Age-Related Differences in the Large-Scale Resting State Executive Network and Relationships with Social Communication Impairments in Autism Spectrum Disorder

Background: The first children diagnosed with autism spectrum disorder (ASD) are now elderly; yet, there is little research on aging in adults with ASD. Abnormalities observed in resting-state functional connectivity (rs-FC) of large-scale brain networks are thought to underlie ASD symptoms. The rs-FC of these networks also declines with normal aging, most strongly in the executive network (EN). This is concerning for aging adults with ASD, since executive functioning has been postulated as a compensatory domain responsible for ameliorating the core symptom, social communication impairments (SCI), in ASD.

Objectives: We aimed to determine age-related differences in EN rs-FC in adults with ASD versus neurotypical (NT) adults. Additionally, we aimed to determine age-related differences in SCI, and the relationship between EN rs-FC and SCI, in adults with ASD. We hypothesized adults with ASD would experience larger age-related changes in EN rs-FC than NT adults. Further, we hypothesized middle-age adults with ASD would have greater SCI and a stronger relationship between SCI and EN rs-FC, than young-adults with ASD.

Methods: Participants were 24 young adult (YA; 18-25 years) and 25 middle-aged (MA; 40-64 years) adult males with high-functioning ASD, and 15 YA-NT and 21 MA-NT adult males. Differences in SCI (measured by the Social Responsiveness Scale -2; SRS-2) between YA and MA adults with ASD were evaluated with a t-test (p<0.05, one-tailed). We used independent component analysis to generate whole-brain rs-FC maps of the EN for all participants. Whole-brain EN comparisons were made using a two-factorial design in Statistical Parametric Mapping-12 and small-volume correction (p<0.05, false discovery rate) using an EN mask (neurosynth.org). An exacerbated aging trajectory of rs-FC decline in ASD was probed with a contrast matrix modeling reduced rs-FC in ASD participants relative to NT participants, and a larger age-related decline between ASD age groups than NT age groups. Rs-FC of six neo-cortical EN nodes was extracted and correlations with SCI were investigated in MA-ASD and YA-ASD groups separately (p<0.05, family-wise error corrected). IQ was entered as a covariate in all analyses.

Results: Although MA-ASD participants demonstrated higher SCI than YA-ASD, this difference was non-significant (p=.13). The EN demonstrated exacerbated age declines in rs-FC of the bilateral dlPFC, with only the left hemisphere surviving statistical correction. Lastly, there was a significant negative correlation between rs-FC of the right dlPFC and SCI in MA-ASD but not YA-ASD participants.

Conclusions: In one of the first aging rs-FC investigations in adults with high-functioning ASD, our findings suggested exacerbating age-related hypoconnectivity in frontal regions of the EN, relative to NT adults. Further, EN hypoconnectivity was related to increased SCI in middle-age adults with ASD only. Findings provide some of the first insights of brain mechanisms underlying core symptoms in older adults with ASD.