2019 Del Monte Symposium Program

Manipulating Brain States Invasive mapping and neuromodulation in human neurological disease

Rochester, New York | October 25-26, 2019

MANIPULATING BRAIN STATES

The Del Monte Symposium Manipulating Brain States – Invasive Mapping and Neuromodulation in Human Neurological Disease Tremendous progress has been made in the deployment of direct brain modulation/stimulation techniques, both non-invasive and intracranially implanted, to treat neurological and neuropsychiatric conditions. The emerging field of neuromodulation stands at the interface of clinical delivery and novel cutting-edge technological advances, and is the process of understanding the capabilities of these techniques and developing the parameters and protocols necessary for effective treatment delivery. Attendees at this meeting will learn of the latest applications, techniques, technologies, and mechanistic accounts of neuromodulation, and will be brought abreast of the clinical conditions that are best suited for treatment with these devices.

At the conclusion of this event, participants should be able to: 1. Recognize the latest applications, techniques, technologies, and mechanistic accounts of neuromodulation, and have been brought abreast of the clinical conditions that are best suited for treatment with these devices.

2. Discuss and share insights gained from numerous facilities regarding neuromodulation techniques and practices.

3. Develop an enriched understanding of the underlying neural mechanisms of neuromodulatory techniques and how they impact the effectiveness of clinical delivery.

Follow us on Twitter @URNeuroscience and tweet along using #DelMonteSymposium 2

AGENDA: FRIDAY, OCTOBER 25 Breakfast

7:30am – 8:15am

Welcome and Introduction (John Foxe, PhD – University of Rochester)

8:20am – 8:30am

David McMullen, MD (NIMH) BY ZOOM/WEB EX “Invasive Neural Recording/Stimulating Funding Opportunities in Mental Health”

8:30am – 8:50am

Session I – Deep Brain Stimulation in Neuropsychiatric and Neurological Disease (I) Suzanne Haber, PhD (University of Rochester; Harvard University) 9:00am – 9:20am “From primate anatomy to human neuroimaging: The circuits that underlie neurostimulation targets for psychiatric disease.”

Patricia Limousin, PhD (University College London) “Deep brain stimulation in the treatment of movement disorders in 2019”

9:20am – 9:40am

Ian Cook, MD (Los Angeles TMS Institute) 9:40am – 10:00am “Translational Neuroscience in Neuromodulation: The Case of Trigeminal Nerve Stimulation” Panel Discussion

(Chairs: Suzanne Haber and John Markman)

Coffee Break

10:00am – 10:30am 10:30am – 11:00am

Session II – Non-invasive Neuromodulation in the Laboratory and Clinic Marom Bikson, PhD (City College of New York) “The targeting limits of transcranial electrical stimulation”

11:00am – 11:20am

Jacinta O’Shea, PhD (University of Oxford) “Neural bases of individual differences in sensorimotor plasticity”

11:20am – 11:40am

Stephanie Buss, MD (Harvard Medical School) “TMS as a biomarker in Alzheimer’s disease and related dementias”

11:40am – 12:00pm

Panel Discussion

12:00pm – 12:30pm

(Chairs: Michel Berg and Steven Silverstein)

Lunch

12:30pm – 2:00pm

Session III – Electrocorticography in Cognitive Neuroscience – Oscillatory Brain Dynamics Sophie Molholm, PhD

(Albert Einstein College of Medicine; University of 2:00pm – 2:20pm Rochester) “Brain mechanisms of enhanced perception following multisensory stimulation: Insights from and scalp electrocorticography (ECoG) electrophysiology” Michael Beauchamp, PhD (Baylor College of Medicine) “Models and Mechanisms of Multisensory Speech Perception”

2:20pm – 2:40pm

Youssef Ezzyat, PhD (Swarthmore College) “Direct brain stimulation during episodic memory”

2:40pm – 3:00pm

Panel Discussion

3:00pm – 3:30pm

(Chairs: John Foxe and Kevin Mazurek)

Coffee Break

3:30pm – 4:00pm

Kilian J. and Caroline F. Schmitt Neuroscience Keynote Address Helen Mayberg, MD

(Icahn School of Medicine at Mt. Sinai; Emory University); (John Foxe Introduction) “Iterative Strategies to Refine and Optimize Deep Brain Stimulation for Depression” Gala Dinner Reception 3

(Genesee Valley Club)

4:00pm – 5:00pm

6:00pm – 10:00pm

AGENDA: SATURDAY, OCTOBER 26 Breakfast

8:00am – 8:40am

Welcome and Introduction (Web Pilcher, MD PhD – University of Rochester)

8:45am – 9:00am

Session IV - Deep Brain Stimulation in Neuropsychiatric and Neurological Disease (II) European Journal of Neuroscience Young Investigator Award Lecture Nanthia Suthana, PhD (UCLA) 9:00am – 9:20am “Recording and stimulation of deep brain activity during real world spatial navigation and memory in humans” Ralph Koek, MD (David Geffen School of Medicine at UCLA) 9:20am – 9:40am “Amygdala Deep Brain Stimulation for Treatment-Refractory Combat PTSD: Data from the first two cases and future aspirations.”

Gregor Thut, PhD (University of Glasgow) 9:40am – 10:00am “Probing and manipulation of brain oscillations & associated functions by combined TMS and EEG” Panel Discussion

(Chairs: Julie Fudge and Sophie Molholm)

Coffee Break

10:00am – 10:30am 10:30am – 11:00am

Session V – Pre-Operative and Intra-Operative Brain Mapping Nitin Tandon, MD (University of Texas, Houston) “Intracortical recordings for understanding and modulating language”

11:00am – 11:20am

Nathan Crone, MD (Johns Hopkins University) 11:20am – 11:40am “The intersection between human functional brain mapping and brain-machine interfaces” Thomas Schlaepfer, MD (Albert-Ludwigs-Universitat Freiburg; Johns Hopkins) “Effects on Affect – Neuromodulation for Treatment Resistant Depression”

11:40am – 12:00pm

Panel Discussion

12:00pm – 12:30pm

(Chairs: Brad Mahon and Web Pilcher)

Lunch

12:30pm – 2:00pm

Session VI – Neuromodulation in Epilepsy Gregory Worrell, MD PhD (Mayo Clinic) 2:00pm – 2:20pm “Integrating Brain Implants with Local and Distributed Computing Devices: A Next Generation Epilepsy Management System” Mark Richardson, MD (Mass General/Harvard) “Basal ganglia-thalamocortical networks in speech”

2:20pm – 2:40pm

Andrew L. Ko, MD (University of Washington) “Closed Loop Deep Brain Stimulation for Essential Tremor”

2:40pm – 3:00pm

Panel Discussion

3:00pm – 3:30pm

(Chair: Michel Berg)

Coffee Break

3:30pm – 4:00pm

The Del Monte Family Neuroscience Keynote Address Itzhak Fried, MD PhD (UCLA); (Web Pilcher introduction) “Neuromodulation of Human Memory: From Single Neurons to Clinical Translation” Closing Remarks and End of Program

4:00pm – 5:00pm 5:15pm

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FRIDAY, OCTOBER 25 7:30 AM Breakfast 8:20 AM Welcome & Introduction by John Foxe, Ph.D.

Session I: Deep Brain Stimulation in Neuropsychiatric and Neurological Disease

David McMullen, M.D.

National Institute of Mental Health

“Invasive Neural Recording/Stimulating Funding Opportunities in Mental Health”

This talk will highlight the various funding opportunities available to explore the neural circuitry underlying mental health disorder. I will discuss opportunities at NIMH, NIH, and through the BRAIN Initiative. The talk will focus on 1) device development, 2) mechanistic studies, and 3) clinical trials. Understanding the circuitry underlying mental health disorders is key to developing novel therapies. I will discuss the state of the field and highlight specific funding opportunities for a newly burgeoning form of research- invasive neural recordings for mental health research.

8:30 AM

David McMullen, M.D.’s portfolio includes invasive and non-invasive device-based approaches to treat a variety of mental health indications such as depression, OCD, anxiety, schizophrenia, amongst other disorders. He oversees device development and biomarker discovery grants as well as clinical trials ranging from first-in-human to pivotal studies intended to obtain FDA regulatory approval. Dr. McMullen also participates in the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. He helps lead programs focused on non-invasive neuromodulation and also works on invasive device development and neuroethics.

Suzanne Haber, Ph.D.

University of Rochester; Harvard University

“From primate anatomy to human neuroimaging: The circuits that underlie neurostimulation targets for psychiatric disease.”

Obsessive-compulsive disorder, major depressive disorder, and addiction are manifestations of dysfunction of cortico-cortical and cortico-basal ganglia networks. The internal capsule, ventral striatum, and medial forebrain bundle are the three subcortical deep brain stimulation targets for these diseases. This talk combines the precision of anatomy in nonhuman primates (NHPs) with high resolution imaging in both NHPs and humans to localize and characterize the position and organization of cortical fibers through these targets. These data are discussed in the context of the connections captured by stimulating each target in patients.

9 AM

Suzanne Haber, PhD, received her PhD in neuro-and bio-behavioral sciences from Stanford University. Her research focuses on the neural network underlying learning and decision-making that leads to the development of action plans. The cortico-cortical and cortico-basal ganglia-thalamic systems are central to this network and comprises a diverse group of structures involved in reward and motivation, cognition and motor control. Pathology of this network is implicated in several mental health disorders including drug addiction, obsessive-compulsive disorder, and depression and anxiety. Her lab is addressing the hypothesis that cortico-cortical and cortico-basal ganglia connections are critical for integrating information across functional domains. The lab is also investigating the organization of cortical fibers within white matter bundles. These studies are important for understanding specific connections that may be abnormal in disease and in developing therapeutic targets for deep brain stimulation.

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FRIDAY, OCTOBER 25 Patricia Limousin, Ph.D. University College London

“Deep brain stimulation in the treatment of movement disorders in 2019”

Deep brain stimulation (DBS) has been used to treat movement disorders for more than 20 years. Although the clinical efficacy and side effects are largely established to treat Parkinson’s disease, dystonia and various tremors, many controversies remain, in particular regarding the heterogeneity of outcome, the role of different targets, and the long-term efficacy. The mechanisms of action of DBS in those different disorders are also debated. New technologies are becoming available in terms of imaging and parameters of stimulation; their possible advantage remains to be established.

9:20 AM

Professor Patricia Limousin is Professor of Neurology at the Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology and Consultant Neurologist at the National Hospital for Neurology and Neurosurgery, London, UK, where she set up the Deep Brain Stimulation Unit. She trained at the University of Grenoble, France. She obtained a PhD on the role of STN DBS to treat Parkinson’s disease. She worked along Professors Benabid and Pollak in Grenoble and has received international recognition for her research on the impact of DBS surgery on the clinical and motor symptoms of Parkinson’s disease, dystonia and other movement disorders.

Ian Cook, M.D.

Los Angeles TMS Institute

“Translational Neuroscience in Neuromodulation: The Case of Trigeminal Nerve Stimulation”

Cranial nerve stimulation methods can address unmet needs for patients with pharmacoresistant neurological and psychiatric disorders. Stimulation of the trigeminal nerve was observed to have anti-epileptic effects in a rodent model; subsequent clinical experiments and neuroimaging and neurophysiologic studies, have iteratively led to more work which culminated in the FDA clearance in 2019 of TNS as first-in-class treatment for pediatric ADHD. In this presentation, we will review this circuitous path from lab observation and clinical serendipity to an approved clinical treatment.

9:40 AM

10 AM

Ian Cook MD, is a Professor Emeritus of Psychiatry and Bioengineering at UCLA, and was Chief Translational Innovation Officer at the UCLA Semel Institute. He now directs the Los Angeles TMS Institute. He has worked to develop neuromodulation interventions for depression, PTSD, ADHD, and epilepsy, with years of NIH, philanthropic, and industry support. He has published over 130 original research articles and is an inventor on over 40 patents on biomedical devices and systems. He received his BSE from Princeton University and his MD from Yale; he completed residency and NIMH fellowship training in Psychiatry at UCLA.

PANEL DISCUSSION Chairs: Suzanne Haber and John Markman

10:30 AM Coffee Break 6

FRIDAY, OCTOBER 25 Session II: Non-invasive Neuromodulation in the Laboratory and Clinic

Marom Bikson, Ph.D. City College of New York

“The targeting limits of transcranial electrical stimulation”

Transcranial electrical stimulation (tES) include tDCS, tACS, HD, Interferential Stimulation, and ECT approaches. Modern method to predict and measure brain current flow support optimization of tES in ways generalizable across approaches. For example, the 4x1 HD electrode montage support targeted cortical stimulation with any waveform. 4x1 HD tACS at frequencies tuned to individual brain network dynamics allows targeting of regional oscillations, now investigated to improve working memory. 1x1 HD has been combined with TMS to identify neuromodulation with directional mm-level specificity. HD Interferential Stimulation and ECT approaches can leverage coupling spatial and temporal aspect of dose.

11 AM

Dr. Marom Bikson is the Shames Professor of Biomedical Engineering at the City College of New York (CCNY) of the City University of New York (CUNY). His research group focuses on rapid medical device translation which spans all stages of device development. Dr. Bikson has published over 250 papers and book chapters and is inventor on over 40 patents. Dr. Bikson is the technology editor for Brain Stimulation journal, founding chairman of the NYC Neuromodulation conferences, and serves on a range of academic, government, and industry panels. He received a Ph.D. in Biomedical Engineering (Neural Engineering specialized) from Case Western Reserve University, in Cleveland, and a B.S. in Biomedical Engineering (Instrumentation Concentration) from Johns Hopkins University, Baltimore.

Jacinta O’Shea, BA, MA, MSc, DPhil (Oxon) University of Oxford

“Neural bases of individual differences in sensorimotor plasticity”

Big Data Neuroimaging has begun to identify modes of neural variation associated with individual differences in healthy and disease states. This raises the future prospect of personalized medicine for psychiatric and neurological disorders. Brain stimulation has distinctive therapeutic potential.

It offers a means to drive functional brain reorganisation in a targeted way. However, individuals differ in response to stimulation, and the factors that determine this are not understood. I will present a causal mechanistic account of individual variation in response to a plasticity protocol with therapeutic benefits in chronic stroke. Explaining phenotypic variation is an essential step towards personalized medicine.

11:20 AM

Dr Jacinta O’Shea is a cognitive neuroscientist with research interests in attention, action and emotion. She is Principal Investigator at the Wellcome Centre for Integrative Neuroimaging at the University of Oxford. Her group specializes in combining brain stimulation with neuroimaging and cognitive manipulations to drive adaptive brain and behaviour change. The ultimate aim is to translate experimental interventions into rational therapeutics for psychiatric and neurological disorders. Jacinta was recently awarded a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society for research that aims to advance personalized precision stimulation to treat depression.

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FRIDAY, OCTOBER 25 Stephanie Buss, M.D. Harvard Medical School

“TMS as a biomarker in Alzheimer’s disease and related dementias”

Novel perturbation biomarkers using TMS and TMS-EEG show promise as future prognostic or therapeutic targets in Alzheimer’s disease (AD), Frontotemporal dementia, and other neurodegenerative disorders. TMS in motor cortex can measure declines in cortical plasticity in AD using intermittent theta burst stimulation. AD and FTD dementia can be distinguished using short-latency afferent inhibition, intracortical facilitation, and short-latency intracortical inhibition.

Cortical hyperexcitability has been recorded across multiple neurodegenerative conditions, and is reflected in several TMS metrics including resting motor threshold, cortical reactivity, and inputoutput relationships. Future directions for use of TMS biomarkers as prognostic measures and therapeutic targets will be discussed.

11:40 AM

12 PM

Stephanie Buss, MD is a practicing cognitive neurologist with a clinical and research focus on neurodegenerative disorders. She completed medical school at Albert Einstein College of Medicine, and residency at Beth Israel Deaconess Medical Center (BIDMC) at Harvard Medical School. She finished her research-focused Behavioral Neurology / Neuropsychiatry Fellowship in 2018, and is now Co-Director of the Memory A2Z Clinic in the Cognitive Neurology Unit at BIDMC. She is currently completing a study investigating TMS markers of neural plasticity and hyperexcitability as prognostic markers of cognitive outcomes at 1-year follow up in mild cognitive impairment (MCI).

PANEL DISCUSSION Chairs: Michel Berg and Steven Silverstein

12:30 PM Lunch

Session III: Electrocorticography in Cognitive Neuroscience - Oscillatory Brain Dynamics

Sophie Molholm, Ph.D.

Albert Einstein College of Medicine; University of Rochester

“Brain mechanisms of enhanced perception following multisensory stimulation: Insights from electrocorticography (ECoG) and scalp electrophysiology”

Objects and events are, for the most part, multisensory, and emanate or reflect multiple forms of energy that in turn stimulate a highly-specialized set of sensory receptors that transmit this information to the nervous system. While the individual sensory systems have been mapped extensively, how multisensory inputs are integrated to impact perception is not well understood. I will discuss ECoG and EEG findings that reveal phase reset as an important mechanism for cross-sensory influences on cortical processing, and make the case that multisensory integration involves a cortical network that unfolds in a manner that is both anatomically and temporally dependent upon the process at hand.

2 PM 8

Dr. Molholm is Professor of Pediatrics, Neuroscience and Psychiatry & Behavioral Sciences at Albert Einstein College of Medicine. As a Cognitive Neuroscientist, she uses psychophysics and brain imaging techniques to probe the brain processes underlying perception and cognition in healthy and clinical groups. Her work is directed at understanding sensory-perceptual processing and how the sensory systems interact in the brain to influence perception and behavior, and investigating how attention impacts these processes. She maintains an active, federally funded, research program, and has published over 80 peer-reviewed articles to date.

FRIDAY, OCTOBER 25 Michael Beauchamp, Ph.D. Baylor College of Medicine

“Models and Mechanisms of Multisensory Speech Perception”

Humans interacting face-to-face make use of auditory cues from the talker’s voice and visual cues from the talker’s mouth to understand speech. I will discuss computational models that use Bayesian principles to predict human speech perception. These models make specific predictions about the neural mechanisms of speech perception, which we test with electrocorticography (ECoG). The anatomical focus of these studies is the posterior superior temporal gyrus and sulcus (pSTS), a key hub for multisensory integration in the human brain.

2:20 PM

Michael completed his undergraduate degree in Biology at Harvard University, studying directionally-selective ganglion cells in the rabbit retina (advisor: Dick Masland). He received his PhD from University of California, San Diego, using fMRI to examine the effects of attention on the motion processing system (advisors: Ted DeYoe and Tom Albright). He then completed a postdoc at the intramural research program of the NIMH (advisors: Alex Martin and Jim Haxby).

His first faculty position was at the University of Texas Medical School in Houston, and in 2015 he moved to Baylor College of Medicine to become the director of the Core for Advanced MRI and Vice-Chair of the Department of Neurosurgery.

Youssef Ezzyat, Ph.D. Swarthmore College

“Direct brain stimulation during episodic memory”

Memory failures are frustrating and often the result of ineffective encoding. These lapses in memory occur in healthy populations and are known to be the result of fluctuations in neural activity during learning. One approach to improving memory outcomes could be through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects. We describe the use of a closed-loop system to monitor, decode, and stimulate neural activity using direct brain recordings in humans. This system improves recall, reveals the lateral temporal cortex to be a reliable target for memory enhancement, and suggests a therapeutic approach for treating memory dysfunction.

2:40 PM

3 PM

Youssef Ezzyat directs the Memory and Cognition Lab at Swarthmore College, which focuses on understanding the electrophysiological mechanisms of episodic memory. His recent work uses methods from machine learning to develop neural decoding models that can guide closed-loop systems to deliver direct brain stimulation during memory encoding. He also uses non-invasive methods (scalp EEG/fMRI) to study how the brain organizes information in long-term memory, and how the structure of our experiences influences the neural mechanisms that organize our memories.

PANEL DISCUSSION Chairs: John Foxe and Kevin Mazurek

3:30 PM Coffee Break 9

FRIDAY, OCTOBER 25 Kilian J. and Caroline F. Schmitt Neuroscience Keynote Address Helen Mayberg, M.D.

Icahn School of Medicine at Mt. Sinai, Emory University

“Iterative Strategies to Refine and Optimize Deep Brain Stimulation for Depression�

It is almost 15 years since the first proof-of-principle report of deep brain stimulation (DBS) for treatment resistant depression. Progress continues, with implementation of refined techniques for surgical targeting and emerging clues as to which patients are most likely to benefit. Additional perspectives on trajectory, time-course, and sustainability of DBS effects have been advanced by device innovations that address mechanisms at the neural level. Current studies are further poised to explore strategies to maximize rehabilitative gains of patients once the DBS itself is optimized. Together, these studies provide a unique opportunity to form a more comprehensive and nuanced understanding of illness and recovery.

4 PM

Helen Mayberg, a neurologist, is Professor of Neurology, Neurosurgery, Psychiatry and Neuroscience, and the Mount Sinai Professor in Neurotherapeutics at the Icahn School of Medicine where she serves as founding Director of the Nash Family Center for Advanced Circuit Therapeutics. She is a member of the National Academy of Medicine, the American Academy of Arts and Sciences and the National Academy of Inventors. Over her career, she and her colleagues have characterized neural systems mediating major depression and its recovery, defined imaging-based illness subtypes to optimize treatment selection and introduced the first use of deep brain stimulation for treatment resistant patients.

6:00 PM Gala Dinner Reception at the Genessee Valley Club

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SATURDAY, OCTOBER 26 8 AM Breakfast 8:45 AM Welcome & Introduction by Web Pilcher, M.D., Ph.D.

Session IV: Deep Brain Stimulation in Neuropsychiatric and Neurological Disease (II)

European Journal of Neuroscience Young Investigator Award Lecture

Nanthia Suthana, Ph.D. UCLA

“Recording and stimulation of deep brain activity during real world spatial navigation and memory in humans”

How the human brain supports accurate navigation of a learned environment has been a topic of active research for nearly a century. I will present a newly development platform that enables wireless and programmable recording and stimulation of deep brain activity during tasks of ambulatory behaviors in humans. Our initial studies using this platform provide the first characterization of neural oscillations in the human medial temporal lobe during ambulatory spatial memory tasks. We also propose the platform for use in future investigations of neural mechanisms underlying freely moving behaviors and testing of novel neuromodulatory therapies in humans.

9 AM

Nanthia Suthana, Ph.D., is an Assistant Professor of Psychiatry, Neurosurgery, and Bioengineering.

She completed her B.S. and Ph.D. in Neuroscience and postdoctoral training at UCLA before joining faculty. She uses intracranial recordings and DBS in patients with implanted electrodes to understand cognitive function and develop novel therapies. She has been awarded a NIH Brain Initiative grant as PI, 3 additional grants as Co-I and the McKnight Technological Innovations Award. She serves as the Associate Director of the Neuromodulation Division at the Semel Institute for Neuroscience, and the Associate Director of Neuroscience outreach for the Brain Research Institute at UCLA.

Ralph Koek, M.D.

David Geffen School of Medicine at UCLA

“Amygdala Deep Brain Stimulation for Treatment-Refractory Combat PTSD: Data from the first two cases and future aspirations.”

We initiated a pilot study of high-frequency, bilateral basolateral amygdala deep brain stimulation (www.ClinicalTrials.gov, NCT#02091843) for treatment-resistant combat PTSD, hypothesizing that failure of fear extinction is driven by amygdala hyperactivity ineffectively suppressed by ventromedial prefrontal cortex inhibition. I will present data on response in subjects 1 (>40% improvement from baseline CAPS 119 sustained > 1.5 year) and 2 (> 9 months sustained improvement in anger dyscontrol), as well as adverse effects, functional outcomes, and preversus 1-year post-stimulation 18-FDG PET data. I will also share our future study plan to employ responsive neurostimulation.

9:20 AM

Dr. Koek received his MD from Wayne State University in Detroit, completed Psychiatry residency at USC and joined UCLA Faculty in 1990, serving as Psychiatry Residency teaching faculty until 2018, including leadership of the Mood Disorders Clinic with Dr. Boghos Yerevanian. Currently he splits his time between providing clinical care to veterans, and, with a multidisciplinary group of clinical neuroscientists, conducting the first investigation of amygdala DBS for treatment-refractory combat PTSD. He has published reviews of treatment-refractory PTSD, psychopharmacology and neuromodulation in PTSD; and the study protocol and preliminary data from the amygdala DBS trial.

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SATURDAY, OCTOBER 26 Gregor Thut, Ph.D. University of Glasgow

“Probing and manipulation of brain oscillations & associated functions by combined TMS and EEG”

A key question in cognitive neuroscience is how brain activity orchestrates brain function. Recent advances assign an important role to oscillatory brain activity. This type of activity is thought to reflect the assembly of neuronal elements into functional networks and can be measured using electro-/magnetoencephalography (EEG/MEG). My talk will cover developments in how to use non-invasive transcranial magnetic stimulation (TMS) to manipulate oscillatory brain activity and examine its roles in brain function. These causal interventions into oscillatory brain activity and function help understanding the brain and identifying new approaches for experimental and clinical interventions into the brain-behaviour relationship.

9:40 AM

10 AM

Gregor Thut, PhD, is Professor of Cognitive Neuroscience at the University of Glasgow, and Director of its Centre for Cognitive Neuroimaging (CCNi). His research interfaces human electrophysiology and non-invasive transcranial brain stimulation, with an emphasis on how dynamic network activity in the human brain, inferred from brain oscillations, relate to perception, attention and cognition. His goal is to develop the existing non-invasive stimulation techniques into more powerful neuroscience tools and clinically effective protocols, to manipulate and better understand the brain-behaviour relationship and the neural processes driving it.

PANEL DISCUSSION Chairs: Julie Fudge and Sophie Molholm

10:30 AM Coffee Break

Session V: Pre-Operative and Intra-Operative Brain Mapping

Nitin Tandon, M.D. University of Texas, Houston

“Intracortical recordings for understanding and modulating language”

My research program uses intracranial recordings in patients with epilepsy to understand a variety of language processes while localizing their seizures. We approach language from a network rather than a localizationist perspective and combine this with stimulation to text network models. We are developing the groundwork for neural prosthetics to decode language in patients rendered aphasic by brain injury.

11 AM 12

Dr. Tandon, Professor of Neurosurgery at UTHealth and Director of the Epilepsy Surgery Program at Memorial Hermann Hospital, studies cognitive functions using imaging and invasive electrophysiology. His U01- and R01-funded research initiatives focus on the understanding of human language using a multimodal approach combining intracranial electroencephalography (icEEG), cortical stimulation, fMRI and tractography. Recent focus has been on developing optimal tools that facilitate high-end analyses of icEEG data and optimized analytic and representational techniques. Other work on neural processing during cognitive control, spatial navigation and episodic memory has facilitated our understanding of normal cognition and altered neurophysiology in the epileptic brain.

SATURDAY, OCTOBER 26 Nathan Crone, M.D. Johns Hopkins University

“The intersection between human functional brain mapping and brainmachine interfaces”

Invasive neural recording techniques originally developed for functional brain mapping prior to epilepsy surgery have been investigated in recent years as a potential avenue for brain-machine interfaces to restore communication in patients with profound motor impairments. I will briefly discuss clinical trials that are underway and in development using this approach, as well as the opportunities and challenges these trials present in the near and far term.

Nathan Crone, M.D. is a Professor in the Johns Hopkins Department of Neurology and Director of the Cognitive Neurophysiology and Brain-Machine Interface Laboratory. Dr. Crone’s research focuses on the use of human intracranial electrophysiology for pre-operative functional mapping, cognitive neuroscience, and brain-machine interfaces.

11:20 AM

Thomas Schlaepfer, M.D.

Albert-Ludwigs-Universitat Freiburg; Johns Hopkins University

“Effects on Affect – Neuromodulation for Treatment Resistant Depression”

While psychotropic drugs for depression work by altering neurochemistry to a large extent in widespread regions of the brain, many of which may be unrelated to the disease. We believe that more focused treatment approaches that modulate specific networks in the brain will prove a more effective approach to help treatment-resistant patients. Whereas existing depression treatments approach this disease as a general brain dysfunction, a more complete and appropriate treatment will arise from thinking of depression as a dysfunction of specific brain networks that mediate mood and reward signals. A better understanding of defined dysfunctions in these networks will invariably lead to a de-stigmatization of psychiatric patients and the medical specialty treating them.

11:40 AM

12 PM

Thomas E. Schlaepfer, MD chairs the Division of Interventional Biological Psychiatry University Hospital Freiburg; he holds a joint appointment as Associate Professor of Psychiatry and Mental Hygiene at Johns Hopkins University. He is a fellow of the American College of Neuropsychopharmacology and chair of the Task Force on Brain Stimulation of the World Federation of Societies of Biological Psychiatry. Dr. Schlaepfer focused the research of his group on translational, functional neuroimaging and clinical effects of neuromodulation interventions (including repetitive transcranial magnetic stimulation, vagus nerve stimulation, magnetic seizure therapy and deep brain stimulation) for treatment resistant major depression.

PANEL DISCUSSION Chairs: Brad Mahon and Web Pilcher

12:30 PM Lunch 13

SATURDAY, OCTOBER 26 Session VI: Neuromodulation in Epilepsy

Gregory Worrell, M.D., Ph.D. Mayo Clinic

“Integrating Brain Implants with Local and Distributed Computing Devices: A Next Generation Epilepsy Management System”

Brain stimulation has emerged as a treatment for neurological and psychiatric disease. Interfacing implantable devices with local and cloud computing resources has the potential to improve disease tracking, management, and efficacy for many diseases. Recent studies in patients with focal epilepsy demonstrate the feasibility of seizure detection, seizure forecasting and therapeutic electrical stimulation. In this talk I review progress on a next generation epilepsy management system where low demand analytics requiring fast response times are embedded in the device, and more complex algorithms for forecasting are implemented off­the­body on local and distributed cloud computing environments.

2 PM

Greg Worrell, MD, PhD is Professor of Neurology and Physiology & Biomedical Engineering at Mayo Clinic in Rochester, Minnesota. He is the Director of Mayo Systems Electrophysiology Laboratory, and was formerly Clinical Neurophysiology Division Chair and Neurology Research Vice-Chair. His research and clinical practice are at the interface of neurology and engineering.

His team is developing next generation devices capable of large-scale neurophysiology, brain state tracking, and therapeutic stimulation. Dr. Worrell received his Ph.D. in Physics from Case Western Reserve University, MD from University of Texas Medical Branch, and Neurology & Epilepsy training at Mayo Clinic & University of Pennsylvania.

Mark Richardson, M.D.

Massachusetts General Hospital/Harvard Medical School

“Basal ganglia-thalamocortical networks in speech”

Actions are not mediated solely by cortical processes but rely on communication within basal ganglia-thalamocortical loops. Speech is one example, but subcortical participation in the perception and production of speech is not well understood. We created a paradigm for simultaneous recording of cortical and subcortical activity during speech, in subjects undergoing deep brain stimulation (DBS) surgery. Our data suggest multiple ways in which the subthalamic nucleus and thalamus may participate in speech planning and modulation. The goal of this work is to create an improved neurophysiological framework for informing novel DBS strategies to improve speech dysfunction in movement disorders.

2:20 PM

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Dr. Richardson is a neurosurgeon-neuroscientist and Director of Functional Neurosurgery at Massachusetts General Hospital. His lab conducts human systems neuroscience research using intracranial recording and stimulation, including the study of cortical-subcortical interactions during speech and the development of novel approaches to closed-loop brain modulation for both movement disorders and epilepsy. He is also the Charles Pappas Associate Professor of Neurosciences at Harvard Medical School, Visiting Associate Professor of Brain and Cognitive Sciences at MIT, and co-director of the MGH-MIT InBRAIN Partnership.

SATURDAY, OCTOBER 26 Andrew L. Ko, M.D. University of Washington

“Closed Loop Deep Brain Stimulation for Essential Tremor”

Deep Brain Stimulation (DBS) for essential tremor is safe and effective. Current open-loop stimulation provides stimulation to control tremor at constant parameters. While effective, this paradigm likely delivers DBS when it is not needed, which is an unneeded drain on battery life, and which potentially exposes patients to unnecessary side-effects of stimulation. We present one method of delivering closed-loop DBS (CL-DBS), which provides therapy based on patient behavior that elicits tremor. This paradigm provides savings in power and is as clinically-effective as traditional DBS during blinded rating. Future directions for work in demand-driven DBS are also presented.

2:40 PM

3 PM

Andrew Ko is a board-certified neurosurgeon and assistant professor at the University of Washington. Dr. Ko earned his M.D. from University of Illinois, Chicago, and completed his neurosurgery residency at the University of Washington. After completion of his fellowship in stereotactic and functional neurosurgery at OHSU Portland, he returned to the UW where he is now head of the Functional and Restorative Neurosurgery Program and a neurosurgeon with the Regional Epilepsy Center at Harborview Medical Center. His clinical interests include imageguided deep brain stimulation, open and stereotactic minimally-invasive surgery for epilepsy, open and percutaneous treatment of trigeminal neuralgia, functional mapping of the brain and surgery for brain tumors. His research interests include deep brain stimulation, functional neurosurgery, epilepsy and pain, with significant emphasis on neuromodulatory treatments for movement disorders in particular, the development of closed-loop or patient-responsive therapies.

PANEL DISCUSSION Chair: Michel Berg

3:30 PM Coffee Break

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SATURDAY, OCTOBER 26 The Del Monte Family Keynote Address Itzhak Fried, M.D., Ph.D. UCLA

“Neuromodulation of Human Memory: From Single Neurons to Clinical Translation”

4 PM

Loss of memory is one of the most dreaded afflictions of the human condition. With the increase in population age and number of patients with memory impairments, we face social calamity of alarming dimensions. The medial temporal lobe (MTL) is central to the transformation of percepts into lasting memories. Yet the neuronal code underlying this transformation in humans remains unclear. Recordings from neurons in patients implanted with electrodes for clinical reasons provide a rare opportunity to bridge physiology with cognition. During sleep these recordings provide insight into the orchestration of several brain rhythms to promote consolidation of memories. Electrical stimulation provides an exciting tool to study causal mechanisms of memory.

During encoding, stimulation at the entorhinal region appear to enhance subsequent memory performance. During slow wave sleep electrical stimulation locked to hippocampal slow waves, results in enhancement of slow wave power as well as improvement in memory performance.

These results may lead to development of closed loop neuro-prosthetic devices- memory aids- yet at the same time, we need to consider the risks and benefits in a Brave New World of enhancement, inception and deletion of memories.

Itzhak Fried, MD, PhD, is Professor of Neurosurgery and Psychiatry and Biobehavioral Sciences at UCLA and Director of the Epilepsy Surgery Program there. Dr. Fried received his MD degree from Stanford University and PhD from UCLA, did his neurosurgical training at Yale, and is Board Certified in Neurosurgery and a Fellow of the American College of Surgeons. He also directs the Cognitive Neurophysiological Laboratory at UCLA and is a Fellow of the American Association for the Advancement of Science While providing neurosurgical care to patients, Dr. Fried’s research has centered on the recording of single neuron activity in awake patients and on the use of these signals coupled with electrical stimulation to understand and modulate the networks underlying human cognition in health and in disease.

5:15 PM Closing Remarks

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UNIVERSITY OF ROCHESTER COMMITTEE SCIENTIFIC PLANNING COMMITTEE

John Foxe, Ph.D.

Webster Pilcher, M.D., Ph.D.

Suzanne Haber, Ph.D.

Julie Fudge, M.D.

Director, The Ernest J. Del Monte Institute for Neuroscience Professor and Chair, Dept. of Neuroscience The Kilian J. and Caroline F. Schmitt Chair in Neuroscience

Professor and Chair, Dept. of Neurosurgery Ernest & Thelma Del Monte Distinguished Professor in Neuromedicine, Dept. of Neurosurgery

Professor, Depts. of Pharmacology and Physiology and Neuroscience Adjunct Professor at Harvard University

Associate Professor, Dept. of Neuroscience

Š Carnegie Mellon

Ben Lee, M.D.

Bradford Mahon, Ph.D.

John Markman, M.D.

Michel Berg, M.D.

Chair & John Romano Professorship of Psychiatry, Dept. of Psychiatry Professor, Dept. of Neuroscience

Scientific Director, Program for Translational Brain Mapping Associate Professor of Psychology at Carnegie Mellon University

Professor, Depts. of Neurosurgery and Neurology

Professor, Dept. of Neurology

Sophie Molholm, Ph.D.

Kevin Mazurek, Ph.D.

Fei Shang

Adjunct Professor, Dept. of Neuroscience Professor, Depts. of Pediatrics, Neuroscience, and Psychiatry and Behavioral Sciences at Albert Einstein College of Medicine

Research Assistant Professor, Dept. of Neuroscience

Neuroscience Ph.D. Student

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