Reward Processing Deficits Research Articles

Reduced striatal activation in response to rewarding motor performance feedback after stroke.

Motor skill learning can help stroke survivors to cope with motor function deficits but requires many repetitions. One factor that keeps patients motivated is obtaining reward upon successfully completing a motor task. It has been suggested that stroke survivors have deficits in reward processing which may negatively impact skill learning. To test the hypothesis that stroke survivors have deficient reward processing during motor skill learning evident in reduced activation in the striatum and its subdivisions in functional magnetic resonance imaging as compared with healthy, age-matched control subjects. Striatal activity in response to performance dependent feedback and monetary reward was measured in 28 subacute stroke patients and 18 age-matched healthy control subjects during the training of visuomotor tracking an arc-shaped trajectory using the wrist (unimpaired side in patients, dominant side in controls) in an fMRI scanner. Despite comparable monetary rewards, stroke patients showed reduced activation in the ventral part (p<0.01), but not in the dorsal part of the striatum (p = 0.11). 14 patients had their lesion extending into the striatum. The nucleus accumbens as part of the ventral striatum was unlesioned in all participants and still showed a marked hypoactivation in stroke patients as compared with controls (p<0.001), a finding that could not be explained by motivational differences between the groups. Striatal hypoactivation in stroke survivors may cause impaired consolidation of motor skills. Stronger rewarding stimuli or drug-mediated enhancement may be needed to normalize reward processing after stroke with positive effects on recovery.

7.3 Neurobiology of Substance Use Disorder Risk and Initial Exposure to Drugs

As more has been learned about the neurobiology of substance use disorders (SUDs) in adults, investigations in children at risk before exposure to abusable substances remain limited. As evidence points out that early experimentation with drugs may be linked to higher rates of later SUD, the mechanisms by which early drug exposure may influence the development of SUD still remain poorly understood. Furthermore, new evidence suggests that deficits in reward processing in the brain may represent putative predispositions for SUD development in youth.

Investigating dopamine and glucocorticoid systems as underlying mechanisms of anhedonia

Anhedonia, a deficit in reward processing, is an endophenotype of several neuropsychiatric conditions. Despite its prevalence and debilitating effects, treatments for anhedonia are lacking, primarily because its underlying mechanisms are poorly understood. Dopamine (DA) has been implicated in anhedonia through its role in reward-related learning; glucocorticoid systems may also be involved in that anhedonia is often preceded by chronic stress. This study investigated DA and glucocorticoid systems in anhedonia using a rat version of the probabilistic reward task (PRT). Adult male Wistar rats were trained on the PRT and then tested following: (1) activation or inhibition of DA activity induced by amphetamine (AMPH) or pramipexole (PRAMI) injections, (2) chronic mild stress (CMS), or (3) glucocorticoid system activation (dexamethasone (DEX)) or inhibition (mifepristone (MIFE)). AMPH increased and PRAMI decreased response bias, pointing to enhanced and diminished reward responsiveness with DA agonism and antagonism, respectively. CMS reduced response bias but only in a subpopulation of rats. DEX also decreased response bias, suggesting that glucocorticoid processes contribute to anhedonia, although glucocorticoid inhibition (MIFE) had no effect. None of the manipulations altered the ability to detect and respond to reward-paired stimuli. These results confirm a role of DA in anhedonia and elucidate the contribution of the glucocorticoid system to this effect. In addition, chronic stress may interfere with normal DA functioning, leading to impaired reward-related learning in some animals. These findings may direct future treatment of anhedonia by targeting DA and glucocorticoid systems, as well as a possible interaction between the two.

Reward-Based Learning as a Function of Severity of Substance Abuse Risk in Drug-Naïve Youth with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is associated with elevated risk for later development of substance use disorders (SUD), specifically because youth with ADHD, similar to individuals with SUD, exhibit deficits in learning abilities and reward processing. Another known risk factor for SUD is familial history of substance dependence. Youth with familial SUD history show reward processing deficits, higher prevalence of externalizing disorders, and higher impulsivity scores. Thus, the main objective of this proof-of-concept study is to investigate whether risk loading (ADHD and parental substance use) for developing SUD in drug-naïve youth impacts reward-related learning. Forty-one drug-naïve youth, stratified into three groups: Healthy Controls (HC, n = 13; neither ADHD nor parental SUD), Low Risk (LR, n = 13; ADHD only), and High Risk (HR, n = 15; ADHD and parental SUD), performed a novel Anticipation, Conflict, and Reward (ACR) task. In addition to conventional reaction time (RT) and accuracy analyses, we analyzed computational variables including learning rates and assessed the influence of learned predictions of reward probability and stimulus congruency on RT. The multivariate ANOVA on learning rate, congruence, and prediction revealed a significant main Group effect across these variables [F(3, 37) = 3.79, p = 0.018]. There were significant linear effects for learning rate (Contrast Estimate = 0.181, p = 0.038) and the influence of stimulus congruency on RTs (Contrast Estimate = 1.16, p = 0.017). Post hoc comparisons revealed that HR youth showed the most significant deficits in accuracy and learning rates, while stimulus congruency had a lower impact on RTs in this group. LR youth showed scores between those of the HC and HR youth. These preliminary results suggest that deficits in learning and in adjusting to task difficulty are a function of increasing risk loading for SUD in drug-naïve youth. These results also highlight the importance of developing and applying computational models to study intricate details in behavior that typical analytic methodology may not be sensitive to.

Altered resting-state hippocampal and caudate functional networks in patients with obstructive sleep apnea.

IntroductionBrain structural injury and metabolic deficits in the hippocampus and caudate nuclei may contribute to cognitive and emotional deficits found in obstructive sleep apnea (OSA) patients. If such contributions exist, resting‐state interactions of these subcortical sites with cortical areas mediating affective symptoms and cognition should be disturbed. Our aim was to examine resting‐state functional connectivity (FC) of the hippocampus and caudate to other brain areas in OSA relative to control subjects, and to relate these changes to mood and neuropsychological scores.MethodsWe acquired resting‐state functional magnetic resonance imaging (fMRI) data from 70 OSA and 89 healthy controls using a 3.0‐Tesla magnetic resonance imaging scanner, and assessed psychological and behavioral functions, as well as sleep issues. After standard fMRI data preprocessing, FC maps were generated for bilateral hippocampi and caudate nuclei, and compared between groups (ANCOVA; covariates, age and gender).ResultsObstructive sleep apnea subjects showed significantly higher levels of anxiety and depressive symptoms over healthy controls. In OSA subjects, the hippocampus showed disrupted FC with the thalamus, para‐hippocampal gyrus, medial and superior temporal gyrus, insula, and posterior cingulate cortex. Left and right caudate nuclei showed impaired FC with the bilateral inferior frontal gyrus and right angular gyrus. In addition, altered limbic‐striatal‐cortical FC in OSA showed relationships with behavioral and neuropsychological variables.ConclusionsThe compromised hippocampal‐cortical FC in OSA may underlie depression and anxious mood levels in OSA, while impaired caudate‐cortical FC may indicate deficits in reward processing and cognition. These findings provide insights into the neural mechanisms underlying the comorbidity of mood and cognitive deficits in OSA.

Using Multilevel Modeling to Examine Blunted Neural Responses to Reward in Major Depression

BackgroundMajor depressive disorder (MDD) is a pernicious disorder characterized by deficits in reward processing. A better understanding of these deficits may help to elucidate the underlying pathophysiology and guide treatment development. MethodsThis study assessed reward positivity and feedback negativity event-related potentials and their difference scores elicited in response to monetary gains and losses among 100 young adults (52 with MDD). Multilevel modeling was used to assess individual- and trial-level change in neural responses over time. ResultsTrial-level analyses indicated that a diagnosis of MDD and depressive symptom severity significantly moderated the trajectory of reward positivity, with individuals with higher symptoms of depression demonstrating less sensitivity to rewards over time. ConclusionsThese results provide further support for reward dysfunction in MDD and highlight important individual differences in the trajectory of neural responses to reward. Future studies are warranted to investigate reward sensitivity over time to elucidate important individual- and trial-level differences in reward processing.

Preschool- and School-Age Irritability Predict Reward-Related Brain Function

Although chronic irritability in childhood is prevalent, impairing, and predictive of later maladjustment, its pathophysiology is largely unknown. Deficits in reward processing are hypothesized to play a role in irritability. The current study aimed to identify how the developmental timing of irritability during preschool- and school-age relates to reward-related brain function during school-age. Children's irritability was assessed during the preschool period (wave 1; ages 3.0-5.9 years) and 3 years later (wave 2; ages 5.9-9.6 years) using a clinical interview. At wave 2, children (N= 46; 28 female and 18 male) performed a monetary incentive delay task in which they received rewards, if they successfully hit a target, or no reward regardless of performance, during functional magnetic resonance imaging. Children with more versus less severe preschool irritability, controlling for concurrent irritability, exhibited altered reward-related connectivity: right amygdala with insula and inferior parietal lobe as well as left ventral striatum with lingual gyrus, postcentral gyrus, superior parietal lobe, and culmen. Children with more versus less severe concurrent irritability, controlling for preschool irritability, exhibited a similar pattern of altered connectivity between left and right amygdalae and superior frontal gyrus and between left ventral striatum and precuneus and culmen. Neural differences associated with irritability were most evident between reward and no-reward conditions when participants missed the target. Preschool-age irritability and concurrent irritability were uniquely associated with aberrant patterns of reward-related connectivity, highlighting the importance of developmental timing of irritability for brain function.

T18. Characterizing Reward Responsiveness in Obsessive-Compulsive Disorder and Schizophrenia Through a Probabilistic Reward Task

Deficits in reward processing occur across the psychiatric spectrum. Identifying common and distinct impairments in the maintenance and integration of reward information may lead to a greater understanding of the mechanisms behind the affective disturbances across schizophrenia (SCZ) and obsessive-compulsive disorder (OCD). Here, we used the probabilistic reward task (PRT) to test the ability to learn implicit reward reinforcement across patients diagnosed with SCZ and OCD.

T217. Measures of Neural Oscillation Synchrony During Reward Processing in Schizophrenia

Relatively little is known about the extent to which reward processing deficits persist in schizophrenia in the absence of response planning and execution demands. We therefore used a passive reward paradigm to assess neural oscillation synchrony during anticipation and receipt of monetary rewards in patients with schizophrenia (n=45) in comparison to demographically-matched healthy controls (n=42).

Developmental Trajectories of the Orbitofrontal Cortex and Anhedonia in Middle Childhood and Risk for Substance Use in Adolescence in a Longitudinal Sample of Depressed and Healthy Preschoolers.

Deficits in reward processing are established in mood and substance use disorders and are known risk factors for these disorders. Volume reductions of the orbitofrontal cortex and the striatum, regions that subserve neural response to reward, have been shown to be related to anhedonia in depressive and substance use disorders. The authors sought to investigate how structural maturation of these regions in childhood varies with level of anhedonia and predicts later substance use. The study employed data from a sample of depressed and healthy preschoolers studied longitudinally that included three waves of neuroimaging from school age to adolescence. Three years after scan 3, at ages 13-18, participants underwent a comprehensive behavioral and substance use assessment. Multilevel modeling was used to investigate the relationship between anhedonia and the growth trajectories of the striatum and orbitofrontal cortex. Zero-inflated Poisson regression models were then used to determine whether the intercepts and slopes of these trajectories predicted later alcohol and marijuana use frequency in adolescence. The anhedonia-by-age interaction was significant in the multilevel modeling of orbitofrontal cortical but not striatal volume. Higher anhedonia ratings were significantly associated with steeper decline in orbitofrontal cortical volume with age. Orbitofrontal cortical volume and thickness at age 12 and trajectory over time significantly and negatively predicted subsequent alcohol and marijuana use frequency but not depression during adolescence. The findings suggest that the development of the orbitofrontal cortex during childhood is strongly linked to experiences of anhedonia and that these growth trajectories predict substance use during a developmentally critical period.

Presentation and Neurobiology of Anhedonia in Mood Disorders: Commonalities and Distinctions.

To focus on the clinical and behavioral presentation of anhedonia in mood disorders, as well as the differences and commonalities in the underlying neurocircuitry. Evidence suggests that depression is characterized by hypofunction of the reward system, while bipolar disorder manifests dysregulation of the behavioral activation system that increases goal-directed reward behavior. Importantly, strong evidence does not exist to suggest significant differences in anhedonia severity between depressed unipolar and bipolar patients, suggesting that there are more nuanced fluctuations in reward processing deficits in bipolar patients depending on their state. Both euthymic unipolar and bipolar patients frequently report residual reward dysfunction, which highlights the potential of reward processing deficits that give rise to the clinical symptom of anhedonia to be trait factors of mood disorders; however, the possibility that therapies are not adequately treating anhedonia could also explain the presence of residual symptoms. Reward processing represents a potential diagnostic and treatment marker for mood disorders. Further research should systematically explore the facets of reward processing in at-risk, affected, and remitted patients.

Neural Correlates of Impaired Reward-Effort Integration in Remitted Bulimia Nervosa.

The integration of reward magnitudes and effort costs is required for an effective behavioral guidance. This reward-effort integration was reported to be dependent on dopaminergic neurotransmission. As bulimia nervosa has been associated with a dysregulated dopamine system and catecholamine depletion led to reward-processing deficits in remitted bulimia nervosa, the purpose of this study was to identify the role of catecholamine dysfunction and its relation to behavioral and neural reward-effort integration in bulimia nervosa. To investigate the interaction between catecholamine functioning and behavioral, and neural responses directly, 17 remitted bulimic (rBN) and 21 healthy individuals (HC) received alpha-methyl-paratyrosine (AMPT) over 24 h to achieve catecholamine depletion in a randomized, crossover study design. We used functional magnetic resonance imaging (fMRI) and the monetary incentive delay (MID) task to assess reward-effort integration in relation to catecholaminergic neurotransmission at the behavioral and neural level. AMPT reduced the ability to integrate rewards and efforts effectively in HC participants. In contrast, in rBN participants, the reduced reward-effort integration was associated with illness duration in the sham condition and unrelated to catecholamine depletion. Regarding neural activation, AMPT decreased the reward anticipation-related neural activation in the anteroventral striatum. This decrease was associated with the AMPT-induced reduction of monetary earning in HC in contrast to rBN participants. Our findings contributed to the theory of a desensitized dopaminergic system in bulimia nervosa. A disrupted processing of reward magnitudes and effort costs might increase the probability of maintenance of bulimic symptoms.

Gut microbiome in ADHD and its relation to neural reward anticipation.

BackgroundMicroorganisms in the human intestine (i.e. the gut microbiome) have an increasingly recognized impact on human health, including brain functioning. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with abnormalities in dopamine neurotransmission and deficits in reward processing and its underlying neuro-circuitry including the ventral striatum. The microbiome might contribute to ADHD etiology via the gut-brain axis. In this pilot study, we investigated potential differences in the microbiome between ADHD cases and undiagnosed controls, as well as its relation to neural reward processing.MethodsWe used 16S rRNA marker gene sequencing (16S) to identify bacterial taxa and their predicted gene functions in 19 ADHD and 77 control participants. Using functional magnetic resonance imaging (fMRI), we interrogated the effect of observed microbiome differences in neural reward responses in a subset of 28 participants, independent of diagnosis.ResultsFor the first time, we describe gut microbial makeup of adolescents and adults diagnosed with ADHD. We found that the relative abundance of several bacterial taxa differed between cases and controls, albeit marginally significant. A nominal increase in the Bifidobacterium genus was observed in ADHD cases. In a hypothesis-driven approach, we found that the observed increase was linked to significantly enhanced 16S-based predicted bacterial gene functionality encoding cyclohexadienyl dehydratase in cases relative to controls. This enzyme is involved in the synthesis of phenylalanine, a precursor of dopamine. Increased relative abundance of this functionality was significantly associated with decreased ventral striatal fMRI responses during reward anticipation, independent of ADHD diagnosis and age.ConclusionsOur results show increases in gut microbiome predicted function of dopamine precursor synthesis between ADHD cases and controls. This increase in microbiome function relates to decreased neural responses to reward anticipation. Decreased neural reward anticipation constitutes one of the hallmarks of ADHD.

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.

Modulation of reward in a live social context as revealed through interactive social neuroscience

ABSTRACTSocial neuroscience research investigating autism spectrum disorder (ASD) has yielded inconsistent findings, despite ASD being well-characterized by difficulties in social interaction and communication through behavioral observation. In particular, specific etiologies and functional and structural assays of the brain in autism have not been consistently identified. To date, most social neuroscience research has focused on a single person viewing static images. Research utilizing interactive social neuroscience featuring dual-brain recording offers great promise for the study of neurodevelopmental disabilities. Reward processing has been implicated in the pathology of ASD, yet mixed findings have brought uncertainty about the role reward processing deficits may play in ASD. The current study employed dual-brain EEG recording to examine reward processing during live interaction and its relation to autistic traits. Sixteen typically developing (TD) adults played a competitive treasure-hunt game against a computer and against a human partner. EEG results revealed enhanced neural sensitivity to reward outcome during live interaction with a human competitor. Further, individuals with higher levels of autistic traits demonstrated reduced sensitivity to reward outcome during live interaction. These findings provide novel insight into reward processing mechanisms associated with autistic traits, as well as support the necessary utility of interactive social neuroscience techniques to study developmental disorders.

Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p < .001). Exploratory analyses indicated withdrawal increased time to initiate the next trial following unexpected punishment trials (p < .001) and response time on reward trials during withdrawal was positively related to nicotine dependence (p < .001). Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and unpleasant stimuli may be particularly effective for alleviating nicotine withdrawal.

Reward Processing Deficits During a Spatial Attention Task in Patients With ADHD: An fMRI Study

Objective: In this study, we aimed to explore how cues signaling rewards and feedbacks about rewards are processed in ADHD. Method: Inside the scanner, 16 healthy children and 19 children with ADHD completed a spatial attention paradigm where cues informed about the availability of reward and feedbacks were provided about the earned reward. Results: In ventral anterior thalamus (VA), the controls exhibited greater activation in response to reward-predicting cues, as compared with no-reward cues, whereby in the ADHD group, the reverse pattern was observed (nonreward > reward). For feedbacks; absence of rewards produced greater activation than presence in the left caudate and frontal eye field for the control group, whereas for the ADHD group, the reverse pattern was again observed (reward > nonreward). Discussion: The present findings indicate that ADHD is associated with difficulty integrating reward contingency information with the orienting and regulatory phases of attention.

Staging & profiling in addiction, can we cross the gap from bench to bedside?

Addictive behaviours are highly common (prevalence worldwide about 10%), with major impact on the individual and society (contributing to 5% of overall DALYs and mortality) [1,2]. Though a number of evidence-based treatments are available, relapse rates remain high, up to 50% within one year of treatment [3,4]. Staging of addictive behaviors might contribute to improve this prognosis by indicating which patient could benefit most from which treatment modality.In DSM-5 clinical staging of addictive disorders is limited to grading the severity of the disorder, based on criterion counts [5]. However, addictive disorders are highly heterogeneous, with distinct clinical profiles and neurobiological underpinnings of the disorder. Reward-processing deficits are considered a hallmark of addiction. Several additional neurobiological deficits have been identified in addicted individuals, such as dysfunction of brain stress systems, anterior cingulate cortex and habenula.These neurobiological deficits may identify clinical subgroups of patients with distinct pathophysiology (profiling), or be related to progression of the disorder (staging). This presentation will focus on clinical staging and profiling of addictive behaviors combining neurobiological findings and clinical practice [6].Disclosure of interestThe author has not supplied his declaration of competing interest.

Depressive Symptoms and the Anticipation and Experience of Uplifting Events in Everyday Life.

Despite proliferation of laboratory-based studies examining reward functioning in depression, few studies have examined these processes in everyday life. We addressed this shortcoming by exploring experience and anticipation of uplifting experiences under ecologically valid conditions METHOD: One hundred fifty-seven young adults, oversampled for depressive symptoms, completed a 14-day diary tracking mood in relation to recent and anticipated positive events RESULTS: Consistent with studies supporting "mood-brightening" effects in depression, participants with greater baseline dysphoria showed stronger associations between elevated daily uplifts and lower daily depressive symptoms, particularly when events were interpersonal in nature. Baseline dysphoria was associated with lower daily anticipation of positive next-day experiences; however, when dysphoric individuals did anticipate positive experiences, they experienced greater reductions in depressed mood CONCLUSION: Results suggest that despite reward processing deficits found in laboratory studies, dysphoric individuals show improvements in mood in conjunction with anticipation and consumption of uplifting events in daily life.

Social defeat disrupts reward learning and potentiates striatal nociceptin/orphanin FQ mRNA in rats.

Mood disorders can be triggered by stress and are characterized by deficits in reward processing, including disrupted reward learning (the ability to modulate behavior according to past rewards). Reward learning is regulated by the anterior cingulate cortex (ACC) and striatal circuits, both of which are implicated in the pathophysiology of mood disorders. Here, we assessed in rats the effects of a potent stressor (social defeat) on reward learning and gene expression in the ACC, ventral tegmental area (VTA), and striatum. Adult male Wistar rats were trained on an operant probabilistic reward task (PRT) and then exposed to 3days of social defeat before assessment of reward learning. After testing, the ACC, VTA, and striatum were dissected, and expression of genes previously implicated in stress was assessed. Social defeat blunted reward learning (manifested as reduced response bias toward a more frequently rewarded stimulus) and was associated with increased nociceptin/orphanin FQ (N/OFQ) peptide mRNA levels in the striatum and decreased Fos mRNA levels in the VTA. Moreover, N/OFQ peptide and nociceptin receptor mRNA levels in the ACC, VTA and striatum were inversely related to reward learning. The behavioral findings parallel previous data in humans, suggesting that stress similarly disrupts reward learning in both species. Increased striatal N/OFQ mRNA in stressed rats characterized by impaired reward learning is consistent with accumulating evidence that antagonism of nociceptin receptors, which bind N/OFQ, has antidepressant-like effects. These results raise the possibility that nociceptin systems represent a molecular substrate through which stress produces reward learning deficits in mood disorders.