Ventral Striatum Response Research Articles

Motor Synchronization to Rhythmic Auditory Stimulation (RAS) Attenuates Dopaminergic Responses in Ventral Striatum in Young Healthy Adults: [11C]-(+)-PHNO PET Study.

Auditory-motor entrainment using rhythmic auditory stimulation (RAS) has been shown to improve motor control in healthy persons and persons with neurologic motor disorders such as Parkinson’s disease and stroke. Neuroimaging studies have shown the modulation of corticostriatal activity in response to RAS. However, the underlying neurochemical mechanisms for auditory-motor entrainment are unknown. The current study aimed to investigate RAS-induced dopamine (DA) responses in basal ganglia (BG) during finger tapping tasks combined with [11C]-(+)-PHNO-PET in eight right-handed young healthy participants. Each participant underwent two PET scans with and without RAS. Binding potential relative to the non-displaceable compartment (BPND) values were derived using the simplified reference tissue method. The task performance was measured using absolute tapping period error and its standard deviation. We found that the presence of RAS significantly improved the task performance compared to the absence of RAS, demonstrated by reductions in the absolute tapping period error (p = 0.007) and its variability (p = 0.006). We also found that (1) the presence of RAS reduced the BG BPND variability (p = 0.013) and (2) the absence of RAS resulted in a greater DA response in the left ventral striatum (VS) compared to the presence of RAS (p = 0.003), These suggest that the absence of external cueing may require more DA response in the left VS associated with more motivational and sustained attentional efforts to perform the task. Additionally, we demonstrated significant age effects on D2/3 R availability in BG: increasing age was associated with reduced D2/3 R availability in the left putamen without RAS (p = 0.026) as well as in the right VS with RAS (p = 0.02). This is the first study to demonstrate the relationships among RAS, DA response/D2/3 R availability, motor responses and age, providing the groundwork for future studies to explore mechanisms for auditory-motor entrainment in healthy elderly and patients with dopamine-based movement disorders.

The benefits of negative yet informative feedback.

We investigated whether negative feedback with information could benefit both behavioral and neural responses. Fifteen participants were scanned with functional magnetic resonance imaging (fMRI) while receiving various feedbacks in a novel perceptual task. Behavioral data showed that reaction times of task performance were faster after receiving negative informative feedback compared to negative confirmatory feedback. The fMRI analysis of the interaction contrast between feedback type (informative vs. confirmatory) and valence (negative vs. positive) showed greater activation in the ventrolateral prefrontal cortex (vlPFC) and the ventral striatum in response to negative informative compared to confirmatory feedback. The psychophysiological interactions (PPI) analyses showed that the vlPFC activation was positively correlated with the amygdala and the rostral cingulate zone (RCZ). The ventral striatum activation was negatively correlated with the dorsolateral prefrontal cortex (dlPFC). These results suggest that negative but informative feedback benefits subsequent performance and its primary function is to elicit positive prediction error (instructive signal) and to induce cognitive control to guide subsequent goal-directed behavior.

Accelerated alcohol use across adolescence predicts early adult symptoms of alcohol use disorder via reward-related neural function.

Alcohol use is commonly initiated during adolescence, with earlier onset known to increase the risk for alcohol use disorder (AUD). Altered function in neural reward circuitry is thought to increase the risk for AUD. To test the hypothesis that adolescent alcohol misuse primes the brain for alcohol-related psychopathology in early adulthood, we examined whether adolescent alcohol consumption rates predicted reward responsivity in the ventral striatum (VS), and in turn, AUD symptoms in adulthood. A total of 139 low income, racially diverse urban males reported on their alcohol use at ages 11, 12, 15, and 17; completed self-reports of personality, psychiatric interviews, and a functional magnetic resonance imaging (fMRI) scan at age 20; and completed a psychiatric interview at age 22. We measured adolescent alcohol use trajectories using latent growth curve modeling and measured neural responses to monetary reward using a VS region of interest. We tested indirect effects of adolescent alcohol use on AUD symptoms at age 22 via VS reward-related reactivity at age 20. Greater acceleration in adolescent alcohol use predicted increased VS response during reward anticipation at age 20. VS reactivity to reward anticipation at age 20 predicted AUD symptoms at age 22, over and above concurrent symptoms. Accelerated adolescent alcohol use predicted AUD symptoms in early adulthood via greater VS reactivity to reward anticipation. Prospective findings support a pathway through which adolescent alcohol use increases the risk for AUD in early adulthood by impacting reward-related neural functioning. These results highlight increased VS reward-related reactivity as a biomarker for AUD vulnerability.

T147. DECREASED STRIATAL REWARD PREDICTION ERROR CODING IN UNMEDICATED SCHIZOPHRENIA PATIENTS

BackgroundReinforcement learning involves flexible adaptation towards a changing environment and is driven by dopaminergic reward prediction error (RPE; outcome (R) – expectation (Q)) signaling in the midbrain and projecting regions, such as the ventral striatum (Schultz, 1998). Schizophrenia patients show heightened dopamine levels in the striatum (Howes et al., 2012) as well as deficits in reinforcement learning (Waltz, 2016) which may be mediated by disrupted prediction error signaling (Heinz and Schlagenhauf, 2010; Schlagenhauf et al., 2014). Using model-based fMRI, the present study aims to assess these neural signals during a reversal learning paradigm in unmedicated schizophrenia patients and healthy individuals.MethodsIn the current study, 19 schizophrenia patients and 23 age- and gender-matched healthy controls completed a reversal learning paradigm (Boehme et al., 2015) during fMRI scanning where subjects had to choose between two neutral stimuli to maximize their reward. A Rescorla Wagner learning model (Single Update, one learning rate) was fitted against the individual choice data using a softmax function. Individual RPE trajectories from the fitted Rescorla Wager learning model were correlated with the BOLD response during feedback onset. Parameter estimates of ventral striaral RPE trajectories were correlated with psychopathology scores from the PANSS (Kay et al., 1987).ResultsIn the reversal learning task, schizophrenia patients chose the correct stimulus less often compared to healthy individuals (percent correct choices: 65.7 ± 10.7 vs. 76.7 ± 7.7; t=3.7, p=0.001). Across all participants, the RPE trajectories correlated with BOLD response in the bilateral ventral striatum (left ventral striatum [-10 12 10], t=7.40, pFWE <0.001, right ventral striatum [10 12 -10], t=6.56, pFWE=0.006). Schizophrenia patients displayed decreased RPE coding in the right ventral striatum compared to healthy individuals ([14 14 -10], t=3.69, pSVC for nucleus accumbens = .015). In patients, extracted parameter estimates from the right ventral striatum correlated negatively with the PANSS total symptoms score (Spearman’s rho =-0.55, p=0.018).DiscussionWe found that unmedicated schizophrenia patients performed worse in the reversal learning task and displayed decreased striatal prediction error signaling. This neural deficit was increased in patients with overall higher symptom severity. While RPE coding seems to be intact in patients receiving antipsychotic medication (Culbreth et al., 2016), our findings are in line with previous studies in unmedicated schizophrenia patients (Reinen et al., 2016; Schlagenhauf et al., 2014). Therefore, deficient neural coding of this core reinforcement learning mechanism may reflect a characteristic of the disorder of schizophrenia and does not result from antipsychotic medication.

Contributions of Reward Sensitivity to Ventral Striatum Activity Across Adolescence and Early Adulthood.

It was examined how ventral striatum responses to rewards develop across adolescence and early adulthood and how individual differences in state‐ and trait‐level reward sensitivity are related to these changes. Participants (aged 8–29 years) were tested across three waves separated by 2 years (693 functional MRI scans) in an accelerated longitudinal design. The results confirmed an adolescent peak in reward‐related ventral striatum, specifically nucleus accumbens, activity. In early to mid‐adolescence, increases in reward activation were related to trait‐level reward drive. In mid‐adolescence to early adulthood decreases in reward activation were related to decreases in state‐level hedonic reward pleasure. This study demonstrates that state‐ and trait‐level reward sensitivity account for reward‐related ventral striatum activity in different phases of adolescence and early adulthood.

Neural computations underpinning the strategic management of influence in advice giving

Research on social influence has focused mainly on the target of influence (e.g., consumer and voter); thus, the cognitive and neurobiological underpinnings of the source of the influence (e.g., politicians and salesmen) remain unknown. Here, in a three-sided advice-giving game, two advisers competed to influence a client by modulating their own confidence in their advice about which lottery the client should choose. We report that advisers’ strategy depends on their level of influence on the client and their merit relative to one another. Moreover, blood-oxygenation-level-dependent (BOLD) signal in the temporo-parietal junction is modulated by adviser’s current level of influence on the client, and relative merit prediction error affects activity in medial-prefrontal cortex. Both types of social information modulate ventral striatum response. By demonstrating what happens in our mind and brain when we try to influence others, these results begin to explain the biological mechanisms that shape inter-individual differences in social conduct.

Learning and Choice in Mood Disorders: Searching for the Computational Parameters of Anhedonia.

Computational approaches are increasingly being used to model behavioral and neural processes in mood and anxiety disorders. Here we explore the extent to which the parameters of popular learning and decision-making models are implicated in anhedonic symptoms of major depression. We first highlight the parameters of reinforcement learning that have been implicated in anhedonia, focusing, in particular, on the role that choice variability (i.e., “temperature”) may play in explaining heterogeneity across previous findings. We then turn to neuroimaging findings implicating attenuated ventral striatum response in anhedonic responses and discuss possible causes of the heterogeneity in the literature. Taken together, the reviewed findings highlight the potential of the computational approach in teasing apart the observed heterogeneity in both behavioral and functional imaging results. Nevertheless, considerable challenges remain, and we conclude with five unresolved questions that seek to address issues highlighted by the reviewed data.

Oxytocin receptor genotype and low economic privilege reverses ventral striatum-social anxiety association

ABSTRACTOxytocin receptor gene (OXTR) polymorphisms, lower ventral striatum (VS) response to social stimuli, and lower economic privilege have been independently associated with depression and anxiety. However, the interactions between these risk factors are unknown. One hundred and fifty-seven healthy adult participants genotyped for OXTR rs237915 completed a common emotion-matching task during functional magnetic resonance imaging. Past economic privilege and depression and anxiety symptoms were concurrently assessed through validated self-report measures. The data revealed an interaction between rs237915 genotype and economic privilege on the neural response to negative faces. C-carriers showed decreased VS activation and increased connectivity between the VS and ventromedial prefrontal cortex with increased economic privilege. TT homozygotes showed the reverse pattern. Low VS response to negative faces predicted increased social anxiety, but only for those with either lower economic privilege or the C allele. For those with both, low VS response was associated with paradoxically lower social anxiety. Findings suggest that economic privilege and OXTR rs237915 genotype may calibrate social motivational neural systems for better or worse. While lower VS response to negative faces may generally constitute a risk factor for social anxiety, lower response to social cues may be a benefit for those with dual risk.

Patients with major depressive disorder exhibit reduced reward size coding in the striatum

BackgroundAnhedonia is a core symptom of major depressive disorder (MDD). While recent evidence suggests that reduced motivation for reward may be a core feature of anhedonia, the abnormalities in modulatory neural responses to variable reward amounts in MDD patients remain unclear. We investigated whether MDD patients' ability to represent variable-sized monetary rewards in the striatum is disrupted. MethodsTwelve MDD patients and 12 healthy volunteers completed an assessment of psychometric status and participated in a functional magnetic resonance imaging (fMRI) task that involved the anticipation of financial reward (monetary incentive delay task). The size of the monetary reward was varied among trial conditions and was cued with geometric stimuli. Patients participated in additional fMRI sessions after a 6-week pharmacological treatment with escitalopram, an SSRI. ResultsIn healthy volunteers, striatal activity increased in proportion to the size of the monetary reward during reward anticipation. This pattern was altered in MDD patients, and significant group-by-reward size interaction effects were observed in the bilateral putamen and the left ventral striatum. Reward sensitivity in motor response and striatum activity at three regions were correlated in healthy controls. In MDD patients, this neurobehavioral coupling was not observed. In addition, changes in the neural reward sensitivity parameter at the left ventral striatum in response to treatment were positively correlated with a reduction of depressive symptoms. ConclusionsPatients with MDD exhibit reduced ability to modulate neural response when adjusting for variable amount of reward. This result suggests that reward size coding in the striatum may represent a neural correlate of motivational anhedonia in MDD patients.

478. An Interleukin-18 Haplotype Predicts Ventral Striatum Response to Positive and Negative Feedback in Young Adult Women but Not Men

478. An Interleukin-18 Haplotype Predicts Ventral Striatum Response to Positive and Negative Feedback in Young Adult Women but Not Men

Impaired prefrontal cognitive control over interference by food images in binge-eating disorder and bulimia nervosa

Binge-eating disorder (BED)characterized by recurrent episodes of binge-eating without inappropriate compensatory behaviors is classified as an official diagnosis in DSM-5. However, the neural bases that differentiate BED from other eating disorders such as bulimia nervosa (BN), are still under debate. Thirty-nine participants (HC, n=14; BN, n=13; BED, n=12) underwent functional MRI while performing a Stroop-Match-to-Sample task. This pilot study investigated how food images interfered with the behavioral performances and blood-oxygenation-level-dependent neuronal activity. Compared to healthy controls, participants with BN showed lower accuracy indicating impaired cognitive control over interference. Compared to healthy controls, participants with BED demonstrated stronger activations in the ventral striatum in response to food images. By contrast, participants with BN exhibited stronger activations in the premotor cortex and dorsal striatum. These aberrant ventral and dorsal frontostriatal activations in response to food images are associated with increased reward sensitivity and habitual binge-eating/purging behaviors in BED and BN.

Social identity shapes social valuation: evidence from prosocial behavior and vicarious reward.

People frequently engage in more prosocial behavior toward members of their own groups, as compared to other groups. Such group-based prosociality may reflect either strategic considerations concerning one's own future outcomes or intrinsic value placed on the outcomes of in-group members. In a functional magnetic resonance imaging experiment, we examined vicarious reward responses to witnessing the monetary gains of in-group and out-group members, as well as prosocial behavior towards both types of individuals. We found that individuals’ investment in their group—a motivational component of social identification—tracked the intensity of their responses in ventral striatum to in-group (vs out-group) members’ rewards, as well as their tendency towards group-based prosociality. Individuals with strong motivational investment in their group preferred rewards for an in-group member, whereas individuals with low investment preferred rewards for an out-group member. These findings suggest that the motivational importance of social identity—beyond mere similarity to group members—influences vicarious reward and prosocial behavior. More broadly, these findings support a theoretical framework in which salient social identities can influence neural representations of subjective value, and suggest that social preferences can best be understood by examining the identity contexts in which they unfold.

Reward-Related Neural Correlates of Antisocial Behavior and Callous–Unemotional Traits in Young Men

BackgroundIndividuals involved in antisocial behavior often engage in excessive reward-driven behavior even in the face of severe punishments, including incarceration. However, the neural mechanisms of reward processing in antisocial behavior have not been examined while considering the heterogeneity of antisocial behavior and specific phases of reward and loss processing. In this study, we investigated the relationship among antisocial behavior, callous–unemotional (CU) traits, and neural activity during the anticipation and receipt of rewards and losses. MethodsA community sample of 144 low-income, racially diverse urban male individuals at risk for antisocial behavior completed self-report measures, a clinical interview, and a functional magnetic resonance imaging scan at 20 years of age. Neural response during the anticipation and receipt of monetary rewards and losses was linked to antisocial behavior and CU traits using a priori ventral striatum region of interest analyses and exploratory whole-brain analyses. ResultsAntisocial behavior, but not CU traits, was related to less ventral striatum response during reward anticipation. There were no significant relationships between neural reactivity and antisocial behavior or CU traits during reward or loss outcomes. Antisocial behavior was also related to less ventrolateral prefrontal cortex reactivity during reward and loss anticipation. ConclusionsThese findings support a hyporeactivity model of reward and loss anticipation in antisocial behavior. Lower striatal reactivity to cues of reward and lower prefrontal regulatory recruitment during reward and loss anticipation may contribute to maladaptive reward-related behavior found in antisocial behavior.

Hierarchical prediction errors in midbrain and septum during social learning.

Social learning is fundamental to human interactions, yet its computational and physiological mechanisms are not well understood. One prominent open question concerns the role of neuromodulatory transmitters. We combined fMRI, computational modelling and genetics to address this question in two separate samples (N = 35, N = 47). Participants played a game requiring inference on an adviser’s intentions whose motivation to help or mislead changed over time. Our analyses suggest that hierarchically structured belief updates about current advice validity and the adviser’s trustworthiness, respectively, depend on different neuromodulatory systems. Low-level prediction errors (PEs) about advice accuracy not only activated regions known to support ‘theory of mind’, but also the dopaminergic midbrain. Furthermore, PE responses in ventral striatum were influenced by the Met/Val polymorphism of the Catechol-O-Methyltransferase (COMT) gene. By contrast, high-level PEs (‘expected uncertainty’) about the adviser’s fidelity activated the cholinergic septum. These findings, replicated in both samples, have important implications: They suggest that social learning rests on hierarchically related PEs encoded by midbrain and septum activity, respectively, in the same manner as other forms of learning under volatility. Furthermore, these hierarchical PEs may be broadcast by dopaminergic and cholinergic projections to induce plasticity specifically in cortical areas known to represent beliefs about others.

Women's responses to stereotypical media portrayals: An fMRI study of sexualized and domestic images of women

AbstractWomen tend to be portrayed in a sexualized or domestic manner in mainstream advertising; importantly this trend holds not only for ads targeting men but also for those targeting women themselves. Such a focus on sexualized portrayals in particular may not seem strategic given a wealth of evidence suggesting that women evaluate these portrayals quite negatively. Consumer attitudes toward domestic portrayals are more mixed but, unsurprisingly, vary according to how much a woman identifies as traditional. If female consumers do not evaluate these common portrayals positively, why might they persist? Past work suggests a disconnect between reported attitudes toward general visual sexual stimuli and physiological and neural responses; therefore, it is plausible that neural responses to stereotypical female portrayals in advertising may be at odds with reported attitudes and may have a bigger impact on consumer behavior. The current study exposed women to sexualized, domestic, and control images in a functional magnetic resonance imaging scanner as an initial test of this idea. We found that participants reported liking both domestic and control images more than sexualized images. In contrast, they showed more activity in regions associated with reward and arousal (ventral striatum and amygdala, respectively) while viewing sexualized images relative to both control and domestic images. Surprisingly, ventral striatum response to sexualized ads was stronger for women who endorsed traditional attitudes than those who reported less traditional attitudes. These results suggest that despite reporting negative attitudes toward sexualized portrayals, women may in fact have a favorable response to these images. Copyright © 2017 John Wiley &amp; Sons, Ltd.

Restructuring Reward Mechanisms in Nicotine Addiction: A Pilot fMRI Study of Mindfulness-Oriented Recovery Enhancement for Cigarette Smokers.

The primary goal of this pilot feasibility study was to examine the effects of Mindfulness-Oriented Recovery Enhancement (MORE), a behavioral treatment grounded in dual-process models derived from cognitive science, on frontostriatal reward processes among cigarette smokers. Healthy adult (N = 13; mean (SD) age 49 ± 12.2) smokers provided informed consent to participate in a 10-week study testing MORE versus a comparison group (CG). All participants underwent two fMRI scans: pre-tx and after 8-weeks of MORE. Emotion regulation (ER), smoking cue reactivity (CR), and resting-state functional connectivity (rsFC) were assessed at each fMRI visit; smoking and mood were assessed throughout. As compared to the CG, MORE significantly reduced smoking (d = 2.06) and increased positive affect (d = 2.02). MORE participants evidenced decreased CR-BOLD response in ventral striatum (VS; d = 1.57) and ventral prefrontal cortex (vPFC; d = 1.7) and increased positive ER-BOLD in VS (dVS = 2.13) and vPFC (dvmPFC = 2.66). Importantly, ER was correlated with smoking reduction (r's = .68 to .91) and increased positive affect (r's = .52 to .61). These findings provide preliminary evidence that MORE may facilitate the restructuring of reward processes and play a role in treating the pathophysiology of nicotine addiction.

Implicit Learning in Transient Global Amnesia and the Role of Stress.

Transient global amnesia (TGA) is a disorder with reversible anterograde disturbance of explicit memory, frequently preceded by an emotionally or physically stressful event. By using magnetic resonance imaging (MRI) following an episode of TGA, small hippocampal lesions have been observed. Hence it has been postulated that the disorder is caused by the stress-related transient inhibition of memory formation in the hippocampus. In experimental studies, stress has been shown to affect both explicit and implicit learning—the latter defined as learning and memory processes that lack conscious awareness of the information acquired. To test the hypothesis that impairment of implicit learning in TGA is present and related to stress, we determined the effect of experimental exposure to stress on hippocampal activation patterns during an implicit learning paradigm in patients who suffered a recent TGA and healthy matched control subjects. We used a hippocampus-dependent aversive learning procedure (context conditioning with the phases habituation, acquisition, and extinction) during functional MRI following experimental stress exposure (socially evaluated cold pressor test). After a control procedure, controls showed successful learning during the acquisition phase, indicated by increased valence, arousal and contingency ratings to the paired (CON+) vs. the non-paired (CON−) conditioned stimulus, and successful extinction of the conditioned responses. Following stress, acquisition was still successful, however extinction was impaired with persistently increased contingency ratings. In contrast, TGA patients showed impairment of conditioned responses and insufficient extinction after the control procedure, indicated by a lack of significant differences between CON+ and CON− for valence and arousal ratings after the acquisition phase and by significantly increased contingency ratings after the extinction. After stress, aversive learning was not successful with non-significant ratings of all parameters. Concerning brain activation patterns after the control procedure, controls showed increased hippocampal response during acquisition after the control procedure. This was not seen after stress exposure. In TGA patients, we observed an increased response in the right ventral striatum in the acquisition phase following stress. These findings suggest that alterations in implicit learning processes, including impaired hippocampal and increased striatal responses, might play a role in TGA pathophysiology, partly related to acute stress.

Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder.

Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2–19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years).CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors.

Peers and parents: a comparison between neural activation when winning for friends and mothers in adolescence.

Rewards reliably elicit ventral striatum activity. More recently studies have shown that vicarious rewards elicit similar activation. Ventral striatum responses to rewards for self peak during adolescence. However, it is currently not well understood how ventral striatum responses to vicarious rewards develop. In this study, we test this question using behavioral and fMRI data. A total of 233 participants aged 9–26 years old played a gambling game in the scanner in which they could win or lose money for themselves, their best friend and mother. Participants rated how close they felt to their friend and mother and how much they liked winning for them. These ratings were positively correlated. On the neural level males showed higher responses to winning for a friend, but there were no age differences. In contrast, there was a quadratic effect of age when winning for mother, showing heightened ventral striatum activity in mid-adolescence. Furthermore, there was an interaction between age and sex; for females responses to winning for friends become stronger with age relative to winning for mothers. In conclusion, this study provided evidence for elevated ventral striatum responses for mothers in mid-adolescence, and a shift in ventral striatum responses towards peers in girls.

Ventromedial Prefrontal Cortex Damage Is Associated with Decreased Ventral Striatum Volume and Response to Reward.

The ventral striatum and ventromedial prefrontal cortex (vmPFC) are two central nodes of the "reward circuit" of the brain. Human neuroimaging studies have demonstrated coincident activation and functional connectivity between these brain regions, and animal studies have demonstrated that the vmPFC modulates ventral striatum activity. However, there have been no comparable data in humans to address whether the vmPFC may be critical for the reward-related response properties of the ventral striatum. In this study, we used fMRI in five neurosurgical patients with focal vmPFC lesions to test the hypothesis that the vmPFC is necessary for enhancing ventral striatum responses to the anticipation of reward. In support of this hypothesis, we found that, compared with age- and gender-matched neurologically healthy subjects, the vmPFC-lesioned patients had reduced ventral striatal activity during the anticipation of reward. Furthermore, we observed that the vmPFC-lesioned patients had decreased volumes of the accumbens subregion of the ventral striatum. Together, these functional and structural neuroimaging data provide novel evidence for a critical role for the vmPFC in contributing to reward-related activity of the ventral striatum. These results offer new insight into the functional and structural interactions between key components of the brain circuitry underlying human affective function and decision-making. Maladaptive decision-making is a common problem across multiple mental health disorders. Developing new pathophysiologically based strategies for diagnosis and treatment thus requires a better understanding of the brain circuits responsible for adaptive decision-making and related psychological subprocesses (e.g., reward valuation, anticipation, and motivation). Animal studies provide evidence that these functions are mediated through direct interactions between two key nodes of a posited "reward circuit," the ventral striatum and the ventromedial prefrontal cortex (vmPFC). For the first time in humans, we demonstrate that damage to the vmPFC results in decreased ventral striatum activity during reward anticipation. These data provide unique evidence on the causal mechanisms by which the vmPFC and ventral striatum interact during the anticipation of rewards.