Neuropathology and neuroimaging studies show atypical brain function in multiple brain regions in autism, likely associated with imbalances in excitatory and inhibitory activity at the neural synapse. Although synaptic processes in autism cannot be non-invasively assessed, assessment of neural processes in terms of oscillatory power, cross-frequency coupling, and functional connectivity can provide insight into these synaptic processes. Our laboratory has observed focal differences in neural oscillatory activity between children with autism spectrum disorders (ASD) and typically developing (TD) controls in the resting state as well as when processing auditory information. These focal irregularities appear to have clinical implications, as they were associated with symptoms and cognitive function. A better understanding of these oscillatory irregularities is needed to develop treatments tailored to modulate brain activity in ASD. We hypothesize that oscillatory activity in ASD is associated with atypical local cross-frequency coupling (CFC) and long-range functional connectivity (FC). The proposed R21 examines these hypotheses by assessing resting-state and auditory system CFC and FC in ASD (N = 150) and TD controls (N = 150+). A strength of the study is that rather than undertaking a functional connectivity 'fishing expedition', specific hypotheses are tested, based on our laboratory's published and emerging findings. In sum, the proposed study determines the specific character and pattern of connectivity abnormalities in autism to better understand brain processes in autism. Given the emergence of clinical trials focusing on modifying synaptic function via the use of glutamatergic and GABAergic compounds, the CFC and FC processes in ASD identified in the proposed study will provide a candidate quantitative means of assessing treatment efficacy. Obtaining insights into basic neural brain processes in ASD will likely also suggest new therapeutic targets (e.g., drugs that restore specific local and long-range neural dynamics). Furthermore, by the end of the study, we will have developed a set of MATLAB whole-brain CFC and FC tools that will be made available to the research community.

Public Health Relevance

The proposed study brings together a team of researchers (psychologists, neuroscientists, computer programmers, bioengineers, and physicists) to study brain connectivity in autism. Using data sets of real-time brain activity already collected in a large sample of children with autism and age-matched typically developing controls, advanced methods will be used to localize brain activity and software developed to examine brain communication. It is hoped that if we can understand how brain communication in individuals with autism breaks down, we can then identify (or perhaps develop) treatments to normalize brain communication.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Gilotty, Lisa
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Children's Hospital of Philadelphia
United States
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Edgar, J Christopher; Heiken, Kory; Chen, Yu-Han et al. (2015) Resting-state alpha in autism spectrum disorder and alpha associations with thalamic volume. J Autism Dev Disord 45:795-804
Berman, Jeffrey I; Liu, Song; Bloy, Luke et al. (2015) Alpha-to-gamma phase-amplitude coupling methods and application to autism spectrum disorder. Brain Connect 5:80-90