Functional connectivity in autism spectrum disorders

Children'S Hosp Of Philadelphia, Philadelphia PA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): 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.