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10.1016/j.biopsych.2008.08.019

Biological psychiatry

Biol Psychiatry

Personality traits are differentially associated with patterns of reward and novelty processing in the human substantia nigra/ventral tegmental area.

The long-standing observation that the novelty-seeking personality trait is a predictor of drug use and other reinforcable risky behaviors raises the question as to how novelty and reward processing functionally interact in mesolimbic dopaminergic circuitry and how this interaction is modulated by the novelty-seeking personality trait. Functional magnetic resonance imaging (fMRI) hemodynamic responses to novelty and reward (monetary incentive) from the substantia nigra/ventral tegmental area (SN/VTA), the nucleus accumbens (NAcc), and the hippocampus of 29 subjects were correlated with novelty-seeking scores. These correlations were compared with those obtained for scores of reward-dependence. The fMRI data were taken from two experiments in which the interaction of novelty and reward was manipulated as a within-subject variable, and long-term memory for the critical stimuli was assessed after 24 hours. Novelty-seeking was positively correlated with SN/VTA activation elicited by novel cues that did not predict reward, whereas reward-dependence was related to activations elicited by novel cues that predicted reward. The positive correlation between SN/VTA responses to novelty and novelty-seeking scores was accompanied by a negative correlation with reward-related SN/VTA activation and memory enhancement. SN/VTA responses to novelty and reward are differentially affected by personality traits of novelty-seeking and reward-dependence. Importantly, novelty-seekers were more responsive to novel cues in the absence of reward and needed less reward to boost their memory for novel cues. These observations strongly suggest that for novelty-seekers, the motivational value of novelty is not necessarily based on actual reward-predicting stimulus properties.

CognitiveConstruct

RewardProcessing

10.1111/j.1530-0277.2008.00806.x

Alcoholism, clinical and experimental research

Alcohol Clin Exp Res

Age at first drink and the first incidence of adult-onset DSM-IV alcohol use disorders.

Existing studies of the association between age at first drink (AFD) and the risk of alcohol use disorders (AUD) suffer from inconsistent levels of control and designs that may inflate associations by failure to control for duration of exposure to risk. This study examined associations between AFD (ages <15 and 15-17 vs. 18+ years) and first incidence of DSM-IV alcohol dependence, abuse, and specific AUD criteria over a 3-year follow-up in a longitudinal study of U.S. drinkers 18 years of age and older at baseline (n = 22,316), controlling for duration of exposure, family history, and a wide range of baseline and childhood risk factors. After adjusting for all risk factors, the incidence of dependence was increased for AFD <15 years (OR = 1.38) and for women only with AFD at ages 15 to 17 (OR = 1.54). The incidence of abuse was increased at AFD <15 and 15 to 17 years (OR = 1.52 and 1.30, respectively). Most dependence criteria showed significant associations with AFD, but hazardous drinking and continued drinking despite interpersonal problems were the only abuse criteria to do so. All associations were nonsignificant after controlling for volume of consumption, except that AFD at all ages <18 combined was associated with a reduced likelihood of impaired control, and AFD at ages 15 to 17 was associated with lower odds of drinking more/longer than intended among heavy-volume drinkers. In a population of low-risk drinkers that excluded those with positive family histories, personality disorders, and childhood risk factors, there were strong associations between early AFD (<18) and the incidence of dependence (OR = 3.79) and continued drinking despite physical/psychological problems (OR = 2.71), but no association with incidence of abuse. There is a robust association between AFD and the risk of AUD that appears to reflect willful rather than uncontrolled heavy drinking, consistent with misuse governed by poor decision-making and/or reward-processing skills associated with impaired executive cognitive function (ECF). Additional research is needed to determine causality in the role of impaired ECF, including longitudinal studies with samples of low-risk adolescents.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2008.07.012

Drug and alcohol dependence

Drug Alcohol Depend

Neurobiological substrates of cue-elicited craving and anhedonia in recently abstinent opioid-dependent males.

Drug-related stimuli may induce craving in addicted patients, prompting drug-seeking behaviour. In addition, studies have shown addicted patients to be less sensitive to pleasant, but non-drug-related, stimuli; a condition generally referred to as anhedonia. The neural correlates of cue-induced craving and anhedonia in opioid-dependent patients are, however, not well understood. We studied brain activation patterns following visual presentation of neutral, pleasant and heroin-related cues. Detoxified opioid-dependent males (n=12) and healthy male control subjects (n=17) underwent functional magnetic resonance imaging (fMRI) while subjects viewed neutral, pleasant and heroin-related images. In addition, subjective cue-elicited craving (OCDUS and DDQ) and anhedonia (SHAPS) were measured. Opioid-dependent subjects, but not control subjects, showed significant increases in activation in hippocampal region and subcortical limbic structures in response to heroin-related stimuli with a significant group x stimulus interaction effect for the subthalamic nucleus (STN). Control subjects, but not opioid-dependent subjects, showed significant increases in activation of anterior frontal areas and basal ganglia while viewing pleasant images with a significant group x stimulus interaction effect for bilateral anterior prefrontal cortex. Regression analyses showed a positive association between cue-elicited craving and ventral tegmental area (VTA) activation in response to heroin-related stimuli in heroin-dependent patients. In addition, a negative correlation was found between self-reported anhedonia and medial prefrontal regions in both groups. Our findings suggest that the VTA is prominently involved in cue-induced opioid craving for heroin stimuli, in addition to mesolimbic and mesocortical pathways as identified in previous research. The present study also provides further evidence for the involvement of the STN in reward processing. Finally, our data support the presence of reduced brain activation in heroin-dependent patients in response to pleasant (non-drug-related) stimuli.

CognitiveConstruct

RewardProcessing

10.1097/WNR.0b013e32830fe98c

Neuroreport

Neuroreport

The left dorsal striatum is involved in the processing of neutral feedback.

In experimental settings, feedback is mostly used to inform about the correctness of a participant's response. Such feedback, however, also provides the information that a response was registered, which is highly significant in any dialog situation. The present functional MRI study investigated the involvement of brain areas in the processing of neutral, verbal feedback. We used an auditory discrimination task with verbal feedback, which immediately informed the participants that their response was registered. We found an increased activation in the left dorsal striatum compared with temporally uncorrelated feedback and the no-feedback condition. Several studies using evaluative feedback suggest that this area participates in reward processing. The present result suggests that it may already be involved in more basic aspects of feedback processing.

CognitiveConstruct

RewardProcessing

10.1073/pnas.0802127105

Proceedings of the National Academy of Sciences of the United States of America

Proc Natl Acad Sci U S A

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

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

CognitiveConstruct

RewardProcessing

10.1016/j.bandc.2008.08.004

Brain and cognition

Brain Cogn

Brain correlates of aesthetic expertise: a parametric fMRI study.

Several studies have demonstrated that acquired expertise influences aesthetic judgments. In this paradigm we used functional magnetic resonance imaging (fMRI) to study aesthetic judgments of visually presented architectural stimuli and control-stimuli (faces) for a group of architects and a group of non-architects. This design allowed us to test whether level of expertise modulates neural activity in brain areas associated with either perceptual processing, memory, or reward processing. We show that experts and non-experts recruit bilateral medial orbitofrontal cortex (OFC) and subcallosal cingulate gyrus differentially during aesthetic judgment, even in the absence of behavioural aesthetic rating differences between experts and non-experts. By contrast, activity in nucleus accumbens (NAcc) exhibits a differential response profile compared to OFC and subcallosal cingulate gyrus, suggesting a dissociable role between these regions in the reward processing of expertise. Finally, categorical responses (irrespective of aesthetic ratings) resulted in expertise effects in memory-related areas such as hippocampus and precuneus. These results highlight the fact that expertise not only modulates cognitive processing, but also modulates the response in reward related brain areas.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2008.07.018

Neuropsychologia

Neuropsychologia

Implicit trustworthiness ratings of self-resembling faces activate brain centers involved in reward.

On the basis of Hamilton's (Hamilton, W. D. (1964). The genetical evolution of social behavior I, II. Journal of Theoretical Biology, 7, 17-52) theory of inclusive fitness, self-facial resemblance is hypothesized as a mechanism for self-referent phenotypic matching by which humans can detect kin. To understand the mechanisms underlying pro-sociality toward self-resembling faces, we investigated the neural correlates of implicit trustworthiness ratings for self-resembling faces. Here we show that idiosyncratic trustworthiness ratings of self-resembling faces predict brain activation in the ventral inferior, middle and medial frontal gyri, substrates involved in reward processing. These findings demonstrate that neural reward centers are implicated in evaluating implicit pro-social behaviors toward self-resembling faces. These findings suggest that humans have evolved to use neurocomputational architecture dedicated to face processing and reward evaluation for the differentiation of kin, which drives implicit idiosyncratic affectively regulated social interactions.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2008.07.008

Biological psychiatry

Biol Psychiatry

Neural hyporesponsiveness and hyperresponsiveness during immediate and delayed reward processing in adult attention-deficit/hyperactivity disorder.

Dysfunctional reward processing, accompanied by a limited ability to tolerate reward delays, has been proposed as an important feature in attention-deficit/hyperactivity disorder (ADHD). Using functional magnetic resonance imaging (fMRI), brain activation in adult patients with ADHD (n=14) and healthy control subjects (n=12) was examined during a series of choices between two monetary reward options that varied by delay to delivery. Compared with healthy control subjects, hyporesponsiveness of the ventral-striatal reward system was replicated in patients with ADHD and was evident for both immediate and delayed rewards. In contrast, delayed rewards evoked hyperactivation in dorsal caudate nucleus and amygdala of ADHD patients. In both structures, neural activity toward delayed rewards was significantly correlated with self-rated ADHD symptom severity. The finding of ventral-striatal hyporesponsiveness during immediate and delayed reward processing in patients with ADHD further strengthens the concept of a diminished neural processing of rewards in ADHD. Hyperactivation during delayed reward processing, gradually increasing along the ventral-to-dorsal extension of the caudate nucleus, and especially the concomitant hyperactivation of the amygdala are in accordance with predictions of the delay aversion hypothesis.

CognitiveConstruct

RewardProcessing

10.1016/j.brainres.2008.07.110

Brain research

Brain Res

Prefrontal cortex and striatal activation by feedback in Parkinson's disease.

Positive feedbacks reinforce goal-directed behavior and evoke pleasure. In Parkinson's disease (PD) the striatal dysfunction impairs motor performance, but also may lead to decreased positive feedback (reward) processing. This study investigates two types of positive feedback processing (monetary feedback and positive informative feedback), both compared to meaningless feedback, in PD patients and elderly healthy controls, using fMRI. In addition, positive informative feedback will be compared to monetary feedback to determine whether positive informative feedback is just as salient as monetary feedback. Healthy controls showed increased activation in the left putamen during the monetary feedback condition compared to both the positive informative and meaningless feedback condition, without an effect in the medial Prefrontal Cortex (mPFC). In contrast, PD patients showed increased activation in the left putamen during the meaningless feedback condition compared to both positive feedback conditions. In addition, PD patients showed increased activation of the mPFC during both positive feedback conditions. This suggests that when confronted with positive feedback, the mPFC compensates for the striatal deficit. In conclusion, striatal activation was seen in healthy controls specifically during the monetary feedback condition. PD patients did not differentiate between both types of positive feedback. If PD patients are provided with positive feedback, the mPFC compensates for the striatal dysfunction. If however, PD patients are provided with meaningless feedback, the mPFC is less stimulated and the striatum becomes prominent. This study thus demonstrates striatal involvement in positive feedback processing and altered positive feedback processing in PD.

CognitiveConstruct

RewardProcessing

10.1162/jocn.2009.21062

Journal of cognitive neuroscience

J Cogn Neurosci

Good vibrations: cross-frequency coupling in the human nucleus accumbens during reward processing.

The nucleus accumbens is critical for reward-guided learning and decision-making. It is thought to "gate" the flow of a diverse range of information (e.g., rewarding, aversive, and novel events) from limbic afferents to basal ganglia outputs. Gating and information encoding may be achieved via cross-frequency coupling, in which bursts of high-frequency activity occur preferentially during specific phases of slower oscillations. We examined whether the human nucleus accumbens engages such a mechanism by recording electrophysiological activity directly from the accumbens of human patients undergoing deep brain stimulation surgery. Oscillatory activity in the gamma (40-80 Hz) frequency range was synchronized with the phase of simultaneous alpha (8-12 Hz) waves. Further, losing and winning small amounts of money elicited relatively increased gamma oscillation power prior to and following alpha troughs, respectively. Gamma-alpha synchronization may reflect an electrophysiological gating mechanism in the human nucleus accumbens, and the phase differences in gamma-alpha coupling may reflect a reward information coding scheme similar to phase coding.

CognitiveConstruct

RewardProcessing

10.1016/j.conb.2008.07.010

Current opinion in neurobiology

Curr Opin Neurobiol

Anchors, scales and the relative coding of value in the brain.

People are alarmingly susceptible to manipulations that change both their expectations and experience of the value of goods. Recent studies in behavioral economics suggest such variability reflects more than mere caprice. People commonly judge options and prices in relative terms, rather than absolutely, and display strong sensitivity to exemplar and price anchors. We propose that these findings elucidate important principles about reward processing in the brain. In particular, relative valuation may be a natural consequence of adaptive coding of neuronal firing to optimise sensitivity across large ranges of value. Furthermore, the initial apparent arbitrariness of value may reflect the brains' attempts to optimally integrate diverse sources of value-relevant information in the face of perceived uncertainty. Recent findings in neuroscience support both accounts, and implicate regions in the orbitofrontal cortex, striatum, and ventromedial prefrontal cortex in the construction of value.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.1371-08.2008

The Journal of neuroscience : the official journal of the Society for Neuroscience

J Neurosci

Dopamine signaling through D1-like versus D2-like receptors in the nucleus accumbens core versus shell differentially modulates nicotine reward sensitivity.

Considerable evidence implicates the mesolimbic dopamine (DA) system in the processing of nicotine's reinforcing properties, specifically the ventral tegmental area (VTA) and the terminal fields of VTA DAergic projections to the "core" (NAcore) and "shell" (NAshell) subdivisions of the nucleus accumbens (NAc). However, the specific roles of DA D(1)-like and D(2)-like receptor subtypes in nicotine reward processing within these NAc subregions have not been elucidated. We report that microinfusions of DA D(1)-like or D(2)-like receptor-specific antagonists into NAcore or NAshell double dissociate the rewarding and aversive properties of systemic or intra-VTA nicotine, and differentially regulate sensitivity to the rewarding properties as well as the motivational valence of either intra-VTA or systemic nicotine administration. Using a place conditioning procedure, NAshell infusions of a D(2)-like receptor antagonist switched the motivational valence of intra-VTA nicotine from aversive to rewarding and potentiated nicotine reward sensitivity to sub-reward threshold intra-VTA nicotine doses. In contrast, NAcore infusions of a D(1)-like receptor antagonist switched intra-VTA nicotine aversion to reward, and potentiated reward sensitivity to sub-reward threshold nicotine doses. Thus, D(1)-like versus D(2)-like receptors in NAcore versus NAshell subdivisions play functionally dissociable roles in modulating systemic or intra-VTA nicotine motivational processing.

CognitiveConstruct

RewardProcessing

10.1016/j.mehy.2008.06.017

Medical hypotheses

Med Hypotheses

Alertness and feeding behaviors in ADHD: does the hypocretin/orexin system play a role?

Increasing evidence has suggested that patients with attention-deficit/hyperactivity disorder (ADHD) may present with a deficit of alertness and sleep disturbances. Recent studies have also pointed out a previously underestimated association between ADHD and abnormal eating behaviors, including binge eating. Since sleep/alertness disturbances and eating disorders may significantly increase the functional impairment of ADHD, gaining insight into their pathophysiology as well as into their treatment is of relevance to provide a better clinical management of patients suffering from ADHD. The hypocretin/orexin system comprises two distinct peptides, located in the hypothalamus, which are involved in several homeostatic functions. In particular, it has been suggested that hypocretin/orexin neurons located in perifornical and dorsomedial hypothalamic nuclei increase arousal, whereas those located in the lateral hypothalamus are primarily implicated in reward processing, stimulating feeding and other reward seeking behaviors. Given the involvement of the hypocretin/orexin system in the control of alertness and reward seeking (including feeding), we hypothesize that hypocretin/orexin neurons located in perifornical and dorsomedial hypothalamic areas are hypoactivated, while those located in the lateral hypothalamus are overactivated in patients with ADHD. If confirmed by further neurophysiological, imaging, and genetics studies, our hypothesis may help us progress in the understanding of the complex pathophysiology of ADHD. This might set the basis for the study of novel molecules, acting on the hypocretin/orexin system, aimed at increasing wakefulness and reducing binge eating and other abnormal reward seeking behaviors in patients with ADHD. We also suggest future studies on the potential therapeutic role of other molecules which have a complex interplay with the hypocretin/orexin system, such as the histamine H(1) receptor agonists, the histamine H(3) receptor antagonists, and the neuropeptide Y receptor antagonists. All this body of research would provide a tremendous opportunity to improve the quality of life of patients with ADHD by means of pathophysiologically oriented treatment.

CognitiveConstruct

RewardProcessing

10.1016/j.brainresrev.2008.07.004

Brain research reviews

Brain Res Rev

Functional neuroimaging of reward processing and decision-making: a review of aberrant motivational and affective processing in addiction and mood disorders.

The adequate integration of reward- and decision-related information provided by the environment is critical for behavioral success and subjective well being in everyday life. Functional neuroimaging research has already presented a comprehensive picture on affective and motivational processing in the healthy human brain and has recently also turned its interest to the assessment of impaired brain function in psychiatric patients. This article presents an overview on neuroimaging studies dealing with reward processing and decision-making by combining most recent findings from fundamental and clinical research. It provides an outline on the neural mechanisms guiding context-adequate reward processing and decision-making processes in the healthy brain, and also addresses pathophysiological alterations in the brain's reward system that have been observed in substance abuse and mood disorders, two highly prevalent classes of psychiatric disorders. The overall goal is to critically evaluate the specificity of neurophysiological alterations identified in these psychiatric disorders and associated symptoms, and to make suggestions concerning future research.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropharm.2008.06.060

Neuropharmacology

Neuropharmacology

Role of lateral hypothalamic orexin neurons in reward processing and addiction.

Orexins (also known as hypocretins) are recently discovered neuropeptides made exclusively in hypothalamic neurons that have been shown to be important in narcolepsy/cataplexy and arousal. Here, we conducted behavioral, anatomical and neurophysiological studies that show that a subset of these cells, located specifically in lateral hypothalamus (LH), are involved in reward processing and addictive behaviors. We found that Fos expression in LH orexin neurons varied in proportion to preference for morphine, cocaine or food. This relationship obtained both in drug naïve rats and in animals during protracted morphine withdrawal, when drug preference was elevated but food preference was decreased. Recent studies showed that LH orexin neurons that project to ventral tegmental area (VTA) have greater Fos induction in association with elevated morphine preference during protracted withdrawal than non-VTA-projecting orexin neurons, indicating that the VTA is an important site of action for orexin's role in reward processing. In addition, we found that stimulation of LH orexin neurons, or microinjection of orexin into VTA, reinstated an extinguished morphine preference. Most recently, using a self-administration paradigm we discovered that the Ox1 receptor antagonist SB-334867 (SB) blocks cocaine-seeking induced by discrete or contextual cues, but not by a priming injection of cocaine. Neurophysiological studies revealed that locally applied orexin often augmented responses of VTA dopamine (DA) neurons to activation of the medial prefrontal cortex (mPFC), consistent with the view that orexin facilitates activation of VTA DA neurons by stimulus-reward associations. We also recently showed that orexin in VTA is necessary for learning a morphine place preference. These findings are consistent with results from others showing that orexin facilitates glutamate-mediated responses, and is necessary for glutamate-dependent long-term potentiation, in VTA DA neurons. We surmise from these studies that LH orexin neurons play an important role in reward processing and addiction, and that LH orexin cells are an important input to VTA for behavioral effects associated with reward-paired stimuli.

CognitiveConstruct

RewardProcessing

10.1016/j.neuro.2008.06.007

Neurotoxicology

Neurotoxicology

Methylmercury and nutrition: adult effects of fetal exposure in experimental models.

Human exposure to the life-span developmental neurotoxicant, methylmercury (MeHg), is primarily via the consumption of fish or marine mammals. Fish are also excellent sources of important nutrients, including selenium and n-3 polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA). Laboratory models of developmental MeHg exposure can be employed to assess the roles of nutrients and MeHg and to identify potential mechanisms of action if the appropriate exposure measures are used. When maternal exposure is protracted, relationships between daily intake and brain mercury are consistent and orderly across species, even when large differences in blood:brain ratios exist. It is well established that low-level developmental MeHg produces sensory deficits. Recent studies also show that perseveration in reversal-learning tasks occurs after gestational exposures that produce low micromolar concentrations in the brain. A no-effect level has not been identified for this effect. These exposures do not affect the acquisition or performance of discrimination learning, set shifting (extradimensional shift), or memory. Reversal-learning deficits may be related to enhanced impact of reinforcers as measured using progressive ratio reinforcement schedules, an effect that could result in perseveration. Also reported is enhanced sensitivity to dopamine reuptake inhibitors and diminished sensitivity to pentobarbital, a GABA(A) agonist. Diets rich in PUFAs or selenium do not protect against MeHg's effects on reversal learning but, by themselves, may diminish variability in performance, enhance attention or psychomotor function and may confer some protection against age-related deficits in these areas. It is hypothesized that altered reward processing, dopamine and GABAergic neurotransmitter systems, and cortical regions associated with choice and perseveration are especially sensitive to developmental MeHg at low exposure levels. Human testing for MeHg's neurotoxicity should emphasize these behavioral domains.

CognitiveConstruct

RewardProcessing

10.1007/s00429-008-0191-3

Brain structure & function

Brain Struct Funct

Noradrenergic transmission in the extended amygdala: role in increased drug-seeking and relapse during protracted drug abstinence.

Studies reviewed here implicate the extended amygdala in the negative affective states and increased drug-seeking that occur during protracted abstinence from chronic drug exposure. Norepinephrine (NE) and corticotropin-releasing factor (CRF) signaling in the extended amygdala, including the bed nucleus of the stria terminalis, shell of the nucleus accumbens, and central nucleus of the amygdala, are generally involved in behavioral responses to environmental and internal stressors. Hyperactivity of stress response systems during addiction drives many negative components of drug abstinence. In particular, NE signaling from the nucleus tractus solitarius (NTS) to the extended amygdala, along with increased CRF transmission within the extended amygdala, are critical for the aversiveness of acute opiate withdrawal as well as stress-induced relapse of drug-seeking for opiates, cocaine, ethanol, and nicotine. NE and CRF transmission in the extended amygdala are also implicated in the increased anxiety that occurs during prolonged abstinence from chronic opiates, cocaine, ethanol, and cannabinoids. Many of these stress-associated behaviors are reversed by NE or CRF antagonists given systemically or locally within the extended amygdala. Finally, increased Fos activation in the extended amygdala and NTS is associated with the enhanced preference for drugs and decreased preference for natural rewards observed during protracted abstinence from opiates and cocaine, indicating that these areas are involved in the altered reward processing associated with addiction. Together, these findings suggest that involvement of the extended amygdala and its noradrenergic afferents in anxiety, stress-induced relapse, and altered reward processing reflects a common function for these circuits in stress modulation of drug-seeking.

CognitiveConstruct

RewardProcessing

10.1093/schbul/sbn092

Schizophrenia bulletin

Schizophr Bull

Emotion, motivation, and reward processing in schizophrenia spectrum disorders: what we know and where we need to go.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2008.06.019

NeuroImage

Neuroimage

Catechol-O-methyltransferase val158met genotype influences neural processing of reward anticipation.

Reward processing depends critically on dopaminergic neurotransmission in the ventral striatum. The common polymorphism val(158)met of catechol-O-methyltransferase (COMT) accounts for significant interindividual variations in dopamine (DA) degradation, although the direct effect of COMT on striatal DA might be limited. Using fMRI we assessed the influence of COMT val(158)met genotype on brain activations elicited by the anticipation of monetary gains and losses in forty-four healthy volunteers. We found that the met(158) allele, which is presumably linked to higher synaptic DA levels, was associated with higher responses in ventral striatum to loss incentives. There was a linear relationship between the number of met(158) alleles and ventral striatal activity. Furthermore, we observed a similar gene-dose effect in the anterior temporal cortex, a region that has been linked to the coupling of sensory information with emotional contents. Temporal cortex also showed enhanced connectivity to the ventral striatum during the processing of incentive stimuli. Increased ventral striatal reactivity to loss incentives related to the met(158) allele might contribute to the observed association of the met(158) allele to higher loss aversion behaviour. Current evidence and our results are compatible with an interpretation that construes this effect of COMT genotype on striatal reactivity as a result of a cortico-striatal interaction.

CognitiveConstruct

RewardProcessing

10.2967/jnumed.108.050849

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

J Nucl Med

Opioid receptor PET reveals the psychobiologic correlates of reward processing.

Little is known about the neurobiologic correlates of human personality. On the basis of the key role of the central opioidergic system in addiction and substance abuse, we investigated the relationship between certain personality traits that are supposed to be relevant in addiction and the opioid receptor status in healthy subjects. We investigated 23 healthy male volunteers who were extensively clinically tested to exclude substance abuse. All of the subjects underwent 1 PET scan with the subtype-nonselective opioidergic radioligand 18F-fluoroethyl-diprenorphine under resting conditions without sensory or cognitive stimulation. Subsequently, the subjects were psychologically tested for the personality traits novelty seeking, harm avoidance, reward dependence, and persistence, according to Cloninger's biosocial model of personality. The binding potential (BP) as a parameter of regional cerebral opioid receptor availability was computed by means of the modified Logan plot using the occipital cortex as a reference region. Further imaging data analysis was performed using statistical parametric mapping; after stereotactic normalization, the correlations were calculated between the regional BP and the psychologic scores on a voxel-by-voxel basis. The correlation analysis between personality dimensions and opioid receptor availability showed a significant (P < 0.001) positive correlation between the scores of reward dependence and the BP of the bilateral ventral striatum with nucleus accumbens (z scores, 4.52 and 4.33, respectively). The additionally performed region-of-interest-based correlation analysis yielded correlation coefficients of r = 0.84 and r = 0.81 for the left and right ventral striata, respectively. No further significant correlations were detectable between the other personality dimensions and cerebral opioid receptor binding. In healthy subjects, personality traits, which might be predisposing for addictive behavior, are correlated to the opioidergic neurotransmission in core structures of the human reward system.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2008.05.022

Neuropsychologia

Neuropsychologia

Altered reward processing in the nucleus accumbens and mesial prefrontal cortex of patients with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is known to be associated with altered medial prefrontal activation in response to threatening stimuli and with behavioural deficits in prefrontal functions such as working memory and attention. Given the importance of these areas and processes for decision-making, this functional magnetic resonance imaging study investigated whether decision-making is altered in patients with PTSD. In particular, the neural response to gain and loss feedback was evaluated in a decision-making task in which subjects could maximise their number of points total by learning a particular response pattern. Behaviourally, controls learned the correct response pattern faster than patients. Functionally, patients and controls differed in their neural response to gains, but not in their response to losses. During the processing of gains in the late phase of learning, PTSD patients as compared to controls showed lower activation in the nucleus accumbens and the mesial PFC, critical structures in the reward pathway. This reduced activation was not due to different rates of learning, since it was similarly present in patients with unimpaired learning performance. These findings suggest that positive outcome information lost its salience for patients with PTSD. This may reflect decreasing motivation as the task progressed.

CognitiveConstruct

RewardProcessing

10.1542/peds.2007-1566

Pediatrics

Pediatrics

What's in a smile? Maternal brain responses to infant facial cues.

Our goal was to determine how a mother's brain responds to her own infant's facial expressions, comparing happy, neutral, and sad face affect. In an event-related functional MRI study, 28 first-time mothers were shown novel face images of their own 5- to 10-month-old infant and a matched unknown infant. Sixty unique stimuli from 6 categories (own-happy, own-neutral, own-sad, unknown-happy, unknown-neutral, and unknown-sad) were presented randomly for 2 seconds each, with a variable 2- to 6-second interstimulus interval. Key dopamine-associated reward-processing regions of the brain were activated when mothers viewed their own infant's face compared with an unknown infant's face. These included the ventral tegmental area/substantia nigra regions, the striatum, and frontal lobe regions involved in (1) emotion processing (medial prefrontal, anterior cingulate, and insula cortex), (2) cognition (dorsolateral prefrontal cortex), and (3) motor/behavioral outputs (primary motor area). Happy, but not neutral or sad own-infant faces, activated nigrostriatal brain regions interconnected by dopaminergic neurons, including the substantia nigra and dorsal putamen. A region-of-interest analysis revealed that activation in these regions was related to positive infant affect (happy > neutral > sad) for each own-unknown infant-face contrast. When first-time mothers see their own infant's face, an extensive brain network seems to be activated, wherein affective and cognitive information may be integrated and directed toward motor/behavioral outputs. Dopaminergic reward-related brain regions are activated specifically in response to happy, but not sad, infant faces. Understanding how a mother responds uniquely to her own infant, when smiling or crying, may be the first step in understanding the neural basis of mother-infant attachment.

CognitiveConstruct

RewardProcessing

10.1111/j.1460-9568.2008.06254.x

The European journal of neuroscience

Eur J Neurosci

Juvenile methylphenidate modulates reward-related behaviors and cerebral blood flow by decreasing cortical D3 receptors.

Attention deficit hyperactivity disorder is associated with reduced cortical blood flow that is reversible with exposure to the psychostimulant methylphenidate (MPH). D3 dopamine receptors modulate stimulant-induced changes in blood flow and are associated with reward processing during young adulthood, but their role in the enduring effects of MPH during development is unknown. Rats were given vehicle (VEH) or MPH (2 mg/kg between postnatal days 20-35) and assessed in young adulthood for regional cerebral blood volume (rCBV) after MPH challenge and mRNA expression levels of dopamine receptors. To probe D3 receptor involvement, juvenile subjects were exposed to VEH, MPH, the D3-preferring agonist +/-7-OHDPAT (0.3 mg/kg), the D3 antagonist nafadotride (Naf; 0.05, 0.5 or 5.0 mg/kg) or a Naf (0.05 mg/kg)/MPH combination, and assessed biochemically and behaviorally. Juvenile MPH exposure increased MPH-induced rCBV in the cingulate and medial prefrontal cortex and thalamus in adulthood. Behaviorally, juvenile MPH- or +/-7-OHDPAT-exposed subjects demonstrated an aversion to cocaine-associated environments, which was prevented by juvenile co-treatment with MPH and Naf, or with adult cortical microinjections of +/-7-OHDPAT. Cortical D3 mRNA levels significantly decreased by 23.8 +/- 6.7% in MPH-treated subjects and normalized with combined Naf/MPH treatment, with no change in the other dopamine receptors. Enhanced cortical responsiveness to psychostimulants may occur through a reduction in D3 receptors, which in turn reduces drug-seeking behavior. These data provide evidence for a postnatal sensitive period when juvenile MPH exposure is able to alter cortical development.

CognitiveConstruct

RewardProcessing

10.1126/science.1155577

Science (New York, N.Y.)

Science

Serotonin modulates behavioral reactions to unfairness.

Serotonin (5-HT) has long been implicated in social behavior and impulsivity, but the mechanisms through which it modulates self-control remain unclear. We observed the effects of manipulating 5-HT function on behavior in the ultimatum game, where players must decide whether to accept or reject fair or unfair monetary offers from another player. Participants with depleted 5-HT levels rejected a greater proportion of unfair offers, but not fair offers, without showing changes in mood, fairness judgment, basic reward processing, or response inhibition. Our results suggest that 5-HT plays a critical role in regulating emotion during social decision-making.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.0021-08.2008

The Journal of neuroscience : the official journal of the Society for Neuroscience

J Neurosci

Reward-dependent modulation of neuronal activity in the primate dorsal raphe nucleus.

The dopamine system has been thought to play a central role in guiding behavior based on rewards. Recent pharmacological studies suggest that another monoamine neurotransmitter, serotonin, is also involved in reward processing. To elucidate the functional relationship between serotonin neurons and dopamine neurons, we performed single-unit recording in the dorsal raphe nucleus (DRN), a major source of serotonin, and the substantia nigra pars compacta, a major source of dopamine, while monkeys performed saccade tasks in which the position of the target indicated the size of an upcoming reward. After target onset, but before reward delivery, the activity of many DRN neurons was modulated tonically by the expected reward size with either large- or small-reward preference, whereas putative dopamine neurons had phasic responses and only preferred large rewards. After reward delivery, the activity of DRN neurons was modulated tonically by the received reward size with either large- or small-reward preference, whereas the activity of dopamine neurons was not modulated except after the unexpected reversal of the position-reward contingency. Thus, DRN neurons encode the expected and received rewards, whereas dopamine neurons encode the difference between the expected and received rewards. These results suggest that the DRN, probably including serotonin neurons, signals the reward value associated with the current behavior.

CognitiveConstruct

RewardProcessing

10.1162/jocn.2009.21012

Journal of cognitive neuroscience

J Cogn Neurosci

The lateral and ventromedial prefrontal cortex work as a dynamic integrated system: evidence from FMRI connectivity analysis.

Recent functional magnetic resonance imaging (fMRI) investigations of the interaction between cognition and reward processing have found that the lateral prefrontal cortex (PFC) areas are preferentially activated to both increasing cognitive demand and reward level. Conversely, ventromedial PFC (VMPFC) areas show decreased activation to the same conditions, indicating a possible reciprocal relationship between cognitive and emotional processing regions. We report an fMRI study of a rewarded working memory task, in which we further explore how the relationship between reward and cognitive processing is mediated. We not only assess the integrity of reciprocal neural connections between the lateral PFC and VMPFC brain regions in different experimental contexts but also test whether additional cortical and subcortical regions influence this relationship. Psychophysiological interaction analyses were used as a measure of functional connectivity in order to characterize the influence of both cognitive and motivational variables on connectivity between the lateral PFC and the VMPFC. Psychophysiological interactions revealed negative functional connectivity between the lateral PFC and the VMPFC in the context of high memory load, and high memory load in tandem with a highly motivating context, but not in the context of reward alone. Physiophysiological interactions further indicated that the dorsal anterior cingulate and the caudate nucleus modulate this pathway. These findings provide evidence for a dynamic interplay between lateral PFC and VMPFC regions and are consistent with an emotional gating role for the VMPFC during cognitively demanding tasks. Our findings also support neuropsychological theories of mood disorders, which have long emphasized a dysfunctional relationship between emotion/motivational and cognitive processes in depression.

CognitiveConstruct

RewardProcessing

10.1111/j.1460-9568.2008.06202.x

The European journal of neuroscience

Eur J Neurosci

Medial orbitofrontal cortex codes relative rather than absolute value of financial rewards in humans.

Functional imaging studies in recent years have confirmed the involvement of orbitofrontal cortex (OFC) in human reward processing and have suggested that OFC responses are context-dependent. A seminal electrophysiological experiment in primates taught animals to associate abstract visual stimuli with differently valuable food rewards. Subsequently, pairs of these learned abstract stimuli were presented and firing of OFC neurons to the medium-value stimulus was measured. OFC firing was shown to depend on the relative value context. In this study, we developed a human analogue of this paradigm and scanned subjects using functional magnetic resonance imaging. The analysis compared neuronal responses to two superficially identical events, which differed only in terms of the preceding context. Medial OFC response to the same perceptual stimulus was greater when the stimulus predicted the more valuable of two rewards than when it predicted the less valuable. Additional responses were observed in other components of reward circuitry, the amygdala and ventral striatum. The central finding is consistent with the primate results and suggests that OFC neurons code relative rather than absolute reward value. Amygdala and striatal involvement in coding reward value is also consistent with recent functional imaging data. By using a simpler and less confounded paradigm than many functional imaging studies, we are able to demonstrate that relative financial reward value per se is coded in distinct subregions of an extended reward and decision-making network.

CognitiveConstruct

RewardProcessing

10.1037/0735-7044.122.2.358

Behavioral neuroscience

Behav Neurosci

Real-time dopamine efflux in the nucleus accumbens core during Pavlovian conditioning.

To assess the role of dopamine input to the nucleus accumbens core in anticipatory learning, fast-scan cyclic voltammetry was combined with appetitive Pavlovian conditioning. One group of rats (Paired) received 16 tone-food pairings for at least four daily sessions while the control group (Unpaired) received the same number of unpaired tone and food presentations. Both groups showed transient dopamine responses during food presentation throughout training, confirming dopamine involvement in reward processing. Only the Paired Group, however, showed consistently timed dopamine transients during the 10-s tone presentation. Transients first appeared near the end of the tone period as each animal acquired the tone-food association and then occurred progressively sooner on subsequent sessions. Later sessions also revealed a consistently timed dopamine response soon after food delivery in Paired animals. Collectively, these results implicate phasic dopamine release in the acquisition of Pavlovian learning and also suggest an early dopamine response to the unconditioned stimulus as training continues.

CognitiveConstruct

RewardProcessing

10.1016/j.neuron.2008.03.014

Neuron

Neuron

Methamphetamine induces chronic corticostriatal depression: too much of a bad thing.

Leading theories of drug addiction propose that repeated drug exposure produces a long-lasting homeostatic dysregulation in brain reward processing that is normalized by drug readministration. In this issue of Neuron, Bamford and colleagues describe a novel neurobiological substrate that may contribute to this effect.

CognitiveConstruct

RewardProcessing

10.1177/1368430207088035

Group processes & intergroup relations : GPIR

Group Process Intergroup Relat

Gender Differences in Emotion Regulation: An fMRI Study of Cognitive Reappraisal.

Despite strong popular conceptions of gender differences in emotionality and striking gender differences in the prevalence of disorders thought to involve emotion dysregulation, the literature on the neural bases of emotion regulation is nearly silent regarding gender differences (Gross, 2007; Ochsner & Gross, in press). The purpose of the present study was to address this gap in the literature. Using functional magnetic resonance imaging, we asked male and female participants to use a cognitive emotion regulation strategy (reappraisal) to down-regulate their emotional responses to negatively valenced pictures. Behaviorally, men and women evidenced comparable decreases in negative emotion experience. Neurally, however, gender differences emerged. Compared with women, men showed (a) lesser increases in prefrontal regions that are associated with reappraisal, (b) greater decreases in the amygdala, which is associated with emotional responding, and (c) lesser engagement of ventral striatal regions, which are associated with reward processing. We consider two non-competing explanations for these differences. First, men may expend less effort when using cognitive regulation, perhaps due to greater use of automatic emotion regulation. Second, women may use positive emotions in the service of reappraising negative emotions to a greater degree. We then consider the implications of gender differences in emotion regulation for understanding gender differences in emotional processing in general, and gender differences in affective disorders.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2008.02.011

Neuropsychologia

Neuropsychologia

Electrophysiological evidence of atypical motivation and reward processing in children with attention-deficit hyperactivity disorder.

Behavioral and neurophysiological evidence suggest that attention-deficit hyperactivity disorder (ADHD) is characterized by the impact of abnormal reward prediction error signals carried by the midbrain dopamine system on frontal brain areas that implement cognitive control. To investigate this issue, we recorded the event-related brain potential (ERP) from typical children and children with ADHD as they navigated a "virtual maze" to find monetary rewards, and physically gave them their accumulated rewards halfway through the task and at the end of the experiment. We found that the amplitude of a reward-related ERP component decreased somewhat for typical children after they received their first payment, but increased for children with ADHD following the payment. This result indicates that children with ADHD are unusually sensitive to the salience of reward and suggests that such sensitivity may be mediated in part by the midbrain dopamine system.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroscience.2008.01.046

Neuroscience

Neuroscience

Stereological estimates of dopaminergic, GABAergic and glutamatergic neurons in the ventral tegmental area, substantia nigra and retrorubral field in the rat.

Midbrain dopamine neurons in the ventral tegmental area, substantia nigra and retrorubral field play key roles in reward processing, learning and memory, and movement. Within these midbrain regions and admixed with the dopamine neurons, are also substantial populations of GABAergic neurons that regulate dopamine neuron activity and have projection targets similar to those of dopamine neurons. Additionally, there is a small group of putative glutamatergic neurons within the ventral tegmental area whose function remains unclear. Although dopamine neurons have been intensively studied and quantified, there is little quantitative information regarding the GABAergic and glutamatergic neurons. We therefore used unbiased stereological methods to estimate the number of dopaminergic, GABAergic and glutamatergic cells in these regions in the rat. Neurons were identified using a combination of immunohistochemistry (tyrosine hydroxylase) and in situ hybridization (glutamic acid decarboxylase mRNA and vesicular glutamate transporter 2 mRNA). In substantia nigra pars compacta 29% of cells were glutamic acid decarboxylase mRNA-positive, 58% in the retrorubral field and 35% in the ventral tegmental area. There were further differences in the relative sizes of the GABAergic populations in subnuclei of the ventral tegmental area. Thus, glutamic acid decarboxylase mRNA-positive neurons represented 12% of cells in the interfascicular nucleus, 30% in the parabrachial nucleus, and 45% in the parainterfascicular nucleus. Vesicular glutamate transporter 2 mRNA-positive neurons were present in the ventral tegmental area, but not substantia nigra or retrorubral field. They were mainly confined to the rostro-medial region of the ventral tegmental area, and represented approximately 2-3% of the total neurons counted ( approximately 1600 cells). These results demonstrate that GABAergic and glutamatergic neurons represent large proportions of the neurons in what are traditionally considered as dopamine nuclei and that there are considerable heterogeneities in the proportions of cell types in the different dopaminergic midbrain regions.

CognitiveConstruct

RewardProcessing

10.1038/nrn2333

Nature reviews. Neuroscience

Nat Rev Neurosci

A common neurobiology for pain and pleasure.

Pain and pleasure are powerful motivators of behaviour and have historically been considered opposites. Emerging evidence from the pain and reward research fields points to extensive similarities in the anatomical substrates of painful and pleasant sensations. Recent molecular-imaging and animal studies have demonstrated the important role of the opioid and dopamine systems in modulating both pain and pleasure. Understanding the mutually inhibitory effects that pain and reward processing have on each other, and the neural mechanisms that underpin such modulation, is important for alleviating unnecessary suffering and improving well-being.

CognitiveConstruct

RewardProcessing

10.1162/jocn.2008.20115

Journal of cognitive neuroscience

J Cogn Neurosci

Inefficiency in self-organized attentional switching in the normal aging population is associated with decreased activity in the ventrolateral prefrontal cortex.

Studies of the aging brain have demonstrated that areas of the frontal cortex, along with their associated top-down executive control processes, are particularly prone to the neurodegenerative effects of age. Here, we investigate the effects of aging on brain and behavior using a novel task, which allows us to examine separate components of an individual's chosen strategy during routine problem solving. Our findings reveal that, contrary to previous suggestions of a specific decrease in cognitive flexibility, older participants show no increased level of perseveration to either the recently rewarded object or the recently relevant object category. In line with this lack of perseveration, lateral and medial regions of the orbito-frontal cortex, which are associated with inhibitory control and reward processing, appear to be functionally intact. Instead, a general loss of efficient problem-solving strategy is apparent with a concomitant decrease in neural activity in the ventrolateral prefrontal cortex and the posterior parietal cortex. The dorsolateral prefrontal cortex is also affected during problem solving, but age-related decline within this region appears to occur at a later stage.

CognitiveConstruct

RewardProcessing

10.1016/j.neuron.2008.01.024

Neuron

Neuron

Behavioral and electrophysiological indices of negative affect predict cocaine self-administration.

The motivation to seek cocaine comes in part from a dysregulation of reward processing manifested in dysphoria, or affective withdrawal. Learning is a critical aspect of drug abuse; however, it remains unclear whether drug-associated cues can elicit the emotional withdrawal symptoms that promote cocaine use. Here we report that a cocaine-associated taste cue elicited a conditioned aversive state that was behaviorally and neurophysiologically quantifiable and predicted subsequent cocaine self-administration behavior. Specifically, brief intraoral infusions of a cocaine-predictive flavored saccharin solution elicited aversive orofacial responses that predicted early-session cocaine taking in rats. The expression of aversive taste reactivity also was associated with a shift in the predominant pattern of electrophysiological activity of nucleus accumbens (NAc) neurons from inhibitory to excitatory. The dynamic nature of this conditioned switch in affect and the neural code reveals a mechanism by which cues may exert control over drug self-administration.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.0033-08.2008

The Journal of neuroscience : the official journal of the Society for Neuroscience

J Neurosci

Appetitive motivation predicts the neural response to facial signals of aggression.

The "behavioral approach system" (BAS) (Gray, 1990) has been primarily associated with reward processing and positive affect. However, additional research has demonstrated that the BAS plays a role in aggressive behavior, heightened experience of anger, and increased attention to facial signals of aggression. Using functional magnetic resonance imaging, we show that variation in the BAS trait in healthy participants predicts activation in neural regions implicated in aggression when participants view facial signals of aggression in others. Increased BAS drive (appetitive motivation) was associated with increased amygdala activation and decreased ventral anterior cingulate and ventral striatal activation to facial signals of aggression, relative to sad and neutral expressions. In contrast, increased behavioral inhibition was associated with increased activation in the dorsal anterior cingulate, a region involved in the perception of fear and threat. Our results provide the first demonstration that appetitive motivation constitutes a significant factor governing the function of neural regions implicated in aggression, and have implications for understanding clinical disorders of aggression.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2007.12.063

NeuroImage

Neuroimage

Associations between dopamine D2-receptor binding and cognitive performance indicate functional compartmentalization of the human striatum.

Based on pharmacological, neuroanatomical, and lesion studies in animals, a functional compartmentalization of the striatal complex has been proposed. However, this has not been convincingly demonstrated in human subjects. Most functions ascribed to the striatum have been linked to its dense dopaminergic innervation, from motor control to higher-order brain functions (e.g., cognition), making the dopamine system a suitable probe for striatal function. Limbic striatum, a region involved in reward processing, has recently been implicated also in episodic memory function. Here we examined striatal dopamine D2-receptor binding in 16 healthy subjects using PET and the radioligand [(11)C]raclopride, in relation to cognitive performance. Receptor availability in limbic striatum was related to performance in tests of episodic memory, but not to tests of verbal fluency and general knowledge. By contrast, D2 binding in associative and sensorimotor striatum was less strongly related to episodic memory, but showed associations to the non-episodic tasks. These findings provide biochemical evidence for a functional compartmentalization of human striatum, and serve as a starting point for a more detailed investigation of striatal biomarkers in the normal brain as well as in neurodegenerative disorders.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2007.12.001

Biological psychiatry

Biol Psychiatry

Euthymic patients with bipolar disorder show decreased reward learning in a probabilistic reward task.

Bipolar disorder (BPD) features cycling mood states ranging from depression to mania with intermittent phases of euthymia. Bipolar disorder subjects often show excessive goal-directed and pleasure-seeking behavior during manic episodes and reduced hedonic capacity during depressive episodes, indicating that BPD might involve altered reward processing. Our goal was to test the hypothesis that BPD is characterized by impairments in adjusting behavior as a function of prior reinforcement history, particularly in the presence of residual anhedonic symptoms. Eighteen medicated BPD subjects and 25 demographically matched comparison subjects performed a probabilistic reward task. To identify putative dysfunctions in reward processing irrespective of mood state, primary analyses focused on euthymic BPD subjects (n = 13). With signal-detection methodologies, response bias toward a more frequently rewarded stimulus was used to objectively assess the participants' propensity to modulate behavior as a function of reinforcement history. Relative to comparison subjects, euthymic BPD subjects showed a reduced and delayed acquisition of response bias toward the more frequently rewarded stimulus, which was partially due to increased sensitivity to single rewards of the disadvantageous stimulus. Analyses considering the entire BPD sample revealed that reduced reward learning correlated with self-reported anhedonic symptoms, even after adjusting for residual manic and anxious symptoms and general distress. The present study provides preliminary evidence indicating that BPD, even during euthymic states, is characterized by dysfunctional reward learning in situations requiring integration of reinforcement information over time and thus offers initial insights about the potential source of dysfunctional reward processing in this disorder.

CognitiveConstruct

RewardProcessing

10.3758/cabn.7.4.309

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Regions of the MPFC differentially tuned to social and nonsocial affective evaluation.

The medial prefrontal cortex (MPFC) reliably activates in social cognition and reward tasks. This study locates distinct areas for each. Participants made evaluative (positive/negative) or social (person/not a person) judgments of pictured positive or negative people and objects in a slow event-related design. Activity in an anterior rostral region (arMPFC) was significantly greater for positive than for negative persons but did not show a valence effect for objects, and this was true regardless of the judgment task. This suggests that the arMPFC is tuned to social valence. Interestingly, however, no regions of the MPFC were found to be responsive to social information independently of valence. A region-of-interest analysis of the para-anterior cingulate cortex (pACC), previously implicated in reward processing, demonstrated sensitivity to the valence of all stimuli, whether persons or objects, across tasks. Affective evaluation may be a general function of the MPFC, with some regions being tuned to more specific domains of information (e.g., social) than are others.

CognitiveConstruct

RewardProcessing

10.1097/MED.0b013e3282f3f4b1

Current opinion in endocrinology, diabetes, and obesity

Curr Opin Endocrinol Diabetes Obes

Peptide YY.

This review discusses recent studies examining the effects of peptide YY on energy homeostasis, highlights the emerging hedonic effects of peptide YY and evaluates the therapeutic potential of the peptide YY system. A role for exogenous PYY3-36 as an anorectic agent in obese humans and rodents has been established and weight loss effects demonstrated in obese rodents. New lines of evidence support a role for endogenous peptide YY in regulating energy homeostasis. The NPY-Y2 receptor mediates the anorectic actions of PYY3-36 with rodent studies implicating the hypothalamus, vagus and brainstem as key target sites. Functional imaging in humans has confirmed that PYY3-36 activates brainstem and hypothalamic regions. The greatest effects, however, were observed within the orbitofrontal cortex, a brain region involved in reward processing. Further evidence for a hedonic role for PYY3-36 is supported by rodent studies showing that PYY3-36 decreases the motivation to seek high-fat food. Rodent studies using selective Y2 agonists and strategies combining PYY3-36/Y2 agonists with other anorectic agents have revealed increased anorectic and weight-reducing effects. Peptide YY plays a role in the integrative regulation of metabolism. The emerging hedonic effects of peptide YY together with the weight-reducing effects observed in obese rodents suggest that targeting the peptide YY system may offer a therapeutic strategy for obesity.

CognitiveConstruct

RewardProcessing

10.1016/j.jpsychires.2007.10.008

Journal of psychiatric research

J Psychiatr Res

Probing reward function in posttraumatic stress disorder: expectancy and satisfaction with monetary gains and losses.

Posttraumatic stress disorder (PTSD) may be associated with dysfunctional reward processing. The present study assessed for such dysfunction in both the expectancy and outcome phases of reward processing. Male Vietnam veterans with (n=15) and without (n=11) combat-related PTSD were administered a wheel of fortune-type gambling task. Self-reported ratings of expectancy and satisfaction were collected respectively before and after each experience of monetary gain or loss. PTSD participants reported both lower expectancy of reward and lower satisfaction with reward when it was received. The latter result was manifest in a failure of PTSD participants to show the greater satisfaction that normally accompanies rewards received under conditions of low expectancy. These results suggest reward function impairment in PTSD related to expectancy, satisfaction, and the expectancy-satisfaction relationship.

CognitiveConstruct

RewardProcessing

10.1176/appi.ajp.2007.07040575

The American journal of psychiatry

Am J Psychiatry

Altered reward processing in women recovered from anorexia nervosa.

Individuals with anorexia nervosa are known to be ascetic and able to sustain self-denial of food as well as most comforts and pleasures in life. Building on previous findings of altered striatal dopamine binding in anorexia nervosa, the authors sought to assess the response of the anterior ventral striatum to reward and loss in this disorder. Striatal responses to a simple monetary reward task were investigated using event-related functional magnetic resonance imaging. To avoid the confounding effects of malnutrition, the authors compared 13 healthy comparison women and 13 women who had recovered from restricting-type anorexia nervosa and had 1 year of normal weight and regular menstrual cycles, without binge eating or purging. Recovered women showed greater hemodynamic activation in the caudate than comparison women. Only the recovered women showed a significant positive relationship between trait anxiety and the percentage change in hemodynamic signal in the caudate during either wins or losses. In contrast, in the anterior ventral striatum, comparison women distinguished positive and negative feedback, whereas recovered women had similar responses to both conditions. Individuals who have recovered from anorexia nervosa may have difficulties in differentiating positive and negative feedback. The exaggerated activation of the caudate, a region involved in linking action to outcome, may constitute an attempt at "strategic" (as opposed to hedonic) means of responding to reward stimuli. The authors hypothesize that individuals with anorexia nervosa have an imbalance in information processing, with impaired ability to identify the emotional significance of a stimulus but increased traffic in neurocircuits concerned with planning and consequences.

CognitiveConstruct

RewardProcessing

10.1097/DBP.0b013e31811430db

Journal of developmental and behavioral pediatrics : JDBP

J Dev Behav Pediatr

Neurocognitive correlates of problem behavior in environmentally at-risk adolescents.

This study prospectively examines the correlation between neurocognitive (NC) functioning and problem behavior in early adolescence. As part of a longitudinal study, African American urban youths of lower socioeconomic status, mean age 12.1 years (SD=1.2, n=111), were administered a battery of 16 NC tasks assessing eight NC systems (two tasks per system) including four systems primarily associated with frontal cortex and four primarily associated with nonfrontal cortex. The former systems included (1) executive cognitive functioning (ECF), (2) cognitive control, (3) working memory, and (4) reward processing. The latter systems included (5) receptive language, (6) spatial cognition, (7) visual cognition, and (8) memory. The Teacher's Report Form of the Achenbach System of Empirically Based Assessment was performed approximately at the same age that the NC assessments were performed. Bivariate correlations were calculated between the eight NC system composite scores and the externalizing scores. Significant negative relationships were found between ECF and receptive language ability and externalizing behavior. Further analyses, using linear regression, showed that receptive language was more predictive of externalizing behavior than ECF. Based on these results we conclude that (1) NC functioning, specifically in ECF and in receptive language systems, was associated with adolescent problem behavior and (2) receptive language was more strongly associated with problem behavior than ECF.

CognitiveConstruct

RewardProcessing

10.1126/science.1145876

Science (New York, N.Y.)

Science

Social comparison affects reward-related brain activity in the human ventral striatum.

Whether social comparison affects individual well-being is of central importance for understanding behavior in any social environment. Traditional economic theories focus on the role of absolute rewards, whereas behavioral evidence suggests that social comparisons influence well-being and decisions. We investigated the impact of social comparisons on reward-related brain activity using functional magnetic resonance imaging (fMRI). While being scanned in two adjacent MRI scanners, pairs of subjects had to simultaneously perform a simple estimation task that entailed monetary rewards for correct answers. We show that a variation in the comparison subject's payment affects blood oxygenation level-dependent responses in the ventral striatum. Our results provide neurophysiological evidence for the importance of social comparison on reward processing in the human brain.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2007.09.044

NeuroImage

Neuroimage

Reward anticipation and outcomes in adult males with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) has been suggested to involve deficits in reward processing. We used functional magnetic resonance imaging (fMRI) to compare the neural responses to reward anticipation and outcomes in 10 adults with ADHD and 10 controls as they played a monetary incentive delay task. Adults with ADHD were unmedicated, and groups were matched for age, verbal IQ and smoking habits. Adults with ADHD showed decreased activation in the ventral striatum during the anticipation of gain, but increased activation of the orbitofrontal cortex in response to gain outcomes. Ventral striatal activation in adults with ADHD during gain anticipation was negatively correlated with self-rated symptoms of hyperactivity and impulsivity. These findings suggest that male adults with ADHD show neural signs of abnormal reward processing. Future studies will have to investigate whether these dysfunctional patterns might be normalized by treatment.

CognitiveConstruct

RewardProcessing

Neuro endocrinology letters

Neuro Endocrinol Lett

Economic decision-making in the ultimatum game by smokers.

No study to date compared degrees of inequity aversion in economic decision-making in the ultimatum game between non-addictive and addictive reinforcers. The comparison is potentially important in neuroeconomics and reinforcement learning theory of addiction. We compared the degrees of inequity aversion in the ultimatum game between money and cigarettes in habitual smokers. Smokers avoided inequity in the ultimatum game more dramatically for money than for cigarettes; i.e., there was a "domain effect" in decision-making in the ultimatum game. Reward-processing neural activities in the brain for non-addictive and addictive reinforcers may be distinct and the insula activation due to cue-induced craving may conflict with unfair offer-induced insula activation. Future studies in neuroeconomics of addiction should employ game-theoretic decision tasks for elucidating reinforcement learning processes in dopaminergic neural circuits.

CognitiveConstruct

RewardProcessing

10.1038/nrn2234

Nature reviews. Neuroscience

Nat Rev Neurosci

Synaptic plasticity and addiction.

Addiction is caused, in part, by powerful and long-lasting memories of the drug experience. Relapse caused by exposure to cues associated with the drug experience is a major clinical problem that contributes to the persistence of addiction. Here we present the accumulated evidence that drugs of abuse can hijack synaptic plasticity mechanisms in key brain circuits, most importantly in the mesolimbic dopamine system, which is central to reward processing in the brain. Reversing or preventing these drug-induced synaptic modifications may prove beneficial in the treatment of one of society's most intractable health problems.

CognitiveConstruct

RewardProcessing

10.1586/14737175.7.10.1337

Expert review of neurotherapeutics

Expert Rev Neurother

Functional MRI in ADHD: a systematic literature review.

Functional MRI (fMRI) research in attention-deficit/hyperactivity disorder (ADHD) is a fast developing and very complex field. Every study appears to show differences in patterns of brain activation between cases and controls, but the interpretation of such differences is not as straightforward as it may seem. We present here a systematic review of the fMRI literature in ADHD; areas covered include executive functions, reward processing, the effects of methylphenidate, comorbidity and spontaneous brain activity in the resting state. To facilitate the interpretation of research in this area, we discuss important conceptual issues, such as the need to take group differences in performance into account or to consider the role of errors. We present common themes that emerge from these studies and we discuss possible reasons for the many discrepancies that were observed. Finally, based on existing literature and current advancements in fMRI research, we discuss the role that fMRI could play in the future as a diagnostic tool or in treatment outcome predictions, and we make predictions for the future directions of research in this field.

CognitiveConstruct

RewardProcessing

10.1007/s00213-007-0957-y

Psychopharmacology

Psychopharmacology (Berl)

Single dose of a dopamine agonist impairs reinforcement learning in humans: behavioral evidence from a laboratory-based measure of reward responsiveness.

The dopaminergic system, particularly D2-like dopamine receptors, has been strongly implicated in reward processing. Animal studies have emphasized the role of phasic dopamine (DA) signaling in reward-related learning, but these processes remain largely unexplored in humans. To evaluate the effect of a single, low dose of a D2/D3 agonist--pramipexole--on reinforcement learning in healthy adults. Based on prior evidence indicating that low doses of DA agonists decrease phasic DA release through autoreceptor stimulation, we hypothesized that 0.5 mg of pramipexole would impair reward learning due to presynaptic mechanisms. Using a double-blind design, a single 0.5-mg dose of pramipexole or placebo was administered to 32 healthy volunteers, who performed a probabilistic reward task involving a differential reinforcement schedule as well as various control tasks. As hypothesized, response bias toward the more frequently rewarded stimulus was impaired in the pramipexole group, even after adjusting for transient adverse effects. In addition, the pramipexole group showed reaction time and motor speed slowing and increased negative affect; however, when adverse physical side effects were considered, group differences in motor speed and negative affect disappeared. These findings show that a single low dose of pramipexole impaired the acquisition of reward-related behavior in healthy participants, and they are consistent with prior evidence suggesting that phasic DA signaling is required to reinforce actions leading to reward. The potential implications of the present findings to psychiatric conditions, including depression and impulse control disorders related to addiction, are discussed.

CognitiveConstruct

RewardProcessing

10.1038/sj.mp.4002086

Molecular psychiatry

Mol Psychiatry

Genetic variation in components of dopamine neurotransmission impacts ventral striatal reactivity associated with impulsivity.

Individual differences in traits such as impulsivity involve high reward sensitivity and are associated with risk for substance use disorders. The ventral striatum (VS) has been widely implicated in reward processing, and individual differences in its function are linked to these disorders. Dopamine (DA) plays a critical role in reward processing and is a potent neuromodulator of VS reactivity. Moreover, altered DA signaling has been associated with normal and pathological reward-related behaviors. Functional polymorphisms in DA-related genes represent an important source of variability in DA function that may subsequently impact VS reactivity and associated reward-related behaviors. Using an imaging genetics approach, we examined the modulatory effects of common, putatively functional DA-related polymorphisms on reward-related VS reactivity associated with self-reported impulsivity. Genetic variants associated with relatively increased striatal DA release (DRD2 -141C deletion) and availability (DAT1 9-repeat), as well as diminished inhibitory postsynaptic DA effects (DRD2 -141C deletion and DRD4 7-repeat), predicted 9-12% of the interindividual variability in reward-related VS reactivity. In contrast, genetic variation directly affecting DA signaling only in the prefrontal cortex (COMT Val158Met) was not associated with variability in VS reactivity. Our results highlight an important role for genetic polymorphisms affecting striatal DA neurotransmission in mediating interindividual differences in reward-related VS reactivity. They further suggest that altered VS reactivity may represent a key neurobiological pathway through which these polymorphisms contribute to variability in behavioral impulsivity and related risk for substance use disorders.

CognitiveConstruct

RewardProcessing

10.1196/annals.1401.029

Annals of the New York Academy of Sciences

Ann N Y Acad Sci

Orbitofrontal cortex function and structure in depression.

The orbitofrontal cortex (OFC) has been implicated in the pathophysiology of major depression by evidence obtained using neuroimaging, neuropathologic, and lesion analysis techniques. The abnormalities revealed by these techniques show a regional specificity, and suggest that some OFC regions which appear cytoarchitectonically distinct also are functionally distinct with respect to mood regulation. For example, the severity of depression correlates inversely with physiological activity in parts of the posterior lateral and medial OFC, consistent with evidence that dysfunction of the OFC associated with cerebrovascular lesions increases the vulnerability for developing the major depressive syndrome. The posterior lateral and medial OFC function may also be impaired in individuals who develop primary mood disorders, as these patients show grey-matter volumetric reductions, histopathologic abnormalities, and altered hemodynamic responses to emotionally valenced stimuli, probabilistic reversal learning, and reward processing. In contrast, physiological activity in the anteromedial OFC situated in the ventromedial frontal polar cortex increases during the depressed versus the remitted phases of major depressive disorder to an extent that is positively correlated with the severity of depression. Effective antidepressant treatment is associated with a reduction in activity in this region. Taken together these data are compatible with evidence from studies in experimental animals indicating that some orbitofrontal and medial prefrontal cortex regions function to inhibit, while others function to enhance, emotional expression. Alterations in the functional balance between these regions and the circuits they form with anatomically related areas of the temporal lobe, striatum, thalamus, and brain stem thus may underlie the pathophysiology of mood disorders, such as major depression.

CognitiveConstruct

RewardProcessing

10.1111/j.1469-8986.2007.00594.x

Psychophysiology

Psychophysiology

Dissociation of neural regions associated with anticipatory versus consummatory phases of incentive processing.

Incentive delay tasks implicate the striatum and medial frontal cortex in reward processing. However, prior studies delivered more rewards than penalties, possibly leading to unwanted differences in signal-to-noise ratio. Also, whether particular brain regions are specifically involved in anticipation or consumption is unclear. We used a task featuring balanced incentive delivery and an analytic strategy designed to identify activity specific to anticipation or consumption. Reaction time data in two independent samples (n=13 and n=8) confirmed motivated responding. Functional magnetic resonance imaging revealed regions activated by anticipation (anterior cingulate) versus consumption (orbital and medial frontal cortex). Ventral striatum was active during reward anticipation but not significantly more so than during consumption. Although the study features several methodological improvements and helps clarify the neural basis of incentive processing, replications in larger samples are needed.

CognitiveConstruct

RewardProcessing

10.1196/annals.1401.021

Annals of the New York Academy of Sciences

Ann N Y Acad Sci

Orbitofrontal cortex and amygdala contributions to affect and action in primates.

The amygdala and orbitofrontal cortex (OFC) work together as part of the neural circuitry guiding goal-directed behavior. This chapter explores the way in which the amygdala and OFC contribute to emotion and reward processing in macaque monkeys, taking into account recent methodological and conceptual advances. Although direct functional interaction of the amygdala and OFC is necessary for some types of stimulus-reward associations, it is not necessary for others. Both regions contribute to the expression of defensive responses to a potential predator. Contrary to the prevailing view, the amygdala and OFC make distinct contributions to emotional responses and reward processing.

CognitiveConstruct

RewardProcessing

10.1017/s1092852900021490

CNS spectrums

CNS Spectr

Opioids: from physical pain to the pain of social isolation.

The opioid systems play an important role in mediating both physical pain and negative affects (eg, the pain of social isolation). From an evolutionary perspective, it is not surprising that the neurocircuitry and neurochemistry of physical pain would overlap with that involved in complex social emotions. Exposure to trauma as well as a range of gene variants in the opioid system may be associated with alterations in opioid systems function, with changes in reward processing, and with vulnerability to substance abuse. A role for interventions with opioid agents in depression and anxiety disorders has been suggested.

CognitiveConstruct

RewardProcessing

10.1196/annals.1412.007

Annals of the New York Academy of Sciences

Ann N Y Acad Sci

Hormonal and genetic influences on processing reward and social information.

Social neuroscience is an emerging interdisciplinary field that combines tools from cognitive, cellular, and molecular neuroscience to understand the neural mechanisms underlying human interactions, emphasizing the complementary nature of different organization levels in the social and biological domains. Previous studies focused on the molecular/neuronal substrates of a variety of complex behaviors, such as parental behavior and pair bonding. Less is known about the various factors influencing interindividual differences in reward processing and decision making in social contexts, both relying upon the dopaminergic system. This review concerns (1) basic electrophysiological findings and recent neuroimaging findings showing that reward processing and social interaction processes share common neural substrates and (2) genetic and hormonal influences on these processes. Recent research combining molecular genetics, endocrinology, and neuroimaging demonstrated that variations in dopamine-related genes and in hormone levels affect the physiological properties of the dopaminergic system in nonhuman primates and modulate the processing of reward and social information in humans. These findings are important because they indicate the neural influence of genes conferring vulnerability to develop neuropathologies such as drug addiction and pathological gambling. Taken together, the reviewed data start to unveil the relationships between genes, hormones, and the functioning of the reward system, as well as decision making in social contexts, and provide a link between molecular, cellular, and social cognitive levels in humans.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2007.07.016

Neuropsychologia

Neuropsychologia

Human oscillatory activity associated to reward processing in a gambling task.

Previous event-related brain potential (ERP) studies have identified a medial frontal negativity (MFN) in response to negative feedback or monetary losses. In contrast, no EEG correlates have been identified related to the processing of monetary gains or positive feedback. This result is puzzling considering the large number of brain regions involved in the processing of rewards. In the present study we used a gambling task to investigate this issue with trial-by-trial wavelet-based time-frequency analysis of the electroencephalographic signal recorded non-invasively in healthy humans. Using this analysis a mediofrontal oscillatory component in the beta range was identified which was associated to monetary gains. In addition, standard time-domain ERP analysis showed an MFN for losses that was associated with an increase in theta power in the time-frequency analysis. We propose that the reward-related beta oscillatory activity signifies the functional coupling of distributed brain regions involved in reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2007.07.029

NeuroImage

Neuroimage

Tit-for-tat: the neural basis of reactive aggression.

Aggressive behavior is a basic form of human social interaction, yet little is known about its neural substrates. We used a laboratory task to investigate the neural correlates of reactive aggression using functional magnetic resonance imaging. The task is disguised as a reaction-time competition between the subject and two opponents and entitles the winner to punish the loser. It seeks to elicit aggression by provocation of the subject. As each single trial in this task is separated into a decision phase, during which the severity of the prospective punishment of the opponent is set, and an outcome phase, during which the actual punishment is applied or received, the paradigm enables us to analyze the neural events during each of these phases. Specific neural responses in areas related to negative affect, cognitive control and reward processing provide additional information about the cognitive, emotional and motivational processes underlying reactive aggressive behavior and afford us with the possibility to test and expand theories on aggression such as the General Aggression Model.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2007.06.038

NeuroImage

Neuroimage

Anticipation of novelty recruits reward system and hippocampus while promoting recollection.

The dopaminergic midbrain, which comprises the substantia nigra and ventral tegmental area (SN/VTA), plays a central role in reward processing. This region is also activated by novel stimuli, raising the possibility that novelty and reward have shared functional properties. It is currently unclear whether functional aspects of reward processing in the SN/VTA, namely, activation by unexpected rewards and cues that predict reward, also characterize novelty processing. To address this question, we conducted an fMRI experiment during which subjects viewed symbolic cues that predicted either novel or familiar images of scenes with 75% validity. We show that SN/VTA was activated by cues predicting novel images as well as by unexpected novel images that followed familiarity-predictive cues, an 'unexpected novelty' response. The hippocampus, a region implicated in detecting and encoding novel stimuli, showed an anticipatory novelty response but differed from the response profile of SN/VTA in responding at outcome to expected and 'unexpected' novelty. In a behavioral extension of the experiment, recollection increased relative to familiarity when comparing delayed recognition memory for anticipated novel stimuli with unexpected novel stimuli. These data reveal commonalities in SN/VTA responses to anticipating reward and anticipating novel stimuli. We suggest that this anticipatory response codes a motivational exploratory novelty signal that, together with anticipatory activation of the hippocampus, leads to enhanced encoding of novel events. In more general terms, the data suggest that dopaminergic processing of novelty might be important in driving exploration of new environments.

CognitiveConstruct

RewardProcessing

10.1073/pnas.0706583104

Proceedings of the National Academy of Sciences of the United States of America

Proc Natl Acad Sci U S A

Genetic modulation of cognitive flexibility and socioemotional behavior in rhesus monkeys.

In human and nonhuman primates, structural variants of the gene encoding the serotonin transporter [5-hydroxytryptamine transporter (5-HTT)] affect the transcription and functional efficacy of 5-HTT. Prior work has shown that structural variants differentially affect function of the amygdala and ventromedial prefrontal cortex (VMPFC), regions important for the regulation and expression of emotion. However, relatively little is known about the impact of 5-HTT allelic variants on cognition. To address this question, we tested rhesus monkeys carrying orthologous structural variants of 5-HTT on a battery of tasks that assess cognitive flexibility, reward processing, and emotion. Here we show that rhesus monkeys carrying two copies of the short allele (SS) of the rhesus 5-HTT gene-linked polymorphic region (rh5-HTTLPR) show significantly reduced cognitive flexibility as measured by two tasks in the battery: object discrimination reversal learning and instrumental extinction. Monkeys with the SS genotype also displayed alterations in socioemotional behavior. Genotype variation was not related to visual perceptual abilities, valuation of food rewards, or the ability to express a wide range of defensive responses. Although emotional alterations associated with 5-HTT variation have been described as the primary phenotype, the present study reports differences in at least one type of cognitive flexibility, which has not been described previously. Because behaviors modulated by the 5-HTTLPR are a subset of those dependent on the VMPFC, analysis of structural and functional correlates of gene variation in this region may inform the nature of the genetic modulation of cognition.

CognitiveConstruct

RewardProcessing

10.1196/annals.1401.019

Annals of the New York Academy of Sciences

Ann N Y Acad Sci

Synergistic and regulatory effects of orbitofrontal cortex on amygdala-dependent appetitive behavior.

This paper will review two avenues of our research in marmosets that have focused on the role of the orbitofrontal cortex (OFC) in amygdala-dependent appetitive behavior. The first demonstrates the important contribution of both the OFC and the amygdala to conditioned reinforcement (CRF). The second reveals the regulatory effects of the OFC on amygdala-dependent autonomic and behavioral arousal in appetitive conditioning. The process of CRF is one way in which an environmental cue can guide emotional behavior. As a consequence of its previous relationship with reward, a cue can take on affective value and reinforce behavior. Lesion studies in marmosets are described that show that CRF is dependent upon both the amygdala and OFC. The synergistic interactions between these structures that have been shown to underlie other aspects of reward processing are then considered with respect to CRF. The results are contrasted with those that show the importance of the OFC in suppressing positive affective responses elicited by the amygdala in response to a conditioned stimulus (CS). Specifically, it will be shown that the OFC is involved in the rapid suppression of conditioned autonomic arousal upon CS withdrawal and in the co-ordination of conditioned autonomic and behavioral responses when adapting to changing reward contingencies. It will be argued that, overall, the OFC plays a critical role in the context-dependent regulation of positive affective responding governed by external cues, in keeping with a role in executive control.

CognitiveConstruct

RewardProcessing

10.1111/j.1601-183X.2007.00344.x

Genes, brain, and behavior

Genes Brain Behav

The utility of behavioral models and modules in molecular analyses of social behavior.

It is extremely difficult to trace the causal pathway relating gene products or molecular pathways to the expression of behavior. This is especially true for social behavior, which being dependent on interactions and communication between individuals is even further removed from molecular-level events. In this review, we discuss how behavioral models can aid molecular analyses of social behavior. Various models of behavior exist, each of which suggest strategies to dissect complex behavior into simpler behavioral 'modules.' The resulting modules are easier to relate to neural processes and thus suggest hypotheses for neural and molecular function. Here we discuss how three different models of behavior have facilitated understanding the molecular bases of aspects of social behavior. We discuss the response threshold model and two different approaches to modeling motivation, the state space model and models of reinforcement and reward processing. The examples we have chosen illustrate how models can generate testable hypotheses for neural and molecular function and also how molecular analyses probe the validity of a model of behavior. We do not champion one model over another; rather, our examples illustrate how modeling and molecular analyses can be synergistic in exploring the molecular bases of social behavior.

CognitiveConstruct

RewardProcessing

10.1093/brain/awm147

Brain : a journal of neurology

Brain

Ageing and early-stage Parkinson's disease affect separable neural mechanisms of mesolimbic reward processing.

The ability to learn stimulus-reward associations on the basis of reward prediction errors critically depends on the mesolimbic dopaminergic system including the dopaminergic midbrain and the ventral striatum. It is known that healthy elderly and patients with Parkinson's disease are less proficient than healthy young adults in learning stimulus-reward contingencies, but it is unclear whether this is due to dysfunctional mesolimbic reward prediction or due to deficiency in processing the rewards per se. We used a well-established event-related fMRI reward-prediction paradigm to address this question. Young adults showed the well-replicated pattern of midbrain and ventral striatal activation for stimuli that predicted monetary reward when compared with stimuli that predicted neutral feedback. Also, as expected, the predicted reward feedback itself did not elicit a mesolimbic response. Healthy elderly subjects and unmedicated early-stage idiopathic Parkinson's disease patients showed the opposite pattern with an absent mesolimbic reward prediction response, but mesolimbic activation to the reward feedback itself. This suggests that the healthy elderly and Parkinson's disease patients were less proficient in learning the predictive value of the reward cues despite preserved mesolimbic processing of reward prediction errors. Parkinson's disease patients additionally displayed a relatively increased response of the anterior cingulate during reward feedback processing and diminished functional connectivity of the midbrain and ventral striatum. Our results are compatible with existing behavioural evidence that both groups exhibit a particularly pronounced deficit in learning from positive feedback and support the view that a tendency to underestimate expected values of reward cues might underlie this deficit. Furthermore, alterations in reward processing in Parkinson's disease extend beyond accelerated ageing effects and include altered connectivity within the mesolimbic system.

CognitiveConstruct

RewardProcessing

10.1100/tsw.2007.122

TheScientificWorldJournal

ScientificWorldJournal

Reward, context, and human behaviour.

Animal models of reward processing have revealed an extensive network of brain areas that process different aspects of reward, from expectation and prediction to calculation of relative value. These results have been confirmed and extended in human neuroimaging to encompass secondary rewards more unique to humans, such as money. The majority of the extant literature covers the brain areas associated with rewards whilst neglecting analysis of the actual behaviours that these rewards generate. This review strives to redress this imbalance by illustrating the importance of looking at the behavioural outcome of rewards and the context in which they are produced. Following a brief review of the literature of reward-related activity in the brain, we examine the effect of reward context on actions. These studies reveal how the presence of reward vs. reward and punishment, or being conscious vs. unconscious of reward-related actions, differentially influence behaviour. The latter finding is of particular importance given the extent to which animal models are used in understanding the reward systems of the human mind. It is clear that further studies are needed to learn about the human reaction to reward in its entirety, including any distinctions between conscious and unconscious behaviours. We propose that studies of reward entail a measure of the animal's (human or nonhuman) knowledge of the reward and knowledge of its own behavioural outcome to achieve that reward.

CognitiveConstruct

RewardProcessing

10.1080/10550490701375285

The American journal on addictions

Am J Addict

An fMRI study of the interaction of stress and cocaine cues on cocaine craving in cocaine-dependent men.

Acute stress is associated with relapse in cocaine addiction, possibly through the activation of craving-related neural circuitry. Neural responses to cocaine cues and acute stress were investigated in an fMRI study. Ten male participants mentally re-enacted personalized scripts about cocaine use and a neutral experience both with and without a stressor present (anticipation of electrical shock). Interaction analysis between script type and stress condition revealed greater activation of the posterior cingulate cortex and of the parietal lobe during the cocaine script in the presence of the stressor. These data suggest that stress may precipitate relapse in cocaine addiction by activating brain areas that mediate reward processing and the attentional and mnemonic bias for drug use reminders.

CognitiveConstruct

RewardProcessing

10.1126/science.1140738

Science (New York, N.Y.)

Science

Neural responses to taxation and voluntary giving reveal motives for charitable donations.

Civil societies function because people pay taxes and make charitable contributions to provide public goods. One possible motive for charitable contributions, called "pure altruism," is satisfied by increases in the public good no matter the source or intent. Another possible motive, "warm glow," is only fulfilled by an individual's own voluntary donations. Consistent with pure altruism, we find that even mandatory, tax-like transfers to a charity elicit neural activity in areas linked to reward processing. Moreover, neural responses to the charity's financial gains predict voluntary giving. However, consistent with warm glow, neural activity further increases when people make transfers voluntarily. Both pure altruism and warm-glow motives appear to determine the hedonic consequences of financial transfers to the public good.

CognitiveConstruct

RewardProcessing

10.1111/j.1467-7687.2007.00600.x

Developmental science

Dev Sci

Socioeconomic gradients predict individual differences in neurocognitive abilities.

Socioeconomic status (SES) is associated with childhood cognitive achievement. In previous research we found that this association shows neural specificity; specifically we found that groups of low and middle SES children differed disproportionately in perisylvian/language and prefrontal/executive abilities relative to other neurocognitive abilities. Here we address several new questions: To what extent does this disparity between groups reflect a gradient of SES-related individual differences in neurocognitive development, as opposed to a more categorical difference? What other neurocognitive systems differ across individuals as a function of SES? Does linguistic ability mediate SES differences in other systems? And how do specific prefrontal/executive subsystems vary with SES? One hundred and fifty healthy, socioeconomically diverse first-graders were administered tasks tapping language, visuospatial skills, memory, working memory, cognitive control, and reward processing. SES explained over 30% of the variance in language, and a smaller but highly significant portion of the variance in most other systems. Statistically mediating factors and possible interventional approaches are discussed.

CognitiveConstruct

RewardProcessing

10.1038/sj.npp.1301467

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Augmented acquisition of cocaine self-administration and altered brain glucose metabolism in adult female but not male rats exposed to a cannabinoid agonist during adolescence.

Marijuana consumption during adolescence has been proposed to be a stepping-stone for adult cocaine addiction. However, experimental evidence for this hypothesis is missing. In this work we chronically injected male and female Wistar rats with either the cannabinoid agonist CP 55,940 (CP; 0.4 mg/kg) or its corresponding vehicle. Adult acquisition (seven 30 min daily sessions) and maintenance (fourteen 2 h daily sessions) of cocaine self-administration (1 mg/kg), food-reinforced operant learning under conditions of normal (ad libitum access to food), and high motivation (food-restriction schedule) were measured. Additionally, brain metabolic activity was analyzed by means of [(18)F]-fluorodeoxyglucose positron emission tomography. During the acquisition phase, female CP-treated rats showed a higher rate of cocaine self-administration as compared to vehicle-treated females and males; no differences were found between both male groups. This effect disappeared in the maintenance phase. Moreover, no differences among groups were evident in the food-reinforced operant task, pointing to the cocaine-specific nature of the effect seen in self-administration rather than a general change in reward processing. Basal brain metabolic activity also changed in CP-treated females when compared to their vehicle-treated counterparts with no differences being found in the males; more specifically we observed a hyper activation of the frontal cortex and a hypo activation of the amygdalo-entorhinal cortex. Our results suggest that a chronic exposure to cannabinoids during adolescence alters the susceptibility to acquire cocaine self-administration, in a sex-specific fashion. This increased susceptibility could be related to the changes in brain metabolic activity induced by cannabinoids during adolescence.

CognitiveConstruct

RewardProcessing

10.1002/mds.21457

Movement disorders : official journal of the Movement Disorder Society

Mov Disord

Controlled study of decision-making and cognitive impairment in Parkinson's disease.

Impulse control disorders (ICD) related to reward-processing dysfunction have been reported in Parkinson's disease (PD). The relationship between clinical markers of limbic dysfunction with demographic variables and cognitive status of PD is incompletely known. Our objective was to further characterize the relationship between limbic and cognitive dysfunction in a representative sample of nondemented PD patients without antecedents of ICD, as assessed by a risk-taking test of decision-making and a comprehensive neuropsychological battery. Prospective, controlled study of 35 nondemented PD patients and 31 matched controls who received the Iowa gambling task (IGT), the Mattis Dementia Rating Scale (MDRS) and verbal fluencies for global cognitive function, the Stroop and digit span tests for executive function, and the Rey Auditory Verbal Learning Test for memory. Compared to controls, PD patients performed significantly worse on the IGT. No clear relationship with demographic variables including dopaminergic treatment and motor response to levodopa (stable or fluctuating) emerged. Performance on the IGT was not related to executive function. In contrast, an inverse relationship was found between the IGT and memory and global cognitive performance, with patients with the better MDRS and memory scores performing significantly worse on the IGT. Our results confirm subclinical dysfunction of the limbic system in nondemented PD patients. Although impaired decision-making appears unrelated to executive dysfunction, patients with the better cognitive status appears more prone to assume risky behaviors.

CognitiveConstruct

RewardProcessing

10.1073/pnas.0702029104

Proceedings of the National Academy of Sciences of the United States of America

Proc Natl Acad Sci U S A

Gene-gene interaction associated with neural reward sensitivity.

Reward processing depends on dopaminergic neurotransmission and is modulated by factors affecting dopamine (DA) reuptake and degradation. We used fMRI and a guessing task sensitive to reward-related activation in the prefrontal cortex and ventral striatum to study how individual variation in genes contributing to DA reuptake [DA transporter (DAT)] and degradation [catechol-o-methyltransferase (COMT)] influences reward processing. Prefrontal activity, evoked by anticipation of reward irrespective of reward probability and magnitude, was COMT genotype-dependent. Volunteers homozygous for the Met allele, associated with lower enzyme activity and presumably greater DA availability, showed larger responses compared with volunteers homozygous for the Val allele. A similar COMT effect was observed in the ventral striatum. As reported previously, the ventral striatum was also found to code gain-related expected value, i.e., the product of reward magnitude and gain probability. Individual differences in ventral striatal sensitivity for value were in part explained by an epistatic gene-gene interaction between COMT and DAT. Although most genotype combinations exhibited the expected activity increase with more likely and larger rewards, two genotype combinations (COMT Met/Met DAT 10R and COMT Val/Val 9R) were associated with blunted ventral striatal responses. In view of a consistent relationship between reduced reward sensitivity and addiction, our findings point to a potential genetic basis for vulnerability to addiction.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.5227-06.2007

The Journal of neuroscience : the official journal of the Society for Neuroscience

J Neurosci

Functional dissociation in frontal and striatal areas for processing of positive and negative reward information.

Reward-seeking behavior depends critically on processing of positive and negative information at various stages such as reward anticipation, outcome monitoring, and choice evaluation. Behavioral and neuropsychological evidence suggests that processing of positive (e.g., gain) and negative (e.g., loss) reward information may be dissociable and individually disrupted. However, it remains uncertain whether different stages of reward processing share certain neural circuitry in frontal and striatal areas, and whether distinct but interactive systems in these areas are recruited for positive and negative reward processing. To explore these issues, we used a monetary decision-making task to investigate the roles of frontal and striatal areas at all three stages of reward processing in the same event-related functional magnetic resonance imaging experiment. Participants were instructed to choose whether to bet or bank a certain number of chips. If they decided to bank or if they lost a bet, they started over betting one chip. If they won a bet, the wager was doubled in the next round. Positive reward anticipation, winning outcome, and evaluation of right choices activated the striatum and medial/middle orbitofrontal cortex, whereas negative reward anticipation, losing outcome, and evaluation of wrong choices activated the lateral orbitofrontal cortex, anterior insula, superior temporal pole, and dorsomedial frontal cortex. These findings suggest that the valence of reward information and counterfactual comparison more strongly predict a functional dissociation in frontal and striatal areas than do various stages of reward processing. These distinct but interactive systems may serve to guide human's reward-seeking behavior.

CognitiveConstruct

RewardProcessing

10.1038/sj.npp.1301408

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression.

Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto-striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system--in which the nucleus accumbens is a key structure--are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression.

CognitiveConstruct

RewardProcessing

10.1196/annals.1390.020

Annals of the New York Academy of Sciences

Ann N Y Acad Sci

Splitting the difference: how does the brain code reward episodes?

Animal research and human brain imaging findings suggest that reward processing involves distinct anticipation and outcome phases. Error terms in popular models of reward learning (such as the temporal difference [TD] model) do not distinguish between the updating of expectations in response to reward cues and outcomes. Thus, correlating a single error term with neural activation assumes recruitment of similar neural substrates at each update. Here, we split the error term to separately model reward prediction and prediction errors, and compare the fit of single versus split error terms to functional magnetic resonance imaging (FMRI) data acquired during a monetary incentive delay task. We speculate and find that while the nucleus accumbens computes gain prediction in response to cues, the mesial prefrontal cortex (MPFC) computes gain prediction errors in response to outcomes. In addition to offering a more comprehensive and anatomically situated view of reward processing, split error terms generate novel predictions about psychiatric symptoms and lesion-induced deficits.

CognitiveConstruct

RewardProcessing

10.1080/09595230601036960

Drug and alcohol review

Drug Alcohol Rev

Imaging stress- and cue-induced drug and alcohol craving: association with relapse and clinical implications.

Stress- and drug-related cues are major factors contributing to high rates of relapse in addictive disorders. Brain imaging studies have begun to identify neural correlates of stress and drug cue-induced craving states. Findings indicate considerable overlap in neural circuits involved in processing stress and drug cues with activity in the corticostriatal limbic circuitry underlying both affective and reward processing. More recent efforts have begun to identify the relationships between neural activity during stress and drug cue exposure and drug relapse outcomes. Findings suggest medial prefrontal, anterior and posterior cingulate, striatal and posterior insula regions to be associated with relapse outcomes. Altered function in these brain regions is associated with stress-induced and drug cue-induced craving states and an increased susceptibility to relapse. Such alterations can serve as markers to identify relapse propensity and a more severe course of addiction. Efficacy of pharmacological and behavioral treatments that specifically target stress and cue-induced craving and arousal responses may also be assessed via alterations in these brain correlates.

CognitiveConstruct

RewardProcessing

10.1007/s00213-007-0741-z

Psychopharmacology

Psychopharmacology (Berl)

Discrete neurochemical coding of distinguishable motivational processes: insights from nucleus accumbens control of feeding.

The idea that nucleus accumbens (Acb) dopamine transmission contributes to the neural mediation of reward, at least in a general sense, has achieved wide acceptance. Nevertheless, debate remains over the precise nature of dopamine's role in reward and even over the nature of reward itself. In the present article, evidence is reviewed from studies of food intake, feeding microstructure, instrumental responding for food reinforcement, and dopamine efflux associated with feeding, which suggests that reward processing in the Acb is best understood as an interaction among distinct processes coded by discrete neurotransmitter systems. In agreement with several theories of Acb dopamine function, it is proposed here that allocation of motor effort in seeking food or food-associated conditioned stimuli can be dissociated from computations relevant to the hedonic evaluation of food during the consummatory act. The former appears to depend upon Acb dopamine transmission and the latter upon striatal opioid peptide release. Moreover, dopamine transmission may play a role in 'stamping in' associations between motor acts and goal attainment and perhaps also neural representations corresponding to rewarding outcomes. Finally, evidence is reviewed that amino acid transmission specifically in the Acb shell acts as a central 'circuit breaker' to flexibly enable or terminate the consummatory act, via descending connections to hypothalamic feeding control systems. The heuristic framework outlined above may help explain why dopamine-compromising manipulations that strongly diminish instrumental goal-seeking behaviors leave consummatory activity relatively unaffected.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2006.11.043

NeuroImage

Neuroimage

Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics.

Alcohol dependence may be associated with dysfunction of mesolimbic circuitry, such that anticipation of nonalcoholic reward fails to activate the ventral striatum, while alcohol-associated cues continue to activate this region. This may lead alcoholics to crave the pharmacological effects of alcohol to a greater extent than other conventional rewards. The present study investigated neural mechanisms underlying these phenomena. 16 detoxified male alcoholics and 16 age-matched healthy volunteers participated in two fMRI paradigms. In the first paradigm, alcohol-associated and affectively neutral pictures were presented, whereas in the second paradigm, a monetary incentive delay task (MID) was performed, in which brain activation during anticipation of monetary gain and loss was examined. For both paradigms, we assessed the association of alcohol craving with neural activation to incentive cues. Detoxified alcoholics showed reduced activation of the ventral striatum during anticipation of monetary gain relative to healthy controls, despite similar performance. However, alcoholics showed increased ventral striatal activation in response to alcohol-associated cues. Reduced activation in the ventral striatum during expectation of monetary reward, and increased activation during presentation of alcohol cues were correlated with alcohol craving in alcoholics, but not healthy controls. These results suggest that mesolimbic activation in alcoholics is biased towards processing of alcohol cues. This might explain why alcoholics find it particularly difficult to focus on conventional reward cues and engage in alternative rewarding activities.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2006.11.034

NeuroImage

Neuroimage

Neural evidence for Reference-dependence in real-market-transactions.

Human decision making has become one of the major research-foci in economics, marketing and in neuroscience. This study integrates perspectives from these disciplines by examining neurophysiological correlates to Reference-dependence of utility evaluations in real market contexts both before and after choice. First, by comparing buying and selling decisions, we observe an activation of the amygdala only in the latter. We interpret this as loss aversion with respect to prior possessions. This finding contributes to the settling of an ongoing fundamental dispute in economic theory by indicating the absence of loss aversion for money in routine transactions. Second, ex post satisfaction statements are accompanied by an activation of the reward processing orbitofrontal cortex, if the evaluation context is framed by a high external reference price instead of a lower internal reference price. This indicates a nonrational Reference-dependence--despite the neoclassical view of a rational Homo Economicus--of satisfaction measures and challenges a central marketing variable.

CognitiveConstruct

RewardProcessing

10.1007/BF03033360

Neurotoxicity research

Neurotox Res

The vulnerability to alcohol and substance abuse in individuals diagnosed with schizophrenia.

Individuals with schizophrenia are at increased risk for developing substance abuse disorders. Here, we consider factors that might elevate their risk for substance abuse. The tendency among schizophrenic individuals to overvalue drug-like rewards and to devalue the potential negative consequences of substance abuse may be a contributing factor to their substance abuse risk. This bias, which may partly reflect the convergence of glutamatergic and dopaminergic input to the limbic striatum, also may contribute to disadvantageous decision-making and other impulsive behavior. This propensity to seek drug-like rewards is augmented by alterations in nicotinic cholinergic, GABAergic, glutamatergic, and cannabinnoid receptor function associated with schizophrenia that increase the abuse liability of low doses of nicotine, ethanol, and perhaps cannabis, and augment the dysphoric effects of higher doses of ethanol and cannabis. The distortions in reward processing and altered response to substances of abuse also increase the likelihood that individuals with schizophrenia will self-medicate their subjective distress with abused substances. The focus on distinctions between motivation and reward with respect to substance abuse risk by schizophrenic patients suggests a need for a reconsideration of the construct of "negative symptoms" for this dually-diagnosed patient group.

CognitiveConstruct

RewardProcessing

10.1136/jnnp.2006.099044

Journal of neurology, neurosurgery, and psychiatry

J Neurol Neurosurg Psychiatry

Enhanced activation of reward mediating prefrontal regions in response to food stimuli in Prader-Willi syndrome.

Individuals with Prader-Willi syndrome (PWS) exhibit severe disturbances in appetite regulation, including delayed meal termination, early return of hunger after a meal, seeking and hoarding food and eating of non-food substances. Brain pathways involved in the control of appetite in humans are thought to include the hypothalamus, frontal cortex (including the orbitofrontal, ventromedial prefrontal, dorsolateral prefrontal and anterior cingulate areas), insula, and limbic and paralimbic areas. We hypothesised that the abnormal appetite in PWS results from aberrant reward processing of food stimuli in these neural pathways. We compared functional MRI blood oxygen level dependent (BOLD) responses while viewing pictures of food in eight adults with PWS and eight normal weight adults after ingestion of an oral glucose load. Subjects with PWS demonstrated significantly greater BOLD activation in the ventromedial prefrontal cortex than controls when viewing food pictures. No significant differences were found in serum insulin, glucose or triglyceride levels between the groups at the time of the scan. Individuals with PWS had an increased BOLD response in the ventromedial prefrontal cortex compared with normal weight controls when viewing pictures of food after an oral glucose load. These findings suggest that an increased reward value for food may underlie the excessive hunger in PWS, and support the significance of the frontal cortex in modulating the response to food in humans. Our findings in the extreme appetite phenotype of PWS support the importance of the neural pathways that guide reward related behaviour in modulating the response to food in humans.

CognitiveConstruct

RewardProcessing

10.1038/sj.npp.1301251

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Prominent burst firing of dopaminergic neurons in the ventral tegmental area during paradoxical sleep.

Dopamine is involved in motivation, memory, and reward processing. However, it is not clear whether the activity of dopamine neurons is related or not to vigilance states. Using unit recordings in unanesthetized head restrained rats we measured the firing pattern of dopamine neurons of the ventral tegmental area across the sleep-wake cycle. We found these cells were activated during paradoxical sleep (PS) via a clear switch to a prominent bursting pattern, which is known to induce large synaptic dopamine release. This activation during PS was similar to the activity measured during the consumption of palatable food. Thus, as it does during waking in response to novelty and reward, dopamine could modulate brain plasticity and thus participate in memory consolidation during PS. By challenging the traditional view that dopamine is the only aminergic group not involved in sleep physiology, this study provides an alternative perspective that may be crucial for understanding the physiological function of PS and dream mentation.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropharm.2006.10.002

Neuropharmacology

Neuropharmacology

Double dissociating effects of sensory stimulation and cocaine on serotonin activity in the occipital and temporal cortices.

Visual cues that become associated with the consumption of psychostimulant drugs energize craving and the intake of the drug by mechanisms of which little is known. In two experiments using in vivo microdialysis in freely moving rats we compared the effects of visual and auditory stimulation with that of cocaine (0, 5, 10, 20mg/kg; i.p.) on the extracellular serotonin (5-HT) activity in the occipital and temporal cortices in relation to behavior. Visual stimulation increased 5-HT in the occipital, but not temporal cortex, parallel to an increase in locomotion. Auditory stimulation decreased 5-HT in the auditory, but not occipital cortex, thus, showing a double dissociated 5-HT response. These data suggest that a locally restricted 5-HT response to sensory stimulation may gate behavioral activity sense-modality selectively. Cocaine affected 5-HT in the occipital cortex and behavioral activity in the same direction as visual stimulation, but in an amplified and prolonged way. In the temporal cortex cocaine also caused an increase in 5-HT. The findings demonstrate common effects of visual stimulation and cocaine on 5-HT activity in the occipital cortex in relation to locomotor activity. The results suggest that concepts of how neutral visual cues become powerful energizers of addiction-related behaviors should be expanded to incorporate not only an acute enhancement of reward processing mechanisms, but, in parallel, also an amplified processing of visual stimuli in the occipital cortex.

CognitiveConstruct

RewardProcessing

10.1111/j.1469-7610.2006.01673.x

Journal of child psychology and psychiatry, and allied disciplines

J Child Psychol Psychiatry

Reward-related decision-making in pediatric major depressive disorder: an fMRI study.

Although reward processing is considered an important part of affective functioning, few studies have investigated reward-related decisions or responses in young people with affective disorders. Depression is postulated to involve decreased activity in reward-related affective systems. Using functional magnetic resonance imaging (fMRI), we examined behavioral and neural responses to reward in young people with depressive disorders using a reward decision-making task. The task involved choices about possible rewards involving varying magnitude and probability of reward. The study design allowed the separation of decision/anticipation and outcome phases of reward processing. Participants were 9-17 years old and had diagnoses of major depressive disorder (MDD), anxiety disorders, or no history of psychiatric disorder. Participants with MDD exhibited less neural response than control participants in reward-related brain areas during both phases of the task. Group differences did not appear to be a function of anxiety. Depressive and anxiety symptoms were associated with activation in reward-related brain areas. Results suggest that depression involves altered reward processing and underscore the need for further investigation of relations among development, affective disorders, and reward processing.

CognitiveConstruct

RewardProcessing

10.1007/978-3-211-45295-0_62

Journal of neural transmission. Supplementum

J Neural Transm Suppl

Placebo effect and dopamine release.

The placebo effect can be encountered in a great variety of medical conditions, but is particularly prominent in pain, depression and Parkinson's disease. It has been shown that placebo responses play a part in the effect of any type of treatment for Parkinson's disease, including drug therapy, deep brain stimulation and dopamine tissue transplantation. Recent studies have demonstrated that the placebo effect in Parkinson's disease is related to the release of substantial amounts of endogenous dopamine in both the dorsal and ventral striatum. As the ventral striatum is involved in reward processing, these observations suggest that the placebo effect may be linked to reward mechanisms. In keeping with this placebo-reward model, most recent experiments have shown activation of the reward circuitry in association with placebo responses in other disorders. In addition, as dopamine is the major neurotransmitter in the reward circuitry, the model predicts that the release of dopamine in the ventral striatum could be involved in mediating placebo responses not only in Parkinson's but also in other medical conditions.

CognitiveConstruct

RewardProcessing

10.1002/mds.21068

Movement disorders : official journal of the Movement Disorder Society

Mov Disord

Body weight in patients with Parkinson's disease.

There is some evidence suggesting that Parkinson's disease (PD) patients exhibit lower body weight when compared to age-matched healthy subjects. Low body mass index (BMI) is correlated with low bone mineral density, both of which are major risk factors for hip fractures. Possible determinants of weight loss in PD patients include hyposmia, impaired hand-mouth coordination, difficulty chewing, dysphagia, intestinal hypomotility, depression, decreased reward processing of dopaminergic mesolimbic regions, nausea, and anorexia as the side effects of medication, and increased energy requirements due to muscular rigidity and involuntary movements. It is unclear whether PD patients in general, or only a subgroup of those affected, definitely show lower BMI in the advanced stages of the disease. We therefore recommend that the body weight of PD patients be monitored monthly as the disease progresses, and that a patient's nutrition should be supplemented with sufficient amounts of vitamin D and calcium to reduce the risk of hip fractures and strengthen bone density. Because meal times may coincide with unpredictable off periods associated with akinesia and impaired hand-mouth coordination, PD patients also need flexible food schedules that accommodate the associated symptoms of this disease.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2006.04.042

Biological psychiatry

Biol Psychiatry

Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder.

Although abnormalities in reward processing have been proposed to underlie attention-deficit/hyperactivity disorder (ADHD), this link has not been tested explicitly with neural probes. This hypothesis was tested by using fMRI to compare neural activity within the striatum in individuals with ADHD and healthy controls during a reward-anticipation task that has been shown previously to produce reliable increases in ventral striatum activity in healthy adults and healthy adolescents. Eleven adolescents with ADHD (5 off medication and 6 medication-naïve) and 11 healthy controls (ages 12-17 y) were included. Groups were matched for age, gender, and intelligence quotient. We found reduced ventral striatal activation in adolescents with ADHD during reward anticipation, relative to healthy controls. Moreover, ventral striatal activation was negatively correlated with parent-rated hyperactive/impulsive symptoms across the entire sample. These findings provide neural evidence that symptoms of ADHD, and impulsivity or hyperactivity in particular, may involve diminished reward anticipation, in addition to commonly observed executive dysfunction.

CognitiveConstruct

RewardProcessing

10.1111/j.1530-0277.2006.00176.x

Alcoholism, clinical and experimental research

Alcohol Clin Exp Res

Glutamate-dopamine cotransmission and reward processing in addiction.

While Dale's principle of "one neuron, one neurotransmitter" has undergone revisions to incorporate evidence of the corelease of atypical neurotransmitters such as neuropeptides, the corelease of classical neurotransmitters has only recently been realized. Surprisingly, numerous studies now indicate that the corelease of neurotransmitters in the mammalian central nervous system is not an obscure and rare phenomenon but is widespread and involves most classical neurotransmitters systems. However, the suggestion that glutamate can be coreleased with dopamine (DA) has remained controversial. Furthermore, glutamate-DA cotransmission has not yet been seriously considered in the context of the neurocircuitry of addiction. If glutamate is in fact coreleased with DA as some evidence now suggests, this may have significant implications for advancing our understanding of the interactive role that these 2 neurotransmitters play in cognitive and reward processes. In this commentary, we review the evidence for and against glutamate as a cotransmitter and discuss the potential role of glutamate-DA corelease in addiction. In particular, we describe a recently proposed model in which coreleased glutamate transmits a temporally precise prediction error signal of reward described by Schultz et al., whereas the function of coreleased DA is to exert prolonged modulatory influences on neuronal activity. In addition, we suggest that as alcohol consumption transitions from recreational use to addiction, there is a corresponding transition in the reward valence signal from better than predicted to worse than predicted.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2006.05.026

Biological psychiatry

Biol Psychiatry

Alterations in reward-related decision making in boys with recent and future depression.

Altered reward processing is postulated to be a feature of depression. Reward processing may be valuable to understanding early-onset depressive disorders, which tend to be chronic and recurrent. Reward-related decision making was examined within a longitudinal study of 221 11-year-old boys, 25 of whom had a depressive disorder at age 10 or 11. Participants completed a behavioral decision-making task involving varying probability and magnitude of obtaining reward. Under conditions involving a high probability of winning, boys with depression failed to distinguish between options involving small or large possible reward. Boys with anxiety or externalizing disorders at age 10 or 11 did not differ from others in their reward-related decisions. Low frequency of choosing the high-probability, large reward option at age 11 predicted depressive disorders, anxiety disorders, and depressive symptoms 1 year later. Furthermore, reward-related decisions predicted later depressive or anxiety disorders even when adjusting for the continuity of such disorders and the presence of concurrent externalizing disorders. Findings are consistent with affective neuroscience models of altered reward processing and diminished positive affect in depression. This study represents a step toward elucidating the motivational and emotional aspects of early-onset depression.

CognitiveConstruct

RewardProcessing

10.1016/j.tins.2006.08.002

Trends in neurosciences

Trends Neurosci

Arousal and reward: a dichotomy in orexin function.

The orexins (or hypocretins) are neuropeptide transmitters made exclusively in hypothalamic neurons that have extensive CNS projections. Previous studies reported that this system is most strongly associated with feeding, arousal and the maintenance of waking. We review here recent studies that reveal a novel and important role for the orexin/hypocretin neuronal system in reward processing and addiction. We propose that the current evidence indicates a dichotomy in orexin function, such that orexin neurons in the lateral hypothalamus regulate reward processing for both food and abused drugs, whereas those in the perifornical and dorsomedial hypothalamus regulate arousal and response to stress. Evidence also indicates roles for lateral hypothalamus orexin neurons and ventral tegmental orexin receptors in reward-based learning and memory.

CognitiveConstruct

RewardProcessing

10.1038/sj.npp.1301182

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

The impact of tryptophan depletion and 5-HTTLPR genotype on passive avoidance and response reversal instrumental learning tasks.

Transient reductions in serotonin levels during tryptophan depletion (TD) are thought to impair reward processing in healthy volunteers, while another facet of the serotonergic system, the serotonin transporter (5-HTTLPR) short allele polymorphism, is implicated in augmented processing of aversive stimuli. We examined the impact and interactions of TD and the serotonin promoter polymorphism genotype on reward and punishment via two forms of instrumental learning: passive avoidance and response reversal. In this study, healthy volunteers (n=35) underwent rapid TD or control procedures and genotyping (n=26) of the 5-HTTLPR for long and short allele variants. In the passive avoidance task, tryptophan-depleted volunteers failed to respond sufficiently to rewarded stimuli compared to the control group. Additionally, long allele homozygous individuals (n=11) were slower to learn to avoid punished stimuli compared to short allele carriers (n=15). TD alone did not produce measurable deficits in probabilistic response reversal errors. However, a significant drug group by genotype interaction was found indicating that in comparison to short allele carriers, tryptophan-depleted individuals homozygous for the long allele failed to appropriately use punishment information to guide responding. These findings extend prior reports of impaired reward processing in TD to include instrumental learning. Furthermore, they demonstrate behavioral differences in responses to punishing stimuli between long allele homozygotes and short allele carriers when serotonin levels are acutely reduced.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.0271-06.2006

The Journal of neuroscience : the official journal of the Society for Neuroscience

J Neurosci

Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning.

The anterior cingulate and orbital cortices and the ventral striatum process different aspects of reward evaluation, whereas the dorsolateral prefrontal cortex and the dorsal striatum are involved in cognitive function. Collectively, these areas are critical to decision making. We mapped the striatal area that receives information about reward evaluation. We also explored the extent to which terminals from reward-related cortical areas converge in the striatum with those from cognitive regions. Using three-dimensional-rendered reconstructions of corticostriatal projection fields along with two-dimensional chartings, we demonstrate the reward and cognitive territories in the primate striatum and show the convergence between these cortical inputs. The results show two labeling patterns: a focal projection field that consists of densely distributed terminal patches, and a diffuse projection consisting of clusters of fibers, extending throughout a wide area of the striatum. Together, these projection fields demonstrate a remarkably large, rostral, reward-related striatal territory that reaches into the dorsal striatum. Fibers from different reward-processing and cognitive cortical areas occupy both separate and converging territories. Furthermore, the diffuse projection may serve a separate integrative function by broadly disseminating general cortical activity. These findings show that the rostral striatum is in a unique position to mediate different aspects of incentive learning. Furthermore, areas of convergence may be particularly sensitive to dopamine modulation during decision making and habit formation.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2006.05.006

International journal of psychophysiology : official journal of the International Organization of Psychophysiology

Int J Psychophysiol

The effect of graded monetary reward on cognitive event-related potentials and behavior in young healthy adults.

Temporal correlates of the brain circuit underlying reward processing in healthy adults remain unclear. The current study investigated the P3 and contingent negative variation (CNV) as putative reward-related temporal markers. The effect of sustained monetary reward on these event-related potentials and on behavior was assessed using a warned reaction-time paradigm in 16 young healthy subjects. Monetary reward (0, 1 and 45 cents) varied across blocks of trials. While the CNV was unaffected by money, P3 amplitude was significantly larger for 45 than the 1 and 0 cent conditions. This effect corresponded to the monotonically positive subjective ratings of interest and excitement on the task (45>1>0). These findings suggest a difference between the P3 and CNV; the P3 is sensitive to the sustained effect of relative reward value, while the CNV does not vary with reward magnitude.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2006.05.009

Neuropsychologia

Neuropsychologia

Brain systems for assessing facial attractiveness.

Attractiveness is a facial attribute that shapes human affiliative behaviours. In a previous study we reported a linear response to facial attractiveness in orbitofrontal cortex (OFC), a region involved in reward processing. There are strong theoretical grounds for the hypothesis that coding stimulus reward value also involves the amygdala. The aim of the present investigation is to address whether the amygdala is also sensitive to reward value in faces, indexed as facial attractiveness. We hypothesized that contrary to the linear effects reported previously in OFC, the amygdala would show a non-linear effect of attractiveness by responding to both high and low attractive faces relative to middle attractive faces. Such a non-linear response would explain previous failures to report an amygdala response to attractiveness. Human subjects underwent fMRI while they were presented with faces that varied in facial attractiveness where the task was either to rate faces for facial attractiveness or for age. Consistent with our hypothesis, right amygdala showed a predicted non-linear response profile with greater responses to highly attractive and unattractive faces compared to middle-ranked faces, independent of task. Distinct patterns of activity were seen across different regions of OFC, with some sectors showing linear effects of attractiveness, others exhibiting a non-linear response profile and still others demonstrating activation only during age judgments. Significant effects were also seen in medial prefrontal and paracingulate cortices, posterior OFC, insula, and superior temporal sulcus during explicit attractiveness judgments. The non-linear response profile of the amygdala is consistent with a role in sensing the value of social stimuli, a function that may also involve specific sectors of the OFC.

CognitiveConstruct

RewardProcessing

10.1037/0735-7044.120.3.744

Behavioral neuroscience

Behav Neurosci

Persistent hunger for sodium makes brain stimulation not so sweet: theoretical comment on Morris et al. (2006).

The rewarding value of a stimulus is not fixed but rather is subjective and can vary with motivational state. M. J. Morris, E. S. Na, A. J. Grippo, and A. K. Johnson (2006) report that generating a prolonged sodium appetite decreases the rewarding value of lateral hypothalamic brain stimulation and sucrose intake. The findings support the idea that a specific motivational state can have strong, nonspecific consequences for reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.neuron.2006.04.008

Neuron

Neuron

Envisioning the reward.

The primary visual cortex (area V1) is for vision. At least, that is what most researchers believe. However, in a recent issue of Science, Shuler and Bear demonstrate a correlate of reward timing in area V1. This surprising result indicates that brain circuits for reward processing are more extensive than expected and that area V1 has more functionality than previously thought.

CognitiveConstruct

RewardProcessing

10.1111/j.1460-9568.2006.04697.x

The European journal of neuroscience

Eur J Neurosci

Variations in the human cannabinoid receptor (CNR1) gene modulate striatal responses to happy faces.

Happy facial expressions are innate social rewards and evoke a response in the striatum, a region known for its role in reward processing in rats, primates and humans. The cannabinoid receptor 1 (CNR1) is the best-characterized molecule of the endocannabinoid system, involved in processing rewards. We hypothesized that genetic variation in human CNR1 gene would predict differences in the striatal response to happy faces. In a 3T functional magnetic resonance imaging (fMRI) scanning study on 19 Caucasian volunteers, we report that four single nucleotide polymorphisms (SNPs) in the CNR1 locus modulate differential striatal response to happy but not to disgust faces. This suggests a role for the variations of the CNR1 gene in underlying social reward responsivity. Future studies should aim to replicate this finding with a balanced design in a larger sample, but these preliminary results suggest neural responsivity to emotional and socially rewarding stimuli varies as a function of CNR1 genotype. This has implications for medical conditions involving hypo-responsivity to emotional and social stimuli, such as autism.

CognitiveConstruct

RewardProcessing

10.1080/09548980500361624

Network (Bristol, England)

Network

Dopamine, prediction error and associative learning: a model-based account.

The notion of prediction error has established itself at the heart of formal models of animal learning and current hypotheses of dopamine function. Several interpretations of prediction error have been offered, including the model-free reinforcement learning method known as temporal difference learning (TD), and the important Rescorla-Wagner (RW) learning rule. Here, we present a model-based adaptation of these ideas that provides a good account of empirical data pertaining to dopamine neuron firing patterns and associative learning paradigms such as latent inhibition, Kamin blocking and overshadowing. Our departure from model-free reinforcement learning also offers: 1) a parsimonious distinction between tonic and phasic dopamine functions; 2) a potential generalization of the role of phasic dopamine from valence-dependent "reward" processing to valence-independent "salience" processing; 3) an explanation for the selectivity of certain dopamine manipulations on motivation for distal rewards; and 4) a plausible link between formal notions of prediction error and accounts of disturbances of thought in schizophrenia (in which dopamine dysfunction is strongly implicated). The model distinguishes itself from existing accounts by offering novel predictions pertaining to the firing of dopamine neurons in various untested behavioral scenarios.

CognitiveConstruct

RewardProcessing

10.2174/187152706784111605

CNS & neurological disorders drug targets

CNS Neurol Disord Drug Targets

Phasic dopamine signaling during behavior, reward, and disease states.

The neurotransmitter dopamine is important in reward processing, however its precise modulatory role is still being investigated. Carbon-fiber microelectrodes can be used to monitor dopamine on a subsecond time scale in the striatum and nucleus accumbens of rats during behavior, and this approach is providing new insights into the mechanisms that control its extracellular concentration as well as the conditions under which it is released. Three main processes govern the amount of dopamine measured extrasynaptically: exocytotic release, neuronal uptake, and diffusion away from the release site. By monitoring local extracellular dopamine concentrations in the striatum following electrical stimulation of dopamine-containing neurons, release, uptake and diffusion can be individually examined and quantified. Dopaminergic neurons have been shown to fire in two firing modes, tonic and bursts at higher frequency. Electrical stimulation can be designed to mimic either mode to examine their effects on dopamine release. Burst firing causes a transient increase in extracellular dopamine while tonic firing causes a new steady-state level. In behaving primates, dopaminergic neurons display short-latency, phasic firing to primary reward and conditioned cues associated with reward. These bursts code differences between actual and predicted rewards. In rats, transient dopamine release in terminal regions that mimics that seen during burst firing has been demonstrated during reward-related cues. Taken together, these studies indicate that phasic dopamine release is a critical mediator of reward-related processes.

CognitiveConstruct

RewardProcessing

10.1007/s00213-006-0366-7

Psychopharmacology

Psychopharmacology (Berl)

Persistent dysfunctional frontal lobe activation in former smokers.

Chronic smoking and nicotine exposure are accompanied by impaired cognitive task performance, modulated cerebral activity in brain imaging studies, and neuritic damage in experimental animals. The profile of the described dysfunctions matches frontal lobe circuits which also play a role in reward processing and reinforcement behavior. However, it is largely unknown if cerebral dysfunctions are reversible or persist during long term abstinence. Cortical activation during auditory target processing (oddball task, P300 component) was recorded with 32-channel EEG in 247 healthy subjects consisting of 84 smokers, 53 former smokers (mean time of abstinence 11.9 years), and 110 never smokers. Both current smokers and former smokers exhibited significantly diminished P300 amplitudes (Cz, Pz) relative to never smokers. Neuroelectric source analysis (low resolution brain electromagnetic tomography) revealed a hypoactivation of the anterior cingulate, orbitofrontal, and prefrontal cortex in smokers compared to never smokers. A similar profile of hypoactivation was observed in former smokers. For the first time, evidence is provided that dysfunctional activation of frontal lobe networks in smokers is also present in long term abstainers.

CognitiveConstruct

RewardProcessing

10.1016/j.physbeh.2006.01.017

Physiology & behavior

Physiol Behav

Sucrose motivation in sweet "sensitive" (C57BL/6J) and "subsensitive" (129P3/J) mice measured by progressive ratio licking.

As compared to C57BL/6J mice, 129P3/J mice show weaker preferences for and lower intakes of dilute sugar solutions. These differences have been attributed to genetic differences in their sweet taste receptor. The two mouse strains do not differ, however, in their intake of concentrated sugar solutions. The post-oral satiating effect of concentrated sugar solutions may mask strain differences in the avidity for these solutions. This hypothesis was investigated using fixed ratio (FR, low demand) and progressive ratio (PR, high demand) operant licking tests (22h/day) to measure sugar appetite. In Experiment 1, sucrose-experienced 129 mice licked less than did B6 mice for 4% but not for 16% sucrose in free access bottle tests and FR operant tests. Yet, in PR tests the 129 mice licked as much for 4% sucrose and more for 16% sucrose than did B6 mice. In Experiment 2, sucrose-naive 129 mice licked less than did B6 mice in FR and PR tests with 0.4% saccharin but the strains did not differ in PR licking in their first test with 16% sucrose. After they were given unconstrained bottle access to 16% sucrose for 3 days, the 129 mice now licked more than B6 mice in a second sucrose PR test. Thus, despite having a less sensitive sweet taste receptor, 129 mice are as much or more motivated to obtain sucrose than are B6 mice and appear to be more influenced by prior experience with sugar. This suggests that the strains differ in their central reward processing of sweet taste.

CognitiveConstruct

RewardProcessing

10.1016/j.neulet.2006.01.061

Neuroscience letters

Neurosci Lett

Activation of insular cortex and subcortical regions related to feedback stimuli in a time estimation task: an fMRI study.

We used functional magnetic resonance imaging to investigate brain activity related to motivational function of informative feedback stimuli in a time estimation task. In that task, subjects pressed a button as a response 3 s after a cue stimulus; a visual feedback stimulus was presented 2 s after the response. In a true feedback condition, subjects received true information (informative feedback) about their time-estimation performance. In the false feedback condition, the same visual signs were used, but they were presented randomly. Therefore, they were not related to actual performance. In the 20 subjects examined, higher hemodynamic responses were identified in the insular cortex, the thalamus, and the striatum by comparing the true feedback condition to the false feedback condition. The time estimation performance and subjective score on motivation were also markedly higher in the true feedback condition. The anterior insular cortex and striatal regions are known to be involved in motivational and reward processing. Therefore, the hemodynamic responses observed in this study suggest that the motivational function of the feedback information is a crucial factor for behavioral learning; it is considered that the informative feedback might serve as an implicit reward for humans.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2006.01.001

NeuroImage

Neuroimage

Prediction error as a linear function of reward probability is coded in human nucleus accumbens.

Reward probability has been shown to be coded by dopamine neurons in monkeys. Phasic neuronal activation not only increased linearly with reward probability upon expectation of reward, but also varied monotonically across the range of probabilities upon omission or receipt of rewards, therefore modeling discrepancies between expected and received rewards. Such a discrete coding of prediction error has been suggested to be one of the basic principles of learning. We used functional magnetic resonance imaging (fMRI) to show that the human dopamine system codes reward probability and prediction error in a similar way. We used a simple delayed incentive task with a discrete range of reward probabilities from 0%-100%. Activity in the nucleus accumbens of human subjects strongly resembled the phasic responses found in monkey neurons. First, during the expectation period of the task, the fMRI signal in the human nucleus accumbens (NAc) increased linearly with the probability of the reward. Second, during the outcome phase, activity in the NAc coded the prediction error as a linear function of reward probabilities. Third, we found that the Nac signal was correlated with individual differences in sensation seeking and novelty seeking, indicating a link between individual fMRI activation of the dopamine system in a probabilistic paradigm and personality traits previously suggested to be linked with reward processing. We therefore identify two different covariates that model activity in the Nac: specific properties of a psychological task and individual character traits.

CognitiveConstruct

RewardProcessing