BackgroundFunctional neuroimaging research in autism spectrum disorder has reported patterns of decreased long-range, within-network, and interhemispheric connectivity. Research has also reported increased corticostriatal connectivity and between-network connectivity for default and attentional networks. Past studies have excluded individuals with autism and low verbal and cognitive performance (LVCP), so connectivity in individuals more significantly affected with autism has not yet been studied. This represents a critical gap in our understanding of brain function across the autism spectrum.MethodsUsing behavioral support procedures adapted from Nordahl, et al. (J Neurodev Disord 8:20–20, 2016), we completed non-sedated structural and functional MRI scans of 56 children ages 7–17, including LVCP children (n = 17, mean IQ = 54), children with autism and higher performance (HVCP, n = 20, mean IQ = 106), and neurotypical children (NT, n = 19, mean IQ = 111). Preparation included detailed intake questionnaires, video modeling, behavioral and anxiety reduction techniques, active noise-canceling headphones, and in-scan presentation of the Inscapes movie paradigm from Vanderwal et al. (Neuroimage 122:222–32, 2015). A high temporal resolution multiband echoplanar fMRI protocol analyzed motion-free time series data, extracted from concatenated volumes to mitigate the influence of motion artifact. All participants had > 200 volumes of motion-free fMRI scanning. Analyses were corrected for multiple comparisons.ResultsLVCP showed decreased within-network connectivity in default, salience, auditory, and frontoparietal networks (LVCP < HVCP) and decreased interhemispheric connectivity (LVCP < HVCP=NT). Between-network connectivity was higher for LVCP than NT between default and dorsal attention and frontoparietal networks. Lower IQ was associated with decreased connectivity within the default network and increased connectivity between default and dorsal attention networks.ConclusionsThis study demonstrates that with moderate levels of support, including readily available techniques, information about brain similarities and differences in LVCP individuals can be further studied. This initial study suggested decreased network segmentation and integration in LVCP individuals. Further imaging studies of LVCP individuals with larger samples will add to understanding of origins and effects of autism on brain function and behavior.Electronic supplementary materialThe online version of this article (10.1186/s13229-018-0248-y) contains supplementary material, which is available to authorized users.

Bowler et al. (Journal of Autism and Developmental Disorders 44(9):2355-2362. doi:10.1007/s10803-014-2105-y, 2014) have suggested that a specific memory impairment in autism spectrum disorders (ASD) arises from hippocampal failure to consolidate multiple related pieces of information. Twenty-four adults diagnosed with ASD and matched healthy controls completed a pattern separation memory task that is known to critically depend on hippocampal involvement. They additionally completed questionnaires regarding anxiety, depression, and behavioral motivation. Specific deficits in pattern separation were significantly correlated with negative emotionality; the best predictor of memory deficit was from a measure of achievement motivation that has also been associated with hyperactivity and impulsivity. In the context of impaired emotion regulation in ASD, there is a need for integrated cognitive, affective, and neural systems approaches to build targeted interventions.

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Many autistic people report overwhelming sensory experiences and also elevated levels of anxiety. Understanding how these experiences are linked to each other can contribute to improved support and intervention for reducing sensory overload and anxiety. This study included 95 young adult participants including autistic adults, non-autistic adults reporting to a psychotherapy clinic with high levels of anxiety, and neurotypical adults with no psychiatric concerns. We measured pupil size using including a baseline task with no auditory stimulus followed by two blocks of simple auditory habituation. In a subset of 80 participants we also measured self-report levels of sensory processing, anxious apprehension, and intolerance of uncertainty. The autism group showed atypical sensory processing on all four measured domains of the Adolescent and Adult Sensory Profile including sensory sensitivity, sensory seeking, sensory avoidance, and low registration subscales. Dimensional analyses across all participants showed significant positive correlations between sensory sensitivity, sensory seeking, and sensory avoidance domains with scores from the Intolerance of Uncertainty Scale-Short Form and Penn State Worry Questionnaire. The autism group showed significantly larger pupil size than other groups at baseline, before any auditory stimulation. There were no group differences in the rate of auditory habituation, nonetheless the overall, absolute larger pupil size remained in the autism group throughout the experiment. We suggest that this and other findings could indicate chronic hyperarousal in many autistic people. Treatment for anxiety in autism should be informed by knowledge of unique aspects of anxiety in autism and consider the role of sensory experience and everyday psychophysiological arousal.

Several models of anxiety in autistic adults have focused on the role of intolerance of uncertainty which has biological and evolutionary bases, as a cognitive explanation for the high prevalence of anxiety in autism. This framework suggests that all people are born with a healthy level of intolerance of uncertainty, and as we develop, this intolerance is lessened as we learn when situations are safe and begin to understand and manage the uncertainty. This process of learning about managing uncertainty does not happen in the same way in those who are high in autistic traits, which could be the reason for the high levels of anxiety symptoms commonly seen in this population. We examined archival data of 199 non-autistic and 55 autistic adults from prior studies in which we collected self-report measures of autistic traits, intolerance of uncertainty, sensory processing, and anxiety. We conducted two path analyses to examine the role of intolerance of uncertainty in anxiety in autistic adults. The first model tested the idea that intolerance of uncertainty, an evolutionary phenomenon common for all people, could explain some of the cognitive aspects of anxiety in autism. The second model suggests that primary neurodevelopmental differences associated with autistic traits underlie the sensory sensitivity and sensory seeking behaviors, which in turn increase intolerance of uncertainty and subsequent anxiety. We found that the “neurodevelopmental” model had better model fit than the “evolutionary stress” model, suggesting that the neurodevelopmental impact of higher levels of autistic traits could moderate a non-autistic trajectory of learning to manage uncertainty as children develop and understand that uncertainty is common and acceptable.