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10.1016/j.psyneuen.2019.104520

Psychoneuroendocrinology

Psychoneuroendocrinology

Reward-related brain activity and behavior are associated with peripheral ghrelin levels in obesity.

While excessive food consumption represents a key factor in the development of obesity, the underlying mechanisms are still unclear. Ghrelin, a gut-brain hormone involved in the regulation of appetite, is impaired in obesity. In addition to its role in eating behavior, this hormone was shown to affect brain regions controlling reward, including the striatum and prefrontal cortex, and there is strong evidence of impaired reward processing in obesity. The present study investigated the possibility that disrupted reward-related brain activity in obesity relates to ghrelin deficiency. Fifteen severely obese subjects (BMI > 35 kg/m) and fifteen healthy non-obese control subjects (BMI < 30 kg/m) were recruited. A guessing-task paradigm, previously shown to activate the ventral striatum, was used to assess reward-related brain neural activity by functional magnetic resonance imaging (fMRI). Fasting blood samples were collected for the measurement of circulating ghrelin. Significant activations in the ventral striatum, ventromedial prefrontal cortex and extrastriate visual cortex were elicited by the fMRI task in both obese and control subjects. In addition, greater reward-related activations were present in the dorsolateral prefrontal cortex, and precuneus/posterior cingulate of obese subjects compared to controls. Obese subjects exhibited longer choice times after repeated reward and lower circulating ghrelin levels than lean controls. Reduced ghrelin levels significantly predicted slower post-reward choices and reward-related hyperactivity in dorsolateral prefrontal cortices in obese subjects. This study provides evidence of association between circulating ghrelin and reward-related brain activity in obesity and encourages further exploration of the role of ghrelin system in altered eating behavior in obesity.

CognitiveConstruct

RewardProcessing

10.1002/hbm.24882

Human brain mapping

Hum Brain Mapp

Pain modulates neural responses to reward in the medial prefrontal cortex.

Pain has been found to promote reward-seeking behaviors, which might be a consequence of modulated brain activities in the reward neural circuitry in a painful state. The present study investigated how pain affected reward processing and reward-related neural activities using fMRI technique. A total of 50 healthy participants were recruited and used for data analyses, with half being treated with topical capsaicin cream and the other half with hand cream (treatment: pain or control). The participants were asked to perform a card-guessing game when their brain activities responding to feedbacks (outcome: win or loss) were recorded. Behavioral results showed that participants in pain group overestimated their correct choices in the card-guess game. Whole-brain fMRI analysis revealed that the main effect of outcome (win vs. loss) activated a typical network of the reward neural circuitry, including the medial prefrontal cortex (mPFC) and the bilateral nucleus accumbens (NAcc). Importantly, the region of interest analysis revealed a significant interaction of treatment and outcome in the mPFC, with increased mPFC neural activity responding to win outcome in pain condition. Moreover, the functional connectivity between the mPFC and the NAcc was decreased in pain condition. We conclude that the pain-induced modulation of the mPFC activity could result in alterations of both the emotional response to and the cognitive evaluation of reward.

CognitiveConstruct

RewardProcessing

10.1016/j.bpsc.2019.10.002

Biological psychiatry. Cognitive neuroscience and neuroimaging

Biol Psychiatry Cogn Neurosci Neuroimaging

Machine Learning Identifies Large-Scale Reward-Related Activity Modulated by Dopaminergic Enhancement in Major Depression.

Theoretical models have emphasized systems-level abnormalities in major depressive disorder (MDD). For unbiased yet rigorous evaluations of pathophysiological mechanisms underlying MDD, it is critically important to develop data-driven approaches that harness whole-brain data to classify MDD and evaluate possible normalizing effects of targeted interventions. Here, using an experimental therapeutics approach coupled with machine learning, we investigated the effect of a pharmacological challenge aiming to enhance dopaminergic signaling on whole-brain response to reward-related stimuli in MDD. Using a double-blind, placebo-controlled design, we analyzed functional magnetic resonance imaging data from 31 unmedicated MDD participants receiving a single dose of 50 mg amisulpride (MDD), 26 MDD participants receiving placebo (MDD), and 28 healthy control subjects receiving placebo (HC) recruited through two independent studies. An importance-guided machine learning technique for model selection was used on whole-brain functional magnetic resonance imaging data probing reward anticipation and consumption to identify features linked to MDD (MDD vs. HC) and dopaminergic enhancement (MDD vs. MDD). Highly predictive classification models emerged that distinguished MDD from HC (area under the curve = 0.87) and MDD from MDD (area under the curve = 0.89). Although reward-related striatal activation and connectivity were among the most predictive features, the best truncated models based on whole-brain features were significantly better relative to models trained using striatal features only. Results indicate that in MDD, enhanced dopaminergic signaling restores abnormal activation and connectivity in a widespread network of regions. These findings provide new insights into the pathophysiology of MDD and pharmacological mechanism of antidepressants at the system level in addressing reward processing deficits among depressed individuals.

CognitiveConstruct

RewardProcessing

10.31887/DCNS.2019.21.3/rblair

Dialogues in clinical neuroscience

Dialogues Clin Neurosci

Dysfunctional neurocognition in individuals with clinically significant psychopathic traits .

The main goal of this review is to consider the main forms of dysfunctional neurocognition seen in individuals with clinically significant psychopathic traits (ie, reduced guilt/empathy and increased impulsive/antisocial behavior). A secondary goal is to examine the extent to which these forms of dysfunction are seen in both adults with psychopathic traits and adolescents with clinically significant antisocial behavior that may also involve callous-unemotional traits (reduced guilt/empathy). The two main forms of neurocognition considered are emotional responding (to distress/pain cues and emotional stimuli more generally) and reward-related processing. Highly related forms of neurocognition, the response to drug cues and moral judgments, are also discussed. It is concluded that dysfunction in emotional responsiveness and moral judgments confers risk for aggression across adolescence and into adulthood. However, reduced reward-related processing, including to drug cues, is only consistently found in adolescents with clinically significant antisocial behavior, not adults with psychopathy. .

CognitiveConstruct

RewardProcessing

10.1177/1747021819892158

Quarterly journal of experimental psychology (2006)

Q J Exp Psychol (Hove)

Prioritised self-referential processing is modulated by emotional arousal.

Stimuli related to the self are processed more efficiently in a variety of cognitive tasks. Recent studies have shown that this self-referential processing bias is modulated by emotion. However, a clear understanding of how emotional valence and arousal affect self-referential processing is still lacking. With a label-shape matching task, Experiment 1 measured a self-prioritisation effect in four different mood states. The results revealed stronger self-prioritisation effects in moods with higher arousal levels and a reliable correlation between the self-prioritisation effect and the arousal level reported by the participants; however, the effect of emotional valence was not statistically reliable. Experiment 2 further showed that alerting cues, known to raise arousal level, effectively increased the self-prioritisation effect in the same label-shape matching task. Experiment 3 clarified that alerting cues do not affect reward processing in a similar label-shape matching task, suggesting that arousal may selectively modulate self-referential processing. These observations provide clear evidence that emotional arousal modulates self-referential processing.

CognitiveConstruct

RewardProcessing

10.1038/s41380-019-0588-9

Molecular psychiatry

Mol Psychiatry

Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence.

Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and Dlgap2-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that DLGAP2 may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.

CognitiveConstruct

RewardProcessing

10.3389/fphys.2019.01375

Frontiers in physiology

Front Physiol

Characterization of a Dopamine Transporter and Its Splice Variant Reveals Novel Features of Dopaminergic Regulation in the Honey Bee.

Dopamine is an important neuromodulator involved in reward-processing, movement control, motivational responses, and other aspects of behavior in most animals. In honey bees (), the dopaminergic system has been implicated in an elaborate pheromonal communication network between individuals and in the differentiation of females into reproductive (queen) and sterile (worker) castes. Here we have identified and characterized a honey bee dopamine transporter (AmDAT) and a splice variant lacking exon 3 (AmDATΔex3). Both transcripts are present in the adult brain and antennae as well as at lower levels within larvae and ovaries. When expressed separately in the oocyte system, AmDAT localizes to the oocyte surface whereas the splice variant is retained at an internal membrane. Oocytes expressing AmDAT exhibit a 12-fold increase in the uptake of [H]dopamine relative to non-injected oocytes, whereas the AmDATΔex3-expressing oocytes show no change in [H]dopamine transport. Electrophysiological measurements of AmDAT activity revealed it to be a high-affinity, low-capacity transporter of dopamine. The transporter also recognizes noradrenaline as a major substrate and tyramine as a minor substrate, but does not transport octopamine, L-Dopa, or serotonin. Dopamine transport via AmDAT is inhibited by cocaine in a reversible manner, but is unaffected by octopamine. Co-expression of AmDAT and AmDATΔex3 in oocytes results in a substantial reduction in AmDAT-mediated transport, which was also detected as a significant decrease in the level of AmDAT protein. This down-regulatory effect is not attributable to competition with AmDATΔex3 for ER ribosomes, nor to a general inhibition of the oocyte's translational machinery. , the expression of both transcripts shows a high level of inter-individual variability. Gene-focused, ultra-deep amplicon sequencing detected methylation of the locus at ten 5'-C-phosphate-G-3' dinucleotides (CpGs), but only in 5-10% of all reads in whole brains or antennae. These observations, together with the localization of the transcript to a few clusters of dopaminergic neurons, imply that methylation is positively linked to its transcription. Our findings suggest that multiple cellular mechanisms, including gene splicing and epigenomic communication systems, may be adopted to increase the potential of a conserved gene to contribute to lineage-specific behavioral outcomes.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2019.01147

Frontiers in neuroscience

Front Neurosci

Accelerated Intermittent Theta-Burst Stimulation as a Treatment for Cocaine Use Disorder: A Proof-of-Concept Study.

There are no effective treatments for cocaine use disorder (CUD), a chronic, relapsing brain disease characterized by dysregulated circuits related to cue reactivity, reward processing, response inhibition, and executive control. Transcranial magnetic stimulation (TMS) has the potential to modulate circuits and networks implicated in neuropsychiatric disorders, including addiction. Although acute applications of TMS have reduced craving in urine-negative cocaine users, the tolerability and safety of administering accelerated TMS to cocaine-positive individuals is unknown. As such, we performed a proof-of-concept study employing an intermittent theta-burst stimulation (iTBS) protocol in an actively cocaine-using sample. Although our main goal was to assess the tolerability and safety of administering three iTBS sessions daily, we also hypothesized that iTBS would reduce cocaine use in this non-treatment seeking cohort. We recruited 19 individuals with CUD to receive three open-label iTBS sessions per day, with approximately a 60-min interval between sessions, for 10 days over a 2-week period (30 total iTBS sessions). iTBS was delivered to left dorsolateral prefrontal cortex (dlPFC) with neuronavigation guidance. Compliance and safety were assessed throughout the trial. Cocaine use behavior was assessed before, during, and after the intervention and at 1- and 4-week follow-up visits. Of the 335 iTBS sessions applied, 73% were performed on participants with cocaine-positive urine tests. Nine of the 14 participants who initiated treatment received at least 26 of 30 iTBS sessions and returned for the 4-week follow-up visit. These individuals reduced their weekly cocaine consumption by 78% in amount of dollars spent and 70% in days of use relative to pre-iTBS cocaine use patterns. Similarly, individuals reduced their weekly consumption of nicotine, alcohol, and THC, suggesting iTBS modulated a common circuit across drugs of abuse. iTBS was well-tolerated, despite the expected occasional headaches. A single participant developed a transient neurological event of uncertain etiology on iTBS day 9 and cocaine-induced psychosis 2 weeks after discontinuation. It thus appears that accelerated iTBS to left dlPFC administered in active, chronic cocaine users is both feasible and tolerable in actively using cocaine participants with preliminary indications of efficacy in reducing both the amount and frequency of cocaine (and other off target drug) use. The neural underpinnings of these behavioral changes could help in the future development of effective treatment of CUD.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2019.11.004

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

Int J Psychophysiol

Interaction of emotion and cognitive control along the psychosis continuum: A critical review.

To better understand how emotion impacts cognitive control is important as both influence adaptive behavior in complex real-life situations. Performance changes in emotion and cognitive control as well as in their interaction are often described in psychotic patients as well as in non-clinical participants who experience psychosis-like symptoms. These changes are linked to low motivation and limited social interaction. However, it is unclear whether these changes are driven by emotion, cognitive control, or an interaction of both. This review provides an overview of neuroimaging evidence on the potential interaction of emotion and cognitive control along the psychosis continuum. The literature confirms that over-sensitivity towards negative and lowered sensitivity towards positive emotional stimuli in tasks exploring emotion-cognitive control interaction are associated with the severity of positive and negative symptoms in psychosis. Changes in the dynamic interplay between emotion and context-sensitive cognitive control, mediated by arousal, motivation, and reward processing may underlie poor interpersonal communication and real-life skills in psychosis. In addition, structural and functional changes in subcortical and cortical associative brain regions (e.g., thalamus, basal ganglia, and angular gyrus) may contribute to alterations in emotion and cognitive control interaction along the psychosis continuum. There is limited evidence on how antipsychotic medication and age at illness-onset affect this interaction.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2019.107710

Drug and alcohol dependence

Drug Alcohol Depend

White matter connectometry among individuals with self-reported family history of drug and alcohol use disorders.

Heredity is an important risk factor for alcoholism. Several studies have been conducted on small groups of alcohol naïve adolescents which show lowered fractional anisotropy of frontal white matter in individuals with a family history of alcohol and substance use disorder (FH+). We compare large adult FH+ and FH- groups using white matter connectometry, different from the previously used global tractography method, as it is more sensitive to regional variability. Imaging and behavioral data from the Human Connectome Project (WU-MINN HCP 1200) was analyzed. Groups of participants were positive (n = 109) and negative (n = 109) for self-reported alcohol and substance use disorders in at least one parent, and stringently matched. Connectometry was performed on diffusion MRI in DSI-Studio using q-space diffeomorphic reconstruction, and multiple regression was completed with 5000 permutations. Analyses showed decreased major tract (>40 mm) connectivity in the FH+ group in left inferior longitudinal fasciculus, bilateral cortico-striatal pathway, left cortico-thalamic pathway, and corpus callosum, compared to the FH- group. For cognitive tasks related to reward processing, inhibition, and monitoring, there were a number of interactions, such that the relationship between identified tracts and behavior differed significantly between groups. Self-reported family history was associated with decreased connectivity in reward signaling pathways, controlling for alcohol consumption and alcohol use disorder. This is the first connectometry study of FH+, and extends the neural basis of the hereditary diathesis of alcoholism beyond that demonstrated with global tractography. Regions associated with FH+ are similar to those associated with alcohol use disorder.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2019.09.021

Biological psychiatry

Biol Psychiatry

Cognition and Reward Circuits in Schizophrenia: Synergistic, Not Separate.

Schizophrenia has been studied from the perspective of cognitive or reward-related impairments, yet it cannot be wholly related to one or the other process and their corresponding neural circuits. We posit a comprehensive circuit-based model proposing that dysfunctional interactions between the brain's cognitive and reward circuits underlie schizophrenia. The model is underpinned by how the relationship between glutamatergic and dopaminergic dysfunction in schizophrenia drives interactions between cognition and reward circuits. We argue that this interaction is synergistic: that is, deficits of cognition and reward processing interact, and this interaction is a core feature of schizophrenia. In adopting this position, we undertake a focused review of animal physiology and human clinical data, and in proposing this synergistic model, we highlight dopaminergic afferents from the ventral tegmental area to nucleus accumbens (mesolimbic circuit) and frontal cortex (mesocortical circuit). We then expand on the role of glutamatergic inputs to these dopamine circuits and dopaminergic modulation of critical excitatory pathways with attention given to the role of glutamatergic hippocampal outputs onto nucleus accumbens. Finally, we present evidence for how in schizophrenia, dysfunction in the mesolimbic and mesocortical circuits and their corresponding glutamatergic inputs gives rise to clinical and cognitive phenotypes and is associated with positive and negative symptom dimensions. The synthesis attempted here provides an impetus for a conceptual shift that links cognitive and motivational aspects of schizophrenia and that can lead to treatment approaches that seek to harmonize network interactions between the brain's cognition and reward circuits with ameliorative effects in each behavioral domain.

CognitiveConstruct

RewardProcessing

10.1016/j.jpain.2019.11.005

The journal of pain

J Pain

The Context of Values in Pain Control: Understanding the Price Effect in Placebo Analgesia.

The experience of pain relief arises from physiological and psychological factors, and attributes such as the commercial features of analgesic treatments have been shown to influence placebo analgesia by affecting treatment expectations. Therefore, treatment valuation from price information should influence the placebo analgesic effect. This hypothesis was tested in a functional magnetic resonance imaging study in which healthy subjects were enrolled in a 2-day experiment. On day 1, the participants (n = 19) had treatment experiences with 2 different placebo creams during a conditioning session without receiving information on treatment price. On day 2, placebo analgesia was tested after providing price information (high vs low) while functional magnetic resonance imaging was performed. The results showed that the higher priced placebo treatment leads to enhanced pain relief. Placebo analgesia in response to the higher priced treatment was associated with activity in the ventral striatum, ventromedial prefrontal cortex, and ventral tegmental area. The behavioral results indicate that the experience of pain was influenced by treatment valuation from price. Our findings reveal that the context of values in pain control is associated with activity in expectation- and reward-related circuitry. PERSPECTIVE: Treatment with higher price was associated with enhanced placebo analgesia, and this effect was influenced by activities in expectation and reward processing brain areas. The context of value such as medical cost influences cognitive evaluation processes to modulate pain. Our study may help evaluate a patient's preference toward high-priced drugs.

CognitiveConstruct

RewardProcessing

10.1038/s41437-019-0282-3

Heredity

Heredity (Edinb)

A hominid-specific shift in cerebellar expression, upstream retrotransposons, and a potential cis-regulatory mechanism: bioinformatics analyses of the mu-opioid receptor gene.

The mu-opioid receptors (MOR, OPRM1) mediate the effects of beta-endorphin and modulate many biological functions including reward processing and addiction. The present study aimed to use bioinformatics to determine OPRM1 brain expression profiles in higher primates and to look for regulatory mechanisms. We used the same computational pipeline to analyze publicly available expression data from postmortem brain regions across humans, chimpanzees, and rhesus macaques. The most intriguing finding was high OPRM1 cerebellar expression in humans and chimpanzees and low expression in macaques. Together with previous reports of low cerebellar OPRM1 expression in mice, this suggests an evolutionary shift in the expression profiles. Bioinformatic analysis of the OPRM1 upstream region revealed a functional CTCF-binding region that evolved from tandem insertions of retrotransposons L1P1 and L1PA1 upstream (-60 kb) of OPRM1. The insertions arose in different time points after the split of small apes from great apes, and their combined sequence is unique. Furthermore, the derived G allele of SNP rs12191876, in the inserted region, is associated with an increased OPRM1 expression in the cerebellum of postmortem human brains (p = 4.7e-5). The derived G allele became the major allele (60-90%) in the populations represented in the 1000 Genomes Project and may be beneficial. This study provides a foundation for building new knowledge about evolutionary differences in OPRM1 brain expression. Further investigations are needed to elucidate the role of the inserted region and its SNPs in OPRM1 expression, and to assess the biological function and relevance of OPRM1 expression in the cerebellum.

CognitiveConstruct

RewardProcessing

10.1038/s41398-019-0644-x

Translational psychiatry

Transl Psychiatry

Meta-analysis of reward processing in major depressive disorder reveals distinct abnormalities within the reward circuit.

Many neuroimaging studies have investigated reward processing dysfunction in major depressive disorder. These studies have led to the common idea that major depressive disorder is associated with blunted responses within the reward circuit, particularly in the ventral striatum. Yet, the link between major depressive disorder and reward-related responses in other regions remains inconclusive, thus limiting our understanding of the pathophysiology of major depressive disorder. To address this issue, we performed a coordinate-based meta-analysis of 41 whole-brain neuroimaging studies encompassing reward-related responses from a total of 794 patients with major depressive disorder and 803 healthy controls. Our findings argue against the common idea that major depressive disorder is primarily linked to deficits within the reward system. Instead, our results demonstrate that major depressive disorder is associated with opposing abnormalities in the reward circuit: hypo-responses in the ventral striatum and hyper-responses in the orbitofrontal cortex. The current findings suggest that dysregulated corticostriatal connectivity may underlie reward-processing abnormalities in major depressive disorder, providing an empirical foundation for a more refined understanding of abnormalities in the reward circuitry in major depressive disorder.

CognitiveConstruct

RewardProcessing

10.1038/s41386-019-0565-7

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Repetitive transcranial magnetic stimulation targeting the insular cortex for reduction of heavy drinking in treatment-seeking alcohol-dependent subjects: a randomized controlled trial.

Insula responses to drug cues are correlated with cravings, and lesions in this area reduce nicotine seeking. Here, we investigated the potential efficacy of repetitive transcranial magnetic stimulation (rTMS) targeting the insula in alcohol addiction. Treatment-seeking alcohol-dependent patients (Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition; N = 56) participated in this double-blind, sham-controlled, randomized trial. Participants received 10 Hz rTMS or sham using an H8 coil, 5 days a week for 3 weeks. Stimulation targeted insular cortex and overlaying regions bilaterally, while excluding anterior prefrontal areas. Craving and self-reported as well as biomarker-based drinking measures were collected at baseline, during treatment, and through 12 weeks. Resting-state magnetic resonance imaging (rsMRI) data were collected before and after treatment. Task-based MRI was used to probe brain correlates of reward processing, affective responses, and alcohol following completion of treatment. A marked overall decrease in craving and drinking measures was observed during treatment, but did not differ between rTMS or sham stimulation. Both groups equally increased their alcohol use following completion of treatment and through the 12-week follow-up. Analysis using seeds in the insula identified differences in resting-state connectivity between active and sham groups at completion of treatment, potentially indicating an ability of treatment to modify insula function. However, while each task robustly replicated brain responses established in the literature, no effects of rTMS were found. Collectively, this study does not support efficacy of rTMS targeting the insula in alcohol addiction.

CognitiveConstruct

RewardProcessing

10.1002/mds.27885

Movement disorders : official journal of the Movement Disorder Society

Mov Disord

Functional inhibitory control dynamics in impulse control disorders in Parkinson's disease.

Impulse control disorders related to alterations in the mesocorticolimbic dopamine network occur in Parkinson's disease (PD). Our objective was to investigate the functional neural substrates of reward processing and inhibitory control in these patients. Eighteen PD patients with impulse control disorders, 17 without this complication, and 18 healthy controls performed a version of the Iowa Gambling Task during functional magnetic resonance scanning under 3 conditions: positive, negative, and mixed feedback. Whole-brain contrasts, regions of interest, time courses, functional connectivity analyses, and brain-behavior associations were examined. PD patients with impulse control disorders exhibited hyperactivation in subcortical and cortical regions typically associated with reward processing and inhibitory control compared with their PD and healthy control counterparts. Time-course analyses revealed that only PD patients with impulse control disorders exhibited stronger signal intensity during the initial versus final periods of the negative-feedback condition in bilateral insula, and right ventral striatum. Interestingly, hyperactivation of all the examined right-lateralized frontostriatal areas during negative feedback was positively associated with impulse control disorder severity. Importantly, positive associations between impulse control disorder severity and regional activations in the right insula and right inferior frontal gyrus, but not the right subthalamic nucleus, were mediated by functional connectivity with the right ventral striatum. During a reward-based task, PD patients with impulse control disorders showed hyperactivation in a right-lateralized network of regions including the subthalamic nucleus that was strongly associated with impulse control disorder severity. In these patients, the right ventral striatum in particular played a critical role in modulating the functional dynamics of right-lateralized inhibitory-control frontal regions when facing penalties. © 2019 International Parkinson and Movement Disorder Society.

CognitiveConstruct

RewardProcessing

10.3389/fncel.2019.00479

Frontiers in cellular neuroscience

Front Cell Neurosci

Reward-Related Behavioral, Neurochemical and Electrophysiological Changes in a Rat Model of Autism Based on Prenatal Exposure to Valproic Acid.

Prenatal exposure to the antiepileptic drug valproic acid (VPA) induces autism spectrum disorder (ASD) in humans and autistic-like behaviors in rodents, which makes it a good model to study the neural underpinnings of ASD. Rats prenatally exposed to VPA show profound deficits in the social domain. The altered social behavior displayed by VPA-exposed rats may be due to either a deficit in social reward processing or to a more general inability to properly understand and respond to social signals. To address this issue, we performed behavioral, electrophysiological and neurochemical experiments and tested the involvement of the brain reward system in the social dysfunctions displayed by rats prenatally exposed to VPA (500 mg/kg). We found that, compared to control animals, VPA-exposed rats showed reduced play responsiveness together with impaired sociability in the three-chamber test and altered social discrimination abilities. In addition, VPA-exposed rats showed altered expression of dopamine receptors together with inherent hyperexcitability of medium spiny neurons (MSNs) in the nucleus accumbens (NAc). However, when tested for socially-induced conditioned place preference, locomotor response to amphetamine and sucrose preference, control and VPA-exposed rats performed similarly, indicating normal responses to social, drug and food rewards. On the basis of the results obtained, we hypothesize that social dysfunctions displayed by VPA-exposed rats are more likely caused by alterations in cognitive aspects of the social interaction, such as the interpretation and reciprocation of social stimuli and/or the ability to adjust the social behavior of the individual to the changing circumstances in the social and physical environment, rather than to inability to enjoy the pleasurable aspects of the social interaction. The observed neurochemical and electrophysiological alterations in the NAc may contribute to the inability of VPA-exposed rats to process and respond to social cues, or, alternatively, represent a compensatory mechanism towards VPA-induced neurodevelopmental insults.

CognitiveConstruct

RewardProcessing

10.1016/j.brainres.2019.146541

Brain research

Brain Res

An EEG marker of reward processing is diminished in Parkinson's disease.

The electroencephalographic signal known as the Reward Positivity (RewP) scales with the reward prediction error following reward receipt. This signal is computationally identical to the dopamine-driven learning process relating to the discrepancy between reward expectation and reward acquisition. The current study aimed to investigate if the RewP is diminished in Parkinson's disease (PD). In this study, 28 people with PD and 28 age- and sex-matched healthy controls completed a reinforcement-learning task. In line with expectations, the RewP was smaller in persons with PD than in controls. Yet contrary to expectations, RewP amplitude did not differ in on vs. off medication conditions, and it was positively correlated with the number of years diagnosed with PD. We propose that this symptom-specific alteration in RewP may be a consequence of a common methodological procedure in PD research (e.g. restricted recruitment) or it might truly be a marker of early-stage disease (e.g. prior to network re-adaptation). These surprising findings motivate separate testable hypotheses for assessing aspects of PD with this novel neural marker of reward.

CognitiveConstruct

RewardProcessing

10.1007/s11920-019-1095-z

Current psychiatry reports

Curr Psychiatry Rep

Effects of Hormonal Contraceptives on Mood: A Focus on Emotion Recognition and Reactivity, Reward Processing, and Stress Response.

We review recent research investigating the relationship of hormonal contraceptives and mood with a focus on relevant underlying mechanisms, such as emotion recognition and reactivity, reward processing, and stress response. Adverse effects of hormonal contraceptives (HCs) on mood seem most consistent in women with a history of depressive symptoms and/or previous negative experience with HC-intake. Current evidence supports a negativity bias in emotion recognition and reactivity in HC-users, although inconsistent to some extent. Some data, however, do indicate a trend towards a blunted reward response and a potential dysregulation of the stress response in some HC-users. HC-effects on psychological and neurophysiological mechanisms underlying mood are likely context-dependent. We provide suggestions on how to address some of the contributing factors to this variability in future studies, such as HC-dose, timing, administration-mode, and individual risk. A better understanding of how and when HCs affect mood is critical to provide adequate contraceptive choices to women worldwide.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2019.102036

NeuroImage. Clinical

Neuroimage Clin

Reduced striatal activation in response to rewarding motor performance feedback after stroke.

Motor skill learning can help stroke survivors to cope with motor function deficits but requires many repetitions. One factor that keeps patients motivated is obtaining reward upon successfully completing a motor task. It has been suggested that stroke survivors have deficits in reward processing which may negatively impact skill learning. To test the hypothesis that stroke survivors have deficient reward processing during motor skill learning evident in reduced activation in the striatum and its subdivisions in functional magnetic resonance imaging as compared with healthy, age-matched control subjects. Striatal activity in response to performance dependent feedback and monetary reward was measured in 28 subacute stroke patients and 18 age-matched healthy control subjects during the training of visuomotor tracking an arc-shaped trajectory using the wrist (unimpaired side in patients, dominant side in controls) in an fMRI scanner. Despite comparable monetary rewards, stroke patients showed reduced activation in the ventral part (p < 0.01), but not in the dorsal part of the striatum (p = 0.11). 14 patients had their lesion extending into the striatum. The nucleus accumbens as part of the ventral striatum was unlesioned in all participants and still showed a marked hypoactivation in stroke patients as compared with controls (p < 0.001), a finding that could not be explained by motivational differences between the groups. Striatal hypoactivation in stroke survivors may cause impaired consolidation of motor skills. Stronger rewarding stimuli or drug-mediated enhancement may be needed to normalize reward processing after stroke with positive effects on recovery.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropharm.2019.107833

Neuropharmacology

Neuropharmacology

Methylphenidate modifies reward cue responses in adults with ADHD: An fMRI study.

Attention deficit hyperactivity disorder (ADHD) has been associated with neural hyposensitivity to reward-predicting cues. Methylphenidate is widely used in the management of the disorder's symptoms, but its effects on reward sensitivity in ADHD are unknown. The current study used fMRI to measure striatal responses to reward-predicting cues in adults with ADHD on and off methylphenidate and a control group, during a classical conditioning task. Responses to cued reward were also explored. Larger differences in the ventral striatum activation to reward cues versus non-reward cues were observed when the ADHD participants were on methylphenidate compared to placebo. In response to cued-reward outcome, an exploratory analysis showed methylphenidate reduced the BOLD time-series correlation between the dorsal striatum and dorsal medial prefrontal cortex. Methylphenidate's therapeutic effects may be mediated by altering reward processing in individuals with ADHD.

CognitiveConstruct

RewardProcessing

10.1002/osp4.363

Obesity science & practice

Obes Sci Pract

Changes in brain activity after weight loss.

The importance of the regulatory role of the brain in directing glucose homeostasis, energy homeostasis, eating behaviour, weight control and obesity is increasingly recognized. Brain activity in (sub)cortical neuronal networks involved in homeostatic control and hedonic responses is generally increased in persons with obesity. Currently, it is not known if these functional changes can be affected by dieting. The aim of the current study was to investigate whether prolonged fasting and/or weight loss influences neuronal brain activity in obese persons. Fourteen participants with obesity were included (two male participants and 12 female participants, body mass index 35.2 ± 1.2 kg m). Whole-brain resting-state functional magnetic resonance imaging was performed after an overnight fast, after a prolonged 48-h fast and after an 8-week weight loss intervention. An 8-week weight loss intervention decreased BOLD signal in areas of the brain involved in salience, sensory motor and executive control. BOLD signal in these areas correlated with leptin levels and body mass index. Weight loss decreased activity in brain areas involved in feeding behaviour and reward processing. These results indicate that these obesity-associated alterations in neuronal activity are related to excessive body weight and might change after weight loss.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2019.102018

NeuroImage. Clinical

Neuroimage Clin

Neural responses to monetary incentives in bipolar disorder.

Although behavioral sensitivity to reward predicts the onset and course of mania in bipolar disorder, the evidence for neural abnormalities in reward processing in bipolar disorder is mixed. To probe neural responsiveness to anticipated and received rewards in the context of bipolar disorder, we scanned individuals with remitted bipolar I disorder (n = 24) and well-matched controls (n = 24; matched for age and gender) using Functional Magnetic Resonance Imaging (FMRI) during a Monetary Incentive Delay (MID) task. Relative to controls, the bipolar group showed reduced NAcc activity during anticipation of gains. Across groups, this blunting correlated with individual differences in impulsive responses to positive emotions (Positive Urgency), which statistically accounted for the association of blunted NAcc activity with bipolar diagnosis. These results suggest that blunted NAcc responses during gain anticipation in the context of bipolar disorder may reflect individual differences in Positive Urgency. These findings may help resolve discrepancies in the literature on neural responses to reward in bipolar disorder, and clarify the relationship between brain activity and the propensity to experience manic episodes.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2019.10.015

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

Stress-induced plasticity and functioning of ventral tegmental dopamine neurons.

The ventral tegmental area dopamine (VTA-DA) mesolimbic circuit processes emotional, motivational, and social reward associations together with their more demanding cognitive aspects that involve the mesocortical circuitry. Coping with stress increases VTA-DA excitability, but when the stressor becomes chronic the VTA-DA circuit is less active, which may lead to degeneration and local microglial activation. This switch between activation and inhibition of VTA-DA neurons is modulated by e.g. corticotropin-releasing hormone (CRH), opioids, brain-derived neurotrophic factor (BDNF), and the adrenal glucocorticoids. These actions are coordinated with energy-demanding stress-coping styles to promote behavioral adaptation. The VTA circuits show sexual dimorphism that is programmed by sex hormones during perinatal life in a manner that can be affected by glucocorticoid exposure. We conclude that insight in the role of stress in VTA-DA plasticity and connectivity, during reward processing and stress-coping, will be helpful to better understand the mechanism of resilience to breakdown of adaptation.

CognitiveConstruct

RewardProcessing

10.1037/abn0000469

Journal of abnormal psychology

J Abnorm Psychol

Reward processing in certain versus uncertain contexts in schizophrenia: An event-related potential (ERP) study.

Disturbances in motivation are prominent in the clinical presentation of people with schizophrenia and might reflect a disturbance in reward processing. Recent advances in affective neuroscience have subdivided reward processing into distinct components, but there are two limitations of the prior work in schizophrenia. First, studies typically focus on only one component rather than on the unfolding of reward processing across multiple stages. Second, studies have not considered the impact of certainty effects, which represent an important contextual factor that impacts processing. We examined whether individuals with schizophrenia show the typical certainty effects across three phases of reward processing: cue evaluation, feedback anticipation, and feedback receipt. Electroencephalography from 74 healthy controls and 92 people with schizophrenia was recorded during a cued gambling task under conditions in which cues indicated forthcoming reward outcomes that were certain or uncertain. Controls demonstrated the expected certainty effects across each stage. Initial cue evaluation (cue P300) was intact in the schizophrenia group, but people with schizophrenia showed diminished certainty effects during feedback anticipation (stimulus-preceding negativity [SPN]) and receipt (feedback reward positivity [fRewP] and feedback P300). During feedback receipt, event-related potentials in people with schizophrenia were similar to controls for the uncertain context but larger than controls for the certain context. Essentially, people with schizophrenia appeared to process certain feedback as though it were uncertain. These findings show, for the first time, that the fundamental distinction between certain and uncertain contexts is altered in schizophrenia at a neural level. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

CognitiveConstruct

RewardProcessing

10.1002/dvg.23341

Genesis (New York, N.Y. : 2000)

Genesis

Generation of a MOR-CreER knock-in mouse line to study cells and neural circuits involved in mu opioid receptor signaling.

Mu opioid receptor (MOR) is involved in various brain functions, such as pain modulation, reward processing, and addictive behaviors, and mediates the main pharmacologic effects of morphine and other opioid compounds. To gain genetic access to MOR-expressing cells, and to study physiological and pathological roles of MOR signaling, we generated a MOR-CreER knock-in mouse line, in which the stop codon of the Oprm1 gene was replaced by a DNA fragment encoding a T2A peptide and tamoxifen (Tm)-inducible Cre recombinase. We show that the MOR-CreER allele undergoes Tm-dependent recombination in a discrete subtype of neurons that express MOR in the adult nervous system, including the olfactory bulb, cerebral cortex, striosome compartments in the striatum, hippocampus, amygdala, thalamus, hypothalamus, interpeduncular nucleus, superior and inferior colliculi, periaqueductal gray, parabrachial nuclei, cochlear nucleus, raphe nuclei, pontine and medullary reticular formation, ambiguus nucleus, solitary nucleus, spinal cord, and dorsal root ganglia. The MOR-CreER mouse line combined with a Cre-dependent adeno-associated virus vector enables robust gene manipulation in the MOR-enriched striosomes. Furthermore, Tm treatment during prenatal development effectively induces Cre-mediated recombination. Thus, the MOR-CreER mouse is a powerful tool to study MOR-expressing cells with conditional gene manipulation in developing and mature neural tissues.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2019.00219

Frontiers in behavioral neuroscience

Front Behav Neurosci

I Knew You Weren't Going to Like Me! Neural Response to Accurately Predicting Rejection Is Associated With Anxiety and Depression.

Anxiety and depression often emerge in adolescence. A normative increase in the desire for peer acceptance may be one of many contributing factors. These shifts occur during a phase of development in which neural reward networks, including structures such as the ventral striatum, undergo critical changes. Despite the salience of peer feedback during adolescence, neural responses to reward have largely been examined in the monetary domain, leaving many open questions about responses to social rewards. Moreover, most paradigms do not tease apart different aspects of reward processing (e.g., receiving feedback, being correct). Anxiety and depression are also associated with alterations in reward networks; however, little is known about how anxiety and depression in adolescence relate to differences in social vs. non-social reward processing. In this study, adolescents ( = 28) underwent fMRI while completing novel monetary and social feedback tasks, which tease apart reward domain (social/monetary), valence (positive/negative), and outcome (correct/incorrect). Participants were shown a pair of stimuli (doors/age-matched peers) and asked to indicate which stimulus would provide positive (win money/social like) or negative (lose money/social dislike) feedback. Participants then received feedback about the purported accuracy of their response. Region-of-interest analyses showed that left ventral striatum response varied by domain (social/monetary), valence (positive/negative), and outcome (correct/incorrect) of reward. Additionally, unique associations between anxiety, depression, and brain function were observed for correct, but not for incorrect trials, in the social, but not monetary task. Specifically, adolescents with high anxiety symptoms, but low depression, displayed greater left ventral striatum activation when correctly identifying peers who gave dislike (vs. like) feedback. Thus, anxious youth exhibited enhanced activation in a brain region implicated in reward processing when they accurately predicted someone was going to dislike them. Higher levels of both depression and anxiety symptoms were associated with greater striatal activation to correctly identifying peers who gave like (vs. dislike) feedback. These results suggest a neural mechanism by which negative prediction biases may be reinforced in anxious youth.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2019.112298

Behavioural brain research

Behav Brain Res

Reward and punishment learning in schizophrenia and bipolar disorder.

Prior studies on reward learning deficits in psychiatric disorders have used probabilistic learning tasks, making it unclear whether impairment is due to the probabilistic nature of the task rather than reward processing. In this study, we tested probabilistic vs. deterministic reward and punishment learning in healthy controls and three patient groups: schizophrenia (SZ), psychotic bipolar disorder (BD), and nonpsychotic BD. Experimental results show that reward learning was impaired in patients with SZ and patients with psychotic BD in the probabilistic learning task compared to patients with nonpsychotic BD and healthy controls. In contrast, punishment learning in the probabilistic task was impaired in patients with nonpsychotic BD compared to the other patient groups and healthy controls. There were no significant differences among all groups in the deterministic learning task scores. We also found that Hamilton Depression Scale scores negatively correlated with probabilistic learning performance. Our data may suggest that reward learning impairment may be due to the nature of the task as well as subtype of BD.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2019.112275

Behavioural brain research

Behav Brain Res

Within-animal comparisons of novelty and cocaine neuronal ensemble overlap in the nucleus accumbens and prefrontal cortex.

Novelty seeking is a personality trait associated with an increased vulnerability for substance abuse. In rodents, elevated novelty seeking has been shown to be a predictor for elevated drug self-administration and compulsive use. While previous studies have shown that both novelty and drugs of abuse have actions within similar mesocorticolimbic regions, little is known as to whether the same neural ensembles are engaged by these two stimuli. Using the TetTag mouse model and Fos immunohistochemistry, we measured neurons engaged by novelty and acute cocaine exposure, respectively in the prefrontal cortex (PFC) and nucleus accumbens (NAc). While there was no significant impact of novelty exposure on the size of the EGFP+ ensemble, we found that cocaine engaged significantly more Fos+ neurons in the NAc, while stress increased the size of the Fos+ ensemble in the PFC. Analysis of ensemble reactivation was specific to the emotional valence of the second stimuli. We found that a greater proportion of the EGFP+ ensemble was reactivated in the groups that paired novelty with a positive (cocaine) or neutral (saline) experience in the NAc, while the novelty/stress paired groups exhibited significantly less ensemble overlap in the PFC. However, only in the NAc shell was this increase in ensemble overlap specific to those exposed to both novelty and cocaine. This suggests that the NAc shell, but not the NAc core or PFC, may play an important role in general reward processing by engaging a similar network of neurons.

CognitiveConstruct

RewardProcessing

10.1111/ejn.14592

The European journal of neuroscience

Eur J Neurosci

Pavlovian-to-instrumental transfer in Anorexia Nervosa: A pilot study on conditioned learning and instrumental responding to low- and high-calorie food stimuli.

Anorexia Nervosa is characterized by persistent restraint eating despite severe negative consequences and often a chronic course of the disease. Recent theoretical models suggest that abnormalities in reward processing and incentive salience of disorder-compatible stimuli as observed in addictive behaviours contribute to the development and maintenance of Anorexia Nervosa. The aim of the present study was to investigate the process of the acquisition of food-related conditioned responses and the influence of conditioned low-calorie and high-calorie food stimuli on instrumental responding for different foods. A Pavlovian-to-instrumental transfer paradigm and questionnaires on eating disorder psychopathology (EDE-Q, EDI-2) were administered to patients with Anorexia Nervosa (n = 39) and healthy controls (n = 41). Results indicated that patients with Anorexia Nervosa showed deficits of the acquisition of knowledge of the experimental contingencies. Nevertheless, in patients with Anorexia Nervosa and healthy controls instrumental responding for low- and high-calorie food rewards was affected by stimuli conditioned to these rewards; no group differences were observed. Importantly, in Anorexia Nervosa, instrumental responding for low-calorie food increased with increasing severity of eating disorder psychopathology suggesting weight-loss directed behaviour. Future studies are warranted to enhance our understanding of deficits of reward-associated learning and to replicate and extend findings with regard to the impact of conditioned stimuli on instrumental responding. At present, our findings suggest that cognitive treatment interventions might be warranted that challenge dysfunctional beliefs about weight loss.

CognitiveConstruct

RewardProcessing

10.1016/B978-0-12-804281-6.00021-5

Handbook of clinical neurology

Handb Clin Neurol

Neurodegenerative disorders of the human frontal lobes.

The frontal lobes play an integral role in human socioemotional and cognitive function. Sense of self, moral decisions, empathy, and behavioral monitoring of goal-states all depend on key nodes within frontal cortex. While several neurodegenerative diseases can affect frontal function, frontotemporal dementia (FTD) has particularly serious and specific effects, which thus provide insights into the role of frontal circuits in homeostasis and adaptive behavior. FTD represents a collection of disorders with specific clinical-pathologic correlates, imaging, and genetics. Patients with FTD and initial prefrontal degeneration often present with neuropsychiatric symptoms such as loss of social decorum, new obsessions, or lack of empathy. In those patients with early anterior temporal degeneration, language (particularly in patients with left-predominant disease) and socioemotional changes (particularly in patients with right-predominant disease) precede eventual frontal dysregulation. Herein, we review a brief history of FTD, initial clinical descriptions, and the evolution of nomenclature. Next, we consider clinical features, neuropathology, imaging, and genetics in FTD-spectrum disorders in relation to the integrity of frontal circuits. In particular, we focus our discussion on behavioral variant FTD given its profound impact on cortical and subcortical frontal structures. This review highlights the clinical heterogeneity of behavioral phenotypes as well as the clinical-anatomic convergence of varying proteinopathies at the neuronal, regional, and network level. Recent neuroimaging and modeling approaches in FTD reveal varying network dysfunction centered on frontal-insular cortices, which underscores the role of the human frontal lobes in complex behaviors. We conclude the chapter reviewing the cognitive and behavioral neuroscience findings furnished from studies in FTD related to executive and socioemotional function, reward-processing, decision-making, and sense of self.

CognitiveConstruct

RewardProcessing

10.1016/j.appet.2019.104480

Appetite

Appetite

Basal ganglia volume and shape in anorexia nervosa.

Reward-centred models have proposed that anomalies in the basal ganglia circuitry that underlies reward learning and habit formation perpetuate anorexia nervosa (AN). The present study aimed to investigate the volume and shape of key basal ganglia regions, including the bilateral caudate, putamen, nucleus accumbens (NAcc), and globus pallidus in AN. The present study combined data from two existing studies resulting in a sample size of 46 women with AN and 56 age-matched healthy comparison (HC) women. Group differences in volume and shape of the regions of interest were examined. Within the AN group, the impact of eating disorder characteristics on volume and shape of the basal ganglia regions were also explored. The shape analyses revealed inward deformations in the left caudate, right NAcc, and bilateral ventral and internus globus pallidus, and outward deformations in the right middle and posterior globus pallidus in the AN group. The present findings appear to fit with the theoretical models suggesting that there are alterations in the basal ganglia regions associated with habit formation and reward processing in AN. Further investigation of structural and functional connectivity of these regions in AN as well as their role in recovery would be of interest.

CognitiveConstruct

RewardProcessing

10.1016/j.bbi.2019.09.023

Brain, behavior, and immunity

Brain Behav Immun

Effects of stress-induced inflammation on reward processing in healthy young women.

Anhedonia, or loss of interest or pleasure, is a feature of depression and transdiagnostic construct in psychopathology. Theory and compelling evidence from preclinical models implicates stress-induced inflammation as a psychobiological pathway to anhedonic behavior; however, this pathway has not been tested in human models. Further, although anhedonia may reflect dysregulation in multiple dimensions of reward, the extent to which stress-induced inflammation alters these dimensions is unclear. Thus, the current experimental study used a standardized laboratory stressor task to elicit an inflammatory response and evaluate effects of stress-induced inflammation on multiple behavioral indices of reward processing. Healthy young women (age 18-25) completed behavioral reward tasks assessing reward learning, motivation, and sensitivity and were randomized to undergo an acute psychosocial stressor (n = 37) or a no-stress active control (n = 17). Tasks were re-administered 90-120 min post-stress to coincide with the peak of the stress-induced inflammatory response. Blood samples were collected for assessment of the pro-inflammatory cytokine interleukin-6 (IL-6) at baseline and 90 and 120 min post stressor. Stress-induced IL-6 was associated with increased response bias during reward learning and increased motivation when probability of receiving a reward was low. Sensitivity to reward in the context of a motivation task was not altered in association with stress-induced IL-6. Contrary to hypotheses, mild increases in IL-6 following acute stress were associated with increased reward responsiveness during reward learning and selective increases in motivation. Results contribute to an emerging and nuanced literature linking inflammation to reward processing, and demonstrate that behavioral effects of stress-induced inflammation may be detected in the laboratory setting. NCT03828604.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2019.09.036

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

How does cannabidiol (CBD) influence the acute effects of delta-9-tetrahydrocannabinol (THC) in humans? A systematic review.

The recent liberalisation of cannabis regulation has increased public and scientific debate about its potential benefits and risks. A key focus has been the extent to which cannabidiol (CBD) might influence the acute effects of delta-9-tetrahydrocannabinol (THC), but this has never been reviewed systematically. In this systematic review of how CBD influences the acute effects of THC we identified 16 studies involving 466 participants. Ten studies were judged at low risk of bias. The findings were mixed, although CBD was found to reduce the effects of THC in several studies. Some studies found that CBD reduced intense experiences of anxiety or psychosis-like effects of THC and blunted some of the impairments on emotion and reward processing. However, CBD did not consistently influence the effects of THC across all studies and outcomes. There was considerable heterogeneity in dose, route of administration and THC:CBD ratio across studies and no clear dose-response profile emerged. Although findings were mixed, this review suggests that CBD may interact with some acute effects of THC.

CognitiveConstruct

RewardProcessing

10.1111/psyp.13481

Psychophysiology

Psychophysiology

Dissociable effects of reward magnitude on fronto-medial theta and FRN during performance monitoring.

Reward processing is influenced by reward magnitude, as previous EEG studies showed changes in amplitude of the feedback-related negativity (FRN) and reward positivity (RewP), or power of fronto-medial theta (FMθ). However, it remains unclear whether these changes are driven by increased reward sensitivity, altered reward predictions, enhanced cognitive control, or a combination of these effects. To address this question, we asked 36 participants to perform a simple gambling task where feedback valence (reward vs. no-reward), its magnitude (small vs. large reward), and expectancy (expected vs. unexpected) were manipulated in a factorial design, while 64-channel EEG was recorded concurrently. We performed standard ERP analyses (FRN and RewP) as well as time-frequency decompositions (FMθ) of feedback-locked EEG data. Subjective reports showed that large rewards were more liked and expected than small ones. At the EEG level, increasing magnitude led to a larger RewP irrespective of expectancy, whereas the FRN was not influenced by this manipulation. In comparison, FMθ power was overall increased when reward magnitude was large, except if it was unexpected. These results show dissociable effects of reward magnitude on the RewP and FMθ power. Further, they suggest, that although large reward magnitude boosts reward processing (RewP), it can nonetheless undermine the need for enhanced cognitive control (FMθ) in case reward is unexpected. We discuss these new results in terms of optimistic bias or positive mood resulting from an increased reward magnitude.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2019.00209

Frontiers in behavioral neuroscience

Front Behav Neurosci

Social and Non-social Reward Processing and Depressive Symptoms Among Sexual Minority Adolescents.

Sexual minority adolescents (SMA) are more likely to suffer from depression, putatively through experiences of social stress and victimization interfering with processing of social reward. Alterations in neural reward networks, which develop during adolescence, confer risk for the development of depression. Employing both social and monetary reward fMRI tasks, this is the first neuroimaging study to examine function in reward circuitry as a potential mechanism of mental health disparities between SMA and heterosexual adolescents. Eight SMA and 38 heterosexual typically developing adolescents completed self-report measures of depression and victimization, and underwent fMRI during monetary and peer social reward tasks in which they received positive monetary or social feedback, respectively. Compared with heterosexual adolescents, SMA had greater interpersonal depressive symptoms and exhibited blunted neural responses to social, but not monetary, reward in socioaffective processing regions that are associated with depressive symptoms. Specifically, compared with heterosexual adolescents, SMA exhibited decreased activation in the right medial prefrontal cortex, left anterior insula (AI), and right temporoparietal junction (TPJ) in response to being liked. Lower response in the right TPJ was associated with greater interpersonal depressive symptoms. These results suggest that interpersonal difficulties and the underlying substrates of response to social reward (perhaps more so than response to monetary reward) may confer risk for development of depressive symptoms in SMA.

CognitiveConstruct

RewardProcessing

10.1002/hbm.24796

Human brain mapping

Hum Brain Mapp

Subcortical structural variations associated with low socioeconomic status in adolescents.

Low socioeconomic status (SES) is associated with a higher probability of multiple exposures (e.g., neighborhood violence, poor nutrition, housing instability, air pollution, and insensitive caregiving) known to affect structural development of subcortical brain regions that subserve threat and reward processing, however, few studies have examined the relationship between SES and such subcortical structures in adolescents. We examined SES variations in volume and surface morphometry of subcortical regions. The sample comprised 256 youth in eighth grade (mean age = 13.9 years), in whom high dimensional deformation mapping of structural 3T magnetic resonance imaging scans was performed. Vertex-wise linear regression analyses examined associations between income to poverty ratio and surfaces of the hippocampus, amygdala, thalamus, caudate, putamen, nucleus accumbens and pallidum, with the covariates age, pubertal status, and intracranial volume. Given sex differences in pubertal development and subcortical maturation at this age, the analyses were stratified by sex. Among males, who at this age average an earlier pubertal stage than females, the relationship between SES and local shape variation in subcortical regions was almost entirely positive. For females, the relationship between SES and local shape variation was negative. Racial identity was associated with SES in our sample, however supplementary analyses indicated that most of the associations between SES and subcortical structure were independent of it. Although these cross-sectional results are not definitive, they are consistent with a scenario where low SES delays structural maturation of subcortical regions involved with threat and reward processing. Future longitudinal studies are needed to test this hypothesis.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2019.00177

Frontiers in behavioral neuroscience

Front Behav Neurosci

Social and Non-social Reward: A Preliminary Examination of Clinical Improvement and Neural Reactivity in Adolescents Treated With Behavioral Therapy for Anxiety and Depression.

Pediatric anxiety and depression are highly prevalent and debilitating disorders that often co-occur. Neural circuitry of reward processing has been shown to be implicated in both, and there is an emerging evidence base linking treatment response to brain patterns of reward processing. The current study aimed to add to this literature by investigating the association between clinical improvement and social and non-social reward in youth previously treated for anxiety and depression. The current study leveraged clinical improvement data from a successful randomized controlled trial testing the efficacy of a transdiagnostic, brief behavioral treatment for youth diagnosed with anxiety or depression. Participants ( = 15) interested in engaging in a neuroimaging follow-up underwent an fMRI scan, during which they completed social (i.e., Face Task) and non-social (i.e., Piñata Task, a youth-friendly monetary incentive delay task) reward tasks. Whole-brain activation and functional connectivity analyses identified neural responses to the tasks separately; a third set of analyses directly compared clinical improvement-related findings to understand the impact of task context on neural reactivity to reward. Activation-based findings were sparse; however, connectivity as a function of degree of treatment response was apparent and robust. Within the context of social reward, significant clusters within frontal and temporal regions driven by happy face contrasts, the social reward stimulus, were observed. This supports connectivity between these regions and both amygdala and ventral striatum seeds as a function of degree of clinical improvement. Connectivity within the context of non-social reward also yielded significant clusters in temporal and parietal regions. Here too, the magnitude and direction of region coupling depended on the degree of clinical improvement and the task conditions. No differences in connectivity by task type as a function of clinical improvement were found. Findings serve as preliminary evidence that neural regions found to be related to clinical improvement within the context of social and non-social reward are similar to regions that have been shown to support reward processing in normative samples. Implications for treatment and future work are discussed.

CognitiveConstruct

RewardProcessing

10.1016/j.clinph.2019.08.015

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

Clin Neurophysiol

Resting state oscillations suggest a motor component of Parkinson's Impulse Control Disorders.

Impulse control disorders (ICDs) in Parkinson's disease (PD) have been associated with cognitive impulsivity and dopaminergic dysfunction and treatment. The present study tests the neglected hypothesis that the neurofunctional networks involved in motor impulsivity might also be dysfunctional in PD-ICDs. We performed blind spectral analyses of resting state electroencephalographic (EEG) data in PD patients with and without ICDs to probe the functional integrity of all cortical networks. Analyses were performed directly at the source level after blind source separation. Discrete differences between groups were tested by comparing patients with and without ICDs. Gradual dysfunctions were assessed by means of correlations between power changes and clinical scores reflecting ICD severity (QUIP score). Spectral signatures of ICDs were found in the medial prefrontal cortex, the dorsal anterior cingulate and the supplementary motor area, in the beta and gamma bands. Beta power changes in the supplementary motor area were found to predict ICDs severity. ICDs are associated with abnormal activity within frequency bands and cortical circuits supporting the control of motor response inhibition. These results bring to the forefront the need to consider, in addition to the classical interpretation based on aberrant mesocorticolimbic reward processing, the issue of motor impulsivity in PD-ICDs and its potential implications for PD therapy.

CognitiveConstruct

RewardProcessing

10.1016/j.jsat.2019.07.008

Journal of substance abuse treatment

J Subst Abuse Treat

Feasibility and acceptability of approach bias modification during methamphetamine withdrawal and related methamphetamine use outcomes.

Approach bias modification (ApBM), a computerised cognitive training task which aims to reduce automatic, impulsive responding to drug-related cues, has been found to reduce alcohol consumption among individuals seeking treatment for their drinking. However, this approach has not been trialled in patients with methamphetamine use disorder (MUD), where altered impulsivity and reward processing are well-established. As such, this study aimed to examine the feasibility and acceptability of four consecutive days of ApBM training during a residential admission for methamphetamine withdrawal. Abstinence rates were examined 2-weeks and 3-months post-discharge. In terms of uptake, 52 of the 99 eligible patients approached agreed to participate and 47 of these 52 commenced training. Uptake and training completion rates (62%) were lower than those achieved in similar trials of ApBM for residential alcohol withdrawal, suggesting there are challenges to its delivery in this setting. This is likely due to the severity of acute methamphetamine withdrawal syndrome and associated behavioural characteristics. However, participants' ratings of the task and reports of post-session craving suggest acceptability was high. Abstinence rates were 61% at 2 weeks and 54% at 3-months, which compare favourably with the abstinence rates observed in a previous large treatment outcome study. The evidence of acceptability and apparent effectiveness suggest future trials of ApBM with MUD patients are warranted. However, ApBM may be more feasible in certain settings or among particular sub-groups where patients are more clinically stable and therefore more likely to complete the training (e.g., residential rehabilitation, after acute withdrawal has subsided).

CognitiveConstruct

RewardProcessing

10.1038/s41598-019-49884-6

Scientific reports

Sci Rep

Goal-directed vs. habitual instrumental behavior during reward processing in anorexia nervosa: an fMRI study.

Previous studies have proposed that altered reward processing and elevated cognitive control underlie the etiology of anorexia nervosa (AN). A newly debated notion suggests altered habit learning and an overreliance on habits may contribute to the persistence of AN. In weight-recovered AN patients, we previously found neuroimaging-based evidence for unaltered reward processing, but elevated cognitive control. In order to differentiate between state versus trait factors, we here contrast the aforementioned hypotheses in a sample of acutely underweight AN (acAN) patients. 37 acAN patients and 37 closely matched healthy controls (HC) underwent a functional MRI while performing an established instrumental motivation task. We found no group differences with respect to neural responses during the anticipation or receipt of reward. However, the behavioral response data showed a bimodal distribution, indicative for a goal-directed (gAN) and a habit-driven (hAN) patient subgroup. Additional analyses revealed decreased mOFC activation during reward anticipation in hAN, which would be in line with a habit-driven response. These findings provide a new perspective on the debate regarding the notion of increased goal-directed versus habitual behavior in AN. If replicable, the observed dissociation between gAN and hAN might help to tailor therapeutic approaches to individual patient characteristics.

CognitiveConstruct

RewardProcessing

10.1176/appi.ajp.2019.18070870

The American journal of psychiatry

Am J Psychiatry

Effect of Intrinsic Patterns of Functional Brain Connectivity in Moderating Antidepressant Treatment Response in Major Depression.

Major depressive disorder is associated with aberrant resting-state functional connectivity across multiple brain networks supporting emotion processing, executive function, and reward processing. The purpose of this study was to determine whether patterns of resting-state connectivity between brain regions predict differential outcome to antidepressant medication (sertraline) compared with placebo. Participants in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study underwent structural and resting-state functional MRI at baseline. Participants were then randomly assigned to receive either sertraline or placebo treatment for 8 weeks (N=279). A region of interest-based approach was utilized to compute functional connectivity between brain regions. Linear mixed-model intent-to-treat analyses were used to identify brain regions that moderated (i.e., differentially predicted) outcomes between the sertraline and placebo arms. Prediction of response to sertraline involved several within- and between-network connectivity patterns. In general, higher connectivity within the default mode network predicted better outcomes specifically for sertraline, as did greater between-network connectivity of the default mode and executive control networks. In contrast, both placebo and sertraline outcomes were predicted (in opposite directions) by between-network hippocampal connectivity. This study identified specific functional network-based moderators of treatment outcome involving brain networks known to be affected by major depression. Specifically, functional connectivity patterns of brain regions between and within networks appear to play an important role in identifying a favorable response for a drug treatment for major depressive disorder.

CognitiveConstruct

RewardProcessing

10.1093/ajcn/nqz204

The American journal of clinical nutrition

Am J Clin Nutr

Weight gain is associated with changes in neural response to palatable food tastes varying in sugar and fat and palatable food images: a repeated-measures fMRI study.

Emerging data suggest that weight gain is associated with changes in neural response to palatable food tastes and palatable food cues, which may serve to maintain overeating. We investigated whether weight gain is associated with neural changes in response to tastes of milkshakes varying in fat and sugar content and palatable food images. We compared changes in neural activity between initially healthy-weight adolescents who gained weight (n = 36) and those showing weight stability (n = 31) over 2-3 y. Adolescents who gained weight compared with those who remained weight stable showed decreases in activation in the postcentral gyrus, prefrontal cortex, insula, and anterior cingulate cortex, and increases in activation in the parietal lobe, posterior cingulate cortex, and inferior frontal gyrus in response to a high-fat/low-sugar compared with low-fat/low-sugar milkshake. Weight gainers also showed greater decreases in activation in the anterior insula and lateral orbitofrontal cortex in response to a high-fat/high-sugar compared with low-fat/low-sugar milkshake than those who remained weight stable. No group differences emerged in response to a low-fat/high-sugar compared with a low-fat/low-sugar milkshake. Weight gainers compared with those who remained weight stable showed greater decreases in activation in the middle temporal gyrus and increases in cuneus activation in response to appetizing compared with unappetizing food pictures. The significant interactions were partially driven by group differences in baseline responsivity and by opposite changes in neural activation in adolescents who remained weight stable. Data suggest that weight gain is associated with a decrease in responsivity of regions associated with taste and reward processing to palatable high-fat- and high-fat/high-sugar food tastes. Data also suggest that avoiding weight gain increases taste sensitivity, which may prevent future excessive weight gain.This trial was registered at clinicaltrials.gov as NCT01949636.

CognitiveConstruct

RewardProcessing

10.3390/brainsci9090230

Brain sciences

Brain Sci

Effects of High Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS) on Delay Discounting in Major Depressive Disorder: An Open-Label Uncontrolled Pilot Study.

Delay discounting (DD) refers to the decrease of a present subjective value of a future reward as the delay of its delivery increases. Major depressive disorder (MDD), besides core emotional and physical symptoms, involves difficulties in reward processing. Depressed patients often display greater temporal discounting rates than healthy subjects. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique applied in several countries to adult patients with treatment resistant depression. Studies suggest that this technique can be used to modulate DD, but no trial has assessed its effects on depressed patients. In this open-label uncontrolled trial, 20 patients diagnosed with MDD and at least stage II treatment resistance criteria underwent 20 HF-rTMS sessions over the dorsolateral prefrontal cortex (dlPFC; 10 Hz, 110% MT, 20 min). Pre-post treatment DD rates were compared. Effects on impulsivity, personality factors, and depressive symptoms were also evaluated. No significant effect of HF-rTMS over the left dlPFC on DD of depressed individuals was observed, although rates seemed to increase after sessions. However, treatment resulted in significant improvement on cognitive impulsivity and depressive symptoms, and was well-tolerated. Despite the limitations involved, this pilot study allows preliminary evaluation of HF-rTMS effects on DD in MDD, providing substrate for further research.

CognitiveConstruct

RewardProcessing

10.1016/j.celrep.2019.08.009

Cell reports

Cell Rep

A Midbrain Circuit that Mediates Headache Aversiveness in Rats.

Migraines are a major health burden, but treatment is limited because of inadequate understanding of neural mechanisms underlying headache. Imaging studies of migraine patients demonstrate changes in both pain-modulatory circuits and reward-processing regions, but whether these changes contribute to the experience of headache is unknown. Here, we demonstrate a direct connection between the ventrolateral periaqueductal gray (vlPAG) and the ventral tegmental area (VTA) that contributes to headache aversiveness in rats. Many VTA neurons receive monosynaptic input from the vlPAG, and cranial nociceptive input increases Fos expression in VTA-projecting vlPAG neurons. Activation of PAG inputs to the VTA induces avoidance behavior, while inactivation of these projections induces a place preference only in animals with headache. This work identifies a distinct pathway that mediates cranial nociceptive aversiveness.

CognitiveConstruct

RewardProcessing

10.7554/eLife.46764

eLife

Elife

Classical conditioning drives learned reward prediction signals in climbing fibers across the lateral cerebellum.

Classical models of cerebellar learning posit that climbing fibers operate according to a supervised learning rule to instruct changes in motor output by signaling the occurrence of movement errors. However, cerebellar output is also associated with non-motor behaviors, and recently with modulating reward association pathways in the VTA. To test how the cerebellum processes reward related signals in the same type of classical conditioning behavior typically studied to evaluate reward processing in the VTA and striatum, we have used calcium imaging to visualize instructional signals carried by climbing fibers across the lateral cerebellum in mice before and after learning. We find distinct climbing fiber responses in three lateral cerebellar regions that can each signal reward prediction. These instructional signals are well suited to guide cerebellar learning based on reward expectation and enable a cerebellar contribution to reward driven behaviors, suggesting a broad role for the lateral cerebellum in reward-based learning.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsz062

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Aberrant reward dynamics in trait anticipatory anhedonia.

As a cardinal feature of several psychiatric disorders, anhedonia includes a consummatory component (deficits in hedonic response to rewards) and an anticipatory component (a reduced motivation to pursue them). Although being conceptualized as impairments of reward system, the neural characterization of reward processing in anhedonia is hampered by the enormous heterogeneity in the reward phase ('wanting' vs 'liking') and comorbidity (inherent to disease states). The current event-related potential (ERP) study examined the reward dynamics of anticipatory anhedonia in a non-clinical sample. Anticipatory and consummatory ERP components were assessed with a monetary incentive delay task in a high anticipatory anhedonia (HAA) group and a low anticipatory anhedonia (LAA) group. HAA vs LAA group showed a diminished reward-related speeding during behavioral performance and reported overall reduced positive affect during anticipation and receipt of outcomes. Importantly, neural dynamics underlying reward processing were negatively associated with anticipatory anhedonia across the anticipatory phase indexed by the contingent negative variation and the consummatory phase indexed by the feedback P3. Our results suggest that anticipatory anhedonia in non-clinical individuals is linked to a poor modulation during both anticipatory and consummatory phases of reward processing.

CognitiveConstruct

RewardProcessing

10.1080/10550887.2019.1643211

Journal of addictive diseases

J Addict Dis

Addictive behaviors in alcohol use disorder: dysregulation of reward processing systems and maladaptive coping strategies.

DSM-5 has included within the substance-related and addictive disorders diagnostic category behavioral addictions, such as gambling disorder. Some scholars also considered ICD-11 compulsive sex as a behavioral addiction. Furthermore, an addiction model of dysfunctional eating behaviors has been proposed. Consistently, the existence of common addiction mechanisms related to substance and non-substance related disorders has been hypothesized. Nevertheless, this approach was called into question, especially considering alternative processes which might be implicated in such conditions. This study aims to compare these opposite theoretical positions concerning substance- and nonsubstance related disorders, investigating the latent structure of addictive behaviors among alcohol use disorder (AUD) individuals. Addictive behaviors were self-reported assessed using the Shorter PROMIS Questionnaire (SPQ). We recruited 456 (59.2% male; 40.8% female) AUD treatment-seeking patients. Two latent structures were tested using a confirmatory factor analytic approach. We compared a one-factor (i.e., common addiction mechanisms) with a two-factor solution (i.e., dysregulation of reward processing systems and maladaptive coping strategies). The two-factor solution showed adequate goodness-of-fit indexes. Specifically, dysregulation of the reward processing systems dimension predicted the SPQ illicit and prescription drugs, gambling, and sex subscales. Conversely, the maladaptive coping strategies dimension predicted the SPQ compulsive buying, binge eating and food restriction subscales. The latent dimensions significantly correlated with each other. Compulsive sex might be preliminarily considered as a behavioral addiction. AUD individuals might show complex patterns of maladaptive behaviors functionally related to different latent processes. Differential treatment approaches are suggested to treat these conditions.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2019.101920

NeuroImage. Clinical

Neuroimage Clin

Resilience to adversity is associated with increased activity and connectivity in the VTA and hippocampus.

Accumulating evidence suggests altered function of the mesolimbic reward system resulting from exposure to early adversity. The present study investigated the combined long-term impact of adversity until young adulthood on neuronal reward processing and its interaction with individual resilience processes. In this functional magnetic resonance imaging study, 97 healthy young adults performed a reward-based decision-making task. Adversity as well as resilience were assessed retrospectively using the validated childhood trauma questionnaire, trauma history questionnaire and a resilience scale. Subjects with high adversity load showed reduced reward-related bottom-up activation in the ventral striatum (VS), ventral tegmental area (VTA) and hippocampus (HP) as compared to the low adversity group. However, high resilience traits in individuals with high adversity load were associated with an increased activation in the VTA and HP, indicating a possible resilience-related protective mechanism. Moreover, when comparing groups with high to low adversity, psychophysiological interaction analyses highlighted an increased negative functional coupling between VS and VTA as well as between VS and anteroventral prefrontal cortex (avPFC) during reward acceptance, and an impaired top-down control of the VS by the avPFC during reward rejection. In turn, combination of high adversity and high resilience traits was associated with an improved functional coupling between VTA, VS and HP. Thereby, the present findings identify neural mechanisms mediating interacting effects of adversity and resilience, which could be targeted by early intervention and prevention.

CognitiveConstruct

RewardProcessing

10.1111/bdi.12834

Bipolar disorders

Bipolar Disord

Affective cognition in bipolar disorder: A systematic review by the ISBD targeting cognition task force.

Impairments in affective cognition are part of the neurocognitive profile and possible treatment targets in bipolar disorder (BD), but the findings are heterogeneous. The International Society of Bipolar Disorder (ISBD) Targeting Cognition Task Force conducted a systematic review to (i) identify the most consistent findings in affective cognition in BD, and (ii) provide suggestions for affective cognitive domains for future study and meta-analyses. The review included original studies reporting behavioral measures of affective cognition in BD patients vs controls following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement. Searches were conducted on PubMed/MEDLINE, EMBASE, and PsychInfo from inception until November 2018. A total of 106 articles were included (of which nine included data for several affective domains); 41 studies assessed emotional face processing; 23 studies investigated reactivity to emotional words and images; 3 investigated explicit emotion regulation; 17 assessed implicit emotion regulation; 31 assessed reward processing and affective decision making. In general, findings were inconsistent. The most consistent findings were trait-related difficulties in facial emotion recognition and implicit emotion regulation, and impairments in reward processing and affective decision making during mood episodes. Studies using eye-tracking and facial emotion analysis revealed subtle trait-related abnormalities in emotional reactivity. The ISBD Task Force recommends facial expression recognition, implicit emotion regulation, and reward processing as domains for future research and meta-analyses. An important step to aid comparability between studies in the field would be to reach consensus on an affective cognition test battery for BD.

CognitiveConstruct

RewardProcessing

10.1016/j.neulet.2019.134473

Neuroscience letters

Neurosci Lett

Cardiac cycle modulates reward feedback processing: An ERP study.

The present study aimed to investigate whether the evaluative processing of action feedback is influenced by the cardiac cycle. To this aim, we examined the influence of the cardiac cycle on an event-related brain potential (ERP) effect that indexed the evaluative processing of action feedback [i.e., an ERP effect that interpreted as a feedback-related negativity (FRN) elicited by "bad" action feedback or a reward positivity (RewP) elicited by "good" action feedback]. Participants performed a gambling task in which they chose one of two stimuli and received an action feedback that indicated monetary gain or loss. Each trial was retrospectively classified into systole and diastole trials; systole trials were defined as those where monetary outcomes were presented during systole, and the diastole trials as those where monetary outcomes were presented during diastole. The results showed that the FRN/RewP was larger for the systole trials than for the diastole trials, which was due to the modulation of gain rather than loss ERPs. These results provide evidence that the natural fluctuation of cardiac afferent signals can modulate the evaluative processing of feedback.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2019.06.027

Biological psychiatry

Biol Psychiatry

Epigenetic Mechanisms of Opioid Addiction.

Opioid use kills tens of thousands of Americans each year, devastates families and entire communities, and cripples the health care system. Exposure to opioids causes long-term changes to brain regions involved in reward processing and motivation, leading vulnerable individuals to engage in pathological drug seeking and drug taking that can remain a lifelong struggle. The persistence of these neuroadaptations is mediated in part by epigenetic remodeling of gene expression programs in discrete brain regions. Although the majority of work examining how epigenetic modifications contribute to addiction has focused on psychostimulants such as cocaine, research into opioid-induced changes to the epigenetic landscape is emerging. This review summarizes our knowledge of opioid-induced epigenetic modifications and their consequential changes to gene expression. Current evidence points toward opioids promoting higher levels of permissive histone acetylation and lower levels of repressive histone methylation as well as alterations to DNA methylation patterns and noncoding RNA expression throughout the brain's reward circuitry. Additionally, studies manipulating epigenetic enzymes in specific brain regions are beginning to build causal links between these epigenetic modifications and changes in addiction-related behavior. Moving forward, studies must leverage advanced chromatin analysis and next-generation sequencing approaches combined with bioinformatics pipelines to identify novel gene networks regulated by particular epigenetic modifications. Improved translational relevance also requires increased focus on volitional drug-intake models and standardization of opioid exposure paradigms. Such work will significantly advance our understanding of how opioids cause persistent changes to brain function and will provide a platform on which to develop interventions for treating opioid addiction.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2019.08.004

Psychiatry research. Neuroimaging

Psychiatry Res Neuroimaging

Neural reward processing in paediatric Tourette syndrome and/or attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is the most common comorbidity in individuals with Tourette syndrome (TS). Yet, it is unclear to what extent TS and ADHD show overlapping or distinct neural abnormalities. ADHD has been associated with altered reward processing, but there are very few studies on reward processing in TS. This study assessed neural activation of basal ganglia and thalamus during reward anticipation and receipt in children with TS and/or ADHD. We analysed mean activations of a priori specified regions of interest during an fMRI monetary incentive delay task. Data was used from 124 children aged 8-12 years (TS n = 47, of which 29 had comorbid ADHD; ADHD n = 29; healthy controls n = 48). ADHD severity across ADHD and TS groups and healthy controls was marginally related to hypoactivation of the right nucleus accumbens during reward anticipation; this effect was not moderated by TS diagnosis. We detected no associations of neural activation with TS. The association between ADHD severity and hypoactivation of the right nucleus accumbens during reward anticipation, independent of the presence or absence of TS, is in line with the view of nucleus accumbens hypoactivation as a dimensional, neurofunctional marker of ADHD severity, transcending the boundaries of primary diagnosis.

CognitiveConstruct

RewardProcessing

10.1016/j.bpsc.2019.06.014

Biological psychiatry. Cognitive neuroscience and neuroimaging

Biol Psychiatry Cogn Neurosci Neuroimaging

Reward-Related Striatal Responses Following Stress in Healthy Individuals and Patients With Bipolar Disorder.

Stress has a major impact on the onset and recurrence of mood episodes in bipolar disorder (BD), but the underlying mechanisms remain unknown. Previous studies have shown distinct time-dependent effects of stress on reward processing in healthy individuals. Impaired reward processing is a core characteristic of BD, and altered reward processing during recovery from stress could influence the development and course of bipolar disorder. We investigated brain responses during reward processing 50 minutes after stress using functional magnetic resonance imaging in 40 healthy control subjects and 40 patients with euthymic BD assigned to either an acute stress test (Trier Social Stress Test) or a no-stress condition. Acute stress increased cortisol levels in both healthy control subjects and patients with BD. Ventral striatal responses to reward outcome were increased in healthy control subjects during stress recovery but not in patients with BD. For anticipation, no differences were found between the groups following stress. For the first time, we show altered reward processing in patients with BD during the recovery phase of stress. These data suggest reduced neural flexibility of hedonic signaling in response to environmental challenges. This may increase the susceptibility to stressful life events in the future and play a role in the development of further psychopathology in the longer term.

CognitiveConstruct

RewardProcessing

10.1038/s41386-019-0499-0

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Orbitofrontal cortex is selectively activated in a primate model of attentional bias to cocaine cues.

Attentional bias to drug-associated cues correlates with extent of current use, and risk of relapse among those attempting abstinence. Electroencephalogram (EEG) and functional imaging measures in clinical studies have previously investigated the neural basis of attentional bias, but the lack of animal models precluded investigation at the single-unit level. To complement results obtained from clinical studies, we have employed a non-human primate model of attentional bias to cocaine cues while simultaneously recording single-unit activity in cortical and striatal regions implicated in reward processing. Rhesus macaques conditioned to associate particular colors with cocaine or water reward performed an attentional bias task, in which those colors served as irrelevant distractors. Concurrently, multiple electrode arrays for recording single-unit activity were acutely implanted into the orbitofrontal cortex, anterior cingulate cortex, dorsal anterior striatum, and ventral striatum. As in clinical studies, attentional bias was indicated by elongated response times on trials with cocaine-associated distractors compared with trials with water-associated, or control unconditioned distractors. In both animals studied, across an unbiased sample of neurons, the orbitofrontal cortex differentiated distractor condition by the proportion of single-units activated, as well as by population response. In one of the two, the anterior cingulate cortex did as well, but neither striatal region did in either animal. These direct measures of single-unit activity in a primate model complement clinical imaging observations suggesting that cortical mechanisms, especially in orbitofrontal cortex, are likely involved in attentional bias to cocaine-associated environmental cues.

CognitiveConstruct

RewardProcessing

10.1002/acn3.50869

Annals of clinical and translational neurology

Ann Clin Transl Neurol

Neural networks associated with body composition in frontotemporal dementia.

Frontotemporal dementia (FTD) is associated with complex changes in eating behavior and metabolism, which potentially affect disease pathogenesis and survival. It is currently not known if body composition changes and changes in fat deposition also exist in FTD, the relationship of these changes in eating behavior and appetite, and whether these changes are centrally mediated. Body composition was measured in 28 people with behavioral-variant frontotemporal dementia (bvFTD), 16 with Alzheimer's disease (AD), and 19 healthy controls, using dual energy x-ray absorptiometry. Changes in body composition were correlated to brain grey matter atrophy using voxel-based morphometry on high-resolution magnetic resonance imaging. Behavioral-variant FTD was characterized by changes in body composition, with increased total fat mass, visceral adipose tissue area (VAT area), and android: gynoid ratio compared to control and AD participants (all P values < 0.05). Changes in body composition correlated to abnormal eating behavior and behavioral change (P < 0.01) and functional decline (P < 0.01). Changes in body composition also correlated to grey matter atrophy involving a distributed neural network that included the hippocampus, amygdala, nucleus accumbens, insula, cingulate, and cerebellum - structures known to be central to autonomic control - as well as the thalamus, putamen, accumbens, and caudate, which are involved in reward processing. Changes in body composition and fat deposition extend the clinical phenomenology in bvFTD beyond cognition and behavior, with changes associated with changes in reward and autonomic processing suggesting that these deficits may be central in FTD.

CognitiveConstruct

RewardProcessing

10.3389/fnut.2019.00118

Frontiers in nutrition

Front Nutr

Induced Pluripotent Stem Cells; New Tools for Investigating Molecular Mechanisms in Anorexia Nervosa.

Anorexia nervosa (AN) is a dramatic psychiatric disorder characterized by dysregulations in food intake and reward processing, involving molecular and cellular changes in several peripheral cell types and central neuronal networks. Genomic and epigenomic analyses have allowed the identification of multiple genetic and epigenetic modifications highlighting the complex pathophysiology of AN. Behavioral and genetic rodent models have been used to recapitulate and investigate, with some limitations, the cellular and molecular changes that potentially underlie eating disorders. In the last 5 years, the use of induced pluripotent stem cells (IPSCs), combined with CRISPR-Cas9 technology, has led to the generation of specific neuronal cell subtypes engineered from human somatic samples, representing a powerful tool to complement observations made in human samples and data collected from animal models. Systems biology using IPSCs has indeed proved to be a valuable approach for the study of metabolic disorders, in addition to neurodevelopmental and psychiatric disorders. The manuscript, while reviewing the main findings related to the genetic, epigenetic, and cellular bases of AN, will present how new studies published, or to be performed, in the field of IPSC-derived cells should improve our current understanding of the pathophysiology of AN and provide potential therapeutic strategies addressing specific endophenotypes.

CognitiveConstruct

RewardProcessing

10.1111/psyp.13469

Psychophysiology

Psychophysiology

Dysfunctional cognitive control and reward processing in adolescents with Internet gaming disorder.

Developmental theories posit that immature cognitive control and excessive reward-seeking capacities may be a risk factor for addictive behaviors during adolescence, but the control and reward capacities have rarely been assessed experimentally in adolescents with Internet gaming disorder (IGD) simultaneously. This electrophysiological study examined inhibitory control and reward processing in adolescents with IGD during a go/no-go task and a gambling task. Behaviorally, the adolescents with IGD exhibited lower inhibitory control, as measured by the accuracy of no-go trials, and more risk seeking, as measured by the proportion of risky choices, than did the controls. Compared with the controls, the adolescents with IGD exhibited decreased no-go P3 and blunted feedback-related negativity (FRN) amplitudes following gains (gain FRN) but not losses. Thus, IGD in adolescents is potentially driven by dysfunction of the control system and the approach system rather than the avoidance system, supporting the neurobiological model of adolescent development.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2019.100690

Developmental cognitive neuroscience

Dev Cogn Neurosci

Puberty and functional brain development in humans: Convergence in findings?

Although there is a long history of studying the influence of pubertal hormones on brain function/structure in animals, this research in human adolescents is young but burgeoning. Here, we provide a comprehensive review of findings from neuroimaging studies investigating the relation between pubertal and functional brain development in humans. We quantified the findings from this literature in which statistics required for standard meta-analyses are often not provided (i.e., effect size in fMRI studies). To do so, we assessed convergence in findings within content domains (reward, facial emotion, social information, cognitive processing) in terms of the locus and directionality (i.e., positive/negative) of effects. Face processing is the only domain with convergence in the locus of effects in the amygdala. Social information processing is the only domain with convergence of positive effects; however, these effects are not consistently present in any brain region. There is no convergence of effects in either the reward or cognitive processing domains. This limited convergence in findings across domains is not the result of null findings or even due to the variety of experimental paradigms researchers employ. Instead, there are critical theoretical, methodological, and analytical issues that must be addressed in order to move the field forward.

CognitiveConstruct

RewardProcessing

10.1037/neu0000555

Neuropsychology

Neuropsychology

The effect of alcohol use on neuroimaging correlates of cognitive and emotional processing in human adolescence.

This article provides an overview of the scientific literature pertaining to the effects of alcohol on neural correlates of cognitive and emotional functioning, including reward processing and cue-reactivity, in adolescence and young adulthood. Peer-reviewed, original research articles that included a neuroimaging assessment of alcohol effects on subsequent cognitive or emotional processing in adolescent or young adult samples were searched (through November 2018) and summarized in the review. Cross-sectional studies provided early evidence of alcohol-related differences in neural processing across a number of cognitive domains. Longitudinal studies have identified neural abnormalities that predate drinking within most domains of cognitive functioning, while a few neural alterations have been observed within the domains of visual working memory, inhibitory control, reward processing, and cue-reactivity that appear to be related to the neurotoxic effect of alcohol use during adolescence. In contrast, neural correlates of emotion functioning appear to be relatively stable to the effects of alcohol. Larger prospective studies are greatly needed to disentangle premorbid factors from neural consequences associated with drinking, and to detect subsets of youth who may be particularly vulnerable to alcohol's effects on cognitive and emotional functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2019.00178

Frontiers in behavioral neuroscience

Front Behav Neurosci

Blunted Social Reward Responsiveness Moderates the Effect of Lifetime Social Stress Exposure on Depressive Symptoms.

Exposure to social stress is a well-established risk factor for the development and recurrence of depression. Reduced neural responsiveness to monetary reward has been associated with greater symptoms following stress exposure. However, it remains unclear whether reduced reward responsiveness serves as a mediator or moderator of the effects of stress on internalizing symptoms or whether similar patterns emerge with responses to social reward. We addressed this issue by measuring lifetime stress exposure and event-related potentials (ERPs) to social reward in 231 emerging adults ( = 18.16, = 0.41 years old). Participants completed the Stress and Adversity Inventory (STRAIN) to assess severity of lifetime stressors and self-report measures of current internalizing symptoms. In addition, participants completed the Island Getaway task in which the reward positivity (RewP) ERP was recorded in response to social acceptance, adjusting for responses to rejection (RewP residual). In this task, participants vote to accept or reject peers and receive reward/acceptance and rejection feedback. Stressors were divided into social and non-social stress severity scores. Analyses were conducted to test social reward responsiveness as a mediator or moderator of the effects of social and non-social stress on internalizing symptoms. Both social and non-social stress exposure over the life course predicted symptoms of depression (s < 0.001) and social anxiety (s < 0.002). The effect of social stress on depression was moderated by the residual RewP to social reward, adjusting for responses to social rejection ( =0.024), such that greater lifetime social stress exposure and a relatively blunted RewP to social reward were associated with greater depressive symptoms. Social reward responsiveness did not mediate effects of stress on internalizing symptoms. Reduced processing of social reward may be a vulnerability for depression that increases risk for symptoms following exposure to social stress. Blunted social reward responsiveness appears to be a relatively unique vulnerability for depression, rather than social anxiety. Results support the utility of ERP measures in measuring individual differences in social reward processing that can be applied to better understand neural processes involved in the development of depression, and highlight the importance of considering specific dimensions of stressful life experiences.

CognitiveConstruct

RewardProcessing

10.1038/s41398-019-0534-2

Translational psychiatry

Transl Psychiatry

Cannabidiol attenuates insular dysfunction during motivational salience processing in subjects at clinical high risk for psychosis.

Accumulating evidence points towards the antipsychotic potential of cannabidiol. However, the neurocognitive mechanisms underlying the antipsychotic effect of cannabidiol remain unclear. We investigated this in a double-blind, placebo-controlled, parallel-arm study. We investigated 33 antipsychotic-naïve subjects at clinical high risk for psychosis (CHR) randomised to 600 mg oral cannabidiol or placebo and compared them with 19 healthy controls. We used the monetary incentive delay task while participants underwent fMRI to study reward processing, known to be abnormal in psychosis. Reward and loss anticipation phases were combined to examine a motivational salience condition and compared with neutral condition. We observed abnormal activation in the left insula/parietal operculum in CHR participants given placebo compared to healthy controls associated with premature action initiation. Insular activation correlated with both positive psychotic symptoms and salience perception, as indexed by difference in reaction time between salient and neutral stimuli conditions. CBD attenuated the increased activation in the left insula/parietal operculum and was associated with overall slowing of reaction time, suggesting a possible mechanism for its putative antipsychotic effect by normalising motivational salience and moderating motor response.

CognitiveConstruct

RewardProcessing

10.1017/S0033291719002010

Psychological medicine

Psychol Med

Anhedonia in chronic pain and prescription opioid misuse.

Both acute and chronic pain can disrupt reward processing. Moreover, prolonged prescription opioid use and depressed mood are common in chronic pain samples. Despite the prevalence of these risk factors for anhedonia, little is known about anhedonia in chronic pain populations. We conducted a large-scale, systematic study of anhedonia in chronic pain, focusing on its relationship with opioid use/misuse, pain severity, and depression. Chronic pain patients across four distinct samples (N = 488) completed the Snaith-Hamilton Pleasure Scale (SHAPS), measures of opioid use, pain severity and depression, as well as the Current Opioid Misuse Measure (COMM). We used a meta-analytic approach to determine reference levels of anhedonia in healthy samples spanning a variety of countries and diverse age groups, extracting SHAPS scores from 58 published studies totaling 2664 psychiatrically healthy participants. Compared to healthy samples, chronic pain patients showed higher levels of anhedonia, with ~25% of patients scoring above the standard anhedonia cut-off. This difference was not primarily driven by depression levels, which explained less than 25% of variance in anhedonia scores. Neither opioid use duration, dose, nor pain severity alone was significantly associated with anhedonia. Yet, there was a clear effect of opioid misuse, with opioid misusers (COMM ⩾13) reporting greater anhedonia than non-misusers. Opioid misuse remained a significant predictor of anhedonia even after controlling for pain severity, depression and opioid dose. Study results suggest that both chronic pain and opioid misuse contribute to anhedonia, which may, in turn, drive further pain and misuse.

CognitiveConstruct

RewardProcessing

10.1016/j.neuint.2019.104521

Neurochemistry international

Neurochem Int

Activation of MORs in the VTA induces changes on cFos expression in different projecting regions: Effect of inflammatory pain.

Chronic pain is a worldwide major health problem and many pain-suffering patients are under opioid based therapy. Epidemiological data show that pain intensity correlates with the risk of misuse of prescription opioids, and other drugs of abuse including alcohol. This increased vulnerability to suffer Substance Use Disorders could be, in part, caused by functional changes that occur over the mesocorticolimbic system, a brain pathway involved in reward processing and addiction. Previous data in rats revealed that inflammatory pain desensitizes mu opioid receptors (MORs) in the ventral tegmental area (VTA). As a consequence, pain alters dopamine release in the nucleus accumbens (NAc) derived from MOR activation in the VTA and also increases intake of high doses of heroine. Given that the VTA neurons target different brain regions, in the present study we first analyzed changes induced by inflammatory pain in the MOR dependent activation pattern of the main VTA projecting areas. To do that, we administered two doses (7 or 14 ng) of DAMGO (MORs agonist) or artificial cerebrospinal fluid (aCSF) focally into the VTA of rats and measured the activation in projection areas by cFos immunohistochemistry. Our results show that focal injections of DAMGO in the VTA increases cFos expression in the majority of its projecting areas, namely NAc, basolateral amygdala (BLA), cingulate cortex (ACC) and bed nucleus of the stria terminalis (BNST), as compared to aCSF. Second, we analyzed whether inflammatory pain would affect to cFos expression using a group of rats injected with CFA in the hind paw. In this case, we found that cFos expression was not significantly different between DAMGO and aCSF administered rats in BLA, ACC and BNST. Our results confirm that inflammatory pain induces desensitization of VTA MORs in a region dependent manner which can be very relevant for addictive behaviours.

CognitiveConstruct

RewardProcessing

10.1002/oby.22572

Obesity (Silver Spring, Md.)

Obesity (Silver Spring)

Effects of Cognitive Strategies on Neural Food Cue Reactivity in Adults with Overweight/Obesity.

Functional magnetic resonance imaging (fMRI) studies of obesity have revealed key roles for reward-related and inhibitory control-related activity in response to food cues. This study examines how cognitive strategies impact neural food cue reactivity. In a within-participants, block-design, fMRI paradigm, 30 participants (24 women; mean BMI = 31.8) used four mind-sets while viewing food: "distract" (cognitive behavioral therapy based), "allow" (acceptance and commitment therapy based), "later" (focusing on long-term negative consequences), and "now" (control; focusing on immediate rewards). Participants rated cravings by noting urges to eat on four-point Likert scales after each block. Self-reported cravings significantly differed among all conditions (pairwise comparisons P < 0.05). Cravings were lowest when participants considered long-term consequences (LATER mind-set: 1.7 [SD 0.7]), were significantly higher when participants used the DISTRACT (1.9 [SD 0.7]) and ALLOW (2.3 [SD 0.9]) mind-sets, and were highest when participants used the NOW mind-set (3.2 [SD 0.7]). These behavioral differences were accompanied by differences in neural food cue reactivity. The LATER mind-set (long-term consequences) led to greater inhibitory-control activity in the dorsolateral prefrontal cortex. The cognitive behavioral therapy-based DISTRACT mind-set was associated with greater activity in executive function and reward-processing areas, whereas the ALLOW mind-set (acceptance and commitment therapy) elicited widespread activity in frontal, reward-processing, and default-mode regions. Because focusing on negative long-term consequences led to the greatest decrease in cravings and increased inhibitory control, this may be a promising treatment strategy for obesity.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2019.08.003

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

Int J Psychophysiol

Neural mechanisms of affective instability and cognitive control in substance use.

We explored the impact of affect on cognitive control as this relates to individual differences in affective instability and substance use. Toward this end, we examined how different dimensions of affective instability interact to predict substance misuse and the effect of this on two event-related potential components, the reward positivity and the late positive potential, which are said to reflect the neural mechanisms of reward and emotion processing, respectively. We recorded the ongoing electroencephalogram from undergraduate students as they navigated two T-maze tasks in search of rewards. One of the tasks included neutral, pleasant, and unpleasant pictures from the International Affective Picture System. Participants also completed several questionnaires pertaining to substance use and personality. A principal components analysis revealed a factor related to affective instability, which we named reactivity. This factor significantly predicted increased substance use. Individuals reporting higher levels of affective reactivity also displayed a larger reward positivity following stimuli with emotional content. The current study uncovered a group of high-risk substance users who were characterized by greater levels of affective reactivity and context-specific increased sensitivity to rewards. These results help to elucidate the complex factors underlying substance use and may facilitate the creation of individually-tailored treatment programs for those struggling with substance use disorders.

CognitiveConstruct

RewardProcessing

10.1007/s10508-019-01521-z

Archives of sexual behavior

Arch Sex Behav

Neural Responses to Sexual Stimuli in Heterosexual and Homosexual Men and Women: Men's Responses Are More Specific.

Patterns of genital arousal in response to gendered sexual stimuli (i.e., sexual stimuli presenting members of only one sex at a time) are more predictive of men's than of women's sexual orientations. Additional lines of evidence may shed light on the nature of these differences. We measured neural activation in homosexual and heterosexual men and women using fMRI while they viewed three kinds of gendered sexual stimuli: pictures of nude individuals, pictures of same-sex couples interacting, and videos of individuals self-stimulating. The primary neural region of interest was the ventral striatum (VS), an area of central importance for reward processing. For all three kinds of stimuli and for both VS activation and self-report, men's responses were more closely related to their sexual orientations compared with women's. Furthermore, men showed a much greater tendency to respond more positively to stimuli featuring one sex than to stimuli featuring the other sex, leading to higher correlations among men's responses as well as higher correlations between men's responses and their sexual orientations. Whole-brain analyses identified several other regions showing a similar pattern to the VS, and none showed an opposite pattern. Because fMRI is measured identically in men and women, our results provide the most direct evidence to date that men's sexual arousal patterns are more gender specific than women's.

CognitiveConstruct

RewardProcessing

10.1080/17470919.2019.1653963

Social neuroscience

Soc Neurosci

Money for me and money for friend: An ERP study of social reward processing in adolescents and adults.

Peer relations during adolescence contribute significantly to the development of socio-cognitive skills and pro-sociality. The current study probed the characteristics of adolescent socio-cognitive processing through a card game where they earn money for self and friend. We investigated the choice preference and temporal dynamics of information processing by measuring ERP responses to wins or losses (valence) directed toward self and friend (recipient). Choice data showed that despite adults and adolescents earning equivalent amounts across recipients combined, adults won significantly more for self than a friend; no such difference was found in adolescents. The ERPs in response to choice outcomes showed that the valence information was processed earlier (at P2) in adults, while it was processed later (at P3) in adolescents. Furthermore, a strong effect of recipient was present in adults later in the time course (at P3), while such an effect was weak in adolescents; if any, adolescents showed sensitivity to recipient information earlier at P2. These ERP data suggest a relatively equal allocation of the P3-mediated attentional process to both self and friend's outcomes in adolescents, which parallels the choice behavior. Collectively our results characterize adolescent pro-sociality toward friends, reflecting the importance of peer relationship during this unique developmental period.

CognitiveConstruct

RewardProcessing

10.1038/s41398-019-0520-8

Translational psychiatry

Transl Psychiatry

Altered orbitofrontal sulcogyral patterns in gambling disorder: a multicenter study.

Gambling disorder is a serious psychiatric condition characterized by decision-making and reward processing impairments that are associated with dysfunctional brain activity in the orbitofrontal cortex (OFC). However, it remains unclear whether OFC functional abnormalities in gambling disorder are accompanied by structural abnormalities. We addressed this question by examining the organization of sulci and gyri in the OFC. This organization is in place very early and stable across life, such that OFC sulcogyral patterns (classified into Types I, II, and III) can be regarded as potential pre-morbid markers of pathological conditions. We gathered structural brain data from nine existing studies, reaching a total of 165 individuals with gambling disorder and 159 healthy controls. Our results, supported by both frequentist and Bayesian statistics, show that the distribution of OFC sulcogyral patterns is skewed in individuals with gambling disorder, with an increased prevalence of Type II pattern compared with healthy controls. Examination of gambling severity did not reveal any significant relationship between OFC sulcogyral patterns and disease severity. Altogether, our results provide evidence for a skewed distribution of OFC sulcogyral patterns in gambling disorder and suggest that pattern Type II might represent a pre-morbid structural brain marker of the disease. It will be important to investigate more closely the functional implications of these structural abnormalities in future work.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2019.00160

Frontiers in behavioral neuroscience

Front Behav Neurosci

Neural Mechanisms Involved in Social Conformity and Psychopathic Traits: Prediction Errors, Reward Processing and Saliency.

Aligning behavior in favor of group norms, i.e., social conformity, can help to successfully adapt to uncertain environments and may result in social approval. This may lead to enhanced feelings of belongingness and is found to be associated with reward-related activations in the brain. Individuals high on psychopathic traits violate group norms regularly. Yet, it is unclear how psychopathic traits are related to neural mechanisms involved in social conformity. This functional magnetic resonance imaging (fMRI) study includes 42 healthy females scoring low or high on the Psychopathic Personality Inventory questionnaire (PPI). Participants were asked to rate the trustworthiness of 120 faces while lying in the scanner. After rating each face, participants were presented with the group rating of European students. In an unanticipated second part participants rated all faces again, allowing us to focus on two main contrasts: (1) "Social conflict": group opinion in conflict with the participant's rating vs. group opinion aligned with participant rating; and (2) "Conformity": conflict trials followed by conformity vs. conflict trials followed by non-conformity. Behaviorally, the two groups showed similar conformity behavior. fMRI results showed that both groups activated the nucleus accumbens (NAc) following alignment, suggesting the central role of prediction errors and reward. The data also showed a significant interaction between group and conformity in the amygdala. Following conflicts, females scoring low on psychopathic traits showed a trend in enhanced amygdala activation for conformity relative to non-conformity. Additionally, results showed a trend significant group effect for non-conformity. Females scoring high on psychopathic traits showed more activation for non-conformity compared to females scoring low on psychopathic traits, suggesting altered emotional salience of experiencing conflict depending on psychopathic traits. Taken together, these results support the importance of investigating the role of relevant traits in adaptive behavior when facing uncertain social situations and the neural mechanisms involved in this process.

CognitiveConstruct

RewardProcessing

10.3389/fnint.2019.00029

Frontiers in integrative neuroscience

Front Integr Neurosci

PET Measures of D1, D2, and DAT Binding Are Associated With Heightened Tactile Responsivity in Rhesus Macaques: Implications for Sensory Processing Disorder.

Sensory processing disorder (SPD), a developmental regulatory condition characterized by marked under- or over-responsivity to non-noxious sensory stimulation, is a common but poorly understood disorder that can profoundly affect mood, cognition, social behavior and adaptive life skills. Little is known about the etiology and neural underpinnings. Clinical research indicates that children with SPD show greater prevalence of difficulties in complex cognitive behavior including working memory, behavioral flexibility, and regulation of sensory and affective functions, which are related to prefrontal cortex (PFC), striatal, and midbrain regions. Neuroimaging may provide insight into mechanisms underlying SPD, and animal experiments provide important evidence that is not available in human studies. Rhesus monkeys ( = 73) were followed over a 20-year period from birth into old age. We focused on a single sensory modality, the tactile system, measured at 5-7 years, because of its critical importance for nourishment, attachment, and social reward in development. Positron emission tomography imaging was conducted at ages 12-18 years to quantify the availability of the D1 and D2 subtypes of the DA receptor (D1R and D2R), and the DA transporter (DAT). Heightened tactile responsivity was related to (a) elevated D1R in PFC overall, including lateral, ventrolateral, medial, anterior cingulate (aCg), frontopolar, and orbitofrontal (OFC) subregions, as well as nucleus accumbens (Acb), (b) reduced D2R in aCg, OFC, and substantia nigra/ventral tegmental area, and (c) elevated DAT in putamen. These findings suggest a mechanism by which DA pathways may be altered in SPD. These pathways are associated with reward processing and pain regulation, providing top-down regulation of sensory and affective processes. The balance between top-down cognitive control in the PFC-Acb pathway and bottom-up motivational function of the VTA-Acb-PFC pathway is critical for successful adaptive function. An imbalance in these two systems might explain DA-related symptoms in children with SPD, including reduced top-down regulatory function and exaggerated responsivity to stimuli. These results provide more direct evidence that SPD may involve altered DA receptor and transporter function in PFC, striatal, and midbrain regions. More work is needed to extend these results to humans.

CognitiveConstruct

RewardProcessing

10.1007/s00213-019-05342-9

Psychopharmacology

Psychopharmacology (Berl)

Chronic ketamine abuse is associated with orexin-A reduction and ACTH elevation.

Ketamine has emerged as a major substance of abuse worldwide. Evidence suggests a role of orexin system in reward processing, withdrawal, and stress response. It also interacts with the stress mechanisms of hypothalamic-pituitary-adrenal (HPA) axis to regulate drug-taking behavior. The study aimed to explore the relevance of orexin and stress hormones to chronic ketamine abuse. We enrolled 67 ketamine-dependent (KD) patients and 64 controls. The levels of orexin-A, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline, 1 week, and 2 weeks after ketamine discontinuation. KD patients were assessed by Beck Depression Inventory, Beck Anxiety Inventory, and Visual Analogue Scale for ketamine craving at baseline. Compared with the controls, KD patients had significantly lower orexin-A (0.65 ± 0.12 vs. 0.74 ± 0.10 ng/mL, p < 0.001) and increased ACTH (32.3 ± 16.3 vs. 22.3 ± 11.0 pg/mL, p = 0.008) levels at baseline, whereas cortisol levels were similar between two groups. Levels of the three markers did not correlate with ketamine use variables, craving, depression, or anxiety symptoms. The levels did not alter after 1 or 2 weeks of ketamine discontinuation. Notably, those with higher anxiety had lower orexin-A but increased cortisol levels than did those with lower anxiety. This study showed that KD patients had persistent orexin-A reduction and stress hormone dysregulation in early abstinence. The anxious phenotype of KD might be associated with a lower orexin-A expression. These results point to a promising pathway to investigate the neurochemical mechanisms of ketamine addiction.

CognitiveConstruct

RewardProcessing

10.1037/abn0000456

Journal of abnormal psychology

J Abnorm Psychol

"Reward processing and future life stress: Stress generation pathway to depression": Correction to Mackin et al. (2019).

Reports an error in "Reward processing and future life stress: Stress generation pathway to depression" by Daniel M. Mackin, Roman Kotov, Greg Perlman, Brady D. Nelson, Brandon L. Goldstein, Greg Hajcak and Daniel N. Klein (, 2019[May], Vol 128[4], 305-314). In the article, there is an error in Figure 2 in which the path from "T1-T3 Dependent Life Stress" to "T3 Depression" incorrectly includes a minus sign in front of the estimate value 0.25. Thus, the estimate should be positive and read as follows: =0.25, [0.168, 0.330]. This error does not change the explanation of the results reported in the "Indirect effects of the RewP on depression" section of the Results or any conclusions outlined in the article. (The following abstract of the original article appeared in record 2019-23604-003.) Blunted reward sensitivity and life stress are each depressogenic. Additionally, individuals with clinical and psychosocial vulnerabilities are prone to experience or evoke dependent life stressors (e.g., interpersonal conflict) that, in turn, increase depression risk. However, no previous study has investigated the role of neural vulnerability factors in generating life stress. Therefore, the current study investigated whether a neural measure of reward sensitivity prospectively predicts the generation of life stress, which in turn mediates effects of these neural processes on subsequent depression. Participants were 467 never-depressed adolescent girls. Using event-related potentials, neural sensitivity to the difference between monetary reward and loss (the Reward Positivity [RewP]) was assessed at baseline. Negative life events were assessed twice via interview over the ensuing 18 months, yielding an index of total life stress over the follow-up period. A self-report dimensional measure of depression symptoms was administered at baseline and follow-up. After accounting for baseline age, depression, and race, a blunted RewP predicted greater dependent, but not independent, life stress over the follow-up. Mediation analyses revealed a significant indirect effect of the RewP on follow-up depression through dependent, but not independent, life stress. Our results suggest that neural processing reward and loss plays a crucial role in depressogenic stress generation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

CognitiveConstruct

RewardProcessing

10.1259/bjr.20190165

The British journal of radiology

Br J Radiol

Reward, Control & Decision-Making in Cannabis Use Disorder: Insights from Functional MRI.

The recreational consumption of cannabis has increased significantly across the world with an estimated 180 million people currently using. In the United States, 4.1 million are currently diagnosed with cannabis use disorder. Cannabis dependence and abuse was combined into a single entity as a behavioral disorder with a problematic pattern of cannabis use and termed cannabis use disorder by the Diagnostic and Statistical Manual of Mental Disorders. Chronic use of cannabis has been linked with region-specific effects across the brain mediating reward processing, cognitive control and decision-making that are central to understanding addictive behaviors. This review presents a snapshot of the current literature assessing the effects of chronic cannabis use on human brain function via functional MRI. Studies employing various paradigms and contrasting cognitive activation amongst cannabis users and non-users were incorporated. The effects of trans-del-ta-9-tetrahydrocannabinol (Δ9-THC) in marijuana and other preparations of cannabis are mediated by the endocannabinoid system, which is also briefly introduced.Much variation exists in the current literature regarding the functional changes associated with chronic cannabis use. One possible explanation for this variation is the heterogeneity in study designs, with little implementation of standardized diagnostic criteria when selecting chronic users, distinct time points of participant assessment, differing cognitive paradigms and imaging protocols. As such, there is an urgent requirement for future investigations that further characterize functional changes associated with chronic cannabis use.

CognitiveConstruct

RewardProcessing

10.1371/journal.pcbi.1007224

PLoS computational biology

PLoS Comput Biol

Depressive symptoms are associated with blunted reward learning in social contexts.

Depression is characterized by a marked decrease in social interactions and blunted sensitivity to rewards. Surprisingly, despite the importance of social deficits in depression, non-social aspects have been disproportionally investigated. As a consequence, the cognitive mechanisms underlying atypical decision-making in social contexts in depression are poorly understood. In the present study, we investigate whether deficits in reward processing interact with the social context and how this interaction is affected by self-reported depression and anxiety symptoms in the general population. Two cohorts of subjects (discovery and replication sample: N = 50 each) took part in an experiment involving reward learning in contexts with different levels of social information (absent, partial and complete). Behavioral analyses revealed a specific detrimental effect of depressive symptoms-but not anxiety-on behavioral performance in the presence of social information, i.e. when participants were informed about the choices of another player. Model-based analyses further characterized the computational nature of this deficit as a negative audience effect, rather than a deficit in the way others' choices and rewards are integrated in decision making. To conclude, our results shed light on the cognitive and computational mechanisms underlying the interaction between social cognition, reward learning and decision-making in depressive disorders.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2019.00151

Frontiers in behavioral neuroscience

Front Behav Neurosci

Impact of Stress on Gamma Oscillations in the Rat Nucleus Accumbens During Spontaneous Social Interaction.

Alteration in social behavior is one of the most debilitating symptoms of major depression, a stress related mental illness. Social behavior is modulated by the reward system, and gamma oscillations in the nucleus accumbens (NAc) seem to be associated with reward processing. In this scenario, the role of gamma oscillations in depression remains unknown. We hypothesized that gamma oscillations in the rat NAc are sensitive to the effects of social distress. One group of male rats were exposed to chronic social defeat stress (CSDS) while the other group was left undisturbed (control group). Afterward, a microelectrode array was implanted in the NAc of all animals. Local field potential (LFP) activity was acquired using a wireless recording system. Each implanted rat was placed in an open field chamber for a non-social interaction condition, followed by introducing another unfamiliar rat, creating a social interaction condition, where the implanted rat interacted freely and continuously with the unfamiliar conspecific in a natural-like manner (see Supplementary Videos). We found that the high-gamma band power in the NAc of non-stressed rats was higher during the social interaction compared to a non-social interaction condition. Conversely, we did not find significant differences at this level in the stressed rats when comparing the social interaction- and non-social interaction condition. These findings suggest that high-gamma oscillations in the NAc are involved in social behavior. Furthermore, alterations at this level could be an electrophysiological signature of the effect of chronic social stress on reward processing.

CognitiveConstruct

RewardProcessing

10.3758/s13415-019-00736-w

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Sex differences in reward- and punishment-guided actions.

Differences in the prevalence and presentation of psychiatric illnesses in men and women suggest that neurobiological sex differences confer vulnerability or resilience in these disorders. Rodent behavioral models are critical for understanding the mechanisms of these differences. Reward processing and punishment avoidance are fundamental dimensions of the symptoms of psychiatric disorders. Here we explored sex differences along these dimensions using multiple and distinct behavioral paradigms. We found no sex difference in reward-guided associative learning but a faster punishment-avoidance learning in females. After learning, females were more sensitive than males to probabilistic punishment but less sensitive when punishment could be avoided with certainty. No sex differences were found in reward-guided cognitive flexibility. Thus, sex differences in goal-directed behaviors emerged selectively when there was an aversive context. These differences were critically sensitive to whether the punishment was certain or unpredictable. Our findings with these new paradigms provide conceptual and practical tools for investigating brain mechanisms that account for sex differences in susceptibility to anxiety and impulsivity. They may also provide insight for understanding the evolution of sex-specific optimal behavioral strategies in dynamic environments.

CognitiveConstruct

RewardProcessing

10.1007/s00213-019-05337-6

Psychopharmacology

Psychopharmacology (Berl)

Bupropion increases activation in nucleus accumbens during anticipation of monetary reward.

Bupropion is used for major depressive disorder, smoking cessation aid, and obesity. It blocks reuptake of dopamine and noradrenaline and antagonizes nicotinic acetylcholine receptor. Animal studies showed that bupropion enhanced rewarding effects. In addition, bupropion has the potential to treat patients with reward processing dysfunction. However, neural substrates underlying the bupropion effects on reward function in human subjects are not fully understood. We investigated single-dose administration of bupropion on neural response of reward anticipation in healthy subjects using a monetary incentive delay (MID) task by functional magnetic resonance imaging (fMRI), especially focusing on nucleus accumbens (NAc) activity to non-drug reward stimuli under bupropion treatment. We used a randomized placebo-controlled within-subject crossover design. Fifteen healthy adults participated in two series of an fMRI study, taking either placebo or bupropion. The participants performed the MID task during the fMRI scanning. The effects of bupropion on behavioral performance and blood oxygenation level-dependent (BOLD) signal in NAc during anticipation of monetary gain were analyzed. We found that bupropion significantly increased BOLD responses in NAc during monetary reward anticipation. The increased BOLD responses in NAc were observed with both low and high reward incentive cues. There was no significant difference between placebo and bupropion in behavioral performance. Our findings provide support for the notion that bupropion enhances non-drug rewarding effects, suggesting a possible mechanism underlying therapeutic effects for patients with motivational deficit.

CognitiveConstruct

RewardProcessing

10.3390/brainsci9070173

Brain sciences

Brain Sci

Neural Circuit and Clinical Insights from Intraoperative Recordings During Deep Brain Stimulation Surgery.

Observations using invasive neural recordings from patient populations undergoing neurosurgical interventions have led to critical breakthroughs in our understanding of human neural circuit function and malfunction. The opportunity to interact with patients during neurophysiological mapping allowed for early insights in functional localization to improve surgical outcomes, but has since expanded into exploring fundamental aspects of human cognition including reward processing, language, the storage and retrieval of memory, decision-making, as well as sensory and motor processing. The increasing use of chronic neuromodulation, via deep brain stimulation, for a spectrum of neurological and psychiatric conditions has in tandem led to increased opportunity for linking theories of cognitive processing and neural circuit function. Our purpose here is to motivate the neuroscience and neurosurgical community to capitalize on the opportunities that this next decade will bring. To this end, we will highlight recent studies that have successfully leveraged invasive recordings during deep brain stimulation surgery to advance our understanding of human cognition with an emphasis on reward processing, improving clinical outcomes, and informing advances in neuromodulatory interventions.

CognitiveConstruct

RewardProcessing

10.1080/15374416.2019.1630834

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

J Clin Child Adolesc Psychol

Neural Response to Rewards, Stress and Sleep Interact to Prospectively Predict Depressive Symptoms in Adolescent Girls.

Blunted reward processing both characterizes major depressive disorder and predicts increases in depressive symptoms. However, little is known about the interaction between blunted reward processing and other risk factors in relation to increases in depressive symptoms. Stressful life events and sleep problems are prominent risk factors that contribute to the etiopathogenesis of depression and have been linked to reward dysfunction; these factors may interact with reward dysfunction to predict increased depressive symptoms. In a large sample of 8- to 14-year-old adolescent girls, the current study examined how blunted reward processing, stressful life events, and sleep problems at baseline interacted to predict increases in depressive symptoms 1 year later. Reward processing was indexed by the reward positivity (RewP), an event-related potential elicited during a simple monetary reward paradigm (i.e., Doors task). Two-way interactions confirmed that a blunted RewP predicted increased depressive symptoms at (a) high levels of stress but not average or low levels of stress, and (b) high and average levels of sleep problems but not low levels of sleep problems. Finally, a 3-way interaction confirmed that a blunted RewP predicted increased depressive symptoms at high levels of stress and sleep problems but not average or low levels of stress and sleep problems. Thus, adolescents characterized by low reward response (i.e., blunted RewP) were at an increased risk of developing depressive symptoms if they experienced increased stressful life events or sleep problems; moreover, risk was greatest among adolescents characterized by all 3.

CognitiveConstruct

RewardProcessing

10.1016/j.bpsc.2019.05.012

Biological psychiatry. Cognitive neuroscience and neuroimaging

Biol Psychiatry Cogn Neurosci Neuroimaging

Bidirectional Associations Between Stress and Reward Processing in Children and Adolescents: A Longitudinal Neuroimaging Study.

Aberrations in both neural reward processing and stress reactivity are associated with increased risk for mental illness; yet, how these two factors relate to each other remains unclear. Several studies suggest that stress exposure impacts reward function, thus increasing risk for psychopathology. However, the alternative hypothesis, in which reward dysfunction impacts stress reactivity, has been rarely examined. The current study aimed to test both hypotheses using a longitudinal design. Participants were 38 children (23 girls; 61%) from a prospective cohort study. A standard stress-exposure measure was collected at 7 years of age. Children performed a well-validated imaging reward paradigm at age 10, and a standardized acute psychological stress laboratory protocol was administered both at age 10 and at age 13. Structural equation modeling was used to examine bidirectional associations between stress and neural response to reward anticipation. Higher exposure to stressful life events at age 7 predicted lower neural response to reward anticipation in regions of the basal ganglia at age 10, which included ventral caudate, nucleus accumbens, putamen, and globus pallidus. Lower response to reward anticipation in medial prefrontal and anterior cingulate cortex predicted higher stress reactivity at age 13. Our findings provide support for bidirectional associations between stress and reward processing, in that stress may impact reward anticipation, but also in that reduced reward anticipation may increase susceptibility to stress.

CognitiveConstruct

RewardProcessing

10.3390/jcm8071047

Journal of clinical medicine

J Clin Med

Neural Processing of Disorder-Related Stimuli in Patients with Anorexia Nervosa: A Narrative Review of Brain Imaging Studies.

Abnormalities and alterations in brain function are commonly associated with the etiology and maintenance of anorexia nervosa (AN). Different symptom categories of AN have been correlated with distinct neurobiological patterns in previous studies. The aim of this literature review is to provide a narrative overview of the investigations into neural correlates of disorder-specific stimuli in patients with AN. Although findings vary across studies, a summary of neuroimaging results according to stimulus category allows us to account for methodological differences in experimental paradigms. Based on the available evidence, the following conclusions can be made: (a) the neural processing of visual food cues is characterized by increased top-down control, which enables restrictive eating, (b) increased emotional and reward processing during gustatory stimulation triggers disorder-specific thought patterns, (c) hunger ceases to motivate food foraging but instead reinforces disorder-related behaviors, (d) body image processing is related to increased emotional and hedonic reactions, (e) emotional stimuli provoke increased saliency associated with decreased top-down control and (f) neural hypersensitivity during interoceptive processing reinforces avoidance behavior. Taken together, studies that investigated symptom-specific neural processing have contributed to a better understanding of the underlying mechanisms of AN.

CognitiveConstruct

RewardProcessing

10.1037/abn0000439

Journal of abnormal psychology

J Abnorm Psychol

Neurophysiological activity following rewards and losses among female adolescents and young adults with borderline personality disorder.

Borderline personality disorder (BPD) is a complex and debilitating psychiatric illness. Prior research in adults has shown that neurophysiological deficits in feedback processing and learning from rewards may be central to the development of BPD; however, little research has examined these markers in adolescents and young adults with BPD. The present study used event-related potentials and time-frequency decomposition analysis to probe neural responses to wins and losses in a guessing task among 68 females (13 to 23 years old) either with BPD ( = 35) or no history of mental disorders (healthy control [HC]; = 33). Participants completed a guessing task wherein they won and lost money at equal frequencies while electroencephalogram (EEG) data were acquired. Adolescents and young adults with BPD showed a smaller differentiation between wins and losses in the reward positivity (RewP) relative to HCs. Using time-frequency decomposition, we isolated distinct frequency bands sensitive to wins (delta = < 3Hz) and losses (theta = 4 Hz to 7 Hz). Compared with BPD participants, HCs showed significantly larger delta power to wins, specifically. The groups did not differ in delta power to losses, nor theta power to wins or losses. Collectively, findings implicate altered reward processing in the pathophysiology of BPD and may inform early identification and targeted intervention. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2019.06.058

Journal of affective disorders

J Affect Disord

Differential neural responding to affective stimuli in 6- to 8-year old children at high familial risk for depression: Associations with behavioral reward seeking.

Children of depressed parents are at increased risk for psychopathology. One putative mechanism of risk appears to be altered processing of emotion-related stimuli. Although prior work has evaluated how adolescent offspring of depressed parents may show blunted reward processing compared to low-risk youth, there has been less attention to how young children with this familial history may differ from their peers during middle childhood, a period of critical socio-affective development METHOD: The current study evaluated 56 emotionally healthy 6-to 8-year children who were deemed at high-risk (n = 25) or low-risk (n = 31) for depression based on maternal history of depression. Children completed a behavioral reward seeking task in the laboratory and an fMRI paradigm assessing neural response to happy faces, a social reward. Findings demonstrated that high-risk children showed blunted responding to happy faces in the dorsal striatum compared to low-risk children. Further, lower responding in the dorsal striatum and dorsolateral prefrontal cortex was related to lower behavioral reward seeking, but only in high-risk children. Function within neural reward regions may be altered in high-risk offspring as young as 6- to 8-years of age. Further, neural reward responding may be linked to lower behavioral response to obtain reward in these high-risk offspring.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsz046

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Relationship of sensation seeking with the neural correlates of appetitive conditioning.

Previous research has linked sensation seeking with a heightened risk for drug abuse and other risk-taking behavior. As appetitive conditioning presents a model for the etiology and maintenance of addictive behavior, investigating sensation seeking in a classical conditioning paradigm might elucidate possible pathways toward addiction within this model. Furthermore, the theoretical concept underlying sensation seeking proposes a negative relationship between reward processing and sensation seeking in only moderately arousing situations, which has been neglected by previous research. This study aimed to investigate this inverse relationship in moderately stimulating situations entailing reward processing using functional magnetic resonance imaging. Subjects (N = 38) participated in a classical conditioning paradigm in which a neutral stimulus (CS+) was repeatedly paired with a monetary reward, while another neutral stimulus (CS-) was not. Imaging results revealed a negative relationship between sensation seeking and neural responses in the insula, amygdala and nucleus accumbens during the early phase and in the dorsal anterior cingulate cortex during the late phase of conditioning. These findings suggest reduced reward learning and consequently diminished processing of outcome expectancy in appetitive conditioning in subjects with high sensation seeking scores. The results are discussed with respect to clinical implications.

CognitiveConstruct

RewardProcessing

10.1097/YCO.0000000000000540

Current opinion in psychiatry

Curr Opin Psychiatry

The promise of neurobiological research in anorexia nervosa.

This article reviews new research in the context of existing literature to identify approaches that will advance understanding of the persistence of anorexia nervosa. Neuroscience research in anorexia nervosa has yielded disparate findings: no definitive neural mechanism underlying illness vulnerability or persistence has been identified and no clear neural target for intervention has emerged. Recent advances using structural and functional neuroimaging research, as well as new techniques for applying and combining these approaches, have led to a refined understanding of changes in neural architecture among individuals who are acutely ill, have undergone renourishment, or are in recovery/remission. In particular, advances have come from the incorporation of computational and translational approaches, as well as efforts to link experimental paradigms with illness-relevant behavior. Recent findings converge to suggest abnormalities in systems involved in reward learning and processing among individuals with anorexia nervosa. Anorexia nervosa is associated with neurobiological abnormalities. Aberrant learning and reward processing may contribute to the persistence of illness. To better utilize new techniques to understand the neural mechanisms of persistent anorexia nervosa, it may help to distinguish stages of illness and to link neurobiology with maladaptive behavior.

CognitiveConstruct

RewardProcessing

10.1016/j.ynstr.2019.100182

Neurobiology of stress

Neurobiol Stress

Buprenorphine prevents stress-induced blunting of nucleus accumbens dopamine response and approach behavior to food reward in mice.

Alterations to the mesolimbic dopamine (DA) system are thought to underlie dysfunctional reward processing in stress-related psychiatric disorders. Using in vivio microdialysis in awake freely moving mice, we assessed the effects of stress on the motivational and neurochemical correlates underlying conditioned approach behavior for palatable food in the non-deprived mouse. Mice trained to approach and consume food in a familiar environment exhibited a 30% increase in nucleus accumbens shell (AcbSh) extracellular dopamine levels coincident with approach towards and consumption of the food reward. This effect was not observed in mice that were presented with the food in an unfamiliar environment or were exposed for the first time and were region specific. The addition of an acute environmental stressor (bright light and novel scent) during food exposure decreased DA release and delayed approach to the food. The disruptive impact of acute novelty stress on DA levels and approach behavior was reversed in animals pretreated with buprenorphine, an opioid drug with antidepressant-like and anxiolytic effects. Together, these data indicate that exposure to mild stress reduces incentive drive to approach palatable food via alterations in AcbSh dopamine responsiveness to food reward. Moreover, they implicate the brain opioid system as a potential pharmacological target for counteracting behavioral and neurochemical elements associated with stress.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2019.107138

Neuropsychologia

Neuropsychologia

Disentangling the effects of reward value and probability on anticipatory event-related potentials.

Optimal decision-making requires humans to predict the value and probability of prospective (rewarding) outcomes. The aim of the present study was to evaluate and dissociate the cortical mechanisms activated by information on an upcoming potentially rewarded target stimulus with varying probabilities. Electro-cortical activity was recorded during a cued Go/NoGo experiment, during which cue letters signaled upcoming target letters to which participants had to respond. The probability of target letter appearance after the cue letter and the amount of money that could be won for correct and fast responses were orthogonally manipulated across four task blocks. As expected, reward availability affected a prefrontally distributed reward-related positivity, and a centrally distributed P300-like event-related potential (ERP). Moreover, a late prefrontally distributed ERP was affected by probability information. These results show that information on value and probability, respectively, activates separate mechanisms in the cortex. These results contribute to a further understanding of the neural underpinnings of normal and abnormal reward processing.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2019.00660

Frontiers in neuroscience

Front Neurosci

Subjective Beliefs About Trust and Reciprocity Activate an Expected Reward Signal in the Ventral Striatum.

There is overwhelming evidence that the evaluation of both reward decisions and their associated outcomes are closely linked with bilateral activation of the ventral striatum, with these insights stemming from tasks such as the monetary incentive delay task for lotteries and multiround Trust Games for social settings. The essential element in these tasks is an externally provided cue associated with specific gains/trustworthy partners and losses/non-trustworthy partners. However, in reality people typically use their own beliefs to guide their decision-making and assess the likelihood of positive or and negative outcomes. As when participants assess the relationship between cues and rewards, individuals should anticipate rewards in correspondence to their beliefs, i.e., the higher the belief of obtaining a reward in the future, the higher the anticipation of reward. In this study, we use decision-makers' own, naturally occurring, beliefs about both social and non-social contexts to examine the subsequent outcome of their choices. We hypothesize that mechanisms of belief-mediated reward processing are mediated by neural activation in the ventral striatum. An essential feature of our design is the elicitation of individuals' beliefs prior to the decision-making task itself. Furthermore, our incentivized, non-deceptive, decision-making task distinguishes between social - implemented by a Trust Game - and non-social sources, as well as risk and ambiguity as underlying types of uncertainty. Our main result shows that individual beliefs regarding reciprocity likelihoods in both the Trust Game and the lottery influence the amount invested. Subsequently, only the investment amount in the Trust Game parametrically modulates anticipatory reward and outcome evaluation in the ventral striatum. This study demonstrates a first approach at using participants' subjective sets of beliefs to examine reward processing. We discuss its potential promise, outline some limitations, and propose follow-up studies to extend the current approach.

CognitiveConstruct

RewardProcessing

10.1080/87565641.2019.1636798

Developmental neuropsychology

Dev Neuropsychol

Adolescent Brain Response to Reward Is Associated with a Bias toward Immediate Reward.

The current study examines associations between neural activation to the receipt of monetary reward in a rewarding game task and bias toward immediate reward measured in a behavioral delay discounting task among early adolescents (N = 58, 12-14 years). As expected, heightened brain activation in reward-related regions were correlated with higher bias toward immediate reward. This suggests that bias toward immediate reward in delay discounting tasks may be linked to heightened activation to reward in reward processing regions. This interplay between neural reward processing and bias toward immediate reward might explain the sharp increases in bias toward immediate reward that occur in early adolescence.

CognitiveConstruct

RewardProcessing

10.1038/s41386-019-0462-0

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Profound alteration in reward processing due to a human polymorphism in CHRNA5: a role in alcohol dependence and feeding behavior.

Human genetic variation in the nicotinic receptor gene cluster CHRNA5/A3/B4, in particular the non-synonymous and frequent CHRNA5 variant rs16969968 (α5SNP), has an important consequence on smoking behavior in humans. A number of genetic association studies have additionally implicated the CHRNA5 gene in addictions to other drugs, and also body mass index (BMI). Here, we model the α5SNP, in a transgenic rat line, and establish its role in alcohol dependence, and feeding behavior. Rats expressing the α5SNP consume more alcohol, and exhibit increased relapse to alcohol seeking after abstinence. This high-relapsing phenotype is reflected in altered activity in the insula, linked to interoception, as established using c-Fos immunostaining. Similarly, relapse to food seeking is increased in the transgenic group, while a nicotine treatment reduces relapse in both transgenic and control rats. These findings point to a general role of this human polymorphism in reward processing, and multiple addictions other than smoking. This could pave the way for the use of medication targeting the nicotinic receptor in the treatment of alcohol use and eating disorders, and comorbid conditions in smokers.

CognitiveConstruct

RewardProcessing

10.1016/j.schres.2019.06.019

Schizophrenia research

Schizophr Res

Retinal functioning and reward processing in schizophrenia.

Retinal responses to light, as measured by electroretinography (ERG), have been shown to be reduced in schizophrenia. Data from a prior ERG study in healthy humans indicated that activity of a retinal cell type affected in schizophrenia can be modified by the presence of a food reward. Therefore, we aimed to determine whether ERG amplitudes would be sensitive to the well-documented reward processing impairment in schizophrenia. Flash ERG data from 15 clinically stable people with schizophrenia or schizoaffective disorder and 15 healthy controls were collected under three conditions: baseline, anticipation of a food reward, and immediately after consuming the food reward. At the group level, data indicated that controls' ERG responses varied as a function of salience of the food reward (baseline vs. anticipation vs. consumption) whereas patients' ERG responses did not vary significantly across conditions. Correlations between ERG amplitudes and scores on measures of hedonic capacity (including motivation and pleasure negative symptom ratings for patients) indicated consistent relationships. These data suggest that flash ERG amplitudes may be a sensitive indicator of the integrity of reward processing mechanisms. However, several differences in the direction of findings between this and a prior study in controls point to the need for further investigation of the contributions of a number of key variables to the observed effects.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2019.112051

Behavioural brain research

Behav Brain Res

Affective biases and their interaction with other reward-related deficits in rodent models of psychiatric disorders.

Major depressive disorder (MDD) is one of the leading global causes of disability. Symptoms of MDD can vary person to person, and current treatments often fail to alleviate the poor quality of life that patients experience. One of the two core diagnostic criteria for MDD is the loss of interest in previously pleasurable activities, which suggests a link between the disease aetiology and reward processing. Cognitive impairments are also common in patients with MDD, and more recently, emotional processing deficits known as affective biases have been recognised as a key feature of the disorder. Studies in animals have found similar affective biases related to reward. In this review we consider these affective biases in the context of other reward-related deficits and examine how affective biases associated with learning and memory may interact with the wider behavioural symptoms seen in MDD. We discuss recent developments in how analogues of affective biases and other aspects of reward processing can be assessed in rodents, as well as how these behaviours are influenced in models of MDD. We subsequently discuss evidence for the neurobiological mechanisms contributing to one or more reward-related deficits in preclinical models of MDD, identified using these behavioural assays. We consider how the relationships between these selective behavioural assays and the neurobiological mechanisms for affective bias and reward processing could be used to identify potential treatment strategies.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2019.107130

Neuropsychologia

Neuropsychologia

Mind the gap: Congruence between present and future motivational states shapes prospective decisions.

Poor estimation of one's future actions has been associated with the influence of reward over executive control processes during prospection. However, the neural mechanisms underlying this reward-control trade-off remain poorly understood. In the present study, we take advantage of projection bias, underestimating how motivations will change in the future, to examine brain and behavior changes during prospection about future decisions. To manipulate motivation, we altered satiety (hungry vs. satiated) and asked human participants (N = 25) to place bids on snack foods while undergoing fMRI scanning across two sessions. While hungry, participants bid for the right to consume snacks in both a future congruent motivational state (hungry) and a future incongruent motivational state (satiated). In a second session, while satiated, participants placed bids for the right to immediately consume the items. Imagination of a congruent future state was associated with brain activity in regions implicated in prospection. Imagination of an incongruent future state was related to brain activity in areas related to cognitive control. Projection bias, the difference between bids during incongruent prospection (hungry to satiated, session one) and realization (satiated, session two), was negatively related to thalamic and insular engagement. Bias was positively related to engagement of the ventral striatum, a region involved in reward processing. These results suggest that the relative activation between reward and control systems is influenced by the congruence of present and future motivational states, and shapes bias in predictions about future behavior.

CognitiveConstruct

RewardProcessing

10.1017/S0033291719001557

Psychological medicine

Psychol Med

Stressful life events moderate the effect of neural reward responsiveness in childhood on depressive symptoms in adolescence.

Reward processing deficits have been implicated in the etiology of depression. A blunted reward positivity (RewP), an event-related potential elicited by feedback to monetary gain relative to loss, predicts new onsets and increases in depression symptoms. Etiological models of depression also highlight stressful life events. However, no studies have examined whether stressful life events moderate the effect of the RewP on subsequent depression symptoms. We examined this question during the key developmental transition from childhood to adolescence. A community sample of 369 children (mean age of 9) completed a self-report measure of depression symptoms. The RewP to winning v. losing was elicited using a monetary reward task. Three years later, we assessed stressful life events occurring in the year prior to the follow-up. Youth depressive symptoms were rated by the children and their parents at baseline and follow-up. Stressful life events moderated the effect of the RewP on depression symptoms at follow-up such that a blunted RewP predicted higher depression symptoms in individuals with higher levels of stressful life events. This effect was also evident when events that were independent of the youth's behavior were examined separately. These results suggest that the RewP reflects a vulnerability for depression that is activated by stress.

CognitiveConstruct

RewardProcessing

10.1007/s00213-019-05310-3

Psychopharmacology

Psychopharmacology (Berl)

NMDA receptor antagonists traxoprodil and lanicemine improve hippocampal-prefrontal coupling and reward-related networks in rats.

The N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is known to have not only a rapid antidepressant effect but also dissociative side effects. Traxoprodil and lanicemine, also NMDA antagonists, are candidate antidepressant drugs with fewer side effects. In order to understand their mechanism of action, we investigated the acute effects of traxoprodil and lanicemine on brain connectivity using resting-state functional magnetic resonance imaging (rs-fMRI). Functional connectivity (FC) alterations were examined using interregional correlation networks. Graph theoretical methods were used for whole brain network analysis. As interest in NMDAR antagonists as potential antidepressants was triggered by the antidepressant effect of ketamine, results were compared to previous findings from our ketamine studies. Similar to ketamine but to a smaller extent, traxoprodil increased hippocampal-prefrontal (Hc-PFC) coupling. Unlike ketamine, traxoprodil decreased connectivity within the PFC. Lanicemine had no effect on these properties. The improvement of Hc-PFC coupling corresponds well to clinical result, showing ketamine to have a greater antidepressant effect than traxoprodil, while lanicemine has a weak and transient effect. Connectivity changes overlapping between the drugs as well as alterations of local network properties occurred mostly in reward-related regions. The antidepressant effect of NMDA antagonists appears to be associated with enhanced Hc-PFC coupling. The effects on local network properties and regional connectivity suggest that improvement of reward processing might also be important for understanding the mechanisms underlying the antidepressant effects of these drugs.

CognitiveConstruct

RewardProcessing

10.1177/0269881119855302

Journal of psychopharmacology (Oxford, England)

J Psychopharmacol

A novel approach to evaluate the pharmacodynamics of a selective dopamine D1/D5 receptor partial agonist (PF-06412562) in patients with stable schizophrenia.

PF-06412562 is an orally bioavailable, selective dopamine D1/D5 receptor partial agonist with a non-catechol structure under evaluation for treatment of cognitive impairment in schizophrenia. This randomized, double-blind, placebo-controlled, parallel-group, Phase 1b study examined the pharmacokinetics and pharmacodynamics of three doses of PF-06412562 (3 mg, 9 mg, and 45 mg twice daily) over 15 days in patients with schizophrenia receiving antipsychotics. Primary endpoints included adjunctive safety/tolerability and effects on MATRICS Consensus Cognitive Battery Working Memory domain and reward processing (Monetary Incentive Delay) tasks. Exploratory endpoints included other behavioral/neurophysiological tasks, including the N-back task. Among 95 subjects (78% male; mean age 34.8 years), baseline characteristics were similar across groups. The MATRICS Consensus Cognitive Battery Working Memory composite change from baseline on Day 13 improved in all groups, the smallest improvement was observed in the 45 mg group and was significantly smaller than that in the placebo group (two-sided =0.038). For the Monetary Incentive Delay task (change from baseline in blood-oxygen-level-dependent functional magnetic resonance imaging activation in anterior ventral striatum for the contrast of cue gain>cue no gain on Day 15), no PF-06412562 dose was significantly different from placebo. No doses of PF-06412562 showed a significant difference on two-back task accuracy versus placebo. Adjunctive treatment with PF-06412562 was safe and well tolerated in patients with schizophrenia. PF-06412562 failed to show clinical benefit relative to placebo on assessments of cognition or reward processing in symptomatically stable patients over a 15-day treatment period. Numerous limitations due to the safety study design warrant further efficacy evaluation for this drug mechanism.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2019.05.006

Biological psychiatry

Biol Psychiatry

Joint Attention in Infancy and the Emergence of Autism.

In typical infant development, parents and their children jointly contribute to establishing frequent episodes of joint attention that boost language acquisition and shape social cognition. Here we used novel live eye-tracking technology to evaluate the degree to which autism spectrum disorder (ASD) is related to reduced responding to others' joint attention bids in infancy (RJA) and to a reduced tendency to initiate joint attention episodes (IJA). Because young infants use their gaze for both RJA and IJA, this approach allowed us to quantify these elusive processes early in life. The final sample consisted of 112 infants (54 boys and 58 girls), of whom 81 were at familial risk for ASD and 31 were typically developing low-risk infants. At follow-up (36 months of age), 22 children in the high-risk group were diagnosed with ASD. At 10 months of age, rates of IJA were lower in infants later diagnosed with ASD than in the comparison groups (effect sizes d = 0.78-0.95) and followed an atypical developmental trajectory from 10 to 18 months (p < .002). RJA distinguished infants based on familial ASD risk, albeit not ASD diagnosis. The differences in IJA could not be explained by overall looking time, social preference, eye movement latencies, or number of fixations. This live eye-tracking study suggests that during an important period for the development of social cognition (10-18 months of age), infants later diagnosed with ASD show marked atypicalities in IJA but not in RJA. The results indicate that IJA is an important target for future prodromal intervention trials.

CognitiveConstruct

RewardProcessing

10.1002/jnr.24480

Journal of neuroscience research

J Neurosci Res

Translating striatal activity from brain slice to whole animal neurophysiology: A guide for neuroscience research integrating diverse levels of analysis.

An important goal of this review is highlighting research in neuroscience as examples of multilevel functional and anatomical analyses addressing basic science issues and applying results to the understanding of diverse disorders. The research of Dr. Michael Levine, a leader in neuroscience, exemplifies this approach by uncovering fundamental properties of basal ganglia function and translating these findings to clinical applications. The review focuses on neurophysiological research connecting results from in vitro and in vivo recordings. A second goal is to utilize these research connections to produce novel, accurate descriptions for corticostriatal processing involved in varied, complex functions. Medium spiny neurons in striatum act as integrators combining input with baseline activity creating motivational "events." Basic research on corticostriatal synapses is described and links developed to issues with clinical relevance such as inhibitory gating, self-injurious behavior, and relative reward valuation. Work is highlighted on dopamine-glutamate interactions. Individual medium spiny neurons express both D and D receptors and encode information in a bivalent manner depending upon the mix of receptors involved. Current work on neurophysiology of reward processing has taken advantage of these basic approaches at the cellular and molecular levels. Future directions in studying physiology of reward processing and action sequencing could profit by incorporating the divergent ways dopamine modulates incoming neurochemical signals. Primary investigators leading research teams should mirror Mike Levine's efforts in "climbing the mountain" of scientific inquiry by performing analyses at different levels of inquiry, integrating the findings, and building comprehensive answers to problems unsolvable without this bold approach.

CognitiveConstruct

RewardProcessing

10.1038/s41386-019-0450-4

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Astrocytes determine conditioned response to morphine via glucocorticoid receptor-dependent regulation of lactate release.

To date, neurons have been the primary focus of research on the role of glucocorticoids in the regulation of brain function and pathological behaviors, such as addiction. Astrocytes, which are also glucocorticoid-responsive, have been recently implicated in the development of drug abuse, albeit through as yet undefined mechanisms. Here, using a spectrum of tools (whole-transcriptome profiling, viral-mediated RNA interference in vitro and in vivo, behavioral pharmacology and electrophysiology), we demonstrate that astrocytes in the nucleus accumbens (NAc) are an important locus of glucocorticoid receptor (GR)-dependent transcriptional changes that regulate rewarding effects of morphine. Specifically, we show that targeted knockdown of the GR in the NAc astrocytes enhanced conditioned responses to morphine, with a concomitant inhibition of morphine-induced neuronal excitability and plasticity. Interestingly, GR knockdown did not influence sensitivity to cocaine. Further analyses revealed GR-dependent regulation of astroglial metabolism. Notably, GR knockdown inhibited induced by glucocorticoids lactate release in astrocytes. Finally, lactate administration outbalanced conditioned responses to morphine in astroglial GR knockdown mice. These findings demonstrate a role of GR-dependent regulation of astrocytic metabolism in the NAc and a key role of GR-expressing astrocytes in opioid reward processing.

CognitiveConstruct

RewardProcessing