Associations between atypical intracortical myelin content and neuropsychological functions in middle to older aged adults with ASD.

INTRODUCTION: In vivo myeloarchitectonic mapping based on Magnetic Resonance Imaging (MRI) provides a unique view of gray matter myelin content and offers information complementary to other morphological indices commonly employed in studies of autism spectrum disorder (ASD). The current study sought to determine if intracortical myelin content (MC) and its age-related trajectories differ between middle aged to older adults with ASD and age-matched typical comparison participants. METHODS: Data from 30 individuals with ASD and 36 age-matched typical comparison participants aged 40-70 years were analyzed. Given substantial heterogeneity in both etiology and outcomes in ASD, we utilized both group-level and subject-level analysis approaches to test for signs of atypical intracortical MC as estimated by T1w/T2w ratio. RESULTS: Group-level analyses showed no significant differences in average T1w/T2w ratio or its associations with age between groups, but revealed significant positive main effects of age bilaterally, with T1w/T2w ratio increasing with age across much of the cortex. In subject-level analyses, participants were classified into subgroups based on presence or absence of clusters of aberrant T1w/T2w ratio, and lower neuropsychological function was observed in the ASD subgroup with atypically high T1w/T2w ratio in spatially heterogeneous cortical regions. These differences were observed across several neuropsychological domains, including overall intellectual functioning, processing speed, and aspects of executive function. CONCLUSIONS: The group-level and subject-level approaches employed here demonstrate the value of examining inter-individual variability and provide important preliminary insights into relationships between brain structure and cognition in the second half of the lifespan in ASD, suggesting shared factors contributing to atypical intracortical myelin content and poorer cognitive outcomes for a subset of middle aged to older autistic adults. These atypicalities likely reflect diverse histories of neurodevelopmental deficits, and possible compensatory changes, compounded by processes of aging, and may serve as useful markers of vulnerability to further cognitive decline in older adults with ASD.

Regionally decreased gyrification in middle-aged adults with autism spectrum disorders.

OBJECTIVE: To examine changing features of cortical morphology in middle-aged adults with autism spectrum disorders (ASDs) vs typical comparison (TC) participants, hypothesizing regionally decreased local gyrification index (lGI), given our previous findings of accelerated lGI decline during adolescence. METHODS: After quality assurance, T1-weighted MRI sequences from 20 participants with ASD and 21 TC participants (40-61 years) matched on age were analyzed. lGI, cortical thickness (CT), and surface area (SA) were measured with FreeSurfer version 5.3. Statistical analyses used a general linear model including age, nonverbal IQ, and total brain volume as covariates. Clusters of significant group effects were used as regions of interest for behavioral analyses. RESULTS: Clusters of decreased lGI were observed bilaterally in the ASD group with large effect sizes in insular and anterior cingulate (ACC), left postcentral, and middle frontal and right orbitofrontal and supramarginal regions. lGI was also shown to decline with age across groups in bilateral precentral and right supramarginal clusters. No significant group, age, or group-by-age interaction effects were observed for CT or SA in this age group. lGI showed a significant correlation with Social Responsiveness Scale total scores in a right caudal ACC cluster in the TC group only, while several correlations were found in the ASD group between executive function scores and clusters in the bilateral insula and right orbitofrontal cortex. CONCLUSION: The pattern of regionally decreased lGI observed here in middle-aged adults with ASDs is consistent with an abnormal trajectory of cortical folding changes across different stages of life in ASDs, as shown in previous studies.