Yale School of Medicine Receives $27.7 Million Grant Toward Autism Research

Yale School of Medicine (YSM) was awarded a $27.7 million grant from Aligning Research to Impact Autism (ARIA) to develop non-invasive functional communication methods through large-scale brain modeling in autism spectrum disorder (ASD). “We are grateful to the ARIA initiative for its vision and generous support of this transformative work. It has the potential to change fundamentally how we treat children with severe neurodevelopmental disorders,” says Nancy J. Brown, MD, the Jean and David W. Wallace Dean of Yale School of Medicine. “It underscores the strength of partnership in driving innovative solutions and transforming lives.”

Led by Murat Günel, MD, chair of the Department of Neurosurgery, Sterling Professor of Neurosurgery, and professor of genetics and of neuroscience at YSM, the interdisciplinary research project aims to leverage state-of-the-art technologies and cross-departmental expertise to develop large brain models that will serve as the basis for personalized, circuit-based therapies.

ASD affects 1 in 36 children in the United States and 1 in 100 children worldwide, presenting with myriad challenges, including language and social communication difficulties, repetitive behaviors, and sensory processing issues. Autism often co-occurs with epilepsy, mood conditions, and sleep disturbance. The variability in symptoms and the intricate nature of the brain's involvement make treating the co-features associated with autism particularly challenging. Current treatments focus on managing symptoms through behavioral therapy, medication, and educational support, but there remains an unmet need for more effective and personalized interventions.

Yale seeks to address this treatment gap by identifying the brain circuits responsible for key ASD-related co-features and to modify those circuits non-invasively in real-time to benefit people with autism. The research will initially focus on identifying novel approaches to establish or improve verbal and non-verbal communication, as well as co-occurring conditions such as sleep disturbances and anxiety. By understanding the neural circuits responsible for these morbidities, Yale aims to develop non-invasive neuromodulation techniques to restore their function.

A key strength of this project is the integration of data from three distinct cohorts: individuals with ASD, patients with drug-resistant epilepsy, and those with Angelman Syndrome, a condition marked by severe speech and language impairments, sleep disturbances, and anxiety due to a single gene mutation. The study will collect noninvasive clinical and behavioral evaluations developed for use in multi-site autism studies in parallel with advanced neural and imaging technologies. The inclusion of epilepsy patients, in particular, offers a significant advantage due to the collection of intracranial recordings during the course of epilepsy monitoring and treatment—an area of expertise for the Yale neurosurgical team. These recordings allow for a detailed examination of circuit-level functions, informing our understanding of autism in ways not otherwise possible.

“Our vision is to translate our understanding of brain circuitry into practical treatments that restore neurological function,” Günel explains. “This integrated approach will not only improve outcomes for individuals with autism but also pave the way for addressing other neurodevelopmental disorders.”

Central to the research initiative is the use of mathematical and computer algorithms to decode complex neural signals and create large brain models. By integrating patient data from imaging, intracranial electroencephalogram recordings, and other sources, these models will represent virtual replicas of patients’ brains. Using these models, researchers can pinpoint precise neural targets for intervention. Continuously updated with patient data, these comprehensive simulations will provide deep insights and facilitate meaningful comparisons across individuals and groups, enhancing the precision of therapeutic interventions.

Günel explains, “Using advanced AI and machine learning techniques, we can create individualized brain models that simulate potential treatments, thereby refining our approaches before clinical application.”

The project brings together more than 30 individuals from many Yale departments, schools, and centers, including neurosurgery, neurology, psychiatry, psychology, engineering, statistics and data science, applied mathematics, law, and digital ethics. This collaborative effort ensures that each aspect of autism—from neural circuitry to behavioral manifestations to ethics—is examined through multiple lenses.

The Yale Child Study Center, renowned for its work in child development and neurodevelopmental disorders, will play a central role in the clinical care of patients involved in the study. Advanced imaging techniques will be provided by the Yale Biomedical Imaging Institute and the Wu Tsai Institute, ensuring precise mapping of brain structures and functions. The School of Engineering & Applied Science’s expertise in computational modeling and AI will support large brain modeling aspects of the initiative. Lastly, Günel notes that a pivotal element of this initiative is the major collaboration with Yale New Haven Health, which ensures that clinical translational projects have the necessary infrastructure and support, facilitating seamless integration of research findings into clinical practice.

Brown emphasizes the significance of Yale’s collaborative spirit: “By bringing together experts and resources from across the university and collaborating with Yale New Haven Health System to make this work accessible to patients, we harness the power of interdisciplinary research to achieve breakthroughs that would not transpire in isolation.”

About Aligning Research to Impact Autism

Aligning Research to Impact Autism (ARIA) is a scientific initiative to accelerate understanding and treatment of autism and related neurodevelopmental conditions through alignment, collaboration, and cutting-edge research. ARIA connects emerging research, insights, and promising technologies from across scientific fields to create more therapeutic opportunities for people with profound autism and people on the spectrum who seek additional support. Its focus areas include building a clinical trial and translational research network to rapidly develop and test new therapies, funding frontier science, and facilitating data sharing. ARIA is led by Managing Director Ekemini Riley, PhD, of the Coalition for Aligning Science and Scientific Director Matthew State, PhD, of the University of California, San Francisco. Learn more at ariaroadmap.org.