Date of Award

January 2021

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Dustin Scheinost

Abstract

Autism spectrum disorder (ASD) is putatively characterized by abnormal connectivity and lateralization of large-scale functional networks in school-age children. However, previous studies have not directly investigated if differences in cerebral lateralization between ASD and typically-developing peers are present during pre-symptomatic stages of the disorder in infancy, leaving the time of onset of these differences unknown. We used a voxel-based method—which examines each voxel’s connectivity to every other voxel in each hemisphere—to study connectivity lateralization in school-age children with ASD and infants later meeting Autism Diagnostic Observation Schedule (ADOS) criteria for ASD. Analyses were performed in two unique samples: 1) 733 school-age children with ASD and typically developing peers from ABIDE database, and 2) 71 infants at high risk (HR) and normal risk (NR) for ASD with data collected longitudinally 1-month and 9-months from the NDAR database. Comparing school-age children with ASD (n=301) to typically developing peers (n=432), we identified four regions that demonstrated group differences in connectivity: right posterior cingulate cortex (PCC), right posterior superior temporal gyrus, right extrastriate cortex, and right anterior prefrontal cortex. Together, these regions contributed to alterations in the default mode and salience networks. At 1-month, none of these regions exhibited group differences between infants meeting ADOS criteria for ASD (n=10), HR-nonASD (n=15), or NR (n=18) infants. However, by 9-months, two of these regions (right PCC and right extrastriate cortex) exhibited atypical connectivity in infants meeting criteria for ASD (n=11) and HR-nonASD infants (n=24) compared to NR infants (n=22), demonstrating that differences in default mode network lateralization emerge early in postnatal development. These findings support the hypothesis that ASD is associated with altered network development, observable prior to the age of a reliable clinical diagnosis.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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