Autism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, reflected in exaggerated and variable responses to sensory stimuli. Attentional engagement is known to be regulated by the locus ceruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether, under different attentional task demands, individuals with ASD exhibit a different profile of LC activity compared with typically developing controls. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses, an established correlate for LC activity, were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared with controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed specifically in response to task-relevant events, providing confirmation that the group differences most likely were specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD.SIGNIFICANCE STATEMENT Individuals with autism spectrum disorder (ASD) exhibit atypical attentional behaviors, including altered sensory responses and atypical fixedness, but the neural mechanism underlying these behaviors remains elusive. One candidate mechanism is atypical locus ceruleus (LC) activity, as the LC plays a critical role in attentional modulation. Specifically, LC activity is involved in regulating the trade-off between environmental exploration and focused attention. This study shows that, under tightly controlled conditions, task-evoked pupil responses, an LC activity proxy, are lower in individuals with ASD than in controls, but only in the presence of task-irrelevant stimuli. This suggests that individuals with ASD evince atypical modulation of LC activity in accordance with changes in attentional demands, offering a mechanistic account for attentional atypicalities in ASD.

Autism spectrum disorder (ASD) is currently viewed as a disorder of cortical systems connectivity, with a heavy emphasis being on the structural integrity of white matter tracts. However, the majority of the literature to date has focused on children with ASD. Understanding the integrity of white matter tracts in adults may help reveal the nature of ASD pathology in adulthood and the potential contributors to cognitive impairment. This study examined white matter water diffusion using diffusion tensor imaging in relation to neuropsychological measures of cognition in a sample of 45 adults with ASD compared to 20 age, gender, and full‐scale‐IQ‐matched healthy volunteers. Tract‐based spatial statistics were used to assess differences in diffusion along white matter tracts between groups using permutation testing. The following neuropsychological measures of cognition were assessed: processing speed, attention vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. Results indicated that fractional anisotropy (FA) was significantly reduced in adults with ASD in the anterior thalamic radiation ( P = 0.022) and the right cingulum ( P = 0.008). All neuropsychological measures were worse in the ASD group, but none of the measures significantly correlated with reduced FA in either tract in the adults with ASD or in the healthy volunteers. Together, this indicates that the tracts that are the most impacted in autism may not be (at least directly) responsible for the behavioral deficits in ASD. Autism Res 2020, 13: 702–714 . © 2020 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary White matter tracts are the data cables in the brain that efficiently transfer information, and damage to these tracts could be the cause for the abnormal behaviors that are associated with autism. We found that two long‐range tracts (the anterior thalamic radiation and the cingulum) were both impaired in autism but were not directly related to the impairments in behavior. This suggests that the abnormal tracts and behavior are the effects of another underlying mechanism.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Social-cognitive challenges in individuals with autism spectrum disorder (ASD) are often assessed using caregiver report or performance-based instruments. This study compared caregiver report and performance-based measures of social cognition to examine convergence. A total of 128 verbal individuals with ASD were administered performance-based tests of social cognition assessing theory of mind, and one family member completed a measure of social cognition. Caregiver reports of social cognition were weakly and not significantly correlated with performance-based test scores. Caregiver- and performance-based measures converged for children compared with adults and for participants with lower intellectual ability. More research is needed to develop social-cognitive measures that incorporate caregiver perspectives and are robust across individuals with ASD of all ages and levels of intellectual functioning.

Autism ResearchVolume 12, Issue 5 p. 700-714 COMMENTARY Gaps in Current Autism Research: The Thoughts of the Autism Research Editorial Board and Associate Editors David G. Amaral, David G. AmaralSearch for more papers by this authorGeorge M. Anderson, George M. AndersonSearch for more papers by this authorAnthony Bailey, Anthony BaileySearch for more papers by this authorRaphe Bernier, Raphe BernierSearch for more papers by this authorSomer Bishop, Somer BishopSearch for more papers by this authorGene Blatt, Gene BlattSearch for more papers by this authorRicardo Canal-Bedia, Ricardo Canal-Bedia orcid.org/0000-0003-0247-0295 Search for more papers by this authorTony Charman, Tony Charman orcid.org/0000-0003-1993-6549 Search for more papers by this authorGeraldine Dawson, Geraldine DawsonSearch for more papers by this authorPetrus J. de Vries, Petrus J. de VriesSearch for more papers by this authorEmanuel Dicicco-Bloom, Emanuel Dicicco-BloomSearch for more papers by this authorCheryl Dissanayake, Cheryl Dissanayake orcid.org/0000-0002-8771-4027 Search for more papers by this authorYoko Kamio, Yoko Kamio orcid.org/0000-0003-0240-3041 Search for more papers by this authorRajesh Kana, Rajesh Kana orcid.org/0000-0002-8329-1493 Search for more papers by this authorNaila Z. Khan, Naila Z. KhanSearch for more papers by this authorAllison Knoll, Allison KnollSearch for more papers by this authorFrank Kooy, Frank Kooy orcid.org/0000-0003-2024-0485 Search for more papers by this authorJanet Lainhart, Janet LainhartSearch for more papers by this authorPat Levitt, Pat LevittSearch for more papers by this authorKatherine Loveland, Katherine LovelandSearch for more papers by this authorNancy Minshew, Nancy MinshewSearch for more papers by this authorRalph-Axel Mueller, Ralph-Axel Mueller orcid.org/0000-0001-7299-6757 Search for more papers by this authorDeclan Murphy, Declan MurphySearch for more papers by this authorPeter Mundy, Peter MundySearch for more papers by this authorSara Palencia, Sara PalenciaSearch for more papers by this authorJennifer Pinto-Martin, Jennifer Pinto-MartinSearch for more papers by this authorAlexia Rattazzi, Alexia RattazziSearch for more papers by this authorSally Rogers, Sally RogersSearch for more papers by this authorWendy L. Stone, Wendy L. StoneSearch for more papers by this authorSara Jane Webb, Sara Jane WebbSearch for more papers by this authorAndrew Whitehouse, Andrew WhitehouseSearch for more papers by this author David G. Amaral, David G. AmaralSearch for more papers by this authorGeorge M. Anderson, George M. AndersonSearch for more papers by this authorAnthony Bailey, Anthony BaileySearch for more papers by this authorRaphe Bernier, Raphe BernierSearch for more papers by this authorSomer Bishop, Somer BishopSearch for more papers by this authorGene Blatt, Gene BlattSearch for more papers by this authorRicardo Canal-Bedia, Ricardo Canal-Bedia orcid.org/0000-0003-0247-0295 Search for more papers by this authorTony Charman, Tony Charman orcid.org/0000-0003-1993-6549 Search for more papers by this authorGeraldine Dawson, Geraldine DawsonSearch for more papers by this authorPetrus J. de Vries, Petrus J. de VriesSearch for more papers by this authorEmanuel Dicicco-Bloom, Emanuel Dicicco-BloomSearch for more papers by this authorCheryl Dissanayake, Cheryl Dissanayake orcid.org/0000-0002-8771-4027 Search for more papers by this authorYoko Kamio, Yoko Kamio orcid.org/0000-0003-0240-3041 Search for more papers by this authorRajesh Kana, Rajesh Kana orcid.org/0000-0002-8329-1493 Search for more papers by this authorNaila Z. Khan, Naila Z. KhanSearch for more papers by this authorAllison Knoll, Allison KnollSearch for more papers by this authorFrank Kooy, Frank Kooy orcid.org/0000-0003-2024-0485 Search for more papers by this authorJanet Lainhart, Janet LainhartSearch for more papers by this authorPat Levitt, Pat LevittSearch for more papers by this authorKatherine Loveland, Katherine LovelandSearch for more papers by this authorNancy Minshew, Nancy MinshewSearch for more papers by this authorRalph-Axel Mueller, Ralph-Axel Mueller orcid.org/0000-0001-7299-6757 Search for more papers by this authorDeclan Murphy, Declan MurphySearch for more papers by this authorPeter Mundy, Peter MundySearch for more papers by this authorSara Palencia, Sara PalenciaSearch for more papers by this authorJennifer Pinto-Martin, Jennifer Pinto-MartinSearch for more papers by this authorAlexia Rattazzi, Alexia RattazziSearch for more papers by this authorSally Rogers, Sally RogersSearch for more papers by this authorWendy L. Stone, Wendy L. StoneSearch for more papers by this authorSara Jane Webb, Sara Jane WebbSearch for more papers by this authorAndrew Whitehouse, Andrew WhitehouseSearch for more papers by this author First published: 26 April 2019 https://doi.org/10.1002/aur.2101Citations: 16Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume12, Issue5May 2019Pages 700-714 RelatedInformation

Background: Schizophrenia and autism share many behavioral and neurological similarities, including altered white matter tract structure. However, because schizophrenia and autism are rarely compared directly, it is difficult to establish whether white matter abnormalities are disorder-specific or are common across these disorders that share some symptomatology. Methods: In the current study, we compared white matter water diffusion using tensor imaging in 25 adults with autism, 15 adults with schizophrenia, all with IQ scores above 88, and 19 neurotypical adults. Results: Although the three groups evinced no statistically significant differences in measures of fractional anisotropy (FA), the schizophrenia group showed significantly greater mean diffusivity (MD; Cohen's d > 0.77), due to greater radial diffusivity (RD; Cohen's d > 0.92), compared to both the autism and control groups. This effect was evident across the brain rather than specific to a particular tract. Conclusions: The greater MD and RD in schizophrenia appears to be diagnosis-specific. The altered diffusion may reflect subtle abnormalities in myelination, which could be a potential mechanism underlying the widespread behavioral deficits associated with schizophrenia.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that reduces obsessive–compulsive symptoms. There is limited evidence supporting its efficacy for repetitive behaviors (RRBs) in autistic spectrum disorder (ASD). We conducted a randomized controlled trial (RCT) of fluoxetine in 158 individuals with ASD (5–17 years). Following 14 treatment weeks (mean dose 11.8 mg/day), no significant differences were noted on the Children’s Yale-Brown Obsessive Compulsive Scale; the proportion of responders was similar (fluoxetine: 36%; placebo: 41%). There were similar rates of AEs (e.g., insomnia, diarrhea, vomiting); high rates of activation were reported in both groups (fluoxetine: 42%; placebo: 45%). Overly cautious dosing/duration may have prevented attainment of a therapeutic level. Results are consistent with other SSRI RCTs treating RRBs in ASD. Trial Registration: clinicaltrials.gov Identifier: NCT00515320.

Autism spectrum disorder (ASD) is characterized by a variety of social and non-social behavioral deficits. One potential mechanism that could unify this diverse profile of behaviors is slower processing speed. Seventy-six high-functioning adults with ASD were compared to 64 matched controls on standardized measures of processing speed. Participants with ASD were significantly slower on all measures, and on the composite score from the three tests (d's > .65). ASD participants with slower processing speeds scored higher on the ADOS Communication and Reciprocal Social Interaction scale (r = .34). These findings provide evidence of slower processing speeds in adults with ASD, and that this may be contributing to impairments in social communication skills. Interventions that improve processing speed might improve social communication abilities in ASD.

This study extends prior memory reports in autism spectrum disorders (ASD) by investigating memory for narratives after longer recall periods and by examining developmental aspects of narrative memory using a cross‐sectional design. Forty‐seven older children/adolescents with ASD and 31 youth with typical development (TD) and 39 adults with ASD and 45 TD adults were compared on memory for stories from standardized measures appropriate for each age group at three intervals (immediate, 30 min, and 2 day). Both the youth with and without ASD had difficulty with memory for story details with increasing time intervals. More of the youths with ASD performed in the range of impairment when recalling the stories 2 days later as compared to the TD group. The adults with ASD had more difficulty on memory for story details with increasing delay and were poorer at recall of thematic information (needed to create a gist) across the three delay conditions as compared to the TD group. Analyses of the individual results suggested that memory for details of most of the adults with ASD was not impaired when applying a clinical standard; however, a significant percentage of the adults with ASD did not make use of thematic information to organize the narrative information, which would have helped them to remember the stories. The youth with and without ASD performed similarly when both were at a stage of development when memory for details is the primary strategy. The adults with ASD had difficulty with use organizational strategies to support episodic memory. Autism Res 2017, 10: 1523–1532. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Background: Autism spectrum disorder (ASD) and schizophrenia are neurodevelopmental conditions that are characterized by significant social impairment. Emerging genomic and neurobiological evidence has increasingly pointed to shared pathophysiologic mechanisms in the two disorders. Overlap in social impairment may reflect similar underlying neural dysfunction in social-cognitive brain networks, yet few studies have directly compared brain function and communication between those with ASD and schizophrenia.Methods: Outpatients with schizophrenia (n=36), ASD (n=33), and healthy volunteers (n=37) completed a visual perspective-taking task during functional neuroimaging at 3T to assess similarities and differences in fronto-temporal brain function and connectivity during social-cognitive processing. Analyses employed general linear models to examine differences in amplitude of BOLD-signal response between disorder groups, and computed functional connectivity coefficients to investigate differences in the connectivity profiles of networks implicated in social cognition.Results: Despite similar behavioral impairments, participants with ASD and schizophrenia evidenced distinct neural abnormalities during perspective-taking. Functional activation results indicated reduced temporoparietal junction and medial prefrontal activity in ASD compared to schizophrenia (all P-uncor < 0.002). Functional connectivity analyses further revealed significantly greater local orbitofrontal connectivity in ASD than schizophrenia (all P-FDR < 0.028) during perspective-taking. Differences in brain activation and connectivity were unrelated to antipsychotic medication dose.Conclusions: Autism and schizophrenia are characterized by similar social-cognitive impairments that may stem from different underlying abnormalities in the functional organization and communication of the social brain. (C) 2017 Elsevier B.V. All rights reserved.

This study examined differences between adults with autism spectrum disorder (ASD; N = 40) and typical community volunteers (N = 25) on measures of stressful life events, perceived stress, and biological stress response (cardiovascular and cortisol reactivity) during a novel social stress task. Additional analyses examined the relationship between stress and social functioning as measured by the Social Adjustment Scale-II and the Waisman Activities of Daily Living scale. Results indicated that adults with ASD experienced significantly more stressful life events and perceived stress, and greater systolic blood pressure reactivity than typical community volunteers. Results also indicated that perceived stress and stressful life events were significantly associated with social disability. Interventions targeting stress management might improve social function in adults with ASD.

BACKGROUND:Individuals with autism spectrum disorder (ASD) experience marked challenges with social function by definition, but few modifiable predictors of social functioning in ASD have been identified in extant research. This study hypothesized that deficits in social cognition and motor function may help to explain poor social functioning in individuals with ASD.METHOD:Cross-sectional data from 108 individuals with ASD and without intellectual disability ages 9 through 27.5 were used to assess the relationship between social cognition and motor function, and social functioning.RESULTS:Results of hierarchical multiple regression analyses revealed that greater social cognition, but not motor function, was significantly associated with better social functioning when controlling for sex, age, and intelligence quotient. Post-hoc analyses revealed that, better performance on second-order false belief tasks was associated with higher levels of socially adaptive behavior and lower levels of social problems.CONCLUSIONS:Our findings support the development and testing of interventions that target social cognition in order to improve social functioning in individuals with ASD. Interventions that teach generalizable skills to help people with ASD better understand social situations and develop competency in advanced perspective taking have the potential to create more durable change because their effects can be applied to a wide and varied set of situations and not simply a prescribed set of rehearsed situations.

Cognitive remediation is a promising approach to treating core cognitive deficits in adults with autism, but rigorously controlled trials of comprehensive interventions that target both social and non‐social cognition over a sufficient period of time to impact functioning are lacking. This study examined the efficacy of cognitive enhancement therapy (CET) for improving core cognitive and employment outcomes in adult autism. Verbal adult outpatients with autism spectrum disorder (N = 54) were randomized to an 18‐month, single‐blind trial of CET, a cognitive remediation approach that integrates computer‐based neurocognitive training with group‐based training in social cognition, or an active enriched supportive therapy (EST) comparison focused on psychoeducation and condition management. Primary outcomes were composite indexes of neurocognitive and social‐cognitive change. Competitive employment was a secondary outcome. Intent‐to‐treat analyses indicated that CET produced significant differential increases in neurocognitive function relative to EST (d = .46, P = .013). Both CET and EST were associated with large social‐cognitive improvements, with CET demonstrating an advantage at 9 (d = .58, P = 0.020), but not 18 months (d = .27, P = 0.298). Effects on employment indicated that participants treated with CET were significantly more likely to gain competitive employment than those in EST, OR = 6.21, P = 0.023, which was mediated by cognitive improvement. CET is a feasible and potentially effective treatment for core cognitive deficits in adult autism spectrum disorder. The treatment of cognitive impairments in this population can contribute to meaningful improvements in adult outcomes. Autism Res 2018, 11: 519–530. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.Lay SummaryCognitive enhancement therapy (CET), an 18‐month cognitive remediation intervention designed to improve thinking and social understanding, was found to be more effective than supportive therapy at improving mental quickness, attention, and employment in adults living with autism. Social understanding was equally improved in CET and supportive therapy. Cognitive remediation interventions are feasible and may confer significant functional benefits to adults with autism.

Autism and schizophrenia share multiple phenotypic and genotypic markers, and there is ongoing debate regarding the relationship of these two disorders. To examine whether cortical dynamics are similar across these disorders, we directly compared fMRI responses to visual, somatosensory and auditory stimuli in adults with autism (N=15), with schizophrenia (N=15), and matched controls (N=15). All participants completed a one-back letter detection task presented at fixation (to control attention) while task-irrelevant sensory stimulation was delivered to the different modalities. We focused specifically on the response amplitudes and the variability in sensory fMRI responses of the two groups, given the evidence of greater trial-to-trial variability in adults with autism. Both autism and schizophrenia individuals showed weaker signal-to-noise ratios (SNR) in sensory-evoked responses compared to controls (d>0.42), but for different reasons. For the autism group, the fMRI response amplitudes were indistinguishable from controls but were more variable trial-to-trial (d=0.47). For the schizophrenia group, response amplitudes were smaller compared to autism (d=0.44) and control groups (d=0.74), but were not significantly more variable (d<0.29). These differential group profiles suggest (1) that greater trial-to-trial variability in cortical responses may be specific to autism and is not a defining characteristic of schizophrenia, and (2) that blunted response amplitudes may be characteristic of schizophrenia. The relationship between the amplitude and the variability of cortical activity might serve as a specific signature differentiating these neurodevelopmental disorders. Identifying the neural basis of these responses and their relationship to the underlying genetic bases may substantially enlighten the understanding of both disorders.

Autism has been associated with abnormalities in sensory and attentional processing. Here, we assessed these processes independently in the visual and auditory domains using a visual contrast-discrimination task and an auditory modulation-depth discrimination task. To evaluate changes in sensory function by attention, we measured behavioral performance (discrimination accuracy) when subjects were cued to attend and respond to the same stimulus (frequent valid cue) or cued to attend to one stimulus and respond to the non-cued stimulus (infrequent invalid cue). The stimuli were presented at threshold to ensure equal difficulty across participants and groups. Results from fifteen high-functioning adult individuals with autism and fifteen matched controls revealed no significant differences in visual or auditory discrimination thresholds across groups. Furthermore, attention robustly modulated performance accuracy (performance was better for valid than invalid cues) in both sensory modalities and to an equivalent extent in both groups. In conclusion, when using this well-controlled method, we found no evidence of atypical sensory function or atypical attentional modulation in a group of high functioning individuals with clear autism symptomatology.

GENERAL COMMENTARY article Front. Integr. Neurosci., 09 November 2016 Volume 10 - 2016 | https://doi.org/10.3389/fnint.2016.00036

An fMRI study was used to measure the brain activation of a group of adults with high-functioning autism compared to a Full Scale and Verbal IQ and age-matched control group during an n-back working memory task with letters. The behavioral results showed comparable performance, but the fMRI results suggested that the normal controls might use verbal codes to perform the task, while the adults with autism might use visual codes. The control group demonstrated more activation in the left than the right parietal regions, whereas the autism group showed more right lateralized activation in the prefrontal and parietal regions. The autism group also had more activation than the control group in the posterior regions including inferior temporal and occipital regions. The analysis of functional connectivity yielded similar patterns for the two groups with different hemispheric correlations. The temporal profile of the activity in the prefrontal regions was more correlated with the left parietal regions for the control group, whereas it was more correlated with the right parietal regions for the autism group.

Multiple hypotheses have been offered to explain the impaired face-processing behavior and the accompanying underlying disruptions in neural circuitry among individuals with autism. We explored the specificity of atypical face-processing activation and potential alterations to fusiform gyrus (FG) morphology as potential underlying mechanisms. Adolescents with high functioning autism (HFA) and age-matched typically developing (TD) adolescents were scanned with sMRI and fMRI as they observed human and animal faces. In spite of exhibiting comparable face recognition behavior, the HFA adolescents evinced hypo-activation throughout the face-processing system in response to unfamiliar human, but not animal, faces. They also exhibited greater activation in affective regions of the face-processing network in response to animal, but not human, faces. Importantly, this atypical pattern of activation in response to human faces was not related to atypical structural properties of the FG. This atypical neural response to human faces in autism may stem from abnormalities in the ability to represent the reward value of social (i.e. conspecific) stimuli.