Alexander Li Cohen, M.D., Ph.D. - US grants

Autism Spectrum Disorder (ASD) affects 1:59 children and is associated with a heterogeneous mix of disabling and difficult to manage symptoms; however, accurate localization of specific symptoms may allow for novel individualized therapies. To investigate the common symptom of poor face recognition, we recently used a new technique, `lesion network mapping', to identify a brain network that is consistently and specifically associated with face recognition deficits in patients with acquired prosopagnosia (face blindness after stroke).This proposal investigates whether there a common circuit for the transdiagnostic symptom/construct of face recognition impairment, i.e., are brain regions affected by acquired prosopagnosia also affected in children with ASD who display atypical face processing. This proposal addresses two key gaps in current knowledge: 1) do brain regions implicated by acquired prosopagnosia also demonstrate abnormalities in patients with ASD that correlate with face processing ability; and 2) do specific brain connectivity differences explain some or all of the observed heterogenicity in face-evoked brain activity, face-recognition abilities, and potentially social affect in individuals with ASD. Presently, no publicly available dataset contains the complete set of measures to address these gaps. This application proposes prospective data collection to address this gap. Adolescent subjects, with and without ASD, will undergo behavioral assessments of face processing ability, social impairment, and ASD symptom severity along with structural, task, and `resting-state' functional MRI acquisition. Recruitment will be enriched with subjects with known face recognition difficulties to capture a range of face processing abilities. This proposal has the potential to generate biomarkers or treatment targets for trials of therapeutic intervention for face recognition deficits across populations. Furthermore, if successful, this project will provide a model for identifying the neuroanatomy for many symptoms present in ASD and other neurodevelopmental disorders. This Mentored Patient-Oriented Career Development Award application directly aligns with the National Institute of Mental Health Strategic Objectives (SOs), as it will help define the connectome abnormalities of face recognition impairment (SO1.3), inform the development of early biomarkers predictive of face recognition impairment (SO2.2), and shed light on potential mechanistic treatment targets to improve these abilities (SO3.1). The proposal also provides important opportunities for training and career development to enable Dr. Cohen to become an independent investigator. Dr. Cohen has experience in using neuroimaging tools to understand brain connectivity, and with this award, he will gain training in: (1) the design, acquisition, and analysis of a MRI-based study in a pediatric clinical population; (2) the selection, collection, and analysis of pediatric behavioral assessments; and (3) the validation of lesion-based neuroimaging findings. Ultimately, the proposed program will provide a strong foundation for an independent research career devoted to the understanding and treatment of symptoms in ASD and other neurodevelopmental disorders.