Highlights Evidence suggests neuroimaging-based sex differences in ASD are age-dependent. Most studies collapse across age, possibly masking sex-by-diagnosis effects. Sex-by-diagnosis effects overlap with regions showing typical sexual dimorphism. Findings discussed in the context of genetic and endocrine sex effects on the brain. Future research would benefit from a lifespan approach in large-sample studies.

Background: Research suggests adults with autism spectrum disorder (ASD) may use executive functions to compensate for social difficulties. Given hallmark age-related declines in executive functioning and the executive brain network in normal aging, there is concern that older adults with ASD may experience further declines in social functioning as they age. In a male-only sample, we hypothesized: 1) older adults with ASD would demonstrate greater ASD-related social behavior than young adults with ASD, 2) adults with ASD would demonstrate a greater age group reduction in connectivity of the executive brain network than neurotypical (NT) adults, and 3) that behavioral and neural mechanisms of executive functioning would predict ASD-related social difficulties in adults with ASD.Methods: Participants were a cross-sectional sample of non-intellectually disabled young (ages 18-25) and middle-aged (ages 40-70) adult men with ASD and NT development (young adult ASD: n=24; middle-age ASD: n=25; young adult NT: n=15; middle-age NT: n=21). We assessed ASD-related social behavior via the self-report Social Responsiveness Scale-2 (SRS-2) Total Score, with exploratory analyses of the Social Cognition Subscale. We assessed neural executive function via connectivity of the resting-state executive network (EN) as measured by independent component analysis. Correlations were investigated between SRS-2 Total Scores (with exploratory analyses of the Social Cognition Subscale), EN functional connectivity of the dorsolateral prefrontal cortex (dlPFC), and a behavioral measure of executive function, Tower of London (ToL) Total Moves. Results:We did not confirm a significant age group difference for adults with ASD on the SRS-2 Total Score; however, exploratory analysis revealed middle-age men with ASD had higher scores

The constituent nano-fibrils of bacterial cellulose are of interest to many researchers because of their purity and excellent mechanical properties. Mechanisms to disrupt the network structure of bacterial cellulose (BC) to isolate bacterial cellulose nanofibrils (BCN) are limited. This work focuses on liquid-phase dispersions of BCN in a range of organic solvents.It builds on work to disperse similarly intractable nanomaterials, such as single-walled carbon nanotubes, where optimum dispersion is seen for solvents whose surface energies are close to the surface energy of the nanomaterial; bacterial cellulose is shown to disperse in a similar fashion. Inverse gas chromatrogrphy was used to determine the surface energy of bacterial cellulose, under relevant conditions, by quantifying the surface heterogeneity of the material as a function of coverage. Films of pure BCN were prepared from dispersions in a range of solvents; the extent of BCN exfoliation is shown to have a strong effect on the mechanical properties of BC films, and to fit models based on the volumetric density of nanofibril junctions. Such control offers new routes to producing robust cellulose films of bacterial cellulose nanofibrils.

Research studying aging in adults with autism spectrum disorder (ASD) is growing, but longitudinal work is needed. Autistic adults have increased risk of dementia, altered hippocampal volumes and fornix integrity, and verbal memory difficulties compared with neurotypical (NT) adults. This study examined longitudinal aging in middle-age adults with ASD versus a matched NT group, and compared findings with cross-sectional age effects across a broad adult age range. Participants were 194 adults with (n = 106; 74 male) and without (n = 88; 52 male) ASD, ages 18-71. Participants (n = 45; 40-70 age range) with two visits (2-3 years apart) were included in a longitudinal analysis. Hippocampal volume, fornix fractional anisotropy (FA), and verbal memory were measured via T1-weighted MRI, diffusion tensor imaging, and the Rey Auditory Verbal Learning Test, respectively. Longitudinal mixed models were used for hippocampal system variables and reliable change index categories were used for Auditory Verbal Learning Test analyses. Multivariate regression was used for cross-sectional analyses. Middle-age adults with ASD had greater longitudinal hippocampal volume loss and were more likely to show clinically meaningful decline in short-term memory, compared with NT. In contrast, cross-sectional associations between increasing age and worsening short-term memory were identified in NT, but not autistic adults. Reduced fornix FA and long-term memory in ASD were found across the broad cross-sectional age range. These preliminary longitudinal findings suggest accelerated hippocampal volume loss in ASD and slightly higher rates of clinically-meaningful decline in verbal short-term memory. Contradictory cross-sectional and longitudinal results underscore the importance of longitudinal aging research in autistic adults. Lay SummaryAutistic adults have increased risk of dementia, differences in brain memory structures, and difficulty with memory compared with neurotypical (NT) adults. However, there are no publications that follow the same middle-age autistic adults over time to see how their brain and memory change. Our preliminary findings in a small middle-age autism sample suggest a key memory brain structure, the hippocampus, may shrink faster over 2-3 years compared with NT, and short-term memory may become more challenging for some. Across a broad adult range, autistic adults also had reduced integrity of connections to the hippocampus and greater challenges with long-term memory. In our larger sample across a broad Broc A. Pagni and Melissa J. M. Walsh contributed equally to this work.

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Background:The integrity and connectivity of the frontal lobe, which subserves fluency, may be compromised by both ASD and aging. Alternate networks often integrate to help compensate for compromised functions during aging. We used network analyses to study how compensation may overcome age-related compromised in individuals with ASD.Method: Participants consisted of middle-aged (40-60; n=24) or young (18-25; n=18) righthanded males who have a diagnosis of ASD, and age-and IQ-matched control participants (n=20, 14, respectively). All performed tests of language and executive functioning and a fluency functional MRI task. We first used group individual component analysis (ICA) for each of the 4 groups to determine whether different networks were engaged. An SPM analysis was used to compare activity detected in the network nodes from the ICA analyses. Results:The individuals with ASD performed more slowly on two cognitive tasks (Stroop word reading and Trailmaking Part A). The 4 groups engaged different networks during the fluency fMRI task despite equivalent performance. Comparisons of specific regions within these networks indicated younger individuals had greater engagement of the thalamus and supplementary speech area, while older adults engaged the superior temporal gyrus. Individuals with ASD did not disengage from the Default Mode Network during word generation. Conclusion:Interactions between diagnosis and aging were not found in this study of young and middle-aged men, but evidence for differential engagement of compensatory networks was observed.

Adults with autism spectrum disorder (ASD) experience high rates of depression and anxiety, and some evidence suggests mindfulness-based stress reduction (MBSR) is effective in reducing these symptoms. However, the neural mechanisms of symptom alleviation, and benefit of MBSR beyond education/support groups are unknown.Maladaptive forms of self-reflection are linked to ASD, depression, and anxiety. In this pilot study, we hypothesized (a) MBSR would reduce depression and anxiety in adults with ASD and (b) a mechanism of symptom alleviation would be increased blood oxygen level-dependent signal in neural self-reflection hubs. Twenty-eight adults were randomly assigned to an 8-week MBSR group (n = 15) or a support group (n = 13) that met for the same amount of time with relaxation education materials.Based on previous self-reflection literature in ASD, regions of interest (ROIs) were middle cingulate cortex (MCC) and ventromedial prefrontal cortex (vmPFC). Only the MBSR group demonstrated significant reductions in depression, and neither group significantly changed in anxiety. Only the MBSR group increased activity of right MCC during self-reflection, and the increase correlated with depression alleviation.There were no changes in vmPFC for the MBSR group or either ROI for the support/ education group. Seed-to-voxel connectivity analysis revealed that only the MBSR group increased functional connectivity between right MCC and pre/postcentral gyrus, suggesting MBSR may increase primary sensorimotor input to higher order cognitive brain regions. Taken together, MBSR may be effective for reducing depression in adults with ASD, and the neural mechanism may be increasing frontal circuit involvement during self-directed thought. K E Y W O R D S anxiety, autism, cingulate cortex, depression, functional connectivity, functional MRI, mindfulness, self-reflection | 1151 PAGNI et Al.

Research aimed at understanding cognitive and brain aging in adults with autism spectrum disorder (ASD) is growing, but critical longitudinal work is scant. Adults with ASD struggle with tasks involving visual memory compared with neurotypical adults (NT). This may be related to differences in size or integrity of the hippocampus and its’ primary structural connectivity pathway, the fornix. The aim of this study was to describe preliminary findings of longitudinal aging trajectories in short- and long-term visual memory abilities in middle-age and older adults with ASD, compared with matched NT adults. We then evaluated baseline multi-modal imaging metrics of the hippocampal system, including the relatively novel metric of free-water, as potential correlates of longitudinal memory change in the ASD group. Middle-age and older adults with ASD (n = 25) and matched NT adults (n = 25) between the ages of 40 and 70 years were followed longitudinally at ~2-year intervals (range 2–5 years). Participants completed the Wechsler Memory Scale III Visual Reproduction task. Longitudinal mixed models were utilized to detect group differences in memory change with baseline age and sex as covariates. Hippocampal volume was measured via T1-weighted MRI images with FreeSurfer. Fornix fractional anisotropy and hippocampal and fornix free-water were measured from diffusion tensor imaging scans. Exploratory correlations were run between individual hippocampal system metrics and longitudinal slopes of visual memory change. There was a significant group by time interaction for long-term visual memory, such that middle-age and older adults with ASD declined faster than matched NT adults. There was no group by time interaction for short-term visual memory. Baseline hippocampal free-water was the only hippocampal system metric that correlated with long-term visual memory change in the ASD group. As one of the first longitudinal cognitive and brain aging studies in middle-age and older adults with ASD, our findings suggest vulnerabilities for accelerated long-term visual memory decline, compared to matched NT adults. Further, baseline hippocampal free-water may be a predictor of visual memory change in middle-age and older adults with ASD. These preliminary findings lay the groundwork for future prognostic applications of MRI for cognitive aging in middle-age and older adults with ASD.