Binding of Multiple Features in Memory by High-Functioning Adults with Autism Spectrum Disorder

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Neuroimaging studies have uncovered structural and functional alterations in the cingulate cortex in individuals with autism spectrum disorders (ASD). Such abnormalities may underlie neurochemical imbalance. In order to characterize the neurochemical profile, the current study examined the concentration of brain metabolites in dorsal ACC (dACC) and posterior cingulate cortex (PCC) in high-functioning adults with ASD. Twenty high-functioning adults with ASD and 20 age-and-IQ-matched typically developing (TD) peers participated in this Proton magnetic resonance spectroscopy (1H-MRS) study. LCModel was used in analyzing the spectra to measure the levels of N-Acetyl aspartate (NAA), choline (Cho), creatine (Cr), and glutamate/glutamine (Glx) in dACC and PCC. Groups were compared using means for the ratio of each metabolite to their respective Cr levels as well as on absolute internal-water-referenced measures of each metabolite. There was a significant increase in Cho in PCC for ASD adults, with a marginal increase in dACC. A reduction in NAA/Cr in dACC was found in ASD participants, compared to their TD peers. No significant differences in Glx/Cr or Cho/Cr were found in dACC. There were no statistically significant group differences in the absolute concentration of NAA, Cr, Glx, or NAA/Cr, Cho/Cr, and Glx/Cr in the PCC. Differences in the metabolic properties of dACC compared to PCC were also found. Results of this study provide evidence for possible cellular and metabolic differences in the dACC and PCC in adults with ASD. This may suggest neuronal dysfunction in these regions and may contribute to the neuropathology of ASD. Autism Res 2016, 9: 643-657. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Objective: Prospective memory (PM) is the ability to remember to carry out an intended action. Working memory is the ability to store information in mind while processing potentially distracting information. The few previous studies of PM in autism spectrum disorder (ASD) have yielded inconsistent findings. Studies of working memory ability in ASD have suggested a selective impairment of “visual working memory.” However, it remains unclear whether any such impairment is the result of diminished (domain-specific; visual/verbal) storage capacity or diminished (domain-general) processing capacity. We aim to clarify these issues and explore the relation between PM and working memory in ASD. Method: Seventeen adults with ASD and 17 age- and IQ-matched comparison participants completed experimental measures of both event-based (perform action x when event y occurs) and time-based (perform action a at time b) PM, plus a self-report measure of PM skills. Participants also completed a working memory test battery. Results: Participants with ASD self-reported diminished PM skill, and showed diminished performance on the time-based, but not event-based, PM task. On the working memory test battery, visual but not verbal storage capacity was diminished among participants with ASD, as was processing ability. Whereas visual storage was associated with event-based PM task performance among comparison participants, verbal storage was associated among ASD participants. Conclusions: ASD appears to involve a selective deficit in time-based PM and a selective difficulty with aspects of working memory that depend on the storage of visual information. However, event-based PM may be achieved through compensatory strategies in ASD.

Quality of life: A case-controlled long-term follow-up study, comparing young high-functioning adults with autism spectrum disorders with adults with other psychiatric disorders diagnosed in childhood

Bone microarchitecture in adolescent boys with autism spectrum disorder

Inflexibility in Autism Spectrum Disorder: Need for certainty and atypical emotion processing share the blame

Inhibitory control deficits are common in autism spectrum disorder (ASD) and associated with more severe repetitive behaviors. Inhibitory control deficits may reflect slower execution of stopping processes, or a reduced ability to delay the onset of behavioral responses in contexts of uncertainty. Previous studies have documented relatively spared stopping processes in ASD, but whether inhibitory control deficits in ASD reflect failures to delay response onset has not been systematically assessed. Further, while improvements in stopping abilities and response slowing are seen through adolescence/early adulthood in health, their development in ASD is less clear. A stop-signal test (SST) was administered to 121 individuals with ASD and 76 age and IQ-matched healthy controls (ages 5-28). This test included 'GO trials' in which participants pressed a button when a peripheral target appeared and interleaved 'STOP trials' in which they were cued to inhibit button-presses when a stop-signal appeared at variable times following the GO cue. STOP trial accuracy, RT of the stopping process (SSRT), and reaction time (RT) slowing during GO trials were examined. Relative to controls, individuals with ASD had reduced accuracy on STOP trials. SSRTs were similar across control and ASD participants, but RT slowing was reduced in patients compared to controls. Age-related increases in stopping ability and RT slowing were attenuated in ASD. Reduced stopping accuracy and RT slowing were associated with more severe repetitive behaviors in ASD. Our findings show that inhibitory control deficits in ASD involve failures to strategically delay behavioral response onset. These results suggest that reduced preparatory behavioral control may underpin inhibitory control deficits as well as repetitive behaviors in ASD. Typical age-related improvements in inhibitory control during late childhood/early adolescence are reduced in ASD, highlighting an important developmental window during which treatments may mitigate cognitive alterations contributing to repetitive behaviors.

BackgroundInhibitory control and attention processing atypicalities are implicated in various diseases, including autism spectrum disorders (ASD). These cognitive functions can be tested by using visually guided saccade-based paradigms in children, adolescents and adults to determine the time course of such disorders.MethodsIn this study, using Gap, Step, Overlap and Antisaccade tasks, we analyzed the oculomotor behavior of 82 children, teenagers and adults with high functioning ASD and their peer typically developing (TD) controls in a two-year follow-up study under the auspices of the InFoR-Autism project. Analysis of correlations between oculomotors task measurements and diagnostic assessment of attentional (ADHD-RS and ADHD comorbidity indices) and executive functioning (BRIEF scales) were conducted in order to evaluate their relationship with the oculomotor performance of participants with ASD.ResultsAs indicated by the presence of a Gap and Overlap effects in all age groups, the oculomotor performances of ASD participants showed a preserved capability in overt attention switching. In contrast, the difference in performances of ASD participants in the Antisaccade task, compared to their TD peers, indicated an atypical development of inhibition and executive functions. From correlation analysis between our oculomotor data and ADHD comorbidity index, and scores of attention and executive function difficulties, our findings support the hypothesis that a specific dysfunction of inhibition skills occurs in ASD participants that is independent of the presence of ADHD comorbidity.LimitationsThese include the relatively small sample size of the ASD group over the study’s two-year period, the absence of an ADHD-only control group and the evaluation of a TD control group solely at the study’s inception.ConclusionsChildren and teenagers with ASD have greater difficulty in attention switching and inhibiting prepotent stimuli. Adults with ASD can overcome these difficulties, but, similar to teenagers and children with ASD, they make more erroneous and anticipatory saccades and display a greater trial-to-trial variability in all oculomotor tasks compared to their peers. Our results are indicative of a developmental delay in the maturation of executive and attentional functioning in ASD and of a specific impairment in inhibitory control.

Autonomic arousal explains social cognitive abilities in high-functioning adults with autism spectrum disorder

IntroductionDespite extensive investigation, the neurophysiological underpinnings of ASD remain poorly understood; a predominant hypothesis relates to the activity of the brain’s mu-rhythm (defined as the frequency band ranging between 8–14 Hz topographically centered over the sensorimotor cortex) and the so-called “Mirror Neuron System” (MNS), considered as an execution-imagination-observation matching system. In particular, mirror neurons (MN) are bimodal neurons located in the ventral premotor cortex, discharging both when a goal-directed action is performed and when it is observed. Previous studies investigating mu-wave suppression in individuals with ASD were limited by having consistently employed video clips filmed with a fixed camera position, hence not including the potential movement of the observer towards the other person (a condition perceived as more ecological and close to reality).ObjectivesAim of this study was to investigate differences in mu-wave modulation in individuals with Autism Spectrum Disorder (ASD) without intellectual disabilities with respect to a group of neurotypical controls (NT).MethodsThirty individuals with ASD and thirty NT underwent an EEG recording while watching short videos depicting goal-oriented action filmed from a fixed position, zooming in on the scene, and approaching the scene by means of a steadycam. Afterwards, participants underwent a rating task to evaluate their subjective viewing experience.ResultsSteadycam videos elicited enhanced event-related desynchronization (ERD), suggestive of an enhanced neural activity, in the NT group, and a reduced ERD in the ASD group, with respect to the other filming conditions. ASD participants also showed difficulties in returning to baseline mu-power levels after watching videos filmed from a fixed position. NT reported to feel more comfortable watching videos with movement, whereas participants with ASD did not exhibit differences between conditions.ConclusionsThe ecological nature of video recording (i.e., visual stimuli filmed with a steadycam) seems to have an opposite effect on the ASD an NT population, as it enhances mu-wave suppression in NT, and reduces it in individuals with ASD, bringing them to a level of desynchronization closer to the one of NT. Understanding these differences might help developing tailored interventions to support perceptual, cognitive, and social processes of people with ASD.Disclosure of InterestNone Declared

Language impairments, a hallmark feature of autism spectrum disorders (ASD), have been related to neuroanatomical and functional abnormalities. Abnormal lateralization of the functional language network, increased reliance on visual processing areas, and increased posterior brain activation have all been reported in ASD and proposed as explanatory models of language difficulties. Nevertheless, inconsistent findings across studies have prevented a comprehensive characterization of the functional language network in ASD. The aim of this study was to quantify common and consistent patterns of brain activation during language processing in ASD and typically developing control (TD) participants using a meta-analytic approach. Activation likelihood estimation (ALE) meta-analysis was used to examine 22 previously published functional Magnetic Resonance Imaging (fMRI)/positron emission tomography studies of language processing (ASD: N = 328; TD: N = 324). Tasks included in this study addressed semantic processing, sentence comprehension, processing figurative language, and speech production. Within-group analysis showed largely overlapping patterns of language-related activation in ASD and TD groups. However, the ASD participants, relative to TD participants, showed: (1) more right hemisphere activity in core language areas (i.e., superior temporal gyrus and inferior frontal gyrus), particularly in tasks where they had poorer performance accuracy; (2) bilateral MTG hypo-activation across many different paradigms; and (3) increased activation of the left lingual gyrus in tasks where they had intact performance. These findings show that the hypotheses reviewed here address the neural and cognitive aspects of language difficulties in ASD across all tasks only in a limited way. Instead, our findings suggest the nuances of language and brain in ASD in terms of its context-dependency. Autism Res 2016, 9: 1046-1057. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

To improve early identification of autism spectrum disorder (ASD), we need objective, reliable, and accessible measures. To that end, a previous study demonstrated that a tablet-based application (app) that assessed several autism risk behaviors distinguished between toddlers with ASD and non-ASD toddlers. Using vocal data collected during this study, we investigated whether vocalizations uttered during administration of this app can distinguish among toddlers aged 16-31 months with typical development (TD), language or developmental delay (DLD), and ASD. Participant's visual and vocal responses were recorded using the camera and microphone in a tablet while toddlers watched movies designed to elicit behaviors associated with risk for ASD. Vocalizations were then coded offline. Results showed that (a) children with ASD and DLD were less likely to produce words during app administration than TD participants; (b) the ratio of syllabic vocalizations to all vocalizations was higher among TD than ASD or DLD participants; and (c) the rates of nonsyllabic vocalizations were higher in the ASD group than in either the TD or DLD groups. Those producing more nonsyllabic vocalizations were 24 times more likely to be diagnosed with ASD. These results lend support to previous findings that early vocalizations might be useful in identifying risk for ASD in toddlers and demonstrate the feasibility of using a scalable tablet-based app for assessing vocalizations in the context of a routine pediatric visit. LAY SUMMARY: Although parents often report symptoms of autism spectrum disorder (ASD) in infancy, we are not yet reliably diagnosing ASD until much later in development. A previous study tested a tablet-based application (app) that recorded behaviors we know are associated with ASD to help identify children at risk for the disorder. Here we measured how children vocalize while they watched the movies presented on the tablet. Children with ASD were less likely to produce words, less likely to produce speechlike sounds, and more likely to produce atypical sounds while watching these movies. These measures, combined with other behaviors measured by the app, might help identify which children should be evaluated for ASD. Autism Res 2020, 13: 1373-1382. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

The Interoception Sensory Questionnaire (ISQ) is a self-report instrument used to assess the characteristics of interoceptive processing in individuals with autism spectrum disorder (ASD). Previous studies have shown that scores of the ISQ are more appropriate than other subjective measures for evaluating difficulties in interoceptive processing in individuals with ASD. Yet, no prior research has demonstrated the validation of the ISQ in Japanese samples. This study attempted to validate the Japanese version of the ISQ (ISQ-J) by examining its psychometric properties. We confirmed the score distribution, internal consistency, and factor structure in Japanese samples. We also examined the relationships with other interoceptive questionnaires. In addition, we compared the scores of the ISQ-J between adolescents and adults with ASD participants and control participants. Results of confirmatory factor analyses showed that the reliability of the ISQ-J in adults with ASD reached an acceptable level of a one-factor structure with excellent internal consistency (α = 0.963). The result of the ISQ-J showed a significant positive correlation with the measure of awareness of interoceptive sensitivity for localized bodily states; on the other hand, a significant negative correlation was found with those integrated bodily states. In addition, the ISQ-J scores were significantly higher in the ASD group than in the control group. The current findings depend on self-report data (including a diagnosis of ASD) to measure validity constructs. Additionally, since the ISQ-J was surveyed in adults with ASD, it is unclear whether similar the results would be obtained if the ISQ-J were conducted with children. These results indicate the validity and reliability of the ISQ-J and provide a tool for assessing confusion of interoceptive information in Japanese adults with ASD.

Recent proposals have suggested the potential for neural biomarkers to improve clinical trial processes in neurodevelopmental conditions; however, few efforts have identified whether chronological age-based adjustments will be necessary (as used in standardized behavioral assessments). Event-related potentials (ERPs) demonstrate early differences in the processing of faces vs. objects in the visual processing system by 4 years of age and age-based improvement (decreases in latency) through adolescence. Additionally, face processing has been proposed to be related to social skills as well as autistic social-communication traits. While previous reports suggest delayed latency in individuals with autism spectrum disorder (ASD), extensive individual and age based heterogeneity exists. In this report, we utilize a sample of 252 children with ASD and 118 children with typical development (TD), to assess the N170 and P100 ERP component latencies (N170L and P100L, respectively), to upright faces, the face specificity effect (difference between face and object processing), and the inversion effect (difference between face upright and inverted processing) in relation to age. First, linear mixed models (LMMs) were fitted with fixed effect of age at testing and random effect of participant, using all available data points to characterize general age-based development in the TD and ASD groups. Second, LMM models using only the TD group were used to calculate age-based residuals in both groups. The purpose of residualization was to assess how much variation in ASD participants could be accounted for by chronological age-related changes. Our data demonstrate that the N170L and P100L responses to upright faces appeared to follow a roughly linear relationship with age. In the ASD group, the distribution of the age-adjusted residual values suggest that ASD participants were more likely to demonstrate slower latencies than would be expected for a TD child of the same age, similar to what has been identified using unadjusted values. Lastly, using age-adjusted values for stratification, we found that children who demonstrated slowed age-adjusted N170L had lower verbal and non-verbal IQ and worse face memory. These data suggest that age must be considered in assessing the N170L and P100L response to upright faces as well, and these adjusted values may be used to stratify children within the autism spectrum.

One of the few replicated functional brain differences between individuals with autism spectrum disorders (ASD) and neurotypical (NT) controls is reduced language lateralization. However, most prior reports relied on comparisons of group-level activation maps or functional markers that had not been validated at the individual-subject level, and/or used tasks that do not isolate language processing from other cognitive processes, complicating interpretation. Furthermore, few prior studies have examined functional responses in other brain networks, as needed to determine the spatial selectivity of the effect. Using functional magnetic resonance imaging (fMRI), we compared language lateralization between 28 adult ASD participants and carefully pairwise-matched controls, with the language regions defined individually using a well-validated language "localizer" task. Across two language comprehension paradigms, ASD participants showed less lateralized responses due to stronger right hemisphere activity. Furthermore, this effect did not stem from a ubiquitous reduction in lateralization of function across the brain: ASD participants did not differ from controls in the lateralization of two other large-scale networks-the Theory of Mind network and the Multiple Demand network. Finally, in an exploratory study, we tested whether reduced language lateralization may also be present in NT individuals with high autism-like traits. Indeed, autistic trait load in a large set of NT participants (n = 189) was associated with less lateralized language responses. These results suggest that reduced language lateralization is robustly associated with autism and, to some extent, with autism-like traits in the general population, and this lateralization reduction appears to be restricted to the language system. LAY SUMMARY: How do brains of individuals with autism spectrum disorders (ASD) differ from those of neurotypical (NT) controls? One of the most consistently reported differences is the reduction of lateralization during language processing in individuals with ASD. However, most prior studies have used methods that made this finding difficult to interpret, and perhaps even artifactual. Using robust individual-level markers of lateralization, we found that indeed, ASD individuals show reduced lateralization for language due to stronger right-hemisphere activity. We further show that this reduction is not due to a general reduction of lateralization of function across the brain. Finally, we show that greater autistic trait load is associated with less lateralized language responses in the NT population. These results suggest that reduced language lateralization is robustly associated with autism and, to some extent, with autism-like traits in the general population. Autism Res 2020, 13: 1746-1761. © 2020 International Society for Autism Research and Wiley Periodicals LLC.