Ventral Striatum Response Research Articles

Multiple value signals in dopaminergic midbrain and their role in avoidance contexts

The role of dopaminergic brain regions in avoidance behaviour is unclear. Active avoidance requires motivation, and the latter is linked to increased activity in dopaminergic regions. However, avoidance is also often tethered to the prospect of punishment, a state typically characterized by below baseline levels of dopaminergic function. Avoidance has been considered from the perspective of two-factor theories where the prospect of safety is considered to act as a surrogate for reward, leading to dopamine release and enhanced motivational drive. Using fMRI we investigated predictions from two-factor theory by separating the neural representation of a conventional net expected value, which is negative in the case of avoidance, from an adjusted expected value which factors in a possibility of punishment and is larger for both big rewards and big (predictably avoidable) punishments. We show that neural responses in ventral striatum and ventral tegmental area/substantial nigra (VTA/SN) covaried with net expected value. Activity in VTA/SN also covaried with an adjusted expected value, as did activity in anterior insula. Consistent with two-factor theory models, the findings indicate that VTA/SN and insula process an adjusted expected value during avoidance behaviour.

Ventral striatum activity when watching preferred pornographic pictures is correlated with symptoms of Internet pornography addiction

One type of Internet addiction is excessive pornography consumption, also referred to as cybersex or Internet pornography addiction. Neuroimaging studies found ventral striatum activity when participants watched explicit sexual stimuli compared to non-explicit sexual/erotic material. We now hypothesized that the ventral striatum should respond to preferred pornographic compared to non-preferred pornographic pictures and that the ventral striatum activity in this contrast should be correlated with subjective symptoms of Internet pornography addiction. We studied 19 heterosexual male participants with a picture paradigm including preferred and non-preferred pornographic materials. Subjects had to evaluate each picture with respect to arousal, unpleasantness, and closeness to ideal. Pictures from the preferred category were rated as more arousing, less unpleasant, and closer to ideal. Ventral striatum response was stronger for the preferred condition compared to non-preferred pictures. Ventral striatum activity in this contrast was correlated with the self-reported symptoms of Internet pornography addiction. The subjective symptom severity was also the only significant predictor in a regression analysis with ventral striatum response as dependent variable and subjective symptoms of Internet pornography addiction, general sexual excitability, hypersexual behavior, depression, interpersonal sensitivity, and sexual behavior in the last days as predictors. The results support the role for the ventral striatum in processing reward anticipation and gratification linked to subjectively preferred pornographic material. Mechanisms for reward anticipation in ventral striatum may contribute to a neural explanation of why individuals with certain preferences and sexual fantasies are at-risk for losing their control over Internet pornography consumption.

The influence of contextual reward statistics on risk preference

Decision theories mandate that organisms should adjust their behaviour in the light of the contextual reward statistics. We tested this notion using a gambling choice task involving distinct contexts with different reward distributions. The best fitting model of subjects' behaviour indicated that the subjective values of options depended on several factors, including a baseline gambling propensity, a gambling preference dependent on reward amount, and a contextual reward adaptation factor. Combining this behavioural model with simultaneous functional magnetic resonance imaging we probed neural responses in three key regions linked to reward and value, namely ventral tegmental area/substantia nigra (VTA/SN), ventromedial prefrontal cortex (vmPFC) and ventral striatum (VST). We show that activity in the VTA/SN reflected contextual reward statistics to the extent that context affected behaviour, activity in the vmPFC represented a value difference between chosen and unchosen options while VST responses reflected a non-linear mapping between the actual objective rewards and their subjective value. The findings highlight a multifaceted basis for choice behaviour with distinct mappings between components of this behaviour and value sensitive brain regions.

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Reduced sensitivity to positive feedback is common in patients with major depressive disorder (MDD). However, findings regarding negative feedback are ambiguous, with both exaggerated and blunted responses being reported. The ventral striatum (VS) plays a major role in processing valenced feedback, and previous imaging studies have shown that the locus of controls (self agency v. external agency) over the outcome influences VS response to feedback. We investigated whether attributing the outcome to one's own action or to an external agent influences feedback processing in patients with MDD. We hypothesized that depressed participants would be less sensitive to the feedback attribution reflected by an altered VS response to self-attributed gains and losses. Using functional MRI and a motion prediction task, we investigated the neural responses to self-attributed (SA) and externally attributed (EA) monetary gains and losses in unmedicated patients with MDD and healthy controls. We included 21 patients and 25 controls in our study. Consistent with our prediction, healthy controls showed a VS response influenced by feedback valence and attribution, whereas in depressed patients striatal activity was modulated by valence but was insensitive to attribution. This attribution insensitivity led to an altered ventral putamen response for SA - EA losses in patients with MDD compared with healthy controls. Depressed patients with comorbid anxiety disorder were included. These results suggest an altered assignment of motivational salience to SA losses in patients with MDD. Altered striatal response to SA negative events may reinforce the belief of not being in control of negative outcomes contributing to a cycle of learned helplessness.

A Neurocomputational Model of Altruistic Choice and Its Implications

We propose a neurocomputational model of altruistic choice and test it using behavioral and fMRI data from a task in which subjects make choices between real monetary prizes for themselves and another. We show that a multi-attribute drift-diffusion model, in which choice results from accumulation of a relative value signal that linearly weights payoffs for self and other, captures key patterns of choice, reaction time, and neural response in ventral striatum, temporoparietal junction, and ventromedial prefrontal cortex. The model generates several novel insights into the nature of altruism. It explains when and why generous choices are slower or faster than selfish choices, and why they produce greater response in TPJ and vmPFC, without invoking competition between automatic and deliberative processes or reward value for generosity. It also predicts that when one's own payoffs are valued more than others', some generous acts may reflect mistakes rather than genuinely pro-social preferences.

History of Depression and Frontostriatal Connectivity During Reward Processing in Late Adolescent Boys

Given that depression in men is associated with risk for seriously adverse consequences, evaluating how putative neural mechanisms of depression—such as reward-related frontostriatal connectivity—may be altered in late adolescent boys with a history of depression is an important research aim. Adolescents and adults with depression have been demonstrated to show blunted striatal response and heightened medial prefrontal cortex (mPFC) activation to winning reward. Function in reward circuits appears to be best understood as coordination of regions within frontostriatal circuitry, and alterations to this circuitry could occur in those with a history of depression. The current study evaluated functional connectivity between the nucleus accumbens and mPFC in a sample of 166 ethnically diverse boys with and without a history of depression. Participants completed an fMRI monetary reward paradigm at age 20. Lifetime history of depression and other psychiatric illnesses was measured prospectively and longitudinally, using structured clinical interviews at 7 time points from ages 8 to 20. Boys with a history of depression showed heightened positive connectivity between the nucleus accumbens and the mPFC relative to boys with no psychiatric history when winning rewards relative to losing rewards. This altered frontostriatal connectivity pattern was also associated with greater number of depressive episodes in the boys’ lifetime. History of depression in late adolescent boys may be associated with altered coordination between the nucleus accumbens and mPFC when winning reward. This coordination could reflect oversignaling of the mPFC to dampen typical ventral striatum response or enhance weak ventral striatum response.

BDNF Val66Met polymorphism influence on striatal blood-level-dependent response to monetary feedback depends on valence and agency

Animal work implicates the brain-derived neurotrophic factor (BDNF) in function of the ventral striatum (VS), a region known for its role in processing valenced feedback. Recent evidence in humans shows that BDNF Val66Met polymorphism modulates VS activity in anticipation of monetary feedback. However, it remains unclear whether the polymorphism impacts the processing of self-attributed feedback differently from feedback attributed to an external agent. In this study, we emphasize the importance of the feedback attribution because agency is central to computational accounts of the striatum and cognitive accounts of valence processing. We used functional magnetic resonance imaging and a task, in which financial gains/losses are either attributable to performance (self-attributed, SA) or chance (externally-attributed, EA) to ask whether BDNF Val66Met polymorphism predicts VS activity. We found that BDNF Val66Met polymorphism influenced how feedback valence and agency information were combined in the VS and in the right inferior frontal junction (IFJ). Specifically, Met carriers’ VS response to valenced feedback depended on agency information, while Val/Val carriers’ VS response did not. This context-specific modulation of valence effectively amplified VS responses to SA losses in Met carriers. The IFJ response to SA losses also differentiated Val/Val from Met carriers. These results may point to a reduced allocation of attention and altered motivational salience to SA losses in Val/Val compared to Met carriers. Implications for major depressive disorder are discussed.

Decision-making and trait impulsivity in bipolar disorder are associated with reduced prefrontal regulation of striatal reward valuation

Bipolar disorder is characterized by impaired decision-making captured in impulsivity and risk-taking. We sought to determine whether this is driven by a failure to effectively weight the lower-order goal of obtaining a strongly desired reward in relation to higher-order goals, and how this relates to trait impulsivity and risk-taking. We hypothesized that in bipolar disorder the weighting of valuation signals converging on ventromedial prefrontal cortex are more heavily weighted towards ventral striatum inputs (lower-order), with less weighting of dorsolateral prefrontal cortex inputs (higher-order). Twenty euthymic patients with bipolar disorder not in receipt of antipsychotic medication and 20 case-matched controls performed a roulette task during functional magnetic resonance imaging. Activity in response to high-probability (‘safe’) and low-probability (‘risky’) prospects was measured during both anticipation, and outcome. In control subjects, anticipatory and outcome-locked activity in dorsolateral prefrontal cortex was greater for safe than risky reward prospects. The bipolar disorder group showed the opposite pattern with preferential response to risky rewards. This group also showed increased anticipatory and outcome-locked activity in ventral striatum in response to rewards. In control subjects, however, ventromedial prefrontal activation was positively associated with both ventral striatum and dorsolateral prefrontal activity; patients evidenced a strong positive association with ventral striatum, but a negative association with dorsolateral prefrontal cortex. Response to high-probability rewards in dorsolateral prefrontal cortex was inversely associated with trait impulsivity and risk-taking in the bipolar disorder group. Our findings suggest that clinically impulsive and risky decision-making are related to subjective valuation that is biased towards lower-order preference, with diminished integration of higher-order goals. The findings extend a functional neuroanatomical account of disorders characterized by clinically impulsive decision-making, and provide targets for evaluating interventions that foster self-control.

Clarifying the neural basis for incentive salience of tobacco cues in smokers

In functional magnetic resonance imaging (fMRI) studies, smoking cues have been found to elicit increases in brain activity in regions associated with processing rewarding and emotional stimuli. However, most smoking cue studies to date have reported effects relative to neutral control stimuli with no incentive properties, making it unclear whether the observed activation pertains to value in general or the value of cigarettes in particular. The current fMRI study sought to clarify the neural activity reflecting tobacco-specific incentive value versus domain-general incentive value by examining smoking cues, neutral cues, and a third set of cues, monetary cues, which served as an active control condition. Participants were 42 male daily smokers. Compared to neutral cues, significantly greater activation was found in the left ventral striatum in response to tobacco and money cues. Monetary cues also elicited significantly increased activation in the right inferior frontal gyrus and cuneus compared to the other two cue types. Overall, the results suggest that the salience of monetary cues was the highest and, as a result, might have reduced the incentive salience of tobacco cues.

Effects of social context on feedback-related activity in the human ventral striatum

It is now well established that activation of the ventral striatum (VS) encodes feedback related information, in particular, aspects of feedback validity, reward magnitude, and reward probability. More recent findings also point toward a role of VS in encoding social context of feedback processing. Here, we investigated the effect of social observation on neural correlates of feedback processing. To this end, subjects performed a time estimation task and received positive, negative, or uninformative feedback. In one half of the experiment subjects thought that an experimenter closely monitored their face via a camera. We successfully replicated an elevated VS response to positive relative to negative feedback. Further, our data demonstrate that this reward-related activation of the VS is increased during observation by others. Using uninformative feedback as reference condition, we show that specifically VS activation during positive feedback was modulated by observation manipulation. Our findings support accounts which posit a role of VS in integrating social context into the processing of feedback and, in doing so, signaling its social relevance.

Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD

Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD.

A cross-sectional and longitudinal analysis of reward-related brain activation: Effects of age, pubertal stage, and reward sensitivity

Neurobiological models suggest that adolescents are driven by an overactive ventral striatum (VS) response to rewards that may lead to an adolescent increase in risk-taking behavior. However, empirical studies showed mixed findings of adolescents’ brain response to rewards. In this study, we aimed to elucidate the relationship between reward-related brain activation and risky decision-making. In addition, we examined effects of age, puberty, and individuals’ reward sensitivity. We collected two datasets: Experiment 1 reports cross-sectional brain data from 75 participants (ages 10–25) who played a risky decision task. Experiment 2 presents a longitudinal extension in which a subset of these adolescents (n=33) was measured again 2years later. Results showed that (1) a reward-related network including VS and medial PFC was consistently activated over time, (2) the propensity to choose the risky option was related to increased reward-related activation in VS and medial PFC, and (3) longitudinal comparisons indicated that self-reported reward sensitivity was specifically related to VS activation over time. Together, these results advance our insights in the brain circuitry underlying reward processing across adolescence.

EPA-1455 - Reward anticipation in schizophrenia: A functional magnetic resonance imaging study

Introduction Previous studies have reported that patient with schizophrenia have preserved hedonic capacity, but impaired ability to anticipate future reward (anticipatory anhedonia) that, according to some authors, may underlie other aspects of negative symptoms, such as avolition. Objectives/Aims The aim of our study was to demonstrate an impairment of reward anticipation in patients with deficit schizophrenia (DS), characterized by primary and persistent negative symptoms, but not in those with non-deficit schizophrenia (NDS) with respect to healthy controls (HC), by means of functional magnetic resonance imaging (fMRI). Methods fMRI was recorded during the execution of the ’Monetary Incentive Delay’ task in 11 patients with DS, 23 patients with NDS and 23 HC, during the anticipation of five different outcomes, small (SR) or large (LR) reward, small (SP) or large (LP) punishment or no-outcome (NO). Results The ventral striatum response to reward anticipation was preserved in subjects with schizophrenia. Only patients with DS, compared with HC, showed a significant reduction in the left caudate during the anticipation of reward. The reduced activity of the caudate correlated with the scores for avolition but not for anhedonia. Conclusion Our preliminary data suggest an involvement of the caudate in the abnormal processing of reward stimuli in patients with DS and show that avolition and anhedonia are subtended by different functional abnormalities.

Fatal attraction: Ventral striatum predicts costly choice errors in humans

Animals approach rewards and cues associated with reward, even when this behavior is irrelevant or detrimental to the attainment of these rewards. Motivated by these findings we study the biology of financially-costly approach behavior in humans. Our subjects passively learned to predict the occurrence of erotic rewards. We show that neuronal responses in ventral striatum during this Pavlovian learning task stably predict an individual's general tendency towards financially-costly approach behavior in an active choice task several months later. Our data suggest that approach behavior may prevent some individuals from acting in their own interests.

When “Your” reward is the same as “My” reward: Self-construal priming shifts neural responses to own vs. friends' rewards

Is it possible for neural responses to others' rewards to be as strong as those for the self? Although prior fMRI studies have demonstrated that watching others get rewards can activate one's own reward centers, such vicarious reward activation has always been less strong than responses to rewards for oneself. In the present study we manipulated participants' self-construal (independent vs. interdependent) and found that, when an independent self-construal was primed, subjects showed greater activation in the bilateral ventral striatum in response to winning money for the self (vs. for a friend) during a gambling game. However, priming an interdependent self-construal resulted in comparable activation in these regions in response to winning money for the self and for a friend. Our findings suggest that interdependence may cause people to experience rewards for a close other as strongly as they experience rewards for the self.

An altered neural response to reward may contribute to alcohol problems among late adolescents with an evening chronotype

Evening chronotypes not only differ from morning-types in their sleep and circadian timing, but they are prone to problematic outcomes involving reward function, including affective disturbance, sensation seeking, and substance involvement. We explored the neural mechanisms underlying these chronotype differences by comparing the neural response to reward in morning- and evening-types. Using a monetary reward fMRI paradigm, we compared the neural response to reward in 13 morning-types and 21 evening-types (all 20 y/o males). Region-of-interest (ROI) analyses focused on the medial prefrontal cortex (mPFC) and ventral striatum (VS), comparing the chronotype groups in these ROIs during anticipation and outcome conditions, and adjusting for time of scan. Chronotype groups were also compared on measures of sensation-seeking, substance involvement, and sleep quality. Evening-types reported significantly greater levels of alcohol dependence and worse sleep quality. Furthermore, evening-types showed an altered neural response to reward relative to morning-types, specifically, reduced mPFC reactivity during reward anticipation and increased VS reactivity during win outcome. In turn, less activation in the mPFC region in response to reward was associated with greater alcohol consumption, while increased activation in the VS in response to reward was associated with more symptoms of alcohol dependence. Increased reward-related problems among evening-types may be accompanied by altered neural responses to reward.

Dissociable cortical and ventral striatal responses to painful somatosensory stimulation measured using functional MRI imaging

INTRODUCTION Investigation of the neural responses of chronic pain have traditionally involved establishing the BOLD fMRI response to acute pain in a nodal network that has been referred to as the ‘pain matrix’ or the ‘pain neuromatrix’ (1). However, Melzack originally used the term ‘matrix’ because the system to which he referred was multimodal in function and lacked specificity. This might explain why, over 20 years after the term was coined, there has been little translational benefit to patients in terms of improved management of chronic pain states despite numerous studies examining the ‘pain matrix response’. The basal ganglia form part of this matrix and are worthy of further investigation. Destruction of nigrostriatal neurones in the ventral basal ganglia are associated with reduced pain thresholds, the inverse effect occurring with nigrostriatal stimulation(2). However, inactivation of the accumbens core in the ventral basal ganglia with local anaesthetic has demonstrated a hyperalgesic response (3). Molecular imaging has been used to examine the differential roles of dorsal and ventral basal ganglia in pain perception (4) . These authors found that whilst nigrostriatal D2-dopamine activity correlates with sensory and affective ratings, in accumbens the dopamine response is positively associated with negative affect and fear ratings during pain, aspects of the pain experience that are thought to better explain interindividual variations in chronic pain (5) and response to analgesia. In establishing a region of interest approach to the investigation of chronic pain through the application of acutely painful stimuli, the ventral striatum may therefore be an important target. The role of the ventral striatum in response to aversive stimuli is receiving increasing attention, in counterpart to studies of its responsivity to rewarding stimuli. Recent work (6) suggests that the differential striatal responses to acute pain may provide a meaningful insight into the neural substrates of chronic pain perception, including idiopathic pain disorders and the functional somatic syndromes, where activation of the ‘pain matrix’ as a whole has proved unable to. We have investigated the brain response to somatosensory pain, specifically examining the response of the ventral striatum in contrast to other components of the ‘pain matrix’.

Neural correlates of reward and loss sensitivity in psychopathy

Psychopathy is a personality disorder associated with callous and impulsive behavior and criminal recidivism. It has long been theorized that psychopaths have deficits in processing reward and punishment. Here, we use structural and functional magnetic resonance imaging to examine the neural correlates of reward and loss sensitivity in a group of criminal psychopaths. Forty-one adult male prison inmates (n = 18 psychopaths and n = 23 non-psychopaths) completed a functional magnetic resonance imaging task involving the gain or loss of money. Across the entire sample of participants, monetary gains elicited robust activation within the ventral striatum (VS). Although psychopaths and non-psychopaths did not significantly differ with respect to overall levels of VS response to reward vs loss, we observed significantly different correlations between VS responses and psychopathy severity within each group. Volumetric analyses of striatal subregions revealed a similar pattern of correlations, specifically for the right accumbens area within VS. In a separate sample of inmates (n = 93 psychopaths and n = 117 non-psychopaths) who completed a self-report measure of appetitive motivation, we again found that the correlation with psychopathy severity differed between groups. These convergent results offer novel insight into the neural substrates of reward and loss processing in psychopathy.

Closing the Gate in the Limbic Striatum: Prefrontal Suppression of Hippocampal and Thalamic Inputs

Many brain circuits control behavior by integrating information arising from separate inputs onto a common target neuron. Neurons in the ventral striatum (VS) receive converging excitatory afferents from the prefrontal cortex (PFC), hippocampus (HP), and thalamus, among other structures, and the integration of these inputs is critical for goal-directed behaviors. Although HP inputs have been described as gating PFC throughput in the VS, recent data reveal that the VS desynchronizes from the HP during epochs of burst-like PFC activity related to decision making. It is therefore possible that PFC inputs locally attenuate responses to other glutamatergic inputs to the VS. Here, we found that delivering trains of stimuli to the PFC suppresses HP- and thalamus-evoked synaptic responses in the VS, in part through activation of inhibitory processes. This interaction may enable the PFC to exert influence on basal ganglia loops during decision-making instances with minimal disturbance from ongoing contextual inputs.

The Roles of Reward, Default, and Executive Control Networks in Set-Shifting Impairments in Schizophrenia

Patients with schizophrenia (SZ) show deficits on tasks of rapid reinforcement learning, like probabilistic reversal learning (PRL), but the neural bases for those impairments are not known. Recent evidence of relatively intact sensitivity to negative outcomes in the ventral striatum (VS) in many SZ patients suggests that PRL deficits may be largely attributable to processes downstream from feedback processing, involving both the activation of executive control task regions and deactivation of default mode network (DMN) components. We analyzed data from 29 chronic SZ patients and 21 matched normal controls (NCs) performing a PRL task in an MRI scanner. Subjects were presented with eight pairs of fractal stimuli, for 50 trials each. For each pair, subjects learned to choose the more frequently-rewarded (better) stimulus. Each time a criterion was reached, the better stimulus became the worse one, and the worse became the better. Responses to feedback events were assessed through whole-brain and regions-of-interest (ROI) analyses in DMN. We also assessed correlations between BOLD signal contrasts and clinical measures in SZs. Relative to NCs, SZ patients showed comparable deactivation of VS in response to negative feedback, but reduced deactivation of DMN components including medial prefrontal cortex (mPFC). The magnitudes of patients' punishment-evoked deactivations in VS and ventromedial PFC correlated significantly with clinical ratings for avolition/anhedonia. These findings suggest that schizophrenia is associated with a reduced ability to deactivate components of default mode networks, following the presentation of informative feedback and that motivational deficits in SZ relate closely to feedback-evoked activity in reward circuit components. These results also confirm a role for ventrolateral and dorsomedial PFC in the execution of response-set shifts.