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10.1038/npp.2015.155

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Genome-Wide DNA Methylation Profiling Reveals Epigenetic Changes in the Rat Nucleus Accumbens Associated With Cross-Generational Effects of Adolescent THC Exposure.

Drug exposure during critical periods of development is known to have lasting effects, increasing one's risk for developing mental health disorders. Emerging evidence has also indicated the possibility for drug exposure to even impact subsequent generations. Our previous work demonstrated that adolescent exposure to Δ(9)-tetrahydrocannabinol (THC), the main psychoactive component of marijuana (Cannabis sativa), in a Long-Evans rat model affects reward-related behavior and gene regulation in the subsequent (F1) generation unexposed to the drug. Questions, however, remained regarding potential epigenetic consequences. In the current study, using the same rat model, we employed Enhanced Reduced Representation Bisulfite Sequencing to interrogate the epigenome of the nucleus accumbens, a key brain area involved in reward processing. This analysis compared 16 animals with parental THC exposure and 16 without to characterize relevant systems-level changes in DNA methylation. We identified 1027 differentially methylated regions (DMRs) associated with parental THC exposure in F1 adults, each represented by multiple CpGs. These DMRs fell predominantly within introns, exons, and intergenic intervals, while showing a significant depletion in gene promoters. From these, we identified a network of DMR-associated genes involved in glutamatergic synaptic regulation, which also exhibited altered mRNA expression in the nucleus accumbens. These data provide novel insight into drug-related cross-generational epigenetic effects, and serve as a useful resource for investigators to explore novel neurobiological systems underlying drug abuse vulnerability.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2015.05.020

Journal of affective disorders

J Affect Disord

Neural correlates of successful psychotherapy of depression in adolescents.

While major effort has been put in investigating neural correlates of depression and its treatment in adults, less is known about the effects of psychotherapy in adolescents. Given the concordance of the ventral striatum, amygdala, hippocampus and the subgenual anterior cingulate cortex (sgACC) as correlates of depression and their involvement in reward processing, we used functional magnetic resonance imaging (fMRI) during performance of a monetary reward task in an intervention versus waitlist-control design to investigate the clinical and neural effects of cognitive behavioral group therapy (CBT-G). 22 medication naïve adolescents with major depressive disorder were scanned before and after five sessions of CBT-G (PAT-I), or before and after five weeks of waiting (PAT-W). Changes in symptom scales were analyzed along with neural activation changes within the amygdala, hippocampus, sgACC and ventral striatum regions of interest (ROI). Psychometric assessments and ROI activation remained unchanged in PAT-W. In PAT-I, significant reduction in clinical symptoms accompanied significant changes in brain activation within the left amygdala, left hippocampus and bilateral sgACC. In line with previous findings in adults, pre-to-post-activation changes in the bilateral sgACC correlated with pre-to-post and pre-to-follow-up symptom improvement, and individual expressions of sgACC activation before treatment were related to pre-to-follow-up therapeutic success. Future studies should include larger sample sizes. Successful group psychotherapy of depression in adolescents was related to signal changes in brain regions previously demonstrated to be reliably linked with successful, particularly pharmacological treatment in adults.

CognitiveConstruct

RewardProcessing

10.1113/JP270492

The Journal of physiology

J Physiol

Nicotine and the adolescent brain.

Adolescence encompasses a sensitive developmental period of enhanced clinical vulnerability to nicotine, tobacco, and e-cigarettes. While there are sociocultural influences, data at preclinical and clinical levels indicate that this adolescent sensitivity has strong neurobiological underpinnings. Although definitions of adolescence vary, the hallmark of this period is a profound reorganization of brain regions necessary for mature cognitive and executive function, working memory, reward processing, emotional regulation, and motivated behavior. Regulating critical facets of brain maturation are nicotinic acetylcholine receptors (nAChRs). However, perturbations of cholinergic systems during this time with nicotine, via tobacco or e-cigarettes, have unique consequences on adolescent development. In this review, we highlight recent clinical and preclinical data examining the adolescent brain's distinct neurobiology and unique sensitivity to nicotine. First, we discuss what defines adolescence before reviewing normative structural and neurochemical alterations that persist until early adulthood, with an emphasis on dopaminergic systems. We review how acute exposure to nicotine impacts brain development and how drug responses differ from those seen in adults. Finally, we discuss the persistent alterations in neuronal signaling and cognitive function that result from chronic nicotine exposure, while highlighting a low dose, semi-chronic exposure paradigm that may better model adolescent tobacco use. We argue that nicotine exposure, increasingly occurring as a result of e-cigarette use, may induce epigenetic changes that sensitize the brain to other drugs and prime it for future substance abuse.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsv060

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Temporal dynamics of musical emotions examined through intersubject synchrony of brain activity.

To study emotional reactions to music, it is important to consider the temporal dynamics of both affective responses and underlying brain activity. Here, we investigated emotions induced by music using functional magnetic resonance imaging (fMRI) with a data-driven approach based on intersubject correlations (ISC). This method allowed us to identify moments in the music that produced similar brain activity (i.e. synchrony) among listeners under relatively natural listening conditions. Continuous ratings of subjective pleasantness and arousal elicited by the music were also obtained for the music outside of the scanner. Our results reveal synchronous activations in left amygdala, left insula and right caudate nucleus that were associated with higher arousal, whereas positive valence ratings correlated with decreases in amygdala and caudate activity. Additional analyses showed that synchronous amygdala responses were driven by energy-related features in the music such as root mean square and dissonance, while synchrony in insula was additionally sensitive to acoustic event density. Intersubject synchrony also occurred in the left nucleus accumbens, a region critically implicated in reward processing. Our study demonstrates the feasibility and usefulness of an approach based on ISC to explore the temporal dynamics of music perception and emotion in naturalistic conditions.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2015.04.018

Drug and alcohol dependence

Drug Alcohol Depend

Individualized relapse prediction: Personality measures and striatal and insular activity during reward-processing robustly predict relapse.

Nearly half of individuals with substance use disorders relapse in the year after treatment. A diagnostic tool to help clinicians make decisions regarding treatment does not exist for psychiatric conditions. Identifying individuals with high risk for relapse to substance use following abstinence has profound clinical consequences. This study aimed to develop neuroimaging as a robust tool to predict relapse. 68 methamphetamine-dependent adults (15 female) were recruited from 28-day inpatient treatment. During treatment, participants completed a functional MRI scan that examined brain activation during reward processing. Patients were followed 1 year later to assess abstinence. We examined brain activation during reward processing between relapsing and abstaining individuals and employed three random forest prediction models (clinical and personality measures, neuroimaging measures, a combined model) to generate predictions for each participant regarding their relapse likelihood. 18 individuals relapsed. There were significant group by reward-size interactions for neural activation in the left insula and right striatum for rewards. Abstaining individuals showed increased activation for large, risky relative to small, safe rewards, whereas relapsing individuals failed to show differential activation between reward types. All three random forest models yielded good test characteristics such that a positive test for relapse yielded a likelihood ratio 2.63, whereas a negative test had a likelihood ratio of 0.48. These findings suggest that neuroimaging can be developed in combination with other measures as an instrument to predict relapse, advancing tools providers can use to make decisions about individualized treatment of substance use disorders.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2015.05.002

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

Short- and long-lasting consequences of novelty, deviance and surprise on brain and cognition.

When one encounters a novel stimulus this sets off a cascade of brain responses, activating several neuromodulatory systems. As a consequence novelty has a wide range of effects on cognition; improving perception and action, increasing motivation, eliciting exploratory behavior, and promoting learning. Here, we review these benefits and how they may arise in the brain. We propose a framework that organizes novelty's effects on brain and cognition into three groups. First, novelty can transiently enhance perception. This effect is proposed to be mediated by novel stimuli activating the amygdala and enhancing early sensory processing. Second, novel stimuli can increase arousal, leading to short-lived effects on action in the first hundreds of milliseconds after presentation. We argue that these effects are related to deviance, rather than to novelty per se, and link them to activation of the locus-coeruleus norepinephrine system. Third, spatial novelty may trigger the dopaminergic mesolimbic system, promoting dopamine release in the hippocampus, having longer-lasting effects, up to tens of minutes, on motivation, reward processing, and learning and memory.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2015.05.005

Neuropsychologia

Neuropsychologia

The impact of Parkinson's disease and subthalamic deep brain stimulation on reward processing.

Due to its position in cortico-subthalamic and cortico-striatal pathways, the subthalamic nucleus (STN) is considered to play a crucial role not only in motor, but also in cognitive and motivational functions. In the present study we aimed to characterize how different aspects of reward processing are affected by disease and deep brain stimulation of the STN (DBS-STN) in patients with idiopathic Parkinson's disease (PD). We compared 33 PD patients treated with DBS-STN under best medical treatment (DBS-on, medication-on) to 33 PD patients without DBS, but optimized pharmacological treatment and 34 age-matched healthy controls. We then investigated DBS-STN effects using a postoperative stimulation-on/ -off design. The task set included a delay discounting task, a task to assess changes in incentive salience attribution, and the Iowa Gambling Task. The presence of PD was associated with increased incentive salience attribution and devaluation of delayed rewards. Acute DBS-STN increased risky choices in the Iowa Gambling Task under DBS-on condition, but did not further affect incentive salience attribution or the evaluation of delayed rewards. Findings indicate that acute DBS-STN affects specific aspects of reward processing, including the weighting of gains and losses, while larger-scale effects of disease or medication are predominant in others reward-related functions.

CognitiveConstruct

RewardProcessing

10.1152/jn.00278.2015

Journal of neurophysiology

J Neurophysiol

Decision making: effects of methylphenidate on temporal discounting in nonhuman primates.

Decisions are often made based on which option will result in the largest reward. When given a choice between a smaller but immediate reward and a larger delayed reward, however, humans and animals often choose the smaller, an effect known as temporal discounting. Dopamine (DA) neurotransmission is central to reward processing and encodes delayed reward value. Impulsivity, the tendency to act without forethought, is associated with excessive discounting of rewards, which has been documented in patients with attention deficit hyperactivity disorder (ADHD). Both impulsivity and temporal discounting are linked to the dopaminergic system. Methylphenidate (MPH), which blocks the DA transporter and increases extracellular levels of DA in the basal ganglia and prefrontal cortex, is a primary treatment for ADHD and, at low doses, ameliorates impulsivity in both humans and animals. This study tested the hypothesis that low doses of MPH would decrease the discounting rate of rhesus monkeys performing an intertemporal choice task, suggesting a reduction in impulsivity. The results support this hypothesis and provide further evidence for the role of DA in temporal discounting and impulsive behavior.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2015.04.065

NeuroImage

Neuroimage

Functional connectivity of the dorsal and median raphe nuclei at rest.

Serotonin (5-HT) is a neurotransmitter critically involved in a broad range of brain functions and implicated in the pathophysiology of neuropsychiatric illnesses including major depression, anxiety and sleep disorders. Despite being widely distributed throughout the brain, there is limited knowledge on the contribution of 5-HT to intrinsic brain activity. The dorsal raphe (DR) and median raphe (MR) nuclei are the source of most serotonergic neurons projecting throughout the brain and thus provide a compelling target for a seed-based probe of resting-state activity related to 5-HT. Here we implemented a novel multimodal neuroimaging approach for investigating resting-state functional connectivity (FC) between DR and MR and cortical, subcortical and cerebellar target areas. Using [(11)C]DASB positron emission tomography (PET) images of the brain serotonin transporter (5-HTT) combined with structural MRI from 49 healthy volunteers, we delineated DR and MR and performed a seed-based resting-state FC analysis. The DR and MR seeds produced largely similar FC maps: significant positive FC with brain regions involved in cognitive and emotion processing including anterior cingulate, amygdala, insula, hippocampus, thalamus, basal ganglia and cerebellum. Significant negative FC was observed within pre- and postcentral gyri for the DR but not for the MR seed. We observed a significant association between DR and MR FC and regional 5-HTT binding. Our results provide evidence for a resting-state network related to DR and MR and comprising regions receiving serotonergic innervation and centrally involved in 5-HT related behaviors including emotion, cognition and reward processing. These findings provide a novel advance in estimating resting-state FC related to 5-HT signaling, which can benefit our understanding of its role in behavior and neuropsychiatric illnesses.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0126326

PloS one

PLoS One

Accounting for Dynamic Fluctuations across Time when Examining fMRI Test-Retest Reliability: Analysis of a Reward Paradigm in the EMBARC Study.

Longitudinal investigation of the neural correlates of reward processing in depression may represent an important step in defining effective biomarkers for antidepressant treatment outcome prediction, but the reliability of reward-related activation is not well understood. Thirty-seven healthy control participants were scanned using fMRI while performing a reward-related guessing task on two occasions, approximately one week apart. Two main contrasts were examined: right ventral striatum (VS) activation fMRI BOLD signal related to signed prediction errors (PE) and reward expectancy (RE). We also examined bilateral visual cortex activation coupled to outcome anticipation. Significant VS PE-related activity was observed at the first testing session, but at the second testing session, VS PE-related activation was significantly reduced. Conversely, significant VS RE-related activity was observed at time 2 but not time 1. Increases in VS RE-related activity from time 1 to time 2 were significantly associated with decreases in VS PE-related activity from time 1 to time 2 across participants. Intraclass correlations (ICCs) in VS were very low. By contrast, visual cortex activation had much larger ICCs, particularly in individuals with high quality data. Dynamic changes in brain activation are widely predicted, and failure to account for these changes could lead to inaccurate evaluations of the reliability of functional MRI signals. Conventional measures of reliability cannot distinguish between changes specified by algorithmic models of neural function and noisy signal. Here, we provide evidence for the former possibility: reward-related VS activations follow the pattern predicted by temporal difference models of reward learning but have low ICCs.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.4764-14.2015

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

J Neurosci

Longitudinal changes in adolescent risk-taking: a comprehensive study of neural responses to rewards, pubertal development, and risk-taking behavior.

Prior studies have highlighted adolescence as a period of increased risk-taking, which is postulated to result from an overactive reward system in the brain. Longitudinal studies are pivotal for testing these brain-behavior relations because individual slopes are more sensitive for detecting change. The aim of the current study was twofold: (1) to test patterns of age-related change (i.e., linear, quadratic, and cubic) in activity in the nucleus accumbens, a key reward region in the brain, in relation to change in puberty (self-report and testosterone levels), laboratory risk-taking and self-reported risk-taking tendency; and (2) to test whether individual differences in pubertal development and risk-taking behavior were contributors to longitudinal change in nucleus accumbens activity. We included 299 human participants at the first time point and 254 participants at the second time point, ranging between ages 8-27 years, time points were separated by a 2 year interval. Neural responses to rewards, pubertal development (self-report and testosterone levels), laboratory risk-taking (balloon analog risk task; BART), and self-reported risk-taking tendency (Behavior Inhibition System/Behavior Activation System questionnaire) were collected at both time points. The longitudinal analyses confirmed the quadratic age pattern for nucleus accumbens activity to rewards (peaking in adolescence), and the same quadratic pattern was found for laboratory risk-taking (BART). Nucleus accumbens activity change was further related to change in testosterone and self-reported reward-sensitivity (BAS Drive). Thus, this longitudinal analysis provides new insight in risk-taking and reward sensitivity in adolescence: (1) confirming an adolescent peak in nucleus accumbens activity, and (2) underlining a critical role for pubertal hormones and individual differences in risk-taking tendency.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsv044

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Gender-specific modulation of neural mechanisms underlying social reward processing by Autism Quotient.

Autism spectrum disorder refers to a neurodevelopmental condition primarily characterized by deficits in social cognition and behavior. Subclinically, autistic features are supposed to be present in healthy humans and can be quantified using the Autism Quotient (AQ). Here, we investigated a potential relationship between AQ and neural correlates of social and monetary reward processing, using functional magnetic resonance imaging in young, healthy participants. In an incentive delay task with either monetary or social reward, reward anticipation elicited increased ventral striatal activation, which was more pronounced during monetary reward anticipation. Anticipation of social reward elicited activation in the default mode network (DMN), a network previously implicated in social processing. Social reward feedback was associated with bilateral amygdala and fusiform face area activation. The relationship between AQ and neural correlates of social reward processing varied in a gender-dependent manner. In women and, to a lesser extent in men, higher AQ was associated with increased posterior DMN activation during social reward anticipation. During feedback, we observed a negative correlation of AQ and right amygdala activation in men only. Our results suggest that social reward processing might constitute an endophenotype for autism-related traits in healthy humans that manifests in a gender-specific way.

CognitiveConstruct

RewardProcessing

10.1073/pnas.1503358112

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

Proc Natl Acad Sci U S A

Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards.

Prior studies suggest that fructose compared with glucose may be a weaker suppressor of appetite, and neuroimaging research shows that food cues trigger greater brain reward responses in a fasted relative to a fed state. We sought to determine the effects of ingesting fructose versus glucose on brain, hormone, and appetitive responses to food cues and food-approach behavior. Twenty-four healthy volunteers underwent two functional magnetic resonance imaging (fMRI) sessions with ingestion of either fructose or glucose in a double-blinded, random-order cross-over design. fMRI was performed while participants viewed images of high-calorie foods and nonfood items using a block design. After each block, participants rated hunger and desire for food. Participants also performed a decision task in which they chose between immediate food rewards and delayed monetary bonuses. Hormones were measured at baseline and 30 and 60 min after drink ingestion. Ingestion of fructose relative to glucose resulted in smaller increases in plasma insulin levels and greater brain reactivity to food cues in the visual cortex (in whole-brain analysis) and left orbital frontal cortex (in region-of-interest analysis). Parallel to the neuroimaging findings, fructose versus glucose led to greater hunger and desire for food and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods. These findings suggest that ingestion of fructose relative to glucose results in greater activation of brain regions involved in attention and reward processing and may promote feeding behavior.

CognitiveConstruct

RewardProcessing

10.1016/j.brainres.2015.04.040

Brain research

Brain Res

Modulation of the brain activity in outcome evaluation by the presence of an audience: An electrophysiological investigation.

The audience effect refers to the phenomenon that one׳s performance on a task is affected by the presence of others. Here we investigated how the audience effect modulates the neurocognitive signatures underlying people׳s evaluation of their own task performance/outcome. Participants in our study played a gambling game in two social contexts: an "audience" condition and an "alone" condition. The presence of others modulated the feedback-related negativity (FRN), which might reflect enhanced motivational significance or increased reward processing when participants were watched compared to when they were alone. We also observed increased P300 responses to outcome feedback in the audience condition, presumably reflecting more elaborative and sustained evaluation of outcomes in the audience than alone context. This audience effect on the evaluative processes complements previous observations on the social nature of outcome evaluation and extends a traditional topic in social psychology to the neuroscientific field.

CognitiveConstruct

RewardProcessing

10.1016/j.euroneuro.2015.04.015

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Eur Neuropsychopharmacol

Grey matter volumes in treatment naïve vs. chronically treated children with attention deficit/hyperactivity disorder: a combined approach.

Psychostimulants are the first-line treatment in attention deficit/hyperactivity disorder (ADHD), but their effects on brain development remain poorly understood. In particular, previous structural magnetic resonance imaging (sMRI) studies only investigated treatment effects on grey matter (GM) volumes in selected regions of interest (ROIs). In this study, voxel-based morphometry (VBM) was used to assess medication-related GM volume differences across the entire brain. Automated tracing measurements of selected ROIs were also obtained. Three groups (77 participants aged 7-to-13 year old) underwent MRI scans and were compared: never-medicated children with ADHD (n=33), medicated (methylphenidate) children with ADHD (n=20) and typically developing children (TD; n=24). Optimised VBM was used to investigate regional GM volumes, controlling for age and gender. Automated tracing procedures were also used to assess the average volume of the caudate nucleus, the amygdala and the nucleus accumbens. When compared to both medicated children with ADHD and TD children, never-medicated children with ADHD exhibited decreased GM volume in the insula and in the middle temporal gyrus. When compared to TD children, medicated children with ADHD had decreased GM volume in the middle frontal gyrus and in the precentral gyrus. Finally, ROI analyses revealed a significant association between duration of treatment and GM volume of the left nucleus accumbens in medicated children with ADHD. In conclusion, this study documents potential methylphenidate-related GM volume normalization and deviation in previously unexplored brain structures, and reports a positive association between treatment history and GM volume in the nucleus accumbens, a key region for reward-processing.

CognitiveConstruct

RewardProcessing

10.1007/s00415-015-7749-9

Journal of neurology

J Neurol

Deep brain stimulation of the subthalamic nucleus modulates reward processing and action selection in Parkinson patients.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for motor impairments in Parkinson's disease (PD) but its effect on the motivational regulation of action control is still not fully understood. We investigated whether DBS of the STN influences the ability of PD patients to act for anticipated reward or loss, or whether DBS improves action execution independent of motivational valence. 16 PD patients (12 male, mean age = 58.5 ± 10.17 years) treated with bilateral STN-DBS and an age- and gender-matched group of healthy controls (HC) performed a go/no-go task whose contingencies explicitly decouple valence and action. Patients were tested with (ON) and without (OFF) active STN stimulation. For HC, there was a benefit in performing rewarded actions when compared to actions that avoided punishment. PD patients showed such a benefit reliably only when STN stimulation was ON. In fact, the relative behavioral benefit for go for reward over go to avoid losing was stronger in the PD patients under DBS ON than in HC. In PD patients, rather than generally improving motor functions independent of motivational valence, modulation of the STN by DBS improves action execution specifically when rewards are anticipated. Thus, STN-DBS establishes a reliable congruency between action and reward ("Pavlovian congruency") and remarkably enhances it over the level observed in HC.

CognitiveConstruct

RewardProcessing

10.1159/000371886

Molecular neuropsychiatry

Mol Neuropsychiatry

Variants in Ion Channel Genes Link Phenotypic Features of Bipolar Illness to Specific Neurobiological Process Domains.

Recent advances in genome-wide association studies are pointing towards a major role for voltage-gated ion channels in neuropsychiatric disorders and, in particular, bipolar disorder (BD). The phenotype of BD is complex, with symptoms during mood episodes and deficits persisting between episodes. We have tried to elucidate the common neurobiological mechanisms associated with ion channel signaling in order to provide a new perspective on the clinical symptoms and possible endophenotypes seen in BD patients. We propose a model in which the multiple variants in genes coding for ion channel proteins would perturb motivational circuits, synaptic plasticity, myelination, hypothalamic-pituitary-adrenal axis function, circadian neuronal rhythms, and energy regulation. These changes in neurobiological mechanisms would manifest in endophenotypes of aberrant reward processing, white matter hyperintensities, deficits in executive function, altered frontolimbic connectivity, increased amygdala activity, increased melatonin suppression, decreased REM latency, and aberrant myo-inositol/ATP shuttling. The endophenotypes result in behaviors of poor impulse control, motivational changes, cognitive deficits, abnormal stress response, sleep disturbances, and energy changes involving different neurobiological process domains. The hypothesis is that these disturbances start with altered neural circuitry during development, following which multiple environmental triggers may disrupt the neuronal excitability balance through an activity-dependent molecular process, resulting in clinical mood episodes.

CognitiveConstruct

RewardProcessing

10.1080/15374416.2015.1030753

Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53

J Clin Child Adolesc Psychol

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

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

CognitiveConstruct

RewardProcessing

10.1111/adb.12240

Addiction biology

Addict Biol

From mother to child: orbitofrontal cortex gyrification and changes of drinking behaviour during adolescence.

Adolescence is a common time for initiation of alcohol use and alcohol use disorders. Importantly, the neuro-anatomical foundation for later alcohol-related problems may already manifest pre-natally, particularly due to smoking and alcohol consumption during pregnancy. In this context, cortical gyrification is an interesting marker of neuronal development but has not been investigated as a risk factor for adolescent alcohol use. On magnetic resonance imaging scans of 595 14-year-old adolescents from the IMAGEN sample, we computed whole-brain mean curvature indices to predict change in alcohol-related problems over the following 2 years. Change of alcohol use-related problems was significantly predicted from mean curvature in left orbitofrontal cortex (OFC). Less gyrification of OFC was associated with an increase in alcohol use-related problems over the next 2 years. Moreover, lower gyrification in left OFC was related to pre-natal alcohol exposure, whereas maternal smoking during pregnancy had no effect. Current alcohol use-related problems of the biological mother had no effect on offsprings' OFC gyrification or drinking behaviour. The data support the idea that alcohol consumption during pregnancy mediates the development of neuro-anatomical phenotypes, which in turn constitute a risk factor for increasing problems due to alcohol consumption in a vulnerable stage of life. Maternal smoking during pregnancy or current maternal alcohol/nicotine consumption had no significant effect. The OFC mediates behaviours known to be disturbed in addiction, namely impulse control and reward processing. The results stress the importance of pre-natal alcohol exposure for later increases in alcohol use-related problems, mediated by structural brain characteristics.

CognitiveConstruct

RewardProcessing

10.1016/j.jaac.2015.02.012

Journal of the American Academy of Child and Adolescent Psychiatry

J Am Acad Child Adolesc Psychiatry

Increased neural responses to reward in adolescents and young adults with attention-deficit/hyperactivity disorder and their unaffected siblings.

Attention-deficit/hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder associated with abnormal reward processing. Limited and inconsistent data exist about the neural mechanisms underlying this abnormality. Furthermore, it is not known whether reward processing is abnormal in unaffected siblings of participants with ADHD. We used event-related functional magnetic resonance imaging (fMRI) to investigate brain responses during reward anticipation and receipt with an adapted monetary incentive delay task in a large sample of adolescents and young adults with ADHD (n = 150), their unaffected siblings (n = 92), and control participants (n = 108), all of the same age. Participants with ADHD showed, relative to control participants, increased responses in the anterior cingulate, anterior frontal cortex, and cerebellum during reward anticipation, and in the orbitofrontal, occipital cortex and ventral striatum. Responses of unaffected siblings were increased in these regions as well, except for the cerebellum during anticipation and ventral striatum during receipt. ADHD in adolescents and young adults is associated with enhanced neural responses in frontostriatal circuitry to anticipation and receipt of reward. The findings support models emphasizing aberrant reward processing in ADHD, and suggest that processing of reward is subject to familial influences. Future studies using standard monetary incentive delay task parameters are needed to replicate our findings.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2015.03.035

Journal of affective disorders

J Affect Disord

Perceived life stress exposure modulates reward-related medial prefrontal cortex responses to acute stress in depression.

Major depressive disorder (MDD) is often precipitated by life stress and growing evidence suggests that stress-induced alterations in reward processing may contribute to such risk. However, no human imaging studies have examined how recent life stress exposure modulates the neural systems that underlie reward processing in depressed and healthy individuals. In this proof-of-concept study, 12 MDD and 10 psychiatrically healthy individuals were interviewed using the Life Events and Difficulties Schedule (LEDS) to assess their perceived levels of recent acute and chronic life stress exposure. Additionally, each participant performed a monetary incentive delay task under baseline (no-stress) and stress (social-evaluative) conditions during functional MRI. Across groups, medial prefrontal cortex (mPFC) activation to reward feedback was greater during acute stress versus no-stress conditions in individuals with greater perceived stressor severity. Under acute stress, depressed individuals showed a positive correlation between perceived stressor severity levels and reward-related mPFC activation (r=0.79, p=0.004), whereas no effect was found in healthy controls. Moreover, for depressed (but not healthy) individuals, the correlations between the stress (r=0.79) and no-stress (r=-0.48) conditions were significantly different. Finally, relative to controls, depressed participants showed significantly reduced mPFC gray matter, but functional findings remained robust while accounting for structural differences. Small sample size, which warrants replication. Depressed individuals experiencing greater recent life stress recruited the mPFC more under stress when processing rewards. Our results represent an initial step toward elucidating mechanisms underlying stress sensitization and recurrence in depression.

CognitiveConstruct

RewardProcessing

10.1037/neu0000197

Neuropsychology

Neuropsychology

Discounting of future rewards in behavioural variant frontotemporal dementia and Alzheimer's disease.

The clinical differential diagnosis of Alzheimer's disease (AD) and behavioral-variant frontotemporal dementia (bvFTD) can no longer rely only on episodic memory impairment or executive dysfunctions, as highlighted by recent findings showing that both diseases could present with similar impairments. Objective cognitive tests assessing specific symptoms, such as impulsivity in bvFTD, are thus crucially needed. The aim of this study was to evaluate the differences in impulsivity between bvFTD and AD using a delay-discounting paradigm. An ecological delay-discounting test was administrated to 70 participants including 30 ADs, 20 bvFTD and 20 controls. AD patients were divided according to the severity of the disease into mild or moderate group. The delay-discounting score, reflecting the total percentage of impulsive choice across the entire task, was analyzed for each group. This score showed that bvFTD patients were significantly more impulsive than controls and AD patients at mild or moderate stage. AD patients, regardless of disease stage, did not differ from controls. ROC analyses revealed high and significant area under the curve (AUC, 95% confidence interval) for this score to differentiate bvFTD from AD (0.704) or controls (0.904), or both group (AD + controls; AUC = 0.791). The total delay-discounting score provided by our task showed that it could accurately differentiate bvFTD patients from AD and controls. These results support the relevancy of using tests inspired by experimental psychoeconomics and taping into reward processing to increase the distinction between both diseases.

CognitiveConstruct

RewardProcessing

10.1016/j.schres.2015.03.030

Schizophrenia research

Schizophr Res

Motivation and effort in individuals with social anhedonia.

It has been proposed that anhedonia may, in part, reflect difficulties in reward processing and effortful decision making. The current study aimed to replicate previous findings of effortful decision making deficits associated with elevated anhedonia and expand upon these findings by investigating whether these decision making deficits are specific to elevated social anhedonia or are also associated with elevated positive schizotypy characteristics. The current study compared controls (n=40) to individuals elevated on social anhedonia (n=30), and individuals elevated on perceptual aberration/magical ideation (n=30) on the Effort Expenditure for Rewards Task (EEfRT). Across groups, participants chose a higher proportion of hard tasks with increasing probability of reward and reward magnitude, demonstrating sensitivity to probability and reward values. Contrary to our expectations, when the probability of reward was most uncertain (50% probability), at low and medium reward values, the social anhedonia group demonstrated more effortful decision making than either individuals high in positive schizotypy or controls. The positive schizotypy group only differed from controls (making less effortful choices than controls) when reward probability was lowest (12%) and the magnitude of reward was the smallest. Our results suggest that social anhedonia is related to intact motivation and effort for monetary rewards, but that individuals with this characteristic display a unique and perhaps inefficient pattern of effort allocation when the probability of reward is most uncertain. Future research is needed to better understand effortful decision making and the processing of reward across a range of individual difference characteristics.

CognitiveConstruct

RewardProcessing

10.1016/j.tem.2015.03.005

Trends in endocrinology and metabolism: TEM

Trends Endocrinol Metab

Distinctive striatal dopamine signaling after dieting and gastric bypass.

Highly palatable and/or calorically dense foods, such as those rich in fat, engage the striatum to govern and set complex behaviors. Striatal dopamine signaling has been implicated in hedonic feeding and the development of obesity. Dieting and bariatric surgery have markedly different outcomes on weight loss, yet how these interventions affect central homeostatic and food reward processing remains poorly understood. Here, we propose that dieting and gastric bypass produce distinct changes in peripheral factors with known roles in regulating energy homeostasis, resulting in differential modulation of nigrostriatal and mesolimbic dopaminergic reward circuits. Enhancement of intestinal fat metabolism after gastric bypass may also modify striatal dopamine signaling contributing to its unique long-term effects on feeding behavior and body weight in obese individuals.

CognitiveConstruct

RewardProcessing

10.1038/npp.2015.110

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Reward Processing in Unipolar and Bipolar Depression: A Functional MRI Study.

Differentiating bipolar disorders (BD) from unipolar depression (UD) remains a major clinical challenge. The identification of neurobiological markers may help to differentiate these disorders, particularly during depressive episodes. This cross-sectional study, including 33 patients with UD, 33 patients with BD, and 34 healthy controls, is one of the first to directly compare UD and BD with respect to reward processing. A card-guessing paradigm was employed and brain activity associated with reward processing was investigated by means of fMRI. A 3 (group) × 2 (condition: reward>control, loss>control) ANOVA was conducted using the nucleus accumbens (NAcc) as ROI. Furthermore, a whole-brain approach was applied. A functional connectivity analysis was performed to characterize diagnosis-related alterations in the functional coupling between the NAcc and other brain areas. The ANOVA revealed higher activity for healthy controls (HCs) than for BD and UD in the NAcc during reward processing. Moreover, UD showed a higher functional connectivity between the NAcc and the VTA than HC. The patients groups could be differentiated in that BD showed a decreased activation, in the reward condition, of the NAcc, caudate nucleus, thalamus, putamen, insula, and prefrontal areas compared with UD. These results may help to refine the understanding of neural correlates of reward processing in both disorders, and to understand the neural underpinnings of anhedonia, a core symptom of depressive episodes.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0122798

PloS one

PLoS One

Goal or gold: overlapping reward processes in soccer players upon scoring and winning money.

Social rewards are important incentives for human behavior. This is especially true in team sports such as the most popular one worldwide: soccer. We investigated reward processing upon scoring a soccer goal in a standard two-versus-one situation and in comparison to winning in a monetary incentive task. The results show a strong overlap in brain activity between the two conditions in established reward regions of the mesolimbic dopaminergic system, including the ventral striatum and ventromedial pre-frontal cortex. The three main components of reward-associated learning, i.e., reward probability (RP), reward reception (RR) and reward prediction errors (RPE) showed highly similar activation in both con-texts, with only the RR and RPE components displaying overlapping reward activity. Passing and shooting behavior did not correlate with individual egoism scores, but we observe a positive correlation be-tween egoism and activity in the left middle frontal gyrus upon scoring after a pass versus a direct shot. Our findings suggest that rewards in the context of soccer and monetary incentives are based on similar neural processes.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22807

Human brain mapping

Hum Brain Mapp

The neural basis of the abnormal self-referential processing and its impact on cognitive control in depressed patients.

Persistent pondering over negative self-related thoughts is a central feature of depressive psychopathology. In this study, we sought to investigate the neural correlates of abnormal negative self-referential processing (SRP) in patients with Major Depressive Disorder and its impact on subsequent cognitive control-related neuronal activation. We hypothesized aberrant activation dynamics during the period of negative and neutral SRP in the rostral anterior cingulate cortex (rACC) and in the amygdala in patients with major depressive disorder. Additionally, we assumed abnormal activation in the fronto-cingulate network during Stroop task execution. 19 depressed patients and 20 healthy controls participated in the study. Using an event-related functional magnetic resonance imaging (fMRI) design, negative, positive and neutral self-referential statements were displayed for 6.5 s and followed by incongruent or congruent Stroop conditions. The data were analyzed with SPM8. In contrast to controls, patients exhibited no significant valence-dependent rACC activation differences during SRP. A novel finding was the significant activation of the amygdala and the reward-processing network during presentation of neutral self-referential stimuli relative to baseline and to affective stimuli in patients. The fMRI analysis of the Stroop task revealed a reduced BOLD activation in the right fronto-parietal network of patients in the incongruent condition after negative SRP only. Thus, the inflexible activation in the rACC may correspond to the inability of depressed patients to shift their attention away from negative self-related stimuli. The accompanying negative affect and task-irrelevant emotional processing may compete for neuronal resources with cognitive control processes and lead thereby to deficient cognitive performance associated with decreased fronto-parietal activation.

CognitiveConstruct

RewardProcessing

10.3389/fnint.2015.00023

Frontiers in integrative neuroscience

Front Integr Neurosci

The medial prefrontal cortex is crucial for the maintenance of persistent licking and the expression of incentive contrast.

We examined the role of the medial prefrontal cortex (mPFC) in reward processing and the control of consummatory behavior. Rats were trained in an operant licking procedure in which they received alternating access to solutions with relatively high and low levels of sucrose (20 and 4%, w/v). Each level of sucrose was available for fixed intervals of 30 s over 30 min test sessions. Over several days of training, rats came to lick persistently when the high level of sucrose was available and suppressed licking when the low level of sucrose was available. Pharmacological inactivations of the mPFC, specifically the rostral part of the prelimbic area, greatly reduced intake of the higher value fluid and only slightly increased intake of the lower value fluid. In addition, the inactivations altered within-session patterns and microstructural measures of licking. Rats licked equally for the high and low levels of sucrose at the beginning of the test sessions and "relearned" to reduce intake of the low value fluid over the test sessions. Durations of licking bouts (clusters of licks with inter-lick intervals <0.5 s) were reduced for the high value fluid and there were many more brief licking bouts (<1 s) when the low value fluid was available. These effects were verified using an alternative approach (optogenetic silencing using archaerhodopsin) and were distinct from inactivation of the ventral striatum, which simply increased overall intake. Our findings suggest that the mPFC is crucial for the maintenance of persistent licking and the expression of learned feeding strategies.

CognitiveConstruct

RewardProcessing

10.1002/ajmg.b.32310

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

Am J Med Genet B Neuropsychiatr Genet

Causal discovery in an adult ADHD data set suggests indirect link between DAT1 genetic variants and striatal brain activation during reward processing.

Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder affecting both children and adults. One of the candidate genes for ADHD is DAT1, encoding the dopamine transporter. In an attempt to clarify its mode of action, we assessed brain activity during the reward anticipation phase of the Monetary Incentive Delay (MID) task in a functional MRI paradigm in 87 adult participants with ADHD and 77 controls (average age 36.5 years). The MID task activates the ventral striatum, where DAT1 is most highly expressed. A previous analysis based on standard statistical techniques did not show any significant dependencies between a variant in the DAT1 gene and brain activation [Hoogman et al. (2013); Neuropsychopharm 23:469-478]. Here, we used an alternative method for analyzing the data, that is, causal modeling. The Bayesian Constraint-based Causal Discovery (BCCD) algorithm [Claassen and Heskes (2012); Proceedings of the 28th Conference on Uncertainty in Artificial Intelligence] is able to find direct and indirect dependencies between variables, determines the strength of the dependencies, and provides a graphical visualization to interpret the results. Through BCCD one gets an opportunity to consider several variables together and to infer causal relations between them. Application of the BCCD algorithm confirmed that there is no evidence of a direct link between DAT1 genetic variability and brain activation, but suggested an indirect link mediated through inattention symptoms and diagnostic status of ADHD. Our finding of an indirect link of DAT1 with striatal activity during reward anticipation might explain existing discrepancies in the current literature. Further experiments should confirm this hypothesis. © 2015 Wiley Periodicals, Inc.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2015.04.002

Neuropsychologia

Neuropsychologia

Blunted neural responses to monetary risk in high sensation seekers.

The sensation-seeking trait is a valid predictor of various risk-taking behaviors. However, the neural underpinnings of risk processing in sensation seeking are yet unclear. The present event-related potential (ERP) study examined electrophysiological correlates associated with different stages of risky reward processing in sensation seeking. Twenty-one high sensation seekers (HSS) and 22 low sensation seekers (LSS) performed a simple two-choice gambling task. Behaviorally, whereas LSS exhibited a risk-averse pattern, HSS showed a risk-neutral pattern. During the anticipation stage, an increased stimulus-preceding negativity was elicited by high-risk compared to low-risk choices in LSS but not in HSS. During the outcome-appraisal stage, the feedback-related negativity, when calculated as the difference between losses and gains, was enhanced in response to the high-risk versus low-risk outcomes, which appeared for LSS but not for HSS. Further, HSS as compared to LSS exhibited a diminished P300 to both gains and losses. These findings suggest that risk-taking behavior in sensation seeking is expressed as blunted neural responses to risk in the anticipation stage and in the outcome-appraisal stage, which represents a candidate target for drug prevention.

CognitiveConstruct

RewardProcessing

10.1186/s11689-015-9107-8

Journal of neurodevelopmental disorders

J Neurodev Disord

Neural mechanisms of negative reinforcement in children and adolescents with autism spectrum disorders.

Previous research has found accumulating evidence for atypical reward processing in autism spectrum disorders (ASD), particularly in the context of social rewards. Yet, this line of research has focused largely on positive social reinforcement, while little is known about the processing of negative reinforcement in individuals with ASD. The present study examined neural responses to social negative reinforcement (a face displaying negative affect) and non-social negative reinforcement (monetary loss) in children with ASD relative to typically developing children, using functional magnetic resonance imaging (fMRI). We found that children with ASD demonstrated hypoactivation of the right caudate nucleus while anticipating non-social negative reinforcement and hypoactivation of a network of frontostriatal regions (including the nucleus accumbens, caudate nucleus, and putamen) while anticipating social negative reinforcement. In addition, activation of the right caudate nucleus during non-social negative reinforcement was associated with individual differences in social motivation. These results suggest that atypical responding to negative reinforcement in children with ASD may contribute to social motivational deficits in this population.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2015.03.049

Behavioural brain research

Behav Brain Res

Harmonic and frequency modulated ultrasonic vocalizations reveal differences in conditioned and unconditioned reward processing.

Novelty and sensation seeking (NSS) and ultrasonic vocalizations (USVs) are both used as measures of individual differences in reward sensitivity in rodent models. High responders in the inescapable novelty screen have a greater response to low doses of amphetamine and acquire self-administration more rapidly, while the novelty place preference screen is positively correlated with compulsive drug seeking. These screens are uncorrelated and implicated in separate drug abuse models. 50 kHz USVs measure affective state in rats and are evoked by positive stimuli. NSS and USVs are each implicated in drug response, self-administration, and reveal differences in individual behavior, yet their relationship with each other is not understood. The present study screened rats for their response to novelty and measured USVs of all call types in response to heterospecific play to determine the relationships between these individual difference traits. Generally, we hypothesized that 50k Hz USVs would be positively correlated with the NPP screen, and that 22 kHz would be positively correlated with the IEN screen. Results indicate none of the screens were correlated indicating they are measuring different individual difference traits. However, examination of the subtypes of USVs indicated harmonic USVs and the novelty place preference were positively correlated. Harmonic 50 kHz USVs increased in response to reward associated context, suggesting animals conditioned to the heterospecific tickle arena and anticipated rewarding stimuli, while FM only increased in response to tickling. USV subtypes can be used to elucidate differences in attribution of incentive value across conditioned stimuli and receipt of rewarding stimuli. These data provide strong support that harmonic and FM USVs can be used to understand reward processing in addition to NSS.

CognitiveConstruct

RewardProcessing

Basic and clinical neuroscience

Basic Clin Neurosci

The Blockade of D1/D2-Like Dopamine Receptors within the Dentate Gyrus of Hippocampus Decreased the Reinstatement of Morphine-Extinguished Conditioned Place Preference in Rats.

The hippocampus (HIP), the primary brain structure related to learning and memory, receives sparse but comprehensive dopamine innervations and contains dopamine D1/D2-like receptors. It is demonstrated that dopamine receptors in dentate gyrus (DG) region of HIP have a remarkable function in spatial reward processing. Much less is known about the involvement of HIP and its D1/D2 dopamine receptors in drug-seeking behaviors, more particularly, in the morphine extinguished conditioned place preference (CPP). To find out the role of D1/D2-like receptors within the DG in morphine-seeking behaviors, forty adult male albino Wistar rats weighing 220-280g were unilaterally implanted by a cannula into the DG. The CPP paradigm was done; conditioning score and locomotors activity were recorded by Ethovision software. All drugs/vehicles were microinjected one day after extinction (just before the CPP test) into the DG as reinstatement day. The results showed that intra-DG administration of different dose of SCH23390 (0.25, 1 and 4μg/0.5μl saline), as a selective D1-like receptor antagonist and sulpiride (0.25, 1 and 4μg/0.5μl DMSO), as a selective D2-like receptor antagonist dose-dependently attenuated the morphine-extinguished CPP reinstated by priming injection of morphine (1 mg/kg;sc). It can be concluded that D1/D2-like receptors within this region have an important role in morphine-seeking behaviors in extinguished rats.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsv036

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Higher incentives can impair performance: neural evidence on reinforcement and rationality.

Standard economic thinking postulates that increased monetary incentives should increase performance. Human decision makers, however, frequently focus on past performance, a form of reinforcement learning occasionally at odds with rational decision making. We used an incentivized belief-updating task from economics to investigate this conflict through measurements of neural correlates of reward processing. We found that higher incentives fail to improve performance when immediate feedback on decision outcomes is provided. Subsequent analysis of the feedback-related negativity, an early event-related potential following feedback, revealed the mechanism behind this paradoxical effect. As incentives increase, the win/lose feedback becomes more prominent, leading to an increased reliance on reinforcement and more errors. This mechanism is relevant for economic decision making and the debate on performance-based payment.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0119089

PloS one

PLoS One

Diagnostic classification of schizophrenia patients on the basis of regional reward-related FMRI signal patterns.

Functional neuroimaging has provided evidence for altered function of mesolimbic circuits implicated in reward processing, first and foremost the ventral striatum, in patients with schizophrenia. While such findings based on significant group differences in brain activations can provide important insights into the pathomechanisms of mental disorders, the use of neuroimaging results from standard univariate statistical analysis for individual diagnosis has proven difficult. In this proof of concept study, we tested whether the predictive accuracy for the diagnostic classification of schizophrenia patients vs. healthy controls could be improved using multivariate pattern analysis (MVPA) of regional functional magnetic resonance imaging (fMRI) activation patterns for the anticipation of monetary reward. With a searchlight MVPA approach using support vector machine classification, we found that the diagnostic category could be predicted from local activation patterns in frontal, temporal, occipital and midbrain regions, with a maximal cluster peak classification accuracy of 93% for the right pallidum. Region-of-interest based MVPA for the ventral striatum achieved a maximal cluster peak accuracy of 88%, whereas the classification accuracy on the basis of standard univariate analysis reached only 75%. Moreover, using support vector regression we could additionally predict the severity of negative symptoms from ventral striatal activation patterns. These results show that MVPA can be used to substantially increase the accuracy of diagnostic classification on the basis of task-related fMRI signal patterns in a regionally specific way.

CognitiveConstruct

RewardProcessing

10.3389/fncel.2015.00025

Frontiers in cellular neuroscience

Front Cell Neurosci

Modulation of the glutamatergic transmission by Dopamine: a focus on Parkinson, Huntington and Addiction diseases.

Dopamine (DA) plays a major role in motor and cognitive functions as well as in reward processing by regulating glutamatergic inputs. In particular in the striatum the release of DA rapidly influences synaptic transmission modulating both AMPA and NMDA receptors. Several neurodegenerative and neuropsychiatric disorders, including Parkinson, Huntington and addiction-related diseases, manifest a dysregulation of glutamate and DA signaling. Here, we will focus our attention on the mechanisms underlying the modulation of the glutamatergic transmission by DA in striatal circuits.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2015.02.069

NeuroImage

Neuroimage

Evidence for an anterior-posterior differentiation in the human hippocampal formation revealed by meta-analytic parcellation of fMRI coordinate maps: focus on the subiculum.

Previous studies, predominantly in experimental animals, have suggested the presence of a differentiation of function across the hippocampal formation. In rodents, ventral regions are thought to be involved in emotional behavior while dorsal regions mediate cognitive or spatial processes. Using a combination of modeling the co-occurrence of significant activations across thousands of neuroimaging experiments and subsequent data-driven clustering of these data we were able to provide evidence of distinct subregions within a region corresponding to the human subiculum, a critical hub within the hippocampal formation. This connectivity-based model consists of a bilateral anterior region, as well as separate posterior and intermediate regions on each hemisphere. Functional connectivity assessed both by meta-analytic and resting fMRI approaches revealed that more anterior regions were more strongly connected to the default mode network, and more posterior regions were more strongly connected to 'task positive' regions. In addition, our analysis revealed that the anterior subregion was functionally connected to the ventral striatum, midbrain and amygdala, a circuit that is central to models of stress and motivated behavior. Analysis of a behavioral taxonomy provided evidence for a role for each subregion in mnemonic processing, as well as implication of the anterior subregion in emotional and visual processing and the right posterior subregion in reward processing. These findings lend support to models which posit anterior-posterior differentiation of function within the human hippocampal formation and complement other early steps toward a comparative (cross-species) model of the region.

CognitiveConstruct

RewardProcessing

10.1002/mds.26177

Movement disorders : official journal of the Movement Disorder Society

Mov Disord

Dopamine signals and physiological origin of cognitive dysfunction in Parkinson's disease.

The pathological hallmark of Parkinson's disease (PD) is the degeneration of midbrain dopamine neurons. Cognitive dysfunction is a feature of PD patients even at the early stages of the disease. Electrophysiological studies on dopamine neurons in awake animals provide contradictory accounts of the role of dopamine. These studies have established that dopamine neurons convey a unique signal associated with rewards rather than cognitive functions. Emphasizing their role in reward processing leads to difficulty in developing hypothesis as to how cognitive impairments in PD are associated with the degeneration of dopamine circuitry. A hint to resolve this contradiction came from recent electrophysiological studies reporting that dopamine neurons transmit more diverse signals than previously thought. These studies suggest that dopamine neurons are divided into at least two functional subgroups, one signaling "motivational value" and the other signaling "salience." The former subgroup fits well with the conventional reward theory, whereas the latter subgroup has been shown to transmit signals related to salient but non-rewarding experiences such as aversive stimulations and cognitively demanding situations. This article reviews recent advances in understanding the non-reward functions of dopamine, and then discusses the possibility that cognitive dysfunction in PD is at least partially caused by the degeneration of the dopamine neuron subgroup signaling the salience of events in the environment.

CognitiveConstruct

RewardProcessing

10.1111/nyas.12634

Annals of the New York Academy of Sciences

Ann N Y Acad Sci

Dance experience sculpts aesthetic perception and related brain circuits.

Previous research on aesthetic preferences demonstrates that people are more likely to judge a stimulus as pleasing if it is familiar. Although general familiarity and liking are related, it is less clear how motor familiarity, or embodiment, relates to a viewer's aesthetic appraisal. This study directly compared how learning to embody an action impacts the neural response when watching and aesthetically evaluating the same action. Twenty-two participants trained for 4 days on dance sequences. Each day they physically rehearsed one set of sequences, passively watched a second set, listened to the music of a third set, and a fourth set remained untrained. Functional MRI was obtained prior to and immediately following the training period, as were affective and physical ability ratings for each dance sequence. This approach enabled precise comparison of self-report methods of embodiment with nonbiased, empirical measures of action performance. Results suggest that after experience, participants most enjoy watching those dance sequences they danced or observed. Moreover, brain regions involved in mediating the aesthetic response shift from subcortical regions associated with dopaminergic reward processing to posterior temporal regions involved in processing multisensory integration, emotion, and biological motion.

CognitiveConstruct

RewardProcessing

10.1002/ejp.687

European journal of pain (London, England)

Eur J Pain

Reward responsiveness in patients with chronic pain.

It is proposed that changes in reward processing in the brain are involved in the pathophysiology of pain based on experimental studies. The first aim of the present study was to investigate if reward drive and/or reward responsiveness was altered in patients with chronic pain (PCP) compared to controls matched for education, age and sex. The second aim was to investigate the relationship between reward processing and nucleus accumbens volume in PCP and controls. Nucleus accumbens is central in reward processing and its structure has been shown to be affected by chronic pain conditions in previous studies. Reward drive and responsiveness were assessed with the Behavioral Inhibition Scale/Behavioral Activation Scale, and nucleus accumbens volumes obtained from T1-weighted brain MRIs obtained at 3T in 19 PCP of heterogeneous aetiologies and 20 age-, sex- and education-matched healthy controls. Anhedonia was assessed with Beck's Depression Inventory II. The PCP group had significantly reduced scores on the reward responsiveness, but not reward drive. There was a trend towards smaller nucleus accumbens volume in the PCP compared to control group. There was a significant positive partial correlation between reward responsiveness and nucleus accumbens volume in the PCP group adjusted for anhedonia, which was significantly different from the same relationship in the control group. Reward responsiveness is reduced in chronic pain patients of heterogeneous aetiology, and this reduction was associated with nucleus accumbens volume. Reduced reward responsiveness could be a marker of chronic pain vulnerability, and may indicate reduced opioid function.

CognitiveConstruct

RewardProcessing

10.1007/s00213-015-3883-4

Psychopharmacology

Psychopharmacology (Berl)

The effects of nicotine dependence and acute abstinence on the processing of drug and non-drug rewards.

Drug addiction may be characterised by a hypersensitivity to drug rewards and a hyposensitivity to non-drug rewards. This imbalance may become further polarised during acute abstinence. (i) Examine the differences between dependent and occasional smokers in choices for, motivation for and self-reported wanting and liking of cigarette and non-drug rewards. (ii) Examine the effects of 12-h nicotine abstinence on these metrics. Dependent (n = 20) and occasional, non-dependent smokers (n = 20) were tested after ad libitum smoking and ≥12-h of nicotine abstinence. A novel task was developed (Drug, Reward and Motivation-Choice (DReaM-Choice)) in which different rewards (cigarettes, music and chocolate) could be won. In each trial, participants chose between two rewards and then could earn the chosen reward via repeated button-pressing. Participants subsequently 'consumed' and rated subjective liking of the rewards they had won. Compared with occasional smokers, dependent smokers made more choices for (p < 0.001), pressed more for (p = 0.046) and reported more wanting (p = 0.007) and liking (p < 0.001) of cigarettes, and also made fewer choices for chocolate (p = 0.005). There were no differences between the groups on button-pressing for chocolate or music. However, the balance between drug and non-drug reward processing was different between the groups across all metrics. Twelve-hour nicotine abstinence led to more cigarette choices (p < 0.001) and fewer music choices (p = 0.042) in both groups. Nicotine dependence was associated with a hypersensitivity to cigarette rewards, but we found little evidence indicating a hyposensitivity to non-drug rewards. Our findings question the moderating influence of dependence on how acute nicotine abstinence affects reward processing.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsv024

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Diminished social reward anticipation in the broad autism phenotype as revealed by event-related brain potentials.

Diminished responsivity to reward incentives is a key contributor to the social-communication problems seen in autism spectrum disorders (ASDs). Social motivation theories suggest that individuals with ASD do not experience social interactions as rewarding, leading to negative consequences for the development of brain circuitry subserving social information. In this study, we examined neural responses to social and non-social reward anticipation in 35 typically developing young adults, examining modulation of reward sensitivity by level of autistic traits. Using an Event-related potential incentive-delay task incorporating novel, more ecologically valid forms of reward, higher expression of autistic traits was associated with an attenuated P3 response to the anticipation of social (simulated real-time video feedback from an observer), but not non-social (candy), rewards. Exploratory analyses revealed that this was unrelated to mentalizing ability. The P3 component reflects motivated attention to reward signals, suggesting attenuated motivation allocation specific to social incentives. The study extends prior findings of atypical reward anticipation in ASD, demonstrating that attenuated social reward responsiveness extends to autistic traits in the range of typical functioning. Results support the development of innovative paradigms for investigating social and non-social reward responsiveness. Insight into vulnerabilities in reward processing is critical for understanding social function in ASD.

CognitiveConstruct

RewardProcessing

10.1038/npp.2015.54

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Reward Anticipation Is Differentially Modulated by Varenicline and Nicotine in Smokers.

Recidivism rates for cigarette smokers following treatment often exceed 80%. Varenicline is the most efficacious pharmacotherapy currently available with cessation rates of 25-35% following a year of treatment. Although the in vivo binding properties are well known, varenicline's neurobiological mechanisms of action are still poorly understood. Varenicline acts as a nicotinic receptor partial agonist or antagonist depending on the presence or absence of nicotine and has been implicated in the reduction of reward signaling more broadly. The current study probed anticipatory reward processing using a revised monetary incentive delay task during fMRI in cohorts of smokers and non-smokers who completed a two-drug, placebo-controlled, double-blind crossover study. All participants underwent ~17 days of order-balanced varenicline and placebo pill administration and were scanned under each condition wearing a transdermal nicotine or placebo patch. Consistent with nicotine's ability to enhance the rewarding properties of nondrug stimuli, acute nicotine administration enhanced activation in response to reward-predicting monetary cues in both smokers and non-smokers. In contrast, varenicline reduced gain magnitude processing, but did so only in smokers. These results suggest that varenicline's downregulation of anticipatory reward processing in smokers, in addition to its previously demonstrated reduction in the negative affect associated with withdrawal, independently and additively alter distinct brain circuits. These effects likely contribute to varenicline's efficacy as a pharmacotherapy for smoking cessation.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2015.00024

Frontiers in behavioral neuroscience

Front Behav Neurosci

Helping or punishing strangers: neural correlates of altruistic decisions as third-party and of its relation to empathic concern.

Social norms are a cornerstone of human society. When social norms are violated (e.g., fairness) people can either help the victim or punish the violator in order to restore justice. Recent research has shown that empathic concern influences this decision to help or punish. Using functional magnetic resonance imaging (fMRI) we investigated the neural underpinnings of third-party help and punishment and the involvement of empathic concern. Participants saw a person violating a social norm, i.e., proposing unfair offers in a dictator game, at the expense of another person. The participants could then decide to either punish the violator or help the victim. Our results revealed that both third-party helping as well as third-party punishing activated the bilateral striatum, a region strongly related with reward processing, indicating that both altruistic decisions share a common neuronal basis. In addition, also different networks were involved in the two processes compared with control conditions; bilateral striatum and the right lateral prefrontal cortex (lPFC) during helping and bilateral striatum as well as left lPFC and ventral medial prefrontal cortex (vmPFC) during punishment. Further we found that individual differences in empathic concern influenced whether people prefer to help or to punish. People with high empathic concern helped more frequently, were faster in their decision and showed higher activation in frontoparietal regions during helping compared with punishing. Our findings provide insights into the neuronal basis of human altruistic behavior and social norm enforcement mechanism.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.4744-14.2015

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

J Neurosci

Obesity is associated with decreased μ-opioid but unaltered dopamine D2 receptor availability in the brain.

Neurochemical pathways involved in pathological overeating and obesity are poorly understood. Although previous studies have shown increased μ-opioid receptor (MOR) and decreased dopamine D2 receptor (D2R) availability in addictive disorders, the role that these systems play in human obesity still remains unclear. We studied 13 morbidly obese women [mean body mass index (BMI), 42 kg/m(2)] and 14 nonobese age-matched women, and measured brain MOR and D2R availability using PET with selective radioligands [(11)C]carfentanil and [(11)C]raclopride, respectively. We also used quantitative meta-analytic techniques to pool previous evidence on the effects of obesity on altered D2R availability. Morbidly obese subjects had significantly lower MOR availability than control subjects in brain regions relevant for reward processing, including ventral striatum, insula, and thalamus. Moreover, in these areas, BMI correlated negatively with MOR availability. Striatal MOR availability was also negatively associated with self-reported food addiction and restrained eating patterns. There were no significant differences in D2R availability between obese and nonobese subjects in any brain region. Meta-analysis confirmed that current evidence for altered D2R availability in obesity is only modest. Obesity appears to have unique neurobiological underpinnings in the reward circuit, whereby it is more similar to opioid addiction than to other addictive disorders. The opioid system modulates motivation and reward processing, and low μ-opioid availability may promote overeating to compensate decreased hedonic responses in this system. Behavioral and pharmacological strategies for recovering opioidergic function might thus be critical to curb the obesity epidemic.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2015.02.012

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

A reward-centred model of anorexia nervosa: a focussed narrative review of the neurological and psychophysiological literature.

This focussed narrative review examines neurobiological and psychophysiological evidence supporting a role for altered reward processes in the development and maintenance of anorexia nervosa (AN). In AN, there does not appear to be a generalised inability to experience reward. Rather, data suggest that a reluctance to gain weight leads to an aversive appraisal of food- and taste-related stimuli. As a result, cues compatible with this aberrant mode of thinking become rewarding for the individual. Evidence also suggests that attribution of motivational salience to such cues promotes anorectic behaviours. These findings are consistent with models in which interactions between cognition and reward are important in eliciting the anorectic "habit". A model is proposed which is consistent with elements of other theoretical frameworks, but differs in that its emphasis is towards neural overlaps between AN and addiction. It is consistent with AN being a reward-based learned behaviour in which aberrant cognitions related to eating and shape alter functioning of central reward systems. It proposes that the primary neural problem responsible for the development, maintenance, and treatment resistance is centred in the striatal reward system. This helps shift the emphasis of aetiological models towards reward processing, particularly in the context of illness-compatible cues. Furthermore, it suggests that continuing to explore the utility and valued nature of AN in the patient's life would be a useful inclusion in treatment and prevention models.

CognitiveConstruct

RewardProcessing

10.1037/xan0000052

Journal of experimental psychology. Animal learning and cognition

J Exp Psychol Anim Learn Cogn

Stress increases cue-triggered "wanting" for sweet reward in humans.

Stress can increase reward pursuits: This has traditionally been seen as an attempt to relieve negative affect through the hedonic properties of a reward. However, reward pursuit is not always proportional to the pleasure experienced, because reward processing involves distinct components, including the motivation to obtain a reward (i.e., wanting) and the hedonic pleasure during the reward consumption (i.e., liking). Research conducted on rodents demonstrates that stress might directly amplify the cue-triggered wanting, suggesting that under stress wanting can be independent from liking. Here, we aimed to test whether a similar mechanism exists in humans. We used analog of a Pavlovian-Instrumental Transfer test (PIT) with an olfactory reward to measure the cue triggered wanting for a reward but also the sensory hedonic liking felt during the consumption of the same reward. The analog of a PIT procedure, in which participants learned to associate a neutral image and an instrumental action with a chocolate odor, was combined with either a stress-inducing or stress-free behavioral procedure. Results showed that compared with participants in the stress-free condition, those in the stress condition mobilized more effort in instrumental action when the reward-associated cue was displayed, even though they did not report the reward as being more pleasurable. These findings suggest that, in humans, stress selectively increases cue-triggered wanting, independently of the hedonic properties of the reward. Such a mechanism supports the novel explanation proposed by animal research as to why stress often produces cue-triggered bursts of binge eating, relapses in drug addiction, or gambling.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2015.00090

Frontiers in psychology

Front Psychol

Mindfulness meditation modulates reward prediction errors in a passive conditioning task.

Reinforcement learning models have demonstrated that phasic activity of dopamine neurons during reward expectation encodes information about the predictability of reward and cues that predict reward. Self-control strategies such as those practiced in mindfulness-based approaches is claimed to reduce negative and positive reactions to stimuli suggesting the hypothesis that such training may influence basic reward processing. Using a passive conditioning task and fMRI in a group of experienced mindfulness meditators and age-matched controls, we tested the hypothesis that mindfulness meditation influence reward and reward prediction error (PE) signals. We found diminished positive and negative PE-related blood-oxygen level-dependent (BOLD) responses in the putamen in meditators compared with controls. In the meditator group this decrease in striatal BOLD responses to reward PE was paralleled by increased activity in posterior insula, a primary interoceptive region. Critically, responses in the putamen during early trials of the conditioning procedure (run 1) were elevated in both meditators and controls. Overall, these results provide evidence that experienced mindfulness meditators are able to attenuate reward prediction signals to valenced stimuli, which may be related to interoceptive processes encoded in the posterior insula.

CognitiveConstruct

RewardProcessing

10.1002/brb3.293

Brain and behavior

Brain Behav

Altered reward processing in pathological computer gamers--ERP-results from a semi-natural gaming-design.

Internet Gaming Disorder has been added as a research diagnosis in section III for the DSM-V. Previous findings from neuroscientific research indicate an enhanced motivational attention toward cues related to computer games, similar to findings in substance-related addictions. On the other hand in clinical observational studies tolerance effects are reported by patients with Internet Gaming disorder. In the present study we investigated whether an enhanced motivational attention or tolerance effects are present in patients with Internet Gaming Disorder. A clinical sample from the Outpatient Clinic for Behavioral Addictions in Mainz, Germany was recruited, fulfilling the diagnostic criteria for Internet Gaming Disorder. In a semi-natural EEG design participants played a computer game during the recording of event-related potentials to assess reward processing. The results indicated an attenuated P300 for patients with Internet Gaming Disorder in response to rewards in comparison to healthy controls, while the latency of N100 was prolonged and the amplitude of N100 was increased. Our findings support the hypothesis that tolerance effects are present in patients with Internet Gaming Disorder, when actively playing computer games. In addition, the initial orienting toward the gaming reward is suggested to consume more capacity for patients with Internet Gaming Disorder, which has been similarly reported by other studies with other methodological background in disorders of substance-related addictions.

CognitiveConstruct

RewardProcessing

10.1111/ejn.12855

The European journal of neuroscience

Eur J Neurosci

Intrinsic membrane plasticity via increased persistent sodium conductance of cholinergic neurons in the rat laterodorsal tegmental nucleus contributes to cocaine-induced addictive behavior.

The laterodorsal tegmental nucleus (LDT) is a brainstem nucleus implicated in reward processing and is one of the main sources of cholinergic afferents to the ventral tegmental area (VTA). Neuroplasticity in this structure may affect the excitability of VTA dopamine neurons and mesocorticolimbic circuitry. Here, we provide evidence that cocaine-induced intrinsic membrane plasticity in LDT cholinergic neurons is involved in addictive behaviors. After repeated experimenter-delivered cocaine exposure, ex vivo whole-cell recordings obtained from LDT cholinergic neurons revealed an induction of intrinsic membrane plasticity in regular- but not burst-type neurons, resulting in increased firing activity. Pharmacological examinations showed that increased riluzole-sensitive persistent sodium currents, but not changes in Ca(2+) -activated BK, SK or voltage-dependent A-type potassium conductance, mediated this plasticity. In addition, bilateral microinjection of riluzole into the LDT immediately before the test session in a cocaine-induced conditioned place preference (CPP) paradigm inhibited the expression of cocaine-induced CPP. These findings suggest that intrinsic membrane plasticity in LDT cholinergic neurons is causally involved in the development of cocaine-induced addictive behaviors.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22773

Human brain mapping

Hum Brain Mapp

Enhanced neural responsiveness to reward associated with obesity in the absence of food-related stimuli.

Obesity has been characterized by alterations in brain structure and function associated with emotion processing and regulation. Particularly, aberrations in food-related reward processing have been frequently demonstrated in obese subjects. However, it remains unclear whether reward-associated functional aberrations in obesity are specific for food-related stimuli or represent a general deficit in reward processing, extending to other stimulus domains. Given the crucial role of rewarding effects in the development of obesity and the ongoing discussion on overlapping neurobiological traits of obesity and psychiatric disorders such as depression and substance-related disorders, this study aimed to investigate the possibility of altered reward processing in obese subjects to occur in the absence of food-related stimuli during a monetary reward condition. Twenty-nine healthy obese subjects (body mass index >30) and 29 healthy, age-, and sex-matched control subjects of normal weight underwent functional MRI during a frequently used card guessing paradigm. A Group × Condition (win vs. loss) ANOVA was conducted to investigate differences between obese and normal-weight subjects. We found significant Group × Condition interaction effects in brain areas involved in emotion regulation and reward processing including the insula, the striatum, and the orbitofrontal cortex (OFC). This interaction was predominantly driven by a significant increase in blood oxygenation level dependent (BOLD) response in obese individuals while experiencing reward. Enhanced neural activation in obesity during reward processing seems to be apparent even in the absence of food-related stimuli and, thus, might point to generalized dysfunctions in reward-related brain circuits in obese individuals.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22771

Human brain mapping

Hum Brain Mapp

Impact of aging on frontostriatal reward processing.

Healthy aging is associated with a progressive decline across a range of cognitive functions. An important factor underlying this decline may be the age-related impairment in stimulus-reward processing. Several studies have investigated age-related effects, but compared young versus old subjects. This is the first study to investigate the effect of aging on brain activation during reward processing within a continuous segment of the adult life span. We scanned 49 healthy adults aged 40-70 years, using functional MRI. We adopted a simple reward task, which allowed separate evaluation of neural responses to reward anticipation and receipt. The effect of reward on performance accuracy and speed was not related to age, indicating that all subjects could perform the task correctly. We identified a whole-brain significant age-related decline of ventral striatum activation during reward anticipation as compared to neutral anticipation. Importantly, the specificity of this finding was underscored by the observation that there was no general decline in activation during anticipation. Activation in the ventral striatum increased with age during reward receipt as compared to receiving neutral outcome. Finally, activation in the ventromedial prefrontal cortex during outcome was not affected by age. Our data demonstrate that the typical shift in striatal activation from reward receipt to reward anticipation in young adults disappears with healthy aging. These changes are consistent the well-ocumented age-related decline of striatal dopamine availability, and may provide a stepping stone for further research of age-related neurodegenerative diseases.

CognitiveConstruct

RewardProcessing

10.3389/fphar.2015.00006

Frontiers in pharmacology

Front Pharmacol

Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies.

The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides (enkephalins, endorphins, and dynorphins). The endogenous cannabinoid system comprises lipid neuromodulators (endocannabinoids), enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2. These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction. Both opioid and cannabinoid receptors are coupled to G proteins and are expressed throughout the brain reinforcement circuitry. Extending classical pharmacology, research using genetically modified mice has provided important progress in the identification of the specific contribution of each component of these endogenous systems in vivo on reward process. This review will summarize available genetic tools and our present knowledge on the consequences of gene knockout on reinforced behaviors in both systems, with a focus on their potential interactions. A better understanding of opioid-cannabinoid interactions may provide novel strategies for therapies in addicted individuals.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsv008

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Compassion-based emotion regulation up-regulates experienced positive affect and associated neural networks.

Emotion regulation research has primarily focused on techniques that attenuate or modulate the impact of emotional stimuli. Recent evidence suggests that this mode regulation can be problematic in the context of regulation of emotion elicited by the suffering of others, resulting in reduced emotional connectedness. Here, we investigated the effects of an alternative emotion regulation technique based on the up-regulation of positive affect via Compassion-meditation on experiential and neural affective responses to depictions of individuals in distress, and compared these with the established emotion regulation strategy of Reappraisal. Using fMRI, we scanned 15 expert practitioners of Compassion-meditation either passively viewing, or using Compassion-meditation or Reappraisal to modulate their emotional reactions to film clips depicting people in distress. Both strategies effectively, but differentially regulated experienced affect, with Compassion primarily increasing positive and Reappraisal primarily decreasing negative affect. Imaging results showed that Compassion, relative to both passive-viewing and Reappraisal increased activation in regions involved in affiliation, positive affect and reward processing including ventral striatum and medial orbitfrontal cortex. This network was shown to be active prior to stimulus presentation, suggesting that the regulatory mechanism of Compassion is the stimulus-independent endogenous generation of positive affect.

CognitiveConstruct

RewardProcessing

10.1080/17470919.2015.1013223

Social neuroscience

Soc Neurosci

Understanding social hierarchies: The neural and psychological foundations of status perception.

Social groups across species rapidly self-organize into hierarchies, where members vary in their level of power, influence, skill, or dominance. In this review, we explore the nature of social hierarchies and the traits associated with status in both humans and nonhuman primates, and how status varies across development in humans. Our review finds that we can rapidly identify social status based on a wide range of cues. Like monkeys, we tend to use certain cues, like physical strength, to make status judgments, although layered on top of these more primitive perceptual cues are sociocultural status cues like job titles and educational attainment. One's relative status has profound effects on attention, memory, and social interactions, as well as health and wellness. These effects can be particularly pernicious in children and adolescents. Developmental research on peer groups and social exclusion suggests teenagers may be particularly sensitive to social status information, but research focused specifically on status processing and associated brain areas is very limited. Recent evidence from neuroscience suggests that there may be an underlying neural network, including regions involved in executive, emotional, and reward processing, that is sensitive to status information. We conclude with questions for future research as well as stressing the need to expand social neuroscience research on status processing to adolescents.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22760

Human brain mapping

Hum Brain Mapp

Oxytocin selectively facilitates learning with social feedback and increases activity and functional connectivity in emotional memory and reward processing regions.

In male Caucasian subjects, learning is facilitated by receipt of social compared with non-social feedback, and the neuropeptide oxytocin (OXT) facilitates this effect. In this study, we have first shown a cultural difference in that male Chinese subjects actually perform significantly worse in the same reinforcement associated learning task with social (emotional faces) compared with non-social feedback. Nevertheless, in two independent double-blind placebo (PLC) controlled between-subject design experiments we found OXT still selectively facilitated learning with social feedback. Similar to Caucasian subjects this OXT effect was strongest with feedback using female rather than male faces. One experiment performed in conjunction with functional magnetic resonance imaging showed that during the response, but not feedback phase of the task, OXT selectively increased activity in the amygdala, hippocampus, parahippocampal gyrus and putamen during the social feedback condition, and functional connectivity between the amygdala and insula and caudate. Therefore, OXT may be increasing the salience and reward value of anticipated social feedback. In the PLC group, response times and state anxiety scores during social feedback were associated with signal changes in these same regions but not in the OXT group. OXT may therefore have also facilitated learning by reducing anxiety in the social feedback condition. Overall our results provide the first evidence for cultural differences in social facilitation of learning per se, but a similar selective enhancement of learning with social feedback under OXT. This effect of OXT may be associated with enhanced responses and functional connectivity in emotional memory and reward processing regions.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2015.01.011

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

Int J Psychophysiol

Abnormal reward functioning across substance use disorders and major depressive disorder: Considering reward as a transdiagnostic mechanism.

A common criticism of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2013) is that its criteria are based more on behavioral descriptions than on underlying biological mechanisms. Increasingly, calls have intensified for a more biologically-based approach to conceptualizing, studying, and treating psychological disorders, as exemplified by the Research Domain Criteria Project (RDoC). Among the most well-studied neurobiological mechanisms is reward processing. Moreover, individual differences in reward sensitivity are related to risk for substance abuse and depression. The current review synthesizes the available preclinical, electrophysiological, and neuroimaging literature on reward processing from a transdiagnostic, multidimensional perspective. Findings are organized with respect to key reward constructs within the Positive Valence Systems domain of the RDoC matrix, including initial responsiveness to reward (physiological 'liking'), approach motivation (physiological 'wanting'), and reward learning/habit formation. In the current review, we (a) describe the neural basis of reward, (b) elucidate differences in reward activity in substance abuse and depression, and (c) suggest a framework for integrating these disparate literatures and discuss the utility of shifting focus from diagnosis to process for understanding liability and co-morbidity. Ultimately, we believe that an integrative focus on abnormal reward functioning across the full continuum of clinically heterogeneous samples, rather than within circumscribed diagnostic categories, might actually help to refine the phenotypes and improve the prediction of onset and recovery of these disorders.

CognitiveConstruct

RewardProcessing

10.1007/978-3-319-13665-3_8

Current topics in behavioral neurosciences

Curr Top Behav Neurosci

Smoking abstinence and neurocognition: implications for cessation and relapse.

In this chapter, we review the last decade of research on the effects of smoking abstinence on various forms of neurocognition, including executive function (working memory, sustained attention, response inhibition), reward processing, and cue-reactivity. In our review we identify smoking abstinence-induced deficits in executive function mediated by effects on frontal circuitry, which in turn is known to be affected by modulation of cholinergic, dopaminergic, and other neurotransmitter systems. We also review evidence that smoking abstinence blunts reactivity to non-drug reinforcers-a finding that is consistent with results in the animal literature. Finally, our review of cue-reactivity indicates that smoking abstinence does not appear to amplify cue-provoked craving, although it may increase attentional bias to smoking-related cues. Inconsistencies across findings and potential contributing factors are discussed. In addition, we review the literature on the effects of nicotine and non-nicotine factors in neurocognition. Finally, we provide a multi-factor model and an agenda for future research on the effects of smoking abstinence on neurocognition. The model includes four distinct yet interacting factors, including: Negative Reinforcement, Drug-Reward Bias, Goal and Skill Interference, and Non-Cognitive Factors. Additional research is needed to further evaluate the scope and time-course of abstinence-induced changes in neurocognition, the mechanisms that underlie these changes and the specific role of these processes in drug reinforcement, lapse, and relapse.

CognitiveConstruct

RewardProcessing

10.1016/j.neuron.2014.12.049

Neuron

Neuron

Neural mechanisms of incentive salience in naturalistic human vision.

What role does reward play in real-world human vision? Reward coding in the midbrain is thought to cause the rapid prioritization of reward-associated visual stimuli. However, existing evidence for this incentive salience hypothesis in vision is equivocal, particularly in naturalistic circumstances, and little is known about underlying neural systems. Here we use human fMRI to test whether reward primes perceptual encoding of naturalistic visual stimuli and to identify the neural mechanisms underlying this function. Participants detected a cued object category in briefly presented images of city- and landscapes. Using multivoxel pattern analysis in visual cortex, we found that the encoding of reward-associated targets was enhanced, whereas encoding of reward-associated distractors was suppressed, with the strength of this effect predicted by activity in the dopaminergic midbrain and a connected cortical network. These results identify a novel interaction between neural systems responsible for reward processing and visual perception in the human brain.

CognitiveConstruct

RewardProcessing

10.1016/j.alcohol.2014.12.004

Alcohol (Fayetteville, N.Y.)

Alcohol

BDNF Val66Met and reward-related brain function in adolescents: role for early alcohol consumption.

Changes in reward processing have been identified as one important pathogenetic mechanism in alcohol addiction. The nonsynonymous single nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene (rs6265/Val66Met) modulates the central nervous system activity of neurotransmitters involved in reward processing such as serotonin, dopamine, and glutamate. It was identified as crucial for alcohol consumption in healthy adults and, in rats, specifically related to the function in the striatum, a region that is commonly involved in reward processing. However, studies in humans on the association of BDNF Val66Met and reward-related brain functions and its role for alcohol consumption, a significant predictor of later alcohol addiction, are missing. Based on an intermediate phenotype approach, we assessed the early orientation toward alcohol and alcohol consumption in 530 healthy adolescents that underwent a monetary incentive delay task during functional magnetic resonance imaging. We found a significantly lower response in the putamen to reward anticipation in adolescent Met carriers with high versus low levels of alcohol consumption. During reward feedback, Met carriers with low putamen reactivity were significantly more likely to orient toward alcohol and to drink alcohol 2 years later. This study indicates a possible effect of BDNF Val66Met on alcohol addiction-related phenotypes in adolescence.

CognitiveConstruct

RewardProcessing

10.1038/npp.2015.18

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Neural Correlates of Aggression in Medication-Naive Children with ADHD: Multivariate Analysis of Morphometry and Tractography.

Aggression is widely observed in children with attention deficit/hyperactivity disorder (ADHD) and has been frequently linked to frustration or the unsatisfied anticipation of reward. Although animal studies and human functional neuroimaging implicate altered reward processing in aggressive behaviors, no previous studies have documented the relationship between fronto-accumbal circuitry-a critical cortical pathway to subcortical limbic regions-and aggression in medication-naive children with ADHD. To address this, we collected behavioral measures and parental reports of aggression and impulsivity, as well as structural and diffusion MRI, from 30 children with ADHD and 31 healthy controls (HC) (mean age, 10±2.1 SD). Using grey matter morphometry and probabilistic tractography combined with multivariate statistical modeling (partial least squares regression and support vector regression), we identified anomalies within the fronto-accumbal circuit in childhood ADHD, which were associated with increased aggression. More specifically, children with ADHD showed reduced right accumbal volumes and frontal-accumbal white matter connectivity compared with HC. The magnitude of the accumbal volume reductions within the ADHD group was significantly correlated with increased aggression, an effect mediated by the relationship between the accumbal volume and impulsivity. Furthermore, aggression, but not impulsivity, was significantly explained by multivariate measures of fronto-accumbal white matter connectivity and cortical thickness within the orbitofrontal cortex. Our multi-modal imaging, combined with multivariate statistical modeling, indicates that the fronto-accumbal circuit is an important substrate of aggression in children with ADHD. These findings suggest that strategies aimed at probing the fronto-accumbal circuit may be beneficial for the treatment of aggressive behaviors in childhood ADHD.

CognitiveConstruct

RewardProcessing

10.1038/srep08184

Scientific reports

Sci Rep

A concurrent excitation and inhibition of dopaminergic subpopulations in response to nicotine.

Midbrain dopamine (DA) neurons are key players in motivation and reward processing. Increased DA release is thought to be central in the initiation of drug addiction. Whereas dopamine neurons are generally considered to be activated by drugs such as nicotine, we report here that nicotine not only induces excitation of ventral tegmental area (VTA) DA cells but also induces inhibition of a subset of VTA DA neurons that are anatomically segregated in the medial part of the VTA. These opposite responses do not correlate with the inhibition and excitation induced by noxious stimuli. We show that this inhibition requires D2 receptor (D2-R) activation, suggesting that a dopaminergic release is involved in the mechanism. Our findings suggest a principle of concurrent excitation and inhibition of VTA DA cells in response to nicotine. It promotes unexplored roles for DA release in addiction contrasting with the classical views of reinforcement and motivation, and give rise to a new interpretation of the mode of operation of the reward system.

CognitiveConstruct

RewardProcessing

10.1016/j.cell.2015.01.003

Cell

Cell

Decoding neural circuits that control compulsive sucrose seeking.

The lateral hypothalamic (LH) projection to the ventral tegmental area (VTA) has been linked to reward processing, but the computations within the LH-VTA loop that give rise to specific aspects of behavior have been difficult to isolate. We show that LH-VTA neurons encode the learned action of seeking a reward, independent of reward availability. In contrast, LH neurons downstream of VTA encode reward-predictive cues and unexpected reward omission. We show that inhibiting the LH-VTA pathway reduces "compulsive" sucrose seeking but not food consumption in hungry mice. We reveal that the LH sends excitatory and inhibitory input onto VTA dopamine (DA) and GABA neurons, and that the GABAergic projection drives feeding-related behavior. Our study overlays information about the type, function, and connectivity of LH neurons and identifies a neural circuit that selectively controls compulsive sugar consumption, without preventing feeding necessary for survival, providing a potential target for therapeutic interventions for compulsive-overeating disorder.

CognitiveConstruct

RewardProcessing

10.1111/acer.12591

Alcoholism, clinical and experimental research

Alcohol Clin Exp Res

Binge-like consumption of ethanol and other salient reinforcers is blocked by orexin-1 receptor inhibition and leads to a reduction of hypothalamic orexin immunoreactivity.

Orexin (OX) neurons originating in the lateral hypothalamus (LH) are ideally positioned to modulate reward processing as they form connections with several key brain regions known to be involved in the reward pathway. Consistent with these findings, a growing number of studies have implicated the OX system in modulating the rewarding properties of several drugs of abuse, including ethanol (EtOH). However, the role of the OX system in excessive binge-like EtOH intake remains relatively unexplored. Here, we assessed changes in OX immunoreactivity (IR) in the hypothalamus following repeated cycles of binge-like EtOH drinking and assessed the participation of the OX-1 receptor (OX1R) in binge-like EtOH consumption. The drinking-in-the-dark (DID) paradigm was used to model binge-like EtOH drinking in male C57BL/6J mice. In the first experiment, mice experienced 1 or 3 cycles of binge-like EtOH or sucrose drinking with DID procedures to assess changes in OX IR in distinct subregions of the hypothalamus. Subsequent experiments examined binge-like EtOH and saccharin drinking following peripheral injections of 0.0, 5.0, or 10.0 mg/kg SB-334867 (SB), a selective OX1R antagonist. Finally, mice were given peripheral injections of SB and open-field locomotor activity was measured. Relative to water drinking controls, binge-like consumption of EtOH and sucrose resulted in a marked reduction in OX IR in the LH. Inhibition of the OX1R via SB blunted EtOH and saccharin drinking, but did not alter open-field locomotor activity. Our observed reduction in OX IR in the LH indicates that the OX system in engaged during binge-like consumption of EtOH and sucrose. The observation that inhibition of the OX1R signaling blunted binge-like EtOH, and saccharin drinking suggests that reward-related OX circuits originating in the LH participate in the consumption of salient reinforcers regardless of calories.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2014.12.018

Drug and alcohol dependence

Drug Alcohol Depend

Using behavioral economics to predict opioid use during prescription opioid dependence treatment.

Research grounded in behavioral economics has previously linked addictive behavior to disrupted decision-making and reward-processing, but these principles have not been examined in prescription opioid addiction, which is currently a major public health problem. This study examined whether pre-treatment drug reinforcement value predicted opioid use during outpatient treatment of prescription opioid addiction. Secondary analyses examined participants with prescription opioid dependence who received 12 weeks of buprenorphine-naloxone and counseling in a multi-site clinical trial (N=353). Baseline measures assessed opioid source and indices of drug reinforcement value, including the total amount and proportion of income spent on drugs. Weekly urine drug screens measured opioid use. Obtaining opioids from doctors was associated with lower pre-treatment drug spending, while obtaining opioids from dealers/patients was associated with greater spending. Controlling for demographics, opioid use history, and opioid source frequency, patients who spent a greater total amount (OR=1.30, p<.001) and a greater proportion of their income on drugs (OR=1.31, p<.001) were more likely to use opioids during treatment. Individual differences in drug reinforcement value, as indicated by pre-treatment allocation of economic resources to drugs, reflects propensity for continued opioid use during treatment among individuals with prescription opioid addiction. Future studies should examine disrupted decision-making and reward-processing in prescription opioid users more directly and test whether reinforcer pathology can be remediated in this population.

CognitiveConstruct

RewardProcessing

10.1093/ijnp/pyu004

The international journal of neuropsychopharmacology

Int J Neuropsychopharmacol

Erotic stimulus processing under amisulpride and reboxetine: a placebo-controlled fMRI study in healthy subjects.

Impaired sexual function is increasingly recognized as a side effect of psychopharmacological treatment. However, underlying mechanisms of action of the different drugs on sexual processing are still to be explored. Using functional magnetic resonance imaging, we previously investigated effects of serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic and antidopaminergic medication on neural correlates of visual sexual stimulation in a new sample of subjects. Nineteen healthy heterosexual males (mean age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent reboxetine (4 mg/d), the antidopaminergic agent amisulpride (200mg/d), and placebo were included and studied with functional magnetic resonance imaging within a randomized, double-blind, placebo-controlled, within-subjects design during an established erotic video-clip task. Subjective sexual functioning was assessed using the Massachusetts General Hospital-Sexual Functioning Questionnaire. Relative to placebo, subjective sexual functioning was attenuated under reboxetine along with diminished neural activations within the caudate nucleus. Altered neural activations correlated with decreased sexual interest. Under amisulpride, neural activations and subjective sexual functioning remained unchanged. In line with previous interpretations of the role of the caudate nucleus in the context of primary reward processing, attenuated caudate activation may reflect detrimental effects on motivational aspects of erotic stimulus processing under noradrenergic agents.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsycho.2015.01.005

Biological psychology

Biol Psychol

Allostatic dysregulation of natural reward processing in prescription opioid misuse: autonomic and attentional evidence.

Chronic pain patients who misuse prescription opioids may suffer from allostatic dysregulation of natural reward processing. Hence, this study examined whether prescription opioid misusers with chronic pain (n=72) evidenced decreased natural reward responsiveness relative to non-misusers with chronic pain (n=26). Subjects completed a dot probe task containing pain-related, opioid-related, and natural reward stimuli while attentional bias (AB) scores and heart rate variability (HRV) responses were assessed. Compared to non-misusers, misusers evidenced significantly more attenuated HRV responses to opioid, pain, and natural reward cues presented during the dot probe task. These significant between-groups differences in HRV were largest during attention to natural reward cues, but became non-significant in a sensitivity analysis controlling for opioid dosing. In addition, non-misusers evidenced an AB toward natural reward cues, whereas misusers did not. Findings suggest that opioid misusers exhibit attentional and autonomic deficits during reward processing.

CognitiveConstruct

RewardProcessing

10.1002/aur.1451

Autism research : official journal of the International Society for Autism Research

Autism Res

Electrodermal Response to Reward and Non-Reward Among Children With Autism.

Pervasive social difficulties among individuals with autism spectrum disorder (ASD) are often construed as deriving from reduced sensitivity to social stimuli. Behavioral and neurobiological evidence suggests that typical individuals show preferential processing of social (e.g., voices, faces) over nonsocial (e.g., nonvocal sounds, images of objects) information, whereas individuals with ASD may not. This reduction in sensitivity may reflect disrupted reward processing [Dawson & Bernier, ], with significant developmental consequences for affected individuals. In this study, we explore effects of social and monetary reward on behavioral and electrodermal responses (EDRs) among 8- to 12-year-old boys with (n = 18) and without (n = 18) ASD, with attention to the potential moderating effects of stimulus familiarity. During a simple matching task, participants with and without ASD had marginally slower reactions during social vs. nonsocial reward, and boys with ASD had less accurate responses than controls. Compared to baseline, reward and non-reward conditions elicited more frequent and larger EDRs for participants as a whole, and both groups showed similar patterns of EDR change within reward blocks. However, boys with and without ASD differed in their EDRs to non-reward, and response amplitude was correlated with social and emotional functioning. These findings provide some support for altered reward responding in ASD at the autonomic level, and highlight the discontinuation of reward as an important component of reward-based learning that may play a role in shaping behavior and guiding specialized brain development to subserve social behavior and cognition across the lifespan.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsu158

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Altered neural reward and loss processing and prediction error signalling in depression.

Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2014.00430

Frontiers in behavioral neuroscience

Front Behav Neurosci

State-dependent μ-opioid modulation of social motivation.

Social mammals engage in affiliative interactions both when seeking relief from negative affect and when searching for pleasure and joy. These two motivational states are both modulated by μ-opioid transmission. The μ-opioid receptor (MOR) system in the brain mediates pain relief and reward behaviors, and is implicated in social reward processing and affiliative bonding across mammalian species. However, pharmacological manipulation of the μ-opioid system has yielded opposite effects on rodents and primates: in rodents, social motivation is generally increased by MOR agonists and reduced by antagonists, whereas the opposite pattern has been shown in primates. Here, we address this paradox by taking into account differences in motivational state. We first review evidence for μ-opioid mediation of reward processing, emotion regulation, and affiliation in humans, non-human primates, rodents and other species. Based on the consistent cross-species similarities in opioid functioning, we propose a unified, state-dependent model for μ-opioid modulation of affiliation across the mammalian species. Finally, we show that this state-dependent model is supported by evidence from both rodent and primate studies, when species and age differences in social separation response are taken into account.

CognitiveConstruct

RewardProcessing

10.1002/cne.23730

The Journal of comparative neurology

J Comp Neurol

Evidence for limited D1 and D2 receptor coexpression and colocalization within the dorsal striatum of the neonatal mouse.

The striatum is the major input nucleus of the basal ganglia involved in reward processing, goal-directed behaviors, habit learning, and motor control. The striatum projects to the basal ganglia output nuclei via the "direct" and "indirect" pathways, which can be distinguished by their projection fields and their opposing effects on behavior. In adult animals, the functional opposition is modulated by the differential actions of D1 and D2 dopamine receptors (D1R, D2R), the expression of which is largely separated between these pathways. To determine whether a similar degree of separation exists earlier in development, we used dual-label immunohistochemistry to map dorsal-striatal D1R and D2R expression at the promoter level in postnatal day 0 (PD0) Drd1a-tdTomato/Drd2-GFP BAC transgenic mice, and at the receptor level by costaining for native D1R and D2R in wildtype (WT) PD0 animals. To assess for potential molecular interactions between D1R and D2R we also employed a recently developed proximity-ligation assay (PLA). Limited coexpression and colocalization of the D1R and D2R proteins was found in clusters of neurons endemic to the "patch" compartment as identified by costaining with tyrosine hydroxylase, but not outside these clusters. Moreover, in contrast to our recent findings where we failed to detect a D1R-D2R PLA signal in the adult striatum, in PD0 striatum we did identify a clear PLA signal for this pair of receptors. This colocalization at close proximity points to a possible role for D1R/D2R-mediated crosstalk in early striatal ontogeny.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsu162

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Neural dissociation of food- and money-related reward processing using an abstract incentive delay task.

Food is an innate reward stimulus related to energy homeostasis and survival, whereas money is considered a more general reward stimulus that gains a rewarding value through learning experiences. Although the underlying neural processing for both modalities of reward has been investigated independently from one another, a more detailed investigation of neural similarities and/or differences between food and monetary reward is still missing. Here, we investigated the neural processing of food compared with monetary-related rewards in 27 healthy, normal-weight women using functional magnetic resonance imaging. We developed a task distinguishing between the anticipation and the receipt of either abstract food or monetary reward. Both tasks activated the ventral striatum during the expectation of a reward. Compared with money, greater food-related activations were observed in prefrontal, parietal and central midline structures during the anticipation and lateral orbitofrontal cortex (lOFC) during the receipt of food reward. Furthermore, during the receipt of food reward, brain activation in the secondary taste cortex was positively related to the body mass index. These results indicate that food-dependent activations encompass to a greater extent brain regions involved in self-control and self-reflection during the anticipation and phylogenetically older parts of the lOFC during the receipt of reward.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0114569

PloS one

PLoS One

Prodromal Huntington disease as a model for functional compensation of early neurodegeneration.

Functional compensation demonstrated as mechanism to offset neuronal loss in early Alzheimer disease may also occur in other adult-onset neurodegenerative diseases, particularly Huntington disease (HD) with its genetic determination and gradual changes in structural integrity. In HD, neurodegeneration typically initiates in the dorsal striatum, successively affecting ventral striatal areas. Investigating carriers of the HD mutation with evident dorsal, but only minimal or no ventral striatal atrophy, we expected to find evidence for compensation of ventral striatal functioning. We investigated 14 pre- or early symptomatic carriers of the mutation leading to HD and 18 matched healthy controls. Participants underwent structural T1 magnetic resonance imaging (MRI) and functional MRI during a reward task that probes ventral striatal functioning. Motor functioning and attention were assessed with reaction time (RT) tasks. Structural images confirmed a specific decrease of dorsal striatal but only marginal ventral striatal volume in HD relative to control subjects, paralleling prolonged RT in the motor response tasks. While behavioral performance in the reward task during fMRI scanning was unimpaired, reward-related fMRI signaling in the HD group was differentially enhanced in the bilateral ventral striatum and in bilateral orbitofrontal cortex/anterior insula, as another region sensitive to reward processing. We provide evidence for the concept of functional compensation in premanifest HD which may suggest a defense mechanism in neurodegeneration. Given the so far inevitable course of HD with its genetically determined endpoint, this disease may provide another model to study the different aspects of the concept of functional compensation.

CognitiveConstruct

RewardProcessing

10.1162/jocn_a_00777

Journal of cognitive neuroscience

J Cogn Neurosci

Common and unique representations in pFC for face and place attractiveness.

Although previous neuroimaging research has identified overlapping correlates of subjective value across different reward types in the ventromedial pFC (vmPFC), it is not clear whether this "common currency" evaluative signal extends to the aesthetic domain. To examine this issue, we scanned human participants with fMRI while they made attractiveness judgments of faces and places-two stimulus categories that are associated with different underlying rewards, have very different visual properties, and are rarely compared with each other. We found overlapping signals for face and place attractiveness in the vmPFC, consistent with the idea that this region codes a signal for value that applies across disparate reward types and across both economic and aesthetic judgments. However, we also identified a subregion of vmPFC within which activity patterns for face and place attractiveness were distinguishable, suggesting that some category-specific attractiveness information is retained in this region. Finally, we observed two separate functional regions in lateral OFC: one region that exhibited a category-unique response to face attractiveness and another region that responded strongly to faces but was insensitive to their value. Our results suggest that vmPFC supports a common mechanism for reward evaluation while also retaining a degree of category-specific information, whereas lateral OFC may be involved in basic reward processing that is specific to only some stimulus categories.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2014.00410

Frontiers in behavioral neuroscience

Front Behav Neurosci

Are Extremes of Consumption in Eating Disorders Related to an Altered Balance between Reward and Inhibition?

The primary defining characteristic of a diagnosis of an eating disorder (ED) is the "disturbance of eating or eating-related behavior that results in the altered consumption or absorption of food" (DSM V; American Psychiatric Association, 2013). There is a spectrum, ranging from those who severely restrict eating and become emaciated on one end to those who binge and overconsume, usually accompanied by some form of compensatory behaviors, on the other. How can we understand reasons for such extremes of food consummatory behaviors? Recent work on obesity and substance use disorders has identified behaviors and neural pathways that play a powerful role in human consummatory behaviors. That is, corticostriatal limbic and dorsal cognitive neural circuitry can make drugs and food rewarding, but also engage self-control mechanisms that may inhibit their use. Importantly, there is considerable evidence that alterations of these systems also occur in ED. This paper explores the hypothesis that an altered balance of reward and inhibition contributes to altered extremes of response to salient stimuli, such as food. We will review recent studies that show altered sensitivity to reward and punishment in ED, with evidence of altered activity in corticostriatal and insula processes with respect to monetary gains or losses, and tastes of palatable foods. We will also discuss evidence for a spectrum of extremes of inhibition and dysregulation behaviors in ED supported by studies suggesting that this is related to top-down self-control mechanisms. The lack of a mechanistic understanding of ED has thwarted efforts for evidence-based approaches to develop interventions. Understanding how ED behavior is encoded in neural circuits would provide a foundation for developing more specific and effective treatment approaches.

CognitiveConstruct

RewardProcessing

10.1016/j.brainres.2014.12.024

Brain research

Brain Res

Differential roles of medial prefrontal subregions in the regulation of drug seeking.

The prefrontal cortex plays an important role in shaping cognition and behavior. Many studies have shown that medial prefrontal cortex (mPFC) plays a key role in seeking, extinction, and reinstatement of cocaine seeking in rodent models of relapse. Subregions of mPFC appear to play distinct roles in these behaviors, such that the prelimbic cortex (PL) is proposed to drive cocaine seeking and the infralimbic cortex (IL) is proposed to suppress cocaine seeking after extinction. This dichotomy of mPFC function may be a general attribute, as similar dorsal-ventral distinctions exist for expression vs. extinction of fear conditioning. However, other results indicate that the role of mPFC neurons in reward processing is more complex than a simple PL-seek vs. IL-extinguish dichotomy. Both PL and IL have been shown to drive and inhibit drug seeking (and other types of behaviors) depending on a range of factors including the behavioral context, the drug-history of the animal, and the type of drug investigated. This heterogeneity of findings may reflect multiple subcircuits within each of these PFC areas supporting unique functions. It may also reflect the fact that the mPFC plays a multifaceted role in shaping cognition and behavior, including those overlapping with cocaine seeking and extinction. Here we discuss research leading to the hypothesis that dorsal and ventral mPFC differentially control drug seeking and extinction. We also present recent results calling the absolute nature of a PL vs. IL dichotomy into question. Finally, we consider alternate functions for mPFC that correspond less to response execution and inhibition and instead incorporate the complex cognitive behavior for which the mPFC is broadly appreciated.

CognitiveConstruct

RewardProcessing

10.1176/appi.ajp.2014.13121700

The American journal of psychiatry

Am J Psychiatry

Reward-based spatial learning in unmedicated adults with obsessive-compulsive disorder.

The authors assessed the functioning of mesolimbic and striatal areas involved in reward-based spatial learning in unmedicated adults with obsessive-compulsive disorder (OCD). Functional MRI blood-oxygen-level-dependent response was compared in 33 unmedicated adults with OCD and 33 healthy, age-matched comparison subjects during a reward-based learning task that required learning to use extramaze cues to navigate a virtual eight-arm radial maze to find hidden rewards. The groups were compared in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudorandomly to experimentally prevent learning. Both groups learned to navigate the maze to find hidden rewards, but group differences in neural activity during navigation and reward processing were detected in mesolimbic and striatal areas. During navigation, the OCD group, unlike the healthy comparison group, exhibited activation in the left posterior hippocampus. Unlike healthy subjects, participants in the OCD group did not show activation in the left ventral putamen and amygdala when anticipating rewards or in the left hippocampus, amygdala, and ventral putamen when receiving unexpected rewards (control condition). Signal in these regions decreased relative to baseline during unexpected reward receipt among those in the OCD group, and the degree of activation was inversely associated with doubt/checking symptoms. Participants in the OCD group displayed abnormal recruitment of mesolimbic and ventral striatal circuitry during reward-based spatial learning. Whereas healthy comparison subjects exhibited activation in this circuitry in response to the violation of reward expectations, unmedicated OCD participants did not and instead over-relied on the posterior hippocampus during learning. Thus, dopaminergic innervation of reward circuitry may be altered, and future study of anterior/posterior hippocampal dysfunction in OCD is warranted.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2014.11.001

Developmental cognitive neuroscience

Dev Cogn Neurosci

Neural processing of reward in adolescent rodents.

Immaturities in adolescent reward processing are thought to contribute to poor decision making and increased susceptibility to develop addictive and psychiatric disorders. Very little is known; however, about how the adolescent brain processes reward. The current mechanistic theories of reward processing are derived from adult models. Here we review recent research focused on understanding of how the adolescent brain responds to rewards and reward-associated events. A critical aspect of this work is that age-related differences are evident in neuronal processing of reward-related events across multiple brain regions even when adolescent rats demonstrate behavior similar to adults. These include differences in reward processing between adolescent and adult rats in orbitofrontal cortex and dorsal striatum. Surprisingly, minimal age related differences are observed in ventral striatum, which has been a focal point of developmental studies. We go on to discuss the implications of these differences for behavioral traits affected in adolescence, such as impulsivity, risk-taking, and behavioral flexibility. Collectively, this work suggests that reward-evoked neural activity differs as a function of age and that regions such as the dorsal striatum that are not traditionally associated with affective processing in adults may be critical for reward processing and psychiatric vulnerability in adolescents.

CognitiveConstruct

RewardProcessing

10.1017/S1092852914000674

CNS spectrums

CNS Spectr

Early-life adversity and adolescent depression: mechanisms involving the ventral striatum.

Early-life adversity is a well-established risk factor for the development of depression later in life. Here we discuss the relationship between early-life adversity and depression, focusing specifically on effects of early-life caregiver deprivation on alterations in the neural and behavioral substrates of reward-processing. We also examine vulnerability to depression within the context of sensitive periods of neural development and the timing of adverse exposure. We further review the development of the ventral striatum, a limbic structure implicated in reward processing, and its role in depressive outcomes following early-life adversity. Finally, we suggest a potential neurobiological mechanism linking early-life adversity and altered ventral striatal development. Together these findings may help provide further insight into the role of reward circuitry dysfunction in psychopathological outcomes in both clinical and developmental populations.

CognitiveConstruct

RewardProcessing

10.1016/j.addbeh.2014.11.034

Addictive behaviors

Addict Behav

Bridging the gap between the neurocognitive lab and the addiction clinic.

In the past decennium there has been an enormous increase in new insights in cognitive mechanisms of addiction and their neural substrates. These candidate neurocognitive mechanisms, particularly those associated with "drive" and "control" aspects of addiction, are clearly involved in substance use problems but do not yet provide a full explanation. The neurocognitive mechanisms addressed in the present perspective are attentional bias, reward processing (both drive aspects) and error-processing and cognitive control (both control aspects). The time has come to transfer these recent insights more consistently to clinical practice by studying their relevance for diagnosis and treatment in patient samples. The present perspective echoes the development of recent initiatives such as the RDoC system to integrate developments in neuroscience into clinical practice. The aim of this article is to open new vistas for addiction diagnosis and treatment and to discuss why and how these neurocognitive aspects of addictive behavior can be used in clinical practice. In addition, present problematic issues and a future research agenda are provided.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2014.09.019

Biological psychiatry

Biol Psychiatry

Striatal Hypersensitivity During Stress in Remitted Individuals with Recurrent Depression.

Increased sensitivity to stress and dysfunctional reward processing are two primary characteristics of major depressive disorder (MDD) that may persist after remission. Preclinical work has established the pivotal role of the striatum in mediating both stress and reward responses. Human neuroimaging studies have corroborated these preclinical findings and highlighted striatal dysfunction in MDD in response to reward but have yet to investigate striatal function during stress, in particular in individuals with recurrent depression. A validated mild psychological stress task involving viewing of negative stimuli during functional magnetic resonance imaging was conducted in 33 remitted individuals with a history of recurrent major depressive disorder (rMDD) and 35 matched healthy control subjects. Cortisol and anxiety levels were assessed throughout scanning. Stress-related activation was investigated in three striatal regions: caudate, nucleus accumbens, and putamen. Psychophysiologic interaction analyses probed connectivity of regions with central structures of the neural stress circuitry, such as the amygdala and hippocampus. The task increased cortisol and anxiety levels, although to a greater extent in rMDD individuals than healthy control subjects. In response to the negative stimuli, rMDD individuals, but not controls, also exhibited significantly potentiated caudate, nucleus accumbens, and putamen activations and increased caudate-amygdala and caudate-hippocampus connectivity. The findings highlight striatal hypersensitivity in response to a mild psychological stress in rMDD, as manifested by hyperactivation and hyperconnectivity with the amygdala and hippocampus. Striatal hypersensitivity during stress might thus constitute a trait mark of depression, providing a potential neural substrate for the interaction between stress and reward dysfunction in MDD.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2014.09.024

Biological psychiatry

Biol Psychiatry

Hunger does not motivate reward in women remitted from anorexia nervosa.

Hunger enhances sensitivity to reward, yet individuals with anorexia nervosa (AN) are not motivated to eat when starved. This study investigated brain response to rewards during hunger and satiated states to examine whether diminished response to reward could underlie food restriction in AN. Using a delay discounting monetary decision task known to discriminate brain regions contributing to processing of immediate rewards and cognitive control important for decision making regarding future rewards, we compared 23 women remitted from AN (RAN group; to reduce the confounding effects of starvation) with 17 healthy comparison women (CW group). Monetary rewards were used because the rewarding value of food may be confounded by anxiety in AN. Interactions of Group (RAN, CW) × Visit (hunger, satiety) revealed that, for the CW group, hunger significantly increased activation in reward salience circuitry (ventral striatum, dorsal caudate, anterior cingulate cortex) during processing of immediate reward, whereas satiety increased activation in cognitive control circuitry (ventrolateral prefrontal cortex, insula) during decision making. In contrast, brain response in reward and cognitive neurocircuitry did not differ during hunger and satiety in the RAN group. A main effect of group revealed elevated response in the middle frontal gyrus for the RAN group compared with the CW group. Women remitted from AN failed to increase activation of reward valuation circuitry when hungry and showed elevated response in cognitive control circuitry independent of metabolic state. Decreased sensitivity to the motivational drive of hunger may explain the ability of individuals with AN to restrict food when emaciated. Difficulties in valuating emotional salience may contribute to inabilities to appreciate the risks inherent in this disorder.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2014.08.020

Biological psychiatry

Biol Psychiatry

Anticipatory reward processing in addicted populations: a focus on the monetary incentive delay task.

Advances in brain imaging techniques have allowed neurobiological research to temporally analyze signals coding for the anticipation of reward. In addicted populations, both hyporesponsiveness and hyperresponsiveness of brain regions (e.g., ventral striatum) implicated in drug effects and reward system processing have been reported during anticipation of generalized reward. We discuss the current state of knowledge of reward processing in addictive disorders from a widely used and validated task: the monetary incentive delay task. Only studies applying the monetary incentive delay task in addicted and at-risk adult populations are reviewed, with a focus on anticipatory processing and striatal regions activated during task performance as well as the relationship of these regions with individual difference (e.g., impulsivity) and treatment outcome variables. We further review drug influences in challenge studies as a means to examine acute influences on reward processing in abstinent, recreationally using, and addicted populations. Generalized reward processing in addicted and at-risk populations is often characterized by divergent anticipatory signaling in the ventral striatum. Although methodologic and task variations may underlie some discrepant findings, anticipatory signaling in the ventral striatum may also be influenced by smoking status, drug metabolites, and treatment status in addicted populations. Divergent results across abstinent, recreationally using, and addicted populations demonstrate complexities in interpreting findings. Future studies would benefit from focusing on characterizing how impulsivity and other addiction-related features relate to anticipatory striatal signaling over time. Additionally, identifying how anticipatory signals recover or adjust after protracted abstinence will be important in understanding recovery processes.

CognitiveConstruct

RewardProcessing

Cellular and molecular biology (Noisy-le-Grand, France)

Cell Mol Biol (Noisy-le-grand)

Morphine-induced conditioned place preference and the alterations of p-ERK, p-CREB and c-fos levels in hypothalamus and hippocampus: the effects of physical stress.

The hypothalamus and hippocampus are important areas involved in stress responses and reward processing. In addition, ERK/CREB pathway plays a critical role in the control of cellular responses to stress and reward. In the current study, effects of acute and subchronic stress on the alteration of p-ERK, p-CREB and c-fos levels in the hypothalamus and hippocampus of saline- or morphine-treated animals during morphine-induced conditioned place preference (CPP) procedure were investigated. Male Wistar rats were divided into two saline- and morphine-treated supergroups. Each supergroup includes of control, acute stress and subchronic stress groups. In all of groups, the CPP procedure was done, afterward the alternation of p-ERK/ERK ratio, p-CREB/CREB ratio and c-fos level in the hypothalamus and hippocampus were estimated by Western blot analysis. The results indicated that in saline- or morphine-treated animals, p-ERK/ERK ratio, p-CREB/CREB ratio and c-fos level increased after application of acute and subchronic stress (except for p-ERK/ERK ratio in morphine-control group). Our findings revealed that in saline- or morphine-treated animals, acute and subcronic stress increased the p-ERK/ERK ratio, p-CREB/CREB ratio and c-fos level in the hypothalamus and hippocampus and this enhancement in morphine-treated animals, was more considerable than that in saline-treated animals.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2014.00935

Frontiers in human neuroscience

Front Hum Neurosci

Are there benefits of social overinclusion? Behavioral and ERP effects in the Cyberball paradigm.

Social participation can be examined using the Cyberball paradigm, a virtual ball-tossing game. Reducing the involvement of the participant is supposed to activate a neural alarm system, and to threaten fundamental social needs. Our previous findings indicate that the latter process can be linked to an enhancement of the centro-parietal P3 amplitude, signaling a modulation of the subjective expectancy of involvement. A preceding more frontal ERP component, the P2, does not depend of the probability of involvement, but reflects the appraisal of social reward. In this experiment, we examined whether overinclusion of participants enhances the satisfaction of social needs, reduces the P3 amplitude correspondingly, and affects central reward processing. In the control condition, participants (n = 40) were included (two co-player, ball possession 33%), and overincluded (ball possession 46%) in the experimental condition. In a counterbalanced design, we also controlled for the order of conditions. As predicted, overinclusion increased the satisfaction of social needs, with exception of "self esteem", and reduced the P3 amplitude. As for the frontal P2, overinclusion only enhanced the amplitudes if the less frequent involvement (condition: inclusion) was experienced previously. The behavioral and P3 data suggest that the feelings of social belonging, meaningful existence, and control are related to the subjective expectancy of social involvement, and can be described in terms of a linear continuum ranging from exclusion to overinclusion. In contrast, appraisal of social rewards does not depend on the probability of involvement.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2014.00382

Frontiers in behavioral neuroscience

Front Behav Neurosci

Symptom dimensions are associated with reward processing in unmedicated persons at risk for psychosis.

There is growing evidence that reward processing is disturbed in schizophrenia. However, it is uncertain whether this dysfunction predates or is secondary to the onset of psychosis. Studying 21 unmedicated persons at risk for psychosis plus 24 healthy controls (HCs) we used a incentive delay paradigm with monetary rewards during functional magnetic resonance imaging. During processing of reward information, at-risk individuals performed similarly well to controls and recruited the same brain areas. However, while anticipating rewards, the high-risk sample exhibited additional activation in the posterior cingulate cortex, and the medio- and superior frontal gyrus, whereas no significant group differences were found after rewards were administered. Importantly, symptom dimensions were differentially associated with anticipation and outcome of the reward. Positive symptoms were correlated with the anticipation signal in the ventral striatum (VS) and the right anterior insula (rAI). Negative symptoms were inversely linked to outcome-related signal within the VS, and depressive symptoms to outcome-related signal within the medial orbitofrontal cortex (mOFC). Our findings provide evidence for a reward-associated dysregulation that can be compensated by recruitment of additional prefrontal areas. We propose that stronger activations within VS and rAI when anticipating a reward reflect abnormal processing of potential future rewards. Moreover, according to the aberrant salience theory of psychosis, this may predispose a person to positive symptoms. Additionally, we report evidence that negative and depressive symptoms are differentially associated with the receipt of a reward, which might demonstrate a broader vulnerability to motivational and affective symptoms in persons at-risk for psychosis.

CognitiveConstruct

RewardProcessing

10.1177/1087054714558872

Journal of attention disorders

J Atten Disord

A meta-analysis of decision-making and attention in adults with ADHD.

Deficient reward processing has gained attention as an important aspect of ADHD, but little is known about reward-based decision-making (DM) in adults with ADHD. This article summarizes research on DM in adult ADHD and contextualizes DM deficits by comparing them to attention deficits. Meta-analytic methods were used to calculate average effect sizes for different DM domains and continuous performance task (CPT) measures. None of the 59 included studies (DM: 12 studies; CPT: 43; both: 4) had indications of publication bias. DM and CPT measures showed robust, small to medium effects. Large effect sizes were found for a drift diffusion model analysis of the CPT. The results support the existence of DM deficits in adults with ADHD, which are of similar magnitude as attention deficits. These findings warrant further examination of DM in adults with ADHD to improve the understanding of underlying neurocognitive mechanisms.

CognitiveConstruct

RewardProcessing

10.1016/j.psychres.2014.11.006

Psychiatry research

Psychiatry Res

Probabilistic reward learning in adults with Attention Deficit Hyperactivity Disorder--an electrophysiological study.

Attention Deficit Hyperactivity Disorder (ADHD) is hypothesized to be characterized by altered reinforcement sensitivity. The main aim of the present study was to assess alterations in the electrophysiological correlates of monetary reward processing in adult patients with ADHD of the combined subtype. Fourteen adults with ADHD of the combined subtype and 14 healthy control participants performed an active and an observational probabilistic reward-based learning task while an electroencephalogramm (EEG) was recorded. Regardless of feedback valence, there was a general feedback-related negativity (FRN) enhancement in combination with reduced learning performance during both active and observational reward learning in patients with ADHD relative to healthy controls. Other feedback-locked potentials such as the P200 and P300 and response-locked potentials were unaltered in the patients. There were no significant correlations between learning performance, FRN amplitudes and clinical symptoms, neither in the overall group involving all participants, nor in patients or controls considered separately. This pattern of findings might reflect generally impaired reward prediction in adults with ADHD of the combined subtype. We demonstrated for the first time that patients with ADHD of the combined subtype show not only deficient active reward learning but are also impaired when learning by observing other people׳s outcomes.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2014.10.025

NeuroImage

Neuroimage

Sparse regularization techniques provide novel insights into outcome integration processes.

By exploiting information that is contained in the spatial arrangement of neural activations, multivariate pattern analysis (MVPA) can detect distributed brain activations which are not accessible by standard univariate analysis. Recent methodological advances in MVPA regularization techniques have made it feasible to produce sparse discriminative whole-brain maps with highly specific patterns. Furthermore, the most recent refinement, the Graph Net, explicitly takes the 3D-structure of fMRI data into account. Here, these advanced classification methods were applied to a large fMRI sample (N=70) in order to gain novel insights into the functional localization of outcome integration processes. While the beneficial effect of differential outcomes is well-studied in trial-and-error learning, outcome integration in the context of instruction-based learning has remained largely unexplored. In order to examine neural processes associated with outcome integration in the context of instruction-based learning, two groups of subjects underwent functional imaging while being presented with either differential or ambiguous outcomes following the execution of varying stimulus-response instructions. While no significant univariate group differences were found in the resulting fMRI dataset, L1-regularized (sparse) classifiers performed significantly above chance and also clearly outperformed the standard L2-regularized (dense) Support Vector Machine on this whole-brain between-subject classification task. Moreover, additional L2-regularization via the Elastic Net and spatial regularization by the Graph Net improved interpretability of discriminative weight maps but were accompanied by reduced classification accuracies. Most importantly, classification based on sparse regularization facilitated the identification of highly specific regions differentially engaged under ambiguous and differential outcome conditions, comprising several prefrontal regions previously associated with probabilistic learning, rule integration and reward processing. Additionally, a detailed post-hoc analysis of these regions revealed that distinct activation dynamics underlay the processing of ambiguous relative to differential outcomes. Together, these results show that L1-regularization can improve classification performance while simultaneously providing highly specific and interpretable discriminative activation patterns.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2014.11.014

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

The role of high-frequency oscillatory activity in reward processing and learning.

Oscillatory activity has been proposed as a key mechanism in the integration of brain activity of distant structures. Particularly, high frequency brain oscillatory activity in the beta and gamma range has received increasing interest in the domains of attention and memory. In addition, a number of recent studies have revealed an increase of beta-gamma activity (20-35 Hz) after unexpected or relevant positive reward outcomes. In the present manuscript we review the literature on this phenomenon and we propose that this activity is a brain signature elicited by unexpected positive outcomes in order to transmit a fast motivational value signal to the reward network. In addition, we hypothesize that beta-gamma oscillatory activity indexes the interaction between attentional and emotional systems, and that it directly reflects the appearance of unexpected positive rewards in learning-related contexts.

CognitiveConstruct

RewardProcessing

10.1016/j.ntt.2014.11.007

Neurotoxicology and teratology

Neurotoxicol Teratol

Effects of prenatal cocaine exposure on early postnatal rodent brain structure and diffusion properties.

Prenatal cocaine exposure has been associated with numerous behavioral phenotypes in clinical populations, including impulsivity, reduced attention, alterations in social behaviors, and delayed language and sensory-motor development. Detecting associated changes in brain structure in these populations has proven difficult, and results have been inconclusive and inconsistent. Due to their more controlled designs, animal models may shed light on the neuroanatomical changes caused by prenatal cocaine; however, to maximize clinical relevance, data must be carefully collected using translational methods. The goal of this study was two-fold: (1) to determine if prenatal cocaine alters developmental neuroanatomy using methods that are available to human researchers, specifically structural MRI and diffusion tensor imaging, and (2) to determine the feasibility of rodent in vivo neuroimaging for usage in longitudinal studies of developmental disorders. Cocaine-exposed (prenatal days 1-20, 30mg/kg/day) rat pups were sedated and imaged live using diffusion tensor imaging and postmortem (fixed) using magnetic resonance histology on postnatal day 14. Volume and diffusion properties in whole brain as well as specific regions of interest were then assessed from the resulting images. Whole brain analyses revealed that cocaine-exposed animals showed no change in whole brain volume. Additionally, we found alterations in fractional anisotropy across regions associated with reward processing and emotional regulation, especially in the thalamus and globus pallidus, as well as sex-dependent effects of cocaine in the right cortex. Reductions in fractional anisotropy were paired with reductions only in axial diffusivity, which preliminarily suggests that the changes observed here may be due to axonal damage, as opposed to reductions in myelination of the affected regions/pathways. Our data indicate that prenatal cocaine may target a number of developing brain structures but does not result in overt changes to brain volumes. These results highlight not only the brain alterations that result from prenatal cocaine but also the advancements in live imaging that allow longitudinal study designs in other models.

CognitiveConstruct

RewardProcessing

10.1016/j.clinph.2014.08.025

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

Clin Neurophysiol

Anterior cingulate activity to monetary loss and basal ganglia activity to monetary gain uniquely contribute to the feedback negativity.

The feedback negativity (FN) is an event-related potential that differentiates unfavorable versus favorable outcomes. Although thought to reflect error-related activity within the anterior cingulate cortex, recent work indicates the FN may also reflect reward-related activity that has been linked to the basal ganglia. To date, it remains unclear how to reconcile these conflicting perspectives. We decomposed the FN by applying time-frequency analysis to isolate activity unique to monetary losses and gains. The FN was recorded from 84 individuals during a laboratory gambling task. Two signals contributed to the FN elicited by unpredictable outcomes: theta activity (4-7Hz) was increased following monetary loss, and delta activity (<3Hz) was increased following monetary gain. Predictable outcomes elicited delta but not theta activity. Source analysis revealed distinct generators, with loss-related theta localized to the anterior cingulate cortex and gain-related delta to a possible source in the striatum. Symptoms of depression, anxiety, and stress reactivity were specifically associated with blunted gain-related delta. The FN may be a composite of loss- and gain-related neural activity, reflecting distinct facets of reward processing. Gain-related delta activity may provide unique information about reward dysfunction in major depression and other internalizing psychopathology.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2014.00395

Frontiers in behavioral neuroscience

Front Behav Neurosci

Frontostriatal circuits and the development of bulimia nervosa.

Bulimia nervosa (BN) is characterized by both recurrent episodes of binge eating that are, in part, defined by a sense of loss of control and compensatory behaviors to avoid weight gain. Impulsive behaviors are also common in individuals with BN, indicating more pervasive difficulties in behavioral self-regulation. Findings from functional and anatomical neuroimaging studies of individuals with BN suggest dysfunction in the dorsal frontostriatal circuits that support self-regulatory capacities and habit learning and in overlapping ventral circuits that support reward processing and reward-based learning. In this review, we describe the normal development of frontostriatal circuits and then present behavioral and neuroimaging data from adolescents and adults with BN. These data suggest that the abnormal maturation of frontostriatal circuits may contribute to the habitual binge-eating and purging behaviors of BN. Future longitudinal imaging studies will improve understanding of how these circuits contribute to the developmental trajectory of BN and will inform novel interventions that could target or prevent the impulsive and habit-like features of this disorder.

CognitiveConstruct

RewardProcessing

10.1093/cercor/bhu275

Cerebral cortex (New York, N.Y. : 1991)

Cereb Cortex

A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses.

Fundamental aspects of human behavior operate outside of conscious awareness. Yet, theories of conditioned responses in humans, such as placebo and nocebo effects on pain, have a strong emphasis on conscious recognition of contextual cues that trigger the response. Here, we investigated the neural pathways involved in nonconscious activation of conditioned pain responses, using functional magnetic resonance imaging in healthy participants. Nonconscious compared with conscious activation of conditioned placebo analgesia was associated with increased activation of the orbitofrontal cortex, a structure with direct connections to affective brain regions and basic reward processing. During nonconscious nocebo, there was increased activation of the thalamus, amygdala, and hippocampus. In contrast to previous assumptions about conditioning in humans, our results show that conditioned pain responses can be elicited independently of conscious awareness and our results suggest a hierarchical activation of neural pathways for nonconscious and conscious conditioned responses. Demonstrating that the human brain has a nonconscious mechanism for responding to conditioned cues has major implications for the role of associative learning in behavioral medicine and psychiatry. Our results may also open up for novel approaches to translational animal-to-human research since human consciousness and animal cognition is an inherent paradox in all behavioral science.

CognitiveConstruct

RewardProcessing

10.1016/j.regpep.2014.11.003

Regulatory peptides

Regul Pept

Orexin administration to mice that underwent chronic stress produces bimodal effects on emotion-related behaviors.

Orexin plays diverse roles in regulating behaviors, such as sleep and wake, reward processing, arousal, and stress and anxiety. The orexin system may accomplish these multiple tasks through its complex innervations throughout the brain. The emerging evidence indicates a role of orexin in emotional behaviors; however, most of the previous studies have investigated the function of orexin in naïve animals. Here, we examined a functional role of orexin in mice that had been exposed to repeated stress. Chronic social defeat stress produced differential social interaction behaviors in mice (susceptible versus resilient) and these two groups of mice displayed different levels of prepro-orexin in the hypothalamus. Exogenously added orexin A to the brain induced an antidepressant-like effect in only the susceptible mice but not in the resilient mice. In contrast, orexin A and orexin B infused together produced an anxiogenic effect in only the resilient mice and not in the susceptible mice. Furthermore, we found that the antidepressant-like effect of orexin A is mediated by the bed nucleus of the stria terminalis (BNST) after exposure to chronic restraint stress. These findings reveal a bimodal effect of the orexin system in regulating emotional behavior that depends on stress susceptibility.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2014.09.013

Drug and alcohol dependence

Drug Alcohol Depend

Altered neural correlates of reward and loss processing during simulated slot-machine fMRI in pathological gambling and cocaine dependence.

Individuals with gambling or substance-use disorders exhibit similar functional alterations in reward circuitry suggestive of a shared underlying vulnerability in addictive disorders. Additional research into common and unique alterations in reward-processing in substance-related and non-substance-related addictions may identify neural factors that could be targeted in treatment development for these disorders. To investigate contextual reward-processing in pathological gambling, a slot-machine fMRI task was performed by three groups (with pathological gambling, cocaine dependence and neither disorder; N = 24 each) to determine the extent to which two groups with addictions (non-substance-related and substance-related) showed similarities and differences with respect to each other and a non-addicted group during anticipatory periods and following the delivery of winning, losing and 'near-miss' outcomes. Individuals with pathological gambling or cocaine dependence compared to those with neither disorder exhibited exaggerated anticipatory activity in mesolimbic and ventrocortical regions, with pathological-gambling participants displaying greater positive possible-reward anticipation and cocaine-dependent participants displaying more negative certain-loss anticipation. Neither clinical sample exhibited medial frontal or striatal responses that were observed following near-miss outcomes in healthy comparison participants. Alterations in anticipatory processing may be sensitive to the valence of rewards and content-disorder-specific. Common and unique findings in pathological gambling and cocaine dependence with respect to anticipatory reward and near-miss loss processing suggest shared and unique elements that might be targeted through behavioral or pharmacological interventions in the treatment of addictions.

CognitiveConstruct

RewardProcessing

10.1016/j.cub.2014.09.044

Current biology : CB

Curr Biol

The role of reward in word learning and its implications for language acquisition.

The exact neural processes behind humans' drive to acquire a new language--first as infants and later as second-language learners--are yet to be established. Recent theoretical models have proposed that during human evolution, emerging language-learning mechanisms might have been glued to phylogenetically older subcortical reward systems, reinforcing human motivation to learn a new language. Supporting this hypothesis, our results showed that adult participants exhibited robust fMRI activation in the ventral striatum (VS)--a core region of reward processing--when successfully learning the meaning of new words. This activation was similar to the VS recruitment elicited using an independent reward task. Moreover, the VS showed enhanced functional and structural connectivity with neocortical language areas during successful word learning. Together, our results provide evidence for the neural substrate of reward and motivation during word learning. We suggest that this strong functional and anatomical coupling between neocortical language regions and the subcortical reward system provided a crucial advantage in humans that eventually enabled our lineage to successfully acquire linguistic skills.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2014.10.051

Behavioural brain research

Behav Brain Res

Role of intra-hippocampal orexin 1 and orexin 2 receptors in conditioned place preference induced by chemical stimulation of the lateral hypothalamus.

Evidence from animal models suggests a role for orexinergic system in reward processing and drug addiction. The lateral hypothalamus (LH) orexin neurons send projections to the dorsal hippocampus (CA1 region) which plays a pivotal role in reward processes. Moreover, it has been shown that orexin containing terminals and orexin receptors are distributed in the hippocampal formation. In this study, we assessed the role of orexin 1 (OX1r) and orexin2 (OX2r) receptors in the CA1 on the development of LH stimulation-induced conditioned place preference (CPP). Animals weighing 230-280 g were unilaterally implanted by two separate cannulae into the LH and CA1. The CPP paradigm was done; SB334867 and TCSOX229, as selective OX1r and OX2r antagonists (1, 3, 10 and 30 nM/0.5 μl DMSO) administrated into the CA1 prior to intra-LH carbachol microinjection (250 nM; the most effective dose) during the 3-days conditioning phase, respectively. Conditioning scores and locomotor activities were recorded by Ethovision software on the test day. The results showed that the administration of OX1r and OX2r antagonists into the CA1 attenuated the development of CPP induced by chemical stimulation of the LH. However, this decrease in OX1r antagonist treated groups was more significant than that in OX2r antagonist treated animals. Our findings suggest that OX1 and OX2 receptors in the CA1 region of the hippocampus were involved in the development of CPP induced by chemical stimulation of the LH and the efficiency of OX1 receptors in this phenomenon was more considerable than OX2 receptors in rats.

CognitiveConstruct

RewardProcessing

10.1016/j.alcohol.2014.06.010

Alcohol (Fayetteville, N.Y.)

Alcohol

Sleep and circadian contributions to adolescent alcohol use disorder.

Adolescence is a time of marked changes across sleep, circadian rhythms, brain function, and alcohol use. Starting at puberty, adolescents' endogenous circadian rhythms and preferred sleep times shift later, often leading to a mismatch with the schedules imposed by secondary education. This mismatch induces circadian misalignment and sleep loss, which have been associated with affect dysregulation, increased drug and alcohol use, and other risk-taking behaviors in adolescents and adults. In parallel to developmental changes in sleep, adolescent brains are undergoing structural and functional changes in the circuits subserving the pursuit and processing of rewards. These developmental changes in reward processing likely contribute to the initiation of alcohol use during adolescence. Abundant evidence indicates that sleep and circadian rhythms modulate reward function, suggesting that adolescent sleep and circadian disturbance may contribute to altered reward function, and in turn, alcohol involvement. In this review, we summarize the relevant evidence and propose that these parallel developmental changes in sleep, circadian rhythms, and neural processing of reward interact to increase risk for alcohol use disorder (AUD).

CognitiveConstruct

RewardProcessing

10.1037/a0038339

Psychological review

Psychol Rev

Hierarchical control over effortful behavior by rodent medial frontal cortex: A computational model.

The anterior cingulate cortex (ACC) has been the focus of intense research interest in recent years. Although separate theories relate ACC function variously to conflict monitoring, reward processing, action selection, decision making, and more, damage to the ACC mostly spares performance on tasks that exercise these functions, indicating that they are not in fact unique to the ACC. Further, most theories do not address the most salient consequence of ACC damage: impoverished action generation in the presence of normal motor ability. In this study we develop a computational model of the rodent medial prefrontal cortex that accounts for the behavioral sequelae of ACC damage, unifies many of the cognitive functions attributed to it, and provides a solution to an outstanding question in cognitive control research-how the control system determines and motivates what tasks to perform. The theory derives from recent developments in the formal study of hierarchical control and learning that highlight computational efficiencies afforded when collections of actions are represented based on their conjoint goals. According to this position, the ACC utilizes reward information to select tasks that are then accomplished through top-down control over action selection by the striatum. Computational simulations capture animal lesion data that implicate the medial prefrontal cortex in regulating physical and cognitive effort. Overall, this theory provides a unifying theoretical framework for understanding the ACC in terms of the pivotal role it plays in the hierarchical organization of effortful behavior.

CognitiveConstruct

RewardProcessing