2019 Duke Center for Autism Annual Report

Duke Center for Autism and Brain Development Exchange on Erwin 2608 Erwin Road, Suite 300 Durham, NC 27705 Hock Plaza 2424 Erwin Road, Suite 501 Durham, NC 27705 For Clinical Appointments: 919.681.7148 For Research Inquiries: 888.691.1062 autismresearch@dm.duke.edu Website: www.autismcenter.duke.edu Director Geraldine Dawson, PhD William Cleland Distinguished Professor Department of Psychiatry and Behavioral Sciences Associate Director Nicole Heilbron, PhD Associate Professor Department of Psychiatry and Behavioral Sciences Associate Director Linmarie Sikich, MD Faculty Department of Psychiatry and Behavioral Sciences Duke Clinical Research Institute Director, Translational Research Yong-Hui Jiang, MD, PhD Professor Department of Medicine Division of Medical Genetics Director, Early Intervention Services Jill Howard, PhD Assistant Professor Department of Psychiatry and Behavioral Sciences Director of Operations Samantha Bowen, PhD Director, Data Management and Analysis Core Scott Compton, PhD Associate Professor Department of Psychiatry and Behavioral Sciences Director, Neurophysiology Laboratories Michael Murias, PhD Assistant Research Professor Duke Institute for Brain Sciences Liaison, Duke Pediatric Primary Care Jeffrey Baker, MD, PhD Professor Department of Pediatrics

Duke Center for Autism and Brain Development Annual Report July 1, 2018 – June 30, 2019 Letter from the Director

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Research Highlights

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Searching for Genetic Clues

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Using Brain Imaging to Assess the Effects of Novel Autism Treatments

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Large, Rigorous Study Seeks to Identify Autism Biomarkers

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The International Society for Autism Research (INSAR) Annual Meeting

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Addressing Questions about Universal Screening for Autism

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Using Technology to Improve Autism Screening

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Duke Center for Autism Participates in DIBS Distinguished Lecture & Symposium

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By the Numbers

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Duke Center for Autism and Brain Development Highlights July 2018– June 2019

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Clinical Services

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Social Workers Provide Wide Range of Support

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Transitioning to Adulthood

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Training

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Using Machine Learning to Help Our Understanding of Autism

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Trainee Spotlight

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Building Partnerships to Support Early Diagnosis and Intervention in Africa

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Community

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Challenging the Way People Think about ‘Normal’

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Duke Center for Autism Participates in DIBS Discovery Day

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Duke Center for Autism Hosts “Music 2 the Max” Event

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Duke Emergency Department Raises Funds for Duke Center for Autism

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Dear Friends, When I was in graduate school, I was taught that autism could not be detected until a child was three years of age. We knew little about the causes of autism and had little to offer in terms of effective treatments.

As I hope you will see from our annual report, we’ve made great strides in our understanding and treatment of autism. Advances in genetics are shedding light on the causes of autism and providing clues to its molecular basis. New brain imaging methods are providing a remarkably detailed picture of the dynamic and changing nature of the brain. We are part of a nationwide collaboration that is identifying biomarkers for autism so we can design better clinical trials and detect autism earlier. These biomarkers are being used to identify infants at risk for autism so that early behavioral intervention can be offered at the earliest age possible. We are taking advantage of new technologies, such as computer vision analysis, and combining them with data science and machine learning, to create novel tools for early detection that can be used in primary care. The Center’s research is addressing fundamental questions that directly impact policy and practice, such as how can we reduce disparities in access to diagnosis and treatment here in North Carolina and worldwide?

While exciting research at the Duke Center for Autism continues to push the envelope in early detection and treatments for autism, the Duke Autism Clinic strives to meet families where they are today, whether that is getting a first-time diagnosis, developing peer relationships, or making a successful transition to high school. Using an interdisciplinary team approach, clinicians work to meet the needs of the whole child, including both behavioral and physical health needs. Working collaboratively with other providers throughout the Duke University Health System, our goal is an individualized, comprehensive, compassionate approach to clinical care. We adopt a lifespan perspective for each person we serve.

Through the Center’s focus on neurodiversity, we support and celebrate the talents of adults on the spectrum whether that adult is a Duke undergraduate student, a Duke employee, or a young person being seen at our clinic who is preparing for the next step after high school.

A major goal is to increase capacity for autism research and services through training. One of the most gratifying parts of my job is getting to know the wide range of trainees who help with our studies and provide clinical services. Whether the trainee is an undergraduate student who is still deciding what they want to do for their career or a medical resident who is honing their research or clinical skills, each one fills me with hope for the future. Their energy, talents, and commitment ensure that we will continue to make progress in meeting the needs of people with autism and their families.

Finally, I want to thank the many people who partner with us and make a real difference. I hope you’ll enjoy reading about the 73-year-old father who is running 3,000 miles to raise money for autism research, the Duke Emergency Department employees who raised funds to support the Center, and the Canadian member of Parliament who challenged us to think differently about autism and other disabilities. These are just a few of the people who have donated their time and support to the Center’s efforts. Without their generosity, our work would not be possible.

Warm regards,

Geraldine Dawson, PhD Director

Research Only two drugs are approved by the FDA to treat autism, and neither of them are designed to directly address the core symptoms of social challenges and repetitive behaviors.

Searching for Genetic Clues

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he Center’s scientists and clinicians are addressing this unmet need in several ways.

One way is to search for specific mutations in the genes of children with autism, and to study how those mutations affect certain molecular pathways in the brain.

That’s the approach being taken by physicianscientist Yong-Hui Jiang, MD, PhD. “If you understand better why a mutation causes the autism you may be able to develop a novel treatment,” he says.

“I’m a clinical geneticist,” he says. “I see patients in the clinic with neurodevelopmental disorders, and I try to help understand the cause and how to help these patients.”

Mutations in about 100 genes have been strongly linked to autism, but there are likely many, many more. One of the strongly linked mutations occurs in the SCN2A gene. It’s present in less than 1 percent of people with autism, but even so, it’s still one of the most common mutations seen in people with autism, who are a diverse group.

SCN2A is important in facilitating communication between brain cells. It regulates sodium channels, which are the portals in brain cells that let in signals in the form of sodium ions. “If you are missing this channel or it has abnormal function, the neuronal activity will be affected,” Jiang says. The mutation is also linked to a certain type of early onset epilepsy.

In his clinic he might see a child with autism who has a mutation in a gene not previously linked to autism.

Is that mutation causing the symptoms of autism?

“You won’t be able to resolve this question very easily in the clinic so you need to take it back to the lab to see if you can produce the evidence,” he says.

He combines genetics and neurobiology to try to untangle the ways in which mutations cause changes in brain development and behavior.

About 20 percent of people with autism have an identifiable genetic mutation. There’s not a lot of commonality among the mutations, however.

“If you are missing this channel or it has abnormal function, the neuronal activity will be affected.”

Yong-Hui Jiang, MD, PhD

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Jiang says his research path encompasses three steps. The first step is to use cell cultures in the lab to investigate whether cells with SCN2A mutations have malfunctioning sodium channels. “In cell culture, we did see the mutation affect the function,” he says.

“But because it’s a cellular model, it doesn’t reflect the complexity of behavior.”

That leads to step two, which is to introduce this mutation into mice and see whether it gives rise to some of the behaviors seen in people with autism, such as repetitive behaviors and differences in social interaction. Jiang and collaborators, Scott Soderling, PhD, and William Wetsel, PhD, are working on this step now. They have produced a line of mice carrying a mutation that mimics the mutation in humans.

They will soon start testing the behavior of these mice and evaluating the function of their brain cells by measuring electrical current in their brains.

The third step will be to see whether drugs that modulate the function of sodium channels have any effect on the abnormal sodium channels and behaviors in the mice. “You treat the mice like human

patients and see if the drug treatment can improve or correct abnormal behavior or function,” says Jiang. There are a number of sodium-channel drugs already approved for other conditions, and Jiang and his group will start with these. If none of them works, they’ll try to develop a new treatment.

Jiang’s lab is investigating other autism-related genes as well, including SHANK 2, SHANK 3, and the Angelman syndrome gene. Eventually he hopes that these studies of different mutations will illuminate some shared mechanisms that can explain how disparate genetic mutations lead to similar results in the brain.

And if that’s the case, there’s a possibility that a single drug could prove helpful for people with a variety of different genetic mutations.

While that possibility is still far down the road, Jiang, Soderling, and Wetsel are doing the type of research necessary to get there. They keep the long game in mind—their desire to use genetics and neurobiology to help patients and their families.

Eventually researchers at the Center hope that these studies of different mutations will illuminate some shared mechanisms that can explain how disparate genetic mutations lead to similar results in the brain.

This could pave the way for new treatments.

Annual Report 2019

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Research Using Brain Imaging to Assess the Effects of Novel Autism Treatments

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hildren with autism who participated in the Center’s first study to evaluate the efficacy of treatment with umbilical cord blood experienced improvements in language and social functioning six months after treatment. Were those improvements associated with changes in the brain?

That’s the question neurobiologist Kimberly Carpenter, PhD, set out to answer.

Carpenter, assistant professor of psychiatry and behavioral sciences, is an expert on both brain imaging and autism. She analyzed brain images based on magnetic resonance imaging (MRI) of children who participated in the study several years ago of umbilical cord blood as a treatment for autism.

The small study led by Joanne Kurtzberg, MD, and Geraldine Dawson, PhD involved 25 children with autism who all received infusions of their own cord blood, which had been banked at birth.

Working closely with Allen Song, PhD, Carpenter compared the before-and-after MRIs of 19 children whose images were complete enough for the analysis. Song directs Duke’s Brain Imaging and Analysis Center and was responsible for collecting and processing the images.

Above: MRI brain connections in the temporal lobe that improved after treatment.

“Our part of the study was looking at whether there were any changes in brain connectivity,” Carpenter says. “The idea is that cord blood might work by dampening neuroinflammation in the brain, and that might facilitate brain development in a way that supports behavioral change.”

Specifically, she was looking for increased connectivity in the white matter, which she calls the “information highway of the brain.”

To measure connectivity, Song and Carpenter used a technique called diffusion tensor imaging or DTI. “DTI uses information about water movement in the brain to tell you about the organization of the white matter,” she explains. “By using the flow of water, you get an idea of where information is traveling in the

“The idea is that cord blood might work by dampening neuroinflammation in the brain, and that might facilitate brain development in a way that supports behavioral change.”

Kimberly Carpenter, PhD

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brain, how well it is traveling, and how connected the regions of the brain are.”

Indeed, for children who showed improvements in language, she found increased connectivity in the white matter in areas Allen Song, PhD of the brain that support language, including parts of the left temporal lobe. And in children who showed improvements in social engagement, she found increased connectivity in the areas that support social interaction, including the superior temporal sulcus, which is responsible for interpreting facial expressions. Furthermore, the more improvement the child experienced, the greater the increase in connectivity.

“The fiber count increased and there was more structural integrity,” Carpenter says. “To keep with the highway metaphor, we saw more lanes, so there were more places for information to travel.”

To Carpenter, the results were striking because they were just what she expected. That doesn’t always happen in scientific research. “It’s so satisfying,” she says, “and it made me believe in the data.”

Because all the children received the treatment and there was no control group, it’s impossible to know whether the improvements were a result of the cord blood. The purpose of the study was to establish the safety of the treatment and investigate its potential for further research. “It’s a very preliminary study with exciting results,” Carpenter says. “There were definite changes in the brain that correlate with improvements in behavior, but what caused those improvements the next trial will show.”

And the next trial is well underway. Center researchers, led by Joanne Kurtzberg, MD, Geraldine

Above: MRI brain tractography in a child with autism

Dawson, PhD, and Jessica Sun, MD, have finished gathering data in a study of 180 participants, and are beginning to analyze it. Half of the participants received cord blood during the first treatment and half received a placebo infusion. Six months later, the groups switched. The study was double-blind, meaning neither researchers nor families knew the sequence of treatments for any particular child.

The results were not “unblinded” until after all the assessments had been performed, including clinical and parental observation, vocabulary tests, EEGs, eye-tracking tests, and MRIs. Carpenter and Song will be analyzing these brain images as well. If the correlations between behavior and brain connectivity are as clear as before, it could mean this type of MRI analysis could be used to measure the effectiveness of medicines or behavioral treatments for autism in future clinical trials.

Carpenter, K., Major, S., Tallman, C., Chen, L., Franz, L., Sun, J., Kurtzberg, J., Song, A., and Dawson, G. (2019). White matter tract changes associated with clinical improvement in an open-label trial assessing autologous umbilical cord blood for treatment of young children with autism. Stem Cells Translational Medicine.

To Carpenter, the results were striking because they were just what she expected. That doesn’t always happen in scientific research. “It’s so satisfying,” she says, “and it made me believe in the data.”

Annual Report 2019

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Research Large, Rigorous Study Seeks to Identify Autism Biomarkers

Families from across the US participated in the NIH Autism Biomarkers Consortium. Shown (from left to right) are Dr. Jill Howard; a participant and his family; Laura Nations, a clinician on the study; and Lori Reinhart-Mercer, the study coordinator.

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or many medical conditions, it’s relatively straightforward to measure whether a person with the condition is getting better after receiving a treatment. Autism, however, is by its very nature difficult to define or measure. Symptoms vary widely across people and at different ages. Yet developing ways to quantify clinical outcomes in people with autism is critical for evaluating novel treatments.

In collaboration with investigators nationwide, researchers at the Duke Center for Autism and Brain Development have been studying ways to reliably measure outcomes that could be used in autism clinical trials.

Autism affects how the brain functions and how a person processes information, especially information relating to the social world. The approach the Center

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investigators are taking is to establish replicable and quantifiable indices, or “biomarkers,” that can be used to track improvements in brain function and attention that are related to clinical improvement. Such biomarkers also might make it possible to identify those people most likely to benefit from a particular treatment.

As part of this effort, the Center is participating in a multisite study called the Autism Biomarkers Consortium for Clinical Trials, or ABC-CT. In addition to Duke, the other participating universities are Yale, Harvard, UCLA, and the University of Washington.

The study is focusing on several potential biomarkers that measure attention via eye-tracking, and brain activity via electroencephalography (EEG).

Almost 400 children with autism or typical development, ages 6-11 years, are being assessed

at three timepoints: baseline, baseline plus 6 weeks, and baseline plus 6 months. At each visit, they are evaluated in myriad ways, including clinical observation and parental questionnaires in addition to eye-tracking and EEG assessments.

James McPartland, PhD, associate professor of child psychiatry and child psychology at Yale, is the principal investigator of the study. “The scientific benefit of these kinds of biomarkers is having more sensitive, more objective, and more scalable tools to use in clinical trials to measure whether a drug or behavioral treatment is working,” he says. “The practical benefit is we broaden investment in clinical trials in autism. For a disorder as prevalent as autism, there is a relative scarcity of pharma company investment in drug discovery.”

ABC-CT, funded by the National Institutes of Health, also includes representatives from government

agencies. And the group is working closely with the FDA to ensure that its findings will indeed be useful for clinical trials. “We are such a diverse group of stakeholders,” McPartland says. “There are a lot of brains and a lot of discussion going into all the decisions we make.”

The potential biomarkers being investigated relate to children’s social communicative function. For example, researchers use eye-tracking to see how much attention children pay to key social features, such as a person’s eyes, while watching videos of people and objects.

Another promising candidate is a brain signal related to the ability to process information about people’s faces. Called the N170, it’s a signature pattern in the EEG signal that occurs about 170 milliseconds after a person sees a face. “It’s the insignia that the brain is recognizing a face as a face,” says McPartland. In

Samantha Major, MHSc, shows an electrode net to a child before an EEG.

In collaboration with investigators nationwide, scientists at the Duke Center for Autism and Brain Development have been studying ways to reliably measure outcomes that could be used in autism clinical trials.

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Research

Duke hosted the annual meeting of the Autism Biomarkers Consortium investigators. Shown (left to right) are Sara Webb, PhD, Univ. of Washington; James McPartland, PhD, Yale; Geraldine Dawson, PhD, Duke; William Potter, MD, PhD, NIMH; Ann Wagner, PhD, NIMH; Fred Shic, PhD, Univ. of Washington; and Alice Kau, PhD, NICHD.

neurotypical people, the time lapse is about 170 milliseconds. For those on the autism spectrum it’s 10 to 20 percent slower, a discovery published in 2004 by McPartland and Geraldine Dawson, PhD, the director of Duke’s Center for Autism and Brain Development.

N170 varies from person to person, which highlights another possible benefit of biomarkers—the ability to target treatment. In a hypothetical example, those with the slowest N170 might benefit from a treatment that wouldn’t help those with a faster N170, or vice versa.

Any useful biomarker needs to come with data about how that characteristic might change over time in the absence of treatment. That’s why each child in the ABC-CT study is assessed at three timepoints.

Because the study is intended to produce tools that can be used in clinical trials, it’s run like a clinical trial.

Every single aspect is rigorously standardized. The five sites have the same equipment, calibrated the same way, and everyone performing the assessments has the same training and is monitored to ensure consistency. Every timepoint consists of two visits, and everything that happens in those two visits happens in the same order each time.

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“It’s designed like a treatment study without any treatment,” says Samantha Major, MHSc, who oversees the EEG and eye-tracking labs at the Duke Center for Autism.

Major and her team conduct each EEG or eye tracking assessment exactly the same way—or as close to the same as possible when working with children. They fill out a detailed and time-stamped log of each assessment to indicate if anything unusual happened, such as if the child was restless or pulled on the net of electrodes midway through.

“I interact with the children to collect the highest quality data I can,” she says.

The N170 appears to be an especially reliable biomarker. It was accepted into the FDA’s Biomarker Qualification Program, which means that the FDA deemed it promising enough to undergo the FDA review for qualification. Further data analysis will assess whether the biomarker is reliable and linked to clinical improvement.

McPartland and the rest of the investigative team are excited for this part of the process. “We’re on the cusp of having a big complete dataset that we can really make some important discoveries with,” he says.

The International Society for Autism Research (INSAR) Annual Meeting

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Duke students and faculty share their results at the 2019 INSAR meeting. Top (left to right) – Jordan Hashemi, PhD, Dmitry Isaev, Steven Espinosa, Geraldine Dawson, PhD, David Carlson, PhD, and Guillermo Sapiro, PhD. Bottom (left to right) Kevin Ramseur, MS, Jill Howard, PhD, and Geraldine Dawson, PhD.

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# of 2019 INSAR posters and presentations for which Duke Center for Autism faculty and staff were authors

he International Society for Autism Research (INSAR) is a scientific and professional organization whose mission is “to improve the lives of people affected by autism by promoting the highest quality research.” INSAR’s Annual Meeting gives ASD researchers and trainees from around the world the opportunity to exchange and disseminate new scientific findings.

Duke Center for Autism investigators and trainees were actively involved in this year’s meeting, and Dr. Dawson also served in the role of INSAR Past President.

Annual Report 2019

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Research Addressing Questions about Universal Screening for Autism Should pediatricians screen all toddlers for autism?

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he American Academy of Pediatrics says yes, recommending that all toddlers be screened for autism at 18-month and 24-month wellchild visits. But the U.S. Preventive Services Task Force maintains there are too many unanswered questions about the benefits and burdens of universal screening. How many typically developing children are unnecessarily referred for further evaluation, creating worry for families and costing time and money? Does the screening tool work equally well for families from different socioeconomic or ethnic groups? And how many children on the autism spectrum do the current screening approaches miss?

These are critical questions that Geraldine Dawson, PhD, Scott Kollins, PhD, Eliana Perrin, MD and other Center faculty are addressing through a large NIHfunded study being conducted in Duke primary care.

“Universal screening that is uniformly administered with high fidelity and high integrity is really important,” says Scott Kollins, PhD. “We know that if you get early intervention for autism, it improves outcomes. Every month that goes by without diagnosis, you’re missing opportunities to get started on intervention and to work on language and social skills.”

The Center aims to address the questions raised by the Task Force as part of a large study, called A+. The A+ Study, funded by a $12.5 million Autism Centers of Excellence (ACE) grant from the National Institutes of Health, is led

by Dawson and Kollins. The study focused on autism screening is enrolling and following thousands of toddlers who are patients in the Duke Health system to study how well current screening approaches work for detecting autism and related disorders, including attention-deficit/hyperactivity disorder.

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“Every month that goes by without diagnosis, you’re missing opportunities to get started on intervention and to work on language and social skills.”

Scott Kollins, PhD

The Duke Autism Center of Excellence research program focuses on early detection and new treatments for autism and ADHD, two conditions that often co-occur.

All A+ study participants are screened for autism at 18 or 24 months and again at three years of age. The screening tool is a parent questionnaire called the M-CHAT, which consists of 20 questions such as, “If you point at something across the room, does your child look at it?”

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Research

The Duke Autism Center for Excellence research program faculty and staff meet annually with an advisory board comprised of autism and ADHD experts and parents of children with autism.

“Our design for the study is really well positioned to address and answer these questions,” says Kollins, who co-directs the ACE research program with Geraldine Dawson, PhD. All A+ Study participants are screened for autism at 18 or 24 months and again at three years of age. The screening tool is a parent questionnaire called the M-CHAT, which consists of 20 questions such as, “If you point at something across the room, does your child look at it?” and “Does your child play pretend or make-believe?” Certain responses trigger follow-up questions.

Because all the children are re-screened at three years of age, the study will be able to quantify how many children on the autism spectrum were missed by the first screening.

With additional funding from the National Institute of Child Health and Human Development (NICHHD),

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“I let the study team know how they can conduct the study without burdening the clinical staff, and I share with our faculty why they and their patients may benefit from the study.”

Eliana Perrin, MD, MPH

the A+ Study will also address other concerns raised by the Task Force. The investigators are examining whether the socioeconomic status, ethnicity, and other characteristics of the family affect the performance of the M-CHAT. They are also collecting information about the experience from the family’s point of view.

Dawson explains, “We want to better understand whether families experience screening as burdensome, and how to improve the process if they do.”

As the parent of a child with both autism and ADHD, Kollins has experienced the ups and downs of screening and diagnosis firsthand. “The benefits far outweigh the risks from this parent’s experience,” he says.

The study will illuminate how parents from a wide variety of backgrounds experience the screening, which is important because it could affect how they respond to the results of the test, including whether they decide to pursue further testing and treatment.

Over the course of the five-year study, several thousand children who are patients at Duke will participate. In a project this big, success depends on working closely with the pediatricians to make sure the screenings go smoothly in the clinics. Duke pediatricians already screen all toddlers for autism, but data for the study have to be collected according to a particular protocol. It’s also crucial that the needs of the project don’t disrupt the clinics’ ability to provide high quality care to patients and education to trainees. Eliana Perrin, MD, MPH, professor of pediatrics and chief of the Division of Primary Care in the Department of Pediatrics, is a co-investigator in the study and plays a key role along with other

primary care physicians in facilitating the research in a busy clinical setting.

“I let the study team know how they can conduct the study without burdening the clinical staff, and I share with our faculty why they and their patients may benefit from the study,” Perrin says. “I want this project to go well not just for the Duke Center for Autism but for our division—and, most importantly, for our patients and learners who are in clinic.”

If all continues to go well, the Center should have data to answer the Task Force’s questions in several years.

Ultimately, the goal of this large project is to provide more definite answers to how best to screen for autism and other neurodevelopmental disorders, such as ADHD. The hope is that improved screening will reduce disparities in access to early diagnosis and intervention and improve long-term outcomes.

As the parent of a child with both autism and ADHD, Kollins has experienced the ups and downs of screening and diagnosis firsthand. “The benefits far outweigh the risks from this parent’s experience,” he says.

Annual Report 2019

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Research Using Technology to Improve Autism Screening

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lthough autism can be diagnosed by 18 months, the average age of diagnosis in the United States is four years. Early interventions have been shown to help children with autism reach their full potential, so we’re working hard to shrink that gap. One major barrier is the lack of feasible, scalable, and objective autism screening tools that rely on direct observation of the child’s behavior. Current screening methods rely on parent report and don’t work as effectively with parents who have lower levels of literacy or don’t understand the questions being asked. Research suggests that many children are missed.

At the Center, researchers are harnessing advances in technology to address the issue. Engineer Guillermo Sapiro, PhD, and Center Director Geraldine Dawson, PhD, have brought together their shared knowledge to create a digital screening tool that parents, caregivers, and clinicians could use to screen toddlers and young children. If the test indicated the child was at risk for autism, parents and clinicians would arrange for a more thorough evaluation.

The screening tool has been through several iterations in the last few years. The Duke team is working on validating the most recent version, while continuing to improve the design for future versions. “We’re working to make it as accessible and friendly as possible to the user,” says Sapiro, professor of electrical and computer engineering.

The screening tool consists of a series of very short movies and games. While the toddler watches and responds, the in-phone camera collects data on the toddler’s gaze, attention, and emotional expressions.

Movements of landmarks on the child’s face, including the eyes, eyebrows, nose, and lips, are then tracked.

One movie shows a girl playing with toys while interacting with her mother. Toddlers who may be at risk for autism spend more time looking at the toys and less time observing the social interaction between the girl and her mother. Another movie

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shows someone singing nursery rhymes, which elicits smiles from typically developing toddlers.

The current version is being tested in Duke pediatric primary care clinics. The screening tool is being used during a child’s 18-month old well-child visit and will be compared to an autism screening questionnaire that is now used by most physicians. Sapiro and Dawson hope that the screening tool will be more accurate. It may also be more accessible for parents who might struggle to understand and fill out a questionnaire.

In addition to its usefulness for screening, the digital screening tool may help discover new measurable characteristics of autism, called biomarkers, which could be useful in clinical trials.

Over the next four years, thousands of children who are participating in the NIH-funded Duke Autism Center of Excellence (ACE) study will use the tool.

The ACE participants are also being professionally evaluated for autism and other neurodevelopmental disorders, so the team will be able to analyze how well the tool identifies children at risk for autism.

Based on encouraging data from the previous iterations, the team is hopeful that the most recent version will perform well. Eventually, they hope it will be widely and freely distributed to help parents quickly and easily learn whether their child could benefit from a professional evaluation. Sapiro notes

While the toddler watches and responds, the in-phone camera collects data on the toddler’s gaze, attention, and emotional expressions. Movements of landmarks on the child’s face, including the eyes, eyebrows, nose, and lips, are then tracked.

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Research High-end lab equipment can measure eye tracking extremely precisely, but the precision depends on participants keeping their heads still and going through a series of calibration procedures. This type of equipment is also expensive, making it difficult to use in community or home settings.

A toddler watching movies while sitting in someone’s lap is not likely to stay perfectly still or follow calibration instructions.

“It has to be super flexible,” Chang says. “The tradeoff in gaining more flexibility is we lose a lot of precision.”

The team makes up for the loss in precision in several ways. The movies are designed so that the targets of attention are separated as much as possible. That makes it easier to determine whether the toddler is looking at the toys (on the far left of the screen) or the social interaction (on the far right).

Top: Todd Calnan, technical director in the Center’s eye-tracking lab, assesses how well the lab’s equipment is working. This expensive eye-tracking equipment is standard in the field. Bottom: George Chang (left) and Guillermo Sapiro, PhD share the results of their work demonstrating that eye-tracking can be achieved using the camera in an iPhone.

that all children have their hearing tested at birth and their vision tested at school. He thinks autism screening should be just as routine.

Zhuoqing “George” Chang, a PhD candidate in electrical and computer engineering, has been working on the digital screening tool since 2013, using a public domain software when available and writing new software when necessary. Right now, the screening tool is being tested as an iPhone or iPad app, but the team will be able to modify the software, which relies on machine learning, by “retraining” it for different operating systems and devices.

Designing the program to work on a small handheld device has presented a number of challenges.

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In addition to collecting data about gaze and emotion, the tool also collects data about movement. Using facial landmarks, the tool can determine whether the children are able to hold their heads steady, and how quickly they turn when a caregiver says their name. Games also collect data about how quickly and where children touch the screen. This kind of data is important because children with autism have differences in motor control compared to typically developing children.

Chang says the current version of the tool is a huge improvement compared to the previous versions.

“We are collecting extra information we think will be helpful in an assessment of autism risk,” he says.

And he’s continuing to make the tool even more user friendly and precise. For example, even though formal calibration isn’t possible, presenting simple moving stimuli at the beginning of the process will help the software “learn” how to more accurately interpret facial movements from each individual user.

“I really like working with these very meaningful real-life applications,” Chang says. “I think it has the potential to make a big impact.”

Dawson, G., and Sapiro, G. (2019). The potential for digital behavioral measurement tools to transform the detection and diagnosis of autism spectrum disorder. JAMA Pediatrics.

Duke Center for Autism participates in DIBS Distinguished Lecture & Symposium

Top: (left to right) Members of Duke faculty, Guillermo Sapiro, PhD, Alison Adcock, MD, PhD, Kafui Dzirasa, MD, PhD, and David Carlson, PhD presented their work at the DIBS Distinguished Lecture and Symposium. Dawson chaired the symposium. Bottom left: Jordan Hashemi, PhD, Duke postdoctoral associate, presents his work. Right: Joshua Gordon, MD, PhD, Director, NIMH, and keynote speaker, tweets about the research of Elena Tennenbaum, PhD, postdoctoral associate.

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he Duke Institute for Brain Sciences (DIBS) hosted its inaugural Distinguished Lecture & Symposium in February 2019, entitled, “From Brain Circuits to Behavior: How Technology is Transforming the Science of Mental Health.” The event featured Joshua Gordon, MD, PhD, Director of the National Institute for Mental Health, as keynote speaker, as well as presentations by Duke faculty and a poster session.

Many Duke Center for Autism faculty and staff were involved in the event.

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Duke Center for Autism and Brain Development FY19

By the Numbers Clinical Services P hone calls:

8915 total calls to the Autism Clinic phone line 3 15 for new patient appointments 2 6% increase from FY18 to FY19

828 MaestroCare referrals

(37% increase from FY18 to FY19)

patient 320 343 new visits

12 consults

214

clinical autism diagnostic evaluations research diagnostic evaluations

3,419 total appointments for 750 unique patients (15% increase from FY18 to FY19)

6 types of clinical intervention services offered to

infants through young adults with autism: parent coaching, early behavioral intervention, social skills training, emotional and behavioral regulation, cognitive-behavioral therapy, and medication

23 New autism-related scientific journal publications

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4,522 combined total of Duke Center for Autism followers on Facebook and Twitter

1 Intern

4 Fellows

4 Postdocs

5 Graduate/ medical students

14 Clinic observers

34 4 Undergraduates

3 Undergraduates

3 Graduate practicum students Trainees

16 Gap-year students 28 Faculty

5 Graduate students 4 Postdocs 35 Staff

92 13

Duke-sponsored autism awareness and education community outreach events reaching over 1,400 community members, including the annual DIBS Discovery Day, annual Autism Awareness Month event with the Honourable Mike Lake, and a music event for children with ASD

Faculty/students/staff employed full or part time

Research > $52.5 million in total sponsored autism research funding

4,593 individuals enrolled in Duke Autism Volunteer Research Registry (38% increase from FY18!)

9 clinical studies focused on

improving detection and treatment of ASD Annual Report 2019

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Clinical Services There’s no such thing as a typical day for the clinical social workers at the Duke Autism Clinic, which is part of the Duke Center for Autism and Brain Development.

Social Workers Provide Wide Range of Support

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n any given day, a social worker might be on the floor playing with a child while screening for autism or other developmental conditions.

Or on the phone connecting an out-of-town family to services at a community-based agency.

Or in an office with parents, coaching them on strategies for helping with their child’s self-injurious behavior.

Or on the computer, filling out a public school special education form for a Spanish-speaking parent with no home internet.

But no matter what the social workers are doing, it’s all about support.

“As clinical social workers, we provide direct support to the child and their family,” says Mary Beth Hooks, MSW, LCSW. Parent Alicia Clemens can attest to that. “I would be lost without Mary Beth,” she says. “She has helped me so much.” Clemens first came to the Duke Center for Autism and Brain Development when her daughter Rylee started having learning and social problems in kindergarten.

At the Center, Rylee was diagnosed with autism and ADHD, and Clemens began a crash course in learning about both conditions as well as how to

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secure resources available to her and her daughter.

“I educated myself through materials Mary Beth provided me,” Clemens says. “She emailed me constantly providing materials.”

A big part of what the Center’s social workers do is to help families coordinate all the different types of care their children need. The services of many specialists are available through the Center, including psychologists, psychiatrists, pediatricians, early-intervention specialists, and social workers.

Others at Duke whose expertise might be brought to bear include neurologists, speech-language therapists, occupational therapists, geneticists, gastroenterologists, and specialists in eating disorders.

The social workers also help coordinate care beyond the borders of Duke, connecting the dots among the health system, the public school system, and community-based resources.

In Clemens’ case, Hooks helped her navigate the process of getting an individualized education program (IEP) for Rylee at her school, and also suggested avenues for securing educational financial assistance.

Clemens lives almost two hours away from Duke, so Hooks helped her find therapy providers for Rylee closer to home. Still, they return to Duke regularly for doctor appointments, and when they do, Clemens says Hooks always checks in. Even between visits Hooks

keeps in touch. Clemens says, “Mary Beth will email me, ‘How are things going? How are you doing?’”

way to communicate with the kids, figuring out what works for them and what makes them open up.”

Hooks thrives on interacting with individual children and their families, and providing emotional as well as logistical support. “I have so much admiration for the families,” she says. “I love being able to walk alongside a parent or family as they are going through these challenging issues.”

Whether working with parents or children, all the social workers in the Duke Autism Clinic place a priority on making people feel comfortable. If a child or adult with autism is sensitive to noise or particularly likes certain toys, the social workers will use that information to help the person feel at ease.

For children and families who live nearby, the Center can provide therapy for children and adolescents and their parents. The type and duration depend on the child and the need. “If we are providing therapy, we would have a treatment plan for that child and might be working directly with that individual and coaching the family,” Hooks says. “If we are providing more of a supportive role to the psychiatrist or psychologist, we may be providing more parent support.”

Both Hooks and her colleague Itala Azzarelli, MSW, LCSW, have felt drawn to children with autism since their college days, when each of them cared for people with autism. Azzarelli says, “I love finding a

“We try to create a culture of safety for our patients and families, not just physical safety but emotional safety,” Hooks says. “When they go out in public they don’t always feel that.”

Azzarelli explains that for some families, going to the grocery store can involve a meltdown and judgmental stares of strangers. “When it’s hard doing normal dayto-day things, parents can feel isolated and that no one understands,” Azzarelli says. “That’s why it’s important to provide this support and help them get connected to other parents. It’s a relief to them when they hear about other families having the same struggles.”

Hooks agrees, saying, “Families and kids come here to feel understood.”

As social workers in the Duke Autism Clinic, Itala Azzarelli, MSW, LCSW (left) and Mary Beth Hooks, MSW, LSCW enjoy working with children and adults with autism and their families.

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Clinical Services Transitioning to Adulthood

W

hen Amy first arrived at Duke as an undergraduate student, she spent a lot of time feeling confused. “I didn’t understand how everyone else seemed to know what to do,” she says. “It felt like there was some network that I wasn’t plugged into at all.” (Amy’s name has been changed to protect her privacy.)

Amy, who identifies as being on the autism spectrum, is a senior at Duke from California studying engineering and neuroscience.

In her first year she also struggled with roommate conflicts and all the sensory stimulation of a typical college day. “The dining halls can be incredibly overwhelming,” she says. “Trying to find a place to sit when there are so many visual cues to look at, so many people. . . . It’s hard to process.”

Things started looking up when Amy met Tara Chandrasekhar, MD, aka Dr. C. “Dr. C. is amazing,” Amy says. “She focuses on ‘What can we do to make sure you get the best experience possible?’”

Chandrasekhar is a psychiatrist who works part-time at the Duke Center for Autism and Brain Development and part-time at Duke Counseling and Psychological Services. She is working hard to improve the experience of all students at Duke who have autism, ADHD, or learning differences.

Chandrasekhar has a special interest in helping people on the spectrum navigate the transition from adolescence to adulthood. She points out that people with autism are often well supported in the K-12 years, but may suddenly lose services and support after twelfth grade. “It’s a big point of vulnerability when they hit that cliff,” she says. Some people aren’t prepared for college or working and end up staying at home. For individuals who go to community college or a university, there are pluses and minuses to the new environment.

“The positives of going to college are that you might be able to find a group of likeminded individuals or a group that coalesces around shared goals,”

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Chandrasekhar says. “College is a little more accepting of difference.”

On the other hand, colleges are stimulating and social places, presenting unique challenges for some students. “College can feel like an incredibly lonely place for students on the spectrum,” Chandrasekhar says. “I’ve had students tell me in college you’re expected to be social all the time, and that’s very exhausting.”

Chandrasekhar is working to improve the experience of students on the spectrum at Duke.

In 2016, she founded Neurodiversity Connections on campus. “The aim of the group is focused on raising awareness of neurodiversity on campus,” Chandrasekhar says.

“We’re creating the connections and knowledge base so we can be more effective in helping students.”

Members include representatives from Student Health, Counseling and Psychological Services, Duke Reach, the Academic Resource Center, the Student Disability Access Office, the Career Center, the Global Education Office, and a student representative. “The more we talk about it on campus, the more people are interested in joining,” Chandrasekhar says. “It’s really exciting.”

”The aim of the group is focused on raising awareness of neurodiversity on campus.”

Tara Chandrasekhar, MD

Duke Neurodiversity Connections makes presentations, provides tips for teaching neurodiverse students, and works with other campus organizations such as the Disability and Access Initiative. In February, the group sponsored a screening of Autism in Love, a documentary about the challenges and joys faced by autistic adults seeking or navigating romantic relationships. The evening included a Q&A with the film’s director, Matt Fuller. Students handed out brochures about Neurodiversity Connections before the film.

Through Neurodiversity Connections and other work, Chandrasekhar would like to help Duke become more proactive rather than reactive in meeting the needs of neurodiverse students. “These students are here because they are academically brilliant, and Duke can benefit from having them on our campus,” she says.

“It’s in everyone’s interest to support their needs.”

One of those needs is community. To address that, Chandrasekhar organized a group called the Clubhouse for neurodiverse students, including Amy. “It’s a place to get together and hang out where we can talk about the concerns we have that other people might not share,” Amy says. “A place where you don’t feel like you have to be anybody but yourself.” She says it’s a relief not to have to think about whether she’s making enough eye contact or twitching her fingers too much.

“It’s a social group, not a support group,” Amy says.

“But it ends up being just a little bit of both, because that’s what friends do, right?”

Raghav Swaminathan, an adult on the spectrum who works at the Duke Center for Autism (center in top Tweet) poses with the film’s director, Matt Fuller (left), and Dr. Madhav Swaminathan at the screening of Autism in Love.

Duke Neurodiversity Connections makes presentations, provides tips for teaching neurodiverse students, and works with other campus organizations such as the Disability and Access Initiative.

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Training PhD student Yitong Li works with a team of clinicians, scientists, and engineers at the Center to develop machine-learning techniques that are shedding light on how the brain functions in autism.

Using Machine Learning to Help Our Understanding of Autism

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s a PhD student in electrical and computer engineering, Yitong Li didn’t know much about autism, brain signals, or electroencephalogram (EEG) assessments when he started working with the Center a few years ago. But he has a deep understanding of machinelearning, and he is using that knowledge to help open new doors in understanding brain functioning in autism.

At the Center, he works on a team of clinicians, scientists, and engineers devoted to developing machine-learning techniques that can shed light on how the brain works and offer better ways of assessing the effects of treatments.

“It’s this idea of team science,” says David Carlson, PhD, assistant professor in the Departments of Civil and Environmental Engineering and Biostatistics and Bioinformatics, who is Li’s mentor. “To move forward on big science, we need everyone’s expertise because no one person can do it.”

Li and Carlson work closely with Guillermo Sapiro, PhD, and Center Director Geraldine Dawson, PhD, looking for ways to take advantage of the power of machine learning to advance autism research. “We want to make sure we’re not just doing math for the sake of math,” Carlson says, “but that we’re doing

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Duke Center for Autism and Brain Development

math that will help us achieve our clinical goals faster.”

Li’s first project with the Center was to use EEG data collected in a clinical trial to see if he could use machine learning to distinguish brain signals collected before treatment from brain signals after treatment. “Machine learning defines features in a different way than the features we define,” Li says.

“Those patterns may not be understood by humans but are understood by machines.”

Carlson explains, “Machine learning is a funny thing— you write an algorithm that learns an algorithm. You write Yitong Li, code that looks at data, and PhD Student every time it sees a new data point, it’s going to use that experience to learn how to make better predictions in the future.”

The clinical trial provided data from 22 children who received an infusion of their own umbilical cord blood, based on the hypothesis that products in the cord blood might reduce inflammation in the brain. The children did show improvements in social

Electrophysiology is one of several tools that Center researchers are using to detect whether a treatment has improved brain function.

“Machine learning is a funny thing—you write an algorithm that learns an algorithm. You write code that looks at data, and every time it sees a new data point, it’s going to use that experience to learn how to make better predictions in the future.”

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Training behavior and language, according to lab-based assessments and reports from parents and clinicians.

All the children in the study had EEG assessments before the infusion and at 6 and 12 months

That’s where Li came in. To tackle the problem, he started with techniques used in voice and facial recognition, then added in his own innovations to make the method work with brain signals.

From a machine-learning perspective, the project presented several challenges. For one thing, there were only 22 children, which is nothing like the enormous datasets (so-called “big data”) usually used in machine learning. But for each of those children, there was a very large amount of EEG data.

Carlson calls this type of project “little big data.”

“In fact, a lot of the techniques Yitong is developing are designed to make better use of little big data,” Carlson says.

After designing software, Li was able to use machine learning to identify changes in the EEG signal that occurred after treatment with cord blood. “What

Work by Duke Center for Autism researchers was featured in WIRED magazine in May 2019.

afterward. The EEG data were collected while the children were watching three one-minute videos designed to evaluate social response.

An EEG read-out represents brain signals collected from 120 different electrodes placed on the scalp.

These signals measure neural activity. There are numerous features one can extract from the EEG signal. For example, different types of brain activity can be associated with oscillations at a certain frequency. It is also possible to measure whether two signals from distinct parts of the brain are operating independently or are connected. Current approaches measure each of these features separately, whereas machine learning can examine them simultaneously.

”Yitong created a new type of artificial neural network that used state-of-the-art techniques to understand how the brain was changing after treatment.”

David Carlson, PhD

Understanding subtypes of autism based on patterns of brain activity might allow us to predict which children would respond to a given treatment.

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Duke Center for Autism and Brain Development

Trainees moving on Recognizing our staff and trainees that moved on this year to the next phase of their careers: Elie Abdelnour, MD Psychiatry Residency Program Washington University in St. Louis Kayla Belvin Physician’s Assistant Program Wake Forest University School of Medicine Jessica Buttinger, MS MD Program Central Michigan University College of Medicine

Yitong did was create a new type of artificial neural network that used state-of-the-art techniques to understand how the brain was changing after treatment,” Carlson says.

Li then turned his attention to a different problem: which of the children had brain-signal patterns that were most similar to each other? Looking at relationships like this could help scientists discover different subtypes of autism. Understanding subtypes of autism based on patterns of brain activity might allow us to predict which children would respond to a given treatment.

Many types of machine-learning are described as “black box” because the algorithms that the computer uses to recognize patterns are not articulated. But the techniques developed by Li and Carlson have what’s called “interpretable features,” meaning that the software identifies the features it’s using to distinguish one set of brain signals from another.

This allows the clinical team to understand what specific features of the brain change after treatment and what features may correlate to subtypes of autism, which in turn could predict treatment response. “That’s the novelty of our work,” Li says.

Sarah Edmunds, MS Clinical-Research Postdoctoral Fellow Department of Psychiatry, Harvard Medical School & Division of Developmental Medicine, Boston Children’s Hospital Marc (Ryan) Jackson Master’s in Physiology Program Georgetown University

Shelby Johnson Clinical Psychology PhD Program Washington State University

Andréa Kaniuka, MA PhD Program, Public Health Sciences UNC-Charlotte

Margaret Katherine McCoy Master’s of Social Work Program University of Denver School of Social Work Eliana Rabinovitz School-Child Clinical PsyD Fellowship Yeshiva University Ferkauf School of Graduate Psychology Ava Rohloff Master’s in Clinical Mental Health Counseling Program UNC-Charlotte

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Training Trainee Spotlight: Psychiatry Resident Alexandra Bey, MD, PhD

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hile completing a PhD in neurobiology, Alexandra Bey, MD, PhD, spent six years studying the neural circuitry and behavior of mice that were genetically engineered to have mutations known to be associated with autism.

Bey, now a resident in the Department of Psychiatry, says, “I was interested in working in child psychiatry and I liked genetics too, so I made genetic models of autism in mice.”

Alexandra Bey, MD, PhD (right) with collaborator and faculty member, Maura Sabatos-DeVito, PhD

Working in the lab of physicianscientist Yong-Hui Jiang, MD, PhD (see page 6), Bey was looking for correlations between brain regions and autism-related behavior, such as social avoidance. One of the tools she used to quantify mouse behavior was a computerized videotracking system called EthoVision. It allowed her to track and quantify the movements of mice in an enclosed space including, for example, whether they approached an object or another mouse in the enclosure, and which they spent the most time with.

After completing her PhD, she returned for her last year of medical school with a renewed interest in clinical work.

“When I went back to medical school, I realized I knew very little about people with autism,” she says. That led her to Geraldine Dawson, PhD, the director of the Center for Autism and Brain Development, who suggested that she get involved in the Center, first by coming in and observing clinical assessments.

Bey was also interested in developing measures that could be translated from animal to human studies, which could provide consistency across clinical trials that begin with mice before moving on to humans.

Given her extensive background with EthoVision, Dawson suggested Bey collaborate with Maura SabatosDeVito, PhD, who has been studying whether EthoVision can be used to quantify behavioral differences in children. The goal is to see whether measurements collected by the technology could be used as reliable biomarkers in the evaluation and testing of new drugs and behavioral treatments for autism (see page 10 to learn about the ABC-CT biomarker study).

“I’m thinking about what we can measure with EthoVision and what variables would be meaningful to extract,” Bey says. “It gleans information that a human observer might not pick up, like how fast did the child move?”

Here’s how it works: a parent and child enter a room wearing special t-shirts—red for the child and purple for the parent—that allow a video camera in the ceiling to track the movements of the two people over time. The room can be set up to evaluate specific situations for a certain length of time. The parent might be instructed to sit on one side of a room that has a collection of toys in the center. Does the child leave the parent to investigate the toys? Does the child bring a toy back to the parent to share it? How

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frequently does the child move and how fast? Does the child spend more time with the parent or with the toys?

Data collected by the video-tracking software has been gathered as part of several previous and ongoing studies at the Center, and Bey is comparing the results to observations by trained professionals as well as parent reports.

While much of the data remains to be analyzed, Bey says there have been several interesting outcomes so far. Perhaps not surprisingly, children who have high levels of hyperactivity as reported by their parents do indeed move more and faster in the room than other children. Also, children with more impaired functioning, such as lower communication skills and lower IQ, spend less time than other children playing with the toys in the center. They tend to either stay next to the parent or move about the room. “It appears that children who have higher cognitive ability can direct their own play with these toys without needing the parent very close by to facilitate play,” Bey says.

Top: Room set-up for parent-child interaction.

Middle: Child with both autism and ADHD (left) and child with autism only (right) during free play.

Currently, diagnosing and evaluating autism relies heavily on observations of behavior made by trained professionals. While video tracking would never replace clinical observation, it has the potential to provide objective measurements that would be less time-consuming and easier to standardize across multiple sites for large clinical trials. Compared to other possible biomarkers, such as EEG and labbased eye-tracking, video tracking would be more naturalistic and potentially easier for children.

Bey’s collaborator and mentor, Maura SabatosDeVito, PhD, says, “The nicest thing about a parent-child interaction is that it’s something all kids generally enjoy. It’s very dynamic and very naturalistic and provides rich information about parent and child engagement patterns.” Sabatos-DeVito is a medical instructor at the Center who is working with Bey on evaluating video-tracking software.

Bottom: Child with both autism and ADHD (left) and child with autism only (right) during parent-child interaction.

When Bey finishes her residency, she hopes to do a fellowship in child psychiatry, followed by a career that combines research and clinical work with people with autism. “My dream goal would be to look between species—mice and humans—to find biomarkers that work in both,” she says, “with the ultimate goal of using these biomarkers to translate basic science findings from animal studies into effective treatments to improve the lives of people with autism.”

Sabatos-DeVito, M., Murias, M., Dawson, G., Howell, T., Yuan, A., Marsan, S., Bernier, R., Brandt, C., Chawarska, K., Dzuira, J., Faja, S., Jeste, S., Naples, A., Nelson, C., Sugar, C., Shic, F., Webb, S., & McPartland, J., Autism Biomarkers Consortium for Clinical Trials (2019). Methodological considerations in the use of Noldus EthoVision XT video tracking of children with autism in multi-site clinical trials. Biological Psychology.

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Training Building Partnerships to Support Early Diagnosis and Intervention in Africa

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utism affects individuals across the globe.

Yet in most parts of the world, children and adults with autism do not have ready access to diagnostic services or treatment.

Lauren Franz, MBChB, MPH, a child and adolescent psychiatrist, wants to improve access for children with autism and their families in Africa. Along with local colleagues, Franz is working on projects in South Africa and Tanzania.

The needs are stark. As Franz wrote in an editorial published in Spectrum in January: “As many as three in five children in sub-Saharan Africa are at risk of developmental disabilities, due, at least in part, to poverty, malnutrition and social deprivation. Yet services are extremely limited.”

Franz grew up in South Africa and did her medical training there. She practiced as a physician in Namibia and the province of KwaZulu-Natal in South Africa. She saw firsthand the lack of resources and opportunity. “Being on the ground and feeling the frustration of lack of resources and appropriate infrastructure really made me interested in the bigger picture,” she says. She decided to earn a degree in public health, and train further in general psychiatry, child and adolescent psychiatry, and global health to explore that bigger picture and understand “the systemic things you can manipulate.”

standardized collection of materials and activities to screen and assess for autism. Such an approach is widely used in the United States and European countries to inform the diagnosis of autism, but its use in most parts of the world is limited because of barriers related to cost, culture, language, and supervision.

“Diagnostic training is seen as a first step towards capacity building in early identification and intervention,” Franz says.

As part of the project, three occupational therapists— Simon Mallya, Vivian Mdavire, and Ignace Tarimo— traveled to Cape Town for diagnostic training in November. The occupational therapists work at a medical university called Kilimanjaro Christian Medical Center (KCMC) in Moshi, Tanzania. Duke already has a partnership with KCMC through the Duke Global Health Institute, so it was a natural place for Franz to start.

Petrus de Vries, MBChB, FRCPsych, PhD, provided the training. He is a professor at the University of Cape Town and the founder and director of CARA. “Professor Petrus de Vries is the only certified ‘gold standard’ diagnostic trainer on the continent, so we’ve supported him to train our colleagues in Tanzania,” Franz says.

Now she’s putting those experiences and lessons to good use. For several years, with support from the National Institutes of Health (NIH), she’s been collaborating with partners here and in South Africa to build capacity for autism diagnosis and behavioral intervention in South Africa. Now she’s beginning to do similar work in Tanzania.

Working in partnership with the Duke Center for Autism and Brain Development, the Duke Global Health Institute (DGHI), and the Center for Autism Research in Africa (CARA), Franz is supporting the training of providers in Tanzania to use a

”Diagnostic training is seen as a first step towards capacity building in early identification and intervention.”

Lauren Franz, MBChB, MPH

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One of the occupational therapists, Simon Mallya, says the needs are high in Tanzania. “There are a lot of children with features suggestive of autism [who] are not engaged in proper follow-up of therapy at any appreciable level,” he says. “Historically, there is misdiagnosis of children with autism, late diagnosis, or only severe cases are identified.” He enjoyed the training and looks forward to helping grow the project so that more providers can be trained, and more children will be able to receive early diagnosis and intervention.

Back in Moshi, he and the other two therapists are now practicing the diagnostic methods, and will be submitting videos of themselves using the materials and activities with children. “The videos will allow for supervision to support growth in their confidence

and abilities,” Franz says. “That’s such a critical step. That’s the beginning of developing a shared diagnostic language.”

Eventually, Franz hopes the diagnostic materials and activities can be translated and adapted culturally for Tanzania. Mallya agrees, noting that Swahili is the first language of most Tanzanian children.

Capacity building in diagnostic skills is only the first step toward Franz’s ultimate goal, which is to increase services available to autistic children.

“Diagnosis and intervention need to go hand in hand,” she says. To that end, two of the KCMC occupational therapists will be attending a training workshop in September in South Africa on an early intervention method called the Early Start Denver Model (ESDM),

Diagnostic training with colleagues from the University of the Free State, the University of Cape Town, and Kilimanjaro Christian Medical Center in Tanzania

Capacity building in diagnostic skills is only the first step toward Franz’s ultimate goal, which is to increase services available to autistic children. “Diagnosis and intervention need to go hand in hand,” she says.

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Training which was has been shown to improve outcomes for children with autism. ESDM was developed by Sally Rogers, PhD, and Geraldine Dawson, PhD, director of the Duke Center for Autism and Brain Development.

Franz has already certified three South African therapists to international ESDM standards at the Center for Autism Research in Africa, supported by a career development award from NIH. As part of Franz’s ongoing study, these certified therapists are partnering with schools to train nonspecialist providers referred to as early childhood development workers. These early childhood development workers, in turn, coach caregivers in the use of ESDM intervention strategies.

Early evaluations are promising, and a pilot project aiming to enroll children and caregivers is underway.

The caregivers will receive 12 sessions of coaching from the early childhood development workers.

If the results are good, the model of using non-

specialist providers, working under supervision, could be used not only in South Africa and Tanzania, but other low-resource settings. “The work in South Africa is around how do we take a complex intervention model like ESDM and tailor it to a lowresource setting in a sustainable way?” Franz says.

In everything she does, Franz looks for ways to build capacity, leverage partnerships, share resources, and strengthen or create systems. She hopes that the work she has started in South Africa and Tanzania will continue to grow as the people she has trained spread out and train others. “What I love most about what I do is that there is such a capacity-building component,” she says. “It’s incredibly rewarding.”

Franz, L., Adewumi, K., Chambers, N., Viljoen, M., Baumgartner, J. N., & de Vries, P. J. (2018). Providing early detection and early intervention for autism spectrum disorder in South Africa: stakeholder perspectives from the Western Cape province.

Journal of Child and Adolescent Mental Health.

Caregiver coaching training with colleagues from the University of Cape Town, Western Cape Education Department Schools, and Kilimanjaro Christian Medical Center in Tanzania

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Community Father of son with autism urges moving from inclusion to a purpose-filled life

Challenging the Way People Think about ‘Normal’

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he Honourable Mike Lake’s Twitter account description neatly sums up his busy life: “Canadian Conservative Member of Parliament for Edmonton-Wetaskiwin. Shadow Minister for Youth, Sport and Accessibility. #Autism parent. @EdmontonOilers fan.” (“Shadow Minister” refers to the fact that his party is not currently in power.)

What the words cannot convey is the extraordinary bond Lake shares with his 23-year-old son, Jaden, who has autism. Experiencing their love in person was the highlight of Lake’s April 15 presentation at Duke, “Expect More: An Autism Adventure,” an evening event recognizing Autism Awareness Month.

Together, he and Jaden challenged how we think about the people around us, emphasizing that we all have unique abilities and challenges.

The Duke Center for Autism and Brain Development organized the event, attended by more than 100 faculty, students, staff, and community members. It took place in the Duke Institute for Brain Sciences, which also co-sponsored the event.

Before the presentation, Mike and Jaden sat down for a brief interview, accompanied by their friend Julie. Mike did most of the talking, but Jaden, who is nonverbal, nonetheless communicated his opinion quite effectively—his body language said, “OK, another interview. I’m going to tune out and play with my smartphone”—an activity familiar to any parent of a young adult.

The three had traveled to North Carolina by car, from Ottawa—a 12-hour drive—with a stopover in Washington, D.C. Most of us groan at the thought of spending so much time in the car but, Lake said,

The Honourable Mike Lake, PC, MP (left) and son Jaden with Geraldine Dawson, PhD

“Jaden loves the movement of travel,” so it’s an opportunity to do their favorite thing: spend time together. Nonetheless, travel can be wearying, so after a few minutes, Julie and Jaden departed for some pre-event down time. That left a few minutes to learn more about this extraordinary family.

Mike has been a global autism advocate since Jaden was a youngster. When asked what is most important to him about advocacy, Lake replied, “We want to challenge the way people think about ‘normal.’” Inclusion [of people with different abilities] is good, he said, but it’s not the ultimate goal.

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Community “I want us to move beyond inclusion to contribution— to do a better job of unlocking each person’s potential,” he said. “OUR purpose is to help others find THEIR purpose.” As an example, he described Jaden’s work at his school library, where he separates books into piles and re-shelves them alphabetically—much more quickly and efficiently than his classmates.

That’s because Jaden excels at numbers and letters, especially when combined with concrete, understandable tasks. Shelving library books fills the bill, giving him both a purpose and a sense of belonging.

At the same time, Jaden experiences challenges in more abstract areas. “He doesn’t understand the concept of danger,” Lake said. He makes certain to hold Jaden’s hand when they are out, because if Jaden sees a large dog—he loves dogs—across the street, he will immediately run to the dog without regard to oncoming traffic. “You can teach him to look left and right before crossing, but he doesn’t know how to estimate the speed of oncoming cars or the threat they pose if he crosses the street.”

Asked what still surprises him after all these years of advocacy, Lake responded, “How much work we need to do around autism awareness.”

Another surprise, he said, “in the best possible way, is how responsive people are to the message—how little convincing people take to understand the importance of understanding and inclusion.”

In 10 years, Lake hopes to see much more progress in reducing stigma and increasing awareness of autism around the world. One way to do that, he said, is to leverage the work being done by international agencies such as UNICEF. “We must reach out to the most vulnerable people around the world,” he said. His background in international development and banking made working with the Global Autism Partnership a natural fit. The group’s work centers on reducing stigma and, “helping individuals with autism and their families in a meaningful way.”

In her welcoming remarks, Geraldine Dawson, PhD, Director of the Duke Center for Autism and Brain Development, echoed Lake’s positive message, describing the event as, “a celebration” of neurodiversity, the broader autism community, and the valuable contributions of people with autism to society. Dawson, an international expert in early diagnosis and treatment of autism, has known Mike and Jaden Lake for years, and praised Lake’s work as a global autism advocate.

“He and Jaden are amazing ambassadors for people with autism, not just in North America, but around the world,” she said. “His inspiring message reminds us all that we need to do more to make sure that people with autism are fully included in our communities and workplaces.”

A key component of Mike Lake’s life philosophy is summed up in a quote from the late John Wooden, famed UCLA basketball coach: “You can’t live a perfect day without doing something for someone who will never be able to repay you.” As the audience learned Monday night, Lake and Jaden are living as many perfect days as possible.

Together, he and Jaden challenged how we think about the people around us, emphasizing that we all have unique abilities and challenges.

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Duke Center for Autism and Brain Development

Duke Neurobiology Graduate Student Winston Liu helps a Discovery Day attendee examine a brain.

Duke Center for Autism Participates in DIBS Discovery Day

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he Duke Institute for Brain Sciences (DIBS) hosted another successful DIBS Discovery Day in March of 2019 with record-breaking attendance of 565 children and adults from the local community. Kids enjoyed activities like touching a real brain and coloring brain pictures, while adults browsed scientific exhibits designed by Duke undergraduate students, graduate students, and postdocs. This year, the Duke Center for Autism co-sponsored a sensory-friendly hour held before the event’s official start that attracted 75 people and gave children and adults on the spectrum or with other developmental issues the opportunity to attend in advance of the crowds.

Nick and Adam Nickerson present Dr. Geri Dawson with a check from 3,000 Miles for Autism fundraising.

Nick Nickerson and 3,000 Miles for Autism Donate to Duke Center for Autism

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HANK YOU to Mr. Nick Nickerson, founder of 3,000 Miles for Autism!

Mr. Nickerson is the father of Adam, an adult with autism, and a passionate advocate for autism research. At age 73, Mr. Nickerson has nearly completed his goal of running 3,000 miles to raise funds for autism research. “In 2017, I decided to dedicate the rest of my life to raising money to be donated to autism research,” he said.

The Duke Center for Autism and Brain Development has been the fortunate recipient of nearly four thousand dollars raised by Mr. Nickerson that have gone toward our research program. We are amazed by his athletic achievement and truly appreciate the support we have received from 3,000 Miles for Autism!

Kimberly Blackshear, right, and Lori Reinhart-Mercer set up the Center’s information table and set out healthy snacks for attendees at DIBS Discovery Day. Annual Report 2019

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Community Duke Center for Autism Hosts “Music 2 the Max” Event

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ver 30 children on the autism spectrum and their families gathered at the Duke Institute for Brain Sciences (DIBS) “Cube” on December 1st, 2018 to participate in the Duke Center for Autism’s inaugural “Music 2 the Max” event. The event was planned by Center staff members Elie Abdelnour, Samantha Bowen, Charlotte Stoute, Elizabeth Sturdivant, and Alexandra Valladares, along with William Dawson, Musician in Residence and Performing Arts Coordinator for the Arts & Health at Duke program.

Participants took part in three unique workshop stations that gave them the opportunity to try out different ways of making music. William Dawson led the ukulele station where kids played open-tuned ukuleles and sang songs together. Max Puhala and Berk Ozturk from Chapel-Hill based organization Push Play Sing guided kids in playing electronic music on keyboards, drum machines, and other electronic devices. At the instrument making station, participants decorated their own cardboard and rubber band instruments. With help from experienced musician Elie Abdelnour, MD, they were then able to play them through an amplifier with special sound effects. At the end of the event, all the participants and their families participated in a special podcast that can be heard at https://www.youtube.com/watch?v=85qEhXidYEc&t=0s.

Participants and staff posing in their rockin’ sunglasses that everyone received at the end of the event.

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Duke Center for Autism and Brain Development

“Thank you so much for the opportunity to attend Music to the Max. My daughter had a wonderful time! She especially loved the chance to play the ukulele and the Push & Play session...The event was well organized with lots of volunteers to make the event run smoothly.

It was a really fun day!”

Back row: Keith Valentine, Jillian Padilla, [a visiting nurse], Stephanie Hannah, Tracie Hazelett, Liz Indence, Vicki Sutter, Breanne Hamlett Front row: Jill Howard, PhD, Mackenzie Hathaway, Shelby Ferry, Tara Chandrasekhar, MD, Sarah Edmunds, MS

Center staff and faculty at the annual Triangle Walk for Autism Speaks event.

Duke Emergency Department Raises Funds for Duke Center for Autism

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e are very grateful to the Duke Emergency Department for the support they showed our Center in honor of Autism Awareness Month this year. Led

by Vicki Sutter, BSN, RN, the department raised over $200 for the Duke Center for Autism and Brain Development in April.

The Emergency Department was interested in donating to the Duke Center for Autism because of their frequent engagement with patients with autism. In light of this, Ms. Sutter asked if members of our Center’s clinical team could provide the ED staff with guidance for interacting with people on the autism spectrum in medical settings. Psychiatrist Tara Chandrasekhar, MD, psychologist Jill Howard, PhD, and intern Sarah Edmunds, MS, enjoyed meeting with the ED team to give them some tips on best practices. Small changes in the lighting of an exam room or ways of communicating with a patient with autism, who are sometimes nonverbal, can make a real difference.

Sutter remarked, “In the Emergency Department, we encounter patients with autism in various age groups.

Working with this special patient population encouraged us to reach out to the Duke Center for Autism for more education.

We also really wanted to raise awareness in our department and sold autism ribbons and buttons, with all proceeds going to the autism center. Working at Duke has been so amazing, and the collaborative effort between our department and the autism center has been a wonderful experience for our patients and our staff!”

We were thrilled to have professional golfer Ernie Els and his wife Liezl visit our Center in April 2019. Here post doc Jordan Hashemi, PhD, is giving Ernie a demonstration of one of our autism screening tools. The Els, parents of a son with autism, are autism advocates and founders of the Els for Autism Foundation.

“In the Emergency Department, we encounter patients with autism in various age groups.”

Annual Report 2019

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Thank You

We wish to express our gratitude to the following agencies, foundations, and individuals who generously supported the work of the Duke Center for Autism in FY2019.

Department of Defense Marcus Foundation National Institutes of Health National Science Foundation Simons Foundation Mr. James Barrett and Dr. Stacey Coulter Mrs. Lori A. Bullis Mr. Paul Attilio DiMarco and Mrs. Sherri DiMarco Duke Hospital Emergency Department Employees Mr. William Florence and Ms. Joy Seppala Mr. and Mrs. David Fullerton Ms. Jill Ann Jenkins Mr. Rushabh Modi Mr. Ted and Mrs. Mary Moore Mr. Nick Nickerson / 3,000 Miles for Autism Mrs. Jane O’Brien Ms. Vesna Papoe Mr. James Schwab and Mrs. Kimberly Schwab Drs. Harry and Andrea Stylli Mr. Matthew Trzyna and Mrs. Dianne Trzyna Mr. David Zalik and Ms. Helen Zalik

WE WELCOME YOUR SUPPORT By giving to the Duke Center for Autism and Brain Development, you are joining in our mission to help each individual with autism reach his or her fullest potential.

As part of Duke University, the Duke Center for Autism and Brain Development is a 501(c)(3) nonprofit organization. The Federal Tax ID number for the program is 56-0532129.

How to contribute: By secure website: You can make your secure online gift by visiting https://www.gifts.duke.edu and entering “Duke Center for Autism and Brain Development” in the search bar.

By check: Please make all gifts payable to “Duke University,” with Duke Center for Autism referenced in the “memo” portion of your check, and mail it to: Duke Health Development and Alumni Affairs Attn: J. Steven Barnes 300 W. Morgan Street, Ste. 1200 Durham, NC 27701

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Duke Center for Autism and Brain Development

Kids enjoyed playing music at the Center’s “Music 2 the Max” event in December 2018.

NIH Autism Center of Excellence