Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Abstract This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies

Adults with autism spectrum disorders exhibit decreased sensitivity to reward parameters when making effort-based decisions

Background: Efficient effort expenditure to obtain rewards is critical for optimal goal-directed behavior and learning. Clinical observation suggests that individuals with autism spectrum disorders (ASD) may show dysregulated reward-based effort expenditure, but no behavioral study to date has assessed effort-based decision-making in ASD. Methods: The current study compared a group of adults with ASD to a group of typically developing adults on the Effort Expenditure for Rewards Task (EEfRT), a behavioral measure of effort-based decision-making. In this task, participants were provided with the probability of receiving a monetary reward on a particular trial and asked to choose between either an “easy task” (less motoric effort) for a small, stable reward or a “hard task” (greater motoric effort) for a variable but consistently larger reward. Results: Participants with ASD chose the hard task more frequently than did the control group, yet were less influenced by differences in reward value and probability than the control group. Additionally, effort-based decision-making was related to repetitive behavior symptoms across both groups. Conclusions: These results suggest that individuals with ASD may be more willing to expend effort to obtain a monetary reward regardless of the reward contingencies. More broadly, results suggest that behavioral choices may be less influenced by information about reward contingencies in individuals with ASD. This atypical pattern of effort-based decision-making may be relevant for understanding the heightened reward motivation for circumscribed interests in ASD

Future Directions for Research in Autism Spectrum Disorders

This article suggests future directions for research aimed at improved understanding of the etiology and pathophysiology of autism spectrum disorder (ASD) as well as pharmacologic and psychosocial interventions for ASD across the lifespan. The past few years have witnessed unprecedented transformations in the understanding of ASD neurobiology, genetics, early identification, and early intervention. However, recent increases in ASD prevalence estimates highlight the urgent need for continued efforts to translate novel ASD discoveries into effective interventions for all individuals with ASD. In this article we highlight promising areas for ongoing and new research expected to quicken the pace of scientific discovery and ultimately the translation of research findings into accessible and empirically supported interventions for those with ASD. We highlight emerging research in the following domains as particularly promising and pressing: (1) preclinical models; (2) experimental therapeutics; (3) early identification and intervention; (4) psychiatric comorbidities and the Research Domain Criteria (RDoC) initiative; (5) ecological momentary assessment; (6) neurotechnologies; and (7) the needs of adults with ASD. Increased research emphasis in these areas has the potential to hasten the translation of knowledge on the etiological mechanisms of ASD to psychosocial and biological interventions to reduce the burden of ASD on affected individuals and their families

Intact hedonic responses to sweet tastes in autism spectrum disorder

The Sweet Taste Test (STT) is a standardized measure designed to index the ability to detect differences in sweet tastes (sweet taste sensitivity) and hedonic responses to sweet tastes (sweet taste liking). Profiles of response on the STT suggest enhanced hedonic responses to sweet tastes in psychiatric disorders characterized by dysfunctional reward processing systems, including binge-eating disorders and substance use disorders, and a putative mechanism governing STT responses is the brain opioid system. The present study examined STT responses in 20 adults with autism spectrum disorder (ASD) and 38 healthy control adults. There were no differences in sweet taste sensitivity or hedonic response to sweet tastes between the ASD and control groups. Within the ASD sample, ASD symptom severity was associated with sweet taste sensitivity, but not hedonic response to sweet taste. Results may ultimately shed light on brain opioid system functioning in ASD

Late Positive Potential ERP Responses to Social and Nonsocial Stimuli in Youth with Autism Spectrum Disorder

We examined the late positive potential (LPP) event related potential in response to social and nonsocial stimuli from 9-19 years old youth with (n = 35) and without (n = 34) ASD. Social stimuli were faces with positive expressions and nonsocial stimuli were related to common restricted interests in ASD (e.g., electronics, vehicles, etc.). The ASD group demonstrated relatively smaller LPP amplitude to social stimuli and relatively larger LPP amplitude to nonsocial stimuli. There were no group differences in subjective ratings of images, and there were no significant correlations between LPP amplitude and ASD symptom severity within the ASD group. LPP results suggest blunted motivational responses to social stimuli and heightened motivational responses to nonsocial stimuli in youth with ASD

Common and distinct neural features of social and non-social reward processing in autism and social anxiety disorder

Autism spectrum disorders (ASDs) and social anxiety disorder (SAD) are both characterized by social dysfunction, but no study to date has compared neural responses to social rewards in ASDs and SAD. Neural responses during social and non-social reward anticipation and outcomes were examined in individuals with ASD (n = 16), SAD (n = 15) and a control group (n = 19) via functional magnetic resonance imaging. Analyses modeling all three groups revealed increased nucleus accumbens (NAc) activation in SAD relative to ASD during monetary reward anticipation, whereas both the SAD and ASD group demonstrated decreased bilateral NAc activation relative to the control group during social reward anticipation. During reward outcomes, the SAD group did not differ significantly from the other two groups in ventromedial prefrontal cortex activation to either reward type. Analyses comparing only the ASD and SAD groups revealed greater bilateral amygdala activation to social rewards in SAD relative to ASD during both anticipation and outcome phases, and the magnitude of left amygdala hyperactivation in the SAD group during social reward anticipation was significantly correlated with the severity of trait anxiety symptoms. Results suggest reward network dysfunction to both monetary and social rewards in SAD and ASD during reward anticipation and outcomes, but that NAc hypoactivation during monetary reward anticipation differentiates ASD from SAD

Neural mechanisms of negative reinforcement in children and adolescents with autism spectrum disorders

Abstract Background Previous research has found accumulating evidence for atypical reward processing in autism spectrum disorders (ASD), particularly in the context of social rewards. Yet, this line of research has focused largely on positive social reinforcement, while little is known about the processing of negative reinforcement in individuals with ASD. Methods The present study examined neural responses to social negative reinforcement (a face displaying negative affect) and non-social negative reinforcement (monetary loss) in children with ASD relative to typically developing children, using functional magnetic resonance imaging (fMRI). Results We found that children with ASD demonstrated hypoactivation of the right caudate nucleus while anticipating non-social negative reinforcement and hypoactivation of a network of frontostriatal regions (including the nucleus accumbens, caudate nucleus, and putamen) while anticipating social negative reinforcement. In addition, activation of the right caudate nucleus during non-social negative reinforcement was associated with individual differences in social motivation. Conclusions These results suggest that atypical responding to negative reinforcement in children with ASD may contribute to social motivational deficits in this population

Increased reward value of non-social stimuli in children and adolescents with autism

An econometric choice task was used to estimate the implicit reward value of social and non-social stimuli related to restricted interests in children and adolescents with (n = 12) and without (n = 22) autism spectrum disorder (ASD). Mixed effects logistic regression analyses revealed that groups differed in valuation of images related to restricted interests: control children were indifferent to cash payouts to view these images, but children with ASD were willing to receive less cash payout to view these images. Groups did not differ in valuation of social images or non-social images not related to restricted interests. Results highlight that motivational accounts of ASD should also consider the reward value of non-social stimuli related to restricted interests in ASD (Dichter and Adolphs, 2012)

Neural Mechanisms of Emotion Regulation in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is characterized by high rates of comorbid internalizing and externalizing disorders. One mechanistic account of these comorbidities is that ASD is characterized by impaired emotion regulation (ER) that results in deficits modulating emotional responses. We assessed neural activation during cognitive reappraisal of faces in high functioning adults with ASD. Groups did not differ in looking time, pupilometry, or subjective ratings of faces during reappraisal. However, instructions to increase positive and negative emotional responses resulted in less increase in nucleus accumbens and amygdala activations (respectively) in the ASD group, and both regulation instructions resulted in less change in dorsolateral prefrontal cortex activation in the ASD group. Results suggest a potential mechanistic account of impaired ER in ASD

Status of the RFQ linac installation and conditioning of the Linear IFMIF Prototype Accelerator

Abstract The Radio Frequency Quadrupole (RFQ) linac and 1.6 MW RF power system of the Linear IFMIF Prototype Accelerator (LIPAc) facility in the International Fusion Energy Research Center (IFERC) in Rokkasho (Japan) has been installed and conditioned. During the assembly and tuning process, the RFQ cavity was protected with a temporary tent from the potential deterioration of performance caused by dust. The vacuum in the cavity was improved through the 100 °C baking process of the cavity. The high power test of the 175 MHz RF systems up to 200 kW in CW for each of the eight RF chains was performed for checking its stable output reproducibility in Japan, before connecting 9–3/16 inch coaxial transmission lines from the RF chains to the RF input couplers of the cavity. It was confirmed that the eight RF chains provided the balanced RF power to the single RFQ cavity in-phase using a feedback loop and a synchronization system. The peak power in the cavity achieved 150 kW in the pulsed mode, which corresponds approximately to the required electric field to accelerate proton beam. Such RF conditioning process is ongoing to achieve 600 kW approximately required for deuteron beam commissioning planned in 2018