Reward-related Neural Activity Research Articles

Genetic variation in endocannabinoid signaling: Anxiety, depression, and threat- and reward-related brain functioning during the transition into adolescence

BackgroundThe endocannabinoid system modulates neural activity throughout the lifespan. In adults, neuroimaging studies link a common genetic variant in fatty acid amide hydrolase (FAAH C385A)—an enzyme that regulates endocannabinoid signaling—to reduced risk of anxiety and depression, and altered threat- and reward-related neural activity. However, limited research has investigated these associations during the transition into adolescence, a period of substantial neurodevelopment and increased psychopathology risk. MethodsThis study included FAAH genotype and longitudinal neuroimaging and neurobehavioral data from 4811 youth (46% female; 9–11 years at Baseline, 11–13 years at Year 2) from the Adolescent Brain Cognitive DevelopmentSM Study. Linear mixed models examined the effects of FAAH and the FAAH x time interaction on anxiety and depressive symptoms, amygdala reactivity to threatening faces, and nucleus accumbens (NAcc) response to happy faces during the emotional n-back task. ResultsA significant main effect of FAAH on depressive symptoms was observed, such that depressive symptoms were lower across both timepoints in those with the AA genotype compared to both AC and CC genotypes (p’s<0.05). There were no significant FAAH x time interactions for anxiety, depression, or neural responses (p’s>0.05). Additionally, there were no main effects of FAAH on anxiety or neural responses (p’s>0.05). ConclusionsOur findings add to emerging evidence linking the FAAH C385A variant to lower risk of psychopathology, and extend these findings to a developmental sample. In particular, we found lower depressive symptoms in FAAH AA genotypes compared to AC and CC genotypes. Future research is needed to characterize the role of the FAAH variant and the eCB system more broadly in neurodevelopment and psychiatric risk.

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.

VIP interneurons in sensory cortex encode sensory and action signals but not direct reward signals

Vasoactive intestinal peptide (VIP) interneurons in sensory cortex modulate sensory responses based on global exploratory behavior and arousal state, but their function during non-exploratory, goal-directed behavior is not well understood. In particular, whether VIP cells are activated by sensory cues, reward-seeking actions, or directly by reinforcement is unclear. We trained mice on a Go/NoGo whisker touch detection task that included a delay period and other features designed to separate sensory-evoked, action-related, and reward-related neural activity. Mice had to lick in response to a whisker stimulus to receive a variable-sized reward. Using two-photon calcium imaging, we measured ΔF/F responses of L2/3 VIP neurons in whisker somatosensory cortex (S1) during behavior. In both expert and novice mice, VIP cells were strongly activated by whisker stimuli and goal-directed actions (licking), but not by reinforcement. VIP cells showed somatotopic whisker tuning that was spatially organized relative to anatomical columns in S1, unlike lick-related signals which were spatially widespread. In expert mice, lick-related VIP responses were suppressed, not enhanced, when a reward was delivered, and the amount of suppression increased with reward size. This reward-related suppression was not seen in novice mice, where reward delivery was not yoked to licking. These results indicate that besides arousal and global state variables, VIP cells are activated by local sensory features and goal-directed actions, but not directly by reinforcement. Instead, our results are consistent with a role for VIP cells in encoding the expectation of reward associated with motor actions.

Asymmetric and adaptive reward coding via normalized reinforcement learning.

Learning is widely modeled in psychology, neuroscience, and computer science by prediction error-guided reinforcement learning (RL) algorithms. While standard RL assumes linear reward functions, reward-related neural activity is a saturating, nonlinear function of reward; however, the computational and behavioral implications of nonlinear RL are unknown. Here, we show that nonlinear RL incorporating the canonical divisive normalization computation introduces an intrinsic and tunable asymmetry in prediction error coding. At the behavioral level, this asymmetry explains empirical variability in risk preferences typically attributed to asymmetric learning rates. At the neural level, diversity in asymmetries provides a computational mechanism for recently proposed theories of distributional RL, allowing the brain to learn the full probability distribution of future rewards. This behavioral and computational flexibility argues for an incorporation of biologically valid value functions in computational models of learning and decision-making.

Trajectory of aberrant reward processing in patients with bipolar disorder – A longitudinal fMRI study

BackgroundBipolar disorder (BD), and especially the mania phenotype, is characterized by heightened reward responsivity and aberrant reward processing. In this longitudinal fMRI study, we investigated neuronal response during reward anticipation as the computed expected value (EV) and outcome evaluation as reward prediction error (RPE) in recently diagnosed patients with BD. MethodsEighty remitted patients with BD and 60 healthy controls (HC) underwent fMRI during which they performed a card guessing task. Of these, 41 patients and 36 HC were re-scanned after 16 months. We compared reward-related neural activity between groups at baseline and longitudinally and assessed the impact of mood relapse. ResultsPatients showed lower RPE signal in areas of the ventrolateral prefrontal cortex (vlPFC) than HC. In these regions, the HC showed decrease in RPE signal over time, which was absent in patients. Patients further exhibited decreased EV signal in the occipital cortex across baseline and follow-up. Patients who remained in remission showed normalization of the EV signal at follow-up. Baseline activity in the identified regions was not associated with subsequent relapse. LimitationsFollow-up scans were only available in a relatively small sample. Medication status, follow-up time and BD illness duration prior to diagnosis varied. ConclusionsLower RPE signal in the vlPFC in patients with BD at baseline and its lack of normative reduction over time may represent a trait marker of dysfunctional reward-based learning or habituation. The increase in EV signal in the occipital cortex over time in patients who remained in remission may indicate normalization of reward anticipation activity.

Reward-Related Neural Activity Associated With General Psychopathology in 9- And 10-Year-Olds From the ABCD Study

The general psychopathology factor (P) accounts for variance common to all mental disorders through a dimensional, multi-domain approach. Relatedly, reward-processing abnormalities have been identified as a transdiagnostic feature across multiple psychopathologies. The present study examined reward-related brain function as a predictor of P over and above relevant demographic and self-report measures. Investigating multi-domain predictors of P may help identify early risk indicators in preadolescence when psychopathology begins to emerge.

Mixed Selectivity in the Cerebellar Purkinje-Cell Response during Visuomotor Association Learning.

Although the cerebellum has been traditionally considered to be exclusively involved in motor control, recent anatomic and clinical studies show that it also has a role in reward-processing. However, the way in which the movement-related and the reward-related neural activity interact at the level of the cerebellar cortex and contribute toward learning is still unclear. Here, we studied the simple spike activity of Purkinje cells in the mid-lateral cerebellum when 2 male monkeys learned to associate a right or left-hand movement with one of two visual symbolic cues. These cells had distinctly different discharge patterns between an overtrained symbol-hand association and a novel symbol-hand association, responding in association with the movement of both hands, although the kinematics of the movement did not change between the two conditions. The activity change was not related to the pattern of the visual symbols, the movement kinematics, the monkeys' reaction times, or the novelty of the visual symbols. The simple spike activity changed throughout the learning process, but the concurrent complex spikes did not instruct that change. Although these neurons also have reward-related activity, the reward-related and movement-related signals were independent. We suggest that this mixed selectivity may facilitate the flexible learning of difficult reinforcement learning problems.SIGNIFICANCE STATEMENT The cerebellum receives both motor-related and reward-related information. However, it is unclear how these two signals interact at the level of cerebellar cortex and contribute to learning nonmotor skills. Here we show that in the mid-lateral cerebellum, the reward information is encoded independently from the motor information such that during reward-based learning, only the reward information carried by the Purkinje cells inform learning while the motor information remains unchanged with learning.

Cognitive effort exertion enhances electrophysiological responses to rewarding outcomes.

Recent work has highlighted neural mechanisms underlying cognitive effort-related discounting of anticipated rewards. However, findings on whether effort exertion alters the subjective value of obtained rewards are inconsistent. Here, we provide a more nuanced account of how cognitive effort affects subsequent reward processing in a novel task designed to assess effort-induced modulations of the Reward Positivity, an event-related potential indexing reward-related neural activity. We found that neural responses to both gains and losses were significantly elevated in trials requiring more versus less cognitive effort. Moreover, time-frequency analysis revealed that these effects were mirrored in gain-related delta, but not in loss-related theta band activity, suggesting that people ascribed more value to high-effort outcomes. In addition, we also explored whether individual differences in behavioral effort discounting rates and reward sensitivity in the absence of effort may affect the relationship between effort exertion and subsequent reward processing. Together, our findings provide evidence that cognitive effort exertion can increase the subjective value of subsequent outcomes and that this effect may primarily rely on modulations of delta band activity.

Acute stress reduces reward-related neural activity: Evidence from the reward positivity

Stress and blunted reward processing are risk factors for Major Depressive Disorder (MDD). The experience of acute stress reduces fMRI correlates of reward-related neural activity; however, few studies have examined how acute stress impacts measures of reward derived from event-related potentials (ERPs). The current study examined the impact of an acute stressor on the Reward Positivity (RewP), an ERP that indexes reward sensitivity, in twenty-six college students. Participants completed a monetary reward task while they placed their left hand in cold water set at 13 degrees Celsius (i.e., acute stress condition) and again while their hand was placed in room temperature water (i.e., control condition). These conditions were separated by one week and performed in a counter-balanced order across participants. The results revealed that the RewP amplitude was blunted in the acute stress condition compared to the control condition. Moreover, there was a trend toward this effect interacting with self-reported depressive symptoms: the RewP was reduced only among individuals who reported low depressive symptoms. The current study suggests that an acute stressor reduces the RewP, and that this effect might be moderated by current depressive symptoms. Future studies might examine the temporal association between reward processing and stress —and how they interact to predict depressive symptoms. LAY SUMMARY: The current study examined the impact of acute stress on the brain’s reward system. The results indicated that acute stress reduced activity within the brain’s reward system, particularly among individuals with low depressive symptoms.

Anhedonia is Associated With Attenuated Reward-Related Neural Activity During Cue-Evaluation and Motor-Preparation

Functional resonance magnetic imaging (fMRI) research indicates anhedonia is associated with blunted neural activity during reward-anticipation. However, due to low temporal resolution of fMRI, the time course of these associations remains largely unknown. We leveraged the strong temporal resolution of event-related potentials (ERPs) to examine associations between anhedonia and electrocortical activity across three temporally distinct stages of reward-anticipation: cue-evaluation, motor-preparation, and feedback-anticipation.

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.

Reward related ventral striatal activity and differential response to sertraline versus placebo in depressed individuals.

Medications to treat major depressive disorder (MDD) are not equally effective across patients. Given that neural response to rewards is altered in MDD and given that reward-related circuitry is modulated by dopamine and serotonin, we examined, for the first time, whether reward-related neural activity moderated response to sertraline, an antidepressant medication that targets these neurotransmitters. 222 unmedicated adults with MDD randomized to receive sertraline (n=110) or placebo (n=112) in the EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study completed demographic and clinical assessments, and pre-treatment functional magnetic resonance imaging while performing a reward task. We tested whether an index of reward system function in the ventral striatum (VS), a key reward circuitry region, moderated differential response to sertraline versus placebo, assessed with the Hamilton Rating Scale for Depression over 8 weeks. We observed a significant moderation effect of the reward index, reflecting the temporal dynamics of VS activity, on Week-8 depression levels (Fs≥9.67,ps≤0.002). Specifically, VS responses that were abnormal with respect to predictions from reinforcement learning theory were associated with lower Week-8 depression symptoms in the sertraline versus placebo arms. Thus, a more abnormal pattern of pre-treatment VS dynamic response to reward expectancy (expected outcome value) and prediction error (difference between expected and actual outcome), likely reflecting serotonergic and dopaminergic deficits, was associated with better response to sertraline than placebo. Pre-treatment measures of reward-related VS activity may serve as objective neural markers to advance efforts to personalize interventions by guiding individual-level choice of antidepressant treatment.Trial Registration:NCT01407094; http://clinicaltrials.gov/show/NCT01407094

Time-Frequency Delta Activity to Social Feedback Demonstrates Differential Associations With Depression and Social Anxiety Symptoms.

Social feedback is highly salient and particularly relevant when investigating the pathophysiology of depression and social anxiety. A bourgeoning body of research has demonstrated an association between reward-related delta activity and psychopathology. However, a critical limitation is that these findings are derived from neural responses to monetary feedback, and time-frequency representation of social feedback remains unexplored. In addition, no study has isolated the differential/unique associations of positive valence and the intrinsic rewarding experience of being correct with reward-related neural activity. In the present study, 204 participants underwent electroencephalography (EEG) while they completed a novel paradigm comprised of monetary and social feedback tasks that were matched in trial structure, timing, and feedback stimuli. For each task, participants were instructed to correctly identify one of two doors that would provide positive feedback (monetary win behind the door) or one of two peers who would provide positive feedback (social like); or to correctly identify the door or peer that would provide negative feedback (money loss behind the door/social dislike). A principal component analysis (PCA) was conducted on the time-frequency data and revealed two factors in the delta and one factor in the theta frequency ranges. Results indicated that the lower-frequency delta factor (delta-low) was greater to correct vs. incorrect feedback, more so for social vs. monetary tasks, while the higher-frequency delta factor (delta-high) was greater to correct vs. incorrect feedback for social like, social dislike, and monetary win tasks, but not the monetary loss task. In contrast, the theta factor was greater to incorrect relative to correct feedback in negative valence (lose money/social dislike) but not positive valence (win money/social like) tasks. Furthermore, greater delta-high activity for social feedback was associated with greater social anxiety symptoms, whereas lesser delta-high activity for social feedback was associated with greater depressive symptoms. Finally, greater theta activity to monetary feedback was associated with greater depressive symptoms. The present study provides novel evidence demonstrating unique social vs. monetary feedback-related delta and theta activity, and differential associations between delta activity with depression and social anxiety symptoms. These findings highlight the importance of investigating feedback-related neural responses in the social domain.

Reward-Related Brain Activity Prospectively Predicts Increases in Alcohol Use in Adolescents

Altered activity within reward-related neural regions, including the ventral striatum (VS) and medial prefrontal cortex (mPFC), is associated with concurrent problematic substance use. The aims of the present study were (a) to identify patterns of reward-related neural activity that prospectively predicted changes in alcohol use 2 years after magnetic resonance imaging in a sample of adolescents, and (b) to examine whether these patterns differed by sex. We also tested whether depression symptoms or impulsivity mediated associations between neural activity and future alcohol use. Participants were 262 adolescents (129 male and 133 female) of Mexican origin who completed the Monetary Incentive Delay task during a functional magnetic resonance imaging scan at age 16. Participants reported on their alcohol use at ages 16 and18. Results indicated that different patterns of reward-related neural activity predicted future increases in alcohol use for male and female adolescents. In boys, higher VS activity during reward anticipation and average ventral mPFC activity during reward feedback predicted increases inalcohol use from age 16 to 18 years; in girls, higher dorsal mPFC activity and blunted VS activity during reward anticipation predicted increases in alcohol use from age 16 to 18 years. Depression symptoms or impulsivity did not mediate these associations. The results suggest that different pathways of risk may lead to problematic alcohol use for adolescent boys and girls. These sex differences in neural risk pathways have important implications for prevention and intervention approaches targeting Mexican-origin youth.

Sex Differences in the Relationship Between Inflammation and Reward Sensitivity: A Randomized Controlled Trial of Endotoxin

BackgroundThere are robust sex differences in the prevalence of depression. Inflammation and anhedonia may play a role in understanding these sex differences. Indeed, sex differences in inflammation-induced neural responses to reward may provide insight into the sex gaps in depression, but no study has examined this question. MethodsAs such, the current study examined whether there were sex differences in reward-related neural activity (i.e., ventral striatum [VS] activity) in response to an experimental inflammatory challenge. Human participants (N = 115; 69 female) were randomly assigned to receive either placebo or low-dose endotoxin, which increases inflammation in a safe, time-limited manner. Two hours after receiving placebo or endotoxin (the height of the inflammatory response to endotoxin), participants completed a task in which they anticipated monetary reward in a functional magnetic resonance imaging scanner. ResultsResults demonstrated that endotoxin (vs. placebo) led to reduced VS activity in anticipation of reward and that there were sex differences in this effect. Specifically, in female participants, endotoxin (vs. placebo) led to decreased VS activity in anticipation of reward, but this effect was not present in male participants. In addition, within the endotoxin condition, decreases in VS activity in anticipation of reward were related to increases in inflammation for female but not male participants. ConclusionsThese findings may have implications for understanding how inflammation may contribute to sex differences in rates of depression.

Longitudinal increases in reward-related neural activity in early adolescence: Evidence from event-related potentials (ERPs)

Adolescence is frequently described as a developmental period characterized by increased sensitivity to rewards. However, previous research on age-related changes in the neural response to gains and losses have produced mixed results, with only some studies reporting potentiated neural responses during adolescence. The current study examined the ERP responses to gains and losses during a simple monetary reward (i.e., Doors) task in a large and longitudinal sample of 248 adolescent females assessed at two time points, separated by two years. At baseline, when the sample was 8- to 14-years-old, age related to larger (i.e., more positive) ERP responses to both gains and losses; moreover, age-related effects were stronger in relation to gains than losses. Overall, the amplitude of the ERP response to gains, but not losses, significantly increased from baseline to follow-up; however, this effect was moderated by age, such that reward-related ERPs only increased longitudinally among the younger participants. At the follow-up assessment, ERP responses to gains and losses were equally related to age. Collectively, these within- and between-subjects findings suggest a relatively specific developmental increase in reward-related neural activity during late childhood and early adolescence.

Hypomania and depression associated with distinct neural activity for immediate and future rewards.

Bipolar spectrum and unipolar depressive disorders have been associated with distinct and opposite profiles of reward-related neural activity. These opposite profiles may reflect a differential preexisting vulnerability for both types of disorders. In support, recent ERP studies find that, following reward feedback, a larger reward positivity (RewP) is associated with greater vulnerability for bipolar spectrum disorders, whereas a smaller RewP is associated with greater vulnerability for depression. However, prior studies have investigated only immediate rewards and have not examined dimensions of both bipolar disorder and unipolar depression within the same sample. The present study is the first to investigate feedback-related ERP correlates of proneness to hypomania and unipolar depressive tendencies within the same sample and to expand our scope to include future rewards. Participants completed a modified time estimation task where the same monetary reward was available immediately or at one of five different future dates. Results revealed proneness to hypomania and unipolar depressive tendencies were related to an elevated and blunted RewP, respectively, but only following immediate rewards (i.e., today). Following rewards in the distant future (e.g., 8months), proneness to hypomania and depressive tendencies were associated with elevated and blunted amplitudes for the P3, respectively, a subsequent ERP component reflecting motivational salience during extended feedback processing. Furthermore, these opposing profiles were independent of, and significantly different from, one another. These results suggest that feedback-related ERPs following immediate and future rewards are candidate biomarkers that can physiologically separate vulnerability for bipolar spectrum from unipolar depressive disorders.

Contextual valence modulates the effect of choice on incentive processing.

Previous research has demonstrated that reward-related neural activity is enhanced for choice relative to no-choice opportunities in the gain context. The current event-related potential study examined whether this modulatory effect of choice can be observed in both the gain and the loss contexts across anticipatory and consummatory phases of incentive processing. Thirty-two participants performed a simple choice task during which choices were made either by themselves (a choice condition) or by a computer (a no-choice condition) during a gain context (gain vs nongain) and a loss context (nonloss vs loss). Behaviorally, participants reported a higher level of perceived control in the choice than the no-choice condition as well as in the gain than loss context. During the anticipatory phase, the choice relative to the no-choice condition elicited an increased cue-P3 in the loss context and an enhanced stimulus-preceding negativity in the gain context. During the consummatory phase, the choice condition elicited a larger reward positivity (ΔRewP) than the no-choice condition in the gain relative to the loss context but a comparable feedback P3 across contexts. These findings demonstrate that the crucial role of voluntary choice in reward processing is contingent upon contextual valence.

Differences in Neural Response to Romantic Stimuli in Monogamous and Non-Monogamous Men.

In non-human animal research, studies comparing socially monogamous and promiscuous species of voles (Microtus) have identified some key neural differences related to monogamy and non-monogamy. Specifically, densities of the vasopressin V1a receptor and dopamine D2 receptors in subcortical reward-related and limbic areas of the brain have been linked to monogamous behavior in prairie voles (Microtus ochrogaster). Similar brain areas have been shown to be correlated with feelings of romantic love in monogamously pair-bonded humans. Humans vary in the degree to which they engage in (non-)monogamous behaviors. The present study examined the differences in neural activation in response to sexual and romantic stimuli in monogamous (n=10) and non-monogamous (n=10) men. Results indicated that monogamous men showed more reward-related neural activity when viewing romantic pictures compared to non-monogamous men. Areas with increased activation for monogamous men were all in the right hemisphere and included the thalamus, accumbens, striatum, pallidum, insula, and orbitofrontal cortex. There were no significant differences between groups in activation to sexual stimuli. These results demonstrate that the neural processing of romantic images is different for monogamous and non-monogamous men. There is some overlap in the neural areas showing increased activation in monogamous men in the present study and the neural areas that show differences in the vole models of monogamy and affiliation. Future research will be needed to clarify whether similar factors are contributing to the neural differences seen in monogamous and non-monogamous humans and voles.

How mimicry influences the neural correlates of reward: An fMRI study

Mimicry has been suggested to function as a “social glue”, a key mechanism that helps to build social rapport. It leads to increased feeling of closeness toward the mimicker as well as greater liking, suggesting close bidirectional links with reward. In recent work using eye-gaze tracking, we have demonstrated that the reward value of being mimicked, measured using a preferential looking paradigm, is directly proportional to trait empathy (Neufeld and Chakrabarti, 2016). In the current manuscript, we investigated the reward value of the act of mimicking, using a simple task manipulation that involved allowing or inhibiting spontaneous facial mimicry in response to dynamic expressions of positive emotion. We found greater reward-related neural activity in response to the condition where mimicry was allowed compared to that where mimicry was inhibited. The magnitude of this link from mimicry to reward response was positively correlated to trait empathy.