Temporal progression of pupil dilation and gaze behavior to emotion expressions in preschoolers with autism spectrum disorder.

Previous work has shown divergent pupil dilation (PD) and gaze behavior in individuals with autism spectrum disorder (ASD), which may relate to the development of social difficulties in early life. Here, we investigated temporal dynamics of both phenotypes during naturalistic videos of a person displaying facial emotion expressions in 61 autistic and 61 non-autistic preschoolers. PD was segmented into three serial time components derived from a principal component analysis. Growth curve analysis was applied to analyze changes in looking time on eye and mouth regions over time. Groups did not differ in PD time components. Growth curve analysis revealed initially shorter looking times on the eyes and longer looking times on the mouth in autistic versus non-autistic preschoolers. However, a reversion of this pattern was observed over time, suggesting a delayed compensatory increase in eye attention during prolonged viewing periods in autistic children. Positive and negative associations of PD components and gaze behavior over time indicated a dynamic temporal relationship during emotion viewing. Our findings emphasize the need to apply time-sensitive measures in ecologically valid research, which may index etiological mechanisms of social difficulties in ASD.

Fluid Intelligence Is (Much) More than Working Memory Capacity: An Experimental Analysis.

Empirical evidence suggests a great positive association between measures of fluid intelligence and working memory capacity, which implied to some researchers that fluid intelligence is little more than working memory. Because this conclusion is mostly based on correlation analysis, a causal relationship between fluid intelligence and working memory has not yet been established. The aim of the present study was therefore to provide an experimental analysis of this relationship. In a first study, 60 participants worked on items of the Advanced Progressive Matrices (APM) while simultaneously engaging in one of four secondary tasks to load specific components of the working memory system. There was a diminishing effect of loading the central executive on the APM performance, which could explain 15% of the variance in the APM score. In a second study, we used the same experimental manipulations but replaced the dependent variable with complex working memory span tasks from three different domains. There was also a diminishing effect of the experimental manipulation on span task performance, which could now explain 40% of the variance. These findings suggest a causal effect of working memory functioning on fluid intelligence test performance, but they also imply that factors other than working memory functioning must contribute to fluid intelligence.

Sensory salience processing moderates attenuated gazes on faces in autism spectrum disorder: a case-control study.

BACKGROUND: Attenuated social attention is a key marker of autism spectrum disorder (ASD). Recent neuroimaging findings also emphasize an altered processing of sensory salience in ASD. The locus coeruleus-norepinephrine system (LC-NE) has been established as a modulator of this sensory salience processing (SSP). We tested the hypothesis that altered LC-NE functioning contributes to different SSP and results in diverging social attention in ASD. METHODS: We analyzed the baseline eye-tracking data of the EU-AIMS Longitudinal European Autism Project (LEAP) for subgroups of autistic participants (n = 166, age = 6-30 years, IQ = 61-138, gender [female/male] = 41/125) or neurotypical development (TD; n = 166, age = 6-30 years, IQ = 63-138, gender [female/male] = 49/117) that were matched for demographic variables and data quality. Participants watched brief movie scenes (k = 85) depicting humans in social situations (human) or without humans (non-human). SSP was estimated by gazes on physical and motion salience and a corresponding pupillary response that indexes phasic activity of the LC-NE. Social attention is estimated by gazes on faces via manual areas of interest definition. SSP is compared between groups and related to social attention by linear mixed models that consider temporal dynamics within scenes. Models are controlled for comorbid psychopathology, gaze behavior, and luminance. RESULTS: We found no group differences in gazes on salience, whereas pupillary responses were associated with altered gazes on physical and motion salience. In ASD compared to TD, we observed pupillary responses that were higher for non-human scenes and lower for human scenes. In ASD, we observed lower gazes on faces across the duration of the scenes. Crucially, this different social attention was influenced by gazes on physical salience and moderated by pupillary responses. LIMITATIONS: The naturalistic study design precluded experimental manipulations and stimulus control, while effect sizes were small to moderate. Covariate effects of age and IQ indicate that the findings differ between age and developmental subgroups. CONCLUSIONS: Pupillary responses as a proxy of LC-NE phasic activity during visual attention are suggested to modulate sensory salience processing and contribute to attenuated social attention in ASD.

Processing of social and monetary rewards in autism spectrum disorders.

BACKGROUND: Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD. AIMS: Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD. METHOD: Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.6 years of age) and 181 typically developing participants (7.6-30.8 years of age). RESULTS: Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD. CONCLUSIONS: Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

Atypical Arousal Regulation in Children With Autism but Not With Attention-Deficit/Hyperactivity Disorder as Indicated by Pupillometric Measures of Locus Coeruleus Activity.

BACKGROUND: Atypical arousal regulation may explain slower mean reaction time (MRT) in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder compared with typical development. The locus coeruleus-norepinephrine system (LC-NE) underlies arousal regulation and adapts its activity to the utility of a task. LC-NE tonic and phasic activity are indexed by baseline pupil size (BPS) and stimulus-evoked pupillary response (SEPR). METHODS: The study assessed pupillometry in ASD (n = 31, 3 female/28 male), attention-deficit/hyperactivity disorder (n = 28, 3 female/25 male), and typically developing control subjects (n = 31, 16 female/15 male) during a visuospatial reaction-time task that manipulates arousal by conditions with low and high task utility. We estimated linear mixed models of BPS, SEPR, and MRT in a per-trial analysis to investigate arousal regulation of task performance. RESULTS: Slower MRT occurred in the ASD group compared with the typically developing control group during low-utility conditions while controlling for dimensional ASD and attention-deficit/hyperactivity disorder symptoms. In low-utility conditions, BPS and SEPR were inversely related and both were associated with faster MRT. Increased ASD symptoms across groups were associated with higher BPS during low-utility conditions. Changes in BPS and SEPR between task-utility conditions were smaller in the ASD group. CONCLUSIONS: Slower visuospatial task performance in ASD is specific to low task utility. Arousal was associated with task performance and showed altered activity in ASD. Increased BPS during low-utility conditions suggested increased LC-NE tonic activity as an ASD symptom marker in children. Smaller changes in BPS and SEPR in ASD indicated attenuated LC-NE activity adaptation in response to high-utility conditions. Slower performance and atypical arousal regulation are probably associated with attenuated LC-NE activity adaptation.

Pupillometric measures of altered stimulus-evoked locus coeruleus-norepinephrine activity explain attenuated social attention in preschoolers with autism spectrum disorder.

Attenuated social attention has been described as a reduced preference for social compared to geometric motion in preschoolers with autism spectrum disorder (ASD). The locus coeruleus-norpinephrine (LC-NE) system modulates sensory reactivity and is a promising underlying mechanism. LC-NE activity is indexed by a stimulus-evoked pupillary response (SEPR) and partially by a luminance-adaptation pupillary response (LAPR), which were both shown to be aberrant in ASD. We examined whether SEPR and LAPR explain an attenuated social motion preference. We applied pupillometry via video-based eye tracking in young children (18-65 months) with ASD (n = 57) and typically developing (TD) children (n = 39) during a preferential looking paradigm of competing social and geometric motion and a changing light condition paradigm. We found an attenuated social motion preference in the ASD compared to the TD group. This was accompanied by atypical pupillometry showing a smaller SEPR to social motion, a larger SEPR to geometric motion and a reduced LAPR to a dark screen. SEPR but not LAPR explained the group difference in social motion preference. An ASD diagnosis was statistically predicted by the social motion preference, while this effect was mediated by the inclusion of SEPR to geometric and social motion. Our findings suggest a decreased sensory reactivity to social and increased reactivity to non-social motion in ASD, which may concurrently contribute to an attenuated social attention. The LC-NE system is supported as a promising underlying mechanism of altered social attention in young children with ASD, while the specificity of findings remains to be addressed.

Sensorische Auffälligkeiten bei Autismus-Spektrum-Störung: Validierung und Adaptation des englischsprachigen "Sensory Perception Quotient" (SPQ) von Tavassoli und Kollegen.

Although the DSM-5 has emphasised the relevance of sensory abnormalities in autism spectrum disorders (ASD), there are hardly any measures to assess them in German speaking countries. The present study translated the "Sensory Perception Questionnaire" (SPQ) by Tavassoli et al. (2014) to German and validated this scale. The SPQ is a self-rating scale for adults which focuses on perceptual aspects rather than cognitive or motivational antecedents or consequences of such perceptual processes. A total of 188 subjects participated in this study, including n=85 participants with ASD and n=103 neurotypical controls. The autism spectrum quotient (AQ) and the empathy quotient (EQ) were also administered, the IQ was measured using the CFT20-R, and participants were clinically evaluated using the SKID-I. Alternative items were generated to improve the semantic and psychometric properties of the SPQ. Of the 92 original SPQ items, 33 separated the clinical groups significantly and linguistically clearly in the sense of sensory hyper-sensitivity. These items covered primarily the sensory modalities of hearing, touch and vision. Increased sensory hyper-sensitivity was associated with greater scores in the AQ and increased slightly with increasing age. Sensory hyper-sensitivity in participants with ASD was, however, not significantly correlated with the EQ and the IQ. Due to the item-analytical rather than dimensional item selection, the short versions presented here exhibit a clearly better group separation with comparable concurrent validities when compared to Tavassoli's short version of the scale. Pending replication and proper norming, the SPQ short version presented here can be employed for screening purposes and supplement the clinical diagnostic process.

In-depth characterization of neuroradiological findings in a large sample of individuals with autism spectrum disorder and controls.

BACKGROUND: Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions associated with quantitative differences in cortical and subcortical brain morphometry. Qualitative assessment of brain morphology provides complementary information on the possible underlying neurobiology. Studies of neuroradiological findings in ASD have rendered mixed results, and await robust replication in a sizable and independent sample. METHODS: We systematically and comprehensively assessed neuroradiological findings in a large cohort of participants with ASD and age-matched controls (total N = 620, 348 ASD and 272 controls), including 70 participants with intellectual disability (47 ASD, 23 controls). We developed a comprehensive scoring system, augmented by standardized biometric measures. RESULTS: There was a higher incidence of neuroradiological findings in individuals with ASD (89.4 %) compared to controls (83.8 %, p = .042). Certain findings were also more common in ASD, in particular opercular abnormalities (OR 1.9, 95 % CI 1.3-3.6) and mega cisterna magna (OR 2.4, 95 % CI 1.4-4.0) reached significance when using FDR, whereas increases in macrocephaly (OR 2.0, 95 % CI 1.2-3.2), cranial deformities (OR 2.4, 95 % CI: 1.0-5.8), calvarian / dural thickening (OR 1.5, 95 % CI 1.0-2.3), ventriculomegaly (OR 3.4, 95 % CI 1.3-9.2), and hypoplasia of the corpus callosum (OR 2.7, 95 % CI 1.1-6.3) did not survive this correction. Furthermore, neuroradiological findings were more likely to occur in isolation in controls, whereas they clustered more frequently in ASD. The incidence of neuroradiological findings was higher in individuals with mild intellectual disability (95.7 %), irrespective of ASD diagnosis. CONCLUSION: There was a subtly higher prevalence of neuroradiological findings in ASD, which did not appear to be specific to the condition. Individual findings or clusters of findings may point towards the neurodevelopmental mechanisms involved in individual cases. As such, clinical MRI assessments may be useful to guide further etiopathological (genetic) investigations, and are potentially valuable to fundamental ASD research.

An German Short-Version of the "Sensory Perception Quotient" for Adults With Autism Spectrum Disorder.

Sensory features in autism spectrum disorder (ASD) have received increasing interest in clinical work and research during the recent years. With the Sensory Perception Quotient (SPQ), Tavasolli and colleagues have produced a self-rating scale for adults with ASD that measures sensory hyper-sensitivity in different sensory modalities, without also tapping cognitive or motivational aspects that precede or follow autistic sensory experiences. Here, we present the results of a translation of the SPQ to German and its short version as well as their validation in samples of autistic or neuro-typical participants. We, furthermore, present the psychometric properties and validities of Tavasolli's original SPQ-short version as well as an alternative short version based on different psychometric item-selection criteria. We can show here that our alternative SPQ-short version, overlapping with the original short-version in 61% of its items, exhibits superior reliabilities, reasonable concurrent validities with other related measures. It, furthermore, exhibits excellent differentiation between autistic and non-autistic samples, underscoring its utility as a screening instrument in research and a clinical instrument to supplement the ASD diagnostic process.

Arousal-modulated memory encoding and retrieval in adults with autism spectrum disorder.

Recently, we have shown that pupil dilation during a recognition memory task can serve as an index of memory retrieval difficulties in autism. At the time of publication, we were unaware of specific data-analysis methods that can be used to shed further light on the origins of such memory related pupil dilation. Specifically, by distinguishing "tonic" from "phasic" changes in pupil dilation and considering their temporal progression, it is possible to draw inferences about the functional integrity of a locus coeruleus-norepinephrine system (LC-NE) that is known to play a key role in regulating memory encoding and retrieval processes. We therefore apply these analyses to our previously published eye-tracking data of adults with ASD (N = 24) and neurotypical development (TD, N = 30) during the recognition memory task. In this re-analysis, we related pupil dilation during encoding and retrieval to recognition accuracy in a per-trial analysis of linear mixed models. In ASD, we replicated attenuated recognition accuracy, which was accompanied by attenuated pupil dilation during encoding and retrieval. Group differences in pupil dilation during retrieval occurred late during the trial (after 1.75 s) and indicated an altered top-down processing like attenuated attribution of semantic salience in response to previously encoded stimuli. In addition, only in the ASD group were higher pupil dilation during encoding and lower pupil dilation during retrieval associated with decreased recognition accuracy. This supports altered modulation of memory encoding and retrieval in ASD, with LC-NE phasic activity as promising underlying mechanism. LAY SUMMARY: We investigated the changes of pupil size during memory testing in autism spectrum disorder. Adults with ASD remembered fewer items correctly than neurotypical individuals (TD). This reduced memory was related to increased pupillary responses at study and decreased pupil dilation at test only for adults with ASD indicating a different modulation of memory by the locus coeruleus.

Interindividual Differences in Cortical Thickness and Their Genomic Underpinnings in Autism Spectrum Disorder.

OBJECTIVE: Autism spectrum disorder (ASD) is accompanied by highly individualized neuroanatomical deviations that potentially map onto distinct genotypes and clinical phenotypes. This study aimed to link differences in brain anatomy to specific biological pathways to pave the way toward targeted therapeutic interventions. METHODS: The authors examined neurodevelopmental differences in cortical thickness and their genomic underpinnings in a large and clinically diverse sample of 360 individuals with ASD and 279 typically developing control subjects (ages 6-30 years) within the EU-AIMS Longitudinal European Autism Project (LEAP). The authors also examined neurodevelopmental differences and their potential pathophysiological mechanisms between clinical ASD subgroups that differed in the severity and pattern of sensory features. RESULTS: In addition to significant between-group differences in "core" ASD brain regions (i.e., fronto-temporal and cingulate regions), individuals with ASD manifested as neuroanatomical outliers within the neurotypical cortical thickness range in a wider neural system, which was enriched for genes known to be implicated in ASD on the genetic and/or transcriptomic level. Within these regions, the individuals' total (i.e., accumulated) degree of neuroanatomical atypicality was significantly correlated with higher polygenic scores for ASD and other psychiatric conditions, and it scaled with measures of symptom severity. Differences in cortical thickness deviations were also associated with distinct sensory subgroups, especially in brain regions expressing genes involved in excitatory rather than inhibitory neurotransmission. CONCLUSIONS: The study findings corroborate the link between macroscopic differences in brain anatomy and the molecular mechanisms underpinning heterogeneity in ASD, and provide future targets for stratification and subtyping.

The Revised Children's Communication Checklist-2 (CCC-R): Factor Structure and Psychometric Evaluation.

The Children's Communication Checklist-2 (CCC-2) is often applied to assess pragmatic language impairment which is highly prevalent in autism spectrum disorder (ASD) and several mental health conditions. We replicated previous findings on the limited applicability of the CCC-2 in clinical samples and the inconsistent findings concerning the factor structure. The aim of the present study was, thus, to develop a concise, simplified, and revised version of the CCC-2 in a large German-speaking sample. Four groups of children and adolescents aged 4 to 17 years were included: ASD (n = 195), intellectual disability (ID, n = 83), diverse mental health conditions (MHC, n = 144) and a typically developing control group (TD, n = 417). We reduced the original number of items from 70 to 39, based on item analysis, exploratory factor analysis and the exclusion of communication-unrelated items. The revised version, CCC-R (α = 0.96), consists of two empirically derived factors: a pragmatic-language (α = 0.96) and a grammatical-semantic-language factor (α = 0.93). All clinical groups (ASD, ID, and MHC) had significantly increased CCC-R total scores, with the highest scores being in the neurodevelopmental disorder groups (ASD and ID). In addition, we found group-specific patterns of elevated pragmatic-language scores in the ASD group and grammatical-semantic scores in the ID group. The CCC-R was comparable to the CCC-2 in distinguishing ASD from the other groups. The CCC-R is proposed as a simplified and easily applied, clinical questionnaire for caregivers, assessing pragmatic language impairments across neurodevelopmental disorders and mental health conditions. LAY SUMMARY: The CCC-2 is a questionnaire designed to identify children who have problems in the social use of language, however, it is limited in its clinical application and exhibits inconsistent factors. We have created a shorter and simpler version of the CCC-2 that we have called the CCC-R which overcomes the previous limitations of the CCC-2. It consists of two subscales: pragmatic language and grammatical-semantic language. The CCC-R can be used as a short and clinically relevant caregiver questionnaire which assesses pragmatic language impairments in children and adolescents. Autism Res 2021, 14: 759-772. © 2021 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals LLC.

Saccade dysmetria indicates attenuated visual exploration in autism spectrum disorder.

BACKGROUND: Visual exploration in autism spectrum disorder (ASD) is characterized by attenuated social attention. The underlying oculomotor function during visual exploration is understudied, whereas oculomotor function during restricted viewing suggested saccade dysmetria in ASD by altered pontocerebellar motor modulation. METHODS: Oculomotor function was recorded using remote eye tracking in 142 ASD participants and 142 matched neurotypical controls during free viewing of naturalistic videos with and without human content. The sample was heterogenous concerning age (6-30 years), cognitive ability (60-140 IQ), and male/female ratio (3:1). Oculomotor function was defined as saccade, fixation, and pupil-dilation features that were compared between groups in linear mixed models. Oculomotor function was investigated as ASD classifier and features were correlated with clinical measures. RESULTS: We observed decreased saccade duration (∆M = -0.50, CI [-0.21, -0.78]) and amplitude (∆M = -0.42, CI [-0.12, -0.72]), which was independent of human video content. We observed null findings concerning fixation and pupil-dilation features (POWER = .81). Oculomotor function is a valid ASD classifier comparable to social attention concerning discriminative power. Within ASD, saccade features correlated with measures of restricted and repetitive behavior. CONCLUSIONS: We conclude saccade dysmetria as ASD oculomotor phenotype relevant to visual exploration. Decreased saccade amplitude and duration indicate spatially clustered fixations that attenuate visual exploration and emphasize endogenous over exogenous attention. We propose altered pontocerebellar motor modulation as underlying mechanism that contributes to atypical (oculo-)motor coordination and attention function in ASD.

Repetitive Behavior in Children and Adolescents: Psychometric Properties of the German Version of the Repetitive Behavior Scale-Revised.

Restricted repetitive behaviors (RRBs) are a core feature of autism spectrum disorders (ASD) and further occur in intellectual disability (ID), mental disorders (MD), and in typically developed people (TD). There is a need of a valid and reliable measure to record RRBs as transdiagnostic symptom, which captures RRBs heterogeneity and evaluates severity. The Repetitive Behavior Scale-Revised (RBS-R) is an established screening instrument for RRBs, but was predominantly limited to ASD samples. We examined the psychometric properties of the German version of the RBS-R in 948 participants with ASD, ID, MD and TD aged 4 to 17 years. The suitability was proofed delivering a four-factor solution, good internal consistency, external validity as well as group, age, and sex effects.

Study protocol of the multi-centre, randomised controlled trial of the Frankfurt Early Intervention Programme A-FFIP versus early intervention as usual for toddlers and preschool children with Autism Spectrum Disorder (A-FFIP study).

BACKGROUND: Naturalistic developmental behavioural interventions (NDBI) have been shown to improve autism-specific symptoms in young children with Autism Spectrum Disorder (ASD). NDBI approaches, such as the ASD-specific Frankfurt Early Intervention Programme for ASD (A-FFIP), are based on ASD-specific developmental and learning aspects. A-FFIP is a low-intensity intervention which can easily be implemented in the local health care/social welfare system. The aim of the present study is to establish 1-year efficacy of the manualised early intervention programme A-FFIP in toddlers and preschool children with ASD. It is hypothesised that A-FFIP will result in improved ASD-specific symptoms compared to early intervention as usual (EIAU). Child- and family-specific secondary outcomes, as well as moderators and mediators of outcome, will be explored. METHODS/DESIGN: A prospective, multi-centre, parallel-group, randomised controlled, phase-III trial comparing A-FFIP versus EIAU. A total of 134 children (A-FFIP: 67, EIAU: 67) aged 24-66 months at baseline assessment meeting the criteria for ASD (DSM-5) will be included. The primary outcome is the absolute change of the total score of the Brief Observation of Social Communication Change (BOSCC-AT) between baseline (T2) and 1-year follow-up (T6). The treatment effect will be tested, adjusted for relevant covariates applying a mixed model for repeated measures. Secondary outcomes are BOSCC social communication and repetitive-behaviour scores, single ASD symptoms, language, cognition, psychopathology, parental well-being and family quality of life. Predictors, moderators and mediating mechanisms will be explored. DISCUSSION: If efficacy of the manualised A-FFIP early intervention is established, the current study has the potential to change clinical practice strongly towards the implementation of a low-intensity, evidence-based, natural early intervention in ASD. Early intervention in ASD requires specialist training, which subsequently needs to be developed or included into current training curricula. TRIAL REGISTRATION: German Registry for Clinical Trials (Deutscher Register Klinischer Studien, DRKS); ID: 00016330. Retrospectively registered on 4 January 2019. URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016330.

Pupil dilation during visuospatial orienting differentiates between autism spectrum disorder and attention-deficit/hyperactivity disorder.

BACKGROUND: Previous research demonstrated atypical attention in children with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Regarding visual orienting, findings suggest a differential impairment: Atypical orienting to relatively unexpected targets in ASD, and atypical processing of alerting cues in ADHD. The locus coeruleus-norepinephrine (LC-NE) system plays an important role in exploiting alerting cues to increase attention and task performance. The present study's aim was to examine differential subcortical processes underlying visual orienting in ASD and ADHD with pupil dilation (PD) as index of LC activity. METHODS: Pupil dilation (PD) progression metrics during visual orienting were calculated for task-evoked PD locked to cue, stimulus onset, and behavioral response. Group differences in PD and reaction time (RT) were compared between children with ASD without ADHD (ASD-) (N = 18), ADHD without ASD (ADHD-) (N = 28), both disorders (ASD + ADHD) (N = 14), and typically developing children (TD) (N = 31) using linear mixed models (LMM). To further explore the modulatory role of the LC-NE system group differences in the effect of task-evoked PD metrics on RT were examined exploratively. RESULTS: ASD (+ADHD) showed slower orienting responses to relatively unexpected spatial target stimuli as compared to TD, which was accompanied by higher PD amplitudes relative to ADHD- and TD. In ADHD-, shorter cue-evoked PD latencies relative to ASD-, ASD + ADHD, and TD were found. Group differences in the effect of cue- and stimulus-evoked PD amplitudes on RT were found in ASD- relative to TD. CONCLUSIONS: Study findings provide new evidence for a specific role of the LC-NE system in impaired reflexive orienting responses in ASD, and atypical visual processing of alerting cues in ADHD.

Pupil Dilation Progression Modulates Aberrant Social Cognition in Autism Spectrum Disorder.

Progression of pupil dilation (PD) in response to visual stimuli may indicate distinct internal processes. No study has been performed on PD progression during a social cognition task. Here, we describe PD progression during the Movie for the Assessment of Social Cognition (MASC) test in n = 23 adolescents with Autism Spectrum Disorder (ASD) and n = 24 age, IQ and sex-matched neurotypical controls (NTC). The MASC consists of 43 video sequences depicting human social interactions, each followed by a multiple-choice question concerning characters' mental states. PD progression data were extracted by eye tracking and controlled for fixation behavior. Segmenting PD progression during video sequences by principal component analysis, three sequential PD components were unveiled. In ASD compared with NTC, a distinct PD progression was observed with increased constriction amplitude, increased dilation latency, and increased dilation amplitude that correlated with PD progression components. These components predicted social cognition performance. The first and second PD components correlated positively with MASC behavioral performance in ASD but negatively in NTC. These PD components may be interpreted as indicators of sensory-perceptual processing and attention function. In ASD, aberrant sensory-perceptual processing and attention function could contribute to attenuated social cognition performance. This needs to be tested by additional studies combining the respective cognitive tests and the outlined PD progression analysis. Phasic activity of the locus coeruleus-norepinephrine system is discussed as putatively shared underlying mechanism. Autism Res2019. © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: In adolescents with autism, we found an altered pupil dilation during watching scenes of human interactions. Early pupil dilation correlated positively with the number of correct answers to questions about the shown human interactions. Our findings suggest that aberrant sensory processing and attention function may contribute to altered social cognition in autism.

The locus coeruleus-norepinephrine system as pacemaker of attention - a developmental mechanism of derailed attentional function in autism spectrum disorder.

Children with autism spectrum disorder (ASD) exhibit diminished visual engagement to environmental stimuli. Aberrant attentional function provides an explanation by reduced phasic alerting and orienting to exogenous stimuli. We review aberrant attentional function (alerting, orienting and attentional control) in children with ASD as studied by neurocognitive and neurophysiological tasks as well as magnetic resonance imaging studies. The locus coeruleus-norepinephrine (LC-NE) system is outlined as a pacemaker of attentional function. The LC-NE system regulates adaptive gain in synaptic signal transmission, which moderates phasic alerting ('promoting') and the activation of the ventral frontoparietal attention network within orienting ('permitting'). In children with ASD, atypical LC-NE activity is proposed as underlying mechanism of aberrant attentional function. It may manifest as (i) increased tonic activity with reduced phasic reactivity to exogenous stimuli, (ii) attenuated bottom-up signalling mitigating salience and predictive reward attribution during phasic alerting, and (iii) reduced activation of the ventral frontoparietal attention system attenuating orienting to exogenous stimuli. Increased tonic pupil dilation and aberrant pupil reactivity are discussed as indicators of atypical LC-NE activity. Pupillometry is outlined as feasible method to assess alerting, orienting and attentional control that can be dissected from the pupil dilation time course. In children with ASD, aberrant attentional function through atypical LC-NE activity is proposed as developmental mechanism leading to reduced social attention as well as social interaction and communication impairments.