Autism spectrum disorders (ASD) are a group of pervasive developmental disorders characterized by deficits in social interaction and communication, and rigid or stereotypical behaviors. These complex behavioral problems arise, in part, from deficits in more basic sensory and motor systems. The thalamus plays a central role in processing sensory information and modulating overall cortical activity. Consequently, dysfunction of the thalamus and its connections with the cortex may account for some of the symptoms of ASD. Indeed, there is growing evidence that the structure and function of the thalamus is abnormal in ASD and contributes to ASD symptoms. Despite emerging evidence of thalamic abnormalities in ASD, several critical gaps in our knowledge about thalamic pathology in ASD remain. First, thalamocortical networks are organized topographically such that separate thalamic nuclei project to specific cortical areas raising the distinct possibility that thalamocortical networks may selectively affected in ASD. Second, we know virtually nothing about the post-natal developmental trajectories of thalamocortical networks in ASD. This is critical given mounting evidence that the developmental trajectories of the brain are altered in ASD. Moreover, the severity of ASD symptoms varies across the lifespan. Consequently, a complete understanding of thalamic circuitry in ASD and the relationship between thalamocortical network disturbances and ASD phenotypes will require systematic mapping of thalamocortical networks across the lifespan. This proposal will begin to address these critical gaps. Using an innovative resting-state fMRI method, we will determine if thalamocortical networks are altered in ASD (Aim 1);examine the developmental trajectories of thalamocortical networks in ASD (Aim 2);and establish the functional relevance of thalamocortical networks to the expression of ASD symptoms (Aim 3). The proposed work will contribute to our understanding of brain-basis of ASD.
Public Health Relevance: This work will contribute to our understanding of the brain-basis of ASD and provide useful biomarkers that will further our understanding of the etiology of ASD and contribute to the development of new treatments.
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