Atypical neural activity at the brain surface is frequently reported in individuals with autism spectrum disorder (ASD). Many researchers hypothesize that this atypical surface neural activity is due to an incorrect balance in the brain chemicals that control the firing rate of neurons. Although there is evidence to support this hypothesis, a more important influence on surface brain rhythms may be the contribution of deeper and more central brain structures to surface brain activity. One of these deep brain structures - the thalamus - is a central rely station that controls the flow of information from th outside world into the brain and thus controls the pattern of surface brain activity. Given the central role of the thalamus in modulating and coordinating neural activity, understanding the contribution of the thalamus to surface neural abnormalities in ASD is of high priority. The proposed R21 examines the most fundamental brain oscillation: resting-state (RS) alpha (8 to 12 Hz). RS alpha oscillations are strongest when at rest but modulated when performing tasks, with alpha rhythms providing a foundation for local and long-range communication. Focusing on RS alpha activity is optimal as: (1) RS alpha is the dominant brain oscillation, with a high signalto-noise ratio making RS alpha a sensitive probe, and (2) the thalamic nuclei and thalamocortical pathways modulating cortical RS alpha are known, allowing for a hypothesis- driven assessment of association between cortical alpha activity and thalamic structure. Our laboratory's published data show that (a) thalamic structure (specifically volume) is related to this RS brain rhythm, and (b) this fundamental brain rhythm is abnormal in idiopathic ASD. Taken together, these findings suggest that thalamic abnormalities might account for cortical brain neural abnormalities in ASD. To formally examine this hypothesis, children with idiopathic ASD and typically developing controls (TDC) aged 12-to-16-years-old will be recruited (N = 26 per group), and non-invasive multimodal imaging (magnetoencephalography, MEG, and structural and diffusion MRI) will examine associations between thalamic structure and function and properties of the resting-state brain alpha rhythm (strength of local activity as well as localand long-range functional connectivity). Establishing the role of thalamic and thalamocortical abnormalities in idiopathic ASD will inform the biological basis of ASD, will potentially account for the broad array of phenotypic domains in ASD given the central role of thalamus, and will indicate the need for new treatments that target restoration of thalamic function.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
