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10.1016/j.neuropsychologia.2016.07.037

Neuropsychologia

Neuropsychologia

Willing to wait: Elevated reward-processing EEG activity associated with a greater preference for larger-but-delayed rewards.

While almost everyone discounts the value of future rewards over immediate rewards, people differ in their so-called delay-discounting. One of the several factors that may explain individual differences in delay-discounting is reward-processing. To study individual-differences in reward-processing, however, one needs to consider the heterogeneity of neural-activity at each reward-processing stage. Here using EEG, we separated reward-related neural activity into distinct reward-anticipation and reward-outcome stages using time-frequency characteristics. Thirty-seven individuals first completed a behavioral delay-discounting task. Then reward-processing EEG activity was assessed using a separate reward-learning task, called a reward time-estimation task. During this EEG task, participants were instructed to estimate time duration and were provided performance feedback on a trial-by-trial basis. Participants received monetary-reward for accurate-performance on Reward trials, but not on No-Reward trials. Reward trials, relative to No-Reward trials, enhanced EEG activity during both reward-anticipation (including, cued-locked delta power during cue-evaluation and pre-feedback alpha suppression during feedback-anticipation) and reward-outcome (including, feedback-locked delta, theta and beta power) stages. Moreover, all of these EEG indices correlated with behavioral performance in the time-estimation task, suggesting their essential roles in learning and adjusting performance to maximize winnings in a reward-learning situation. Importantly, enhanced EEG power during Reward trials, as reflected by stronger 1) pre-feedback alpha suppression, 2) feedback-locked theta and 3) feedback-locked beta, was associated with a greater preference for larger-but-delayed rewards in a separate, behavioral delay-discounting task. Results highlight the association between a stronger preference toward larger-but-delayed rewards and enhanced reward-processing. Moreover, our reward-processing EEG indices detail the specific stages of reward-processing where these associations occur.

CognitiveConstruct

RewardProcessing

10.1503/jpn.150234

Journal of psychiatry & neuroscience : JPN

J Psychiatry Neurosci

Dysfunctional insular connectivity during reward prediction in patients with first-episode psychosis.

Increasing evidence indicates that psychosis is associated with abnormal reward processing. Imaging studies in patients with first-episode psychosis (FEP) have revealed reduced activity in diverse brain regions, including the ventral striatum, insula and anterior cingulate cortex (ACC), during reward prediction. However, whether these reductions in local brain activity are due to altered connectivity has rarely been explored. We applied dynamic causal modelling and Bayesian model selection to fMRI data during the Salience Attribution Task to investigate whether patients with FEP showed abnormal modulation of connectivity between the ventral striatum, insula and ACC induced by rewarding cues and whether these changes were related to positive psychotic symptoms and atypical antipsychotic medication. The model including reward-induced modulation of insula-ACC connectivity was the best fitting model in each group. Compared with healthy controls ( = 19), patients with FEP ( = 29) revealed reduced right insula-ACC connectivity. After subdividing patients according to current antipsychotic medication, we found that the reduced insula-ACC connectivity relative to healthy controls was observed only in untreated patients ( = 17), not in patients treated with antipsychotics ( = 12), and that it correlated negatively with unusual thought content in untreated patients with FEP. The modest sample size of untreated patients with FEP was a limitation of our study. This study indicates that insula-ACC connectivity during reward prediction is reduced in untreated patients with FEP and related to the formation of positive psychotic symptoms. Our study further suggests that atypical antipsychotics may reverse connectivity between the insula and the ACC during reward prediction.

CognitiveConstruct

RewardProcessing

10.1038/npp.2016.179

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Attenuation of Frontostriatal Connectivity During Reward Processing Predicts Response to Psychotherapy in Major Depressive Disorder.

There are few reliable predictors of response to antidepressant treatments. In the present investigation, we examined pretreatment functional brain connectivity during reward processing as a potential predictor of response to Behavioral Activation Treatment for Depression (BATD), a validated psychotherapy that promotes engagement with rewarding stimuli and reduces avoidance behaviors. Thirty-three outpatients with major depressive disorder (MDD) and 20 matched controls completed two runs of the monetary incentive delay task during functional magnetic resonance imaging after which participants with MDD received up to 15 sessions of BATD. Seed-based generalized psychophysiological interaction analyses focused on task-based connectivity across task runs, as well as the attenuation of connectivity from the first to the second run of the task. The average change in Beck Depression Inventory-II scores due to treatment was 10.54 points, a clinically meaningful response. Groups differed in seed-based functional connectivity among multiple frontostriatal regions. Hierarchical linear modeling revealed that improved treatment response to BATD was predicted by greater connectivity between the left putamen and paracingulate gyrus during reward anticipation. In addition, MDD participants with greater attenuation of connectivity between several frontostriatal seeds, and midline subcallosal cortex and left paracingulate gyrus demonstrated improved response to BATD. These findings indicate that pretreatment frontostriatal functional connectivity during reward processing is predictive of response to a psychotherapy modality that promotes improving approach-related behaviors in MDD. Furthermore, connectivity attenuation among reward-processing regions may be a particularly powerful endophenotypic predictor of response to BATD in MDD.

CognitiveConstruct

RewardProcessing

10.1503/jpn.160010

Journal of psychiatry & neuroscience : JPN

J Psychiatry Neurosci

Accelerated aging of the putamen in patients with major depressive disorder.

Growing evidence indicates that major depressive disorder (MDD) is characterized by accelerated biological aging, including greater age-related changes in physiological functioning. The disorder is also associated with abnormal neural reward circuitry, particularly in the basal ganglia (BG). Here we assessed age-related changes in BG volume in both patients with MDD and healthy control participants. We obtained whole-brain -weighted images from patients with MDD and healthy controls. We estimated grey matter volumes of the BG, including the nucleus accumbens, caudate, pallidum and putamen. Volumes were assessed using multivariate analysis of covariance (MANCOVA) with age as a covariate, followed by appropriate post hoc tests. We included 232 individuals (116 patients with MDD) in our analysis. The MANCOVA yielded a significant group × age interaction ( = 0.043). Analyses for each region yielded a significant group × age interaction in the putamen (univariate test, = 0.005; permutation test, = 0.004); this effect was not significant in the other regions. The negative association between age and putamen volume was twice as large in the MDD than in the control group (-35.2 v. -16.7 mm/yr), indicating greater age-related volumetric decreases in the putamen in individuals with MDD than in controls. These findings are cross-sectional; future studies should assess the longitudinal impact of accelerated aging on anhedonia and neural indices of reward processing. Our results indicate that putamen aging is accelerated in patients with MDD. Thus, the putamen may uniquely contribute to the adverse long-term effects of depressive psychopathology and may be a useful target for the treatment of MDD across the lifespan.

CognitiveConstruct

RewardProcessing

10.1017/S0954579416000742

Development and psychopathology

Dev Psychopathol

Prefrontal mechanisms of comorbidity from a transdiagnostic and ontogenic perspective.

Accumulating behavioral and genetic research suggests that most forms of psychopathology share common genetic and neural vulnerabilities and are manifestations of a relatively few core underlying processes. These findings support the view that comorbidity mostly arises, not from true co-occurrence of distinct disorders, but from the behavioral expression of shared vulnerability processes across the life span. The purpose of this review is to examine the role of the prefrontal cortex (PFC) in the shared vulnerability mechanisms underlying the clinical phenomena of comorbidity from a transdiagnostic and ontogenic perspective. In adopting this perspective, we suggest complex transactions between neurobiologically rooted vulnerabilities inherent in PFC circuitry and environmental factors (e.g., parenting, peers, stress, and substance use) across development converge on three key PFC-mediated processes: executive functioning, emotion regulation, and reward processing. We propose that individual differences and impairments in these PFC-mediated functions provide intermediate mechanisms for transdiagnostic symptoms and underlie behavioral tendencies that evoke and interact with environmental risk factors to further potentiate vulnerability.

CognitiveConstruct

RewardProcessing

10.1007/s11682-016-9607-5

Brain imaging and behavior

Brain Imaging Behav

Non-demented Parkinson's disease patients with apathy show decreased grey matter volume in key executive and reward-related nodes.

Apathy is a common but poorly understood neuropsychiatric disturbance in Parkinson's disease (PD). In a recent study using event-related brain potentials we demonstrated impaired reward processing and compromised mesocortico-limbic pathways in PD patients with clinical symptoms of apathy. Here we aimed to further investigate the involvement of reward circuits in apathetic PD patients by assessing potential differences in brain structure. Using structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) we quantified grey matter volume (GMV) in a sample of 18 non-demented and non-depressed PD patients with apathy, and 18 matched non-apathetic patients. Both groups were equivalent in terms of sociodemographic characteristics, disease stage, cognitive performance and L-Dopa equivalent daily dose. Apathetic patients showed significant GMV loss in cortical and subcortical brain structures. Various clusters of cortical GMV decrease were found in the parietal, lateral prefrontal cortex, and orbitofrontal cortex (OFC). The second largest cluster of GMV loss was located in the left nucleus accumbens (NAcc), a subcortical structure that is a key node of the human reward circuit. Isolated apathy in our sample is explained by the combined GMV loss in regions involved in executive functions, and cortical and subcortical structures of the mesolimbic reward pathway. The correlations observed between apathy and cognition suggests apathy as a marker of more widespread brain degeneration even in a sample of non-demented PD patients.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2016.09.016

NeuroImage. Clinical

Neuroimage Clin

Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome.

Motivational signals influence a wide variety of cognitive processes and components of behavioral performance. Cognitive dysfunction in patients with childhood chronic fatigue syndrome (CCFS) may be closely associated with a low motivation to learn induced by impaired neural reward processing. However, the extent to which reward processing is impaired in CCFS patients is unclear. The aim of the present functional magnetic resonance imaging (fMRI) study was to determine whether brain activity in regions related to reward sensitivity is impaired in CCFS patients. fMRI data were collected from 13 CCFS patients (mean age, 13.6 ± 1.0 years) and 13 healthy children and adolescents (HCA) (mean age, 13.7 ± 1.3 years) performing a monetary reward task. Neural activity in high- and low-monetary-reward conditions was compared between CCFS and HCA groups. Severity of fatigue and the reward obtained from learning in daily life were evaluated by questionnaires. Activity of the putamen was lower in the CCFS group than in the HCA group in the low-reward condition, but not in the high-reward condition. Activity of the putamen in the low-reward condition in CCFS patients was negatively and positively correlated with severity of fatigue and the reward from learning in daily life, respectively. We previously revealed that motivation to learn was correlated with striatal activity, particularly the neural activity in the putamen. This suggests that in CCFS patients low putamen activity, associated with altered dopaminergic function, decreases reward sensitivity and lowers motivation to learn.

CognitiveConstruct

RewardProcessing

10.1192/bjpo.bp.115.001586

BJPsych open

BJPsych Open

Ventral striatum dysfunction in children and adolescents with reactive attachment disorder: functional MRI study.

Child maltreatment is a major risk factor for psychopathology, including reactive attachment disorder (RAD). To examine whether neural activity during reward processing was altered in children and adolescents with RAD. Sixteen children and adolescents with RAD and 20 typically developing (TD) individuals performed tasks with high and low monetary rewards while undergoing functional magnetic resonance imaging. Significantly reduced activity in the caudate and nucleus accumbens was observed during the high monetary reward condition in the RAD group compared with the TD group (=0.015, family-wise error-corrected cluster level). Significant negative correlations between bilateral striatal activity and avoidant attachment were observed in the RAD and TD groups. Striatal neural reward activity in the RAD group was markedly decreased. The present results suggest that dopaminergic dysfunction occurs in the striatum of children and adolescents with RAD, leading towards potential future risks for psychopathology. None. © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2016.09.004

NeuroImage. Clinical

Neuroimage Clin

Effects of craving behavioral intervention on neural substrates of cue-induced craving in Internet gaming disorder.

Internet gaming disorder (IGD) is characterized by high levels of craving for online gaming and related cues. Since addiction-related cues can evoke increased activation in brain areas involved in motivational and reward processing and may engender gaming behaviors or trigger relapse, ameliorating cue-induced craving may be a promising target for interventions for IGD. This study compared neural activation between 40 IGD and 19 healthy control (HC) subjects during an Internet-gaming cue-reactivity task and found that IGD subjects showed stronger activation in multiple brain areas, including the dorsal striatum, brainstem, substantia nigra, and anterior cingulate cortex, but lower activation in the posterior insula. Furthermore, twenty-three IGD subjects (CBI + group) participated in a craving behavioral intervention (CBI) group therapy, whereas the remaining 17 IGD subjects (CBI - group) did not receive any intervention, and all IGD subjects were scanned during similar time intervals. The CBI + group showed decreased IGD severity and cue-induced craving, enhanced activation in the anterior insula and decreased insular connectivity with the lingual gyrus and precuneus after receiving CBI. These findings suggest that CBI is effective in reducing craving and severity in IGD, and it may exert its effects by altering insula activation and its connectivity with regions involved in visual processing and attention bias.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.1872-15.2016

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

J Neurosci

Field Potential Oscillations in the Bed Nucleus of the Stria Terminalis Correlate with Compulsion in a Rat Model of Obsessive-Compulsive Disorder.

The bed nucleus of the stria terminalis (BNST) is implicated in anxiety and reward processing, both of which are associated with obsessive-compulsive disorder (OCD). Specific neuronal groups in the BNST related to anxiety and reward have been identified, but quantitative data about the information carried by local field potential (LFP) signals in this area during obsession/compulsion are lacking. Here we investigate the BNST LFP in the schedule-induced polydipsia, an animal model of OCD. We implanted electrodes bilaterally in the BNST and random control brain regions in 32 male Wistar rats, and recorded corresponding LFP during compulsive and noncompulsive behavior. We first applied high-frequency (100 Hz) electrical stimulation through the implanted electrodes and analyzed its effects on compulsive behavior. We then performed time-frequency analysis of LFPs and statistically compared the normalized power of δ (1-4 Hz), θ (4-8 Hz), α (8-12 Hz), β (12-30 Hz), and lower γ (30-45 Hz) bands between different groups. Our data showed that the normalized δ, β, and γ powers in the right BNST were specifically correlated with compulsive behaviors. δ and γ oscillations increased and decreased during the initiation phase of compulsion, respectively, whereas β increased after compulsion stopped. Moreover, the effect of BNST electrical stimulation, in terms of suppression of compulsion, was significantly correlated with the percentage change of these bands during compulsion. Our research reveals potential biomarkers and underlying neurophysiological mechanisms of compulsion and warrants further assessment of the use of LFP for closed-loop neuromodulation in OCD. Although specific neuronal groups in the bed nucleus of the stria terminalis (BNST) related to anxiety and reward circuitries have been identified, psychopathological information carried by local field potentials in the BNST has not yet been described. We discovered that normalized powers of the right BNST δ, β, and γ oscillations were highly correlated with compulsion. Specifically, δ and γ oscillations increased and decreased during the initiation phase of compulsion, respectively, whereas β increased after compulsion stopped. Such correlations were not found in other parts of the brain during compulsion, or in the BNST during noncompulsive behavior. Current findings reveal real-time neurophysiological biomarkers of compulsion and warrant further assessment of the use of local field potentials for closed-loop neuromodulation for OCD.

CognitiveConstruct

RewardProcessing

10.1136/eb-2016-102430

Evidence-based mental health

Evid Based Ment Health

Exercising control over bipolar disorder.

Following extensive research exercise has emerged as an effective treatment for major depressive disorder, and it is now a recognised therapy alongside other interventions. In contrast, there is a paucity of research examining the therapeutic effects of exercise for those with bipolar disorder. Given that dysfunctional reward processing is central to bipolar disorder, research suggests that exercise can perhaps be framed as a reward-related event that may have the potential to precipitate a manic episode. The behavioural activation system (BAS) is a neurobehavioural system that is associated with responding to reward and provides an appropriate framework to theoretically examine and better understand the effects of exercise treatment on bipolar disorder. This article discusses recent research findings and provides an overview of the extant literature related to the neurobiological underpinnings of BAS and exercise as they relate to bipolar disorder. This is important clinically because depending on mood state in bipolar disorder, we postulate that exercise could be either beneficial or deleterious with positive or negative effects on the illness. Clearly, this complicates the evaluation of exercise as a potential treatment in terms of identifying its optimal characteristics in this population.

CognitiveConstruct

RewardProcessing

10.1111/jcpp.12643

Journal of child psychology and psychiatry, and allied disciplines

J Child Psychol Psychiatry

Children with ADHD symptoms show decreased activity in ventral striatum during the anticipation of reward, irrespective of ADHD diagnosis.

Changes in reward processing are thought to be involved in the etiology of attention-deficit/hyperactivity disorder (ADHD), as well as other developmental disorders. In addition, different forms of therapy for ADHD rely on reinforcement principles. As such, improved understanding of reward processing in ADHD could eventually lead to more effective treatment options. However, differences in reward processing may not be specific to ADHD, but may be a trans-diagnostic feature of disorders that involve ADHD-like symptoms. In this event-related fMRI study, we used a child-friendly version of the monetary incentive delay task to assess performance and brain activity during reward anticipation. Also, we collected questionnaire data to assess reward sensitivity in daily life. For final analyses, data were available for 27 typically developing children, 24 children with ADHD, and 25 children with an autism spectrum disorder (ASD) and ADHD symptoms. We found decreased activity in ventral striatum during anticipation of reward in children with ADHD symptoms, both for children with ADHD as their primary diagnosis and in children with autism spectrum disorder and ADHD symptoms. We found that higher parent-rated sensitivity to reward was associated with greater anticipatory activity in ventral striatum for children with ADHD symptoms. In contrast, there was no relationship between the degree of ADHD symptoms and activity in ventral striatum. We provide evidence of biological and behavioral differences in reward sensitivity in children with ADHD symptoms, regardless of their primary diagnosis. Ultimately, a dimensional brain-behavior model of reward sensitivity in children with symptoms of ADHD may be useful to refine treatment options dependent on reward processing.

CognitiveConstruct

RewardProcessing

10.7554/eLife.12669

eLife

Elife

Amygdala-ventral striatum circuit activation decreases long-term fear.

In humans, activation of the ventral striatum, a region associated with reward processing, is associated with the extinction of fear, a goal in the treatment of fear-related disorders. This evidence suggests that extinction of aversive memories engages reward-related circuits, but a causal relationship between activity in a reward circuit and fear extinction has not been demonstrated. Here, we identify a basolateral amygdala (BLA)-ventral striatum (NAc) pathway that is activated by extinction training. Enhanced recruitment of this circuit during extinction learning, either by pairing reward with fear extinction training or by optogenetic stimulation of this circuit during fear extinction, reduces the return of fear that normally follows extinction training. Our findings thus identify a specific BLA-NAc reward circuit that can regulate the persistence of fear extinction and point toward a potential therapeutic target for disorders in which the return of fear following extinction therapy is an obstacle to treatment.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2016.00413

Frontiers in neuroscience

Front Neurosci

Higher Adolescent Body Mass Index Is Associated with Lower Regional Gray and White Matter Volumes and Lower Levels of Positive Emotionality.

Adolescent obesity is associated with an increased chance of developing serious health risks later in life. Identifying the neurobiological and personality factors related to increases in adiposity is important to understanding what drives maladaptive consummatory and exercise behaviors that result in obesity. Previous research has largely focused on adults with few findings published on interactions among adiposity, brain structure, and personality. In this study, Voxel Based Morphometry (VBM) was used to identify associations between gray and white matter volumes and increasing adiposity, as measured by Body Mass Index percentile (BMI%), in 137 adolescents (age range: 9-20 years, BMI% range: 5.16-99.56). Variations in gray and white matter volume and BMI% were then linked to individual differences in personality measures from the Multidimensional Personality Questionnaire (MPQ). After controlling for age and other covariates, BMI% correlated negatively with gray matter volume in the bilateral caudate (right: partial r = -0.338, left: r = -0.404), medial prefrontal cortex (partial r = -0.339), anterior cingulate (partial r = -0.312), bilateral frontal pole (right: partial r = -0.368, left: r = -0.316), and uncus (partial r = -0.475) as well as white matter volume bilaterally in the anterior limb of the internal capsule (right: partial r = -0.34, left: r = -0.386), extending to the left middle frontal subgyral white matter. Agentic Positive Emotionality (PEM-AG) was correlated negatively with BMI% (partial r = -0.384). PEM-AG was correlated positively with gray matter volume in the right uncus (partial r = 0.329). These results suggest that higher levels of adiposity in adolescents are associated with lower trait levels in reward-related personality domains, as well as structural variations in brain regions associated with reward processing, control, and sensory integration.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2016.01288

Frontiers in psychology

Front Psychol

Editorial: Reward Processing in Motivational and Affective Disorders.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2016.00165

Frontiers in behavioral neuroscience

Front Behav Neurosci

Editorial: At Risk for Neuropsychiatric Disorders: An Affective Neuroscience Approach to Understanding the Spectrum.

CognitiveConstruct

RewardProcessing

10.2147/NDT.S111818

Neuropsychiatric disease and treatment

Neuropsychiatr Dis Treat

Neurobiology of hedonic tone: the relationship between treatment-resistant depression, attention-deficit hyperactivity disorder, and substance abuse.

Anhedonia, defined as the state of reduced ability to experience feelings of pleasure, is one of the hallmarks of depression. Hedonic tone is the trait underlying one's characteristic ability to feel pleasure. Low hedonic tone represents a reduced capacity to experience pleasure, thus increasing the likelihood of experiencing anhedonia. Low hedonic tone has been associated with several psychopathologies, including major depressive disorder (MDD), substance use, and attention-deficit hyperactivity disorder (ADHD). The main neural pathway that modulates emotional affect comprises the limbic-cortical-striatal-pallidal-thalamic circuits. The activity of various components of the limbic-cortical-striatal-pallidal-thalamic pathway is correlated with hedonic tone in healthy individuals and is altered in MDD. Dysfunction of these circuits has also been implicated in the relative ineffectiveness of selective serotonin reuptake inhibitors used to treat anxiety and depression in patients with low hedonic tone. Mood disorders such as MDD, ADHD, and substance abuse share low hedonic tone as well as altered activation of brain regions involved in reward processing and monoamine signaling as their features. Given the common features of these disorders, it is not surprising that they have high levels of comorbidities. The purpose of this article is to review the neurobiology of hedonic tone as it pertains to depression, ADHD, and the potential for substance abuse. We propose that, since low hedonic tone is a shared feature of MDD, ADHD, and substance abuse, evaluation of hedonic tone may become a diagnostic feature used to predict subtypes of MDD, such as treatment-resistant depression, as well as comorbidities of these disorders.

CognitiveConstruct

RewardProcessing

10.1007/s00125-016-4095-0

Diabetologia

Diabetologia

Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity.

Variations in FTO are the strongest common genetic determinants of adiposity, and may partly act by influencing dopaminergic signalling in the brain leading to altered reward processing that promotes increased food intake. Therefore, we investigated the impact of such an interaction on body composition, and peripheral and brain insulin sensitivity. Participants from the Tübingen Family study (n = 2245) and the Malmö Diet and Cancer study (n = 2921) were genotyped for FTO SNP rs8050136 and ANKK1 SNP rs1800497. Insulin sensitivity in the caudate nucleus, an important reward area in the brain, was assessed by fMRI in 45 participants combined with intranasal insulin administration. We found evidence of an interaction between variations in FTO and an ANKK1 polymorphism that associates with dopamine (D2) receptor density. In cases of reduced D2 receptor availability, as indicated by the ANKK1 polymorphism, FTO variation was associated with increased body fat and waist circumference and reduced peripheral insulin sensitivity. Similarly, altered central insulin sensitivity was observed in the caudate nucleus in individuals with the FTO obesity-risk allele and diminished D2 receptors. The effects of variations in FTO are dependent on dopamine D2 receptor density (determined by the ANKK1 polymorphism). Carriers of both risk alleles might, therefore, be at increased risk of obesity and diabetes.

CognitiveConstruct

RewardProcessing

10.1007/s00213-016-4383-x

Psychopharmacology

Psychopharmacology (Berl)

Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis 'amotivational' hypotheses.

Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence. The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning. In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state. Cann-CBD reduced the likelihood of high-effort choices relative to placebo (p = 0.042) and increased sensitivity to expected value compared to both placebo (p = 0.014) and Cann + CBD (p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (p = 0.007). Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.

CognitiveConstruct

RewardProcessing

10.1111/adb.12436

Addiction biology

Addict Biol

The gut in the brain: the effects of bariatric surgery on alcohol consumption.

Obesity represents a major medical and public health problem worldwide. Efforts have been made to develop novel treatments, and among them bariatric surgery is used as an effective treatment to achieve significant, long-term weight loss and alleviate medical problems related to obesity. Alcohol use disorder (AUD) is also a leading cause of morbidity and mortality worldwide. Recent clinical studies have revealed a concern for bariatric surgery patients developing an increased risk for alcohol consumption, and for AUD. A better understanding of the relationship between bariatric surgery and potential later development of AUD is important, given the critical need of identifying patients at high risk for AUD. This paper reviews current clinical and basic science research and discusses potential underlying mechanisms. Special emphasis in this review is given to recent work suggesting that, alterations in alcohol metabolism/pharmacokinetics resulting from bariatric surgery are unlikely to be the primary or at least the only explanation for increased alcohol use and development of AUD, as changes in brain reward processing are also likely to play an important role. Additional studies are needed to clarify the potential role and mechanisms of how bariatric surgery may increase alcohol use and lead to AUD development.

CognitiveConstruct

RewardProcessing

10.1016/j.neuron.2016.07.047

Neuron

Neuron

Reverse Replay of Hippocampal Place Cells Is Uniquely Modulated by Changing Reward.

Hippocampal replays are episodes of sequential place cell activity during sharp-wave ripple oscillations (SWRs). Conflicting hypotheses implicate awake replay in learning from reward and in memory retrieval for decision making. Further, awake replays can be forward, in the same order as experienced, or reverse, in the opposite order. However, while the presence or absence of reward has been reported to modulate SWR rate, the effect of reward changes on replay, and on replay direction in particular, has not been examined. Here we report divergence in the response of forward and reverse replays to changing reward. While both classes of replays were observed at reward locations, only reverse replays increased their rate at increased reward or decreased their rate at decreased reward, while forward replays were unchanged. These data demonstrate a unique relationship between reverse replay and reward processing and point to a functional distinction between different directions of replay. VIDEO ABSTRACT.

CognitiveConstruct

RewardProcessing

10.1111/acps.12629

Acta psychiatrica Scandinavica

Acta Psychiatr Scand

Depression, marijuana use and early-onset marijuana use conferred unique effects on neural connectivity and cognition.

Marijuana (MJ) use is common. Research shows risks for psychiatric illnesses, including major depressive disorder (MDD) and cognitive deficits with MJ use, particularly early-onset use. We investigated cognitive function, functional connectivity, and genetic risk with MDD alone and combined with MJ use, and differences between early-vs. late-onset/non-MJ use in youth. A total of 74 youth in four groups were studied: healthy control, MDD, frequent MJ use and current/past MDD plus frequent MJ use. Psychiatric symptoms, cognitive performance and demographics were measured. Default mode network (DMN) brain connectivity was determined. Risk alleles in six genes of interest were evaluated. DMN differences among groups in reward-processing and motor control regions were found; the effects of MJ use and MDD were distinct. Early-onset MJ use was associated with lower IQ and hyperconnectivity within areas of the DMN. Early-onset MJ use was associated with the BDNF risk allele. Cognitive deficits linked with early-onset MJ use were present within several years after MJ use began and may result from, predispose to, or share a common cause with early-onset MJ use. The DMN was affected by MDD, MJ and their combination, as well as by early-onset MJ use. BDNF carrier state may predispose to early-onset MJ use.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2016.08.005

Psychiatry research. Neuroimaging

Psychiatry Res Neuroimaging

The link between callous-unemotional traits and neural mechanisms of reward processing: An fMRI study.

Callous-unemotional (CU) traits, i.e., unconcernedness and lack of prosocial feelings, may manifest in Conduct Disorder (CD), but also in Oppositional Defiant Disorder (ODD) and Attention Deficit Hyperactivity Disorder (ADHD). These disorders have been associated with aberrant reward processing, while the influence of CU traits is unclear. Using functional Magnetic Resonance Imaging (fMRI), we examined whether CU traits affect the neural circuit for reward. A Monetary Incentive Delay (MID) task was administered to 328 adolescents and young adults with varying levels of CU traits: 40 participants with ODD/CD plus ADHD, 101 participants with ADHD only, 84 siblings of probands with ADHD and 103 typically developing (TD) individuals. During reward anticipation, CU traits related negatively to medial prefrontal cortex (mPFC) activity, independent of ADHD symptoms and ODD/CD diagnosis. Our results indicate that CU traits are a valuable dimension for assessing the neural basis of reward processing.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.1402-16.2016

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

J Neurosci

The Nucleus Reuniens of the Midline Thalamus Gates Prefrontal-Hippocampal Modulation of Ventral Tegmental Area Dopamine Neuron Activity.

The circuitry mediating top-down control of dopamine (DA) neurons in the ventral tegmental area (VTA) is exceedingly complex. Characterizing these networks will be critical to our understanding of fundamental behaviors, such as motivation and reward processing, as well as several disease states. Previous work suggests that the medial prefrontal cortex (mPFC) exerts a profound influence on VTA DA neuron firing. Recently, our group reported that inhibition of the infralimbic subdivision of the medial prefrontal cortex (ilPFC) increases the proportion of VTA DA neurons that are spontaneously active (i.e., "population activity") and that this effect depends on activity in the ventral subiculum of the hippocampus (vSub). However, there is no direct projection from the mPFC to the vSub. Anatomical evidence suggests that communication between the two structures is mediated by the nucleus reuniens of the midline thalamus (RE). Here, we used in vivo electrophysiological and behavioral approaches in rats to explore the role of the RE in the circuitry governing VTA DA neuron firing. We show that pharmacological stimulation of the RE enhances VTA DA neuron population activity and amphetamine-induced hyperlocomotion, a behavioral indicator of an over-responsive DA system. Furthermore, the effect of RE stimulation on population activity is prevented if vSub is also inhibited. Finally, pharmacological inhibition of ilPFC enhances VTA DA neuron population activity, but this effect does not occur if RE is also inhibited. These findings suggest that disruption of ilPFC-RE-vSub communication could lead to a dysregulated, hyperdopaminergic state, and may play a role in psychiatric disorders. Dopamine (DA) neurons in the ventral tegmental area (VTA) are involved in a variety of fundamental brain functions. To understand the neurobiological basis for these functions it is essential to identify regions controlling DA neuron activity. The medial prefrontal cortex (mPFC) is emerging as a key regulator of DA neuron activity, but the circuitry by which it exerts its influence remains poorly described. Here, we show that the nucleus reuniens of the midline thalamus gates mPFC control of VTA DA neuron firing by the hippocampus. These data identify a unique role for this corticothalamic-hippocampal circuit, and suggest that dysfunction in these regions likely influences the pathophysiology of psychiatric disorders.

CognitiveConstruct

RewardProcessing

10.1007/s11682-016-9585-7

Brain imaging and behavior

Brain Imaging Behav

Imbalanced functional link between reward circuits and the cognitive control system in patients with obsessive-compulsive disorder.

Altered reward processing and cognitive deficits are often observed in patients with obsessive-compulsive disorder (OCD); however, whether the imbalance in activity between reward circuits and the cognitive control (CC) system is associated with compulsive behavior remains unknown. Sixty-eight OCD patients and 33 cognitively normal (CN) healthy subjects participated in this resting-state functional magnetic resonance imaging study. Alterations in the functional connectivity between reward circuits and the CC system were quantitatively assessed and compared between the groups. A Granger causality analysis was used to determine the causal informational influence between and within reward circuits and the CC system across all subjects. OCD patients showed a dichotomous pattern of enhanced functional coupling in their reward circuits and a weakened functional coupling in their CC system when compared to CN subjects. Neural correlates of compulsive behavior were primarily located in the reward circuits and CC system in OCD patients. Importantly, the CC system exerted a reduced interregional causal influence over the reward system in OCD patients relative to its effect in CN subjects. The limitations of this study are that it was a cross-sectional study and the potential effects of environmental and genetic factors were not explored. OCD patients showed an imbalance in the functional link between reward circuits and the CC system at rest. This bias toward a loss of control may define a pathological state in which subjects are more vulnerable to engaging in compulsive behaviors.

CognitiveConstruct

RewardProcessing

10.1038/npp.2016.161

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Dissociable Effects of Cocaine Dependence on Reward Processes: The Role of Acute Cocaine and Craving.

The relative impact of chronic vs acute cocaine on dependence-related variability in reward processing in cocaine-dependent individuals (CD) is not well understood, despite the relevance of such effects to long-term outcomes. To dissociate these effects, CD (N=15) and healthy controls (HC; N=15) underwent MRI two times while performing a monetary incentive delay task. Both scans were identical across subjects/groups, except that, in a single-blind, counterbalanced design, CD received intravenous cocaine (30 mg/70 kg) before one session (CD+cocaine) and saline in another (CD+saline). Imaging analyses focused on activity related to anticipatory valence (gain/loss), anticipatory magnitude (small/medium/large), and reinforcing outcomes (successful/unsuccessful). Drug condition (cocaine vs saline) and group (HC vs CD+cocaine or CD+saline) did not influence valence-related activity. However, compared with HC, magnitude-related activity for gains was reduced in CD in the left cingulate gyrus post-cocaine and in the left putamen in the abstinence/saline condition. In contrast, magnitude-dependent activity for losses increased in CD vs HC in the right inferior parietal lobe post-cocaine and in the left superior frontal gyrus post-saline. Across outcomes (ie, successful and unsuccessful) activity in the right habenula decreased in CD in the abstinence/saline condition vs acute cocaine and HC. Cocaine-dependent variability in outcome- and loss-magnitude activity correlated negatively with ratings of cocaine craving and positively with how high subjects felt during the scanning session. Collectively, these data suggest dissociable effects of acute cocaine on non-drug reward processes, with cocaine consumption partially ameliorating dependence-related insensitivity to reinforcing outcomes/'liking', but having no discernible effect on dependence-related alterations in incentive salience/'wanting'. The relationship of drug-related affective sequelae to non-drug reward processing suggests that CD experience a general alteration of reward function and may be motivated to continue using cocaine for reasons beyond desired drug-related effects. This may have implications for individual differences in treatment efficacy for approaches that rely on reinforcement strategies (eg, contingency management) and for the long-term success of treatment.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2016.08.031

Behavioural brain research

Behav Brain Res

Effects of striatal lesions on components of choice: Reward discrimination, preference, and relative valuation.

The striatum is a key structure involved in reward processing and choice. Recently, we have developed a paradigm to explore how components of reward processing work together or independently during choice behavior. These components include reward discrimination, preference and relative valuation, and the goal of the present study was to determine how the striatum is involved in these dissociable components during this novel free choice paradigm. We tested choice utilizing two different outcome series with one being a more straightforward single-option discrimination anchored by a 0 reward outcome, and the other as a multi-option outcome discrimination of greater difficulty. We compared the free choice reward task to a sequential reward task and an extinction task. Striatal lesions impaired responding only in the free choice version with alterations in both appetitive and consummatory measures. Ventral striatal lesions had greater impact altering discrimination, preference and relative valuation in both the single and multi-option week studies. A major factor involved in these deficits was a significant aversion to the multi-option that contained a larger outcome option but with a longer delay to reward. Dorsal striatal lesions caused less impairment even leading to enhanced choice behavior compared to control animals during the more difficult multi-option free choice series. Overall, the results suggest that the context of action is crucial when linking striatal function to choice behavior and its diverse components. The implications include the idea that striatal involvement in decision-making is increased when responses are self-paced and diverse in a more naturalistic environment.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2016.08.024

NeuroImage

Neuroimage

Theta oscillations integrate functionally segregated sub-regions of the medial prefrontal cortex.

Reinforcement learning requires the dynamic interplay of several specialized networks distributed across the brain. A potential mechanism to establish accurate temporal coordination among these paths is through the synchronization of neuronal activity to a common rhythm of neuronal firing. Previous EEG studies have suggested that theta oscillatory activity might be crucial in the integration of information from motivational and attentional paths that converge into the medial Prefrontal Cortex (mPFC) during reward-guided learning. However, due to the low spatial resolution of EEG, this hypothesis has not been directly tested. Here, by combining EEG and fMRI, we show that theta oscillations serve as common substrate for the engagement of separated sub-regions within the mPFC (the pre-Supplementary Motor Area and the dorsomedial Prefrontal Cortex), underlying different cognitive operations (encoding of outcome valence and unsigned prediction errors) through separate functional paths (the Salience and the Central Executive Networks).

CognitiveConstruct

RewardProcessing

10.1210/en.2016-1381

Endocrinology

Endocrinology

Morphological and Physiological Interactions Between GnRH3 and Hypocretin/Orexin Neuronal Systems in Zebrafish (Danio rerio).

GnRH neurons integrate internal and external cues to control sexual maturation and fertility. Homeostasis of energy balance and food intake correlates strongly with the status of reproduction. Neuropeptides secreted by the hypothalamus involved in modulating energy balance and feeding may play additional roles in the regulation of reproduction. Hypocretin (Hcrt) (also known as orexin) is one such peptide, primarily controlling sleep/wakefulness, food intake, and reward processing. There is a growing body of evidence indicating that Hcrt/orexin (Hcrt) modulates reproduction through interacting with the hypothalamo-pituitary-gonadal axis in mammals. To explore potential morphological and functional interactions between the GnRH and Hcrt neuronal systems, we employed a variety of experimental approaches including confocal imaging, immunohistochemistry, and electrophysiology in transgenic zebrafish, in which fluorescent proteins are genetically expressed in GnRH3 and Hcrt neurons. Our imaging data revealed close apposition and direct connection between GnRH3 and Hcrt neuronal systems in the hypothalamus during larval development through adulthood. Furthermore, the Hcrt receptor (HcrtR) is expressed in GnRH3 neurons. Electrophysiological data revealed a reversible inhibitory effect of Hcrt on GnRH3 neuron electrical activity, which was blocked by the HcrtR antagonist almorexant. In addition, Hcrt had no effect on the electrical activity of GnRH3 neurons in the HcrtR null mutant zebrafish (HcrtR). Our findings demonstrate a close anatomical and functional relationship between Hcrt and GnRH neuronal systems in zebrafish. It is the first demonstration of a link between neuronal circuits controlling sleeping/arousal/feeding and reproduction in zebrafish, an important animal model for investigating the molecular genetics of development.

CognitiveConstruct

RewardProcessing

10.1080/00952990.2016.1209512

The American journal of drug and alcohol abuse

Am J Drug Alcohol Abuse

Mechanisms and genetic factors underlying co-use of nicotine and alcohol or other drugs of abuse.

Concurrent use of tobacco and alcohol or psychostimulants represents a major public health concern, with use of one substance influencing consumption of the other. Co-abuse of these drugs leads to substantial negative health outcomes, reduced cessation, and high economic costs, but the underlying mechanisms are poorly understood. Epidemiological data suggest that tobacco use during adolescence plays a particularly significant role. Adolescence is a sensitive period of development marked by major neurobiological maturation of brain regions critical for reward processing, learning and memory, and executive function. Nicotine exposure during this time produces a unique and long-lasting vulnerability to subsequent substance use, likely via actions at cholinergic, dopaminergic, and serotonergic systems. In this review, we discuss recent clinical and preclinical data examining the genetic factors and mechanisms underlying co-use of nicotine and alcohol or cocaine and amphetamines. We evaluate the critical role of nicotinic acetylcholine receptors throughout, and emphasize the dearth of preclinical studies assessing concurrent drug exposure. We stress important age and sex differences in drug responses, and highlight a brief, low-dose nicotine exposure paradigm that may better model early use of tobacco products. The escalating use of e-cigarettes among youth necessitates a closer look at the consequences of early adolescent nicotine exposure on subsequent alcohol and drug abuse.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsw116

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

The µ-opioid system promotes visual attention to faces and eyes.

Paying attention to others' faces and eyes is a cornerstone of human social behavior. The µ-opioid receptor (MOR) system, central to social reward-processing in rodents and primates, has been proposed to mediate the capacity for affiliative reward in humans. We assessed the role of the human MOR system in visual exploration of faces and eyes of conspecifics. Thirty healthy males received a novel, bidirectional battery of psychopharmacological treatment (an MOR agonist, a non-selective opioid antagonist, or placebo, on three separate days). Eye-movements were recorded while participants viewed facial photographs. We predicted that the MOR system would promote visual exploration of faces, and hypothesized that MOR agonism would increase, whereas antagonism decrease overt attention to the information-rich eye region. The expected linear effect of MOR manipulation on visual attention to the stimuli was observed, such that MOR agonism increased while antagonism decreased visual exploration of faces and overt attention to the eyes. The observed effects suggest that the human MOR system promotes overt visual attention to socially significant cues, in line with theories linking reward value to gaze control and target selection. Enhanced attention to others' faces and eyes represents a putative behavioral mechanism through which the human MOR system promotes social interest.

CognitiveConstruct

RewardProcessing

10.1007/s40429-016-0114-y

Current addiction reports

Curr Addict Rep

Sex Effects of Marijuana on Brain Structure and Function.

Tetrahydrocannabinol (Δ-THC), the primary ingredient in marijuana, exerts its effects across several neurological and biological systems that interact with the endocrine system. Thus, differential effects of Δ-THC are likely to exist based on sex and hormone levels. We reviewed the existing literature to determine sex-based effects of Δ-THC on neural structure and functioning. The literature demonstrates differences in male and female marijuana users on brain structure, reward processing, attention, motor coordination, and sensitivity to withdrawal. However, inconsistencies exist in the literature regarding how marijuana affects men and women differentially, and more work is needed to understand these mechanisms. While extant literature remains inconclusive, differentiation between male and female marijuana users is likely due to neurological sexual dimorphism and differential social factors at play during development and adulthood. Sex has important implications for marijuana use and the development of cannabis use disorders and should be considered in the development of prevention and treatment strategies.

CognitiveConstruct

RewardProcessing

10.2174/1381612822666160805155922

Current pharmaceutical design

Curr Pharm Des

Adolescent Cannabis Use: What is the Evidence for Functional Brain Alteration?

Cannabis use typically commences during adolescence, a period during which the brain undergoes profound remodeling in areas that are high in cannabinoid receptors and that mediate cognitive control and emotion regulation. It is therefore important to determine the impact of adolescent cannabis use on brain function. We investigate the impact of adolescent cannabis use on brain function by reviewing the functional magnetic resonance imaging studies in adolescent samples. We systematically reviewed the literature and identified 13 functional neuroimaging studies in adolescent cannabis users (aged 13 to 18 years) performing working memory, inhibition and reward processing tasks. The majority of the studies found altered brain function, but intact behavioural task performance in adolescent cannabis users versus controls. The most consistently reported differences were in the frontal-parietal network, which mediates cognitive control. Heavier use was associated with abnormal brain function in most samples. A minority of studies controlled for the influence of confounders that can also undermine brain function, such as tobacco and alcohol use, psychopathology symptoms, family history of psychiatric disorders and substance use. Emerging evidence shows abnormal frontal-parietal network activity in adolescent cannabis users, particularly in heavier users. Brain functional alterations may reflect a compensatory neural mechanism that enables normal behavioural performance. It remains unclear if cannabis exposure drives these alterations, as substance use and mental health confounders have not been systematically examined.

CognitiveConstruct

RewardProcessing

10.1016/bs.irn.2016.05.001

International review of neurobiology

Int Rev Neurobiol

Imaging the Gambling Brain.

Neuroimaging studies examining the neurobiological basis of gambling disorder (GD) have increased over the past decade. Functional magnetic resonance imaging studies during appetitive cue and reward processing tasks demonstrate altered functioning in frontostriatal brain areas, including the ventral striatum and the ventromedial prefrontal cortex. Findings suggest differences in how the anticipation and outcome of rewards are processed in individuals with GD. Future research requires larger sample sizes and should include appropriate clinical reference groups. Overall, studies to date highlight a common pathophysiology between substance-based addictions and GD, the latter offering a unique condition in which to examine nonchemical factors in addiction.

CognitiveConstruct

RewardProcessing

10.1016/j.cortex.2016.07.009

Cortex; a journal devoted to the study of the nervous system and behavior

Cortex

Your misery is no longer my pleasure: Reduced schadenfreude in Huntington's disease families.

Schadenfreude - pleasure at others' misfortunes - has been systematically related to ventral striatum activity. This brain region is affected early in individuals with manifest and pre-manifest Huntington's disease (HD). However, the experience of schadenfreude has not yet been investigated in HD. In this study, 21 manifest HD patients, 19 first-degree asymptomatic relatives, and 23 healthy controls performed an experimental task designed to trigger schadenfreude, envy (another social emotion acting as an affective control condition), and control situations. Both HD patients and first-degree relatives experienced lower schadenfreude in response to others' misfortunes, with no group differences in ratings of envy and control conditions. These results offer unprecedented evidence of a highly specific impairment in reward processing, extending previous reports in manifest and pre-manifest HD individuals. Moreover, these findings suggest that early striatal impairments may be related to reduced feelings of schadenfreude. In sum, our work contributes to the understanding of emotional impairments in early stages of HD, while shedding light on their neural correlates.

CognitiveConstruct

RewardProcessing

10.1186/s11689-016-9163-8

Journal of neurodevelopmental disorders

J Neurodev Disord

Erratum to: Neural correlates of reward processing in adults with 22q11 deletion syndrome.

[This corrects the article DOI: 10.1186/s11689-016-9158-5.].

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2016.07.020

Drug and alcohol dependence

Drug Alcohol Depend

Examining the interaction between cognitive control and reward sensitivity in substance use dependence.

Drug dependence is characterized by altered reward processing and poor cognitive control, expressed as a preference for immediate rewards and impaired inhibitory control, respectively. To examine the interaction between reward processing (via the presence or absence of reward) and mechanisms of inhibitory control in drug dependence, the current study used the Monetary Incentive Control Task (MICT) to examine whether a group of opiate dependent persons demonstrated greater difficulty exerting control over immediate rewards compared to neutral stimuli. The MICT is a Go/Stop paradigm that examines inhibitory control over immediate rewards. Performance of 32 opiate dependent individuals was compared to 29 healthy controls. Opiate users demonstrated poorer inhibitory performance than controls, irrespective of cues signaling immediate reward. Whereas control participants' responses were modulated by probability cues, the opiate group did not show a capacity to up-regulate their cognitive control performance. The present results suggest a general decrease in cognitive control in opiate dependence, accompanied by a reduced ability to optimally modulate behavior in accordance with external cues. Opiate users and controls did not differ in the interaction between cognitive control and reward. The study highlights important issues for future research to consider when further examining this interaction in drug dependence.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2016.07.044

Behavioural brain research

Behav Brain Res

Dopamine antagonism does not impair learning of Pavlovian conditioned approach to manipulable or non-manipulable cues but biases responding towards goal tracking.

Dopamine's (DA) role in reward-processing is currently discussed as either providing a teaching signal to guide learning or mediating the transfer of incentive salience (i.e. motivational aspects) from unconditioned stimuli (US) to conditioned stimuli (CS). We used a Pavlovian conditioned approach (PCA) procedure to further investigate DAs contribution to these processes. Experiment 1 assessed the acquisition of PCA to a manipulable lever cue for 7days under DA-blockade with Flupenthixol (FLU; 225μg/kg) or Saline (SAL) treatment, followed by 6-days off-drug testing. FLU decreased the number of conditioned responses (CR) during the treatment phase, but cessation of treatment resulted in an immediate increase in CR to levels comparable to SAL controls; notably, CR in FLU-treated rats were restricted to goal tracking behaviour. During continued off-drug testing, rats from the FLU group developed sign tracking with a similar temporal pattern as controls. In experiment 2, acquisition of PCA to a non-manipulable auditory cue was investigated. FLU reduced the number of CR during treatment, and removing DA antagonism resulted in a similar rapid increase of CR as seen in experiment 1. These data complement other reports by demonstrating that, independently from the physical properties of the CS, DA is not required for learning predictive aspects of a CS-US relationship but for the development of behaviour (namely sign tracking) which is based on the motivational aspects of a CS-US relationship.

CognitiveConstruct

RewardProcessing

10.1093/cercor/bhw197

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

Cereb Cortex

A Hedonism Hub in the Human Brain.

Human values are abstract ideals that motivate behavior. The motivational nature of human values raises the possibility that they might be underpinned by brain structures that are particularly involved in motivated behavior and reward processing. We hypothesized that variation in subcortical hubs of the reward system and their main connecting pathway, the superolateral medial forebrain bundle (slMFB) is associated with individual value orientation. We conducted Pearson's correlation between the scores of 10 human values and the volumes of 14 subcortical structures and microstructural properties of the medial forebrain bundle in a sample of 87 participants, correcting for multiple comparisons (i.e.,190). We found a positive association between the value that people attach to hedonism and the volume of the left globus pallidus (GP).We then tested whether microstructural parameters (i.e., fractional anisotropy and myelin volume fraction) of the slMFB, which connects with the GP, are also associated to hedonism and found a significant, albeit in an uncorrected level, positive association between the myelin volume fraction within the left slMFB and hedonism scores. This is the first study to elucidate the relationship between the importance people attach to the human value of hedonism and structural variation in reward-related subcortical brain regions.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.0347-16.2016

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

J Neurosci

Prefrontal Cortex to Accumbens Projections in Sleep Regulation of Reward.

Sleep profoundly affects the emotional and motivational state. In humans and animals, loss of sleep often results in enhanced motivation for reward, which has direct implications for health risks as well as potential benefits. Current study aims at understanding the mechanisms underlying sleep deprivation (SDe)-induced enhancement of reward seeking. We found that after acute SDe, mice had an increase in sucrose seeking and consumption but not food intake, suggesting a selective enhancement of motivation for reward. In the nucleus accumbens (NAc), a key brain region regulating emotional and motivational responses, we observed a decrease in the ratio of the overall excitatory over inhibitory synaptic inputs onto NAc principle neurons after SDe. The shift was partly mediated by reduced glutamatergic transmission of presynaptic origin. Further analysis revealed that there was selective reduction of the glutamate release probability at the medial prefrontal cortex (mPFC)-to-NAc synapses, but not those from the hippocampus, thalamus, or the basal lateral amygdala. To reverse this SDe-induced synaptic alteration, we expressed the stabilized step function opsin (SSFO) in the mPFC; optogenetic stimulation of SSFO at mPFC-to-NAc projection terminals persistently enhanced the action potential-dependent glutamate release. Intra-NAc optogenetic stimulation of SSFO selectively at mPFC-to-NAc terminals restored normal sucrose seeking in mice after SDe without affecting food intake. These results highlight the mPFC-to-NAc projection as a key circuit-based target for sleep to regulate reward-motivated behaviors. Sleep loss, a costly challenge of modern society, has profound physiological and psychological consequences, including altered reward processing of the brain. The current study aims at understanding the mechanisms underlying sleep deprivation-induced enhancement of reward seeking. We identify that the medial prefrontal cortex (mPFC)-to-nucleus accumbens (NAc) glutamatergic transmission is selectively weakened following acute sleep deprivation, whose restoration normalizes reward seeking in sleep-deprived mice. These results suggest a possibility of normalizing sleep deprivation-induced abnormal reward seeking by targeting specific neural projections, and they demonstrate the mPFC-to-NAc glutamatergic projection as a key circuit-based target for sleep to regulate reward-motivated behaviors.

CognitiveConstruct

RewardProcessing

10.1038/srep30588

Scientific reports

Sci Rep

Neural markers of social and monetary rewards in children with Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder.

Recent theories of decision making propose a shared value-related brain mechanism for encoding monetary and social rewards. We tested this model in children with Attention-Deficit/Hyperactivity Disorder (ADHD), children with Autism Spectrum Disorder (ASD) and control children. We monitored participants' brain dynamics using high density-electroencephalography while they played a monetary and social reward tasks. Control children exhibited a feedback Error-Related Negativity (fERN) modulation and Anterior Cingulate Cortex (ACC) source activation during both tasks. Remarkably, although cooperation resulted in greater losses for the participants, the betrayal options generated greater fERN responses. ADHD subjects exhibited an absence of fERN modulation and reduced ACC activation during both tasks. ASD subjects exhibited normal fERN modulation during monetary choices and inverted fERN/ACC responses in social options than did controls. These results suggest that in neurotypicals, monetary losses and observed disloyal social decisions induced similar activity in the brain value system. In ADHD children, difficulties in reward processing affected early brain signatures of monetary and social decisions. Conversely, ASD children showed intact neural markers of value-related monetary mechanisms, but no brain modulation by prosociality in the social task. These results offer insight into the typical and atypical developments of neural correlates of monetary and social reward processing.

CognitiveConstruct

RewardProcessing

10.1017/S0033291716001586

Psychological medicine

Psychol Med

A multidimensional approach to impulsivity in Parkinson's disease: measurement and structural invariance of the UPPS Impulsive Behaviour Scale.

Poor impulse control is a common feature in patients with Parkinson's disease (PD). However, before testing whether patients with PD and controls differ in impulsivity, one must assess whether impulsivity measures are invariant across groups. Consequently, we examined (a) the measurement and structural invariance of a scale assessing changes in four dimensions of impulsivity (urgency, lack of premeditation, lack of perseverance and sensation seeking) among patients with PD and controls; and (b) whether the four impulsivity traits relate differentially to risky decisions by patients. Close relatives of 78 patients with idiopathic PD and 96 control participants were given the short Urgency-Premeditation-Perseverance-Sensation seeking Impulsive Behaviour Scale (UPPS), which assesses changes in four dimensions of impulsivity. Participants also completed the Game of Dice Task (GDT), a laboratory measure of risk taking. Multigroup confirmatory factor analyses supported measurement invariance across groups, whereas structural invariance was not confirmed. Patients with PD showed greater variability and higher impulsivity than controls. Furthermore, patients with impulse control disorders (ICDs) demonstrated even greater levels of sensation seeking than patients without ICDs. Finally, lower premeditation and greater perseverance were significantly associated with greater risk taking in patients with PD, and higher agonist dopaminergic doses with less risky choices on the GDT. The questionnaire appears to function comparably across patients and controls. Thus, group comparisons on the questionnaire can be considered valid. Mean differences between groups on the dimensions of impulsivity may reflect executive impairments and/or abnormal reward processing in patients with PD, which may lead to risky behaviours.

CognitiveConstruct

RewardProcessing

10.1002/hbm.23292

Human brain mapping

Hum Brain Mapp

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct-disordered juvenile offenders.

Psychopathy is a serious psychiatric phenomenon characterized by a pathological constellation of affective (e.g., callous, unemotional), interpersonal (e.g., manipulative, egocentric), and behavioral (e.g., impulsive, irresponsible) personality traits. Though amygdala subregional defects are suggested in psychopathy, the functionality and connectivity of different amygdala subnuclei is typically disregarded in neurocircuit-level analyses of psychopathic personality. Hence, little is known of how amygdala subregional networks may contribute to psychopathy and its underlying trait assemblies in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral (BLA) and centromedial (CMA) amygdala networks in relation to affective, interpersonal, and behavioral traits of psychopathy, in conduct-disordered juveniles with a history of serious delinquency (N = 50, mean age = 16.83 ± 1.32). As predicted, amygdalar connectivity profiles exhibited dissociable relations with different traits of psychopathy. Interpersonal psychopathic traits not only related to increased connectivity of BLA and CMA with a corticostriatal network formation accommodating reward processing, but also predicted stronger CMA connectivity with a network of cortical midline structures supporting sociocognitive processes. In contrast, affective psychopathic traits related to diminished CMA connectivity with a frontolimbic network serving salience processing and affective responding. Finally, behavioral psychopathic traits related to heightened BLA connectivity with a frontoparietal cluster implicated in regulatory executive functioning. We suggest that these trait-specific shifts in amygdalar connectivity could be particularly relevant to the psychopathic phenotype, as they may fuel a self-centered, emotionally cold, and behaviorally disinhibited profile. Hum Brain Mapp 37:4017-4033, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2016.00949

Frontiers in psychology

Front Psychol

Commentary: Differential associations between obesity and behavioral measures of impulsivity.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2016.03.074

Journal of affective disorders

J Affect Disord

Preliminary investigation of the relationships between sleep duration, reward circuitry function, and mood dysregulation in youth offspring of parents with bipolar disorder.

Altered reward circuitry function is observed in individuals with bipolar disorder (BD) and their unaffected offspring (OBP). While OBP are at elevated risk for BD, modifiable risk factors that may exacerbate neural vulnerabilities in OBP remain under-characterized. As sleep loss is strongly linked to mania in BD, this study tested associations between sleep duration, reward circuitry function, and mood dysregulation in OBP. Two groups of youth unaffected with BD (9-17yr) completed a number-guessing fMRI reward paradigm: 25 OBP and 21 age-sex-IQ-matched offspring of control parents with non-BD psychopathology (OCP), to differentiate risk for BD from risk for psychopathology more broadly. Regressions tested effects of group status, self-reported past-week sleep duration, and their interaction on neural activity and bilateral ventral striatum (VS) functional connectivity to win>control. Correlations with parent-reported mood dysregulation were assessed. Group effects were observed for right posterior insula activity (OCP>OBP) and VS-left posterior insula connectivity (OBP>OCP). Groupsleep duration interactions were observed for left dorsal anterior-mid-cingulate (daMCC) activity and VS-left anterior insula/ventrolateral prefrontal cortex (VLPFC) connectivity. Specifically, sleep duration and daMCC activity were positively related in OBP, but negatively related in OCP and sleep duration and VS-left anterior insula/VLPFC connectivity were negatively related in OBP, but positively in OCP. Additionally, increased VS-left posterior insula connectivity and VS-left anterior insula/VLPFC connectivity were associated with greater mood dysregulation in OBP only. Cross-sectional design and small sample size. Altered reward-related VS-insula connectivity could represent a neural pathway underpinning mood dysregulation in OBP, and may be modulated by shortened sleep duration.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2016.07.006

Drug and alcohol dependence

Drug Alcohol Depend

Anticipatory reward processing among cocaine-dependent individuals with and without concurrent methadone-maintenance treatment: Relationship to treatment response.

Cocaine dependence among opioid-dependent methadone-maintained individuals is a significant public health problem and is particularly challenging to treat. The neurobiology of this clinically complex population has not been previously assessed using fMRI. fMRI data from cocaine-dependent, methadone-maintained (CD-MM) patients (n=24), cocaine-dependent (CD) patients (n=20) and healthy comparison (HC) participants (n=21) were acquired during monetary incentive delay task performance. All patients were scanned prior to treatment for cocaine dependence. Between-group differences in anticipatory reward and loss processing were assessed using whole-brain ANOVAs in SPM12 (pFWE<0.05). Correlations between durations of abstinence during treatment and BOLD responses within the insula and caudate were also explored. Main effects of diagnostic group, primarily involving decreased BOLD responses among CD-MM patients in comparison to HCs, were observed during anticipatory reward and loss processing within regions of posterior cingulate cortex, precuneus, inferior frontal gyrus and dorsolateral prefrontal cortex. BOLD responses within the right caudate were negatively associated with percentage of cocaine-negative urines during treatment among CD-MM patients, but not among non-methadone-maintained CD patients. These data suggest neurofunctional differences that may be related to treatment outcomes for behavioral therapies between cocaine-dependent individuals with and without methadone-maintenance treatment. These findings may relate to differences in treatment efficacies and to the elevated relapse rates observed in methadone-maintained populations.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0158947

PloS one

PLoS One

The Role of Social Novelty in Risk Seeking and Exploratory Behavior: Implications for Addictions.

Novelty preference or sensation seeking is associated with disorders of addiction and predicts rodent compulsive drug use and adolescent binge drinking in humans. Novelty has also been shown to influence choice in the context of uncertainty and reward processing. Here we introduce a novel or familiar neutral face stimuli and investigate its influence on risk-taking choices in healthy volunteers. We focus on behavioural outcomes and imaging correlates to the prime that might predict risk seeking. We hypothesized that subjects would be more risk seeking following a novel relative to familiar stimulus. We adapted a risk-taking task involving acceptance or rejection of a 50:50 choice of gain or loss that was preceded by a familiar (pre-test familiarization) or novel face prime. Neutral expression faces of males and females were used as primes. Twenty-four subjects were first tested behaviourally and then 18 scanned using a different variant of the same task under functional MRI. We show enhanced risk taking to both gain and loss anticipation following novel relative to familiar images and particularly for the low gain condition. Greater risk taking behaviour and self-reported exploratory behaviours was predicted by greater right ventral putaminal activity to novel versus familiar contexts. Social novelty appears to have a contextually enhancing effect on augmenting risky choices possibly mediated via ventral putaminal dopaminergic activity. Our findings link the observation that novelty preference and sensation seeking are important traits predicting the initiation and maintenance of risky behaviours, including substance and behavioural addictions.

CognitiveConstruct

RewardProcessing

10.1038/npjschz.2016.20

NPJ schizophrenia

NPJ Schizophr

Deficits in context-dependent adaptive coding of reward in schizophrenia.

Theoretical principles of information processing and empirical findings suggest that to efficiently represent all possible rewards in the natural environment, reward-sensitive neurons have to adapt their coding range dynamically to the current reward context. Adaptation ensures that the reward system is most sensitive for the most likely rewards, enabling the system to efficiently represent a potentially infinite range of reward information. A deficit in neural adaptation would prevent precise representation of rewards and could have detrimental effects for an organism's ability to optimally engage with its environment. In schizophrenia, reward processing is known to be impaired and has been linked to different symptom dimensions. However, despite the fundamental significance of coding reward adaptively, no study has elucidated whether adaptive reward processing is impaired in schizophrenia. We therefore studied patients with schizophrenia (n=27) and healthy controls (n=25), using functional magnetic resonance imaging in combination with a variant of the monetary incentive delay task. Compared with healthy controls, patients with schizophrenia showed less efficient neural adaptation to the current reward context, which leads to imprecise neural representation of reward. Importantly, the deficit correlated with total symptom severity. Our results suggest that some of the deficits in reward processing in schizophrenia might be due to inefficient neural adaptation to the current reward context. Furthermore, because adaptive coding is a ubiquitous feature of the brain, we believe that our findings provide an avenue in defining a general impairment in neural information processing underlying this debilitating disorder.

CognitiveConstruct

RewardProcessing

10.1186/s11689-016-9158-5

Journal of neurodevelopmental disorders

J Neurodev Disord

Neural correlates of reward processing in adults with 22q11 deletion syndrome.

22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic neurotransmission in 22q11DS, which may contribute to the increased vulnerability for psychosis. A dysfunctional motivational reward system is considered one of the salient features in psychosis and thought to be related to abnormal dopaminergic neurotransmission. The functional anatomy of the brain reward circuitry has not yet been investigated in 22q11DS. This study aims to investigate neural activity during anticipation of reward and loss in adult patients with 22q11DS. We measured blood-oxygen-level dependent (BOLD) activity in 16 patients with 22q11DS and 12 healthy controls during a monetary incentive delay task using a 3T Philips Intera MRI system. Data were analysed using SPM8. During anticipation of reward, the 22q11DS group alone displayed significant activation in bilateral middle frontal and temporal brain regions. Compared to healthy controls, significantly less activation in bilateral cingulate gyrus extending to premotor, primary motor and somatosensory areas was found. During anticipation of loss, the 22q11DS group displayed activity in the left middle frontal gyrus and anterior cingulate cortex, and relative to controls, they showed reduced brain activation in bilateral (pre)cuneus and left posterior cingulate. Within the 22q11DS group, COMT Val hemizygotes displayed more activation compared to Met hemizygotes in right posterior cingulate and bilateral parietal regions during anticipation of reward. During anticipation of loss, COMT Met hemizygotes compared to Val hemizygotes showed more activation in bilateral insula, striatum and left anterior cingulate. This is the first study to investigate reward processing in 22q11DS. Our preliminary results suggest that people with 22q11DS engage a fronto-temporal neural network. Compared to healthy controls, people with 22q11DS primarily displayed reduced activity in medial frontal regions during reward anticipation. COMT hemizygosity affects responsivity of the reward system in this condition. Alterations in reward processing partly underlain by the dopamine system may play a role in susceptibility for psychosis in 22q11DS.

CognitiveConstruct

RewardProcessing

10.1038/npp.2016.128

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

How the Brain Wants What the Body Needs: The Neural Basis of Positive Alliesthesia.

Discontinuing unhealthy behaviors, such as overeating or drug use, depends upon an individual's ability to overcome the influence of environmental reward cues. The strength of that influence, however, varies greatly depending upon the internal state of the body. Characterizing the relationship between interoceptive signaling and shifting drug cue valuation provides an opportunity for understanding the neural bases of how changing internal states alter reward processing more generally. A total of 17 cigarette smokers rated the pleasantness of cigarette pictures when they were nicotine sated or nicotine abstinent. On both occasions, smokers also underwent functional magnetic resonance imaging (fMRI) scanning while performing a visceral interoceptive attention task and a resting-state functional connectivity scan. Hemodynamic, physiological, and behavioral parameters were compared between sated and abstinent scans. The relationships between changes in these parameters across scan sessions were also examined. Smokers rated cigarette pictures as significantly more pleasant while nicotine abstinent than while nicotine sated. Comparing abstinent with sated scans, smokers also exhibited significantly decreased mid-insula, amygdala, and orbitofrontal activity while attending to interoceptive signals from the body. Change in interoceptive activity within the left mid-insula predicted the increase in smoker's pleasantness ratings of cigarette cues. This increase in pleasantness ratings was also correlated with an increase in resting-state functional connectivity between the mid-insula and the ventral striatum and ventral pallidum. These findings support a model wherein interoceptive processing in the mid-insula of withdrawal signals from the body potentiates the motivational salience of reward cues through the recruitment of hedonic 'hot spots' within the brain's reward circuitry.

CognitiveConstruct

RewardProcessing

10.1111/ejn.13342

The European journal of neuroscience

Eur J Neurosci

Deep brain stimulation in the central nucleus of the amygdala decreases 'wanting' and 'liking' of food rewards.

We investigated the potential of deep brain stimulation (DBS) in the central nucleus of the amygdala (CeA) in rats to modulate functional reward mechanisms. The CeA is the major output of the amygdala with direct connections to the hypothalamus and gustatory brainstem, and indirect connections with the nucleus accumbens. Further, the CeA has been shown to be involved in learning, emotional integration, reward processing, and regulation of feeding. We hypothesized that DBS, which is used to treat movement disorders and other brain dysfunctions, might block reward motivation. In rats performing a lever-pressing task to obtain sugar pellet rewards, we stimulated the CeA and control structures, and compared stimulation parameters. During CeA stimulation, animals stopped working for rewards and rejected freely available rewards. Taste reactivity testing during DBS exposed aversive reactions to normally liked sucrose tastes and even more aversive taste reactions to normally disliked quinine tastes. Interestingly, given the opportunity, animals implanted in the CeA would self-stimulate with 500 ms trains of stimulation at the same frequency and current parameters as continuous stimulation that would stop reward acquisition. Neural recordings during DBS showed that CeA neurons were still active and uncovered inhibitory-excitatory patterns after each stimulus pulse indicating possible entrainment of the neural firing with DBS. In summary, DBS modulation of CeA may effectively usurp normal neural activity patterns to create an 'information lesion' that not only decreased motivational 'wanting' of food rewards, but also blocked 'liking' of rewards.

CognitiveConstruct

RewardProcessing

10.1080/17588928.2016.1213226

Cognitive neuroscience

Cogn Neurosci

Reward-based plasticity of spatial priority maps: Exploiting inter-subject variability to probe the underlying neurobiology.

Recent evidence indicates that the attentional priority of objects and locations is altered by the controlled delivery of reward, reflecting reward-based attentional learning. Here, we take an approach hinging on intersubject variability to probe the neurobiological bases of the reward-driven plasticity of spatial priority maps. Specifically, we ask whether an individual's susceptibility to the reward-based treatment can be accounted for by specific predictors, notably personality traits that are linked to reward processing (along with more general personality traits), but also gender. Using a visual search protocol, we show that when different target locations are associated with unequal reward probability, different priorities are acquired by the more rewarded relative to the less rewarded locations. However, while males exhibit the expected pattern of results, with greater priority for locations associated with higher reward, females show an opposite trend. Critically, both the extent and the direction of reward-based adjustments are further predicted by personality traits indexing reward sensitivity, indicating that not only male and female brains are differentially sensitive to reward, but also that specific personality traits further contribute to shaping their learning-dependent attentional plasticity. These results contribute to a better understanding of the neurobiology underlying reward-dependent attentional learning and cross-subject variability in this domain.

CognitiveConstruct

RewardProcessing

10.1038/nrrheum.2016.112

Nature reviews. Rheumatology

Nat Rev Rheumatol

Affective disturbance in rheumatoid arthritis: psychological and disease-related pathways.

In addition to recurrent pain, fatigue, and increased rates of physical disability, individuals with rheumatoid arthritis (RA) have an increased prevalence of some mental health disorders, particularly those involving affective or mood disturbances. This narrative Review provides an overview of mental health comorbidities in RA, and discusses how these comorbidities interact with disease processes, including dysregulation of inflammatory responses, prolonged difficulties with pain and fatigue, and the development of cognitive and behavioural responses that could exacerbate the physical and psychological difficulties associated with RA. This article describes how the social context of individuals with RA affects both their coping strategies and their psychological responses to the disease, and can also impair responses to treatment through disruption of patient-physician relationships and treatment adherence. Evidence from the literature on chronic pain suggests that the resulting alterations in neural pathways of reward processing could yield new insights into the connections between disease processes in RA and psychological distress. Finally, the role of psychological interventions in the effective and comprehensive treatment of RA is discussed.

CognitiveConstruct

RewardProcessing

10.3758/s13415-016-0443-2

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Intolerance of uncertainty and insula activation during uncertain reward.

Individuals with high intolerance of uncertainty (IU) have been shown to exhibit abnormal threat responding, which may be mediated by hyperactive anterior insula (aINS) response to uncertainty. Research has indicated that individuals with high IU also exhibit abnormal positive valence responding, suggesting that IU may impact responding to uncertainty regardless of the valence of the potential outcome. To date, no study has investigated the neural processes associated with IU and response to uncertain positive stimuli, such as rewards. Therefore, this study was designed to examine the association between individual differences in IU and neural activation during uncertain reward using functional magnetic resonance imaging (fMRI). Thirty-seven adults completed a self-report measure of IU and a reward task during fMRI. Consistent with the threat literature, greater IU was associated with increased aINS activation during uncertain reward. This association was more robust for the prospective IU subscale, a dimension characterized by worry about future events. Together with prior studies, these findings provide evidence that IU is related to abnormal threat and reward responding, and that these deficits may be similarly linked to hyperactive aINS response to uncertainty.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2016.07.008

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

Untangling the neurobiology of coping styles in rodents: Towards neural mechanisms underlying individual differences in disease susceptibility.

Considerable individual differences exist in trait-like patterns of behavioral and physiological responses to salient environmental challenges. This individual variation in stress coping styles has an important functional role in terms of health and fitness. Hence, understanding the neural embedding of coping style variation is fundamental for biobehavioral neurosciences in probing individual disease susceptibility. This review outlines individual differences in trait-aggressiveness as an adaptive component of the natural sociobiology of rats and mice, and highlights that these reflect the general style of coping that varies from proactive (aggressive) to reactive (docile). We propose that this qualitative coping style can be disentangled into multiple quantitative behavioral domains, e.g., flexibility/impulse control, emotional reactivity and harm avoidance/reward processing, that each are encoded into selective neural circuitries. Since functioning of all these brain circuitries rely on fine-tuned serotonin signaling, autoinhibitory control mechanisms of serotonergic neuron (re)activity are crucial in orchestrating general coping style. Untangling the precise neuromolecular mechanisms of different coping styles will provide a roadmap for developing better therapeutic strategies of stress-related diseases.

CognitiveConstruct

RewardProcessing

10.1016/j.cortex.2016.05.021

Cortex; a journal devoted to the study of the nervous system and behavior

Cortex

Ventral striatal hyperconnectivity during rewarded interference control in adolescents with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by cognitive deficits (e.g., interference control) and altered reward processing. Cognitive control is influenced by incentive motivation and according to current theoretical models, ADHD is associated with abnormal interactions between incentive motivation and cognitive control. However, the neural mechanisms by which reward modulates cognitive control in individuals with ADHD are unknown. We used event-related functional resonance imaging (fMRI) to study neural responses during a rewarded Stroop color-word task in adolescents (14-17 years) with ADHD (n = 25; 19 boys) and healthy controls (n = 33; 22 boys). Adolescents with ADHD showed increased reward signaling within the superior frontal gyrus and ventral striatum (VS) relative to controls. Importantly, functional connectivity analyses revealed a hyperconnectivity between VS and motor control regions in the ADHD group, as a function of reward-cognitive control integration. Connectivity was associated with performance improvement in controls but not in the ADHD group, suggesting inefficient connectivity. Adolescents with ADHD show increased neural sensitivity to rewards and its interactions with interference control in VS and motor regions, respectively. The findings support theoretical models of altered reward-cognitive control integration in individuals with ADHD.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsycho.2016.07.008

Biological psychology

Biol Psychol

Individual differences in the time course of reward processing: Stage-specific links with depression and impulsivity.

Reward dysfunction has been implicated in a wide range of psychological disorders, including internalizing and externalizing psychopathology. Basic neuroscience research has shown that reward is a multistage process, yet it is unclear how specific stages relate to individual differences in reward sensitivity. The current study utilized event-related potentials elicited during a monetary incentive task to parse sub-stages within anticipatory and consummatory reward processing. Effects of depressive symptoms and trait impulsivity were examined at each sub-stage (N=92). Reward anticipation modulated neural activity across three sub-stages: cue detection (cue-P3), approach behavior (contingent negative variation, CNV), and outcome anticipation (stimulus preceding negativity). Reward delivery modulated activity across two sub-stages: initial evaluation (reward positivity, RewP), and allocation of attention (feedback-P3). Sensation seeking predicted faster reaction times, as well as cue-P3 and RewP amplitudes. Depression and lack of premeditation interacted to predict CNV and RewP amplitudes. Results demonstrate that individual differences in reward functioning are stage-specific.

CognitiveConstruct

RewardProcessing

10.1001/jamapsychiatry.2016.1161

JAMA psychiatry

JAMA Psychiatry

Association of Marijuana Use With Blunted Nucleus Accumbens Response to Reward Anticipation.

Marijuana use may alter ventral striatal response to reward, which might heighten susceptibility to substance use disorder. Longitudinal research is needed to determine the effects of marijuana use on neural function involved in reward response. To determine whether marijuana use among young adults prospectively affects nucleus accumbens (NAcc) activation during reward anticipation. One hundred eight young adults were recruited from the Michigan Longitudinal Study, an ongoing study of youth at high risk for substance use disorder and a contrast sample of control families. Participants underwent 3 consecutive functional magnetic resonance imaging scans at approximate ages of 20 (time 1), 22 (time 2), and 24 (time 3) years. Self-report data on marijuana and other drug use occasions were collected annually since age 11 years. Cross-lagged models were used to test the association of marijuana use with neural response in the NAcc to reward anticipation during a monetary incentive delay task controlling for sex, age, other substance use, and family history of substance use disorder. Of 108 participants, 39 (36.1%) were female and mean (SD) age at baseline was 20.1 (1.4) years. Greater marijuana use was associated with later blunted activation in the NAcc during reward anticipation (time 1 to time 2: β = -0.26, P = .04; time 2 to time 3: β = -0.25, P = .01). When the cross-lagged model was tested with the inclusion of previous and concurrent cigarette use, the effect of marijuana use from time 2 to time 3 remained significant (β = -0.29; P = .005) and the effect of cigarette use was nonsignificant. The findings of this study indicate that marijuana use is associated with decreased neural response in the NAcc during the anticipation of nondrug rewards. Over time, marijuana use may alter anticipatory reward processing in the NAcc, which may increase the risk for continued drug use and later addiction.

CognitiveConstruct

RewardProcessing

10.1001/jamapsychiatry.2016.1135

JAMA psychiatry

JAMA Psychiatry

Polygenic Risk of Psychosis and Ventral Striatal Activation During Reward Processing in Healthy Adolescents.

Psychotic disorders are characterized by attenuated activity in the brain's valuation system in key reward processing areas, such as the ventral striatum (VS), as measured with functional magnetic resonance imaging. To examine whether common risk variants for psychosis are associated with individual variation in the VS. A cross-sectional study of a large cohort of adolescents from the IMAGEN study (a European multicenter study of reinforcement sensitivity in adolescents) was performed from March 1, 2008, through December 31, 2011. Data analysis was conducted from October 1, 2015, to January 9, 2016. Polygenic risk profile scores (RPSs) for psychosis were generated for 1841 healthy adolescents. Sample size and characteristics varied across regression analyses, depending on mutual information available (N = 1524-1836). Reward-related brain function was assessed with blood oxygen level dependency (BOLD) in the VS using the monetary incentive delay (MID) task, distinguishing reward anticipation and receipt. Behavioral impulsivity, IQ, MID task performance, and VS BOLD were regressed against psychosis RPS at 4 progressive P thresholds (P < .01, P < .05, P < .10, and P < .50 for RPS models 1-4, respectively). In a sample of 1841 healthy adolescents (mean age, 14.5 years; 906 boys and 935 girls), we replicated an association between increasing psychosis RPS and reduced IQ (matrix reasoning: corrected P = .003 for RPS model 2, 0.4% variance explained), supporting the validity of the psychosis RPS models. We also found a nominally significant association between increased psychosis RPS and reduced MID task performance (uncorrected P = .03 for RPS model 4, 0.2% variance explained). Our main finding was a positive association between psychosis RPS and VS BOLD during reward anticipation at all 4 psychosis RPS models and for 2 P thresholds for reward receipt (RPS models 1 and 3), correcting for the familywise error rate (0.8%-1.9% variance explained). These findings support an association between psychosis RPS and VS BOLD in adolescents. Genetic risk for psychosis may shape an individual's response to rewarding stimuli.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2016.00100

Frontiers in psychiatry

Front Psychiatry

Reward Learning, Neurocognition, Social Cognition, and Symptomatology in Psychosis.

Patients with psychosis spectrum disorders exhibit deficits in social and neurocognition, as well as hallmark abnormalities in motivation and reward processing. Aspects of reward processing may overlap behaviorally and neurobiologically with some elements of cognitive functioning, and abnormalities in these processes may share partially overlapping etiologies in patients. However, whether reward processing and cognition are associated across the psychoses and linked to state and trait clinical symptomatology is unclear. The present study examined associations between cognitive functioning, reward learning, and clinical symptomatology in a cross-diagnostic sample. Patients with schizophrenia (SZ; n = 37), bipolar I disorder with psychosis (BD; n = 42), and healthy controls (n = 29) were assessed for clinical symptoms (patients only), neurocognitive functioning using the MATRICS Battery (MCCB) and reward learning using the probabilistic reward task (PRT). Groups were compared on neurocognition and PRT response bias, and associations between PRT response bias and neurocognition or clinical symptoms were examined controlling for demographic variables and PRT task difficulty (discriminability). Patients with SZ performed worse than controls on most measures of neurocognition; patients with BD exhibited deficits in some domains between the level of patients with SZ and controls. The SZ - but not BD - group exhibited deficits in social cognition compared to controls. Patients and controls did not differ on PRT response bias, but did differ on PRT discriminability. Better response bias across the sample was associated with poorer social cognition, but not neurocognition; conversely, discriminability was associated with neurocognition but not social cognition. Symptoms of psychosis, particularly negative symptoms, were associated with poorer response bias across patient groups. Reward learning was associated with symptoms of psychosis - in particular negative symptoms - across diagnoses, and was predictive of worse social cognition. Reward learning was not associated with neurocognitive performance, suggesting that, across patient groups, social cognition but not neurocognition may share common pathways with this aspect of reinforcement learning. Better understanding of how cognitive dysfunction and reward processing deficits relate to one another, to other key symptom dimensions (e.g., psychosis), and to diagnostic categories, may help clarify shared etiological pathways and guide efforts toward targeted treatment approaches.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2016.00294

Frontiers in human neuroscience

Front Hum Neurosci

Intermittent Theta Burst Stimulation Increases Reward Responsiveness in Individuals with Higher Hedonic Capacity.

Repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex (DLPFC) has been documented to influence striatal and orbitofrontal dopaminergic activity implicated in reward processing. However, the exact neuropsychological mechanisms of how DLPFC stimulation may affect the reward system and how trait hedonic capacity may interact with the effects remains to be elucidated. In this sham-controlled study in healthy individuals, we investigated the effects of a single session of neuronavigated intermittent theta burst stimulation (iTBS) on reward responsiveness, as well as the influence of trait hedonic capacity. We used a randomized crossover single session iTBS design with an interval of 1 week. We assessed reward responsiveness using a rewarded probabilistic learning task and measured individual trait hedonic capacity (the ability to experience pleasure) with the temporal experience of pleasure scale questionnaire. As expected, the participants developed a response bias toward the most rewarded stimulus (rich stimulus). Reaction time and accuracy for the rich stimulus were respectively shorter and higher as compared to the less rewarded stimulus (lean stimulus). Active or sham stimulation did not seem to influence the outcome. However, when taking into account individual trait hedonic capacity, we found an early significant increase in the response bias only after active iTBS. The higher the individual's trait hedonic capacity, the more the response bias toward the rich stimulus increased after the active stimulation. When taking into account trait hedonic capacity, one active iTBS session over the left DLPFC improved reward responsiveness in healthy male participants with higher hedonic capacity. This suggests that individual differences in hedonic capacity may influence the effects of iTBS on the reward system.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2016.00234

Frontiers in neuroscience

Front Neurosci

Effects of Body Mass Index and Body Fat Percent on Default Mode, Executive Control, and Salience Network Structure and Function.

It is well established that obesity decreases overall life expectancy and increases the risk of several adverse health conditions. Mounting evidence indicates that body fat is likely also associated with structural and functional brain changes, reduced cognitive function, and greater impulsivity. However, previously reported differences in brain structure and function have been variable across studies and difficult to reconcile due to sample population and methodological differences. To clarify these issues, we correlated two independent measures of body composition-i.e., body mass index (BMI) and body fat percent (BFP)-with structural and functional neuroimaging data obtained from a cohort of 32 neurologically healthy adults. Whole-brain voxel-wise analyses indicated that higher BMI and BFP were associated with widespread decreases in gray matter volume, white matter volume, and white matter microstructure (including several regions, such as the striatum and orbitofrontal cortex, which may influence value assessment, habit formation, and decision-making). Moreover, closer examination of resting state functional connectivity, white matter volume, and white matter microstructure throughout the default mode network (DMN), executive control network (ECN), and salience network (SN) revealed that higher BMI and BFP were associated with increased SN functional connectivity and decreased white matter volumes throughout all three networks (i.e., the DMN, ECN, and SN). Taken together, these findings: (1) offer a biologically plausible explanation for reduced cognitive performance, greater impulsivity, and altered reward processing among overweight individuals, and (2) suggest neurobiological mechanisms (i.e., altered functional and structural brain connectivity) that may affect overweight individuals' ability to establish and maintain healthy lifestyle choices.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2016.00271

Frontiers in human neuroscience

Front Hum Neurosci

Understanding Neuronal Architecture in Obesity through Analysis of White Matter Connection Strength.

Despite the prevalence of obesity, our understanding of its neurobiological underpinnings is insufficient. Diffusion weighted imaging and calculation of white matter connection strength are methods to describe the architecture of anatomical white matter tracts. This study is aimed to characterize white matter architecture within taste-reward circuitry in a population of obese individuals. Obese (n = 18, age = 28.7 ± 8.3 years) and healthy control (n = 24, age = 27.4 ± 6.3 years) women underwent diffusion weighted imaging. Using probabilistic fiber tractography (FSL PROBTRACKX2 toolbox) we calculated connection strength within 138 anatomical white matter tracts. Obese women (OB) displayed lower and greater connectivity within taste-reward circuitry compared to controls (Wilks' λ < 0.001; p < 0.001). Connectivity was lower in white matter tracts connecting insula, amygdala, prefrontal cortex (PFC), orbitofrontal cortex (OFC) and striatum. Connectivity was greater between the amygdala and anterior cingulate cortex (ACC). This study indicates that lower white matter connectivity within white matter tracts of insula-fronto-striatal taste-reward circuitry are associated with obesity as well as greater connectivity within white matter tracts connecting the amygdala and ACC. The specificity of regions suggests sensory integration and reward processing are key associations that are altered in and might contribute to obesity.

CognitiveConstruct

RewardProcessing

10.3233/JPD-160828

Journal of Parkinson's disease

J Parkinsons Dis

Impulse Control Disorders in Parkinson's Disease are Associated with Alterations in Reward-Related Cortical Oscillations.

Impulse control disorders (ICDs) in Parkinson's disease (PD) are related to treatment with dopamine agonists, which is thought to deregulate the dopaminergic mesolimbic pathway and impair reward evaluation. EEG studies in healthy controls (HCs) have suggested that the increase in theta power observed after negative outcome is a marker of reward processing. To compare outcome-locked, event-related spectral perturbation in a gambling task in PD patients with and without ICDs and in HCs. Twelve PD patients with ICDs, 12 PD patients without ICDs and 14 HCs underwent EEG while performing a gambling task. The groups were compared in terms of (i) the peak EEG power in the theta (4-7 Hz), alpha (8-14 Hz) and beta (15-30 Hz) frequency bands between 200 and 500 ms after the outcome, and (ii) time-frequency plots at Fz, FCz and Cz. Positive outcomes were associated with greater theta power than negative outcomes in patients without ICDs and in HCs, but not in patients with ICDs. Patients with ICDs and HCs displayed greater theta power following unexpectedly high outcomes. HCs displayed greater beta power following high amplitude than low amplitude outcomes, whereas patients with ICD showed the opposite pattern. In PD, ICDs are associated with (i) weaker modulation of frontocentral theta power by reward valence, (ii) greater frontocentral theta power following unexpected, high outcomes, and (iii) a reversal of the effect of risk on beta oscillations. These observations are consistent with an impairment in prediction error computation in the medial prefrontal cortex.

CognitiveConstruct

RewardProcessing

10.1016/j.bandc.2016.06.005

Brain and cognition

Brain Cogn

The procrastinators want it now: Behavioral and event-related potential evidence of the procrastination of intertemporal choices.

Much past research has focused on the correlation between procrastination and personality traits (e.g., impulsivity). According to the temporal motivation theory, procrastinators are impulsive and sensitive to delays in time. However, there is still a lack of direct evidence of the tendency of procrastinators to prefer immediate over future rewards. To investigate this question, we recorded event-related potentials (ERPs) in the brain while participants performed an intertemporal choice task involving both time delay and reward processing. The participants were assigned to a high procrastination group and a low procrastination group according to their scores on self-report measures. We found that high procrastination participants preferred immediate rewards compared to future ones whereas low procrastination participants did not. High procrastinators also exhibited a larger and delayed P2 component, indicating delay time processing and abnormal reward processing. No significant effect associated with procrastination was found on the P300 component. Taken together, these findings suggest that high procrastinators are more impulsive and encode the information of delay time more slowly but with a higher level of motivation-driven attention. The current study substantiates higher impulsivity in procrastination and verifies that a difference exists in the sensitivity to time delay between high and low procrastinators.

CognitiveConstruct

RewardProcessing

10.1038/nature18601

Nature

Nature

Basal forebrain projections to the lateral habenula modulate aggression reward.

Maladaptive aggressive behaviour is associated with a number of neuropsychiatric disorders and is thought to result partly from the inappropriate activation of brain reward systems in response to aggressive or violent social stimuli. Nuclei within the ventromedial hypothalamus, extended amygdala and limbic circuits are known to encode initiation of aggression; however, little is known about the neural mechanisms that directly modulate the motivational component of aggressive behaviour. Here we established a mouse model to measure the valence of aggressive inter-male social interaction with a smaller subordinate intruder as reinforcement for the development of conditioned place preference (CPP). Aggressors develop a CPP, whereas non-aggressors develop a conditioned place aversion to the intruder-paired context. Furthermore, we identify a functional GABAergic projection from the basal forebrain (BF) to the lateral habenula (lHb) that bi-directionally controls the valence of aggressive interactions. Circuit-specific silencing of GABAergic BF-lHb terminals of aggressors with halorhodopsin (NpHR3.0) increases lHb neuronal firing and abolishes CPP to the intruder-paired context. Activation of GABAergic BF-lHb terminals of non-aggressors with channelrhodopsin (ChR2) decreases lHb neuronal firing and promotes CPP to the intruder-paired context. Finally, we show that altering inhibitory transmission at BF-lHb terminals does not control the initiation of aggressive behaviour. These results demonstrate that the BF-lHb circuit has a critical role in regulating the valence of inter-male aggressive behaviour and provide novel mechanistic insight into the neural circuits modulating aggression reward processing.

CognitiveConstruct

RewardProcessing

10.1038/tp.2016.107

Translational psychiatry

Transl Psychiatry

Disentangling the autism-anxiety overlap: fMRI of reward processing in a community-based longitudinal study.

Up to 40% of youth with autism spectrum disorder (ASD) also suffer from anxiety, and this comorbidity is linked with significant functional impairment. However, the mechanisms of this overlap are poorly understood. We investigated the interplay between ASD traits and anxiety during reward processing, known to be affected in ASD, in a community sample of 1472 adolescents (mean age=14.4 years) who performed a modified monetary incentive delay task as part of the Imagen project. Blood-oxygen-level dependent (BOLD) responses to reward anticipation and feedback were compared using a 2x2 analysis of variance test (ASD traits: low/high; anxiety symptoms: low/high), controlling for plausible covariates. In addition, we used a longitudinal design to assess whether neural responses during reward processing predicted anxiety at 2-year follow-up. High ASD traits were associated with reduced BOLD responses in dorsal prefrontal regions during reward anticipation and negative feedback. Participants with high anxiety symptoms showed increased lateral prefrontal responses during anticipation, but decreased responses following feedback. Interaction effects revealed that youth with combined ASD traits and anxiety, relative to other youth, showed high right insula activation when anticipating reward, and low right-sided caudate, putamen, medial and lateral prefrontal activations during negative feedback (all clusters PFWE<0.05). BOLD activation patterns in the right dorsal cingulate and right medial frontal gyrus predicted new-onset anxiety in participants with high but not low ASD traits. Our results reveal both quantitatively enhanced and qualitatively distinct neural correlates underlying the comorbidity between ASD traits and anxiety. Specific neural responses during reward processing may represent a risk factor for developing anxiety in ASD youth.

CognitiveConstruct

RewardProcessing

10.1111/adb.12413

Addiction biology

Addict Biol

Association between pubertal stage at first drink and neural reward processing in early adulthood.

Puberty is a critical time period during human development. It is characterized by high levels of risk-taking behavior, such as increased alcohol consumption, and is accompanied by various neurobiological changes. Recent studies in animals and humans have revealed that the pubertal stage at first drink (PSFD) significantly impacts drinking behavior in adulthood. Moreover, neuronal alterations of the dopaminergic reward system have been associated with alcohol abuse or addiction. This study aimed to clarify the impact of PSFD on neuronal characteristics of reward processing linked to alcohol-related problems. One hundred sixty-eight healthy young adults from a prospective study covering 25 years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. PSFD was determined according to the age at menarche or Tanner stage of pubertal development, respectively. Alcohol-related problems in early adulthood were assessed with the Alcohol Use Disorder Identification Test (AUDIT). During reward anticipation, decreased fMRI activation of the frontal cortex and increased preparatory EEG activity (contingent negative variation) occurred with pubertal compared to postpubertal first alcohol intake. Moreover, alcohol-related problems during early adulthood were increased in pubertal compared to postpubertal beginners, which was mediated by neuronal activation of the right medial frontal gyrus. At reward delivery, increased fMRI activation of the left caudate and higher feedback-related EEG negativity were detected in pubertal compared to postpubertal beginners. Together with animal findings, these results implicate PSFD as a potential modulator of psychopathology, involving altered reward anticipation. Both PSFD timing and reward processing might thus be potential targets for early prevention and intervention.

CognitiveConstruct

RewardProcessing

10.1177/1744806916654145

Molecular pain

Mol Pain

Estrogen-dependent visceral hypersensitivity following stress in rats: An fMRI study.

We used functional MRI and a longitudinal design to investigate the brain mechanisms in a previously reported estrogen-dependent visceral hypersensitivity model. We hypothesized that noxious visceral stimulation would be associated with activation of the insula, anterior cingulate cortex, and amygdala, and that estrogen-dependent, stress-induced visceral hypersensitivity would both enhance activation of these regions and recruit activation of other brain areas mediating affect and reward processing. Ovariectomized rats were treated with estrogen (17 β-estradiol, E2) or vehicle (n = 5 per group) and scanned in a 7T MRI at three different time points: pre-stress (baseline), 2 days post-stress, and 18 days post-stress. Stress was induced via a forced-swim paradigm. In a separate group of ovariectomized rats, E2 treatment induced visceral hypersensitivity at the 2 days post-stress time point, and this hypersensitivity returned to baseline at the 18 days post-stress time point. Vehicle-treated rats show no hypersensitivity following stress. During the MRI scans, rats were exposed to noxious colorectal distention. Across groups and time points, noxious visceral stimulation led to activations in the insula, anterior cingulate, and left amygdala, parabrachial nuclei, and cerebellum. A group-by-time interaction was seen in the right amygdala, ventral striatum-pallidum, cerebellum, hippocampus, mediodorsal thalamus, and pontine nuclei. Closer inspection of the data revealed that vehicle-treated rats showed consistent activations and deactivations across time, whereas estrogen-treated animals showed minimal deactivation with noxious visceral stimulation. This unexpected finding suggests that E2 may dramatically alter visceral nociceptive processing in the brain following an acute stressor. This study is the first to examine estrogen-stress dependent interactions in response to noxious visceral stimulation using functional MRI. Future studies that include other control groups and larger sample sizes are needed to fully understand the interactions between sex hormones, stress, and noxious stimulation on brain activity.

CognitiveConstruct

RewardProcessing

10.1080/00952990.2016.1185434

The American journal of drug and alcohol abuse

Am J Drug Alcohol Abuse

Exercise as an adjunctive treatment for cannabis use disorder.

Despite cannabis being the most widely used illicit substance in the United States, individuals diagnosed with cannabis use disorder (CUD) have few well-researched, affordable treatment options available to them. Although found to be effective for improving treatment outcomes in other drug populations, exercise is an affordable and highly accessible treatment approach that has not been routinely investigated in cannabis users. The aim of this paper is to inform the topic regarding exercise's potential as an adjunctive treatment for individuals with CUD. We reviewed the evidence surrounding cannabis use and its current treatment in the United States, explored the rationale for including exercise in the treatment of substance use disorders (SUDs), and in particular, proposed a biological mechanism (i.e., endocannabinoids (eCBs)) that should be examined when utilizing exercise for the treatment of CUD. Cannabis use is widespread and increasing in the United States. Chronic, heavy cannabis use may dysregulate the endogenous cannabinoid system, which has implications for several psychobiological processes that interact with the eCB system such as reward processing and the stress response. Given that exercise is a potent activator of the eCB system, it is mechanistically plausible that exercise could be an optimal method to supplement cessation efforts by reducing psychophysical withdrawal, managing stress, and attenuating drug cravings. We suggest there is a strong behavioral and physiological rationale to design studies which specifically assess the efficacy of exercise, in combination with other therapies, in treating CUD. Moreover, it will be especially important to include the investigation of psychobiological mechanisms (e.g., eCBs, hippocampal volume), which have been associated with both exercise and SUDs, to examine the broader impact of exercise on behavioral and physiological responses to treatment.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2016.06.003

Psychiatry research. Neuroimaging

Psychiatry Res Neuroimaging

Divergent relationship of depression severity to social reward responses among patients with bipolar versus unipolar depression.

Neuroimaging studies of mood disorders demonstrate abnormalities in brain regions implicated in reward processing. However, there is a paucity of research investigating how social rewards affect reward circuit activity in these disorders. Here, we evaluated the relationship of both diagnostic category and dimensional depression severity to reward system function in bipolar and unipolar depression. In total, 86 adults were included, including 24 patients with bipolar depression, 24 patients with unipolar depression, and 38 healthy comparison subjects. Participants completed a social reward task during 3T BOLD fMRI. On average, diagnostic groups did not differ in activation to social reward. However, greater depression severity significantly correlated with reduced bilateral ventral striatum activation to social reward in the bipolar depressed group, but not the unipolar depressed group. In addition, decreased left orbitofrontal cortical activation correlated with more severe symptoms in bipolar depression, but not unipolar depression. These differential dimensional effects resulted in a significant voxelwise group by depression severity interaction. Taken together, these results provide initial evidence that deficits in social reward processing are differentially related to depression severity in the two disorders.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2016.06.005

Journal of affective disorders

J Affect Disord

Sustained anterior cingulate cortex activation during reward processing predicts response to psychotherapy in major depressive disorder.

The purpose of the present investigation was to evaluate whether pre-treatment neural activation in response to rewards is a predictor of clinical response to Behavioral Activation Therapy for Depression (BATD), an empirically validated psychotherapy that decreases depressive symptoms by increasing engagement with rewarding stimuli and reducing avoidance behaviors. Participants were 33 outpatients with major depressive disorder (MDD) and 20 matched controls. We examined group differences in activation, and the capacity to sustain activation, across task runs using functional magnetic resonance imaging (fMRI) and the monetary incentive delay (MID) task. Hierarchical linear modeling was used to investigate whether pre-treatment neural responses predicted change in depressive symptoms over the course of BATD treatment. MDD and Control groups differed in sustained activation during reward outcomes in the right nucleus accumbens, such that the MDD group experienced a significant decrease in activation in this region from the first to second task run relative to controls. Pretreatment anhedonia severity and pretreatment task-related reaction times were predictive of response to treatment. Furthermore, sustained activation in the anterior cingulate cortex during reward outcomes predicted response to psychotherapy; patients with greater sustained activation in this region were more responsive to BATD treatment. The current study only included a single treatment condition, thus it unknown whether these predictors of treatment response are specific to BATD or psychotherapy in general. Findings add to the growing body of literature suggesting that the capacity to sustain neural responses to rewards may be a critical endophenotype of MDD.

CognitiveConstruct

RewardProcessing

10.2337/dc16-0094

Diabetes care

Diabetes Care

Neuronal Food Reward Activity in Patients With Type 2 Diabetes With Improved Glycemic Control After Bariatric Surgery.

Obesity and type 2 diabetes mellitus (T2DM) are associated with altered food-related neuronal functions. Besides weight loss, substantial improvement of glucose metabolism in patients with T2DM can be achieved by bariatric surgery. We aimed to target the neuronal and behavioral correlates of improved glycemic control after bariatric surgery. Two patient groups with T2DM were recruited. The treatment group (n = 12) consisted of patients who had undergone Roux-en-Y gastric bypass (RYGB) surgery, and a control group consisted of patients who did not undergo surgery (n = 12). The groups were matched for age and current BMI. HbA1c was matched by using the presurgical HbA1c of the RYGB group and the current HbA1c of the nonsurgical group. Neuronal activation during a food reward task was measured using functional MRI (fMRI). Behavioral data were assessed through questionnaires. RYGB improved HbA1c from 7.07 ± 0.50 to 5.70 ± 0.16% (P < 0.05) and BMI from 52.21 ± 1.90 to 35.71 ± 0.84 kg/m(2) (P < 0.001). Behavioral results showed lower wanting and liking scores as well as lower eating behavior-related pathologies for the patients after RYGB than for similar obese subjects without surgery but with impaired glycemic control. The fMRI analysis showed higher activation for the nonsurgical group in areas associated with inhibition and reward as well as in the precuneus, a major connectivity hub in the brain. By contrast, patients after RYGB showed higher activation in the visual, motor, cognitive control, memory, and gustatory regions. In obese patients with diabetes, RYGB normalizes glycemic control and leads to food reward-related brain activation patterns that are different from those of obese patients with less-well-controlled T2DM and without bariatric surgery. The differences in food reward processing might be one factor in determining the outcome of bariatric surgery in patients with T2DM.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsycho.2016.06.002

Biological psychology

Biol Psychol

The effects of reward magnitude on reward processing: An averaged and single trial event-related potential study.

From a neurobiological and motivational perspective, the feedback-related negativity (FRN) and reward positivity (RewP) event-related potential (ERP) components should increase with reward magnitude (reward associated with valence (success/failure) feedback). To test this hypothesis, we recorded participants' electroencephalograms while presenting them with potential monetary rewards ($0.00-$4.96) pre-trial for each trial of a reaction time task and presenting them with valence feedback post-trial. Averaged ERPs time-locked to valence feedback were extracted, and results revealed a valence by magnitude interaction for neural activity in the FRN/RewP time window. This interaction was driven by magnitude affecting RewP, but not FRN, amplitude. Moreover, single trial ERP analyses revealed a reliable correlation between magnitude and RewP, but not FRN, amplitude. Finally, P3b and late positive potential (LPP) amplitudes were affected by magnitude. Results partly support the neurobiological (dopamine) account of the FRN/RewP and suggest motivation affects feedback processing, as indicated by multiple ERP components.

CognitiveConstruct

RewardProcessing

10.1016/j.scog.2016.04.002

Schizophrenia research. Cognition

Schizophr Res Cogn

Are persistent delusions in schizophrenia associated with aberrant salience?

It has been suggested that positive psychotic symptoms reflect 'aberrant salience'. Previously we provided support for this hypothesis in first-episode schizophrenia patients, demonstrating that delusional symptoms were associated with aberrant reward processing, indexed by the Salience Attribution Test (SAT). Here we tested whether salience processing is abnormal in schizophrenia patients with long-standing treatment-refractory persistent delusions (TRS). Eighteen medicated TRS patients and 31 healthy volunteers completed the SAT, on which participants made a speeded response to earn money in the presence of cues. Each cue comprised two visual dimensions, colour and form. Reinforcement probability varied over one of these dimensions (task-relevant), but not the other (task-irrelevant). Participants responded significantly faster on high-probability relative to low-probability trials, representing implicit adaptive salience; this effect was intact in TRS patients. By contrast, TRS patients were impaired on the explicit adaptive salience measure, rating high-probability stimuli less likely to be associated with reward than controls. There was little evidence for elevated aberrant salience in the TRS group. These findings do not support the hypothesis that persistent delusions are related to aberrant motivational salience processing in TRS patients. However, they do support the view that patients with schizophrenia have impaired reward learning.

CognitiveConstruct

RewardProcessing

10.1007/s11571-016-9376-2

Cognitive neurodynamics

Cogn Neurodyn

Functional connectivity between prefrontal cortex and striatum estimated by phase locking value.

The interplay between the prefrontal cortex (PFC) and striatum has an important role in cognitive processes. To investigate interactive functions between the two areas in reward processing, we recorded local field potentials (LFPs) simultaneously from the two areas of two monkeys performing a reward prediction task (large reward vs small reward). The power of the LFPs was calculated in three frequency bands: the beta band (15-29 Hz), the low gamma band (30-49 Hz), and the high gamma band (50-100 Hz). We found that both the PFC and striatum encoded the reward information in the beta band. The reward information was also found in the high gamma band in the PFC, not in the striatum. We further calculated the phase-locking value (PLV) between two LFP signals to measure the phase synchrony between the PFC and striatum. It was found that significant differences occurred between PLVs in different task periods and in different frequency bands. The PLVs in small reward condition were significant higher than that in large reward condition in the beta band. In contrast, the PLVs in the high gamma band were stronger in large reward trials than in small trials. These results suggested that the functional connectivity between the PFC and striatum depended on the task periods and reward conditions. The beta synchrony between the PFC and striatum may regulate behavioral outputs of the monkeys in the small reward condition.

CognitiveConstruct

RewardProcessing

10.1002/hbm.23279

Human brain mapping

Hum Brain Mapp

Abnormal reward circuitry in anorexia nervosa: A longitudinal, multimodal MRI study.

Anorexia nervosa (AN) is a debilitating illness and existing interventions are only modestly effective. This study aimed to determine whether AN pathophysiology is associated with altered connections within fronto-accumbal circuitry subserving reward processing. Diffusion and resting-state functional MRI scans were collected in female inpatients with AN (n = 22) and healthy controls (HC; n = 18) between the ages of 16 and 25 years. Individuals with AN were scanned during the acute, underweight phase of the illness and again following inpatient weight restoration. HC were scanned twice over the same timeframe. Based on univariate and multivariate analyses of fronto-accumbal circuitry, underweight individuals with AN were found to have increased structural connectivity (diffusion probabilistic tractography), increased white matter anisotropy (tract-based spatial statistics), increased functional connectivity (seed-based correlation in resting-state fMRI), and altered effective connectivity (spectral dynamic causal modeling). Following weight restoration, fronto-accumbal structural connectivity continued to be abnormally increased bilaterally with large (partial η  = 0.387; right NAcc-OFC) and moderate (partial η  = 0.197; left NAcc-OFC) effect sizes. Increased structural connectivity within fronto-accumbal circuitry in the underweight state correlated with severity of eating disorder symptoms. Taken together, the findings from this longitudinal, multimodal neuroimaging study offer converging evidence of atypical fronto-accumbal circuitry in AN. Hum Brain Mapp 37:3835-3846, 2016. © 2016 Wiley Periodicals, Inc.

CognitiveConstruct

RewardProcessing

10.1007/s00213-016-4323-9

Psychopharmacology

Psychopharmacology (Berl)

Responses to drugs of abuse and non-drug rewards in leptin deficient ob/ob mice.

Although leptin receptors are found in hypothalamic nuclei classically associated with homeostatic feeding mechanisms, they are also present in brain regions known to regulate hedonic-based feeding, natural reward processing, and responses to drugs of abuse. The ob/ob mouse is deficient in leptin signaling, and previous work has found altered mesolimbic dopamine signaling and sensitivity to the locomotor activating effects of amphetamine in these mice. We directly assessed responses to three drugs of abuse and non-drug rewards in the leptin-deficient ob/ob mouse. Ob/ob mice were tested in assays of sweet preference, novelty seeking, and drug reward/reinforcement. In assays of novelty seeking, novel open field activity and operant sensation seeking were reduced in ob/ob mice, although novel object interaction and novel environment preference were comparable to wild types. We also found that ob/ob mice had specific phenotypes in regard to cocaine: conditioned place preference for 2.5 mg/kg was increased, while the locomotor response to 10 mg/kg was reduced, and cocaine self-administration was the same as wild types. Ob/ob mice also acquired self-administration of the potent opioid remifentanil, but breakpoints for the drug were significantly reduced. Finally, we found significant differences in ethanol drinking in ob/ob mice that correlated negatively with body weight and positively with operant sensation seeking. In conclusion, ob/ob mice displayed task-specific deficits in novelty seeking and dissociable differences in reward/reinforcement associated with cocaine, remifentanil, and ethanol.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2016.00758

Frontiers in psychology

Front Psychol

Combat PTSD and Implicit Behavioral Tendencies for Positive Affective Stimuli: A Brief Report.

Prior cognitive research in posttraumatic stress disorder (PTSD) has focused on automatic responses to negative affective stimuli, including attentional facilitation or disengagement and avoidance action tendencies. More recent research suggests PTSD may also relate to differences in reward processing, which has lead to theories of PTSD relating to approach-avoidance imbalances. The current pilot study assessed how combat-PTSD symptoms relate to automatic behavioral tendencies to both positive and negative affective stimuli. Twenty male combat veterans completed the approach-avoidance task (AAT), Clinician Administered PTSD Scale, Beck Depression Inventory-II, and State-Trait Anger Expression Inventory-II. During the AAT, subjects pulled (approach) or pushed (avoid) a joystick in response to neutral, happy, disgust, and angry faces based on border color. Bias scores were calculated for each emotion type (avoid-approach response latency differences). Main and interaction effects for psychological symptom severity and emotion type on bias score were assessed using linear mixed models. There was a significant interaction between PTSD symptoms and emotion type, driven primarily by worse symptoms relating to a greater bias to avoid happy faces. Post hoc tests revealed that veterans with worse PTSD symptoms were slower to approach as well as quicker to avoid happy faces. Neither depressive nor anger symptoms related to avoid or approach tendencies of emotional stimuli. Posttraumatic stress disorder severity was associated with a bias for avoiding positive affective stimuli. These results provide further evidence that PTSD may relate to aberrant processing of positively valenced, or rewarding stimuli. Implicit responses to rewarding stimuli could be an important factor in PTSD pathology and treatment. Specifically, these findings have implications for recent endeavors in using computer-based interventions to influence automatic approach-avoidance tendencies.

CognitiveConstruct

RewardProcessing

10.1177/0956797616645673

Psychological science

Psychol Sci

The Power of the Like in Adolescence: Effects of Peer Influence on Neural and Behavioral Responses to Social Media.

We investigated a unique way in which adolescent peer influence occurs on social media. We developed a novel functional MRI (fMRI) paradigm to simulate Instagram, a popular social photo-sharing tool, and measured adolescents' behavioral and neural responses to likes, a quantifiable form of social endorsement and potential source of peer influence. Adolescents underwent fMRI while viewing photos ostensibly submitted to Instagram. They were more likely to like photos depicted with many likes than photos with few likes; this finding showed the influence of virtual peer endorsement and held for both neutral photos and photos of risky behaviors (e.g., drinking, smoking). Viewing photos with many (compared with few) likes was associated with greater activity in neural regions implicated in reward processing, social cognition, imitation, and attention. Furthermore, when adolescents viewed risky photos (as opposed to neutral photos), activation in the cognitive-control network decreased. These findings highlight possible mechanisms underlying peer influence during adolescence.

CognitiveConstruct

RewardProcessing

10.1007/s12035-016-9934-y

Molecular neurobiology

Mol Neurobiol

Hypothesizing Music Intervention Enhances Brain Functional Connectivity Involving Dopaminergic Recruitment: Common Neuro-correlates to Abusable Drugs.

The goal of this review is to explore the clinical significance of music listening on neuroplasticity and dopaminergic activation by understanding the role of music therapy in addictive behavior treatment. fMRI data has shown that music listening intensely modifies mesolimbic structural changes responsible for reward processing (e.g., nucleus accumbens [NAc]) and may control the emotional stimuli's effect on autonomic and physiological responses (e.g., hypothalamus). Music listening has been proven to induce the endorphinergic response blocked by naloxone, a common opioid antagonist. NAc opioid transmission is linked to the ventral tegmental area (VTA) dopamine release. There are remarkable commonalities between listening to music and the effect of drugs on mesolimbic dopaminergic activation. It has been found that musical training before the age of 7 results in changes in white-matter connectivity, protecting carriers with low dopaminergic function (DRD2A1 allele, etc.) from poor decision-making, reward dependence, and impulsivity. In this article, we briefly review a few studies on the neurochemical effects of music and propose that these findings are relevant to the positive clinical findings observed in the literature. We hypothesize that music intervention enhances brain white matter plasticity through dopaminergic recruitment and that more research is needed to explore the efficacy of these therapies.

CognitiveConstruct

RewardProcessing

10.1016/j.comppsych.2016.04.011

Comprehensive psychiatry

Compr Psychiatry

Study of positive and negative feedback sensitivity in psychosis using the Wisconsin Card Sorting Test.

Schizophrenia involves marked motivational and learning deficits that may reflect abnormalities in reward processing. The purpose of this study was to examine positive and negative feedback sensitivity in schizophrenia using computational modeling derived from the Wisconsin Card Sorting Test (WCST). We also aimed to explore feedback sensitivity in a sample with bipolar disorder. Eighty-three individuals with schizophrenia and 27 with bipolar disorder were included. Demographic, clinical and cognitive outcomes, together with the WCST, were considered in both samples. Computational modeling was performed using the R syntax to calculate 3 parameters based on trial-by-trial execution on the WCST: reward sensitivity (R), punishment sensitivity (P), and choice consistency (D). The associations between outcome variables and the parameters were investigated. Positive and negative sensitivity showed deficits, but P parameter was clearly diminished in schizophrenia. Cognitive variables, age, and symptoms were associated with R, P, and D parameters in schizophrenia. The sample with bipolar disorder would show cognitive deficits and feedback abnormalities to a lesser extent than individuals with schizophrenia. Negative feedback sensitivity demonstrated greater deficit in both samples. Idiosyncratic cognitive requirements in the WCST might introduce confusion when supposing model-free reinforcement learning. Negative symptoms of schizophrenia were related to lower feedback sensitivity and less goal-directed patterns of choice.

CognitiveConstruct

RewardProcessing

10.1111/adb.12406

Addiction biology

Addict Biol

Bi-directional cannabinoid signalling in the basolateral amygdala controls rewarding and aversive emotional processing via functional regulation of the nucleus accumbens.

Functional connections between the basolateral amygdala (BLA) and nucleus accumbens (NAc) are involved critically in opiate-reward processing. In the BLA, inhibitory GABAergic substrates are inhibited by cannabinoid CB1 receptor (CB1R) activation and can modulate BLA projections to various limbic regions, including the NAc. However, the potential role of CB1R transmission in the regulation of opiate-related memory formation via the BLA → NAc circuit is not understood. Using an unbiased conditioned place preference paradigm in rats, we examined the effects of intra-BLA CB1R modulation by either direct pharmacological activation or blockade of CB1R transmission. We report that intra-BLA CB1R activation switches normally rewarding effects of morphine into strongly aversive effects. In contrast, CB1R blockade strongly potentiates normally subreward threshold effects of morphine. Next, using targeted microinfusions of an NMDA receptor antagonist to either the core or shell (NASh) subdivisions of the NAc, we found that selective blockade of NMDA transmission in the NA shell, but not core, prevented both intra-BLA CB1 blockade-mediated opiate reward potentiation and CB1 activation-mediated aversion effects. Finally, using multi-unit, in vivo electrophysiological recordings in the NASh, we report that the ability of intra-BLA CB1R modulation to control opiate reward salience and motivational valence is associated with distinct reward or aversion neuronal activity patterns and bi-directional regulation of intra-NASh fast-spiking interneurons versus medium spiny neurons. These findings identify a unique mechanism whereby bi-directional BLA CB1R transmission can regulate opiate-related motivational processing and control affective states through functional modulation of mesolimbic neuronal activity.

CognitiveConstruct

RewardProcessing

10.1038/ijo.2016.103

International journal of obesity (2005)

Int J Obes (Lond)

Acute and short-term effects of caloric restriction on metabolic profile and brain activation in obese, postmenopausal women.

Early anthropometric and metabolic changes during a caloric-restricted diet in obese postmenopausal women and correlations between these factors with activity in brain areas involved in processing of visual food related stimuli were investigated. An 8-week prospective intervention study of 18 healthy postmenopausal women, with a body mass index of 30-35 kg m. The first 2 weeks subjects were on an isocaloric diet and 4 weeks on a 1000 kcal restricted diet followed by 2 weeks on an isocaloric diet. Anthropometric and laboratory analyses were performed weekly during the isocaloric diet and three times a week during the caloric-restricted diet. Functional magnetic resonance imaging scans were obtained before and after the caloric restriction in four separate sessions (fasting or sated). Generalized Estimating Equations analysis was used for data analysis. A mean weight loss of 4.2±0.5 kg (4.8%) and a 4.2±0.4 cm decline in waist circumference were achieved. In the first week of caloric restriction, triglyceride, leptin, resistin and adiponectin levels as well as systolic blood pressure decreased and insulin-like growth factor-binding protein 1 levels increased. During and after weight loss, a significant increase in ghrelin levels was observed. Before weight loss, increased activation of the right amygdala was seen in response to food stimuli, and free fatty acids and glucose correlated with activity in various areas involved in food reward processing. After weight loss, fasting ghrelin and sated leptin levels correlated with activity in these areas. Already in the first week of caloric restriction in obese postmenopausal women, various favourable metabolic changes occur before clinically relevant weight loss is achieved. Activity in the amygdala region and correlations of metabolic factors with activity in brain areas involved in food reward processing differ substantially before and after weight loss.

CognitiveConstruct

RewardProcessing

10.3389/fncel.2016.00111

Frontiers in cellular neuroscience

Front Cell Neurosci

Mutual Control of Cholinergic and Low-Threshold Spike Interneurons in the Striatum.

The striatum is the largest nucleus of the basal ganglia and is crucially involved in action selection and reward processing. Cortical and thalamic inputs to the striatum are processed by local networks in which several classes of interneurons play an important, but still poorly understood role. Here we investigated the interactions between cholinergic and low-threshold spike (LTS) interneurons. LTS interneurons were hyperpolarized by co-application of muscarinic and nicotinic receptor antagonists (atropine and mecamylamine, respectively). Mecamylamine alone also caused hyperpolarizations, while atropine alone caused depolarizations and increased firing. LTS interneurons were also under control of tonic GABA, as application of the GABAA receptor antagonist picrotoxin caused depolarizations and increased firing. Frequency of spontaneous GABAergic events in LTS interneurons was increased by co-application of atropine and mecamylamine or by atropine alone, but reduced by mecamylamine alone. In the presence of picrotoxin and tetrodotoxin (TTX), atropine and mecamylamine depolarized the LTS interneurons. We concluded that part of the excitatory effects of tonic acetylcholine (ACh) on LTS interneurons were due to cholinergic modulation of tonic GABA. We then studied the influence of LTS interneurons on cholinergic interneurons. Application of antagonists of somatostatin or neuropeptide Y (NPY) receptors or of an inhibitor of nitric oxide synthase (L-NAME) did not cause detectable effects in cholinergic interneurons. However, prolonged synchronized depolarizations of LTS interneurons (elicited with optogenetics tools) caused slow-onset depolarizations in cholinergic interneurons, which were often accompanied by strong action potential firing and were fully abolished by L-NAME. Thus, a mutual excitatory influence exists between LTS and cholinergic interneurons in the striatum, providing an opportunity for sustained activation of the two cell types. This activation may endow the striatal microcircuits with the ability to enter a high ACh/high nitric oxide regime when adequately triggered by external excitatory stimuli to these interneurons.

CognitiveConstruct

RewardProcessing

10.1016/j.physbeh.2016.05.024

Physiology & behavior

Physiol Behav

MCH receptor deletion does not impair glucose-conditioned flavor preferences in mice.

The post-oral actions of glucose stimulate intake and condition flavor preferences in rodents. Hypothalamic melanin-concentrating hormone (MCH) neurons are implicated in sugar reward, and this study investigated their involvement in glucose preference conditioning in mice. In Exp. 1 MCH receptor 1 knockout (KO) and C57BL/6 wildtype (WT) mice learned to prefer 8% glucose over an initially more-preferred non-nutritive 0.1% sucralose+saccharin (S+S) solution. In contrast, the KO and WT mice preferred S+S to 8% fructose, which is consistent with this sugar's weak post-oral reinforcing action. In Exp. 2 KO and WT mice were trained to drink a flavored solution (CS+) paired with intragastric (IG) infusion of 16% glucose and a different flavored solution (CS-) paired with IG water. Both groups drank more CS+ than CS- in training and preferred the CS+ to CS- in a 2-bottle test. These results indicate that MCH receptor signaling is not required for flavor preferences conditioned by the post-oral actions of glucose. This contrasts with other findings implicating MCH signaling in other types of sugar reward processing.

CognitiveConstruct

RewardProcessing

10.1186/s40337-016-0106-2

Journal of eating disorders

J Eat Disord

Neurobiological model of the persistence of anorexia nervosa.

Anorexia Nervosa (AN) is characterized by the maintenance of an undernourished, or starved, state. Persistent restrictive eating, or the recurrent intake of a diet that is inadequate to sustain a healthy weight, is the central behavior maintaining AN. To understand this disturbance, we need to understand the neural mechanisms that allow or promote the persistent choice of inadequate caloric intake. While a range of neural disturbances have been reported in AN, abnormalities in systems relevant to reward processing and the development of habit systems have been consistently described in both structural and functional neuroimaging studies. Most recently, brain and behavior have been directly examined by investigating the neural underpinnings of restrictive food choice. These recent data suggest that, among individuals with AN, dorsal frontostriatal circuits play a greater role in guiding decisions regarding what to eat than among healthy individuals. This line of research attempts to leverage advances in the field of cognitive neuroscience to further our understanding of persistent maladaptive choices of individuals with AN, in the hope that such advances will help in the development of novel treatments for this potentially fatal disorder.

CognitiveConstruct

RewardProcessing

10.1111/psyp.12672

Psychophysiology

Psychophysiology

Reward-related neural dysfunction across depression and impulsivity: A dimensional approach.

Recent theoretical models underline reward sensitivity as a potential endophenotype for major depressive disorder. Neural and behavioral evidence reveals depression is associated with reduced reward sensitivity. However, reward dysfunction is not unique to depression, as it is also common across disorders of poor impulse control. We examined the interrelationships of depression (Depression, Anxiety, and Stress Scale [DASS-21]) and impulsivity (UPPS-P Impulsive Behavior Scale) with reward sensitivity among a large, representative sample (N = 260). ERPs were recorded to isolate two neural indicators of consummatory reward processing: initial evaluation of rewards in the 250-350 ms time window postonset of feedback (reward positivity [RewP]), and salience to monetary outcomes (P3). Significant interactions were observed between depression and impulsivity facets across these two stages of reward processing: depression and positive urgency predicted RewP amplitude to reward outcomes (win vs. loss); depression and one other impulsivity trait, (lack of) premeditation, predicted P3 amplitude to monetary outcomes. Conversely, high symptoms of depression were related to three biobehavioral profiles: (1) blunted RewP in conjunction with high positive urgency, (2) combination of blunted RewP and low (lack of) premeditation, and (3) blunted P3 to monetary wins/losses, in conjunction with low (lack of) premeditation. Findings illustrate that reward-related dysfunctions may be optimally conceptualized when examining the interactions between dimensions of internalizing and externalizing psychopathology.

CognitiveConstruct

RewardProcessing

10.1038/srep26426

Scientific reports

Sci Rep

When your pain signifies my gain: neural activity while evaluating outcomes based on another person's pain.

The overlap between pain and reward processing pathways leds researchers to hypothesize that there are interactions between them in the human brain. Two hypotheses have been proposed. The "competition hypothesis" posits that reward can reduce pain-related neural activity and vice versa. The "salience hypothesis" suggests that the motivational salience of pain and reward can be mutually reinforced. However, no study has tested these two hypotheses from temporal perspective as we know. In the present study, pictures depicted other people in painful or non-painful situations were used to indicate the valence of outcomes in a gambling task. The event-related potential results revealed an interaction between another person's pain and outcome valence in multiple time stages. Specifically, the amplitudes of the N1 and P3 were enhanced in the win condition compared with the loss condition when the outcome was indicated by painful picture. This interactions between pain and reward support the salience hypothesis but not the competition hypothesis. The present results provide evidence from human subjects that support the salience hypothesis, which claims that observing other people's pain can enhance the salience of reward.

CognitiveConstruct

RewardProcessing

10.1038/npp.2016.70

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Investigating the Impact of a Genome-Wide Supported Bipolar Risk Variant of MAD1L1 on the Human Reward System.

Recent genome-wide association studies have identified MAD1L1 (mitotic arrest deficient-like 1) as a susceptibility gene for bipolar disorder and schizophrenia. The minor allele of the single-nucleotide polymorphism (SNP) rs11764590 in MAD1L1 was associated with bipolar disorder. Both diseases, bipolar disorder and schizophrenia, are linked to functional alterations in the reward system. We aimed at investigating possible effects of the MAD1L1 rs11764590 risk allele on reward systems functioning in healthy adults. A large homogenous sample of 224 young (aged 18-31 years) participants was genotyped and underwent functional magnetic resonance imaging (fMRI). All participants performed the 'Desire-Reason Dilemma' paradigm investigating the neural correlates that underlie reward processing and active reward dismissal in favor of a long-term goal. We found significant hypoactivations of the ventral tegmental area (VTA), the bilateral striatum and bilateral frontal and parietal cortices in response to conditioned reward stimuli in the risk allele carriers compared with major allele carriers. In the dilemma situation, functional connectivity between prefrontal brain regions and the ventral striatum was significantly diminished in the risk allele carriers. Healthy risk allele carriers showed a significant deficit of their bottom-up response to conditioned reward stimuli in the bilateral VTA and striatum. Furthermore, functional connectivity between the ventral striatum and prefrontal areas exerting top-down control on the mesolimbic reward system was reduced in this group. Similar alterations in reward processing and disturbances of prefrontal control mechanisms on mesolimbic brain circuits have also been reported in bipolar disorder and schizophrenia. Together, these findings suggest the existence of an intermediate phenotype associated with MAD1L1.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2016.04.052

Journal of affective disorders

J Affect Disord

State dependent cortico-amygdala circuit dysfunction in bipolar disorder.

Existing models of the pathophysiology of bipolar disorder posit disruption in neural circuits of emotion regulation and reward processing. However, few fMRI studies have compared regional brain activity and connectivity in different mood states in bipolar disorder to determine if manic symptomatology is reflected in specific circuit abnormalities. The purpose of this study was to test the hypothesis that bipolar mania is associated with altered connectivity between cortical regions thought to regulate subcortical structures such as the amygdala and striatum. 28 subjects with bipolar disorder in a manic state, 24 different bipolar subjects in a euthymic state, and 23 matched healthy comparison subjects underwent resting state fMRI scans. Several cortical and sub-cortical structures implicated in the pathogenesis of bipolar disorder were selected for study. We conducted a whole-brain analysis of functional connectivity of these regions. Bipolar mania was differentiated from euthymia by decreased functional connectivity between the amygdala and anterior cingulate cortex (ACC). Mania was also characterized by increased connectivity between amygdala and dorsal frontal cortical structures that are normally anti-correlated in emotion regulation tasks. Both groups of bipolar subjects were prescribed medications. The study was not longitudinal in design. Compared to bipolar subjects in a euthymic state, subjects in the manic state demonstrate disrupted functional connectivity between brain regions involved in the regulation of emotion and the amygdala. This disruption of activity in neural circuits involved in emotion may underlie the emotional dysregulation inherent to a bipolar manic episode.

CognitiveConstruct

RewardProcessing

10.1037/abn0000172

Journal of abnormal psychology

J Abnorm Psychol

Anticipatory reward deficits in melancholia.

Dysfunctional reward processing has long been considered an important feature of major depressive disorder (MDD). However, depression is a heterogeneous construct and the nature of this heterogeneity may contribute to some of the inconsistent empirical findings on reward dysfunction in MDD. The current study examined 1 source of heterogeneity, melancholic symptoms, and its association with reward processing. In individuals with MDD (N = 141) and MDD-free controls (N = 113), electroencephalogram (EEG) alpha asymmetry was measured during a behavioral reward task that probed reward anticipation. Melancholic depression was measured both categorically (Diagnostic and Statistical Manual of Mental Disorders [DSM] diagnosis) and dimensionally (Hamilton Endogenomorphy Scale [HES]). Results showed that a dimensional (and not categorical) definition of melancholia predicted reward processing, with higher melancholic symptoms predicting reduced reward anticipation. Importantly, the effects of melancholic symptoms on reduced reward anticipation remained above and beyond overall depression severity. These results suggest that dysfunctional reward processing may only be associated with melancholic symptoms, not depression in general. (PsycINFO Database Record

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2016.05.021

NeuroImage

Neuroimage

Multiple "buy buttons" in the brain: Forecasting chocolate sales at point-of-sale based on functional brain activation using fMRI.

We set out to forecast consumer behaviour in a supermarket based on functional magnetic resonance imaging (fMRI). Data was collected while participants viewed six chocolate bar communications and product pictures before and after each communication. Then self-reports liking judgement were collected. fMRI data was extracted from a priori selected brain regions: nucleus accumbens, medial orbitofrontal cortex, amygdala, hippocampus, inferior frontal gyrus, dorsomedial prefrontal cortex assumed to contribute positively and dorsolateral prefrontal cortex and insula were hypothesized to contribute negatively to sales. The resulting values were rank ordered. After our fMRI-based forecast an instore test was conducted in a supermarket on n=63.617 shoppers. Changes in sales were best forecasted by fMRI signal during communication viewing, second best by a comparison of brain signal during product viewing before and after communication and least by explicit liking judgements. The results demonstrate the feasibility of applying neuroimaging methods in a relatively small sample to correctly forecast sales changes at point-of-sale.

CognitiveConstruct

RewardProcessing

10.1016/j.yhbeh.2016.05.005

Hormones and behavior

Horm Behav

Cortisol alters reward processing in the human brain.

Dysfunctional reward processing is known to play a central role for the development of psychiatric disorders. Glucocorticoids that are secreted in response to stress have been shown to attenuate reward sensitivity and thereby might promote the onset of psychopathology. However, the underlying neurobiological mechanisms mediating stress hormone effects on reward processing as well as potential sex differences remain elusive. In this neuroimaging study, we administered 30mg cortisol or a placebo to 30 men and 30 women and subsequently tested them in the Monetary Incentive Delay Task. Cortisol attenuated anticipatory neural responses to a verbal and a monetary reward in the left pallidum and the right anterior parahippocampal gyrus. Furthermore, in men, activation in the amygdala, the precuneus, the anterior cingulate, and in hippocampal regions was reduced under cortisol, whereas in cortisol-treated women a signal increase was observed in these regions. Behavioral performance also indicated that reward learning in men is impaired under high cortisol concentrations, while it is augmented in women. These findings illustrate that the stress hormone cortisol substantially diminishes reward anticipation and provide first evidence that cortisol effects on the neural reward system are sensitive to sex differences, which might translate into different vulnerabilities for psychiatric disorders.

CognitiveConstruct

RewardProcessing

10.3945/ajcn.115.126706

The American journal of clinical nutrition

Am J Clin Nutr

Increased colonic propionate reduces anticipatory reward responses in the human striatum to high-energy foods.

Short-chain fatty acids (SCFAs), metabolites produced through the microbial fermentation of nondigestible dietary components, have key roles in energy homeostasis. Animal research suggests that colon-derived SCFAs modulate feeding behavior via central mechanisms. In humans, increased colonic production of the SCFA propionate acutely reduces energy intake. However, evidence of an effect of colonic propionate on the human brain or reward-based eating behavior is currently unavailable. We investigated the effect of increased colonic propionate production on brain anticipatory reward responses during food picture evaluation. We hypothesized that elevated colonic propionate would reduce both reward responses and ad libitum energy intake via stimulation of anorexigenic gut hormone secretion. In a randomized crossover design, 20 healthy nonobese men completed a functional magnetic resonance imaging (fMRI) food picture evaluation task after consumption of control inulin or inulin-propionate ester, a unique dietary compound that selectively augments colonic propionate production. The blood oxygen level-dependent (BOLD) signal was measured in a priori brain regions involved in reward processing, including the caudate, nucleus accumbens, amygdala, anterior insula, and orbitofrontal cortex (n = 18 had analyzable fMRI data). Increasing colonic propionate production reduced BOLD signal during food picture evaluation in the caudate and nucleus accumbens. In the caudate, the reduction in BOLD signal was driven specifically by a lowering of the response to high-energy food. These central effects were partnered with a decrease in subjective appeal of high-energy food pictures and reduced energy intake during an ad libitum meal. These observations were not related to changes in blood peptide YY (PYY), glucagon-like peptide 1 (GLP-1), glucose, or insulin concentrations. Our results suggest that colonic propionate production may play an important role in attenuating reward-based eating behavior via striatal pathways, independent of changes in plasma PYY and GLP-1. This trial was registered at clinicaltrials.gov as NCT00750438.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2016.04.018

Journal of affective disorders

J Affect Disord

Adolescent treatment outcomes for comorbid depression and substance misuse: A systematic review and synthesis of the literature.

The quantitative literature on the treatment of comorbid depression and substance misuse among adolescents was reviewed, including: (1) a synthesis of the empirical evidence of the multiple models of integrated treatment for depression and substance use, (2) an examination of proposed mechanisms underlying symptom change in these integrated treatment models targeting depression and substance use, and (3) a methodological critique and suggestions for future research. We reviewed 15 studies reporting on treatment outcomes among adolescents with comorbid depression and non-tobacco related substance use disorders (SUD) and general misuse. Although there is empirical evidence linking Cognitive-Behavioral Therapy (CBT), Motivational Enhancement Therapy (MET), and Family-Focused Therapy (FFT) to depression and SUD symptom reduction in adolescents, few studies have provided data on mechanisms that may account for this effect. Potential mechanisms include improvements in dysfunctional reward processing and self-efficacy. Although this review highlights promising findings for the treatment of comorbid depression and substance misuse in adolescents, further work is warranted; as such results could have important implications for intervention development.

CognitiveConstruct

RewardProcessing

10.1248/yakushi.15-00262-5

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

Yakugaku Zasshi

Preliminary Evidence for Impaired Brain Activity of Neural Reward Processing in Children and Adolescents with Reactive Attachment Disorder.

Childhood maltreatment, which markedly increases risks for psychopathology, is associated with structural and functional brain differences. Especially, exposure to parental verbal abuse (PVA) or interparental violence during childhood is associated with negative outcomes such as depression, posttraumatic stress disorder (PTSD), and reduced cognitive abilities. Other forms of childhood maltreatment have been associated with brain structure or developmental alteration. Our earlier studies elucidated potential discernible effects of PVA and witnessing domestic violence during childhood on brain morphology, including gray matter volume or cortical thickness. Brain regions that process and convey the adverse sensory input of the abuse might be modified specifically by such experiences, particularly in subjects exposed to a single type of maltreatment. Exposure to multiple types of maltreatment is more commonly associated with morphological alterations in the corticolimbic regions. These findings fit with preclinical studies showing that sensory cortices are highly plastic structures. Using tasks with high and low monetary rewards while subjects underwent functional MRI, we also examined whether neural activity during reward processing was altered, or not, in children and adolescents with reactive attachment disorder (RAD). Significantly reduced activity in the caudate and nucleus accumbens was observed during a high monetary reward condition in the RAD group compared to the typically developed group. The striatal neural reward activity in the RAD group was also markedly decreased. The present results suggest that dopaminergic dysfunction occurred in the striatum in children and adolescents with RAD, potentially leading to a future risk of psychiatric disorders such as dependence.

CognitiveConstruct

RewardProcessing

10.1016/j.tics.2016.04.002

Trends in cognitive sciences

Trends Cogn Sci

Reward Processing and Risk for Depression Across Development.

Striatal response to reward has been of great interest in the typical development and psychopathology literatures. These parallel lines of inquiry demonstrate that although typically developing adolescents show robust striatal response to reward, adolescents with major depressive disorder (MDD) and those at high risk for MDD show a blunted response to reward. Understanding how these findings intersect is crucial for the development and application of early preventative interventions in at-risk children, ideally before the sharp increase in the rate of MDD onset that occurs in adolescence. Robust findings relating blunted striatal response to reward and MDD risk are reviewed and situated within a normative developmental context. We highlight the need for future studies investigating longitudinal development, specificity to MDD, and roles of potential moderators and mediators.

CognitiveConstruct

RewardProcessing

10.2196/resprot.5450

JMIR research protocols

JMIR Res Protoc

Feasibility of PRIME: A Cognitive Neuroscience-Informed Mobile App Intervention to Enhance Motivated Behavior and Improve Quality of Life in Recent Onset Schizophrenia.

Despite improvements in treating psychosis, schizophrenia remains a chronic and debilitating disorder that affects approximately 1% of the US population and costs society more than depression, dementia, and other medical illnesses across most of the lifespan. Improving functioning early in the course of illness could have significant implications for long-term outcome of individuals with schizophrenia. Yet, current gold-standard treatments do not lead to clinically meaningful improvements in outcome, partly due to the inherent challenges of treating a population with significant cognitive and motivational impairments. The rise of technology presents an opportunity to develop novel treatments that may circumvent the motivational and cognitive challenges observed in schizophrenia. The purpose of this study was two-fold: (1) to evaluate the feasibility and acceptability of implementing a Personalized Real-Time Intervention for Motivation Enhancement (PRIME), a mobile app intervention designed to target reward-processing impairments, enhance motivation, and thereby improve quality of life in recent onset schizophrenia, and (2) evaluate the empirical benefits of using an iterative, user-centered design (UCD) process. We conducted two design workshops with 15 key stakeholders, followed by a series of in-depth interviews in collaboration with IDEO, a design and innovation firm. The UCD approach ultimately resulted in the first iteration of PRIME, which was evaluated by 10 RO participants. Results from the Stage 1 participants were then used to guide the next iteration that is currently being evaluated in an ongoing RCT. Participants in both phases were encouraged to use the app daily with a minimum frequency of 1/week over a 12-week period. The UCD process resulted in the following feature set: (1) delivery of text message (short message service, SMS)-based motivational coaching from trained therapists, (2) individualized goal setting in prognostically important psychosocial domains, (3) social networking via direct peer-to-peer messaging, and (4) community "moments feed" to capture and reinforce rewarding experiences and goal achievements. Users preferred an experience that highlighted several of the principles of self-determination theory, including the desire for more control of their future (autonomy and competence) and an approach that helps them improve existing relationships (relatedness). IDEO, also recommended an approach that was casual, friendly, and nonstigmatizing, which is in line with the recovery model of psychosis. After 12-weeks of using PRIME, participants used the app, on average, every other day, were actively engaged with its various features each time they logged in and retention and satisfaction was high (20/20, 100% retention, high satisfaction ratings). The iterative design process lead to a 2- to 3-fold increase in engagement from Stage 1 to Stage 2 in almost each aspect of the platform. These results indicate that the neuroscience-informed mobile app, PRIME, is a feasible and acceptable intervention for young people with schizophrenia.

CognitiveConstruct

RewardProcessing

10.1111/bdi.12387

Bipolar disorders

Bipolar Disord

Mania secondary to focal brain lesions: implications for understanding the functional neuroanatomy of bipolar disorder.

Approximately 3.5 million Americans will experience a manic episode during their lifetimes. The most common causes are psychiatric illnesses such as bipolar I disorder and schizoaffective disorder, but mania can also occur secondary to neurological illnesses, brain injury, or neurosurgical procedures. For this narrative review, we searched Medline for articles on the association of mania with stroke, brain tumors, traumatic brain injury, multiple sclerosis, neurodegenerative disorders, epilepsy, and neurosurgical interventions. We discuss the epidemiology, features, and treatment of these cases. We also review the anatomy of the lesions, in light of what is known about the neurobiology of bipolar disorder. The prevalence of mania in patients with brain lesions varies widely by condition, from <2% in stroke to 31% in basal ganglia calcification. Mania occurs most commonly with lesions affecting frontal, temporal, and subcortical limbic brain areas. Right-sided lesions causing hypo-functionality or disconnection (e.g., stroke; neoplasms) and left-sided excitatory lesions (e.g., epileptogenic foci) are frequently observed. Secondary mania should be suspected in patients with neurological deficits, histories atypical for classic bipolar disorder, and first manic episodes after the age of 40 years. Treatment with antimanic medications, along with specific treatment for the underlying neurologic condition, is typically required. Typical lesion locations fit with current models of bipolar disorder, which implicate hyperactivity of left-hemisphere reward-processing brain areas and hypoactivity of bilateral prefrontal emotion-modulating regions. Lesion studies complement these models by suggesting that right-hemisphere limbic-brain hypoactivity, or a left/right imbalance, may be relevant to the pathophysiology of mania.

CognitiveConstruct

RewardProcessing