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10.3389/fnbeh.2014.00385

Frontiers in behavioral neuroscience

Front Behav Neurosci

Linking online gaming and addictive behavior: converging evidence for a general reward deficiency in frequent online gamers.

Millions of people regularly play so-called massively multiplayer online role playing games (MMORPGs). Recently, it has been argued that MMORPG overuse is becoming a significant health problem worldwide. Symptoms such as tolerance, withdrawal, and craving have been described. Based on behavioral, resting state, and task-related neuroimaging data, we test whether frequent players of the MMORPG "World of Warcraft" (WoW) - similar to drug addicts and individuals with an increased risk for addictions - show a generally deficient reward system. In frequent players of the MMORPG "World of Warcraft" (WoW-players) and in a control group of non-gamers we assessed (1) trait sensitivity to reward (SR), (2) BOLD responses during monetary reward processing in the ventral striatum, and (3) ventral-striatal resting-state dynamics. We found a decreased neural activation in the ventral striatum during the anticipation of both small and large monetary rewards. Additionally, we show generally altered neurodynamics in this region independent of any specific task for WoW players (resting state). On the behavioral level, we found differences in trait SR, suggesting that the reward processing deficiencies found in this study are not a consequence of gaming, but predisposed to it. These findings empirically support a direct link between frequent online gaming and the broad field of behavioral and drug addiction research, thus opening new avenues for clinical interventions in addicted gamers and potentially improving the assessment of addiction-risk in the vast population of frequent gamers.

CognitiveConstruct

RewardProcessing

10.1038/npp.2014.313

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Dissociable deficits of executive function caused by gestational adversity are linked to specific transcriptional changes in the prefrontal cortex.

Poor-quality maternal diet during pregnancy, and subsequent gestational growth disturbances in the offspring, have been implicated in the etiology of multiple neurodevelopmental disorders, including ADHD, schizophrenia, and autism. These disorders are characterized, in part, by abnormalities in responses to reward and errors of executive function. Here, we demonstrate dissociable deficits in reward processing and executive function in male and female mice, solely due to maternal malnutrition via high-fat or low-protein diets. Gestational exposure to a high-fat diet delayed acquisition of a fixed ratio response, and decreased motivation as assessed by progressive ratio. In contrast, offspring of a low-protein diet displayed no deficits in operant learning, but were more prone to assign salience to a cue that predicts reward (sign-tracking) in a Pavlovian-conditioned approach task. In the 5-choice serial reaction time task (5-CSRTT), gestational exposure to a high-fat diet promoted impulsivity, whereas exposure to a low-protein diet led to marked inattention. These dissociable executive function deficits are known to be mediated by the medial prefrontal cortex (PFC), which displays markers of epigenetic dysregulation in neurodevelopmental disorders. Following behavioral characterization, we assayed PFC gene expression using a targeted PCR array and found that both maternal diets increased overall transcription in PFC. Cluster analysis of the relationships between individual transcripts and behavioral outcomes revealed a cluster of primarily epigenetic modulators, whose overexpression was linked to executive function deficits. The overexpression of four genes, DNA methyltransferase 1 (DNMT1), δ-opioid receptor (OPRD1), cannabinoid receptor 1 (CNR1), and catechol-o-methyltransferase (COMT), was strongly associated with overall poor performance. All 5-CSRTT deficits were associated with DNMT1 upregulation, whereas impulsive behavior could be dissociated from inattention by overexpression of OPRD1 or COMT, respectively, as well as a distinct cluster of epigenetic regulators. These data provide molecular support for dissociable domains of executive function.

CognitiveConstruct

RewardProcessing

10.1097/YCO.0000000000000122

Current opinion in psychiatry

Curr Opin Psychiatry

Reward processing dysfunction in major depression, bipolar disorder and schizophrenia.

This article reviews the recent literature on reward processing dysfunction in major depression (MDD), bipolar disorder and schizophrenia, with a focus on approach motivation, reward learning and reward-based decision-making. Emerging evidence indicates the presence of reward processing abnormalities across all three disorders, supporting a transdiagnostic approach. In particular, findings are consistent with a role of abnormal phasic striatal dopamine signaling, which is critical for reinforcement learning, efficient mobilization of effort to obtain reward and allocation of attention to reward-predictive cues. Specifically, reward-related striatal signaling appears blunted in MDD and the negative symptoms of schizophrenia, elevated in bipolar (hypo)mania, and contextually misallocated in the positive symptoms of psychosis. However, whether shared or distinct pathophysiological mechanisms contribute to abnormal striatal signaling across the three disorders remains unknown. New evidence of reward processing abnormalities in MDD, bipolar disorder and schizophrenia has led to a greater understanding of the neural processes associated with symptomatology common across these conditions (e.g., anhedonia). Dissecting various subcomponents of reward processing that map onto partially different neurobiological pathways and investigating their dysregulation in different psychiatric disorders holds promise for developing more targeted, and hopefully efficacious treatment and intervention strategies.

CognitiveConstruct

RewardProcessing

10.7717/peerj.662

PeerJ

PeerJ

Cocaine affects foraging behaviour and biogenic amine modulated behavioural reflexes in honey bees.

In humans and other mammals, drugs of abuse alter the function of biogenic amine pathways in the brain leading to the subjective experience of reward and euphoria. Biogenic amine pathways are involved in reward processing across diverse animal phyla, however whether cocaine acts on these neurochemical pathways to cause similar rewarding behavioural effects in animal phyla other than mammals is unclear. Previously, it has been shown that bees are more likely to dance (a signal of perceived reward) when returning from a sucrose feeder after cocaine treatment. Here we examined more broadly whether cocaine altered reward-related behaviour, and biogenic amine modulated behavioural responses in bees. Bees developed a preference for locations at which they received cocaine, and when foraging at low quality sucrose feeders increase their foraging rate in response to cocaine treatment. Cocaine also increased reflexive proboscis extension to sucrose, and sting extension to electric shock. Both of these simple reflexes are modulated by biogenic amines. This shows that systemic cocaine treatment alters behavioural responses that are modulated by biogenic amines in insects. Since insect reward responses involve both octopamine and dopamine signalling, we conclude that cocaine treatment altered diverse reward-related aspects of behaviour in bees. We discuss the implications of these results for understanding the ecology of cocaine as a plant defence compound. Our findings further validate the honey bee as a model system for understanding the behavioural impacts of cocaine, and potentially other drugs of abuse.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22688

Human brain mapping

Hum Brain Mapp

Impact of COMT Val158Met-polymorphism on appetitive conditioning and amygdala/prefrontal effective connectivity.

Appetitive conditioning is an important mechanism for the development, maintenance, and treatment of psychiatric disorders like substance abuse. Therefore, it is important to identify genetic variations, which impact appetitive conditioning. It has been suggested that the Val(158) Met-polymorphism in the Catechol-O-Methyl-Transferase (COMT) is associated with the alteration of neural processes of appetitive conditioning due to the central role of the dopaminergic system in reward processing. However, no study has so far investigated the relationship between variations in the COMT Val(158) Met-polymorphism and appetitive conditioning. In this fMRI study, an appetitive conditioning paradigm was applied, in which one neutral stimulus (CS+) predicted appetitive stimuli (UCS) while a second neutral stimulus (CS-) was never paired with the UCS. As a main result, we observed a significant association between the COMT Val(158) Met-genotype and appetitive conditioning: skin conductance responses (SCRs) revealed a significant difference between CS+ and CS- in Val/Val-allele carriers but not in the other genotype groups. Val/Val-allele carriers showed increased hemodynamic responses in the amygdala compared with the Met/Met-allele group in the contrast CS+ > CS-. In addition, psychophysiological-interaction analysis revealed increased effective amygdala/ventromedial prefrontal cortex connectivity in Met/Met-allele carriers. The increased amygdala activity points to facilitated appetitive conditioning in Val/Val-allele carriers while the amygdala/prefrontal connectivity results could be regarded as a marker for altered emotion regulation during conditioning, which potentially impacts appetitive learning sensitivity. The SCRs finding indicates a stronger conditioned response in the Val/Val-allele group and dovetails with the neural differences between the groups. These findings contribute to the current research on COMT in emotional processing.

CognitiveConstruct

RewardProcessing

10.1177/1352458514555784

Multiple sclerosis (Houndmills, Basingstoke, England)

Mult Scler

Altered basal ganglia functional connectivity in multiple sclerosis patients with fatigue.

Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis, but its pathophysiological mechanisms are poorly understood. It is in particular unclear whether and how fatigue relates to structural and functional brain changes. We aimed to analyse the association of fatigue severity with basal ganglia functional connectivity, basal ganglia volumes, white matter integrity and grey matter density. In 44 patients with relapsing-remitting multiple sclerosis and 20 age- and gender-matched healthy controls, resting-state fMRI, diffusion tensor imaging and voxel-based morphometry was performed. In comparison with healthy controls, patients showed alteration of grey matter density, white matter integrity, basal ganglia volumes and basal ganglia functional connectivity. No association of fatigue severity with grey matter density, white matter integrity and basal ganglia volumes was observed within patients. In contrast, fatigue severity was negatively correlated with functional connectivity of basal ganglia nuclei with medial prefrontal cortex, precuneus and posterior cingulate cortex in patients. Furthermore, fatigue severity was positively correlated with functional connectivity between caudate nucleus and motor cortex. Fatigue is associated with distinct alterations of basal ganglia functional connectivity independent of overall disability. The pattern of connectivity changes suggests that disruption of motor and non-motor basal ganglia functions, including motivation and reward processing, contributes to fatigue pathophysiology in multiple sclerosis.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2014.00819

Frontiers in human neuroscience

Front Hum Neurosci

Affective and cognitive prefrontal cortex projections to the lateral habenula in humans.

Anterior insula (AI) and dorsal ACC (dACC) are known to process information about pain, loss, adversities, bad, harmful or suboptimal choices and consequences that threaten survival or well-being. Also pregenual ACC (pgACC) is linked to loss and pain, being activated by sad thoughts and regrets. Lateral habenula (LHb) is stimulated by predicted and received pain, discomfort, aversive outcome, loss. Its chronic stimulation makes us feel worse/low and gradually stops us choosing and moving for the suboptimal or punished choices, by direct and indirect (via rostromedial tegmental nucleus, RMTg) inhibition of dorsal raphe nucleus (DRN) and VTA/SNc. The response selectivity of LHb neurons suggests their cortical input from affective and cognitive evaluative regions that make expectations about bad, unpleasant or suboptimal outcomes. Based on these facts I predicted direct dACC, pgACC and AI projections to LHb, which form part of an adversity processing circuit that learns to avoid bad outcomes by suppressing dopamine and serotonin signal. To test this connectivity I used Diffusion Tensor Imaging (DTI). I found dACC, pgACC, AI and caudolateral OFC (clOFC) projections to LHb. I predicted no corticohabenular projections from the reward processing regions: medial OFC (mOFC) and ventral ACC (vACC) because both respond most strongly to good, high valued stimuli and outcomes, inducing dopamine and serotonin release. This lack of LHb projections was confirmed for vACC and likely for mOFC. The surprising findings were the corticohabenular projections from the cognitive prefrontal cortex regions, known for flexible reasoning, planning and combining whatever information are relevant for reaching current goals. I propose that the prefrontohabenular projections provide a teaching signal for value-based choice behavior, to learn to deselect, avoid or inhibit the potentially harmful, low valued or wrong choices, goals, strategies, predictions and ways of doing things, to prevent bad or suboptimal consequences.

CognitiveConstruct

RewardProcessing

10.1007/s10865-014-9607-0

Journal of behavioral medicine

J Behav Med

Neurophysiological evidence for remediation of reward processing deficits in chronic pain and opioid misuse following treatment with Mindfulness-Oriented Recovery Enhancement: exploratory ERP findings from a pilot RCT.

Dysregulated processing of natural rewards may be a central pathogenic process in the etiology and maintenance of prescription opioid misuse and addiction among chronic pain patients. This study examined whether a Mindfulness-Oriented Recovery Enhancement (MORE) intervention could augment natural reward processing through training in savoring as indicated by event-related brain potentials (ERPs). Participants were chronic pain patients at risk for opioid misuse who were randomized to 8 weeks of MORE (n = 11) or a support group control condition (n = 18). ERPs to images representing naturally rewarding stimuli (e.g., beautiful landscapes, intimate couples) and neutral images were measured before and after 8 weeks of treatment. Analyses focused on the late positive potential (LPP)--an ERP response in the 400-1,000 ms time window thought to index allocation of attention to emotional information. Treatment with MORE was associated with significant increases in LPP response to natural reward stimuli relative to neutral stimuli which were correlated with enhanced positive affective cue-responses and reductions in opioid craving from pre- to post-treatment. Findings suggest that cognitive training regimens centered on strengthening attention to natural rewards may remediate reward processing deficits underpinning addictive behavior.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2014.09.008

NeuroImage. Clinical

Neuroimage Clin

Insula and striatum activity in effort-related monetary reward processing in gambling disorder: the role of depressive symptomatology.

The neurobiological underpinnings of effort-related monetary reward processing of gambling disorder have not been previously studied. To date neuroimaging studies lack in large sample sizes and as a consequence less attention has been given to brain reward processing that could potentially be attributed to comorbid conditions such as depressive mood state. We assessed monetary reward processing using an effort-dependent task during 3 tesla functional magnetic resonance imaging. We investigated a large sample of male, right-handed, slot-machine-playing disordered gamblers (DGs; N = 80) as well as age- and smoking-matched male healthy controls (HCs; N = 89). Depressive symptoms were assessed using the Beck Depression Inventory (BDI). DGs and HCs were divided into subgroups ("high" and "low") based on their BDI scores. Effort-related monetary reward processing did not differ between the complete groups of HCs and DGs. Brain activation during receipt of monetary reward though revealed a significant Group × BDI interaction: DGs with higher BDI scores compared to DGs with lower BDI scores showed greater brain activity in the right insula cortex and dorsal striatum while no differences were observed for HCs with higher versus lower BDI scores. Our results suggest that effort-related aspects of monetary motivation, i.e. when monetary output is tied to performance, are not altered in DG. Additionally, our findings strengthen the need for subgroup comparisons in future investigations of the disorder as part of a personalized medicine approach.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2014.00359

Frontiers in behavioral neuroscience

Front Behav Neurosci

Impaired Cross-Talk between Mesolimbic Food Reward Processing and Metabolic Signaling Predicts Body Mass Index.

The anticipation of the pleasure derived from food intake drives the motivation to eat, and hence facilitate overconsumption of food, which ultimately results in obesity. Brain imaging studies provide evidence that mesolimbic brain regions underlie both general as well as food-related anticipatory reward processing. In light of this knowledge, the present study examined the neural responsiveness of the ventral striatum (VS) in participants with a broad BMI spectrum. The study differentiated between general (i.e., monetary) and food-related anticipatory reward processing. We recruited a sample of volunteers with greatly varying body weights, ranging from a low BMI (below 20 kg/m(2)) over a normal (20-25 kg/m(2)) and overweight (25-30 kg/m(2)) BMI, to class I (30-35 kg/m(2)) and class II (35-40 kg/m(2)) obesity. A total of 24 participants underwent functional magnetic resonance imaging while performing both a food and monetary incentive delay task, which allows to measure neural activation during the anticipation of rewards. After the presentation of a cue indicating the amount of food or money to be won, participants had to react correctly in order to earn "snack points" or "money coins," which could then be exchanged for real food or money, respectively, at the end of the experiment. During the anticipation of both types of rewards, participants displayed activity in the VS, a region that plays a pivotal role in the anticipation of rewards. Additionally, we observed that specifically anticipatory food reward processing predicted the individual BMI (current and maximum lifetime). This relation was found to be mediated by impaired hormonal satiety signaling, i.e., increased leptin levels and insulin resistance. These findings suggest that heightened food reward motivation contributes to obesity through impaired metabolic signaling.

CognitiveConstruct

RewardProcessing

10.1093/schbul/sbu153

Schizophrenia bulletin

Schizophr Bull

Fronto-striatal dysfunction during reward processing in unaffected siblings of schizophrenia patients.

Schizophrenia is a psychiatric disorder that is associated with impaired functioning of the fronto-striatal network, in particular during reward processing. However, it is unclear whether this dysfunction is related to the illness itself or whether it reflects a genetic vulnerability to develop schizophrenia. Here, we examined reward processing in unaffected siblings of schizophrenia patients using functional magnetic resonance imaging. Brain activity was measured during reward anticipation and reward outcome in 27 unaffected siblings of schizophrenia patients and 29 healthy volunteers using a modified monetary incentive delay task. Task performance was manipulated online so that all subjects won the same amount of money. Despite equal performance, siblings showed reduced activation in the ventral striatum, insula, and supplementary motor area (SMA) during reward anticipation compared to controls. Decreased ventral striatal activation in siblings was correlated with sub-clinical negative symptoms. During the outcome of reward, siblings showed increased activation in the ventral striatum and orbitofrontal cortex compared to controls. Our finding of decreased activity in the ventral striatum during reward anticipation and increased activity in this region during receiving reward may indicate impaired cue processing in siblings. This is consistent with the notion of dopamine dysfunction typically associated with schizophrenia. Since unaffected siblings share on average 50% of their genes with their ill relatives, these deficits may be related to the genetic vulnerability for schizophrenia.

CognitiveConstruct

RewardProcessing

10.1002/brb3.285

Brain and behavior

Brain Behav

Winning and losing: differences in reward and punishment sensitivity between smokers and nonsmokers.

Smokers show increased brain activation in reward processing regions in response to smoking-related cues, yet few studies have examined secondary rewards not associated with smoking (i.e., money). Inconsistencies exist in the studies that do examine secondary rewards with some studies showing increased brain activation in reward processing brain regions, while others show decreased activation or no difference in activation between smokers and nonsmokers. The goal of the current study is to see if smokers process the evaluation and delivery of equally salient real world rewards similarly or differently than nonsmokers. The current study employed functional magnetic resonance imaging (fMRI) to examine brain responses in smokers and nonsmokers during the evaluation and delivery of monetary gains and losses. In comparison to nonsmokers, smokers showed increased activation in the ventromedial prefrontal cortex to the evaluation of anticipated monetary losses and the brain response. Moreover, smokers compared to nonsmokers showed decreased activation in the inferior frontal gyrus to the delivery of expected monetary gains. Brain activations to both the evaluation of anticipated monetary losses and the delivery of expected monetary gains correlated with increased self-reported smoking craving to relieve negative withdrawal symptoms and craving related to positive aspects of smoking, respectively. Together these results indicate that smokers are hyperresponsive to the evaluation of anticipated punishment and hyporesponsive to the delivery of expected rewards. Although further research is needed, this hypersensitivity to punishments coupled with increased craving may negatively impact quit attempts as smokers anticipate the negative withdrawal symptoms associated with quitting.

CognitiveConstruct

RewardProcessing

10.1111/jcpp.12355

Journal of child psychology and psychiatry, and allied disciplines

J Child Psychol Psychiatry

Neural reactivity to monetary rewards and losses differentiates social from generalized anxiety in children.

The relationship between reward sensitivity and pediatric anxiety is poorly understood. Evidence suggests that alterations in reward processing are more characteristic of depressive than anxiety disorders. However, some studies have reported that anxiety disorders are also associated with perturbations in reward processing. Heterogeneity in the forms of anxiety studied may account for the differences between studies. We used the feedback-negativity, an event-related potential sensitive to monetary gains versus losses (ΔFN), to examine whether different forms of youth anxiety symptoms were uniquely associated with reward sensitivity as indexed by neural reactivity to the receipt of positive and negative monetary outcomes. Participants were 390, eight- to ten-year-old children (175 females) from a large community sample. The ΔFN was measured during a monetary reward task. Self-reports of child anxiety and depression symptoms and temperamental positive emotionality (PE) were obtained. Multiple regression analysis revealed that social anxiety and generalized anxiety symptoms were unique predictors of reward sensitivity after accounting for concurrent depressive symptoms and PE. While social anxiety was associated with a greater ΔFN, generalized anxiety was associated with a reduced ΔFN. Different symptom dimensions of child anxiety are differentially related to alterations in reward sensitivity. This may, in part, explain inconsistent findings in the literature regarding reward processing in anxiety.

CognitiveConstruct

RewardProcessing

10.1152/jn.00086.2014

Journal of neurophysiology

J Neurophysiol

Value and probability coding in a feedback-based learning task utilizing food rewards.

For the consequences of our actions to guide behavior, the brain must represent different types of outcome-related information. For example, an outcome can be construed as negative because an expected reward was not delivered or because an outcome of low value was delivered. Thus behavioral consequences can differ in terms of the information they provide about outcome probability and value. We investigated the role of the striatum in processing probability-based and value-based negative feedback by training participants to associate cues with food rewards and then employing a selective satiety procedure to devalue one food outcome. Using functional magnetic resonance imaging, we examined brain activity related to receipt of expected rewards, receipt of devalued outcomes, omission of expected rewards, omission of devalued outcomes, and expected omissions of an outcome. Nucleus accumbens activation was greater for rewarding outcomes than devalued outcomes, but activity in this region did not correlate with the probability of reward receipt. Activation of the right caudate and putamen, however, was largest in response to rewarding outcomes relative to expected omissions of reward. The dorsal striatum (caudate and putamen) at the time of feedback also showed a parametric increase correlating with the trialwise probability of reward receipt. Our results suggest that the ventral striatum is sensitive to the motivational relevance, or subjective value, of the outcome, while the dorsal striatum codes for a more complex signal that incorporates reward probability. Value and probability information may be integrated in the dorsal striatum, to facilitate action planning and allocation of effort.

CognitiveConstruct

RewardProcessing

10.1186/1756-0500-7-739

BMC research notes

BMC Res Notes

Risky monetary behavior in chronic back pain is associated with altered modular connectivity of the nucleus accumbens.

The nucleus accumbens (NAc) has a well established role in reward processing. Yet, there is growing evidence showing that NAc function, and its connections to other parts of the brain, is also critically involved in the emergence of chronic back pain (CBP). Pain patients are known to perform abnormally in reward-related tasks, which suggests an intriguing link between pain, NAc connectivity, and reward behavior. In the present study, we compared performance on a gambling task (indicating willingness to risk losing money) between healthy pain-free controls (CON) and individuals with CBP. We then measured modular connectivity of each participants' NAc with resting state functional MRI to investigate how connectivity accounts for reward behavior in the presence and absence of pain. We found gain sensitivity was significantly higher in CBP patients. These scores were significantly correlated to connectivity within the NAc module defined by CON subjects ( which had strong connections to the frontal cortex), but not within that defined by CBP patients ( which was more strongly connected to subcortical areas). An important part of our study was based on the precedence that a range of behaviors, from simple to complex, can be predicted from brain activity during rest. Thus, to corroborate our results we compared them closely to an independent study correlating the same connectivity metric to impulsive behaviors in healthy participants. We found that our CBP patients were highly similarin connectivity to this study's highly-impulsive healthy subjects, strengthening the notion that there is an important link between the brain systems that support chronic pain and reward processing. Our results support previous findings that chronic back pain is accompanied by altered connectivity of the NAc. This lends itself to riskier behavior in these patients, a finding which establishes a potential cognitive consequence or co-morbidity of long-term pain and provides a behavioral link to growing research showing that chronic pain is related to abnormal changes in the dopaminergic system.

CognitiveConstruct

RewardProcessing

10.1111/psyp.12370

Psychophysiology

Psychophysiology

The reward positivity: from basic research on reward to a biomarker for depression.

Feedback indicating monetary loss elicits an apparent negative deflection in the event-related potential (ERP) that has been referred to as the feedback error-related negativity, medial frontal negativity, feedback-related negativity, and feedback negativity-all conceptualizations that suggest a negative ERP component that is greater for loss than gain. In the current paper, I review a programmatic line of research indicating that this apparent negativity actually reflects a reward-related positivity (RewP) that is absent or suppressed following nonreward. I situate the RewP within a broader nomological network of reward processing and individual differences in sensitivity to rewards. Further, I review work linking reductions in the RewP to increased depressive symptoms and risk for depression. Finally, I discuss future directions for research on the RewP.

CognitiveConstruct

RewardProcessing

10.1007/s00406-014-0552-2

European archives of psychiatry and clinical neuroscience

Eur Arch Psychiatry Clin Neurosci

Dissociating pathomechanisms of depression with fMRI: bottom-up or top-down dysfunctions of the reward system.

Depression is a debilitating psychiatric disorder characterized among other aspects by the inability to properly experience or respond to reward. However, it remains unclear whether patients with depression present impaired reward system due to abnormal modulatory mechanisms. We investigated the activation of the nucleus accumbens (NAcc), a crucial region involved in reward processing, with functional magnetic resonance imaging using the desire-reason-dilemma paradigm. This task allows tracking the activity of the NAcc during the acceptance or the rejection of previously conditioned reward stimuli. Patients were assigned into subgroups of lower (LA) or higher (HA) NAcc activation according to beta weights. LA patients presented significant hypoactivation in the ventral tegmental area in addition to bilateral ventral striatum, confirming impairments in the bottom-up input to the NAcc. Conversely, HA patients presented significant hyperactivation in prefrontal areas such as the rostral anterior cingulate cortex and the anterior ventral prefrontal cortex in addition to bilateral ventral striatum, suggesting disturbances in the top-down regulation of the NAcc. Demographic and clinical differences explaining the abnormal co-activations of midbrain and prefrontal regions were not identified. Therefore, we provide evidence for dysfunctional bottom-up processing in one potential neurobiological subtype of depression (LA) and dysfunctional top-down modulation in another subtype (HA). We suggest that the midbrain and prefrontal regions are more specific pathophysiological substrates for each depression subtype. Above all, our results encourage the segregation of patients by similar dysfunctional mechanisms of the dopaminergic system, which would finally contribute to disentangle more specific pathogeneses and guide the development of more personalized targets for future therapies.

CognitiveConstruct

RewardProcessing

10.1038/npp.2014.268

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

PPARγ activation attenuates opioid consumption and modulates mesolimbic dopamine transmission.

PPARγ is one of the three isoforms identified for the peroxisome proliferator-activated receptors (PPARs) and is the receptor for the thiazolidinedione class of anti-diabetic medications including pioglitazone. PPARγ has been long studied for its role in adipogenesis and glucose metabolism, but the discovery of the localization in ventral tegmental area (VTA) neurons opens new vistas for a potential role in the regulation of reward processing and motivated behavior in drug addiction. Here, we demonstrate that activation of PPARγ by pioglitazone reduces the motivation for heroin and attenuates its rewarding properties. These effects are associated with a marked reduction of heroin-induced increase in phosphorylation of DARPP-32 protein in the nucleus accumbens (NAc) and with a marked and selective reduction of acute heroin-induced elevation of extracellular dopamine (DA) levels in the NAc shell, as measured by in vivo microdialysis. Through ex vivo electrophysiology in acute midbrain slices, we also show that stimulation of PPARγ attenuates opioid-induced excitation of VTA DA neurons via reduction of presynaptic GABA release from the rostromedial tegmental nucleus (RMTg). Consistent with this finding, site-specific microinjection of pioglitazone into the RMTg but not into the VTA reduced heroin taking. Our data illustrate that activation of PPARγ may represent a new pharmacotherapeutic option for the treatment of opioid addiction.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2014.00130

Frontiers in psychiatry

Front Psychiatry

Unique functional abnormalities in youth with combined marijuana use and depression: an FMRI study.

Prior research has shown a relationship between early onset marijuana (MJ) use and depression; however, this relationship is complex and poorly understood. Here, we utilized passive music listening and fMRI to examine functional brain activation to a rewarding stimulus in 75 participants [healthy controls (HC), patients with major depressive disorder (MDD), frequent MJ users, and the combination of MDD and MJ (MDD + MJ)]. For each participant, a preferred and neutral piece of instrumental music was determined (utilizing ratings on a standardized scale), and each completed two 6-min fMRI scans of a passive music listening task. Data underwent pre-processing and 61 participants were carried forward for analysis (17 HC, 15 MDD, 15 MJ, 14 MDD + MJ). Two statistical analyses were performed using SPM8, an analysis of covariance with two factors (group × music type) and a whole brain, multiple regression analysis incorporating two predictors of interest [MJ use in past 28 days; and Beck Depression Inventory (BDI) score]. We identified a significant group × music type interaction. Post hoc comparisons showed that the preferred music had significantly greater activation in the MDD + MJ group in areas including the right middle and inferior frontal gyri extending into the claustrum and putamen and the anterior cingulate. No significant differences were identified in MDD, MJ, or HC groups. Multiple regression analysis showed that activation in medial frontal cortex was positively correlated with amount of MJ use, and activation in areas including the insula was negatively correlated with BDI score. Results showed modulation in brain activation during passive music listening specific to MDD, frequent MJ users. This supports the suggestion that frequent MJ use, when combined with MDD, is associated with changes in neurocircuitry involved in reward processing in ways that are absent with either frequent MJ use or MDD alone. This could help inform clinical recommendations for youth with MDD.

CognitiveConstruct

RewardProcessing

10.1038/tp.2014.100

Translational psychiatry

Transl Psychiatry

CACNA1C risk variant affects reward responsiveness in healthy individuals.

The variant at rs1006737 in the L-type voltage-gated calcium channel (alpha 1c subunit) CACNA1C gene is reliably associated with both bipolar disorder and schizophrenia. We investigated whether this risk variant affects reward responsiveness because reward processing is one of the central cognitive-motivational domains implicated in both disorders. In a sample of 164 young, healthy individuals, we show a dose-dependent response, where the rs1006737 risk genotype was associated with blunted reward responsiveness, whereas discriminability did not significantly differ between genotype groups. This finding suggests that the CACNA1C risk locus may have a role in neural pathways that facilitate value representation for rewarding stimuli. Impaired reward processing may be a transdiagnostic phenotype of variation in CACNA1C that could contribute to anhedonia and other clinical features common to both affective and psychotic disorders.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0108886

PloS one

PLoS One

Early effects of reward anticipation are modulated by dopaminergic stimulation.

The abilities to predict future rewards and assess the value of reward delivery are crucial aspects of adaptive behavior. While the mesolimbic system, including dopaminergic midbrain, ventral striatum and prefrontal cortex have long been associated with reward processing, recent studies also indicate a prominent role of early visual brain regions. However, the precise underlying neural mechanisms still remain unclear. To address this issue, we presented participants with visual cues predicting rewards of high and low magnitudes and probability (2 × 2 factorial design), while neural activity was scanned using magnetoencephalography. Importantly, one group of participants received 150 mg of the dopamine precursor levodopa prior to the experiment, while another group received a placebo. For the placebo group, neural signals of reward probability (but not magnitude) emerged at ∼ 100 ms after cue presentation at occipital sensors in the event-related magnetic fields. Importantly, these probability signals were absent in the levodopa group indicating a close link. Moreover, levodopa administration reduced oscillatory power in the high (20-30 Hz) and low (13-20 Hz) beta band during both reward anticipation and delivery. Taken together, our findings indicate that visual brain regions are involved in coding prospective reward probability but not magnitude and that these effects are modulated by dopamine.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2014.08.010

Developmental cognitive neuroscience

Dev Cogn Neurosci

Age differences in the impact of peers on adolescents' and adults' neural response to reward.

Prior research suggests that increased adolescent risk-taking in the presence of peers may be linked to the influence of peers on the valuation and processing of rewards during decision-making. The current study explores this idea by examining how peer observation impacts the processing of rewards when such processing is isolated from other facets of risky decision-making (e.g. risk-perception and preference, inhibitory processing, etc.). In an fMRI paradigm, a sample of adolescents (ages 14-19) and adults (ages 25-35) completed a modified High/Low Card Guessing Task that included rewarded and un-rewarded trials. Social context was manipulated by having participants complete the task both alone and while being observed by two, same-age, same-sex peers. Results indicated an interaction of age and social context on the activation of reward circuitry during the receipt of reward; when observed by peers adolescents exhibited greater ventral striatal activation than adults, but no age-related differences were evinced when the task was completed alone. These findings suggest that, during adolescence, peers influence recruitment of reward-related regions even when they are engaged outside of the context of risk-taking. Implications for engagement in prosocial, as well as risky, behaviors during adolescence are discussed.

CognitiveConstruct

RewardProcessing

10.1210/jc.2014-2774

The Journal of clinical endocrinology and metabolism

J Clin Endocrinol Metab

Leptin therapy alters appetite and neural responses to food stimuli in brain areas of leptin-sensitive subjects without altering brain structure.

Leptin is a key regulator of energy intake and expenditure. Individuals with congenital leptin deficiency demonstrate structural and functional brain changes when given leptin. However, whether acquired leptin deficiency may operate similarly is unclear. We set out to determine whether the brains of individuals with acquired leptin deficiency may react to leptin in a similar manner. We used functional magnetic resonance imaging before and after short- and long-term metreleptin treatment in three leptin-sensitive patients with acquired hypoleptinemia. Nine healthy women were scanned as normoleptinemic controls. The setting was an academic medical center. The participants were 3 hypoleptinemic women and nine normoleptinemic, matched women. We used metreleptin, recombinant leptin, therapy for 24 weeks in hypoleptinemic women only. We measured neural changes in response to viewing food as compared to nonfood images. We hypothesized that metreleptin treatment would increase brain activity in areas related to cognitive control and inhibition and would decrease brain activity in areas related to reward processing, as compared to the normoleptinemic counterparts. Unlike patients with congenital leptin deficiency, hypoleptinemic patients demonstrated no structural brain differences from healthy controls and/or structural changes in response to treatment. Short-term metreleptin treatment in leptin-sensitive hypoleptinemic subjects enhances areas involved in detecting the salience and rewarding value of food during fasting, whereas long-term treatment decreases attention to food and the rewarding value of food after feeding. Furthermore, hypothalamic activity is modulated by metreleptin treatment, and leptin decreases functional connectivity of the hypothalamus to key feeding-related areas in these hypoleptinemic subjects. Leptin replacement in acutely hypoleptinemic women did not alter brain structure but did alter functional cortical activity to food cues in key feeding and reward-related areas.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2014.09.026

Behavioural brain research

Behav Brain Res

Comfort for uncertainty in pathological gamblers: a fMRI study.

This study examined neural anticipation of monetary reward in pathological gamblers (PG) by varying the type of uncertainty associated with the reward. Ten PG and ten controls were scanned while deciding whether to accept ("bet" option, featuring high-uncertain monetary rewards) or reject ("safe" option, featuring low-certain rewards) a bet, within situations of decision-making under risk (probability of the "bet" reward is known) or ambiguity (probability of the "bet" reward is unknown). During decision under risk (as compared to ambiguity), controls exhibited activation in brain areas involved in reward processing (putamen), interoception (insula) and cognitive control (dorsolateral prefrontal cortex; middle frontal gyrus). By contrast, PG exhibited no differential brain activation as a function of the type of uncertainty associated with the "bet" option. Moreover, prior choosing of the "safe" option (as compared to "bet" choices), controls exhibited activation in the posterior insula, dorsolateral prefrontal cortex and middle frontal gyrus. By contrast, PG exhibited higher neural activation during the elaboration of "bet" choices, and in motivational-arousal areas (caudate; putamen; posterior insula). Between-groups contrasts revealed that, as compared to controls, PG showed (i) decreased neural activity in the globus pallidus for decision-making under risk, as opposed to decision under ambiguity, and (ii) increased neural activity within the putamen prior to bet choices, as opposed to safe choices. These findings suggest that (i) unlike control participants, a variation in the level of uncertainty associated with monetary rewards seems to have no significant impact on PGs' decision to gamble and (ii) PG exhibit stronger brain activation while anticipating high-uncertain monetary rewards, as compared with lower-certain rewards.

CognitiveConstruct

RewardProcessing

10.1111/obr.12221

Obesity reviews : an official journal of the International Association for the Study of Obesity

Obes Rev

Reward processing in obesity, substance addiction and non-substance addiction.

Similarities and differences between obesity and addiction are a prominent topic of ongoing research. We conducted an activation likelihood estimation meta-analysis on 87 studies in order to map the functional magnetic resonance imaging (fMRI) response to reward in participants with obesity, substance addiction and non-substance (or behavioural) addiction, and to identify commonalities and differences between them. Our study confirms the existence of alterations during reward processing in obesity, non-substance addiction and substance addiction. Specifically, participants with obesity or with addictions differed from controls in several brain regions including prefrontal areas, subcortical structures and sensory areas. Additionally, participants with obesity and substance addictions exhibited similar blood-oxygen-level-dependent fMRI hyperactivity in the amygdala and striatum when processing either general rewarding stimuli or the problematic stimuli (food and drug-related stimuli, respectively). We propose that these similarities may be associated with an enhanced focus on reward--especially with regard to food or drug-related stimuli--in obesity and substance addiction. Ultimately, this enhancement of reward processes may facilitate the presence of compulsive-like behaviour in some individuals or under some specific circumstances. We hope that increasing knowledge about the neurobehavioural correlates of obesity and addictions will lead to practical strategies that target the high prevalence of these central public health challenges.

CognitiveConstruct

RewardProcessing

10.1016/j.brat.2014.08.011

Behaviour research and therapy

Behav Res Ther

Elevated reward-related neural activation as a unique biological marker of bipolar disorder: assessment and treatment implications.

Growing evidence indicates that risk for bipolar disorder is characterized by elevated activation in a fronto-striatal reward neural circuit involving the ventral striatum and orbitofrontal cortex, among other regions. It is proposed that individuals with abnormally elevated reward-related neural activation are at risk for experiencing an excessive increase in approach-related motivation during life events involving rewards or goal striving and attainment. In the extreme, this increase in motivation is reflected in hypomanic/manic symptoms. By contrast, unipolar depression (without a history of hypomania/mania) is characterized by decreased reward responsivity and decreased reward-related neural activation. Collectively, this suggests that risk for bipolar disorder and unipolar depression are characterized by distinct and opposite profiles of reward processing and reward-related neural activation. The objective of the present paper is threefold. First, we review the literature on reward processing and reward-related neural activation in bipolar disorder, and in particular risk for hypomania/mania. Second, we propose that reward-related neural activation reflects a biological marker of differential risk for bipolar disorder versus unipolar depression that may help facilitate psychiatric assessment and differential diagnosis. We also discuss, however, the challenges to using neuroscience techniques and biological markers in a clinical setting for assessment and diagnostic purposes. Lastly, we address the pharmacological and psychosocial treatment implications of research on reward-related neural activation in bipolar disorder.

CognitiveConstruct

RewardProcessing

10.1016/j.jphysparis.2014.08.008

Journal of physiology, Paris

J Physiol Paris

Feedback-related negativity observed in rodent anterior cingulate cortex.

The feedback-related negativity (FRN) refers to a difference in the human event-related potential (ERP) elicited by feedback indicating success versus failure: the difference appears negative when subtracting the success ERP from the failure ERP (Miltner et al., 1997). Although source localization techniques (e.g., BESA) suggest that the FRN is produced in the ACC, the inverse problem (that any given scalp distribution can be produced by an infinite number of possible dipole configurations) limits the certainty of this conclusion. The inverse problem can be circumvented by directly recording from the ACC in animal models. Although a non-human primate homologue of the FRN has been observed in the macaque monkey (e.g. Emeric et al., 2008), a homologue of the FRN has yet to be identified in rodents. We recorded local field potentials (LFPs) directly from the ACC in 6 rodents in a task based on the FRN paradigm. The animals were trained to poke their nose into a lighted port and received a feedback smell indicating whether or not a reward pellet would drop 1.5s later. We observed a FRN-like effect time-locked to the feedback scent whereby the LFP to feedback predicting no-reward was significantly more negative than the LFP to feedback predicting reward. This deflection began on average 130ms before behavioral changes in response to the feedback. Thus, we provide the first evidence of the existence of a rodent homologue of the FRN.

CognitiveConstruct

RewardProcessing

10.1001/jamapsychiatry.2014.1215

JAMA psychiatry

JAMA Psychiatry

Oleoylethanolamide and human neural responses to food stimuli in obesity.

Obesity has emerged as a leading health threat but its biological basis remains insufficiently known, hampering the search for novel treatments. Here, we study oleoylethanolamide, a naturally occurring lipid that has been clearly implicated in weight regulation in animals. However, its role for weight regulation and obesity in humans is still unclear. To investigate associations between plasma oleoylethanolamide levels and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) and functional magnetic resonance imaging response to food stimuli in obese patients and matched control participants. Case-control study of 21 obese patients and 24 matched control participants. Obesity was defined as having a BMI of at least 30. The mean age of participants was 40.8 years and BMIs ranged from 18.2 to 47.5. Interactions between plasma oleoylethanolamide levels and obesity on BMI and functional magnetic resonance imaging response to food stimuli. Associations between oleoylethanolamide and BMI differed significantly depending on whether individuals were obese or not (P = .02). In obese individuals, oleoylethanolamide showed a trend toward a positive correlation with BMI (P = .06, ρ = 0.42), while this relationship was inverse for nonobese control participants (P = .07, ρ = -0.34). Similarly, we found significant interactions between oleoylethanolamide levels and obesity on food-related brain activation in cortical areas associated with reward processing and interoceptive signaling (P = .009). Specifically, nonobese individuals with higher oleoylethanolamide levels had higher insular brain activity (P < .001, ρ = 0.70); again, the relationship trended to be inverse for obese patients (P = .11, ρ = -0.36). These effects were not associated with plasma levels of leptin and anandamide, suggesting an independent role of oleoylethanolamide in hunger-associated interoceptive signaling. Analysis of food craving during the functional magnetic resonance imaging task suggested that the identified brain areas may be involved in suppressing food-liking reactions in nonobese individuals. This study suggests that oleoylethanolamide-mediated signaling plays an important role for hedonic regulation of food craving and obesity in humans and thus may be a valuable target for developing novel antiobesity drugs.

CognitiveConstruct

RewardProcessing

10.1016/j.psyneuen.2014.08.012

Psychoneuroendocrinology

Psychoneuroendocrinology

Hormonal treatment increases the response of the reward system at the menopause transition: a counterbalanced randomized placebo-controlled fMRI study.

Preclinical research using rodent models demonstrated that estrogens play neuroprotective effects if they are administered during a critical period near the time of cessation of ovarian function. In women, a number of controversial epidemiological studies reported that a neuroprotective effect of estradiol may be obtained on cognition and mood-related disorders if hormone therapy (HT) begins early at the beginning of menopause. Yet, little is known about the modulatory effects of early HT administration on brain activation near menopause. Here, we investigated whether HT, initiated early during the menopause transition, increases the response of the reward system, a key brain circuit involved in motivation and hedonic behavior. We used fMRI and a counterbalanced, double-blind, randomized and crossover placebo-controlled design to investigate whether sequential 17β-estradiol plus oral progesterone modulate reward-related brain activity. Each woman was scanned twice while presented with images of slot machines, once after receiving HT and once under placebo. The fMRI results demonstrate that HT, relative to placebo, increased the response of the striatum and ventromedial prefrontal cortex, two areas that have been shown to be respectively involved during reward anticipation and at the time of reward delivery. Our neuroimaging results bridge the gap between animal studies and human epidemiological studies of HT on cognition. These findings establish a neurobiological foundation for understanding the neurofunctional impact of early HT initiation on reward processing at the menopause transition.

CognitiveConstruct

RewardProcessing

10.3969/j.issn.1673-5374.2013.35.009

Neural regeneration research

Neural Regen Res

Brain areas activated by uncertain reward-based decision-making in healthy volunteers.

Reward-based decision-making has been found to activate several brain areas, including the ventrolateral prefrontal lobe, orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mesolimbic dopaminergic system. In this study, we observed brain areas activated under three degrees of uncertainty in a reward-based decision-making task (certain, risky, and ambiguous). The tasks were presented using a brain function audiovisual stimulation system. We conducted brain scans of 15 healthy volunteers using a 3.0T magnetic resonance scanner. We used SPM8 to analyze the location and intensity of activation during the reward-based decision-making task, with respect to the three conditions. We found that the orbitofrontal cortex was activated in the certain reward condition, while the prefrontal cortex, precentral gyrus, occipital visual cortex, inferior parietal lobe, cerebellar posterior lobe, middle temporal gyrus, inferior temporal gyrus, limbic lobe, and midbrain were activated during the 'risk' condition. The prefrontal cortex, temporal pole, inferior temporal gyrus, occipital visual cortex, and cerebellar posterior lobe were activated during ambiguous decision-making. The ventrolateral prefrontal lobe, frontal pole of the prefrontal lobe, orbitofrontal cortex, precentral gyrus, inferior temporal gyrus, fusiform gyrus, supramarginal gyrus, inferior parietal lobule, and cerebellar posterior lobe exhibited greater activation in the 'risk' than in the 'certain' condition (P < 0.05). The frontal pole and dorsolateral region of the prefrontal lobe, as well as the cerebellar posterior lobe, showed significantly greater activation in the 'ambiguous' condition compared to the 'risk' condition (P < 0.05). The prefrontal lobe, occipital lobe, parietal lobe, temporal lobe, limbic lobe, midbrain, and posterior lobe of the cerebellum were activated during decision-making about uncertain rewards. Thus, we observed different levels and regions of activation for different types of reward processing during decision-making. Specifically, when the degree of reward uncertainty increased, the number of activated brain areas increased, including greater activation of brain areas associated with loss.

CognitiveConstruct

RewardProcessing

10.1080/02699931.2014.951030

Cognition & emotion

Cogn Emot

The mediating effect of prefrontal asymmetry on the relationship between the COMT Val(158)Met SNP and trait consummatory positive affect.

The Val(158)Met rs4680 polymorphism in the COMT gene regulates dopamine catabolism in the prefrontal cortex (PFC). Dopamine's involvement in reward experience suggests those with the methionine (Met) variant may exhibit trait-level sensitivity to reward due to more post-synaptic dopamine in the PFC. A physiological mediator of this association may be greater relative left asymmetry in the PFC, a putative biomarker for trait positive emotionality. Electroencephalograms of 120 participants were measured during a task that assesses two aspects of reward processing: pre-reward anticipation and post-reward consummatory affect. Participants provided genetics samples and completed the Temporal Experience of Pleasure Scale (TEPS), which assesses trait-level anticipatory and consummatory positive affect. Met carriers had higher TEPS-Consummatory scores. This effect was mediated by greater relative left activation in the post-reward phase of the task. No effects were observed for the pre-reward phase. Results suggest that frontal asymmetry is an endophenotype between COMT genotype and trait reward responsivity.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2014.07.024

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

The role of serotonin in reward, punishment and behavioural inhibition in humans: insights from studies with acute tryptophan depletion.

Deakin and Graeff proposed that forebrain 5-hydroxytryptamine (5-HT) projections are activated by aversive events and mediate anticipatory coping responses including avoidance learning and suppression of the fight-flight escape/panic response. Other theories proposed 5-HT mediates aspects of behavioural inhibition or reward. Most of the evidence comes from rodent studies. We review 36 experimental studies in humans in which the technique of acute tryptophan depletion (ATD) was used to explicitly address the role of 5-HT in response inhibition, punishment and reward. ATD did not cause disinhibition of responding in the absence of rewards or punishments (9 studies). A major role for 5-HT in reward processing is unlikely but further tests are warranted by some ATD findings. Remarkably, ATD lessened the ability of punishments (losing points or notional money) to restrain behaviour without affecting reward processing in 7 studies. Two of these studies strongly indicate that ATD blocks 5-HT mediated aversively conditioned Pavlovian inhibition and this can explain a number of the behavioural effects of ATD.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsu112

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Adaptive neural reward processing during anticipation and receipt of monetary rewards in mindfulness meditators.

Reward seeking is ubiquitous and adaptive in humans. But excessive reward seeking behavior, such as chasing monetary rewards, may lead to diminished subjective well-being. This study examined whether individuals trained in mindfulness meditation show neural evidence of lower susceptibility to monetary rewards. Seventy-eight participants (34 meditators, 44 matched controls) completed the monetary incentive delay task while undergoing functional magnetic resonance imaging. The groups performed equally on the task, but meditators showed lower neural activations in the caudate nucleus during reward anticipation, and elevated bilateral posterior insula activation during reward anticipation. Meditators also evidenced reduced activations in the ventromedial prefrontal cortex during reward receipt compared with controls. Connectivity parameters between the right caudate and bilateral anterior insula were attenuated in meditators during incentive anticipation. In summary, brain regions involved in reward processing-both during reward anticipation and receipt of reward-responded differently in mindfulness meditators than in nonmeditators, indicating that the former are less susceptible to monetary incentives.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0103653

PloS one

PLoS One

Reduced amygdala and ventral striatal activity to happy faces in PTSD is associated with emotional numbing.

There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1) individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2) that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral) faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing.

CognitiveConstruct

RewardProcessing

10.1038/nn.3779

Nature neuroscience

Nat Neurosci

Reward processing by the lateral habenula in normal and depressive behaviors.

The brain reward circuit has a central role in reinforcing behaviors that are rewarding and preventing behaviors that lead to punishment. Recent work has shown that the lateral habenula is an important part of the reward circuit by providing 'negative value' signals to the dopaminergic and serotonergic systems. Studies have also suggested that dysfunction of the lateral habenula is associated with psychiatric disorders, including major depression. Here, we discuss insights gained from neuronal recordings in monkeys regarding how the lateral habenula processes reward-related information. We then highlight recent optogenetic experiments in rodents addressing normal and abnormal functions of the habenula. Finally, we discuss how deregulation of the lateral habenula may be involved in depressive behaviors.

CognitiveConstruct

RewardProcessing

10.1016/j.brat.2014.07.007

Behaviour research and therapy

Behav Res Ther

Hungry for reward: How can neuroscience inform the development of treatment for Anorexia Nervosa?

Dysfunctional reward from the pursuit of thinness presents a major challenge to recovery from Anorexia Nervosa (AN). We explore the neuroscientific basis of aberrant reward in AN, with the aim of generating novel hypotheses for translational investigation, and elucidate disease mechanisms to inform the development of targeted interventions. Relevant neuroimaging and behavioural studies are reviewed. These suggest that altered eating in AN may be a consequence of aberrant reward processing combined with exaggerated cognitive control. We consider evidence that such aberrant reward processing is reflected in the compulsive behaviours characterising AN, with substantial overlap in the neural circuits implicated in reward processing and compulsivity. Drawing on contemporary neuroscientific theories of substance dependence, processes underpinning the shift from the initially rewarding pursuit of thinness to extreme and compulsive weight control behaviours are discussed. It is suggested that in AN, weight loss behaviour begins as overtly rewarding, goal-directed and positively reinforced, but over time becomes habitual and increasingly negatively reinforced. Excessive habit formation is suggested as one underlying mechanism perpetuating compulsive behaviour. Ongoing research into the behavioural and neural basis of aberrant reward in AN is required to further elucidate mechanisms. We discuss clinical and transdiagnostic implications, and propose that future treatment innovation may benefit from the development of novel interventions targeting aberrant reward processing in AN.

CognitiveConstruct

RewardProcessing

10.1016/j.beproc.2014.07.011

Behavioural processes

Behav Processes

Emotion and relative reward processing: an investigation on instrumental successive negative contrast and ultrasonic vocalizations in the rat.

Incentive contrast effects include changes in behavioral responses after a reward upshift (positive contrast) or downshift (negative contrast). Proposed influences on these behavioral changes are emotional state reactions after experiencing or anticipating a change in reward outcome. Rat ultrasonic vocalizations have been shown to be indicators of emotional state during behavior and anticipatory periods. The objective of the present study was to monitor rodent ultrasounds during incentive contrast using a classical runway procedure called instrumental successive negative contrast. The procedure is one that has been used often to examine incentive relativity because of its reliability in measuring negative contrast effects. Rats were trained to run in the alleyway to receive a high (12 pellets) or low magnitude (1 pellet) outcome. The high magnitude was then shifted to the low and running speeds in the alleyway for the reward and USV emission were compared. Replicating previous work, a negative contrast effect was observed with postshift running speeds significantly slower in the shifted group compared to the unshifted group. USVs did not follow the same pattern with an apparent lack of significant differences between the groups following the reward downshift. We also tested another group of animals using a visual predictive cue in the same runway test. When visual cues predicted high or low magnitude outcome, no incentive contrast was found for the running speeds following an outcome downshift, but a weak contrast effect was observed for the USV emission. These results demonstrate a separation between USVs and behavioral indicators of incentive contrast suggesting that concomitant shifts in negative affect may not be necessary for anticipatory relative reward processes.

CognitiveConstruct

RewardProcessing

10.1001/jamapsychiatry.2014.1031

JAMA psychiatry

JAMA Psychiatry

Reward processing in healthy offspring of parents with bipolar disorder.

Bipolar disorder (BD) is highly familial and characterized by deficits in reward processing. It is not known, however, whether these deficits precede illness onset or are a consequence of the disorder. To determine whether anomalous neural processing of reward characterizes children at familial risk for BD in the absence of a personal history of a psychopathologic disorder. This study compared neural activity and behaviors of children at high and low risk for mania while they anticipate and respond to reward and loss. The study was performed from September 15, 2009, through February 17, 2012, in a university functional magnetic resonance imaging facility and included 8- to 15-year-old children without disorders born to a parent with BD (n = 20 high-risk children) and demographically matched healthy comparison children (n = 25 low-risk children). Neural activity, as measured with functional magnetic resonance imaging, during anticipation and receipt of reward and loss during a monetary incentive delay task. While anticipating losses, high-risk children had less activation in the pregenual cingulate than did their low-risk counterparts (t19 = -2.44, P = .02). When receiving rewards, high-risk children had greater activation in the left lateral orbitofrontal cortex than did low-risk children (t43 = -3.04, P = .004). High-risk children also had weaker functional connectivity between the pregenual cingulate and the right ventrolateral prefrontal cortex while anticipating rewards than did low-risk children (t19 = -4.38, P < .001) but had a stronger connectivity between these regions while anticipating losses (t24 = 2.76, P = .01). Finally, in high- but not low-risk children, novelty seeking was associated with increased striatal and amygdalar activation in the anticipation of losses, and impulsivity was associated with increased striatal and insula activation in the receipt of rewards. Aberrant prefrontal activations and connectivities during reward processing suggest mechanisms that underlie early vulnerabilities for developing dysfunctional regulation of goal pursuit and motivation in children at high risk for mania. Longitudinal studies are needed to examine whether these patterns of neural activation predict the onset of mania and other mood disorders in high-risk children.

CognitiveConstruct

RewardProcessing

10.1111/jcpp.12315

Journal of child psychology and psychiatry, and allied disciplines

J Child Psychol Psychiatry

Neurocognitive predictors of substance use disorders and nicotine dependence in ADHD probands, their unaffected siblings, and controls: a 4-year prospective follow-up.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a risk factor for substance use disorders (SUDs) and nicotine dependence (ND). Neurocognitive deficits may predict the increased risk of developing SUDs and nicotine dependence. This study comprised three groups derived from the Dutch part of the International Multicenter ADHD Genetics (IMAGE) study: ADHD probands (n = 294), unaffected siblings (n = 161), and controls (n = 214). At baseline (age = 12.2), a range of neurocognitive functions was assessed including executive functions (inhibition, working memory, timing), measures of motor functioning (motor timing and tracking) and IQ. After a mean follow-up of 4.2 years, SUDs and ND were assessed. None of the neurocognitive functions predicted later SUDs or ND in ADHD probands, even after controlling for medication use and conduct disorder. Slower response inhibition predicted later nicotine dependence in unaffected siblings (OR = 2.06, 95% CI = 1.22-3.48), and lower IQ predicted increased risk for SUDs in controls (OR = 1.96, 95% CI = 1.12-3.44). Cold executive functions, motor functioning, and IQ did not predict the elevated risk of SUDs and ND in ADHD. Future studies should target 'hot' executive functions such as reward processing as risk factors for SUDs or ND.

CognitiveConstruct

RewardProcessing

10.1038/npp.2014.215

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Hypoactivation of the ventral and dorsal striatum during reward and loss anticipation in antipsychotic and mood stabilizer-naive bipolar disorder.

Increased activity within known reward-processing neurocircuitry (eg, ventral striatum, VS) has been reported among medicated individuals with bipolar disorder (BD) I and II. However, such findings are confounded by the potential ameliorative effects of mood-stabilizing and antipsychotic medications on neural activations. This study tests the hypothesis that a pathophysiological locus of alterations in reward processing is present within the striatum in antipsychotic and lithium-naive individuals with BD. Twenty antipsychotic and lithium-naive individuals with BD II or BD not-otherwise specified (NOS) and 20 matched healthy comparison individuals participated in functional magnetic resonance imaging during the performance of a monetary incentive delay task. Between-group comparisons were conducted using small-volume correction focusing on orthogonal a priori regions of interest centered in the VS and dorsal striatum (DS), respectively. During reward anticipation, unmedicated individuals with BD II/NOS had decreased activity within the DS (but not VS). During loss anticipation, on the other hand, decreased activation within both the VS and DS was observed. Across all participants, DS activity (during reward anticipation) was positively associated with putamen volume. This is the first report of decreased dorsal and ventral striatal activity among unmedicated individuals with BD II/NOS. These data contradict a simple 'reward hypersensitivity' model of BD, and add to a growing body of literature suggesting that blunted reward processing may be a vulnerability factor for both mood- and addiction-related disorders.

CognitiveConstruct

RewardProcessing

10.1038/tp.2014.69

Translational psychiatry

Transl Psychiatry

Dysfunctional dopaminergic neurotransmission in asocial BTBR mice.

Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by pronounced social and communication deficits and stereotyped behaviours. Recent psychosocial and neuroimaging studies have highlighted reward-processing deficits and reduced dopamine (DA) mesolimbic circuit reactivity in ASD patients. However, the neurobiological and molecular determinants of these deficits remain undetermined. Mouse models recapitulating ASD-like phenotypes could help generate hypotheses about the origin and neurophysiological underpinnings of clinically relevant traits. Here we used functional magnetic resonance imaging (fMRI), behavioural and molecular readouts to probe dopamine neurotransmission responsivity in BTBR T(+) Itpr3(tf)/J mice (BTBR), an inbred mouse line widely used to model ASD-like symptoms owing to its robust social and communication deficits, and high level of repetitive stereotyped behaviours. C57BL/6J (B6) mice were used as normosocial reference comparators. DA reuptake inhibition with GBR 12909 produced significant striatal DA release in both strains, but failed to elicit fMRI activation in widespread forebrain areas of BTBR mice, including mesolimbic reward and striatal terminals. In addition, BTBR mice exhibited no appreciable motor responses to GBR 12909. DA D1 receptor-dependent behavioural and signalling responses were found to be unaltered in BTBR mice, whereas dramatic reductions in pre- and postsynaptic DA D2 and adenosine A2A receptor function was observed in these animals. Overall these results document profoundly compromised DA D2-mediated neurotransmission in BTBR mice, a finding that is likely to have a role in the distinctive social and behavioural deficits exhibited by these mice. Our results call for a deeper investigation of the role of dopaminergic dysfunction in mouse lines exhibiting ASD-like phenotypes, and possibly in ASD patient populations.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2014.00092

Frontiers in psychiatry

Front Psychiatry

Cannabinoid Regulation of Brain Reward Processing with an Emphasis on the Role of CB1 Receptors: A Step Back into the Future.

Over the last decades, the endocannabinoid system has been implicated in a large variety of functions, including a crucial modulation of brain-reward circuits and the regulation of motivational processes. Importantly, behavioral studies have shown that cannabinoid compounds activate brain reward mechanisms and circuits in a similar manner to other drugs of abuse, such as nicotine, alcohol, cocaine, and heroin, although the conditions under which cannabinoids exert their rewarding effects may be more limited. Furthermore, there is evidence on the involvement of the endocannabinoid system in the regulation of cue- and drug-induced relapsing phenomena in animal models. The aim of this review is to briefly present the available data obtained using diverse behavioral experimental approaches in experimental animals, namely, the intracranial self-stimulation paradigm, the self-administration procedure, the conditioned place preference procedure, and the reinstatement of drug-seeking behavior procedure, to provide a comprehensive picture of the current status of what is known about the endocannabinoid system mechanisms that underlie modification of brain-reward processes. Emphasis is placed on the effects of cannabinoid 1 (CB1) receptor agonists, antagonists, and endocannabinoid modulators. Further, the role of CB1 receptors in reward processes is investigated through presentation of respective genetic ablation studies in mice. The vast majority of studies in the existing literature suggest that the endocannabinoid system plays a major role in modulating motivation and reward processes. However, much remains to be done before we fully understand these interactions. Further research in the future will shed more light on these processes and, thus, could lead to the development of potential pharmacotherapies designed to treat reward-dysfunction-related disorders.

CognitiveConstruct

RewardProcessing

10.1016/j.jneumeth.2014.08.007

Journal of neuroscience methods

J Neurosci Methods

Automated detection of 50-kHz ultrasonic vocalizations using template matching in XBAT.

Ultrasonic vocalizations (USVs) have been utilized to infer animals' affective states in multiple research paradigms including animal models of drug abuse, depression, fear or anxiety disorders, Parkinson's disease, and in studying neural substrates of reward processing. Currently, the analysis of USV data is performed manually, and thus is time consuming. The goal of the present study was to develop a method for automated USV recognition using a 'template detection' procedure for vocalizations in the 50-kHz range (35-80kHz). The detector is designed to run within XBAT, a MATLAB graphical user interface and extensible bioacoustics tool developed at Cornell University. Results show that this method is capable of detecting >90% of emitted USVs and that time spent analyzing data by experimenters is greatly reduced. Currently, no viable and publicly available methods exist for the automated detection of USVs. The present method, in combination with the XBAT environment is ideal for the USV community as it allows others to (1) detect USVs within a user-friendly environment, (2) make improvements to the detector and disseminate and (3) develop new tools for analysis within the MATLAB environment. The present detector provides an open-source, accurate method for the detection of 50-kHz USVs. Ongoing research will extend the current method for use in the 22-kHz frequency range of ultrasonic vocalizations. Moreover, collaborative efforts among USV researchers may enhance the capabilities of the current detector via changes to the templates and the development of new programs for analysis.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0104185

PloS one

PLoS One

Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years.

Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway.

CognitiveConstruct

RewardProcessing

10.1097/MCO.0000000000000106

Current opinion in clinical nutrition and metabolic care

Curr Opin Clin Nutr Metab Care

The energy balance in cancer cachexia revisited.

To review new putative mechanisms involved in the pathophysiology of a disturbed energy balance in cancer cachexia, which can lead to novel targets for clinical cachexia management. In the context of rapid developments in tumour treatment with potential systemic consequences, this article reviews recent data on energy requirements. Furthermore, we focus on new insights in brown adipose tissue (BAT) activity and reward processing in the brain in relation to the cachexia process. Nearly no new data have been published on energy requirements of cancer patients in the light of comprehensive new therapies in oncology. New developments, such as the introduction of staging with 18F-fluorodeoxyglucose PET-computed tomography scanning, led to the observation that BAT activation may contribute to impaired energy balance in cancer cachexia. Animal and human data to date provide an indication that BAT activation indeed occurs, but its quantitative impact on the degree of cachexia is controversial. The peripheral and central nervous system is known to influence satiation, with a possible role for impaired food reward processing in the brain. To date, there are limited confirmatory data, but this is an interesting new area to explore for better understanding and treating cancer-induced anorexia. The multimodal approach to counteract cancer cachexia should expand its targets to BAT and food reward processing in the brain.

CognitiveConstruct

RewardProcessing

10.1037/bne0000012

Behavioral neuroscience

Behav Neurosci

Extinction and reinstatement of phasic dopamine signals in the nucleus accumbens core during Pavlovian conditioning.

The prediction-error model of dopamine (DA) signaling has largely been confirmed with various appetitive Pavlovian conditioning procedures and has been supported in tests of Pavlovian extinction. Studies have repeatedly shown, however, that extinction does not erase the original memory of conditioning as the prediction-error model presumes, putting the model at odds with contemporary views that treat extinction as an episode of learning rather than unlearning of conditioning. Here, we combined fast-scan cyclic voltammetry (FSCV) with appetitive Pavlovian conditioning to assess DA release directly during extinction and reinstatement. DA was monitored in the nucleus accumbens core, which plays a key role in reward processing. Following at least 4 daily sessions of 16 tone-food pairings, fast-scan cyclic voltammetry was performed while rats received additional tone-food pairings followed by tone alone presentations (i.e., extinction). Acquisition memory was reinstated with noncontingent presentations of reward and then tested with cue presentation. Tone-food pairings produced transient (1- to 3-s) DA release in response to tone. During extinction, the amplitude of the DA response decreased significantly. Following presentation of 2 noncontingent food pellets, subsequent tone presentation reinstated the DA signal. Our results support the prediction-error model for appetitive Pavlovian extinction but not for reinstatement.

CognitiveConstruct

RewardProcessing

10.1186/s12888-014-0229-4

BMC psychiatry

BMC Psychiatry

Risk assessment and reward processing in problem gambling investigated by event-related potentials and fMRI-constrained source analysis.

The temporo-spatial dynamics of risk assessment and reward processing in problem gamblers with a focus on an ecologically valid design has not been examined previously. We investigated risk assessment and reward processing in 12 healthy male occasional gamblers (OG) and in 12 male problem gamblers (PG) with a combined EEG and fMRI approach to identify group-differences in successively activated brain regions during two stages within a quasi-realistic blackjack game. Both groups did not differ in reaction times but event-related potentials in PG and OG produced significantly different amplitudes in middle and late time-windows during high-risk vs. low-risk decisions. Applying an fMRI-constrained regional source model during risk assessment resulted in larger source moments in PG in the high-risk vs. low-risk comparison in thalamic, orbitofrontal and superior frontal activations within the 600-800 ms time window. During reward processing, PG showed a trend to enhanced negativity in an early time window (100-150 ms) potentially related to higher rostral anterior cingulate activity and a trend to centro-parietal group-differences in a later time window (390-440 ms) accompanied by increased superior-frontal (i.e., premotor-related) source moments in PG vs. OG. We suggest that problem gambling is characterized by stronger cue-related craving during risk assessment. Reward processing is associated with early affective modulation followed by increased action preparation for ongoing gambling in PG.

CognitiveConstruct

RewardProcessing

10.1007/s00276-014-1360-0

Surgical and radiologic anatomy : SRA

Surg Radiol Anat

Music and the nucleus accumbens.

Music is a universal feature of human societies over time, mainly because it allows expression and regulation of strong emotions, thus influencing moods and evoking pleasure. The nucleus accumbens (NA), the most important pleasure center of the human brain (dominates the reward system), is the 'king of neurosciences' and dopamine (DA) can be rightfully considered as its 'crown' due to the fundamental role that this neurotransmitter plays in the brain's reward system. Purpose of this article was to review the existing literature regarding the relation between music and the NA. Studies have shown that reward value for music can be coded by activity levels in the NA, whose functional connectivity with auditory and frontal areas increases as a function of increasing musical reward. Listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the NA. The functional connectivity between brain regions mediating reward, autonomic and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences. Musical stimuli can significantly increase extracellular DA levels in the NA. NA DA and serotonin were found significantly higher in animals exposed to music. Finally, passive listening to unfamiliar although liked music showed activations in the NA.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsycho.2014.07.016

Biological psychology

Biol Psychol

Quantifying familial influences on brain activation during the monetary incentive delay task: an adolescent monozygotic twin study.

Although altered brain activation during reward tasks has been found in a number of heritable psychiatric disorders and health outcomes, the familial nature of reward-related brain activation remains unexplored. In this study, we investigated the degree to which the magnitude of mesocorticolimbic reward system signal intensities in anticipation of reward during the monetary incentive delay (MID) task was similar within 46 pairs of adolescent, monozygotic twins. Significant within-pair correlations in brain activation during anticipation of gain were found in one third of the 18 reward-related regions investigated. These regions were the right nucleus accumbens, left and right posterior caudate, right anterior caudate, left insula, and anterior cingulate cortex. This serves as evidence for a shared familial contribution to individual differences in reward related brain activity in certain key reward processing regions.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2014.00778

Frontiers in psychology

Front Psychol

Compulsivity in anorexia nervosa: a transdiagnostic concept.

The compulsive nature of weight loss behaviors central to anorexia nervosa (AN), such as relentless self-starvation and over-exercise, has led to the suggestion of parallels between AN and other compulsive disorders such as obsessive-compulsive disorder (OCD) and addictions. There is a huge unmet need for effective treatments in AN, which has high rates of morbidity and the highest mortality rate of any psychiatric disorder, yet a grave paucity of effective treatments. Viewing compulsivity as a transdiagnostic concept, seen in various manifestations across disorders, may help delineate the mechanisms responsible for the persistence of AN, and aid treatment development. We explore models of compulsivity that suggest dysfunction in cortico-striatal circuitry underpins compulsive behavior, and consider evidence of aberrancies in this circuitry across disorders. Excessive habit formation is considered as a mechanism by which initially rewarding weight loss behavior in AN may become compulsive over time, and the complex balance between positive and negative reinforcement in this process is considered. The physiological effects of starvation in promoting compulsivity, positive reinforcement, and habit formation are also discussed. Further research in AN may benefit from a focus on processes potentially underlying the development of compulsivity, such as aberrant reward processing and habit formation. We discuss the implications of a transdiagnostic perspective on compulsivity, and how it may contribute to the development of novel treatments for AN.

CognitiveConstruct

RewardProcessing

10.1162/jocn_a_00694

Journal of cognitive neuroscience

J Cogn Neurosci

Learning to play it safe (or not): stable and evolving neural responses during adolescent risky decision-making.

Adolescent decision-making is a topic of great public and scientific interest. However, much of the neuroimaging research in this area contrasts only one facet of decision-making (e.g., neural responses to anticipation or receipt of monetary rewards). Few studies have directly examined the processes that occur immediately before making a decision between two options that have varied and unpredictable potential rewards and penalties. Understanding adolescent decision-making from this vantage point may prove critical to ameliorating risky behavior and improving developmental outcomes. In this study, participants aged 14-16 years engaged in a driving simulation game while undergoing fMRI. Results indicated activity in ventral striatum preceded risky decisions and activity in right inferior frontal gyrus (rIFG) preceded safe decisions. Furthermore, participants who reported higher sensation-seeking and sensitivity to reward and punishment demonstrated lower rIFG activity during safe decisions. Finally, over successive games, rIFG activity preceding risky decisions decreased, whereas thalamus and caudate activity increased during positive feedback (taking a risk without crashing). These results indicate that regions traditionally associated with reward processing and inhibition not only drive risky decision-making in the moment but also contribute to learning about risk tradeoffs during adolescence.

CognitiveConstruct

RewardProcessing

10.1017/S0033291714001718

Psychological medicine

Psychol Med

Impaired subjective well-being in schizophrenia is associated with reduced anterior cingulate activity during reward processing.

Patients with schizophrenia have substantially reduced subjective well-being (SW) compared to healthy individuals. It has been suggested that diminished SW may be related to deficits in the neural processing of reward but this has not been shown directly. We hypothesized that, in schizophrenia, lower SW would be associated with attenuated reward-related activation in the reward network. Twenty patients with schizophrenia with a range of SW underwent a functional magnetic resonance imaging (fMRI) reward task. The brain activity underlying reward anticipation and outcome in schizophrenia was examined and compared to that of 12 healthy participants using a full factorial analysis. Region of interest (ROI) analyses of areas within the reward network and whole-brain analyses were conducted to reveal neural correlates of SW. Reward-related neural activity in schizophrenia was not significantly different from that of healthy participants; however, the patients with schizophrenia showed significantly diminished SW. Both ROI and whole-brain analyses confirmed that SW scores in the patients correlated significantly with activity, specifically in the dorsal anterior cingulate cortex (dACC), during both reward anticipation and reward outcome. This association was not seen in the healthy participants. In patients with schizophrenia, reduced activation of the dACC during multiple aspects of reward processing is associated with lower SW. As the dACC has been widely linked to coupling of reward and action, and the link to SW is apparent over anticipation and outcome, these findings suggest that SW deficits in schizophrenia may be attributable to reduced integration of environmental rewarding cues, motivated behaviour and reward outcome.

CognitiveConstruct

RewardProcessing

10.1186/2045-5380-4-7

Biology of mood & anxiety disorders

Biol Mood Anxiety Disord

Increased default mode network activity in socially anxious individuals during reward processing.

Social anxiety has been associated with potentiated negative affect and, more recently, with diminished positive affect. It is unclear how these alterations in negative and positive affect are represented neurally in socially anxious individuals and, further, whether they generalize to non-social stimuli. To explore this, we used a monetary incentive paradigm to explore the association between social anxiety and both the anticipation and consumption of non-social incentives. Eighty-four individuals from a longitudinal community sample underwent functional magnetic resonance imaging (fMRI) while participating in a monetary incentive delay (MID) task. The MID task consisted of alternating cues indicating the potential to win or prevent losing varying amounts of money based on the speed of the participant's response. We examined whether self-reported levels of social anxiety, averaged across approximately 7 years of data, moderated brain activity when contrasting gain or loss cues with neutral cues during the anticipation and outcome phases of incentive processing. Whole brain analyses and analyses restricted to the ventral striatum for the anticipation phase and the medial prefrontal cortex for the outcome phase were conducted. Social anxiety did not associate with differences in hit rates or reaction times when responding to cues. Further, socially anxious individuals did not exhibit decreased ventral striatum activity during anticipation of gains or decreased MPFC activity during the outcome of gain trials, contrary to expectations based on literature indicating blunted positive affect in social anxiety. Instead, social anxiety showed positive associations with extensive regions implicated in default mode network activity (for example, precuneus, posterior cingulate cortex, and parietal lobe) during anticipation and receipt of monetary gain. Social anxiety was further linked with decreased activity in the ventral striatum during anticipation of monetary loss. Socially anxious individuals may increase default mode network activity during reward processing, suggesting high self-focused attention even in relation to potentially rewarding stimuli lacking explicit social connotations. Additionally, social anxiety may relate to decreased ventral striatum reactivity when anticipating potential losses.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0102524

PloS one

PLoS One

Synapse density and dendritic complexity are reduced in the prefrontal cortex following seven days of forced abstinence from cocaine self-administration.

Chronic cocaine exposure in both human addicts and in rodent models of addiction reduces prefrontal cortical activity, which subsequently dysregulates reward processing and higher order executive function. The net effect of this impaired gating of behavior is enhanced vulnerability to relapse. Previously we have shown that cocaine-induced increases in brain-derived neurotrophic factor (BDNF) expression in the medial prefrontal cortex (PFC) is a neuroadaptive mechanism that blunts the reinforcing efficacy of cocaine. As BDNF is known to affect neuronal survival and synaptic plasticity, we tested the hypothesis that abstinence from cocaine self-administration would lead to alterations in neuronal morphology and synaptic density in the PFC. Using a novel technique, array tomography and Golgi staining, morphological changes in the rat PFC were analyzed following 14 days of cocaine self-administration and 7 days of forced abstinence. Our results indicate that overall dendritic branching and total synaptic density are significantly reduced in the rat PFC. In contrast, the density of thin dendritic spines are significantly increased on layer V pyramidal neurons of the PFC. These findings indicate that dynamic structural changes occur during cocaine abstinence that may contribute to the observed hypo-activity of the PFC in cocaine-addicted individuals.

CognitiveConstruct

RewardProcessing

10.3389/fneur.2014.00094

Frontiers in neurology

Front Neurol

Studies on the Q175 Knock-in Model of Huntington's Disease Using Functional Imaging in Awake Mice: Evidence of Olfactory Dysfunction.

Blood oxygen level dependent (BOLD) imaging in awake mice was used to identify differences in brain activity between wild-type, HETzQ175, and HOMzQ175 genotypes in response to the odor of almond. The study was designed to see how alterations in the huntingtin gene in a mouse model of Huntington's disease would affect the perception and processing of almond odor, an evolutionarily conserved stimulus with high emotional and motivational valence. Moreover, the mice in this study were "odor naïve," i.e., never having smelled almond or any nuts. Using a segmented, annotated MRI atlas of the mouse and computational analysis, 17 out of 116 brain regions were identified as responding differently to almond odor across genotypes. These regions included the glomerulus of the olfactory bulb, forebrain cortex, anterior cingulate, subiculum, and dentate gyrus of the hippocampus, and several areas of the hypothalamus. In many cases, these regions showed a gene-dose effect with HETzQ175 mice showing a reduction in brain activity from wild-type that is further reduced in HOMzQ175 mice. Conspicuously absent were any differences in brain activity in the caudate/putamen, thalamus, CA3, and CA1 of the hippocampus and much of the cortex. The glomerulus of the olfactory bulb in HOMzQ175 mice showed a reduced change in BOLD signal intensity in response to almond odor as compared to the other phenotypes suggesting a deficit in olfactory sensitivity.

CognitiveConstruct

RewardProcessing

10.1037/neu0000120

Neuropsychology

Neuropsychology

Functional neuroimaging of the Iowa Gambling Task in older adults.

The neural systems most susceptible to age-related decline mirror the systems linked to decision making. Yet, the neural processes underlying decision-making disparities among older adults are not well understood. We sought to identify neural response patterns that distinguish 2 groups of older adults who exhibit divergent decision-making patterns. Participants were 31 healthy older adults (ages 59-88, 53% female), defined as advantageous or disadvantageous decision-makers based on Iowa Gambling Task (IGT) performance, who completed an alternate version of the IGT while undergoing functional MRI. The groups were indistinguishable on neuropsychological testing. We contrasted the BOLD signal between groups during 3 phases of the decision-making process: Prechoice (preselection), Prefeedback (postselection), and Feedback (receipt of gains/losses). We further examined whether BOLD signal varied as a function of age in each group. We observed greater activation among the IGT-Disadvantageous relative to -Advantageous older adults in the prefrontal cortex during the early phases of the decision-making process (Prechoice), and in posterior brain regions (e.g., the precuneus) during the later phases (Prefeedback and Feedback). We also found that with increasing age, IGT-Advantageous older adults showed increasing activation in the prefrontal cortex during all phases and increasing activation in the posterior cingulate during earlier phases of the decision process. By contrast, the IGT-Disadvantageous older adults exhibited a reduced or reversed trend. These functional differences may be a consequence of altered reward processing or differing compensatory strategies between IGT-Disadvantageous and -Advantageous older adults. This supports the notion that divergent neurobiological aging trajectories underlie disparate decision-making patterns.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2014.06.008

NeuroImage. Clinical

Neuroimage Clin

Striatal connectivity changes following gambling wins and near-misses: Associations with gambling severity.

Frontostriatal circuitry is implicated in the cognitive distortions associated with gambling behaviour. 'Near-miss' events, where unsuccessful outcomes are proximal to a jackpot win, recruit overlapping neural circuitry with actual monetary wins. Personal control over a gamble (e.g., via choice) is also known to increase confidence in one's chances of winning (the 'illusion of control'). Using psychophysiological interaction (PPI) analyses, we examined changes in functional connectivity as regular gamblers and non-gambling participants played a slot-machine game that delivered wins, near-misses and full-misses, and manipulated personal control. We focussed on connectivity with striatal seed regions, and associations with gambling severity, using voxel-wise regression. For the interaction term of near-misses (versus full-misses) by personal choice (participant-chosen versus computer-chosen), ventral striatal connectivity with the insula, bilaterally, was positively correlated with gambling severity. In addition, some effects for the contrast of wins compared to all non-wins were observed at an uncorrected (p < .001) threshold: there was an overall increase in connectivity between the striatal seeds and left orbitofrontal cortex and posterior insula, and a negative correlation for gambling severity with the connectivity between the right ventral striatal seed and left anterior cingulate cortex. These findings corroborate the 'non-categorical' nature of reward processing in gambling: near-misses and full-misses are objectively identical outcomes that are processed differentially. Ventral striatal connectivity with the insula correlated positively with gambling severity in the illusion of control contrast, which could be a risk factor for the cognitive distortions and loss-chasing that are characteristic of problem gambling.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2014.07.036

NeuroImage

Neuroimage

Pre-existing brain states predict risky choices.

Rational decision-making models assume that people resolve an economic problem based on its properties and the underlying utility. Here we challenge this view by examining whether pre-stimulus endogenous neuronal fluctuations can bias economic decisions. We recorded subjects' pre-stimulus neural activation patterns with fMRI before presentation and choice between pairs of certain outcomes and risky gambles. Our results indicate that activities in the left nucleus accumbens and medial frontal gyrus can bias subsequent risky decision making, showing that neuronal activities in regions associated with uncertainty and reward processing are involved in biasing subsequent choice selection. This finding challenges theories which propose that choices merely reveal stable underlying distributions of hedonic utility. Endogenous brain states of this sort might originate from a systematic cause or a stochastic type of neural noise, which can be construed as contextual factors that shape people's decision making.

CognitiveConstruct

RewardProcessing

10.1017/S0033291714000737

Psychological medicine

Psychol Med

Reduced brain reward response during cooperation in first-degree relatives of patients with psychosis: an fMRI study.

Psychosis is characterized by a profound lack of trust and disturbed social interactions. Investigating the neural basis of these deficits is difficult because of medication effects but first-degree relatives show qualitatively similar abnormalities to patients with psychosis on various tasks. This study aimed to investigate neural activation in siblings of patients in response to an interactive task. We hypothesized that, compared to controls, siblings would show (i) less basic trust at the beginning of the task and (ii) reduced activation of the brain reward and mentalizing systems. Functional magnetic resonance imaging (fMRI) data were acquired on 50 healthy siblings of patients with psychosis and 33 healthy controls during a multi-round trust game with a cooperative counterpart. An a priori region-of-interest (ROI) analysis of the caudate, temporoparietal junction (TPJ), superior temporal sulcus (STS), insula and medial prefrontal cortex (mPFC) was performed focusing on the investment and repayment phases. An exploratory whole-brain analysis was run to test for group-wise differences outside these ROIs. The siblings' behaviour during the trust game did not differ significantly from that of the controls. At the neural level, siblings showed reduced activation of the right caudate during investments, and the left insula during repayments. In addition, the whole-brain analysis revealed reduced putamen activation in siblings during investments. The findings suggest that siblings show aberrant functioning of regions traditionally involved in reward processing in response to cooperation, which may be associated with the social reward deficits observed in psychosis.

CognitiveConstruct

RewardProcessing

10.1186/1755-7682-7-29

International archives of medicine

Int Arch Med

Orquestic regulation of neurotransmitters on reward-seeking behavior.

The ventral tegmental area is strongly associated with the reward system. Dopamine is released in areas such as the nucleus accumbens and prefrontal cortex as a result of rewarding experiences such as food, sex, and neutral stimuli that become associated with them. Electrical stimulation of the ventral tegmental area or its output pathways can itself serve as a potent reward. Different drugs that increase dopamine levels are intrinsically rewarding. Although the dopaminergic system represent the cornerstone of the reward system, other neurotransmitters such as endogenous opioids, glutamate, γ-Aminobutyric acid, acetylcholine, serotonin, adenosine, endocannabinoids, orexins, galanin and histamine all affect this mesolimbic dopaminergic system. Consequently, genetic variations of neurotransmission are thought influence reward processing that in turn may affect distinctive social behavior and susceptibility to addiction. Here, we discuss current evidence on the orquestic regulation of different neurotranmitters on reward-seeking behavior and its potential effect on drug addiction.

CognitiveConstruct

RewardProcessing

10.1111/jopy.12113

Journal of personality

J Pers

Functional Neuroscience of Psychopathic Personality in Adults.

Psychopathy is a personality disorder that involves a constellation of traits including callous-unemotionality, manipulativeness, and impulsiveness. Here we review recent advances in the research of functional neural correlates of psychopathic personality traits in adults. We first provide a concise overview of functional neuroimaging findings in clinical samples diagnosed with the PCL-R. We then review studies with community samples that have focused on how individual differences in psychopathic traits (variously measured) relate to individual differences in brain function. Where appropriate, we draw parallels between the findings from these studies and those with clinical samples. Extant data suggest that individuals with high levels of psychopathic traits show lower activity in affect-processing brain areas to emotional/salient stimuli, and that attenuated activity may be dependent on the precise content of the task. They also seem to show higher activity in regions typically associated with reward processing and cognitive control in tasks involving moral processing, decision making, and reward. Furthermore, affective-interpersonal and lifestyle-antisocial facets of psychopathy appear to be associated with different patterns of atypical neural activity. Neuroimaging findings from community samples typically mirror those observed in clinical samples, and largely support the notion that psychopathy is a dimensional construct.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2014.06.019

Drug and alcohol dependence

Drug Alcohol Depend

Enhanced striatal responses during expectancy coding in alcohol dependence.

Individuals with alcohol dependence are known to make disadvantageous decisions, possibly caused by alterations in either reward or punishment sensitivity, which lead to persistent alcohol use despite its adverse consequences. Previous studies in alcohol dependence have mainly focused on reward anticipation processing and results from these studies are mixed. To clarify the nature of the motivational deficit that underlies disadvantageous choice in alcohol dependence, the current study sought to characterize the neural representation of expected value in individuals with alcohol dependence, separating expectancy-related processing of gains and losses, as a function of outcome magnitude and outcome probability. Functional MRI was used to examine brain responses during the expectation of gains and losses in patients with alcohol dependence (n=19) and healthy controls (n=19). The task manipulated outcome magnitude (€1 and €5) and outcome probability (30% and 70%). Compared to healthy controls, patients with alcohol dependence were more responsive to the expectancy of large wins, in the caudate and putamen. This effect was driven by a higher caudate activity in the contrast comparing €5 vs. €1 trials in patients with alcohol dependence. There were no group differences in the responses to the expectancy for loss. The patient group reported lower expectancies of winning in the trial-by-trial ratings. Patients with alcohol dependence showed caudate hyperactivity when expecting wins. The result contrasts with past work using the monetary incentive delay task, showing caudate hypoactivity; the passive nature of our task contrasts with an active response requirement in the MIDT studies.

CognitiveConstruct

RewardProcessing

10.1007/s00429-014-0844-3

Brain structure & function

Brain Struct Funct

Frontal glutamate and reward processing in adolescence and adulthood.

The fronto-limbic network interaction, driven by glutamatergic and dopaminergic neurotransmission, represents a core mechanism of motivated behavior and personality traits. Reward seeking behavior undergoes tremendous changes in adolescence paralleled by neurobiological changes of this network including the prefrontal cortex, striatum and amygdala. Since fronto-limbic dysfunctions also underlie major psychiatric diseases beginning in adolescence, this investigation focuses on network characteristics separating adolescents from adults. To investigate differences in network interactions, the brain reward system activity (slot machine task) together with frontal glutamate concentration (anterior cingulate cortex, ACC) was measured in 28 adolescents and 26 adults employing functional magnetic resonance imaging and magnetic resonance spectroscopy, respectively. An inverse coupling of glutamate concentrations in the ACC and activation of the ventral striatum was observed in adolescents. Further, amygdala response in adolescents was negatively correlated with the personality trait impulsivity. For adults, no significant associations of network components or correlations with impulsivity were found. The inverse association between frontal glutamate concentration and striatal activation in adolescents is in line with the triadic model of motivated behavior stressing the important role of frontal top-down inhibition on limbic structures. Our data identified glutamate as the mediating neurotransmitter of this inhibitory process and demonstrates the relevance of glutamate on the reward system and related behavioral traits like impulsivity. This fronto-limbic coupling may represent a vulnerability factor for psychiatric disorders starting in adolescence but not in adulthood.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0100697

PloS one

PLoS One

Effects of voluntary alcohol intake on risk preference and behavioral flexibility during rat adolescence.

Alcohol use is common in adolescence, with a large portion of intake occurring during episodes of binging. This pattern of alcohol consumption coincides with a critical period for neurocognitive development and may impact decision-making and reward processing. Prior studies have demonstrated alterations in adult decision-making following adolescent usage, but it remains to be seen if these alterations exist in adolescence, or are latent until adulthood. Here, using a translational model of voluntary binge alcohol consumption in adolescents, we assess the impact of alcohol intake on risk preference and behavioral flexibility during adolescence. During adolescence (postnatal day 30-50), rats were given 1-hour access to either a 10% alcohol gelatin mixture (EtOH) or a calorie equivalent gelatin (Control) at the onset of the dark cycle. EtOH consuming rats were classified as either High or Low consumers based on intake levels. Adolescent rats underwent behavioral testing once a day, with one group performing a risk preference task, and a second group performing a reversal-learning task during the 20-day period of gelatin access. EtOH-High rats showed increases in risk preference compared to Control rats, but not EtOH-Low animals. However, adolescent rats did a poor job of matching their behavior to optimize outcomes, suggesting that adolescents may adopt a response bias. In addition, adolescent ethanol exposure did not affect the animals' ability to flexibly adapt behavior to changing reward contingencies during reversal learning. These data support the view that adolescent alcohol consumption can have short-term detrimental effects on risk-taking when examined during adolescence, which does not seem to be attributable to an inability to flexibly encode reward contingencies on behavioral responses.

CognitiveConstruct

RewardProcessing

10.1097/WNR.0000000000000226

Neuroreport

Neuroreport

P300, not feedback error-related negativity, manifests the waiting cost of receiving reward information.

Previous studies have investigated how temporal discounting influences reward processing in the human brain; however, it remains unclear whether a short delay in presenting an outcome affects brain activity related to reward processing that is indexed by the two event-related potential components: the feedback error-related negativity (fERN) and P300 components. The present study used a revised simple gambling task and manipulated the waiting time before reward presentation. Behavioral data showed that participants did not respond differently between conditions; however, they reported more negative emotion under long-waiting conditions than under short-waiting conditions. Event-related potential results showed that fERN was not significantly different between the two conditions, whereas the short-waiting feedback elicited a notably larger P300 amplitude than the long-waiting feedback, particularly in frontal-central regions. The present study shows that P300, not fERN, reflects high-level motivated evaluation of waiting cost in such a decision-making task.

CognitiveConstruct

RewardProcessing

10.1016/j.psyneuen.2014.04.022

Psychoneuroendocrinology

Psychoneuroendocrinology

Cortisol administration induces global down-regulation of the brain's reward circuitry.

Research in rodents and humans has shown divergent effects of the glucocorticoids corticosterone and cortisol (CRT) on reward processing. In rodents, administration of CRT increases reward drive by facilitating dopamine release in the ventral striatum. In humans, correspondingly, risky decision-making increases when CRT levels are elevated. Human stress studies contrariwise show that elevated CRT is accompanied by a decrease in reward-related brain activity. There are however no direct insights into how CRT acts on the reward system in the human brain. Accordingly, we used pharmacological functional magnetic resonance imaging (pharmaco-fMRI) to investigate the effects of CRT on the brain's reward system. In a randomized within-subject design we administered a high dose of CRT (40 mg) and placebo to twenty healthy male volunteers on separate days, and used a monetary incentive delay task to assess the effects of the hormone on the striatum and the amygdala in anticipation of potential reward. In contrast to animal studies, we show that this high dose of CRT strongly decreases activity of the striatum in both reward and non-reward conditions. Furthermore, we observed reductions in activity in the basolateral amygdala, a key regulator of the brain's reward system. Crucially, the overall down-regulation of the brain's reward circuit was verified on the subjective level as subjects reported significantly reduced reward preference after CRT. In sum, we provide here direct evidence in humans that CRT acts on brain regions involved in reward-related behavior, that is, the basolateral amygdala and the striatum. Our findings suggest that CRT in the quantity and time course presently used globally down-regulates the reward system, and thereby decreases motivational processing in general.

CognitiveConstruct

RewardProcessing

10.1016/j.psychres.2014.06.030

Psychiatry research

Psychiatry Res

Differential hedonic experience and behavioral activation in schizophrenia and bipolar disorder.

The Kraepelinian distinction between schizophrenia (SZ) and bipolar disorder (BP) emphasizes affective and volitional impairment in the former, but data directly comparing the two disorders for hedonic experience are scarce. This study examined whether hedonic experience and behavioral activation may be useful phenotypes distinguishing SZ and BP. Participants were 39 SZ and 24 BP patients without current mood episode matched for demographics and negative affect, along with 36 healthy controls (HC). They completed the Chapman Physical and Social Anhedonia Scales, Temporal Experience of Pleasure Scale (TEPS), and Behavioral Activation Scale (BAS). SZ and BP showed equally elevated levels of self-report negative affect and trait anhedonia compared to HC. However, SZ reported significantly lower pleasure experience (TEPS) and behavioral activation (BAS) than BP, who did not differ from HC. SZ and BP showed differential patterns of relationships between the hedonic experience and behavioral activation measures. Overall, the results suggest that reduced hedonic experience and behavioral activation may be effective phenotypes distinguishing SZ from BP even when affective symptoms are minimal. However, hedonic experience differences between SZ and BP are sensitive to measurement strategy, calling for further research on the nature of anhedonia and its relation to motivation in these disorders.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2014.06.058

NeuroImage

Neuroimage

Reward dysfunction in major depression: multimodal neuroimaging evidence for refining the melancholic phenotype.

Reward dysfunction is thought to play a core role in the pathophysiology of major depressive disorder (MDD). Event-related potential (ERP) and functional magnetic resonance imaging (fMRI) studies have identified reward processing deficits in MDD, but these methods have yet to be applied together in a single MDD sample. We utilized multimodal neuroimaging evidence to examine reward dysfunction in MDD. Further, we explored how neurobiological reward dysfunction would map onto subtypes of MDD. The feedback negativity (FN), an ERP index of reward evaluation, was recorded in 34 unmedicated depressed individuals and 42 never-depressed controls during a laboratory gambling task. Ventral striatal (VS) activation to reward was recorded in a separate fMRI session, using an identical task, among a subgroup of 24 depressed individuals and a comparison group of 18 non-depressed controls. FN amplitude was blunted in MDD. This effect was driven by a MDD subgroup characterized by impaired mood reactivity to positive events, a core feature of melancholic MDD. A similar pattern was observed for VS activation, which was also blunted among the MDD subgroup with impaired mood reactivity. Neither FN amplitude nor VS activation was related to the full, DSM-defined melancholic or atypical MDD subtypes. Across the MDD sample, FN amplitude and VS activation were correlated, indicating convergence across methods. These results indicate that not all MDD is characterized by reward dysfunction, and that there is meaningful heterogeneity in reward processing within MDD. The current study offers neurobiological evidence that impaired mood reactivity is a key phenotypic distinction for subtyping MDD, and further suggests that the existing melancholic phenotype may require further refinement.

CognitiveConstruct

RewardProcessing

10.1159/000362328

Developmental neuroscience

Dev Neurosci

The developmental mismatch in structural brain maturation during adolescence.

Regions of the human brain develop at different rates across the first two decades of life, with some maturing before others. It has been hypothesized that a mismatch in the timing of maturation between subcortical regions (involved in affect and reward processing) and prefrontal regions (involved in cognitive control) underlies the increase in risk-taking and sensation-seeking behaviors observed during adolescence. Most support for this 'dual systems' hypothesis relies on cross-sectional data, and it is not known whether this pattern is present at an individual level. The current study utilizes longitudinal structural magnetic resonance imaging (MRI) data to describe the developmental trajectories of regions associated with risk-taking and sensation-seeking behaviors, namely, the amygdala, nucleus accumbens (NAcc) and prefrontal cortex (PFC). Structural trajectories of gray matter volumes were analyzed using FreeSurfer in 33 participants aged 7-30 years, each of whom had at least three high-quality MRI scans spanning three developmental periods: late childhood, adolescence and early adulthood (total 152 scans). The majority of individuals in our sample showed relatively earlier maturation in the amygdala and/or NAcc compared to the PFC, providing evidence for a mismatch in the timing of structural maturation between these structures. We then related individual developmental trajectories to retrospectively assessed self-reported risk-taking and sensation-seeking behaviors during adolescence in a subsample of 24 participants. Analysis of this smaller sample failed to find a relationship between the presence of a mismatch in brain maturation and risk-taking and sensation-seeking behaviors during adolescence. Taken together, it appears that the developmental mismatch in structural brain maturation is present in neurotypically developing individuals. This pattern of development did not directly relate to self-reported behaviors at an individual level in our sample, highlighting the need for prospective studies combining anatomical and behavioral measures.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22571

Human brain mapping

Hum Brain Mapp

Distinct neural responses to conscious versus unconscious monetary reward cues.

Human reward pursuit is often assumed to involve conscious processing of reward information. However, recent research revealed that reward cues enhance cognitive performance even when perceived without awareness. Building on this discovery, the present functional MRI study tested two hypotheses using a rewarded mental-rotation task. First, we examined whether subliminal rewards engage the ventral striatum (VS), an area implicated in reward anticipation. Second, we examined differences in neural responses to supraliminal versus subliminal rewards. Results indicated that supraliminal, but not subliminal, high-value reward cues engaged brain areas involved in reward processing (VS) and task performance (supplementary motor area, motor cortex, and superior temporal gyrus). This pattern of findings is striking given that subliminal rewards improved performance to the same extent as supraliminal rewards. So, the neural substrates of conscious versus unconscious reward pursuit are vastly different-but despite their differences, conscious and unconscious reward pursuit may still produce the same behavioral outcomes.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsu091

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Anticipation of high arousal aversive and positive movie clips engages common and distinct neural substrates.

The neural correlates of anxious anticipation have been primarily studied with aversive and neutral stimuli. In this study, we examined the effect of valence on anticipation by using high arousal aversive and positive stimuli and a condition of uncertainty (i.e. either positive or aversive). The task consisted of predetermined cues warning participants of upcoming aversive, positive, 'uncertain' (either aversive or positive) and neutral movie clips. Anticipation of all affective clips engaged common regions including the anterior insula, dorsal anterior cingulate cortex, thalamus, caudate, inferior parietal and prefrontal cortex that are associated with emotional experience, sustained attention and appraisal. In contrast, the nucleus accumbens and medial prefrontal cortex, regions implicated in reward processing, were selectively engaged during anticipation of positive clips (depicting sexually explicit content) and the mid-insula, which has been linked to processing aversive stimuli, was selectively engaged during anticipation of aversive clips (depicting graphic medical procedures); these three areas were also activated during anticipation of 'uncertain' clips reflecting a broad preparatory response for both aversive and positive stimuli. These results suggest that a common circuitry is recruited in anticipation of affective clips regardless of valence, with additional areas preferentially engaged depending on whether expected stimuli are negative or positive.

CognitiveConstruct

RewardProcessing

10.1021/ac501725u

Analytical chemistry

Anal Chem

Multiple scan rate voltammetry for selective quantification of real-time enkephalin dynamics.

Methionine-enkephalin (M-ENK) and leucine-enkephalin (L-ENK) are small endogenous opioid peptides that have been implicated in a wide variety of complex physiological functions, including nociception, reward processing, and motivation. However, our understanding of the role that these molecules play in modulating specific brain circuits remains limited, largely due to challenges in determining where, when, and how specific neuropeptides are released in tissue. Background-subtracted fast-scan cyclic voltammetry coupled with carbon-fiber microelectrodes has proven to be sensitive and selective for detecting rapidly fluctuating neurochemicals in vivo; however, many challenges exist for applying this approach to the detection of neuropeptides. We have developed and characterized a novel voltammetric waveform for the selective quantification of small tyrosine-containing peptides, such as the ENKs, with rapid temporal (subsecond) and precise spatial (10s of micrometers) resolution. We have established that the main contributor to the electrochemical signal inherent to M-ENK is tyrosine and that conventional waveforms provide poor peak resolution and lead to fouling of the electrode surface. By employing two distinct scan rates in each anodic sweep of this analyte-specific waveform, we have selectively distinguished M-ENK from common endogenous interfering agents, such as ascorbic acid, pH shifts, and even L-ENK. Finally, we have used this approach to simultaneously quantify catecholamine and M-ENK fluctuations in live tissue. This work provides a foundation for real-time measurements of endogenous ENK fluctuations in biological locations, and the underlying concept of using multiple scan rates is adaptable to the voltammetric detection of other tyrosine-containing neuropeptides.

CognitiveConstruct

RewardProcessing

10.1162/jocn_a_00677

Journal of cognitive neuroscience

J Cogn Neurosci

Adolescents adapt more slowly than adults to varying reward contingencies.

It has been suggested that adolescents process rewards differently from adults, both cognitively and affectively. In an fMRI study we recorded brain BOLD activity of adolescents (age range = 14-15 years) and adults (age range = 20-39 years) to investigate the developmental changes in reward processing and decision-making. In a probabilistic reversal learning task, adolescents and adults adapted to changes in reward contingencies. We used a reinforcement learning model with an adaptive learning rate for each trial to model the adolescents' and adults' behavior. Results showed that adolescents possessed a shallower slope in the sigmoid curve governing the relation between expected value (the value of the expected feedback, +1 and -1 representing rewarding and punishing feedback, respectively) and probability of stay (selecting the same option as in the previous trial). Trial-by-trial change in expected values after being correct or wrong was significantly different between adolescents and adults. These values were closer to certainty for adults. Additionally, absolute value of model-derived prediction error for adolescents was significantly higher after a correct response but a punishing feedback. At the neural level, BOLD correlates of learning rate, expected value, and prediction error did not significantly differ between adolescents and adults. Nor did we see group differences in the prediction error-related BOLD signal for different trial types. Our results indicate that adults seem to behaviorally integrate punishing feedback better than adolescents in their estimation of the current state of the contingencies. On the basis of these results, we argue that adolescents made decisions with less certainty when compared with adults and speculate that adolescents acquired a less accurate knowledge of their current state, that is, of being correct or wrong.

CognitiveConstruct

RewardProcessing

10.1016/j.jaac.2014.05.003

Journal of the American Academy of Child and Adolescent Psychiatry

J Am Acad Child Adolesc Psychiatry

Mapping the development of the basal ganglia in children with attention-deficit/hyperactivity disorder.

The basal ganglia are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), but little is known of their development in the disorder. Here, we mapped basal ganglia development from childhood into late adolescence using methods that define surface morphology with an exquisite level of spatial resolution. Surface morphology of the basal ganglia was defined from neuroanatomic magnetic resonance images acquired in 270 youth with DSM-IV-defined ADHD and 270 age- and sex-matched typically developing controls; 220 individuals were scanned at least twice. Using linear mixed model regression, we mapped developmental trajectories from age 4 through 19 years at approximately 7,500 surface vertices in the striatum and globus pallidus. In the ventral striatal surfaces, there was a diagnostic difference in developmental trajectories (t = 5.6, p < .0001). Here, the typically developing group showed surface area expansion with age (estimated rate of increase of 0.54 mm(2) per year, standard error [SE] 0.29 mm(2) per year), whereas the ADHD group showed progressive contraction (decrease of 1.75 mm(2) per year, SE 0.28 mm(2) per year). The ADHD group also showed significant, fixed surface area reductions in dorsal striatal regions, which were detected in childhood at study entry and persisted into adolescence. There was no significant association between history of psychostimulant treatment and developmental trajectories. Progressive, atypical contraction of the ventral striatal surfaces characterizes ADHD, localizing to regions pivotal in reward processing. This contrasts with fixed, nonprogressive contraction of dorsal striatal surfaces in regions that support executive function and motor planning.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsu086

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Reward for food odors: an fMRI study of liking and wanting as a function of metabolic state and BMI.

Brain reward systems mediate liking and wanting for food reward. Here, we explore the differential involvement of the following structures for these two components: the ventral and dorsal striatopallidal area, orbitofrontal cortex (OFC), anterior insula and anterior cingulate. Twelve healthy female participants were asked to rate pleasantness (liking of food and non-food odors) and the desire to eat (wanting of odor-evoked food) during event-related functional magnetic resonance imaging (fMRI). The subjective ratings and fMRI were performed in hunger and satiety states. Activations of regions of interest were compared as a function of task (liking vs wanting), odor category (food vs non-food) and metabolic state (hunger vs satiety). We found that the nucleus accumbens and ventral pallidum were differentially involved in liking or wanting during the hunger state, which suggests a reciprocal inhibitory influence between these structures. Neural activation of OFC subregions was correlated with either liking or wanting ratings, suggesting an OFC role in reward processing magnitude. Finally, during the hunger state, participants with a high body mass index exhibited less activation in neural structures underlying food reward processing. Our results suggest that food liking and wanting are two separable psychological constructs and may be functionally segregated within the cortico-striatopallidal circuit.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2014.04.018

Biological psychiatry

Biol Psychiatry

Reward and affective regulation in depression-prone smokers.

There is a disproportionately high smoking prevalence among individuals who are prone to depression. While depression has been conceptualized as a disorder of dysregulated positive affect and disrupted reward processing, little research has been conducted to determine the role of smoking in these processes among depression-prone smokers. Depression-prone smokers (DP+; n = 34) and smokers not depression-prone (DP-; n = 49) underwent two laboratory sessions, one while smoking abstinent and one while smoking ad libitum, to assess the relative reinforcing value of smoking and reward sensitivity. Using experience sampling methods, participants completed self-report measures of subjective reward, positive affect, and negative affect across 3 days while smoking as usual and 3 days while smoking abstinent. DP+ were two times more likely to work for cigarette puffs versus money in a progressive ratio, choice task (odds ratio 2.05; 95% confidence interval 1.04 to 4.06, p = .039) compared with DP-. Reward sensitivity as measured by the signal detection task did not yield any significant findings. Mixed models regressions revealed a three-way interaction (depression group, smoking phase, and time) for subjective reward, negative affect, and positive affect. For all three of these outcomes, the slopes for DP- and DP+ differed significantly from each other (ps < .05) and the effect of smoking (versus abstinence) over time was greater for DP+ than DP- smokers (ps < .05). These findings indicate that the effects of smoking on reward and positive affect regulation are specific to DP+ smokers and highlight novel targets for smoking cessation treatment in this population.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2014.06.020

NeuroImage

Neuroimage

Gambling for self, friends, and antagonists: differential contributions of affective and social brain regions on adolescent reward processing.

Adolescence is a time of increasing emotional arousal, sensation-seeking and risk-taking, especially in the context of peers. Recent neuroscientific studies have pinpointed to the role of the ventral striatum as a brain region which is particularly sensitive to reward, and to 'social brain' regions, such as the medial prefrontal cortex (mPFC), the precuneus, and the temporal parietal junction, as being particularly responsive to social contexts. However, no study to date has examined adolescents' sensitivity to reward across different social contexts. In this study we examined 249 participants between the ages 8 and 25, on a monetary reward-processing task. Participants could win or lose money for themselves, their best friend and a disliked peer. Winning for self resulted in a mid- to late adolescent specific peak in neural activation in the ventral striatum, whereas winning for a disliked peer resulted in a mid- to late adolescent specific peak in the mPFC. Our findings reveal that ventral striatum and mPFC hypersensitivity in adolescence is dependent on social context. Taken together, these results suggest that increased risk-taking and sensation seeking observed in adolescence might not be purely related to hyperactivity of the ventral striatum, but that these behaviors are probably strongly related to the social context in which they occur.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2014.04.010

NeuroImage. Clinical

Neuroimage Clin

Enhanced subgenual cingulate response to altruistic decisions in remitted major depressive disorder.

Major depressive disorder (MDD) is associated with functional abnormalities in fronto-meso-limbic networks contributing to decision-making, affective and reward processing impairments. Such functional disturbances may underlie a tendency for enhanced altruism driven by empathy-based guilt observed in some patients. However, despite the relevance of altruistic decisions to understanding vulnerability, as well as everyday psychosocial functioning, in MDD, their functional neuroanatomy is unknown. Using a charitable donations experiment with fMRI, we compared 14 medication-free participants with fully remitted MDD and 15 demographically-matched control participants without MDD. Compared with the control group, the remitted MDD group exhibited enhanced BOLD response in a septal/subgenual cingulate cortex (sgACC) region for charitable donation relative to receiving simple rewards and higher striatum activation for both charitable donation and simple reward relative to a low level baseline. The groups did not differ in demographics, frequency of donations or response times, demonstrating only a difference in neural architecture. We showed that altruistic decisions probe residual sgACC hypersensitivity in MDD even after symptoms are fully remitted. The sgACC has previously been shown to be associated with guilt which promotes altruistic decisions. In contrast, the striatum showed common activation to both simple and altruistic rewards and could be involved in the so-called "warm glow" of donation. Enhanced neural response in the depression group, in areas previously linked to altruistic decisions, supports the hypothesis of a possible association between hyper-altruism and depression vulnerability, as shown by recent epidemiological studies.

CognitiveConstruct

RewardProcessing

10.1152/jn.00040.2014

Journal of neurophysiology

J Neurophysiol

Basal forebrain dynamics during a tactile discrimination task.

The nucleus basalis (NB) is a cholinergic neuromodulatory structure that projects liberally to the entire cortical mantle and regulates information processing in all cortical layers. Here, we recorded activity from populations of single units in the NB as rats performed a whisker-dependent tactile discrimination task. Over 80% of neurons responded with significant modulation in at least one phase of the task. Such activity started before stimulus onset and continued for seconds after reward delivery. Firing rates monotonically increased with reward magnitude during the task, suggesting that NB neurons are not indicating the absolute deviation from expected reward amounts. Individual neurons also encoded significant amounts of information about stimulus identity. Such robust coding was not present when the same stimuli were delivered to lightly anesthetized animals, suggesting that the NB neurons contain a sensorimotor, rather than purely sensory or motor, representation of the environment. Overall, these results support the hypothesis that neurons in the NB provide a value-laden representation of the sensorimotor state of the animal as it engages in significant behavioral tasks.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2014.04.007

Psychiatry research

Psychiatry Res

Abstinent adult daily smokers show reduced anticipatory but elevated saccade-related brain responses during a rewarded antisaccade task.

Chronic smoking may result in reduced sensitivity to non-drug rewards (e.g., money), a phenomenon particularly salient during abstinence. During a quit attempt, this effect may contribute to biased decision-making (smoking>alternative reinforcers) and relapse. Although relevant for quitting, characterization of reduced reward function in abstinent smokers remains limited. Moreover, how attenuated reward function affects other brain systems supporting decision-making has not been established. Here, we use a rewarded antisaccade (rAS) task to characterize non-drug reward processing and its influence on inhibitory control, key elements underlying decision-making, in abstinent smokers vs. non-smokers. Abstinent (12-hours) adult daily smokers (N=23) and non-smokers (N=11) underwent fMRI while performing the rAS. Behavioral performances improved on reward vs. neutral trials. Smokers showed attenuated activation in ventral striatum during the reward cue and in superior precentral sulcus and posterior parietal cortex during response preparation, but greater responses during the saccade response in posterior cingulate and parietal cortices. Smokers' attenuated anticipatory responses suggest reduced motivation from monetary reward, while heightened activation during the saccade response suggests that additional circuitry may be engaged later to enhance inhibitory task performance. Overall, this preliminary study highlights group differences in decision-making components and the utility of the rAS to characterize these effects.

CognitiveConstruct

RewardProcessing

10.1503/jpn.130207

Journal of psychiatry & neuroscience : JPN

J Psychiatry Neurosci

Do reward-processing deficits in schizophrenia-spectrum disorders promote cannabis use? An investigation of physiological response to natural rewards and drug cues.

Dysfunctional reward processing is present in individuals with schizophrenia-spectrum disorders (SSD) and may confer vulnerability to addiction. Our objective was to identify a deficit in patients with SSD on response to rewarding stimuli and determine whether this deficit predicts cannabis use. We divided a group of patients with SSD and nonpsychotic controls into cannabis users and nonusers. Response to emotional and cannabis-associated visual stimuli was assessed using self-report, event-related potentials (using the late positive potential [LPP]), facial electromyography and skin-conductance response. Our sample comprised 35 patients with SSD and 35 nonpsychotic controls. Compared with controls, the patients with SSD showed blunted LPP response to pleasant stimuli (p = 0.003). Across measures, cannabis-using controls showed greater response to pleasant stimuli than to cannabis stimuli whereas cannabis-using patients showed little bias toward pleasant stimuli. Reduced LPP response to pleasant stimuli was predictive of more frequent subsequent cannabis use (β = -0.24, p = 0.034). It is not clear if the deficit associated with cannabis use is specific to rewarding stimuli or nonspecific to any kind of emotionally salient stimuli. The LPP captures a reward-processing deficit in patients with SSD and shows potential as a biomarker for identifying patients at risk of heavy cannabis use.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2014.05.023

Neuropsychologia

Neuropsychologia

Greater striatal responses to medication in Parkinson׳s disease are associated with better task-switching but worse reward performance.

Dopaminergic medication in Parkinson's disease has been proposed to improve cognitive processing by modulating the severely depleted dorsal striatum, while impairing reward processing by modulating the relatively intact ventral striatum. However, there is no direct (neural) evidence for this hypothesis. Here we fill this gap by scanning Parkinson's disease patients (n=15) ON and relatively OFF their dopaminergic medication using functional magnetic resonance imaging. During scanning, patients performed a task that enabled the simultaneous measurement of task-switching and reward-related processing. Brain-behavior correlations revealed that medication-related increases (ON-OFF) in switch-related BOLD signal (switch-repeat) in the dorsomedial striatum were associated, on an individual basis, with improvements in task-switching (i.e. a decreased switch cost). Conversely, medication-related increases (ON-OFF) in reward-related BOLD signal (high-low) in the ventromedial striatum were associated, on an individual basis, with impairments in performance in anticipation of reward (i.e. an increased reward cost). Linear regression analyses demonstrated that the positive relationship between medication-related changes in BOLD and the reward cost was unique to the ventromedial striatum, whereas the negative relationship between medication-related changes in BOLD and the switch cost was not unique to the dorsomedial striatum. These findings extend the dopamine overdose hypothesis, according to which dopamine-induced changes in dorsal and ventral striatal processing lead to cognitive improvement and impairment respectively.

CognitiveConstruct

RewardProcessing

10.1016/j.nlm.2014.05.009

Neurobiology of learning and memory

Neurobiol Learn Mem

A role for the lateral dorsal tegmentum in memory and decision neural circuitry.

A role for the hippocampus in memory is clear, although the mechanism for its contribution remains a matter of debate. Converging evidence suggests that hippocampus evaluates the extent to which context-defining features of events occur as expected. The consequence of mismatches, or prediction error, signals from hippocampus is discussed in terms of its impact on neural circuitry that evaluates the significance of prediction errors: Ventral tegmental area (VTA) dopamine cells burst fire to rewards or cues that predict rewards (Schultz, Dayan, & Montague, 1997). Although the lateral dorsal tegmentum (LDTg) importantly controls dopamine cell burst firing (Lodge & Grace, 2006) the behavioral significance of the LDTg control is not known. Therefore, we evaluated LDTg functional activity as rats performed a spatial memory task that generates task-dependent reward codes in VTA (Jo, Lee, & Mizumori, 2013; Puryear, Kim, & Mizumori, 2010) and another VTA afferent, the pedunculopontine nucleus (PPTg, Norton, Jo, Clark, Taylor, & Mizumori, 2011). Reversible inactivation of the LDTg significantly impaired choice accuracy. LDTg neurons coded primarily egocentric information in the form of movement velocity, turning behaviors, and behaviors leading up to expected reward locations. A subset of the velocity-tuned LDTg cells also showed high frequency bursts shortly before or after reward encounters, after which they showed tonic elevated firing during consumption of small, but not large, rewards. Cells that fired before reward encounters showed stronger correlations with velocity as rats moved toward, rather than away from, rewarded sites. LDTg neural activity was more strongly regulated by egocentric behaviors than that observed for PPTg or VTA cells that were recorded by Puryear et al. and Norton et al. While PPTg activity was uniquely sensitive to ongoing sensory input, all three regions encoded reward magnitude (although in different ways), reward expectation, and reward encounters. Only VTA encoded reward prediction errors. LDTg may inform VTA about learned goal-directed movement that reflects the current motivational state, and this in turn may guide VTA determination of expected subjective goal values. When combined it is clear the LDTg and PPTg provide only a portion of the information that dopamine cells need to assess the value of prediction errors, a process that is essential to future adaptive decisions and switches of cognitive (i.e. memorial) strategies and behavioral responses.

CognitiveConstruct

RewardProcessing

10.1111/jcpp.12279

Journal of child psychology and psychiatry, and allied disciplines

J Child Psychol Psychiatry

A longitudinal high-risk study of adolescent anxiety, depression and parent-severity on the developmental course of risk-adjustment.

Adolescence is associated with developments in the reward system and increased rates of emotional disorders. Familial risk for depression may be associated with disruptions in the reward system. However, it is unclear how symptoms of depression and anxiety influence the development of reward-processing over adolescence and whether variation in the severity of parental depression is associated with hyposensitivity to reward in a high-risk sample. We focused on risk-adjustment (adjusting decisions about reward according to the probability of obtaining reward) as this was hypothesized to improve over adolescence. In a one-year longitudinal sample (N = 197) of adolescent offspring of depressed parents, we examined how symptoms of depression and anxiety (generalized anxiety and social anxiety) influenced the development of risk-adjustment. We also examined how parental depression severity influenced adolescent risk-adjustment. Risk-adjustment improved over the course of the study indicating improved adjustment of reward-seeking to shifting contingencies. Depressive symptoms were associated with decreases in risk-adjustment over time while social anxiety symptoms were associated with increases in risk-adjustment over time. Specifically, depression was associated with reductions in reward-seeking at favourable reward probabilities only, whereas social anxiety (but not generalized anxiety) led to reductions in reward-seeking at low reward probabilities only. Parent depression severity was associated with lowered risk-adjustment in offspring and also influenced the longitudinal relationship between risk-adjustment and offspring depression. Anxiety and depression distinctly alter the pattern of longitudinal change in reward-processing. Severity of parent depression was associated with alterations in adolescent offspring reward-processing in a high-risk sample.

CognitiveConstruct

RewardProcessing

10.3389/fnsys.2014.00101

Frontiers in systems neuroscience

Front Syst Neurosci

Translational studies of goal-directed action as a framework for classifying deficits across psychiatric disorders.

The ability to learn contingencies between actions and outcomes in a dynamic environment is critical for flexible, adaptive behavior. Goal-directed actions adapt to changes in action-outcome contingencies as well as to changes in the reward-value of the outcome. When networks involved in reward processing and contingency learning are maladaptive, this fundamental ability can be lost, with detrimental consequences for decision-making. Impaired decision-making is a core feature in a number of psychiatric disorders, ranging from depression to schizophrenia. The argument can be developed, therefore, that seemingly disparate symptoms across psychiatric disorders can be explained by dysfunction within common decision-making circuitry. From this perspective, gaining a better understanding of the neural processes involved in goal-directed action, will allow a comparison of deficits observed across traditional diagnostic boundaries within a unified theoretical framework. This review describes the key processes and neural circuits involved in goal-directed decision-making using evidence from animal studies and human neuroimaging. Select studies are discussed to outline what we currently know about causal judgments regarding actions and their consequences, action-related reward evaluation, and, most importantly, how these processes are integrated in goal-directed learning and performance. Finally, we look at how adaptive decision-making is impaired across a range of psychiatric disorders and how deepening our understanding of this circuitry may offer insights into phenotypes and more targeted interventions.

CognitiveConstruct

RewardProcessing

10.1111/add.12542

Addiction (Abingdon, England)

Addiction

Commentary on Lorains et al. (2014): a potentially important advance is understanding different types of gamblers.

CognitiveConstruct

RewardProcessing

10.1162/jocn_a_00676

Journal of cognitive neuroscience

J Cogn Neurosci

Reward acts on the pFC to enhance distractor resistance of working memory representations.

Working memory and reward processing are often thought to be separate, unrelated processes. However, most daily activities involve integrating these two types of information, and the two processes rarely, if ever, occur in isolation. Here, we show that working memory and reward interact in a task-dependent manner and that this task-dependent interaction involves modulation of the pFC by the ventral striatum. Specifically, BOLD signal during gains relative to losses in the ventral striatum and pFC was associated not only with enhanced distractor resistance but also with impairment in the ability to update working memory representations. Furthermore, the effect of reward on working memory was accompanied by differential coupling between the ventral striatum and ignore-related regions in the pFC. Together, these data demonstrate that reward-related signals modulate the balance between cognitive stability and cognitive flexibility by altering functional coupling between the ventral striatum and the pFC.

CognitiveConstruct

RewardProcessing

10.1111/jcpp.12270

Journal of child psychology and psychiatry, and allied disciplines

J Child Psychol Psychiatry

Reward anticipation and processing of social versus nonsocial stimuli in children with and without autism spectrum disorders.

How children respond to social and nonsocial rewards has important implications for both typical and atypical social-cognitive development. Individuals with autism spectrum disorders (ASD) are thought to process rewards differently than typically developing (TD) individuals. However, there is little direct evidence to support this claim. Two event-related potentials were measured. The stimulus preceding negativity (SPN) was utilized to measure reward anticipation, and the feedback related negativity (FRN) was utilized to measure reward processing. Participants were 6- to 8-year-olds with (N = 20) and without (N = 23) ASD. Children were presented with rewards accompanied by incidental face or nonface stimuli. Nonface stimuli were composed of scrambled face elements in the shape of arrows, controlling for low-level visual properties. Children with ASD showed smaller responses while anticipating and processing rewards accompanied by social stimuli than TD children. Anticipation and processing of rewards accompanied by nonsocial stimuli was intact in children with ASD. This is the first study to measure both reward anticipation and processing in ASD while controlling for reward properties. The findings provide evidence that children with autism have reward anticipation and processing deficits for social stimuli only. Our results suggest that while typically developing children find social stimuli more salient than nonsocial stimuli, children with ASD may have the opposite preference.

CognitiveConstruct

RewardProcessing

10.1037/a0036191

Journal of abnormal psychology

J Abnorm Psychol

Major depression in mothers predicts reduced ventral striatum activation in adolescent female offspring with and without depression.

Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder (MDD). However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for MDD. One way of studying vulnerability is through a high-risk design. Therefore, the aim of the current study was to determine whether reward-related activation of the ventral striatum is reduced in nondepressed daughters of mothers with a history of MDD (high-risk) similarly to currently depressed adolescent girls, compared with healthy controls. By directly comparing groups with a shared risk profile during differing states, we aimed to shed light on the endophenotypic nature of reduced reward processing for adolescent depression. We compared reward-related neural activity through functional magnetic resonance imaging (fMRI) between three groups of female biological offspring (N = 52) of mothers with differential MDD status: (a) currently depressed daughters of mothers with a history of MDD (MDD group; n = 14), (b) age- and socioeconomic status (SES)-matched never-depressed daughters of mothers with a history of MDD (high-risk group; n = 19), and (c) age- and SES-matched control daughters of mothers with no past or current psychopathology in either the mother or the daughter (healthy control group; n = 19). For the outcome phase of the reward task, right-sided ventral striatum activation was reduced for both currently depressed and high-risk girls compared with healthy controls. This ventral striatal activity correlated significantly with maternal depression scores. These findings provide further evidence of aberrant functioning for the United States Department of Health & Human Services, National Institutes of Health, National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC)-defined domain of positive valence systems as a vulnerability factor for MDD and a potential endophenotype for the development of depression.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2014.05.003

Psychiatry research

Psychiatry Res

Functional MRI of pain application in youth who engaged in repetitive non-suicidal self-injury vs. psychiatric controls.

Non-suicidal self-injury (NSSI) is increasingly common in young psychiatric patients. It is unclear why pain, which should be aversive, becomes reinforcing in this context. We hypothesized that pain- and/or reward-processing neurocircuitry would be abnormal in NSSI patients compared with non-NSSI patients. Using functional magnetic resonance imaging, we administered a painfully cold and comparison cool stimulus under two conditions: self-administered and experimenter-administered (as a control). Participants comprised 13 NSSI patients and 15 non-NSSI control patients, who were matched for sex, age, medications, symptoms, and diagnoses. Whole-brain analyses of main effects, as well as correlational analyses with subjective pain and "relief" (suggesting reward), were performed. Significant main effects of group showed greater blood oxygenation level-dependent (BOLD) response for NSSI than controls in right midbrain/pons; culmen; amygdala; and parahippocampal, inferior frontal and superior temporal gyri; as well as orbital frontal cortex (OFC). The correlation between BOLD signal and "relief" was greater in NSSI patients in areas associated with reward/pain and addiction including thalamus, dorsal striatum and anterior precuneus. Post hoc analysis showed reduced functional connectivity between right OFC and anterior cingulate cortex in NSSI youth, implying possible deficits in the neuroregulation of emotional behavior. These findings help inform how pain is associated with reward for NSSI patients but not for non-NSSI patients.

CognitiveConstruct

RewardProcessing

10.1016/j.psyneuen.2014.04.014

Psychoneuroendocrinology

Psychoneuroendocrinology

Differential neural responses to child and sexual stimuli in human fathers and non-fathers and their hormonal correlates.

Despite the well-documented importance of paternal caregiving for positive child development, little is known about the neural changes that accompany the transition to fatherhood in humans, or about how changes in hormone levels affect paternal brain function. We compared fathers of children aged 1-2 with non-fathers in terms of hormone levels (oxytocin and testosterone), neural responses to child picture stimuli, and neural responses to visual sexual stimuli. Compared to non-fathers, fathers had significantly higher levels of plasma oxytocin and lower levels of plasma testosterone. In response to child picture stimuli, fathers showed stronger activation than non-fathers within regions important for face emotion processing (caudal middle frontal gyrus [MFG]), mentalizing (temporo-parietal junction [TPJ]) and reward processing (medial orbitofrontal cortex [mOFC]). On the other hand, non-fathers had significantly stronger neural responses to sexually provocative images in regions important for reward and approach-related motivation (dorsal caudate and nucleus accumbens). Testosterone levels were negatively correlated with responses to child stimuli in the MFG. Surprisingly, neither testosterone nor oxytocin levels predicted neural responses to sexual stimuli. Our results suggest that the decline in testosterone that accompanies the transition to fatherhood may be important for augmenting empathy toward children.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2014.04.003

Developmental cognitive neuroscience

Dev Cogn Neurosci

Developmental changes in the reward positivity: an electrophysiological trajectory of reward processing.

Children and adolescents learn to regulate their behavior by utilizing feedback from the environment but exactly how this ability develops remains unclear. To investigate this question, we recorded the event-related brain potential (ERP) from children (8-13 years), adolescents (14-17 years) and young adults (18-23 years) while they navigated a "virtual maze" in pursuit of monetary rewards. The amplitude of the reward positivity, an ERP component elicited by feedback stimuli, was evaluated for each age group. A current theory suggests the reward positivity is produced by the impact of reinforcement learning signals carried by the midbrain dopamine system on anterior cingulate cortex, which utilizes the signals to learn and execute extended behaviors. We found that the three groups produced a reward positivity of comparable size despite relatively longer ERP component latencies for the children, suggesting that the reward processing system reaches maturity early in development. We propose that early development of the midbrain dopamine system facilitates the development of extended goal-directed behaviors in anterior cingulate cortex.

CognitiveConstruct

RewardProcessing

10.3758/s13415-014-0298-3

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Impaired reward processing by anterior cingulate cortex in children with attention deficit hyperactivity disorder.

Decades of research have examined the neurocognitive mechanisms of cognitive control, but the motivational factors underlying task selection and performance remain to be elucidated. We recently proposed that anterior cingulate cortex (ACC) utilizes reward prediction error signals carried by the midbrain dopamine system to learn the value of tasks according to the principles of hierarchical reinforcement learning. According to this position, disruption of the ACC-dopamine interface can disrupt the selection and execution of extended, task-related behaviors. To investigate this issue, we recorded the event-related brain potential (ERP) from children with attention deficit hyperactivity disorder (ADHD), which is strongly associated with ACC-dopamine dysfunction, and from typically developing children while they navigated a simple "virtual T-maze" to find rewards. Depending on the condition, the feedback stimuli on each trial indicated that the children earned or failed to earn either money or points. We found that the reward positivity, an ERP component proposed to index the impact of dopamine-related reward signals on ACC, was significantly larger with money feedback than with points feedback for the children with ADHD, but not for the typically developing children. These results suggest that disruption of the ACC-dopamine interface may underlie the impairments in motivational control observed in childhood ADHD.

CognitiveConstruct

RewardProcessing

10.1007/s00213-014-3616-0

Psychopharmacology

Psychopharmacology (Berl)

NMDA receptor blockade in the prelimbic cortex activates the mesolimbic system and dopamine-dependent opiate reward signaling.

N-Methyl-D-aspartate (NMDA) receptors in the medial prefrontal cortex (mPFC) are involved in opiate reward processing and modulate sub-cortical dopamine (DA) activity. NMDA receptor blockade in the prelimbic (PLC) division of the mPFC strongly potentiates the rewarding behavioural properties of normally sub-reward threshold doses of opiates. However, the possible functional interactions between cortical NMDA and sub-cortical DAergic motivational neural pathways underlying these effects are not understood. This study examines how NMDA receptor modulation in the PLC influences opiate reward processing via interactions with sub-cortical DAergic transmission. We further examined whether direct intra-PLC NMDA receptor modulation may activate DA-dependent opiate reward signaling via interactions with the ventral tegmental area (VTA). Using an unbiased place conditioning procedure (CPP) in rats, we performed bilateral intra-PLC microinfusions of the competitive NMDA receptor antagonist, (2R)-amino-5-phosphonovaleric acid (AP-5), prior to behavioural morphine place conditioning and challenged the rewarding effects of morphine with DA receptor blockade. We next examined the effects of intra-PLC NMDA receptor blockade on the spontaneous activity patterns of presumptive VTA DA or GABAergic neurons, using single-unit, extracellular in vivo neuronal recordings. We show that intra-PLC NMDA receptor blockade strongly activates sub-cortical DA neurons within the VTA while inhibiting presumptive non-DA GABAergic neurons. Behaviourally, NMDA receptor blockade activates a DA-dependent opiate reward system, as pharmacological blockade of DA transmission blocked morphine reward only in the presence of intra-PLC NMDA receptor antagonism. These findings demonstrate a cortical NMDA-mediated mechanism controlling mesolimbic DAergic modulation of opiate reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2014.05.054

NeuroImage

Neuroimage

Sexually dimorphic functional connectivity in response to high vs. low energy-dense food cues in obese humans: an fMRI study.

Sexually-dimorphic behavioral and biological aspects of human eating have been described. Using psychophysiological interaction (PPI) analysis, we investigated sex-based differences in functional connectivity with a key emotion-processing region (amygdala, AMG) and a key reward-processing area (ventral striatum, VS) in response to high vs. low energy-dense (ED) food images using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in obese persons in fasted and fed states. When fed, in response to high vs. low-ED food cues, obese men (vs. women) had greater functional connectivity with AMG in right subgenual anterior cingulate, whereas obese women had greater functional connectivity with AMG in left angular gyrus and right primary motor areas. In addition, when fed, AMG functional connectivity with pre/post-central gyrus was more associated with BMI in women (vs. men). When fasted, obese men (vs. women) had greater functional connectivity with AMG in bilateral supplementary frontal and primary motor areas, left precuneus, and right cuneus, whereas obese women had greater functional connectivity with AMG in left inferior frontal gyrus, right thalamus, and dorsomedial prefrontal cortex. When fed, greater functional connectivity with VS was observed in men in bilateral supplementary and primary motor areas, left postcentral gyrus, and left precuneus. These sex-based differences in functional connectivity in response to visual food cues may help partly explain differential eating behavior, pathology prevalence, and outcomes in men and women.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0098156

PloS one

PLoS One

Decreased basal ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue.

Reduced basal ganglia function has been associated with fatigue in neurologic disorders, as well as in patients exposed to chronic immune stimulation. Patients with chronic fatigue syndrome (CFS) have been shown to exhibit symptoms suggestive of decreased basal ganglia function including psychomotor slowing, which in turn was correlated with fatigue. In addition, CFS patients have been found to exhibit increased markers of immune activation. In order to directly test the hypothesis of decreased basal ganglia function in CFS, we used functional magnetic resonance imaging to examine neural activation in the basal ganglia to a reward-processing (monetary gambling) task in a community sample of 59 male and female subjects, including 18 patients diagnosed with CFS according to 1994 CDC criteria and 41 non-fatigued healthy controls. For each subject, the average effect of winning vs. losing during the gambling task in regions of interest (ROI) corresponding to the caudate nucleus, putamen, and globus pallidus was extracted for group comparisons and correlational analyses. Compared to non-fatigued controls, patients with CFS exhibited significantly decreased activation in the right caudate (p = 0.01) and right globus pallidus (p = 0.02). Decreased activation in the right globus pallidus was significantly correlated with increased mental fatigue (r2 = 0.49, p = 0.001), general fatigue (r2 = 0.34, p = 0.01) and reduced activity (r2 = 0.29, p = 0.02) as measured by the Multidimensional Fatigue Inventory. No such relationships were found in control subjects. These data suggest that symptoms of fatigue in CFS subjects were associated with reduced responsivity of the basal ganglia, possibly involving the disruption of projections from the globus pallidus to thalamic and cortical networks.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2014.05.040

NeuroImage

Neuroimage

Effects of selective serotonin reuptake inhibition on neural activity related to risky decisions and monetary rewards in healthy males.

Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are commonly prescribed antidepressant drugs targeting the dysfunctional serotonin (5-HT) system, yet little is known about the functional effects of prolonged serotonin reuptake inhibition in healthy individuals. Here we used functional MRI (fMRI) to investigate how a three-week fluoxetine intervention influences neural activity related to risk taking and reward processing. Employing a double-blinded parallel-group design, 29 healthy young males were randomly assigned to receive 3 weeks of a daily dose of 40 mg fluoxetine or placebo. Participants underwent task-related fMRI prior to and after the three-week intervention while performing a card gambling task. The task required participants to choose between two decks of cards. Choices were associated with different risk levels and potential reward magnitudes. Relative to placebo, the SSRI intervention did not alter individual risk-choice preferences, but modified neural activity during decision-making and reward processing: During the choice phase, SSRI reduced the neural response to increasing risk in lateral orbitofrontal cortex, a key structure for value-based decision-making. During the outcome phase, a midbrain region showed an independent decrease in the responsiveness to rewarding outcomes. This midbrain cluster included the raphe nuclei from which serotonergic modulatory projections originate to both cortical and subcortical regions. The findings corroborate the involvement of the normally functioning 5HT-system in decision-making under risk and processing of monetary rewards. The data suggest that prolonged SSRI treatment might reduce emotional engagement by reducing the impact of risk during decision-making or the impact of reward during outcome evaluation.

CognitiveConstruct

RewardProcessing

10.1159/000358918

Developmental neuroscience

Dev Neurosci

The role of the anterior insula in adolescent decision making.

Much recent research on adolescent decision making has sought to characterize the neurobiological mechanisms that underlie the proclivity of adolescents to engage in risky behavior. One class of influential neurodevelopmental models focuses on the asynchronous development of neural systems, particularly those responsible for self-regulation and reward seeking. While this work has largely focused on the development of prefrontal (self-regulation) and striatal (reward processing) circuitry, the present article explores the significance of a different region, the anterior insular cortex (AIC), in adolescent decision making. Although the AIC is known for its role as a cognitive-emotional hub, and is included in some models of adult self-regulation and reward seeking, the importance of the AIC and its maturation in adolescent risk taking has not been extensively explored. In this article we discuss evidence on AIC development, and consider how age-related differences in AIC engagement may contribute to heightened risk taking during adolescence. Based on this review, we propose a model in which the engagement of adolescents in risk taking may be linked in part to the maturation of the AIC and its connectivity to the broader brain networks in which it participates.

CognitiveConstruct

RewardProcessing

10.1159/000358917

Developmental neuroscience

Dev Neurosci

Feedback processing in adolescence: an event-related potential study of age and gender differences.

Adolescence has frequently been characterized as a period of increased risk taking, which may be largely driven by maturational changes in neural areas that process incentives. To investigate age- and gender-related differences in reward processing, we recorded event-related potentials (ERPs) from 80 participants in a gambling game, in which monetary wins and losses were either large or small. We measured two ERP components: the feedback-related negativity (FRN) and the feedback P3 (fP3). The FRN was sensitive to the size of a win in both adult (aged 23-35 years) and adolescent (aged 13-17 years) males, but not in females. Small wins appeared to be less rewarding for males than for females, which may in part explain more approach-driven behavior in males in general. Furthermore, adolescent boys showed both delayed FRNs to high losses and less differentiation in FRN amplitude between wins and losses in comparison to girls. The fP3, which is thought to index the salience of the feedback at a more conscious level than the FRN, was also larger in boys than in girls. Taken together, these results imply that higher levels of risk taking that are commonly reported in adolescent males may be driven both by hypersensitivity to high rewards and insensitivity to punishment or losses.

CognitiveConstruct

RewardProcessing

10.1016/j.neulet.2014.05.011

Neuroscience letters

Neurosci Lett

Brain activity during the flow experience: a functional near-infrared spectroscopy study.

Flow is the holistic experience felt when an individual acts with total involvement. Although flow is likely associated with many functions of the prefrontal cortex (PFC), such as attention, emotion, and reward processing, no study has directly investigated the activity of the PFC during flow. The objective of this study was to examine activity in the PFC during the flow state using functional near-infrared spectroscopy (fNIRS). Twenty right-handed university students performed a video game task under conditions designed to induce psychological states of flow and boredom. During each task and when completing the flow state scale for occupational tasks, change in oxygenated hemoglobin (oxy-Hb) concentration in frontal brain regions was measured using fNIRS. During the flow condition, oxy-Hb concentration was significantly increased in the right and left ventrolateral prefrontal cortex. Oxy-Hb concentration tended to decrease in the boredom condition. There was a significant increase in oxy-Hb concentration in the right and left dorsolateral prefrontal cortex, right and left frontal pole areas, and left ventrolateral PFC when participants were completing the flow state scale after performing the task in the flow condition. In conclusion, flow is associated with activity of the PFC, and may therefore be associated with functions such as cognition, emotion, maintenance of internal goals, and reward processing.

CognitiveConstruct

RewardProcessing