UC San Diego

Autism Spectrum Disorder (ASD) is a highly heterogeneous condition in terms of etiology, symptomatology, and severity. Our existing understanding of ASD derives mainly from research in children and young adults, with little known about neurobiological, cognitive, and behavioral changes later in life. This three-paper dissertation aimed to characterize changes in cortical architecture across middle to older age in ASD and determine how differences relate to cognition and behavior. Data were drawn from an ongoing study of adults with ASD and typical comparison (TC) participants, aged 40-70 years. Study 1 (nASD=20, nTC=21; mean age=50.51 years, SD=6.35; Kohli et al., 2019) examined cortical morphology, including cortical thickness (CT), surface area (SA), and local gyrification index (LGI). LGI, but not CT or SA, was regionally decreased bilaterally in the ASD group. LGI also showed several correlations with executive function scores in the ASD group. Study 2 (nASD=30, nTC=36; mean age=51.50 years, SD=7.09) aimed to identify regionally varying differences in CT and gray-white contrast (GWC) using both group-wise and subject-specific analyses. CT did not differ significantly between groups using either approach. GWC did not differ in the group-wise analysis, but the ASD group showed a greater spatial extent of decreased GWC than controls in subject-specific analyses, along with associations between decreased GWC and ASD symptomatology and dysexecutive symptoms. In the same sample, Study 3 examined intracortical myelin content (MC). Groupwise analyses showed no group differences in average MC or its associations with age. In subject-specific analyses, neuropsychological function differed between subgroups classified by presence or absence of aberrant MC, with poorer performance in the ASD subgroup with atypically high MC in spatially heterogeneous regions. LGI was the only cortical feature demonstrating differences in ASD when examining group level averages, but subject-specific analyses revealed an additional decrease in GWC, along with broad associations between both GWC and MC and neuropsychological function. These complementary approaches demonstrate the importance of accounting for increasing sources of heterogeneity when studying adults with ASD and provide preliminary insights into links between brain structure and behavior in the second half of the lifespan in ASD.