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.

Reduced asymmetry of the hand knob area and decreased sensorimotor u-fiber connectivity in middle-aged adults with autism.

Individuals with autism spectrum disorder (ASD) frequently present with impairments in motor skills (e.g., limb coordination, handwriting and balance), which are observed across the lifespan but remain largely untreated. Many adults with ASD may thus experience adverse motor outcomes in aging, when physical decline naturally occurs. The 'hand knob' of the sensorimotor cortex is an area that is critical for motor control of the fingers and hands. However, this region has received little attention in ASD research, especially in adults after midlife. The hand knob area of the precentral (PrChand) and postcentral (PoChand) gyri was semi-manually delineated in 49 right-handed adults (25 ASD, 24 typical comparison [TC] participants, aged 41-70 years). Using multimodal (T1-weighted, diffusion-weighted, and resting-state functional) MRI, we examined the morphology, ipsilateral connectivity and laterality of these regions. We also explored correlations between hand knob measures with motor skills and autism symptoms, and between structural and functional connectivity measures. Bayesian analyses indicated moderate evidence of group effects with greater right PrChand volume and reduced leftward laterality of PrChand and PoChand volume in the ASD relative to TC group. Furthermore, the right PoC-PrChand u-fibers showed increased mean diffusivity in the ASD group. In the ASD group, right u-fiber volume positively correlated with corresponding functional connectivity but did not survive multiple comparisons correction. Correlations of hand knob measures and behavior were observed in the ASD group but did not survive multiple comparisons correction. Our findings suggest that morphological laterality and u-fiber connectivity of the sensorimotor network, putatively involved in hand motor/premotor function, may be diminished in middle-aged adults with ASD, perhaps rendering them more vulnerable to motor decline in old age. The altered morphology may relate to atypical functional motor asymmetries found in ASD earlier in life, possibly reflecting altered functional asymmetries over time.

Functional connectivity within an anxiety network and associations with anxiety symptom severity in middle-aged adults with and without autism.

Anxiety is highly prevalent in autism spectrum disorders (ASDs). However, few functional magnetic resonance imaging (fMRI) studies of ASDs have focused on anxiety (and fewer still on anxiety in middle-aged adults). Thus, relationships between atypical connectivity and anxiety in this population are poorly understood. The current study contrasted functional connectivity within anxiety network regions across adults (40-64 years) with and without autism, and tested for group by functional connectivity interactions on anxiety. Twenty-two adults with ASDs (16 males) and 26 typical control (TC) adults (22 males) completed the Beck Anxiety Inventory and a resting-state fMRI scan. An anxiety network consisting of 12 regions of interest was defined, based on a meta-analysis in TC individuals and two studies on anxiety in ASDs. We tested for main effects of group and group by anxiety interactions on connectivity within this anxiety network, controlling for head motion using ANCOVA. Results are reported at an FDR adjusted threshold of q < 0.1 (corrected) and p < 0.05 (uncorrected). Adults with ASDs showed higher anxiety and underconnectivity within the anxiety network, mostly involving bilateral insula. Connectivity within the anxiety network in the ASD group showed distinct relationships with anxiety symptoms that did not relate to ASD symptom severity. Functional connectivity involving the bilateral posterior insula was positively correlated with anxiety in the ASD (but not the TC) group. Increased anxiety in middle-aged adults with ASD is associated with atypical functional connectivity, predominantly involving bilateral insula. Results were not related to ASD symptom severity suggesting independence of anxiety-related effects. LAY SUMMARY: Anxiety is very common in adults with autism but the brain basis of this difference is not well understood. We compared functional connectivity between anxiety-related brain regions in middle-aged adults with and without autism. Adults with autism were more anxious and showed weaker functional connections between these regions. Some relationships between functional connectivity and higher anxiety were specific to the autism group. Results suggest that anxiety functions differently in autism.

Supplementary and Premotor Aspects of the Corticospinal Tract Show Links with Restricted and Repetitive Behaviors in Middle-Aged Adults with Autism Spectrum Disorder.

Individuals with autism spectrum disorder (ASD) show motor impairment into adulthood and risk decline during aging, but little is known about brain changes in aging adults with ASD. Few studies of ASD have directly examined the corticospinal tract (CST)-the major descending pathway in the brain responsible for voluntary motor behavior-outside its primary motor (M1) connections. In 26 middle-aged adults with ASD and 26 age-matched typical comparison participants, we used diffusion imaging to examine the microstructure and volume of CST projections from M1, dorsal premotor (PMd), supplementary motor area (SMA), and primary somatosensory (S1) cortices with respect to age. We also examined relationships between each CST sub-tract (-cst), motor skills, and autism symptoms. We detected no significant group or age-related differences in tracts extending from M1 or other areas. However, sub-tracts of the CST extending from secondary (but not primary) motor areas were associated with core autism traits. Increased microstructural integrity of left PMd-cst and SMA-cst were associated with less-severe restricted and repetitive behaviors (RRB) in the ASD group. These findings suggest that secondary motor cortical areas, known to be involved in selecting motor programs, may be implicated in cognitive motor processes underlying RRB in 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.

Local Cortical Gyrification is Increased in Children With Autism Spectrum Disorders, but Decreases Rapidly in Adolescents.

Extensive MRI evidence indicates early brain overgrowth in autism spectrum disorders (ASDs). Local gyrification may reflect the distribution and timing of aberrant cortical expansion in ASDs. We examined MRI data from (Study 1) 64 individuals with ASD and 64 typically developing (TD) controls (7-19 years), and from (Study 2) an independent sample from the Autism Brain Imaging Data Exchange (n = 31/group). Local Gyrification Index (lGI), cortical thickness (CT), and surface area (SA) were measured. In Study 1, differences in lGI (ASD > TD) were found in left parietal and temporal and right frontal and temporal regions. lGI decreased bilaterally with age, but more steeply in ASD in left precentral, right lateral occipital, and middle frontal clusters. CT differed between groups in right perisylvian cortex (TD > ASD), but no differences were found for SA. Partial correlations between lGI and CT were generally negative, but associations were weaker in ASD in several clusters. Study 2 results were consistent, though less extensive. Altered gyrification may reflect unique information about the trajectory of cortical development in ASDs. While early overgrowth tends to be undetectable in later childhood in ASDs, findings may indicate that a trace of this developmental abnormality could remain in a disorder-specific pattern of gyrification.