-exposure.

Memo-lab is also reaching out to other researchers interested in designing novel procedures to treat pathological behaviors with strong environmental triggers, including those present in OCD, behavioral addictions and eating disorders.

Going forward, De Vries and colleagues want to include neurostimulation in these experiments as well. For that, they see the insular cortex as a promising target based, among others, on their recent preclinical observations. In a translational model of

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Cohorts

As a research institute, Amsterdam Neuroscience stimulates cohort studies and registries. Longitudinal data collection can be a crucial source of information in studying neurodevelopmental disorders over time. Longitudinal cohorts are ideal for understanding and exploring progressive diseases or mental health issues.

NESDA Cohort The Netherlands Study of Depression and Anxiety (NESDA) was designed to investigate the course of depression and anxiety disorders, in particular the psychological, social, biological and genetic factors that influence the development and the long-term prognosis of anxiety and depression.

The main aim of NESDA is to determine the (psychological, social, biological and genetic) factors that influence the development and the long-term prognosis of anxiety and depression. In 2004, 2981 participants were recruited with and without symptoms from primary care practices and specialized mental health institutions in the regions of Amsterdam and Leiden, and in the provinces of Groningen, Drenthe and Friesland. In January 2019, the 7th measurement took place, 13 years after the first people were included. Current NESDA cohort consists of 3348 subjects. The contact for the NESDA cohort is Professor Brenda Penninx.

The Netherlands Sleep Registry The Sleep Registry (Slaap register) is an initiative of researchers at the Netherlands Institute for Neuroscience (part of the Royal Appendix 6

Netherlands Academy of Arts and Sciences) and Vrije Universiteit Amsterdam. They believe it is time to join forces to help poor sleepers. The Sleep Registry is led by Professor Eus van Someren, an expert in the field of sleep, who works as the head of the Sleep and Cognition Department at the Netherlands Institute for Neuroscience and is a professor of neurophysiology at the Vrije Univeristiteit Amsterdam.

European funding In 2022, the European Research Council (ERC) of the European Commission awarded its most prestigious grant, the ‘ERC Advanced Grant’ to Van Someren, to study anxiety disorders and chronic insomnia in combination to find a better treatment for insomnia. This is the second time that Professor van Someren receives this prestigious grant. His research team has been trying for years to improve treatment of insomnia to prevent its adverse consequences on mental health. Their discoveries have made the Netherlands the international leader in the field of fundamental research into insomnia.

Combining sleep and anxiety research Via the Dutch Sleep Registry his team is looking for research participants who, in addition

to their poor sleep, also have complaints of anxiety, stress or emotion regulation.

Thousands of people can contribute to the research by filling in questionnaires. Hundreds of them can also take measurements of their brain activity before, during and after sleep in the comfort of their own bed. Treatments will also be tried out, including innovative medication. Van Someren expects that people will find it easier to control their anxiety and post-traumatic stress symptoms if they sleep better.

Amsterdam MS Cohort Clinical progression in MS has a major impact on a patient’s quality of life but can be very difficult to predict. Why do people with MS continue to deteriorate? How can disease progression be stopped? The researchers at the MS Center Amsterdam (MSCA) want to find answers to these questions. Therefore, the MS researchers ask permission to collect clinical data for the Amsterdam MS cohort of all patients who visit the MSCA for regular care, second opinions or research. The Amsterdam MS cohort currently consists of >7,500 people who visited the MSCA. From a good part of them (>1,500) highly detailed longitudinal clinical and research data is collected. With 92

this extensive database, the MSCA aims to find a way to identify mechanisms and milestones leading to progression, and ultimately find and optimize ways to stop patients from progressing altogether.

MeninGene biobank

The MeninGene study is a nationwide prospective cohort study on genetic risk factors for bacterial meningitis which started in 2006 and has included over 3,000 patients in 2022. All specimens collected in this study and its substudies are stored in the MeninGene biobank. These include leftover cerebrospinal fluid samples from the diagnostic lumbar puncture, DNA from the patients and controls, clinical and radiological data, and the causative bacteria from blood and cerebrospinal fluid. Furthermore, samples from a serial sampling substudy and recalled patients are also stored in this biobank. Finally, as part of the MeninGene biobank samples from brain autopsies were collected, resulting in a large collection of bacterial meningitis brain pathology material (MeninGene-Path).

Appendix 6

The availability of these samples in the biobank enabled the researchers from the Neuroinfection Center Amsterdam at Amsterdam UMC to study interaction between genetic characteristics of the bacterial and the patient, of which the results were published in Nature communications in 2019 (Lees J et al, Nat comm 2019). This study showed several regions in the human genome that are associated with susceptibility to meningitis or severe outcome of meningitis. In a separate project they found that changes in genetics of Listeria monocytogenes in bacterial meningitis patients caused the pathogen to become less sensitive to disinfectants used in the food industry, and caused more severe disease (Kremer, CMI 2017).

In another study on long-term sequelae after bacterial meningitis Diederik van de Beek, Matthijs Brouwer and their colleagues used the biobank to identify the responsiveness of patient blood to stimulation with pneumococci and provided clues in how overactivation of the immune system affects patient outcome (Kloek AT et al, Acta Neuropath Comm 2021).

Recently, they found that neurofilament light, a marker of axonal damage in cerebrospinal fluid, is a strong predictor of poor outcome even after correction for clinical parameters of disease severity (Chekrouni, Neurology: NII 2022). Altogether, the MeninGene biobank proved to be a huge resource for scientific research and enabled multiple international cooperative projects.

Alzheimer Dementia Cohort The Amsterdam Dementia Cohort was established in 2000, along with the foundation of the Alzheimer Center Amsterdam by Professor Philip Scheltens. In this clinic, top quality patient care and scientific research are performed in parallel. All patients that visit the Alzheimer Center Amsterdam are asked to consent to the use of their clinical data for scientific purposes. This patient population comprises the Amsterdam Dementia Cohort, which currently consists of almost 7,000 individuals. The Amsterdam Dementia Cohort forms the basis of much of the research conducted by Alzheimer Center Amsterdam. In addition, it is a starting point for many (inter) national collaborations.

Patients that are referred to the Alzheimer Center Amsterdam undergo an elaborate one-day screening battery. This battery consists of, among others, extensive neuropsychological evaluation, a MRI scan, an EEG, and a lumbar puncture. After their baseline visit, the majority of patients visit the clinic annually for follow-up. The Amsterdam Dementia Cohort has evolved into one of the most elaborate clinical databases in the field of dementia research. Additional information on the set-up, content, and data collection procedures within the Amsterdam Dementia Cohort can be found in the reference below (van der Flier & Scheltens, 2018).

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COVID-19 biobank To support fundamental and clinical research related to COVID-19, Amsterdam UMC initiated the COVID-19 Biobank. This biobank has been initiated by clinical departments, laboratories and the central biobank facility. As of March 20, 2020, employees of Amsterdam UMC are collecting samples of COVID-19 patients, resulting in a database with thousands of samples. The biobank aims to enable as much research as possible in patients with COVID-19 by collecting clinical data, DNA and blood samples, among others, from patients hospitalized in Amsterdam UMC with COVID-19.

Funding The Corona Research Fund of Amsterdam UMC supports the study of Professor Diederik van de Beek, co-director of Amsterdam Neuroscience and specialized in neurological infectious, who leads the COVID-19 Biobank project since the start of the COVID-19 pandemic in 2020.

Several publications The relatively young Amsterdam UMC COVID-19 Biobank is a partner in two important studies, published in Science in September 2020.

Partly thanks to this biobank, it has become clearer why some people become so seriously ill with COVID-19. An international consortium of researchers, including researchers from Amsterdam UMC, published these findings on September 24, 2020. The first Science paper, entitled ‘Auto-antibodies against type I IFNs in patients with life-threatening

Appendix 6

COVID-19’, is co-authored by Diederik van de Beek, a neurologist at Amsterdam UMC; over 60 Amsterdam UMC investigators are acknowledged because of their efforts in setting the Amsterdam UMC COVID-19 Biobank.

members and their respective partners. The researchers collect demographics, life history, medical history, genealogy, neuropsychological data and blood samples. Centenarians are followed annually until death.

100-plus study

INCbase: The Inflammatory Consortium Base

Repetitions in the DNA-code influence the chance of AD. To increase our understanding of the heritability of AD, researchers from the Alzheimer Center Amsterdam are comparing repetitive sequences in Alzheimer patients and healthy centenarians. This allows them to use individual genomes to predict who should be treated to prevent AD-associated brain damage, and how they can be treated.

Neuropathy

Neurologist Filip Eftimov’s specific area of interest is chronic inflammatory demyelinating polyneuropathy (CIDP). Eftimov is combining a translational approach to search for biomarkers of disease activity in CIDP and clinical research that focuses on long-term outcome of the disease. As the Principal Investigator of INCbase, a worldwide registry and biobank to describe CIDP phenotypes and long-term outcome, Eftimov will improve diagnostic criteria and develop biomarkers of disease activity. The main goal is to strengthen international collaboration, improve diagnostic criteria, develop biomarkers of disease activity, and contribute to discovering new treatments for this rare disease.

Professor Henne Holstege and her colleagues of the 100-plus study aim to identify the characteristics associated with the escape or delay of cognitive decline. The 100-plus study is an ongoing prospective cohort study of Dutch centenarians who self-reported to be cognitively healthy, their first-degree family

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Clinical trials

Amsterdam Neuroscience has integrated the clinical trial expertise from different therapeutic areas within Amsterdam UMC into peer groups of clinical advisors, headed by the Industry Alliance Office.

The clinical trial teams of Amsterdam Neuroscience provide support and know-how for organizing and executing industry sponsored clinical trials. The emphasis is on rigorous, academically informed clinical trials, capitalizing on our extensive clinical and academic facilities. This allows us to undertake a broad range of trials, from first-in-patient studies up to large national and international multicenter clinical trials.

MR Clean study Neurologist Yvo Roos and radiologist Charles Majoie were pioneers of the MR CLEAN study and the endovascular treatment (EVT) of acute ischemic stroke in which a patient receives a thin catheter through an injection in the groin.

The catheter is advanced into the occluded blood vessel in the brain. The blood clot is then removed from the body through the catheter.

With the MR CLEAN study Roos, Majoie and colleagues demonstrated the effectiveness of cerebral angioplasty, signifying a worldwide breakthrough in the treatment of people who have suffered a major stroke. And they have worked hard on the technology ever since.

Nowadays, patients have much better prospects than five years ago. Patients treated with EVT have less brain damage and fever neurological complaints. Their functioning in society, like walking or getting dressed, is significantly better. A life with severe disabilities can be prevented more often than with the previous treatment. The patients only receive drugs that can dissolve the blood clot. Thanks to the MR CLEAN study, which was published in the New England Journal of Medicine, this type of Appendix 6

treatment is now carried out across the globe and became the standard approach for acute ischemic stroke.

On December 17, 2020, Charles Majoie and Yvo Roos of Amsterdam UMC were awarded the prestigious gold Winkler medal for the MR CLEAN study.

TETRO trial In the Netherlands, at least 100,000 people suffer from obsessive compulsive disorder (OCD). This is characterized by disruptive compulsive thoughts and time-consuming compulsions that can be so disruptive that someone experiences a high level of suffering.

They are often unable to work or study and become socially isolated. From a longer-term perspective, roughly 50% of the people with OCD can’t be remedied with existing care (cognitive behavioral therapy and/ or medication). Currently, there is no good alternative for them. The most far-reaching treatment (brain surgery or deep brain stimulation) is only an option for the most extreme cases.

In the search for a new, promising treatment for treatment-resistant compulsive disorders, Amsterdam Neuroscience researchers from Amsterdam UMC collaborate with several Dutch hospitals and mental health institutions in the so-called TETRO trial. With a grant of €2.8 million from ZonMw, Professor Odile van den Heuvel leads the trial in which 250 patients will participate in a research study for a new, promising treatment for OCD. This promising treatment is repetitive transcranial magnetic stimulation (rTMS).

“We think that the group that does not benefit sufficiently from cognitive behavioral therapy can be helped with this new rTMS treatment,” says Van den Heuvel. “We generate an electric current in the brain with the help of a magnetic field. This allows us to stimulate the brain circuit that is responsible for controlling emotions and behavior. By this means we will bring the brain into an optimal condition to increase the effects of cognitive behavioral therapy.” Patients will undergo rTMS treatment four times a week for a minimum of five weeks and a maximum of seven weeks. Each session is followed by cognitive behavioral therapy.

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Blood test for early diagnosis of Alzheimer’s disease The diagnosis of Alzheimer’s disease (AD) is a complex process and is usually done at an advanced stage of the disease. However, research on AD-specific blood-based or cerebrospinal fluid biomarkers supports the development of diagnostic tests for early detection of AD. The research group led

by Professor of Neurochemistry Charlotte Teunissen of Alzheimer Center Amsterdam studies the blood-based biomarkers for the diagnosis of AD. They published a review in The Lancet Neurology on the current state of the blood test.

The US-based company Quanterix Corporation and the Alzheimer’s Drug Discovery Foundation (ADDF) started investments in the development of a multi-analyte plasma test.

The ADDF funds a series of prospective clinical trials to validate the test in collaboration with Amsterdam UMC and Alzheimer Centrum Amsterdam. Charlotte Teunissen Is leading these clinical studies in collaboration with Quanterix.

Teunissen: “We are in a historic moment with plasma-based biomarkers for AD detection nearing clinical implementation. The funding from the ADDF will help further drive the rapid progress in this area just in time for the arrival of new therapeutics. We will be looking to validate the Simoa multi-analyte test for use in both memory care and primary care settings, in persons with worries about their cognition.”

Appendix 6

Vanishing White Matter trial The Amsterdam Leukodystrophy Center at Amsterdam UMC is conducting a clinical trial in children with Vanishing White Matter (VWM).

In this trial, the researchers evaluate whether the drug Guanabenz is effective in slowing progression, stabilizing, or even improving the brain white matter abnormalities in VWM. Guanabenz is an old and well-known medicine that has been used for decades for the treatment of high blood pressure. It has been approved by the FDA, the American medicines agency.

Given the mechanism of action of Guanabenz, the researchers of the Amsterdam Leukodystrophy Center led by Professor

Marjo van der Knaap estimated it likely to be beneficial in VWM. They had laboratory mice with VWM and treated them with Guanabenz. The results of that study indicate that long-term high-dose Guanabenz treatment ameliorates VWM in these mice and leads to both important improvements in motor function and amelioration of brain pathology. Because it was shown previously that the disease mechanism of VWM and the mode of action of Guanabenz are the same in mice and patients, the researchers expect that long-term treatment with high doses of Guanabenz could also be beneficial in patients with VWM.

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Companies

Valorization is the utilization of scientific knowledge in practice. Examples include the translation of innovation into developing a product or medicine or applying scientific knowledge to a system or process.

Some researchers from the Amsterdam Neuroscience network partnered up and started their own spin-off companies.

Macrobian Biotech

of patented technology, various substances will be developed that act specifically on the dopamine system and restore the affected system. The specificity of the treatment ensures that the patient has the least possible chance of side effects. The company’s work is aimed at delivering a fully tested preclinical drug, and then entering clinical trials with it.

relevant biomarkers into one integrative index improving statistical power and simplifying the assessment of activity. The integrated index can be used for prediction, stratification, or quantification of effects. The analytic method allows EEG biomarkers to be used as a robust secondary endpoint.

NBT Analytics NBT Analytics is a spin-off company from the

In 2017, Dr. Lars van der Heide and Professor Marten Smidt decided to challenge themselves further by founding Macrobian-Biotech, as a spin-off company from the University of Amsterdam. Macrobian-Biotech aims at performing pre-clinical research that leads to novel treatments for disorders that affect the midbrain dopamine system. The company is currently housed at the Amsterdam Science Park, the heart of academic excellence in the Netherlands.

Within the company, new treatments for neurological disorders of the dopamine system are being researched and developed. By means Appendix 6

Vrije Universiteit Amsterdam. The company was founded in August 2015 by Dr. Klaus Linkenkaer-Hansen and Dr. Simon-Shlomo Poil with Professor Hilgo Bruining as Chief Medical Officer. NBT Analytics provides extensive insights on how drugs influence the brain through a comprehensive selection of EEG biomarkers and identification of drug specific indices.

By using machine learning techniques, NBT combines information from multiple biomarkers. Unlike traditional analyses that only focus on one or two spectral biomarkers, NBT Analytics investigates biomarkers from temporal and spatial domains allowing for more comprehensive insights into the effect of an intervention on the brain. NBT combines 97

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Communication & society

To stimulate the alliances within our research institute and pursuit the ability to connect our people, their science and the brain we need communication. Several communication tools have been developed and deployed to increase connections among our researchers and to the outside world.

Amsterdam Neuroscience magazine The Amsterdam Neuroscience MAGAZINE is an annual publication that celebrates the achievements and hard work of the investigators and colleagues in the neuroscience field.

The magazine contains in-depth interviews and short profiles of prominent senior and junior investigators. A must-read for anyone interested in the neuroscience research community in Amsterdam.

Communication channels

Website Twitter

23,200 Total visitors

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2021 edition on resilience (online only) 2020 edition on team science (online and PDF-version) 2019 edition (online and PDF-version)

15,719 Total visitors

Newsletter

LinkedIn

2021

2020

• •

Social media

2021 2021

2021

814

2,604

Total followers

Total followers

2020

2020

397

1,398

Total followers

3,899 Total reads 2020

3,742 Total reads

Total followers

Figure 6.1 Infographic on the Amsterdam Neuroscience communication channels in 2020 and 2021.

There is an overall growth of the digital channels of Amsterdam Neuroscience. Illustrated is a rise of the unique visitors of the Amsterdam Neuroscience website with more than 30%. In a period of one year, the total amount of followers on the Amsterdam Neuroscience social media channels almost doubled. And there is a small increase of people who read the Amsterdam Neuroscience newsletter.

Appendix 6

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Online and hybrid events Amsterdam Neuroscience

Annual meeting 2020 On October 2, 2020, the fifth Annual Meeting of the Amsterdam Neuroscience research institute took place. During this day around 500 online participants joined this virtual Annual Meeting. With a variety of sessions Amsterdam Neuroscience wanted to inform participants on the latest research developments in neuroscience all revolving around this year’s theme: team science.

Amsterdam UMC & COVID-19 research event 2020 On December 3, 2020, the research institutes jointly organized the Amsterdam UMC & COVID-19 Research event entitled ‘Unorthodox Teams, Accelerating Science’. With eighteen young researchers, several supporting experts, a brief interview with Anthony Fauci, and nine illustrative videos we showed a brief outline of the COVID-19 research at Amsterdam UMC.

Appendix 6

Annual meeting 2021 On September 30 and October 1, 2021, the sixth Annual Meeting of the Amsterdam Neuroscience research institute took place.

This year we organized a two-day hybrid event that started with the online poster market in Gather town on Thursday and continued with a plenary program on Friday with 200 attendees live at the Johan Cruijff ArenA and more than 300 participants that joined the Annual Meeting online.

With our easily accessible webinars, each time scientists will be updated within less than 1,5 hours and be inspired to continue to foster the integration of basic research and patient-oriented research.

TN2 webinars series Translational Neuroscience Network (TN2) stands for connecting fundamental and clinical researchers in the field of Translational Neuroscience. In 2020, 2021 and 2022 two TN2 webinar series were organized in which we invited investigators of public and private partners to share their knowledge and explore translational medicine in the field of neurology and psychiatry.

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Books Odile van den Heuvel Parkinson bij de psychiater - Uitgeverij De Geus, 2021

Christiaan Vinkers Hoe zit het nu echt met antidepressiva Uitgeverij Prometheus, 2021

Cyriel Pennartz De code van het bewustzijn - Uitgeverij Prometheus, 2021

Odile van den Heuvel and Sonja Rutten, both psychiatrists working at Amsterdam UMC, published a book where they write about the mental symptoms many patients with Parkinson’s disease experience, such as anxiety, depression and psychosis: ‘Parkinson’s at the psychiatrist’ (‘Parkinson bij de psychiater’ in Dutch). They see the book as an ode to the resilience and creativity of people with Parkinson’s disease (PD).

Psychiatrist and Professor of stress and resilience Christiaan Vinkers and pharmacist Roeland Vis published the Dutch book ‘Hoe zit het nu echt met antidepressiva?’. In this new book, Vinkers discussed the ins and outs of taking antidepressants. There are so many misconceptions about taking these drugs that Vinkers and Vis felt the need to discuss the subject in an accessible way for a wide audience. The book is a revised version of the book ‘Even slikken’ from 2017. They updated the information and added some sections, for instance about the how and why (not) of quitting antidepressants.

“This is not a book for the faint of heart - it is for doubters, puzzlers, worriers, pathfinders and other people curious about what’s going on up there in their head,” says Cyriel Pennartz about his new book. In it, Pennartz takes the reader on an inspiring quest for one of the greatest scientific challenges of the twenty-first century: understanding the relationship between brain and mind.

Pennartz, Professor at the Swammerdam Institute for Life Sciences (SILS) at the University of Amsterdam, has written a popular scientific work in Dutch about how the brain shapes our reality. The issue of consciousness, and especially sensory consciousness, is central in it. How is the brain, this remarkable tissue where it literally crackles with electrical activity, able to let us experience the world with its wealth of qualities as if it’s just regular matter?

According to Pennartz, studying experience and consciousness is not an impassable road.

In fact, over the past thirty years, studies of patients, computer simulations and the electrical behavior of brain cells have paved the way for thorough research into brain mechanisms of consciousness.

The book features twenty personal stories from people with PD, who opened up about their personal experiences in the hope that they can help other patients. For example, to recognize the psychiatric symptoms, being able to talk about difficult topics, to seek help and to find a way to deal with the mental side of PD together with loved ones and therapists. As a reader you get an insight in the perspective of the psychiatrist and you are included in their observations and medical considerations.

Appendix 6

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Annemiek Dols Koorddansers - Uitgeverij Boom, 2021 Annemiek Dols and Moniek van Dijk composed a photography book filled with personal stories of people with bipolar disorder, their loved ones and healthcare professionals to show a realistic image of their lives. The book, published by Boom publishers, is called ‘Tightrope Walkers’ (Koorddansers in Dutch).

Bipolar disorder occurs in 2% of people in the Netherlands, just as often in men and women.

In the Netherlands many people with bipolar disorder have not yet been correctly diagnosed.

People often do not seek help, for example because they are ashamed. Dols: “Now it’s time to break that stigma and illustrate the real lives of people with bipolar disorder and their loved ones.” With this new book Dols and Van Dijk want to open the doors to the lives of people with bipolar disorder and start a new era where psychological problems should not be kept a secret.

Appendix 6

Damiaan Denys Het tekort van het teveel - Uitgeverij: Nijgh & van Ditmar, 2020 In 2020, psychiatrist and philosopher Damiaan Denys published the book ‘The shortage of the excess; (‘Het tekort van het teveel’ in Dutch). In this book, Denys outlines the paradox of mental health care. Denys is known for his honest questions and courageous positions in complex social debates. He thinks and speaks about fear and freedom, (ab)normality, death, and life at the intersection of the disciplines of psychiatry, philosophy and neuroscience.

How can we understand these paradoxes? Do we expect too much from life? Does prosperity bring more unhappiness? Why is mental health care failing? Can we still suffer healthily and normally? Are our expectations too high? Can we still be human?

Something crazy is going on. Western countries have been among the happiest countries in the world for years. Never has prosperity been higher, wealth greater, and quality of life better. These countries are positioned at the top of the world in education, living environment, health, safety and well-being.

Yet four out of ten people suffer from a mental disorder in their lifetime and in the Netherlands one million people undergo treatment for mental health problems every year. We are more prosperous than ever, but we also experience more mental health problems than ever before. We are ranked happier but are suffering more than ever.

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Appendix 7 | Proof-of-Concept & alliance projects (including ABMP projects) As an organization, Amsterdam Neuroscience has organized its research in a focused way along the nine translational research programs, each around specific brain and nervous system diseases, disease mechanisms, or technology innovations. We will continue to keep this focus but also want to stimulate young and promising researchers.

To stimulate young and promising research, in the period 2016-2018, many outstanding proof-of-concept (PoCs) and alliance projects were funded by Amsterdam Neuroscience, for a total of €6.5 million.

For the period 2020-2022, we kickstarted a new round of such projects, with a total of €3 million funding. Here is the index of the internally funded research alliance and PoC projects for the period 2020-2022 ◦

See Amsterdam Neuroscience Proof-ofConcept projects 2016-2022

◦

Amsterdam Brain & Mind Projects (ABMP) projects 2016-2019 ABMP projects

Appendix 7

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Appendix 8 |

Open Science, PhD policy & training, academic culture, Human Resource & ethical review

Amsterdam Neuroscience is the research institute for neuroscience of the three knowledge institutes: Amsterdam UMC, Vrije Universiteit Amsterdam and University of Amsterdam. Therefore, Amsterdam Neuroscience aligns its strategic plans and policy guidelines with the overall strategy of these three organizations. For Open Science, PhD policy, academic culture and team science, Human Resources, diversity and inclusion policy or ethical review, Amsterdam Neuroscience gives consent to policies of its universities and the affiliated university medical centers.

Open Science The international Open Science movement aims to implement a new approach to the scientific process based on cooperative work and sharing of knowledge. In this context, research data and other research processes are freely available, under terms that enable reuse, redistribution and reproduction of the research and its underlying data and methods. Open Science improves trust among researchers as others can verify research findings, it promotes the reuse of research data, it is associated with more attention and higher citation rates, and it promotes building of new collaborations.

As part of Open Science, Amsterdam UMC encourages Open Access (OA) publishing and the reuse of data for future research by other groups. Over the past few years, OA deals have been made with publishers and journals that enable Amsterdam UMC researchers to publish their articles OA at discount rates (up to 100%).

Appendix 8

Support and information regarding OA publishing is provided by the Medical Library for location AMC and by the UBVU for location VUmc. For the reuse of data, it is a prerequisite that research data is stored in a FAIR (Findable, Accessible, Interoperable and Re-usable) way.

The Research data management department can facilitate the creation of FAIR datasets by providing researchers tools for and support with drawing up Data Management Plans.

Amsterdam UMC researchers can use various open data repositories (e.g., Figshare for location AMC and DANS for location VUmc) to share and openly publish their research FAIR data sets. Support regarding storage and archiving is provided by the Research Data Management Helpdesk or the Medical Library for location AMC, and the Research Data Management Department or the UBVU for location VUmc.

PhD policy and training As a PhD degree is obtained at a university, distinct doctorate regulations apply for the University of Amsterdam (location AMC) and the Vrije Universiteit Amsterdam (location VUmc). In Amsterdam UMC location AMC, PhD support is centralized and provided by the Doctoral School, and for PhD candidates at location VUmc, PhD support is provided by both the involved research institute and by the Doctoral School . Support services entail; information provision, administration, PhD education- and training program and support and advice. All processes relating to the PhD trajectory, from enrolment to thesis submission, are administered using the registration system Doctor at location AMC, or by the involved research institute (in collaboration with the office of the dean) using the registration system Hora Finita at location VUmc.

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A central objective of graduate education at Amsterdam Neuroscience is to train the next generation of excellent researchers. In doing so - both at the Amsterdam UMC, the VU Amsterdam and UvA - we follow a set of so-called PhD regulations, that were agreed upon. At the start of each PhD project the head of department, or one of its team members appoints a main (co-)supervisor to instruct the PhD candidate on the standard operating procedures.

Part of this protocol is also that at the start of each project, the PhD candidate files a mandatory Training and Supervision Plan (TSP; that each PhD candidate should file at the beginning of the project) to be evaluated and monitored by the PhD supervisors up to the moment of graduation. The director of the institutes authorizes the TSPs on behalf of the dean. Amsterdam Neuroscience participates in the Graduate School Neurosciences Amsterdam Rotterdam (ONWAR), led by Professor Guus Smit.

Academic culture Amsterdam UMC takes measures to ensure openness, (social) safety, inclusivity and research integrity. The office of the ‘ombudsman’ is responsible for the social safety policy and the complaints procedure.

This office aims to improve social safety and combating unethical and/or undesirable behavior, to increase ownership and responsibility of employees and managers regarding (safety) signals and to promote an

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open reporting culture. Moreover, Amsterdam UMC develops an active diversity and inclusion policy (see for more details Human Resources policy).

Regarding research integrity, Amsterdam UMC aims to provide an academic culture in which researchers are stimulated and supported to perform research to the highest ethical standards. Elaborating on the European and the Netherlands Code of Conduct for Research Integrity, that articulates broad values and principles characterizing research integrity, our Research Code defines local expectations and guidelines for researchers when conducting research at Amsterdam UMC. Since Amsterdam UMC performs various types of research - preclinical, observational, clinical - we have to adhere to numerous standards, rules and regulations and have a quality framework in place. Within this quality framework, Amsterdam UMC has elaborated a so-called Research Roadmap, that clearly states the steps that need to be followed to carry out research in different settings (i.e., preclinical research, clinical trials, research involving human subjects (WMO)); from experimental design and collection of data, to closure and publication of the results.

Dedicated Research Support teams are in place to provide hands-on support and help researchers comply with integrity and quality requirements.

The executive boards have appointed several independent confidential counselors focusing

on research integrity. Any employee or external party involved in research at Amsterdam UMC who has a question about research integrity or suspects research misconduct can discuss this with the confidential counselors. They can mediate and advise about whether or not to file a complaint. Furthermore, they can support the submission of a formal complaint to the research integrity committees, that are established by the executive boards of the UvA and VU Amsterdam (because the universities hold responsibility for research done in their institution, including the medical faculties).

Moreover, the confidential counselors provide research integrity training, for instance for clinical investigators as part of the BROK course. As part of the PhD trajectory, research integrity training is offered to PhD candidates.

Human Resource policy Amsterdam UMC is convinced that science is best pursued with a wide diversity of staff members and teams: individual talented people who each bring their own knowledge, values and experiences to the task and respect each other.

Amsterdam UMC has an active PhD association called ASAP. ASAP offers a professional and social network for PhD candidates at Amsterdam UMC by organizing symposia, workshops, and networking events. Furthermore, ASAP is involved in the training for PhD candidates.

They also represent Amsterdam UMC PhD candidates in the employee’s council, in the Amsterdam UMC Research Board, and national

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PhD student associations. Apart from that, both universities have PhD a council: the VU PhD council and the Central PhD Council of the UvA. Amsterdam UMC has a Principal Investigator system that challenges individual scientists to take up leadership, develop their own research lines and gain visibility. The criteria are: publications over the last 6 years as first or last author that demonstrate one’s own line of research, active research funding of >€200,000 as main applicant, and supervision of >1 PhD candidate as co-promotor. Principal Investigators are appointed annually by the executive board. The Principal Investigator system originated in location AMC, has been adopted in location VUmc in 2017 and is harmonized within Amsterdam UMC since 2019.

Within Amsterdam UMC, several talent programs are offered. The Amsterdam UMC Fellowship (formerly AMC Fellowship) is a five year program that provides (external) highly talented mid career level researchers the opportunity to set up their own research group.

The Tenure track (location AMC and VUmc) is a five year program that guides mid career level researchers to advance to a tenured position. The Career track (location VUmc) is a three to five year program that supports exceptional talents towards professorship.

Amsterdam UMC is working on harmonizing Human Resource policies and aims to develop an integral Talent policy focusing on the

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perspectives of researchers throughout the various levels of their career. Furthermore, both locations of Amsterdam UMC have an incentive scheme for acquisition of prestigious research grants, to stimulate, retain or attract researchers at mid or high career level.

Amsterdam UMC is currently developing new policy on the Recognition and Rewards of research and scientific researchers. Within this new recognition and rewards policy researcher’s performance is being evaluated on five domains: academic research, education, patient care, valorization and leadership. Researchers are expected to show excellence in research and education, but also in at least one of the other domains.

Because different combinations of domains are possible in an academic career, and they can also change with time, this new policy aims to give more attention to the context, to consider the time requirements and the needs of the academics themselves. New measures established within this new policy are for example, more mentoring offered for young researchers, promoting of evidence-based CV for recruitment and selection and funding in the form of fellowships or grants.

Diversity & inclusion policy Amsterdam UMC has endorsed the Charter ‘Talent to the top’, by which it committed itself to improve the gender balance in (sub) top levels. The Gender Equality Plan (GEP) of Amsterdam UMC, which is in line with EU policy guidelines, goes a step further by

expressing the vision of becoming an inclusive organization that represents the cultural and sexual diversity of its environment. The D&I Talent Fellowship is also to be seen in this light. With the ‘Action Plan for 2021 and after: Diversity & Inclusion at Amsterdam UMC: Differences make us stronger together’, policies and measures were introduced to increase the participation of women and individuals from underrepresented groups in Amsterdam UMC, by incorporating the principles of inclusiveness, gender balance and diversity into its talent and career policies. Next to that, dedicated researchers, educators and clinicians, including nurses, include Diversity and Inclusion perspectives in research, education and patient care.

To help female researchers progress to higher levels on the career ladder, part of the NWO Aspasia Grant funds have been transferred to the Women in Science Fund, financially supporting young female scientists to go on international work visits.

Ethical review Medical research involving human subjects, human material or laboratory animals has to be carried out according to national law and regulations. Dedicated ethical committees review research protocols to ensure human and animal safety, and research quality. Both Amsterdam UMC locations have an accredited independent MREC; METC AMC and METc VUmc. MRECs have to approve medical scientific research in which human participants are

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subjected to (medical) procedures or are required to follow rules of behavior (WMO research). Research proposals are only approved if the MREC establishes that the risks and burden for participants are in balance with the potential benefit for medical science or health care. Research with humans that is not subject to the WMO (nWMO) (e.g., research with medical data or interviews) has to satisfy important legal and societal preconditions.

A dedicated review board under the responsibility of the MREC assesses in principle all nWMO research proposals according to predefined ethical and legal criteria.

Applicable legislation and regulations include the Medical Treatment Contracts Act (Wet Geneeskundige Behandelingsovereenkomst; WGBO), General Data Protection Regulation (GDPR or AVG in Dutch), the Code of Conduct for Responsible Use and the Code of Conduct for the Use of Data in Health Research. The two Codes describe rules of conduct for care providers and researchers who wish to use patient material (biomaterials or data).

Dedicated Biobank Review Committees (BTC at location AMC or TcB at location VUmc) review proposals for research involving setting-up a biobank or conducting research with material from an existing biobank. This kind of research has to be reviewed for legal and ethical aspects following the Code of Conduct for Responsible Use. Moreover, research involving the processing of personal data is regulated by the GDPR. The

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Amsterdam UMC research data management department, the legal research support department, or the privacy- or data protection officer support researchers with proper handling and organization of research data, ownership of data and data protection.

Besides ethical committees that focus on protecting humans who participate in scientific research, animal experiments committees (Dierexperimentencommissie, DEC) focus on protecting laboratory animals.

The Experiments on Animals Act stipulates that animal experiments can only be conducted after authorization by the national competent authority (Centrale Commissie Dierproeven, CCD). A proposal for research on laboratory animals is made by a ‘Section 9 officer’ from the research department, in which the effects of the interventions and the number of animals should be kept to a minimum. This proposal is submitted to the CCD and ethically reviewed by a DEC, which advises the CCD accordingly. The DEC weighs the degree of animal discomfort caused by the procedures and decides if this is proportional to the scientific and/or social benefits of the study.

The CCD will decide whether or not to grant the permit after taking into consideration the ethical review by the DEC. Organization & policy Amsterdam University Medical Centers (Amsterdam UMC) are combined one of the most prominent research institutes in the Netherlands, as well as one of the largest

academic hospitals. Amsterdam UMC comprises two Faculties of Medicine: the faculty of the University of Amsterdam (UvA) and faculty of the Vrije Universiteit Amsterdam. These faculties joined forces in June 2018 in an administrative merger. This merger enables Amsterdam UMC to further develop its core business together: complex patient care, scientific research, and education and training.

The Amsterdam UMC research organization The Amsterdam UMC Executive Board consists of five members. Professor Chris Polman is chair and dean of the VU Amsterdam Faculty of Medicine, Professor Hans van Goudoever is vice-chair and dean of the UvA Faculty of Medicine, Ms Frida van den Maagdenberg is the Chief Financial Officer, and the other members are Professor Mark Kramer and Dr. Karen Kruijthof (see Figure 8.1, p. 107). Besides the combined Executive Boards, Amsterdam UMC also shares a research policy advisory organ, called the Amsterdam Research Board (ARB).

The ARB advises the Executive Board on major policy issues regarding scientific research.

Professor Mat Daemen, vice-dean Research of Amsterdam UMC, is the chair of the ARB. The ARB further consists of 1-2 research institute (RI) directors per RI, some positional members: the director of Research Support, Dr. Jessika van Kammen, the vice-dean Valorisation of Research Professor Arjen Brussaard and the chairs of the Committee Talent and Appointments, Professor Yvette van Kooyk and of the Good Research Practice committee, Professor Arnon Kater, as well as

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six independent researchers. Both deans are attendant members of the ARB. Together, these people oversee all fundamental, translational and clinical research within Amsterdam UMC. The training and supervision of PhD candidates are coordinated by the Amsterdam UMC Doctoral School, which is chaired by Professor Christa Boer. The Doctoral School board has six members, one of whom is a PhD candidate.

The research structure is organized in a matrix with divisions and research institutes.

Amsterdam UMC has ten divisions, each headed by a division chair, and encompasses multiple departments and sub-departments.

Each department/sub-department head has integral responsibility for patient care, education and research, as well as for management and finances. The ten current divisions are: 1. Specialisms in Medicine, 2. Surgical Specialisms, 3. Heart Center, 4.

Mother and Child Center, 5. Neurosciences and Psychiatry, 6. Operating Centre and Intensive Care, 7. Imaging Specialisms, 8. Outpatient Clinics, 9. Laboratory Specialisms and 10.

Primary Care, Public Health and Methodology.

Research Institutes To enhance focus and stimulate interdisciplinary collaboration between departmental research groups as well as between both faculties there are eight research institutes, namely Amsterdam Cardiovascular Sciences, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam institute for Infection and Immunity, Amsterdam Movement

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Figure 8.1 Organizational structure of Amsterdam UMC research.

Sciences, Amsterdam Public Health, Amsterdam Reproduction and Development, Cancer Center Amsterdam and Amsterdam Neuroscience. Each research institute covers the whole spectrum from basic biomedical research, through translational and clinical research to the assessment of innovations in

actual clinical practice (see Amsterdam UMC Research). Each institute has its own Board of Directors, a four-year project plan and an annual budget of €500,000 to stimulate innovation based upon the specific project plan. The directors discuss progress and strategic issues during the ARB meetings.

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Research Support Amsterdam UMC has a central support organization to create an environment in which researchers can excel, both by contributing to a stimulating context and by providing practical advice. This organization – Research Support – is comprised of the following units: Research Policy Office, Research Grants Support, medical research ethics committee (METc) bureau, Research Data Management, Clinical Monitoring Center, Legal Research Support, Project administration, Medical Library and output registration and Innovation Exchange Amsterdam (IXA) as depicted in Figure 8.1 (p. 107). The Management Team of Research Support is chaired by Professor Mat Daemen, who is also chair of the Amsterdam Research Board. The other members of the Board of Research Support are Dr. Jessika van Kammen, who is also a member of the Amsterdam Research Board, and Mr. Jan Brand. The double positions of Professor Daemen and Dr. van Kammen are intentional and help to align the development and the execution of research policies, and vice versa: namely the development of policies that respond to the needs of researchers.

Research Support provides hands-on support to researchers, from the development of early ideas into fundable research proposals to the implementation of the outcomes.

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Amsterdam UMC research policy The following parties are involved in Amsterdam UMC’s research policies: •

Executive Board: In general, strategic research decisions are made by the Executive Board.

Specifically, this holds for the appointment of professors, major research investments and strategic participation in national and international initiatives. For particular topics, such as advice on the awarding of fellowships and scholarships for PhD candidates, special committees have been set up by the Executive Board.

•

Division chairs and department heads: Nomination of candidates for Principal Investigator appointments or professorships/associate professorships, are the responsibility of the department heads. Content issues, such as the definition of new and existing research lines and the formation of centers are discussed in the matrix: division and departments together with the research institutes. Additionally, division chairs and department heads can stimulate research activities by, for example, investing in equipment and laboratory facilities.

•

Amsterdam Research Board: Important topics for the Amsterdam Research Board are for example talent policy, societal impact and visibility of research, quality of research and the development of policies on scientific integrity.

•

Research Policy Office: The Research Policy Office plays a role in preparing most central research policies, including the alignment with (inter)national developments and the research policies of the University of Amsterdam and the Vrije Universiteit Amsterdam.

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