Dynamic Eye Tracking as a Predictor and Outcome Measure of Social Skills Intervention in Adolescents and Adults with Autism Spectrum Disorder.

To evaluate an eye tracking task as a predictor and outcome measure of treatment response for autism spectrum disorder (ASD) social skills interventions, adolescents and young adults with ASD completed the eye tracking task before, immediately after, and two months after completing Social Cognition and Interaction Training for Autism (SCIT-A). The study compared SCIT-A participants (n = 20) to participants with ASD who received treatment as usual (TAU; n = 21). Overall, increased visual attention to faces and background objects and decreased attention to hands playing with toys at baseline were associated with improved social functioning immediately following intervention, suggesting this eye tracking task may reliably predict ASD social intervention outcomes.

Neural Mechanisms of Reward Prediction Error in Autism Spectrum Disorder.

Few studies have explored neural mechanisms of reward learning in ASD despite evidence of behavioral impairments of predictive abilities in ASD. To investigate the neural correlates of reward prediction errors in ASD, 16 adults with ASD and 14 typically developing controls performed a prediction error task during fMRI scanning. Results revealed greater activation in the ASD group in the left paracingulate gyrus during signed prediction errors and the left insula and right frontal pole during thresholded unsigned prediction errors. Findings support atypical neural processing of reward prediction errors in ASD in frontostriatal regions critical for prediction coding and reward learning. Results provide a neural basis for impairments in reward learning that may contribute to traits common in ASD (e.g., intolerance of unpredictability).

Rates of Co-occurring Psychiatric Disorders in Autism Spectrum Disorder Using the Mini International Neuropsychiatric Interview.

Individuals with autism spectrum disorder (ASD) often meet criteria for at least one additional psychiatric disorder. The present study evaluated the utility of the Mini International Neuropsychiatric Interview (MINI) in assessing co-occurring psychiatric disorders in children, adolescents, and young adults with ASD. Ninety-one percent of children/adolescents and thirty-one percent of young adults were diagnosed with one or more co-occurring diagnoses using the MINI. MINI diagnostic rates were comparable to those found in the literature on children/adolescents with ASD; however, in young adults, MINI diagnostic rates were lower relative to rates found in the literature on young adults with ASD. Implications for treatment, transitioning to adulthood, and the need for instruments developed specifically to diagnose co-occurring disorders in ASD are discussed.

Social and nonsocial visual prediction errors in autism spectrum disorder.

Impaired predictive coding has been proposed as a framework to explain discrepancies between expectations and outcomes in autism spectrum disorder (ASD) that may contribute to core symptoms of the disorder. However, no eye tracking study has directly addressed this framework in the context of visual predictions of social and nonsocial stimuli. The current study used eye tracking to examine violations of learned visual associations of both social and nonsocial stimuli. Twenty-six adolescents with ASD and 18 typically developing control (TDC) adolescents completed an outcome expectation eye tracking task in which predictive cues correctly (80% of trials) or incorrectly (20% of trials) indicated the location (left or right) of forthcoming social or nonsocial stimuli. During violation trials, individuals with ASD focused their gaze relatively more often on stimuli presented on locations that violated the learned association and less often on locations that corresponded with the learned association. This finding was not moderated by stimulus type (i.e., social vs. nonsocial). Additionally, participants who looked at incorrectly predicted locations more often had significantly greater ASD symptom severity. These results are consistent with theories that characterize ASD as a disorder of prediction and have potential implications for understanding symptoms related to prediction errors in individuals with ASD. Autism Res 2019, 12: 878-883. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Individuals with autism spectrum disorder (ASD) exhibit impairments making predictions that may impact learning. In this study, we used eye tracking methodology and found that individuals with ASD were less likely to look at the predicted location when a visual routine was violated. This pattern was evident for both social and nonsocial images and was associated with greater ASD symptom severity. These findings provide additional support for predictive challenges in ASD.

Functional Connectivity of Frontoparietal and Salience/Ventral Attention Networks Have Independent Associations With Co-occurring Attention-Deficit/Hyperactivity Disorder Symptoms in Children With Autism.

BACKGROUND: Children with autism spectrum disorder (ASD) and co-occurring attention-deficit/hyperactivity disorder (ADHD) symptoms have worse functional outcomes and treatment response than those without ADHD symptoms. There is limited knowledge of the neurobiology of ADHD symptoms in ASD. Here, we test the hypothesis that aberrant functional connectivity of two large-scale executive brain networks implicated in ADHD-the frontoparietal and salience/ventral attention networks-also play a role in ADHD symptoms in ASD. METHODS: We compared resting-state functional connectivity of the two executive brain networks in children with ASD (n = 77) and typically developing control children (n = 82). These two executive brain networks comprise five subnetworks (three frontoparietal, two salience/ventral attention). After identifying aberrant functional connections among subnetworks, we examined dimensional associations with parent-reported ADHD symptoms. RESULTS: Weaker functional connectivity in ASD was present within and between the frontoparietal and salience/ventral attention subnetworks. Decreased functional connectivity within a single salience/ventral attention subnetwork, as well as between two frontoparietal subnetworks, significantly correlated with ADHD symptoms. Furthermore, follow-up linear regressions demonstrated that the salience/ventral attention and frontoparietal subnetworks explain unique variance in ADHD symptoms. These executive brain network-ADHD symptom relationships remained significant after controlling for ASD symptoms. Finally, specificity was also demonstrated through the use of a control brain network (visual) and a control co-occurring symptom domain (anxiety). CONCLUSIONS: The present findings provide novel evidence that both frontoparietal and salience/ventral attention networks' weaker connectivities are linked to ADHD symptoms in ASD. Moreover, co-occurring ADHD in the context of ASD is a source of meaningful neural heterogeneity in ASD.

A potential mechanistic role for neuroinflammation in reward processing impairments in autism spectrum disorder.

Accumulating evidence suggests that autism spectrum disorder (ASD) may be conceptualized within a framework of reward processing impairments. The Social Motivation Theory of Autism posits that reduced motivation to interact with people and decreased pleasure derived from social interactions may derail typical social development and contribute to the emergence of core social communication deficits in ASD. Neuroinflammation may disrupt the development of mesolimbic dopaminergic systems that are critical for optimal functioning of social reward processing systems. This neuroinflammation-induced disturbance of mesolimbic dopaminergic functioning has been substantiated using maternal immune activation rodent models whose offspring show aberrant dopaminergic corticostriatal function, as well as behavioral characteristics of ASD model systems. Preclinical findings are in turn supported by clinical evidence of increased mesolimbic neuroinflammatory responses in individuals with ASD. This review summarizes evidence for reward processing deficits and neuroinflammatory impairments in ASD and examines how immune inflammatory dysregulation may impair the development of dopaminergic mesolimbic circuitry in ASD. Finally, future research directions examining neuroinflammatory effects on reward processing in ASD are proposed.

Altered reward system reactivity for personalized circumscribed interests in autism.

Background: Neurobiological research in autism spectrum disorders (ASD) has paid little attention on brain mechanisms that cause and maintain restricted and repetitive behaviors and interests (RRBIs). Evidence indicates an imbalance in the brain's reward system responsiveness to social and non-social stimuli may contribute to both social deficits and RRBIs. Thus, this study's central aim was to compare brain responsiveness to individual RRBI (i.e., circumscribed interests), with social rewards (i.e., social approval), in youth with ASD relative to typically developing controls (TDCs). Methods: We conducted a 3T functional magnetic resonance imaging (fMRI) study to investigate the blood-oxygenation-level-dependent effect of personalized circumscribed interest rewards versus social rewards in 39 youth with ASD relative to 22 TDC. To probe the reward system, we employed short video clips as reinforcement in an instrumental incentive delay task. This optimization increased the task's ecological validity compared to still pictures that are often used in this line of research. Results: Compared to TDCs, youth with ASD had stronger reward system responses for CIs mostly within the non-social realm (e.g., video games) than social rewards (e.g., approval). Additionally, this imbalance within the caudate nucleus' responsiveness was related to greater social impairment. Conclusions: The current data support the idea of reward system dysfunction that may contribute to enhanced motivation for RRBIs in ASD, accompanied by diminished motivation for social engagement. If a dysregulated reward system indeed supports the emergence and maintenance of social and non-social symptoms of ASD, then strategically targeting the reward system in future treatment endeavors may allow for more efficacious treatment practices that help improve outcomes for individuals with ASD and their families.

Vicarious Effort-Based Decision-Making in Autism Spectrum Disorders.

This study investigated vicarious effort-based decision-making in 50 adolescents with autism spectrum disorders (ASD) compared to 32 controls using the Effort Expenditure for Rewards Task. Participants made choices to win money for themselves or for another person. When choosing for themselves, the ASD group exhibited relatively similar patterns of effort-based decision-making across reward parameters. However, when choosing for another person, the ASD group demonstrated relatively decreased sensitivity to reward magnitude, particularly in the high magnitude condition. Finally, patterns of responding in the ASD group were related to individual differences in consummatory pleasure capacity. These findings indicate atypical vicarious effort-based decision-making in ASD and more broadly add to the growing body of literature addressing social reward processing deficits in ASD.

Social analogical reasoning in school-aged children with autism spectrum disorder and typically developing peers.

Analogical reasoning is an important mechanism for social cognition in typically developing children, and recent evidence suggests that some forms of analogical reasoning may be preserved in autism spectrum disorder. An unanswered question is whether children with autism spectrum disorder can apply analogical reasoning to social information. In all, 92 children with autism spectrum disorder completed a social content analogical reasoning task presented via photographs of real-world social interactions. Autism spectrum disorder participants exhibited performance that was well above chance and was not significantly worse than age- and intelligence quotient-matched typically developing children. Investigating the relationship of social content analogical reasoning performance to age in this cross-sectional dataset indicated similar developmental trajectories in the autism spectrum disorder and typically developing children groups. These findings provide new support for intact analogical reasoning in autism spectrum disorder and have theoretical implications for analogy as a metacognitive skill that may be at least partially dissociable from general deficits in processing social content. As an initial study of social analogical reasoning in children with autism spectrum disorder, this study focused on a basic research question with limited ecological validity. Evidence that children with autism spectrum disorder can apply analogical reasoning ability to social content may have long-range applied implications for exploring how this capacity might be channeled to improve social cognition in daily life.

Social-Emotional Inhibition of Return in Children with Autism Spectrum Disorder Versus Typical Development.

In typical development there is a bias to orient visual attention to social information. Children with ASD do not reliably demonstrate this bias, and the role of attention orienting has not been well studied. We examined attention orienting via the inhibition of return (IOR) mechanism in a spatial cueing task using social-emotional cues; we studied 8- to 17-year-old children with ASD (n = 41) and typically developing controls (TDC) (n = 25). The ASD group exhibited a significantly stronger IOR effect than the TDC group, and the IOR effect correlated positively with social impairments but was unrelated to co-occurring ADHD or anxiety symptoms. The results provide evidence of an early altered attention mechanism that is associated with to core social deficits in ASD.

Abstract analogical reasoning in high-functioning children with autism spectrum disorders.

Children with autism spectrum disorders (ASD) exhibit a deficit in spontaneously recognizing abstract similarities that are crucial for generalizing learning to new situations. This may contribute to deficits in the development of appropriate schemas for navigating novel situations, including social interactions. Analogical reasoning is the central cognitive mechanism that enables typically developing children to understand abstract similarities between different situations. Intriguingly, studies of high-functioning children with ASD point to a relative cognitive strength in basic, nonabstract forms of analogical reasoning. If this analogical reasoning ability extends to abstract analogical reasoning (i.e., between superficially dissimilar situations), it may provide a bridge between a cognitive capability and core ASD deficits in areas such as generalization and categorization. This study tested whether preserved analogical reasoning abilities in ASD can be extended to abstract analogical reasoning, using photographs of real-world items and situations. Abstractness of the analogies was determined via a quantitative measure of semantic distance derived from latent semantic analysis. Children with ASD performed as well as typically developing children at identifying abstract analogical similarities when explicitly instructed to apply analogical reasoning. Individual differences in abstract analogical reasoning ability predicted individual differences in a measure of social function in the ASD group. Preliminary analyses indicated that children with ASD, but not typically developing children, showed an effect of age on abstract analogical reasoning. These results provide new evidence that children with ASD are capable of identifying abstract similarities through analogical reasoning, pointing to abstract analogical reasoning as a potential lever for improving generalization skills and social function in ASD.

Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards.

BACKGROUND: There has been significant progress in identifying genes that confer risk for autism spectrum disorders (ASDs). However, the heterogeneity of symptom presentation in ASDs impedes the detection of ASD risk genes. One approach to understanding genetic influences on ASD symptom expression is to evaluate relations between variants of ASD candidate genes and neural endophenotypes in unaffected samples. Allelic variations in the oxytocin receptor (OXTR) gene confer small but significant risk for ASDs for which the underlying mechanisms may involve associations between variability in oxytocin signaling pathways and neural response to rewards. The purpose of this preliminary study was to investigate the influence of allelic variability in the OXTR gene on neural responses to monetary rewards in healthy adults using functional magnetic resonance imaging (fMRI). METHODS: The moderating effects of three single nucleotide polymorphisms (SNPs) (rs1042778, rs2268493 and rs237887) of the OXTR gene on mesolimbic responses to rewards were evaluated using a monetary incentive delay fMRI task. RESULTS: T homozygotes of the rs2268493 SNP demonstrated relatively decreased activation in mesolimbic reward circuitry (including the nucleus accumbens, amygdala, insula, thalamus and prefrontal cortical regions) during the anticipation of rewards but not during the outcome phase of the task. Allelic variation of the rs1042778 and rs237887 SNPs did not moderate mesolimbic activation during either reward anticipation or outcomes. CONCLUSIONS: This preliminary study suggests that the OXTR SNP rs2268493, which has been previously identified as an ASD risk gene, moderates mesolimbic responses during reward anticipation. Given previous findings of decreased mesolimbic activation during reward anticipation in ASD, the present results suggest that OXTR may confer ASD risk via influences on the neural systems that support reward anticipation.