Reward-related Neural Response Research Articles

Cultural variation inneural responses to social but not monetary reward outcomes.

European Americans view high-intensity, open-mouthed 'excited' smiles more positively than Chinese because they value excitement and other high arousal positive states more. This difference is supported by reward-related neural activity, with European Americans showing greater Nucleus Accumbens (NAcc) activity to excited (vs calm) smiles than Chinese. But do these cultural differences generalize to all rewards, and are they related to real-world social behavior? European American (N = 26) and Chinese (N = 27) participants completed social and monetary incentive delay tasks that distinguished between the anticipation and receipt (outcome) of social and monetary rewards while undergoing Functional Magnetic Resonance Imaging (FMRI). The groups did not differ in NAcc activity when anticipating social or monetary rewards. However, as predicted, European Americans showed greater NAcc activity than Chinese when viewing excited smiles during outcome (the receipt of social reward). No cultural differences emerged when participants received monetary outcomes. Individuals who showed increased NAcc activity to excited smiles during outcome had friends with more intense smiles on social media. These findings suggest that culture plays a specific role in modulating reward-related neural responses to excited smiles during outcome, which are associated with real-world relationships.

Sex differences in emotion- and reward-related neural responses predicting increases in substance use in adolescence

Adolescent substance use is a significant public health problem and there is a need for effective substance use preventions. To develop effective preventions, it is important to identify neurobiological risk factors that predict increases in substance use in adolescence and to understand potential sex differences in risk mechanisms. The present study used functional magnetic resonance imaging and hierarchical linear modeling to examine negative emotion- and reward-related neural responses in early adolescence predicting growth in substance use to middle adolescence in 81 youth, by sex. Adolescent neural responses to negative emotional stimuli and monetary reward receipt were assessed at age 12–14. Adolescents reported on substance use at age 12–14 and at 6 month, and 1, 2, and 3 year follow-ups. Adolescent neural responses did not predict initiation of substance use (yes/no), but, among users, neural responses predicted growth in substance use frequency. For girls, heightened right amygdala responses to negative emotional stimuli in early adolescence predicted growth in substance use frequency through middle adolescence. For boys, blunted left nucleus accumbens and bilateral ventromedial prefrontal cortex responses to monetary reward predicted growth in substance use frequency. Findings suggest different emotion and reward-related predictors of the development of substance use for adolescent girls versus boys.

Reward processing in autism spectrum disorder and psychopathy: a systematic review

AimsEmerging research suggests that aberrant reward processing may underpin much of the social dysfunction we see in psychiatric disorders. Two conditions associated with marked social dysfunction are Autism Spectrum Disorder (ASD) and Psychopathy. However, no review to date has directly contrasted reward processing in both conditions and incorporated literature on social and non-social rewards. This systematic review aims to: (i) identify and compare reward processing abnormalities in ASD and Psychopathy as demonstrated in task-based functional magnetic resonance imaging (fMRI) studies; and (ii) identify correlations between fMRI reward processing abnormalities and manifested symptoms, with a focus on those giving rise to social dysfunction.MethodThe electronic databases PubMed, PsycINFO and EMBASE were searched to identify studies satisfying the following criteria: (i) a validated measure was used to assess ASD or Psychopathy; (ii) the study was published in an English language peer review journal; (iii) the age of participants was 18 years or older; (iv) individuals participated in a reward-based experimental paradigm; and (v) the response to the reward was measure using fMRI.ResultA total of 12 articles were identified that satisfied inclusion criteria. Six studies examined reward processing in ASD and six studies examined reward processing in Psychopathy. All studies in both conditions indicated some degree of abnormal reward-related neural response. The most replicated findings were aberrant responses in the Ventral Striatum (VS). Autism Spectrum Disorder was typified by VS hypoactivation to social and non-social reward, while Psychopathy was associated with VS hyperactivation in response to non-social reward anticipation. No studies were identified of social reward in Psychopathy.ConclusionThe reported fMRI findings correlate with clinical observations in both conditions. Reduced reward response in ASD to a range of social and non-social stimuli would provide a parsimonious account of the social and non-social deficits that characterise the condition. Enhanced responses to the anticipation of reward in Psychopathy provides an account of the ruthless and destructive pursuit of reward-driven behaviours not inhibited by immoral or aversive signals. If, as the literature suggests, reward circuitry dysfunction plays a role in the development and manifestation of symptoms in both conditions, reward processing and its underlying neural circuitry may represent important targets for the development of novel treatment strategies.

Negative Learning Bias in Depression Revisited: Enhanced Neural Response to Surprising Reward Across Psychiatric Disorders

BackgroundPrior work has proposed that major depressive disorder (MDD) is associated with a specific cognitive bias: patients with depression seem to learn more from punishment than from reward. This learning bias has been associated with blunting of reward-related neural responses in the striatum. A key question is whether negative learning bias is also present in patients with MDD and comorbid disorders and whether this bias is specific to depression or shared across disorders. MethodsWe employed a transdiagnostic approach assessing a heterogeneous group of (nonpsychotic) psychiatric patients from the MIND-Set (Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders) cohort with and without MDD but also with anxiety, attention-deficit/hyperactivity disorder, and/or autism (n = 66) and healthy control subjects (n = 24). To investigate reward and punishment learning, we employed a deterministic reversal learning task with functional magnetic resonance imaging. ResultsIn contrast to previous studies, patients with MDD did not exhibit impaired reward learning or reduced reward-related neural activity anywhere in the brain. Interestingly, we observed consistently increased neural responses in the bilateral lateral prefrontal cortex of patients when they received a surprising reward. This increase was not specific to MDD, but generalized to anxiety, attention-deficit/hyperactivity disorder, and autism. Critically, increased prefrontal activity to surprising reward scaled with transdiagnostic symptom severity, particularly that associated with concentration and attention, as well as the number of diagnoses; patients with more comorbidities showed a stronger prefrontal response to surprising reward. ConclusionsPrefrontal enhancement may reflect compensatory working memory recruitment, possibly to counteract the inability to swiftly update reward expectations. This neural mechanism may provide a candidate transdiagnostic index of psychiatric severity.

Neural activity moderates the association between sleep and risky driving behaviors in adolescence

The biological, environmental, and psychosocial changes that occur in adolescence engender an increase in risk taking often linked to the high rates of motor vehicle crashes amongst young drivers. Most U.S. adolescents suffer from poor sleep, which is known to exacerbate the risk of driving crashes; however, research has yet to uncover a neurobiological link between sleep and risky driving in adolescence. Here, we examined potential moderators of the sleep-risk relation in fifty-six adolescents (14–18y/o) as they completed a driving task during fMRI. While poor sleep was associated with increased risky driving (i.e., running more yellow lights), good sleep emerged as a novel buffer against risky driving in lower sensation-seeking adolescents. Neural activity in the ventral striatum (VS), a key node of the risk-taking circuit, also moderated the sleep-risk association: sleep was related to risk-taking in individuals demonstrating high, but not low, VS response during risky decision-making, suggesting that reward-related neural response may underly the connection between sleep and risk-taking in adolescence. This study sheds light on the risk of driving crashes in youth by highlighting sleep as both an exacerbator and a buffer of risky driving in adolescence. Taken together, these results underscore the importance of improving adolescent sleep.

Negative affect amplifies the relation between appetitive-food-related neural responses and weight gain over three-year follow-up among adolescents.

Obesity is a major public health concern that is associated with disruption in food reward-related brain function. This study examined if negative affect and stressful events enhance the relation between the food reward-related neural response and future weight gain. Initially healthy weight adolescents (N = 135) completed fMRI paradigms in which they tasted milkshakes and viewed palatable food images, and reported on negative affect and stressful events at baseline; BMI was measured annually over 3-year follow-up. Whole-brain analyses revealed that among participants with higher negative affect, weight gain over 3-year follow-up was predicted by elevated response to appetitive versus unappetitive food images in the left hippocampus, and elevated response in the vermis and the bilateral precuneus to tastes of milkshake versus tasteless solution. Among participants who experienced more stressful events, elevated right middle occipital gyrus response to milkshakes predicted future weight gain. Profiling analyses suggested that participants with higher negative affect or more stressful events who later gained weight reported engaging in more restrained eating and eating disorder-related behaviors. Results suggest that negative affect or stressful events may amplify the relation of neural response to food and the risk for future weight gain.

Altered reward-related neural responses in non-manifesting carriers of the Parkinson disease related LRRK2 mutation.

Disturbances in reward processing occur in Parkinson's disease (PD) however it is unclear whether these are solely drug-related. We applied an event-related fMRI gambling task to a group of non-manifesting carriers (NMC) of the G2019S mutation in the LRRK2 gene, in order to assess the reward network in an "at risk" population for future development of PD. Sixty-eight non-manifesting participants, 32 of which were non-manifesting non-carriers (NMNC), performed a gambling task which included defined intervals of anticipation and response to both reward and punishment in an fMRI setup. Behavior and cerebral activations were measured using both hypothesis driven and whole brain analysis. NMC demonstrated higher trait anxiety scores (p = 0.04) compared to NMNC. Lower activations were detected among NMC during risky anticipation in the left nucleus accumbens (NAcc) (p = 0.05) and during response to punishment in the right insula (p = 0.02), with higher activations among NMC during safe anticipation in the right insula (p = 0.02). Psycho-Physiological Interaction (PPI) analysis from the NAcc and insula revealed differential connectivity patterns. Whole brain analysis demonstrated divergent between-group activations in distributed cortical regions, bilateral caudate, left midbrain, when participants were required to press the response button upon making their next chosen move. Abnormal neural activity in both the reward and motor networks were detected in NMC indicating involvement of the ventral striatum regardless of medication use in "at risk" individuals for future development of PD.

Dopamine Transporter and Reward Anticipation in a Dimensional Perspective: A Multimodal Brain Imaging Study.

Dopamine function and reward processing are highly interrelated and involve common brain regions afferent to the nucleus accumbens, within the mesolimbic pathway. Although dopamine function and reward system neural activity are impaired in most psychiatric disorders, it is unknown whether alterations in the dopamine system underlie variations in reward processing across a continuum encompassing health and these disorders. We explored the relationship between dopamine function and neural activity during reward anticipation in 27 participants including healthy volunteers and psychiatric patients with schizophrenia, depression, or cocaine addiction, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) multimodal imaging with a voxel-based statistical approach. Dopamine transporter (DAT) availability was assessed with PET and [11C]PE2I as a marker of presynaptic dopamine function, and reward-related neural response was assessed using fMRI with a modified Monetary Incentive Delay task. Across all the participants, DAT availability in the midbrain correlated positively with the neural response to anticipation of reward in the nucleus accumbens. Moreover, this relationship was conserved in each clinical subgroup, despite the heterogeneity of mental illnesses examined. For the first time, a direct link between DAT availability and reward anticipation was detected within the mesolimbic pathway in healthy and psychiatric participants, and suggests that dopaminergic dysfunction is a common mechanism underlying the alterations of reward processing observed in patients across diagnostic categories. The findings support the use of a dimensional approach in psychiatry, as promoted by the Research Domain Criteria project to identify neurobiological signatures of core dysfunctions underling mental illnesses.

Influence of menstrual cycle phase on neural and craving responses to appetitive smoking cues in naturally cycling females.

Functional magnetic resonance imaging (fMRI) has been used extensively in an attempt to understand brain vulnerabilities that mediate maladaptive responses to drug cues. Using perfusion fMRI, we have consistently shown reward-related activation (medial orbitofrontal cortex/ventral striatum) to smoking cues (SCs). Because preclinical and clinical studies generally show that progesterone may reduce reward and craving, we hypothesized that females in the follicular phase of the cycle (FPs; when progesterone levels are low) would have greater reward-related neural responses to SCs compared with females in the luteal phase (LPs). Sated cigarette-dependent premenopausal naturally cycling females underwent pseudo-continuous arterial spin-labeled perfusion fMRI during exposure to 10-min audio visual clips of appetitive SCs and non-SCs. Brain responses to SCs relative to non-SCs were examined among females grouped according to menstrual cycle (MC) phase at the time of scanning (22 FPs, 15 LPs). Craving scores were acquired pre- and post-SC exposure. FPs showed increased neural responses to SCs compared with non-SCs in the medial orbitofrontal cortex (p ≤ .05 corrected), whereas LPs did not. FPs reported SC-elicited craving (p ≤ .005), whereas LPs did not. Within FPs, SC-induced craving correlated with increased neural responses in the anterior insula (r = 0.73, p < .0001). FPs may be more vulnerable to relapse during appetitive SC exposure than LPs. Because the influence of MC phase on drug cue neural activity has not been examined, these results contribute to our knowledge of the neurobiological underpinnings of responses to drug cues, and they highlight the importance of monitoring menstrual cycle phase in all areas of addiction research.

Relationship between Personality Traits and Brain Reward Responses when Playing on a Team

Cooperation is an integral part of human social life and we often build teams to achieve certain goals. However, very little is currently understood about emotions with regard to cooperation. Here, we investigated the impact of social context (playing alone versus playing on a team) on emotions while winning or losing a game. We hypothesized that activity in the reward network is modulated by the social context and that personality characteristics might impact team play. We conducted an event-related functional magnetic resonance imaging experiment that involved a simple game of dice. In the team condition, the participant played with a partner against another two-person team. In the single-player condition, the participant played alone against another player. Our results revealed that reward processing in the right amygdala was modulated by the social context. The main effect of outcome (gains versus losses) was associated with increased responses in the reward network. We also found that differences in the reward-related neural response due to social context were associated with specific personality traits. When playing on a team, increased activity in the amygdala during winning was a unique function of openness, while decreased activity in the ventromedial prefrontal cortex and ventral striatum during losing was associated with extraversion and conscientiousness, respectively. In conclusion, we provide evidence that working on a team influences the affective value of a negative outcome by attenuating the negative response associated with it in the amygdala. Our results also show that brain reward responses in a social context are affected by personality traits related to teamwork.

Reward-related neural responses are dependent on the beneficiary

Prior studies have suggested that positive social interactions are experienced as rewarding. Yet, it is not well understood how social relationships influence neural responses to other persons' gains. In this study, we investigated neural responses during a gambling task in which healthy participants (N = 31; 18 females) could win or lose money for themselves, their best friend or a disliked other (antagonist). At the moment of receiving outcome, person-related activity was observed in the dorsal medial prefrontal cortex (dmPFC), precuneus and temporal parietal junction (TPJ), showing higher activity for friends and antagonists than for self, and this activity was independent of outcome. The only region showing an interaction between the person-participants played for and outcome was the ventral striatum. Specifically, the striatum was more active following gains than losses for self and friends, whereas for the antagonist this pattern was reversed. Together, these results show that, in a context with social and reward information, social aspects are processed in brain regions associated with social cognition (mPFC, TPJ), and reward aspects are processed in primary reward areas (striatum). Furthermore, there is an interaction of social and reward information in the striatum, such that reward-related activity was dependent on social relationship.

Genetic Risk For Nicotine Dependence in the Cholinergic System and Activation of the Brain Reward System in Healthy Adolescents

Genetic variation in a genomic region on chromosome 15q25.1, which encodes the alpha5, alpha3, and beta4 subunits of the cholinergic nicotinic receptor genes, confers risk to smoking and nicotine dependence (ND). Neural reward-related responses have previously been identified as important factors in the development of drug dependence involving ND. Applying an imaging genetics approach in two cohorts (N=487; N=478) of healthy non-smoking adolescents, we aimed to elucidate the impact of genome-wide significant smoking-associated variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster on reward-related neural responses in central regions such as the striatum, orbitofrontal and anterior cingulate cortex (ACC), and personality traits related to addiction. In both samples, carriers of the rs578776 GG compared with AG/AA genotype showed a significantly lower neural response to reward outcomes in the right ventral and dorsal ACC but not the striatum or the orbitofrontal cortex. Rs578776 was unrelated to neural reward anticipation or reward magnitude. Significantly higher scores of anxiety sensitivity in GG compared with AG/AA carriers were found only in sample 1. Associations with other personality traits were not observed. Our findings suggest that the rs578776 risk variant influences susceptibility to ND by dampening the response of the ACC to reward feedback, without recruiting the striatum or orbitofrontal cortex during feedback or anticipation. Thus, it seems to have a major role in the processing of and behavioral adaptation to changing reward outcomes.

Abnormal Responses to Monetary Outcomes in Cortex, but not in the Basal Ganglia, in Schizophrenia

Psychosis has been associated with aberrant brain activity concurrent with both the anticipation and integration of monetary outcomes. The extent to which abnormal reward-related neural signals can be observed in chronic, medicated patients with schizophrenia (SZ), however, is not clear. In an fMRI study involving 17 chronic outpatients with SZ and 17 matched controls, we used a monetary incentive delay (MID) task, in which different-colored shapes predicted gains, losses, or neutral outcomes. Subjects needed to respond to a target within a time window in order to receive the indicated gain or avoid the indicated loss. Group differences in blood-oxygen-level-dependent responses to cues and outcomes were assessed through voxel-wise whole-brain analyses and regions-of-interest analyses in the neostriatum and prefrontal cortex (PFC). Significant group by outcome valence interactions were observed in the medial and lateral PFC, lateral temporal cortex, and amygdalae, such that controls, but not patients, showed greater activation for gains, relative to losses. In the striatum, neural activity was modulated by outcome magnitude in both groups. Additionally, we found that ratings of negative symptoms in patients correlated with sensitivity to obtained losses in medial PFC, obtained gains in lateral PFC, and anticipated gains in left ventral striatum. Sensitivity to obtained gains in lateral PFC also correlated with positive symptom scores in patients. Our findings of systematic relationships between clinical symptoms and neural responses to stimuli associated with rewards and punishments offer promise that reward-related neural responses may provide sensitive probes of the effectiveness of treatments for negative symptoms.

Inflammation-Induced Anhedonia: Endotoxin Reduces Ventral Striatum Responses to Reward

Although inflammatory activity is known to play a role in depression, no work has examined whether experimentally induced systemic inflammation alters neural activity that is associated with anhedonia, a key diagnostic symptom of depression. To investigate this, we examined the effect of an experimental inflammatory challenge on the neural correlates of anhedonia-namely, reduced ventral striatum (VS) activity to reward cues. We also examined whether this altered neural activity related to inflammatory-induced increases in depressed mood. Participants (n = 39) were randomly assigned to receive either placebo or low-dose endotoxin, which increases proinflammatory cytokine levels in a safe manner. Cytokine levels were repeatedly assessed through hourly blood draws; self-reported and observer-rated depressed mood were assessed regularly as well. Two hours after drug administration, neural activity was recorded as participants completed a task in which they anticipated monetary rewards. Results demonstrated that subjects exposed to endotoxin, compared with placebo, showed greater increases in self-reported and observer-rated depressed mood over time, as well as significant reductions in VS activity to monetary reward cues. Moreover, the relationship between exposure to inflammatory challenge and increases in observer-rated depressed mood was mediated by between-group differences in VS activity to anticipated reward. The data reported here show, for the first time, that inflammation alters reward-related neural responding in humans and that these reward-related neural responses mediate the effects of inflammation on depressed mood. As such, these findings have implications for understanding risk of depression in persons with underlying inflammation.

Hypersensitivity to Reward in Problem Gamblers

Recent research has begun to examine the neurophysiologic basis of pathological gambling. However, direct evidence of a behavioral deficit and an accompanying neurofunctional deviation in a realistic gambling context such as Black Jack has not yet been reported. Electroencephalogram was recorded while 20 problem gamblers and 21 control participants played a computerized version of Black Jack. Participants were asked to decide at point scores between 11 and 21 whether they wanted to take another card ("hit") to arrive closer to 21 than the opponent (simulated by computer) or not to take another card ("sit") to avoid going over 21 ("bust"). At a critical point score of 16, problem gamblers decided more often to hit despite losses due to a bust on the preceding trial, whereas control participants decided more often to sit under these conditions. Furthermore, problem gamblers showed more reward-related positive amplitudes in the event-related brain potential than control participants after successful hit decisions at 16. Here we provide experimental evidence for high-risk taking behavior in gamblers and its correlate in event-related brain potentials. Our results suggest that high-risk-taking behavior in problem gamblers is associated with an increased reward-related neural response to infrequent successes of this behavior.

Age-related changes in midbrain dopaminergic regulation of the human reward system

The dopamine system, which plays a crucial role in reward processing, is particularly vulnerable to aging. Significant losses over a normal lifespan have been reported for dopamine receptors and transporters, but very little is known about the neurofunctional consequences of this age-related dopaminergic decline. In animals, a substantial body of data indicates that dopamine activity in the midbrain is tightly associated with reward processing. In humans, although indirect evidence from pharmacological and clinical studies also supports such an association, there has been no direct demonstration of a link between midbrain dopamine and reward-related neural response. Moreover, there are no in vivo data for alterations in this relationship in older humans. Here, by using 6-[(18)F]FluoroDOPA (FDOPA) positron emission tomography (PET) and event-related 3T functional magnetic resonance imaging (fMRI) in the same subjects, we directly demonstrate a link between midbrain dopamine synthesis and reward-related prefrontal activity in humans, show that healthy aging induces functional alterations in the reward system, and identify an age-related change in the direction of the relationship (from a positive to a negative correlation) between midbrain dopamine synthesis and prefrontal activity. These results indicate an age-dependent dopaminergic tuning mechanism for cortical reward processing and provide system-level information about alteration of a key neural circuit in healthy aging. Taken together, our findings provide an important characterization of the interactions between midbrain dopamine function and the reward system in healthy young humans and older subjects, and identify the changes in this regulatory circuit that accompany aging.