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10.1016/j.neuroimage.2021.118478

NeuroImage

Neuroimage

Electrophysiological underpinnings of reward processing: Are we exploiting the full potential of EEG?

Understanding how the brain processes reward is an important and complex endeavor, which has involved the use of a range of complementary neuroimaging tools, including electroencephalography (EEG). EEG has been praised for its high temporal resolution but, because the signal recorded at the scalp is a mixture of brain activities, it is often considered to have poor spatial resolution. Besides, EEG data analysis has most often relied on event-related potentials (ERPs) which cancel out non-phase locked oscillatory activity, thus limiting the functional discriminative power of EEG attainable through spectral analyses. Because these three dimensions -temporal, spatial and spectral- have been unequally leveraged in reward studies, we argue that the full potential of EEG has not been exploited. To back up our claim, we first performed a systematic survey of EEG studies assessing reward processing. Specifically, we report on the nature of the cognitive processes investigated (i.e., reward anticipation or reward outcome processing) and the methods used to collect and process the EEG data (i.e., event-related potential, time-frequency or source analyses). A total of 359 studies involving healthy subjects and the delivery of monetary rewards were surveyed. We show that reward anticipation has been overlooked (88% of studies investigated reward outcome processing, while only 24% investigated reward anticipation), and that time-frequency and source analyses (respectively reported by 19% and 12% of the studies) have not been widely adopted by the field yet, with ERPs still being the dominant methodology (92% of the studies). We argue that this focus on feedback-related ERPs provides a biased perspective on reward processing, by ignoring reward anticipation processes as well as a large part of the information contained in the EEG signal. Finally, we illustrate with selected examples how addressing these issues could benefit the field, relying on approaches combining time-frequency analyses, blind source separation and source localization.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2021.08.010

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

The cue-reactivity paradigm: An ensemble of networks driving attention and cognition when viewing drug and natural reward-related stimuli.

The cue-reactivity paradigm is a widely adopted neuroimaging probe engendering brain activity linked with attentional, affective, and reward processes following presentation of appetitive stimuli. Given the multiple mental operations invoked, we sought to decompose cue-related brain activity into constituent components employing emergent meta-analytic techniques when considering drug and natural reward-related cues. We conducted coordinate-based meta-analyses delineating common and distinct brain activity convergence across cue-reactivity studies (N = 196 articles) involving drug (n = 133) or natural (n = 63) visual stimuli. Across all studies, convergence was observed in limbic, cingulate, insula, and fronto-parieto-occipital regions. Drug-distinct convergence was observed in posterior cingulate, dorsolateral prefrontal, and temporo-parietal regions, whereas distinct-natural convergence was observed in thalamic, insular, orbitofrontal, and occipital regions. We characterized connectivity profiles of identified regions by leveraging task-independent and task-dependent MRI datasets, grouped these profiles into subnetworks, and linked each with putative mental operations. Outcomes suggest multifaceted brain activity during cue-reactivity can be decomposed into elemental processes and indicate that while drugs of abuse usurp the brain's natural-reward-processing system, some regions appear distinct to drug cue-reactivity.

CognitiveConstruct

RewardProcessing

10.1176/appi.neuropsych.20100255

The Journal of neuropsychiatry and clinical neurosciences

J Neuropsychiatry Clin Neurosci

Resting-State Correlations of Fatigue Following Military Deployment.

Persistent fatigue is common among military servicemembers returning from deployment, especially those with a history of mild traumatic brain injury (mTBI). The purpose of this study was to characterize fatigue following deployment using the Multidimensional Fatigue Inventory (MFI), a multidimensional self-report instrument. The study was developed to test the hypothesis that if fatigue involves disrupted effort/reward processing, this should manifest as altered basal ganglia functional connectivity as observed in other amotivational states. Twenty-eight current and former servicemembers were recruited and completed the MFI. All 28 participants had a history of at least one mTBI during deployment. Twenty-six participants underwent resting-state functional MRI. To test the hypothesis that fatigue was associated with basal ganglia functional connectivity, the investigators measured correlations between MFI subscale scores and the functional connectivity of the left and right caudate, the putamen, and the globus pallidus with the rest of the brain, adjusting for the presence of depression. The investigators found a significant correlation between functional connectivity of the left putamen and bilateral superior frontal gyri and mental fatigue scores. No correlations with the other MFI subscales survived multiple comparisons correction. This exploratory study suggests that mental fatigue in military servicemembers with a history of deployment with at least one mTBI may be related to increased striatal-prefrontal functional connectivity, independent of depression. A finding of effort/reward mismatch may guide future treatment approaches.

CognitiveConstruct

RewardProcessing

10.1038/s41593-021-00898-2

Nature neuroscience

Nat Neurosci

Ventral tegmental area GABAergic inhibition of cholinergic interneurons in the ventral nucleus accumbens shell promotes reward reinforcement.

The long-range GABAergic input from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) is relatively understudied, and therefore its role in reward processing has remained unknown. In the present study, we show, in both male and female mice, that long-range GABAergic projections from the VTA to the ventral NAc shell, but not to the dorsal NAc shell or NAc core, are engaged in reward and reinforcement behavior. We show that this GABAergic projection exclusively synapses on to cholinergic interneurons (CINs) in the ventral NAc shell, thereby serving a specialized function in modulating reinforced reward behavior through the inhibition of ventral NAc shell CINs. These findings highlight the diversity in the structural and functional topography of VTA GABAergic projections, and their neuromodulatory interactions across the dorsoventral gradient of the NAc shell. They also further our understanding of neuronal circuits that are directly implicated in neuropsychiatric conditions such as depression and addiction.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2021.07.091

Journal of affective disorders

J Affect Disord

Doors P300 moderates the relationship between reward positivity and current depression status in adults.

Previous research has found deficits in both the reward positivity (RewP) and P300 components of the event-related potential (ERP) in relation to depression. The current study examined whether the P300, elicited from imperative stimuli in a gambling task, relates to depression - and can be utilized in tandem with the RewP to better account for individual differences in depression. In the current study, 80 adults with current depression (M = 39.65, 79% female) and 43 healthy controls (M = 37.02, 81% female) completed clinical interviews, self-report questionnaires, and the doors gambling task while EEG was recorded. Results indicated a reduced P300 to doors stimuli (i.e., doors P300) in depression, especially among depressed individuals reporting heightened anhedonia. Gain and loss feedback P300s did not differ between groups. Moreover, the doors P300 moderated the association between RewP and depression status: individuals with relatively intact reward processing (i.e., larger RewP) were more likely to be currently depressed if they exhibited a reduced P300. The majority of the sample identified as Caucasian which reduces generalizability of current results. Additionally, the current study is cross sectional design which limits insight into how these ERPs coincide with changes in the disorder. The current study demonstrates that a novel P300 component to the doors stimulus appears to be blunted in currently depressed individuals, and that using the doors P300 in combination with the RewP accounts for significantly more variance in depression.

CognitiveConstruct

RewardProcessing

10.1007/s00115-021-01167-0

Der Nervenarzt

Nervenarzt

[Positive cognitive neuroscience : Positive valence systems of the Research Domain Criteria initiative].

In this paper, the domain positive valence systems (PVS) of the Research Domain Criteria (RDoC) matrix and its subconstructs are presented and discussed. The PVS basically reflect different forms and aspects of reward processing. These have been investigated in psychiatry in the context of addiction, schizophrenia and depression for decades; the latter are therefore not the topic of this paper. This article presents the heuristic value of the RDoC system in understanding other disorders and constructs, namely the transdiagnostic symptom of anhedonia, autism spectrum disorder and eating disorders. In addition, it outlines how the PVS domain has also enriched the clinical perspective of traditional psychopathology and stimulated the development of new behavioral measurement instruments. Finally, the limitations and potential future developments of the framework are discussed.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2021.712194

Frontiers in human neuroscience

Front Hum Neurosci

The Effect of Social Distance on Intertemporal Choice of Reward Processing: An Event-Related Potentials Study.

Social factors can affect the processing of intertemporal choice, but the influence of social distance on the rewarding process of intertemporal choice is unclear. Therefore, by designing a novel cognitive resource competition paradigm for undifferentiated intertemporal choice, this article aims to explore the influence of social distance on intertemporal choice reward processing at the electrophysiological level. It was found that compared with the stranger condition, P3a is greater in the friend condition, which means social distance is evaluated in the early stage. In addition, different brain regions in the early stages are taking charge of processing the soon-but-small (SS) and later-but-lager (LL) reward in intertemporal choice. There is an interaction effect between social distance (friend vs. stranger) and intertemporal choice (SS reward vs. LL reward) on P3b. Under friend conditions, the P3b induced by LL reward is more positive than SS reward. Under the condition of choosing the LL reward, the P3b induced by friend is more positive than stranger. This result shows that in the latter stage of reward processing, the evaluation process of time discounting is less sensitive in LL reward for friend caused by lack of cognitive resources which is occupied when dealing with social distance in advance, and thus the degree of time discount was reduced. These findings demonstrate that P3b is the key index of time discounting and immediate and delayed rewards are valued in different brain regions.

CognitiveConstruct

RewardProcessing

10.1097/HRP.0000000000000312

Harvard review of psychiatry

Harv Rev Psychiatry

Neurocognitive Effects of Ketamine and Esketamine for Treatment-Resistant Major Depressive Disorder: A Systematic Review.

Cognitive impairment is commonly present in individuals with treatment-resistant depression, especially in attention, memory, and executive functions. These deficits are related to symptom severity, remission rates, and functional impairments during and after the acute phase of the disorder. Ketamine, an N-methyl-D-aspartate antagonist previously used as an anesthetic, brings promising antidepressant results. This study systematically reviews the neurocognitive effects of ketamine and esketamine in patients with treatment-resistant major depressive disorder. Systematic searches were conducted at Embase, PubMed, and PsycINFO using the terms depression, ketamine, and cognition. Title, abstract, and full-text reading were conducted independently by two of the authors (BSM and CSL). Risk of bias, study design, neuropsychological outcomes, and neuroimaging data were recorded. From a total of 997 hits, 14 articles were included. One study reported cognitive impairment after ketamine treatment for processing speed and verbal memory. Five studies reported improvements in processing speed, verbal memory, visual memory, working memory, or cognitive flexibility. The esketamine study suggested no changes to performance. Lower attention, slower processing speed, and higher working memory are reported as predictors of antidepressant response. Brain areas for emotional and reward processing, including the amygdala, insula, and orbitofrontal cortex, show a normalizing tendency after ketamine. Ketamine and esketamine do not seem to exert significant deleterious neurocognitive effects in the short or long term in individuals with treatment-resistant depression. Results suggest neuropsychological functions and brain areas commonly impaired in treatment-resistant depression may especially benefit from subanesthetic ketamine infusions. Key questions that remain unanswered are discussed.

CognitiveConstruct

RewardProcessing

10.1177/1087054720923061

Journal of attention disorders

J Atten Disord

Neurobiological Basis of Reinforcement-Based Decision-Making in Adults With ADHD Treated With Lisdexamfetamine Dimesylate.

The objective of this study was to examine changes in the activation of the brain reward system following treatment with lisdexamfetamine (LDX) vs. placebo (PL) as a function of clinical improvement in attention deficit/hyperactivity disorder (ADHD) symptoms. Twenty adults with ADHD were included in a randomized cross-over study. Participants underwent two functional magnetic resonance imaging (fMRI) scans, after receiving 3 to 5 weeks of treatment with both LDX and PL. During scanning, participants performed the passive-avoidance learning task to assess reward-related learning using computational variables (e.g., estimated value and prediction error). Pre-treatment to post-treatment symptom change was assessed via the ADHD Rating Scale (ADHD-RS). The imaging contrasts were Object Choose or Object Refuse during the object choice component of the task, modulated by expected value (reward vs. nonreward cue), and Reward vs. Punishment during feedback, modulated by prediction error (expected vs. actual outcome). To address the primary objective, we performed group-level mass univariate analyses between pre-treatment to post-treatment percent change of the ADHD-RS total scores and the four contrast images under the choice and feedback conditions, with significance set at a whole-brain voxel-wise threshold of < .05 with family-wise error (FWE) correction and an extent (cluster) threshold of 50 contiguous voxels. : Improvement in ADHD symptoms was accompanied by significant increases of brain activation during the Object Refuse, Reward and Punishment contrasts in a widespread network including left caudate and putamen, and right orbitofrontal cortex (i.e., reward-related signaling) and left middle frontal, superior frontal, and precentral gyri (i.e., executive control). These findings are the first to show that the . Results support the hypothesis that LDX treatment may restore balance to dysfunction (e.g., hypoactivation) within the brain reward circuitry in adults with ADHD.

CognitiveConstruct

RewardProcessing

10.1177/0253717620927870

Indian journal of psychological medicine

Indian J Psychol Med

Effectiveness of an Integrated Intervention Program for Alcoholism: Electrophysiological Findings.

Neuroelectrophysiological measures such as electroencephalograms (EEGs) in resting state and event-related potentials (ERPs) provide valuable information about the vulnerability and treatment-related changes in persons with alcoholism. This study examined the effectiveness of an Integrated Intervention Program for Alcoholism (IIPA) using electrophysiological measures. Fifty individuals with early onset of alcohol dependence participated. They were grouped randomly into two: the treatment as usual (TAU) group and the treatment group, matched on age (±1 year) and education (±1 year). eyes closed and resting state EEGs and ERPs on cognitive tasks (flanker task, alcohol Go/No-Go task, and single outcome gambling task) were recorded before and after treatment. The TAU group received pharmacotherapy, six days/week yoga sessions, and three sessions/week group therapy on relapse prevention while the treatment group received IIPA along with usual treatment (except yoga) for 18 days. There was no significant difference between the groups pre-treatment. RM-ANOVA for pre- and post-treatment stages showed a significant difference between the two groups in the absolute power of alpha, beta, theta, and delta, during eye closure, in the resting-state EEGs. The treatment group showed significantly larger N200/N2 amplitude in congruent and incongruent conditions (flanker task), N200/N2 amplitude for alcohol No-Go, P300/P3 amplitude for neutral No-Go on alcohol Go/No-Go task, and outcome-related positivity (ORP) amplitude on single outcome gambling task. This exploratory study suggests that IIPA is effective for enhancing relaxation state and attentiveness, decreasing hyperarousal, and ameliorating neurocognitive dysfunctions of conflict-monitoring, response inhibition, and reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.psychres.2021.114123

Psychiatry research

Psychiatry Res

Neural signatures of saliency-mapping in anhedonia: A narrative review.

Anhedonia is the loss of pleasure or motivation to engage in previously enjoyable activities, and is a transdiagnostic symptom associated with significant clinical impairment. Anhedonia is implicated in several different psychiatric disorders, presenting a promising opportunity for transdiagnostic treatment. Thus, developing targeted treatments for anhedonia is of critical importance for population mental health. An important first step in doing so is establishing a thorough understanding of the neural correlates of anhedonia. The Triple Network Model of Psychopathology provides a frame for how brain activity may go awry in anhedonia, specifically in the context of Salience Network (SN) function (i.e., saliency-mapping). We present a narrative review examining saliency-mapping as it relates to anhedonia severity in depressed and transdiagnostic adult samples. Results revealed increased anhedonia to be associated with hyperactivity of the SN at rest and in the context of negative stimuli, as well as a global lack of SN engagement in the context of positive stimuli. Potential treatments for anhedonia are placed within this model, and future directions for research are discussed.

CognitiveConstruct

RewardProcessing

10.1111/add.15651

Addiction (Abingdon, England)

Addiction

Evidence for a hijacked brain reward system but no desensitized threat system in quitting motivated smokers: An fMRI study.

Several aspects of how quitting motivated tobacco use disorder (TUD) subjects and never-smokers differ in terms of reward and threat processing remain unresolved. We aimed to examine aberrant reward and threat processes in TUD and the association with smoking characteristics. A between- and within-subjects fMRI experiment with a 2 (groups) x 4 (stimulus type) factorial design. The experimental paradigm had four conditions: pictures of 1) cigarettes served as drug-related positive cues, 2) food as alternative reward cues, 3) long-term consequences of smoking as drug-related negative cues, and 4) neutral pictures as control. Adult participants (n = 38 TUD subjects & n = 42 never-smokers) were recruited in Berlin, Germany. As contrasts of primary interest, the interactions of group-by-stimulus-type were assessed. Significance threshold correction for multiple testing was carried out with the family wise error method. Correlation analyses were used to test the association with smoking characteristics. The 2x2 interaction of smoking status and stimulus type revealed activations in the brain reward system to drug-related positive cues in TUD subjects (between-subjects effect: P-values ≤ 0.036). As response to drug-related negative cues, TUD subjects showed no reduced activation of the aversive brain network. Within the TUD group, a significant negative association was found between response of the aversive brain system to drug-related negative cues (within-subjects effect: P-values ≤ 0.021) and the number of cigarettes smoked per day (right insula r = -0.386, p = 0.024; left insula r = -0.351, p = 0.042; right ACC r = -0.359, p = 0.037). Moderate smokers with tobacco use disorder appear to have altered brain reward processing of drug-related positive (but not negative) cues compared with never smokers.

CognitiveConstruct

RewardProcessing

10.1038/s42003-021-02426-1

Communications biology

Commun Biol

Single-trial modeling separates multiple overlapping prediction errors during reward processing in human EEG.

Learning signals during reinforcement learning and cognitive control rely on valenced reward prediction errors (RPEs) and non-valenced salience prediction errors (PEs) driven by surprise magnitude. A core debate in reward learning focuses on whether valenced and non-valenced PEs can be isolated in the human electroencephalogram (EEG). We combine behavioral modeling and single-trial EEG regression to disentangle sequential PEs in an interval timing task dissociating outcome valence, magnitude, and probability. Multiple regression across temporal, spatial, and frequency dimensions characterized a spatio-tempo-spectral cascade from early valenced RPE value to non-valenced RPE magnitude, followed by outcome probability indexed by a late frontal positivity. Separating negative and positive outcomes revealed the valenced RPE value effect is an artifact of overlap between two non-valenced RPE magnitude responses: frontal theta feedback-related negativity on losses and posterior delta reward positivity on wins. These results reconcile longstanding debates on the sequence of components representing reward and salience PEs in the human EEG.

CognitiveConstruct

RewardProcessing

10.1055/a-1520-4784

Pharmacopsychiatry

Pharmacopsychiatry

An Oppositional Tolerance Account for Potential Cognitive Deficits Caused by the Discontinuation of Antidepressant Drugs.

Depression is the leading cause of disability worldwide, making antidepressant drugs the most used psychiatric drugs in the USA. Withdrawal effects and rebound symptoms frequently occur after the reduction and/or discontinuation of these drugs. Although these phenomena have been investigated with respect to the clinical symptomatology, no studies have systematically investigated the effects of withdrawal/rebound on general cognition. We present a novel framework based on the idea of allostatic adaptation, which allows to predict how different antidepressants likely impair different cognitive processes as a result of withdrawal and rebound effects. This framework relies on the assumptions that the type of cognitive impairments evoked by an antidepressant is determined by the targeted neurotransmitter systems, while the severity of deficits depends on its half-life. Our model predicts that the severity of detrimental cognitive withdrawal and rebound effects increases with a shorter half-life of the discontinued antidepressant drug. It further proposes drug-specific effects: antidepressants mainly targeting serotonin should primarily impair aversive and emotional processing, those targeting norepinephrine should impair the processing of alerting signals, those targeting dopamine should impair motivational processes and reward processing, and those targeting acetylcholine should impair spatial learning and memory. We hope that this framework will motivate further research to better understand and explain cognitive changes as a consequence of antidepressant discontinuation.

CognitiveConstruct

RewardProcessing

10.1172/JCI146861

The Journal of clinical investigation

J Clin Invest

Targeting diacylglycerol lipase reduces alcohol consumption in preclinical models.

Alcohol use disorder (AUD) is associated with substantial morbidity, mortality, and societal cost, and pharmacological treatment options for AUD are limited. The endogenous cannabinoid (eCB) signaling system is critically involved in reward processing and alcohol intake is positively correlated with release of the eCB ligand 2-Arachidonoylglycerol (2-AG) within reward neurocircuitry. Here we show that genetic and pharmacological inhibition of diacylglycerol lipase (DAGL), the rate limiting enzyme in the synthesis of 2-AG, reduces alcohol consumption in a variety of preclinical models ranging from a voluntary free-access model to aversion resistant-drinking and dependence-like drinking induced via chronic intermittent ethanol vapor exposure in mice. DAGL inhibition during either chronic alcohol consumption or protracted withdrawal was devoid of anxiogenic and depressive-like behavioral effects. Lastly, DAGL inhibition also prevented ethanol-induced suppression of GABAergic transmission onto midbrain dopamine neurons, providing mechanistic insight into how DAGL inhibition could affect alcohol reward. These data suggest reducing 2-AG signaling via inhibition of DAGL could represent an effective approach to reduce alcohol consumption across the spectrum of AUD severity.

CognitiveConstruct

RewardProcessing

10.1124/pharmrev.120.000043

Pharmacological reviews

Pharmacol Rev

Aiding and Abetting Anhedonia: Impact of Inflammation on the Brain and Pharmacological Implications.

Exogenous administration of inflammatory stimuli to humans and laboratory animals and chronic endogenous inflammatory states lead to motivational deficits and ultimately anhedonia, a core and disabling symptom of depression present in multiple other psychiatric disorders. Inflammation impacts neurotransmitter systems and neurocircuits in subcortical brain regions including the ventral striatum, which serves as an integration point for reward processing and motivational decision-making. Many mechanisms contribute to these effects of inflammation, including decreased synthesis, release and reuptake of dopamine, increased synaptic and extrasynaptic glutamate, and activation of kynurenine pathway metabolites including quinolinic acid. Neuroimaging data indicate that these inflammation-induced neurotransmitter effects manifest as decreased activation of ventral striatum and decreased functional connectivity in reward circuitry involving ventral striatum and ventromedial prefrontal cortex. Neurocircuitry changes in turn mediate nuanced effects on motivation that include decreased willingness to expend effort for reward while maintaining the ability to experience reward. Taken together, the data reveal an inflammation-induced pathophysiologic phenotype that is agnostic to diagnosis. Given the many mechanisms involved, this phenotype represents an opportunity for development of novel and/or repurposed pharmacological strategies that target inflammation and associated cellular and systemic immunometabolic changes and their downstream effects on the brain. To date, clinical trials have failed to capitalize on the unique nature of this transdiagnostic phenotype, leaving the field bereft of interpretable data for meaningful clinical application. However, novel trial designs incorporating established targets in the brain and/or periphery using relevant outcome variables (e.g., anhedonia) are the future of targeted therapy in psychiatry. SIGNIFICANCE STATEMENT: Emerging understanding of mechanisms by which peripheral inflammation can affect the brain and behavior has created unprecedented opportunities for development of pharmacological strategies to treat deficits in motivation including anhedonia, a core and disabling symptom of depression well represented in multiple psychiatric disorders. Mechanisms include inflammation and cellular and systemic immunometabolism and alterations in dopamine, glutamate, and kynurenine metabolites, revealing a target-rich environment that nevertheless has yet to be fully exploited by current clinical trial designs and drugs employed.

CognitiveConstruct

RewardProcessing

10.1016/j.nbd.2021.105448

Neurobiology of disease

Neurobiol Dis

Serotonin drives striatal synaptic plasticity in a sex-related manner.

Plasticity at corticostriatal synapses is a key substrate for a variety of brain functions - including motor control, learning and reward processing - and is often disrupted in disease conditions. Despite intense research pointing toward a dynamic interplay between glutamate, dopamine (DA), and serotonin (5-HT) neurotransmission, their precise circuit and synaptic mechanisms regulating their role in striatal plasticity are still unclear. Here, we analyze the role of serotonergic raphe-striatal innervation in the regulation of DA-dependent corticostriatal plasticity. Mice (males and females, 2-6 months of age) were housed in standard plexiglass cages at constant temperature (22 ± 1°C) and maintained on a 12/12h light/dark cycle with food and demineralized water ad libitum. In the present study, we used a knock-in mouse line in which the green fluorescent protein reporter gene (GFP) replaced the I Tph2 exon (Tph2 mice), allowing selective expression of GFP in the whole 5-HT system, highlighting both somata and neuritis of serotonergic neurons. Heterozygous, Tph2, mice were intercrossed to obtain experimental cohorts, which included Wild-type (Tph2), Heterozygous (Tph2), and Mutant serotonin-depleted (Tph2) animals. Using male and female mice, carrying on different Tph2 gene dosages, we show that Tph2 gene modulation results in sex-specific corticostriatal abnormalities, encompassing the abnormal amplitude of spontaneous glutamatergic transmission and the loss of Long Term Potentiation (LTP) in Tph2 mice of both sexes, while this form of plasticity is normally expressed in control mice (Tph2). Once LTP is induced, only the Tph2 female mice present a loss of synaptic depotentiation. We showed a relevant role of the interaction between dopaminergic and serotonergic systems in controlling striatal synaptic plasticity. Overall, our data unveil that 5-HT plays a primary role in regulating DA-dependent corticostriatal plasticity in a sex-related manner and propose altered 5-HT levels as a critical determinant of disease-associated plasticity defects.

CognitiveConstruct

RewardProcessing

10.1016/j.yhbeh.2021.105022

Hormones and behavior

Horm Behav

A causal role of estradiol in human reinforcement learning.

The sex hormone estradiol is hypothesized to play a key role in human cognition, and reward processing specifically, via increased dopamine D1-receptor signalling. However, the effect of estradiol on reward processing in men has never been established. To fill this gap, we performed a double-blind placebo-controlled study in which men (N = 100) received either a single dose of estradiol (2 mg) or a placebo. Subjects performed a probabilistic reinforcement learning task where they had to choose between two options with varying reward probabilities to maximize monetary reward. Results showed that estradiol administration increased reward sensitivity compared to placebo. This effect was observed in subjects' choices, how much weight they assigned to their previous choices, and subjective reports about the reward probabilities. Furthermore, effects of estradiol were moderated by reward sensitivity, as measured through the BIS/BAS questionnaire. Using reinforcement learning models, we found that behavioral effects of estradiol were reflected in increased learning rates. These results demonstrate a causal role of estradiol within the framework of reinforcement learning, by enhancing reward sensitivity and learning. Furthermore, they provide preliminary evidence for dopamine-related genetic variants moderating the effect of estradiol on reward processing.

CognitiveConstruct

RewardProcessing

10.1037/emo0000979

Emotion (Washington, D.C.)

Emotion

Alterations in reward and emotional processing differentiate among adults with a history of childhood maltreatment: Implications for substance use behaviors.

Although childhood maltreatment is a well-established risk factor for a multitude of poor psychosocial outcomes, considerably less is known about mechanisms driving this risk transmission. Recent theoretical models posit that types of childhood maltreatment (deprivation vs. threat) may lead to alterations in reward and emotional processing that confer risk for later psychosocial problems. However, empirical examination of these theories is currently limited. We used a person-centered approach to identify profiles of reward and emotional processing in a sample of 758 adults reporting elevated childhood maltreatment. Latent profile analysis indicated a 3-class solution best fit the data: a blunted reward class ( = 220; 29.0%) characterized by low reward processing and average emotional processing; a disrupted emotional processing class ( = 242; 31.9%) marked by normative levels of reward processing but high emotional pain and experiential avoidance and low distress tolerance; and an emotional resilience class (n = 296; 39.1%) characterized by normative reward and emotional processing. Consistent with theoretical models, the specificity of disruption was differentially associated with dimensions of childhood maltreatment, with individuals in the blunted reward class reporting more childhood neglect and individuals in the disrupted emotional processing class reporting more childhood physical/sexual abuse. These profiles of disrupted reward and emotional processing also showed differential relations with the frequency and affective motivations for lifetime substance use. Findings provide empirical support for novel conceptual models of childhood maltreatment that focus on the consequences that may represent mechanisms for problematic behaviors like substance use. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

CognitiveConstruct

RewardProcessing

10.1037/bne0000424

Behavioral neuroscience

Behav Neurosci

Autonomic arousal tracks outcome salience not valence in monkeys making social decisions.

The evolutionary and neural underpinnings of human prosociality are still being identified. A growing body of evidence suggests that some species find the sight of another individual receiving a reward reinforcing, called vicarious reinforcement, and that this capacity is supported by a network of brain areas including the anterior cingulate cortex (ACC) and the amygdala. At the same time, analyses of autonomic arousal have been increasingly used to contextualize and guide neural research, especially for studies of reward processing. Here, we characterized the autonomic pupil response of eight monkeys across two laboratories in two different versions of a vicarious reinforcement paradigm. Monkeys were cued as to whether an upcoming reward would be delivered to them, another monkey, or nobody and could accept or decline the offer. As expected, all monkeys in both laboratories showed a marked preference for juice to the self, together with a reliable prosocial preference for juice to a social partner compared to juice to nobody. However, contrary to our expectations, we found that pupils were widest in anticipation of juice to the self, moderately sized in anticipation of juice to nobody, and narrowest in anticipation of juice to a social partner. This effect was seen across both laboratories and regardless of specific task parameters. The seemingly paradoxical pupil effect can be explained by a model in which pupil size tracks outcome salience, prosocial tendencies track outcome valence, and the relation between salience and valence is U-shaped. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

CognitiveConstruct

RewardProcessing

10.3389/fnmol.2021.678267

Frontiers in molecular neuroscience

Front Mol Neurosci

Sucrose Consumption Alters Serotonin/Glutamate Co-localisation Within the Prefrontal Cortex and Hippocampus of Mice.

The overconsumption of sugar-sweetened food and beverages underpins the current rise in obesity rates. Sugar overconsumption induces maladaptive neuroplasticity to decrease dietary control. Although serotonin and glutamate co-localisation has been implicated in reward processing, it is still unknown how chronic sucrose consumption changes this transmission in regions associated with executive control over feeding-such as the prefrontal cortex (PFC) and dentate gyrus (DG) of the hippocampus. To address this, a total of 16 C57Bl6 mice received either 5% w/v sucrose or water as a control for 12 weeks using the Drinking-In-The-Dark paradigm ( = 8 mice per group). We then examined the effects of chronic sucrose consumption on the immunological distribution of serotonin (5-HT), vesicular glutamate transporter 3 (VGLUT3) and 5-HT/VGLUT3 co-localised axonal varicosities. Sucrose consumption over 12 weeks decreased the number of 5-HT/VGLUT3 and 5-HT/VGLUT3 varicosities within the PFC and DG. The number of 5-HT/VGLUT3 varicosities remained unchanged within the PFC but decreased in the DG following sucrose consumption. Given that serotonin mediates DG neurogenesis through microglial migration, the number of microglia within the DG was also assessed in both experimental groups. Sucrose consumption decreased the number of DG microglia. Although the DG and PFC are associated with executive control over rewarding activities and emotional memory formation, we did not detect a subsequent change in DG neurogenesis or anxiety-like behaviour or depressive-like behaviour. Overall, these findings suggest that the chronic consumption of sugar alters serotonergic neuroplasticity within neural circuits responsible for feeding control. Although these alterations alone were not sufficient to induce changes in neurogenesis or behaviour, it is proposed that the sucrose consumption may predispose individuals to these cognitive deficits which ultimately promote further sugar intake.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2021.682824

Frontiers in psychology

Front Psychol

State Anhedonia in Young Healthy Adults: Psychometric Properties of the German Dimensional Anhedonia Rating Scale (DARS) and Effects of the COVID-19 Pandemic.

Healthy reward processing is a complex interplay of several components. Recent self-report measures of anhedonia, the decrease or loss of hedonic capacity, take this complexity into account. The Dimensional Anhedonia Rating Scale (DARS) measures interest, motivation, effort and consummatory pleasure across four domains: hobbies, food/drink, social activities and sensory experiences. In the present cross-sectional survey study, we validated the German version of the DARS in a sample of 557 young healthy adults. Factor structure as well as convergent and divergent validity were assessed. As a secondary aim, we examined the effects of the COVID-19 pandemic on state anhedonia and depression severity. Our results suggest good convergent and divergent validity and high internal consistency of the German DARS. The original differentiation of four factors mapping onto the four domains was confirmed and measurement invariance before and during the COVID-19 pandemic was established. We conclude that the DARS is a valid instrument to comprehensively assess state anhedonia in healthy German samples. Future studies should further assess the utility of the German DARS in clinical contexts. In line with many previous studies, participants during the pandemic reported significantly higher levels of depressive symptoms compared to participants in the months before. We found no indication that the COVID-19 pandemic affected state hedonic capacity.

CognitiveConstruct

RewardProcessing

10.3389/fnagi.2021.691710

Frontiers in aging neuroscience

Front Aging Neurosci

Resting-State Functional Connectivity Signatures of Apathy in Community-Living Older Adults.

Apathy predicts poor outcomes in older adults, and its underlying neural mechanism needs further investigation. We examined the association between symptoms of apathy and functional connectivity (FC) in older adults without stroke or dementia. Participants included 48 individuals (mean age = 70.90) living independently in the community, who underwent resting-state fMRI and completed the Apathy Evaluation Scale (AES). Seed-to-voxel analysis (cluster-level p-FDR <0.05, voxel threshold < 0.001) tested the association between AES scores and the whole-brain FC of brain regions involved in reward- and salience-related processing. We found that AES scores were negatively associated with FC of the right insula cortex and right anterior temporal regions (124 voxels, = -5.10) and FC of the left orbitofrontal cortex and anterior cingulate regions (160 voxels, = -5.45), and were positively associated with FC of the left orbitofrontal cortex and left lateral prefrontal (282 voxels, = 4.99) and anterior prefrontal (123 voxels, = 4.52) regions. These findings suggest that apathy in older adults may reflect disruptions in neural connectivity involved in reward- and salience-related processing.

CognitiveConstruct

RewardProcessing

10.1111/nyas.14656

Annals of the New York Academy of Sciences

Ann N Y Acad Sci

Dopamine modulations of reward-driven music memory consolidation.

Music listening provides one of the most significant abstract rewards for humans because hearing music activates the dopaminergic mesolimbic system. Given the strong link between reward, dopamine, and memory, we aimed here to investigate the hypothesis that dopamine-dependent musical reward can drive memory improvements. Twenty-nine healthy participants of both sexes provided reward ratings of unfamiliar musical excerpts that had to be remembered following a consolidation period under three separate conditions: after the ingestion of a dopaminergic antagonist, a dopaminergic precursor, or a placebo. Linear mixed modeling of the intervention data showed that the effect of reward on memory-i.e., the greater the reward experienced while listening to the musical excerpts, the better the memory recollection performance-was modulated by both dopaminergic signaling and individual differences in reward processing. Greater pleasure was consistently associated with better memory outcomes in participants with high sensitivity to musical reward, but this effect was lost when dopaminergic signaling was disrupted in participants with average or low musical hedonia. Our work highlights the flexibility of the human dopaminergic system, which can enhance memory formation not only through explicit and/or primary reinforcers but also via abstract and aesthetic rewards such as music.

CognitiveConstruct

RewardProcessing

10.1016/j.addbeh.2021.107034

Addictive behaviors

Addict Behav

Child reward neurocircuitry and parental substance use history: Findings from the Adolescent Brain Cognitive Development Study.

Substance use research has focused on family history of alcohol use disorders but less on other addictions in biological family members. We examined how parental substance use history relates to reward system functioning, specifically nucleus accumbens (NAcc) and putamen activation at age 9-10 in the Adolescent Brain Cognitive Development (ABCD) Study. This research hopes to address limitations in prior literature by focusing analyses on a large, substance-naïve sample. We included ABCD participants with valid Monetary Incentive Delay task fMRI Baseline data and parent substance use history at project baseline from Data Release 2.0 (N = 10,622). Parent-history-positive (PH+) participants had one or both biological parents with a history of two+problems with alcohol (n = 741; PH+A) and/or other drugs (n = 638; PH+D). Of participants who were parent-history-negative (PH-) for alcohol and/or drugs, a stratified random sample based on six sociodemographic variables was created and matched to the PH+group (PH-A n = 699; PH-D n = 615). The contrast of interest was anticipation of a large reward vs. neutral response. PH+A youth had more activation in the right NAcc during large reward anticipation than PH-A. PH+D youth showed enhanced left putamen activation during large reward anticipation than PH-D youth. Bayesian hypothesis testing showed moderate evidence (BF > 3) in favor of the null hypothesis. These findings suggest that pre-adolescents whose biological parents had a history of substance-related problems show small differences in reward processing compared to their PH- peers.

CognitiveConstruct

RewardProcessing

10.1016/j.pnpbp.2021.110394

Progress in neuro-psychopharmacology & biological psychiatry

Prog Neuropsychopharmacol Biol Psychiatry

The role of the nucleus accumbens and ventral pallidum in feeding and obesity.

Obesity is a growing global epidemic that stems from the increasing availability of highly-palatable foods and the consequent enhanced calorie consumption. Extensive research has shown that brain regions that are central to reward seeking modulate feeding and evidence linking obesity to pathology in such regions have recently started to accumulate. In this review we focus on the contribution of two major interconnected structures central to reward processing, the nucleus accumbens and the ventral pallidum, to obesity. We first review the known literature linking these structures to feeding behavior, then discuss recent advances connecting pathology in the nucleus accumbens and ventral pallidum to obesity, and finally examine the similarities and differences between drug addiction and obesity in the context of these two structures. The understanding of how pathology in brain regions involved in reward seeking and consumption may drive obesity and how mechanistically similar obesity and addiction are, is only now starting to be revealed. We hope that future research will advance knowledge in the field and open new avenues to studying and treating obesity.

CognitiveConstruct

RewardProcessing

10.3389/fphar.2021.685631

Frontiers in pharmacology

Front Pharmacol

Salmon Calcitonin Attenuates Some Behavioural Responses to Nicotine in Male Mice.

The behavioural responses to nicotine involve appetite-regulatory hormones; however, the effects of the anorexigenic hormone amylin on reward-related behaviours induced by nicotine remain to be established. Previous studies have shown that the amylinergic pathway regulates behavioural responses to alcohol, amphetamine and cocaine. Here, we evaluated the effects of salmon calcitonin (sCT), an amylin and calcitonin receptor (CTR) agonist, on nicotine-induced locomotor stimulation and sensitisation as well as dopamine release in the nucleus accumbens (NAc) shell. Moreover, we investigated the effects of sCT on the acquisition and expression of nicotine-induced reward in the conditioned place preference (CPP) paradigm. Finally, we performed Western Blot experiments in an attempt to identify the levels of the amylin receptor components CTRa, CTRb, and RAMP1 in reward-related areas of mice responding differently to repeated injections of sCT and nicotine in the locomotor sensitisation test. We found that sCT blocked nicotine's stimulatory and dopamine-releasing effects and prevented its ability to cause locomotor sensitisation. On the other hand, sCT did not alter nicotine-induced acquisition and expression of CPP. Lastly, sCT-nicotine treated mice from the locomotor sensitisation experiment displayed higher levels of total CTR, i.e. CTRa and CTRb together, in the reward-processing laterodorsal tegmental area (LDTg) of the brain compared to mice treated with vehicle-nicotine. Overall, the present data reveal that activation of CTR or/and amylin receptors attenuates certain nicotine-induced behaviours in male mice, further contributing to the understanding of appetite-regulatory peptides in reward regulation.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2021.693698

Frontiers in behavioral neuroscience

Front Behav Neurosci

Distinct Profiles of 50 kHz Vocalizations Differentiate Between Social Versus Non-social Reward Approach and Consumption.

Social animals tend to possess an elaborate vocal communication repertoire, and rats are no exception. Rats utilize ultrasonic vocalizations (USVs) to communicate information about a wide range of socially relevant cues, as well as information regarding the valence of the behavior and/or surrounding environment. Both quantitative and qualitative acoustic properties of these USVs are thought to communicate context-specific information to conspecifics. Rat USVs have been broadly categorized into 22 and 50 kHz call categories, which can be further classified into subtypes based on their sonographic features. Recent research indicates that the 50 kHz calls and their various subtype profiles may be related to the processing of social and non-social rewards. However, only a handful of studies have investigated USV elicitation in the context of both social and non-social rewards. Here, we employ a novel behavioral paradigm, the social-sucrose preference test, that allowed us to measure rats' vocal responses to both non-social (i.e., 2, 5, and 10% sucrose) and social reward (interact with a Juvenile rat), presented concurrently. We analyzed adult male Long-Evans rats' vocal responses toward social and non-social rewards, with a specific focus on 50 kHz calls and their 14 subtypes. We demonstrate that rats' preference and their vocal responses toward a social reward were both influenced by the concentration of the non-social reward in the maze. In other words, rats showed a trade-off between time spent with non-social or social stimuli along with increasing concentrations of sucrose, and also, we found a clear difference in the emission of flat and frequency-modulated calls in the social and non-social reward zones. Furthermore, we report that the proportion of individual subtypes of 50 kHz calls, as well as the total USV counts, showed variation across different types of rewards as well. Our findings provide a thorough overview of rat vocal responses toward non-social and social rewards and are a clear depiction of the variability in the rat vocalization repertoire, establishing the role of call subtypes as key players driving context-specific vocal responses of rats.

CognitiveConstruct

RewardProcessing

10.1002/oby.23201

Obesity (Silver Spring, Md.)

Obesity (Silver Spring)

Nucleus accumbens microstructure mediates the relationship between obesity and eating behavior in adults.

Basal ganglia regions are part of the brain's reward-processing networks and are implicated in the neurobiology of obesity and eating disorders. This study examines basal ganglia microstructural properties in adults with and without obesity. Diffusion basis spectrum imaging (DBSI) images were analyzed to obtain putative imaging markers of neuroinflammation. Relationships between basal ganglia DBSI metrics and reward sensitivity and eating behaviors were also explored. A total of 46 participants (25 people with obesity; aged 20-40 years; 37 women) were included. Relative to the people in the normal-weight group, people with obesity had smaller caudate and larger nucleus accumbens (NAcc) volumes (p < 0.05) and lower DBSI fiber fraction (reflecting apparent axonal/dendrite density) in NAcc and putamen, higher DBSI nonrestricted fraction (reflecting tissue edema) in NAcc and caudate, and higher DBSI restricted fraction (reflecting tissue cellularity) in putamen (p ≤ 0.01, all). Increased emotional and reward eating behaviors were related to lower NAcc axonal/dendrite density and greater tissue edema (p ≤ 0.002). The relationships between emotional eating and adiposity measures were mediated by NAcc microstructure. These findings provide evidence that microstructural alterations in basal ganglia relate to obesity and insights linking NAcc microstructure and eating behavior in adults.

CognitiveConstruct

RewardProcessing

10.3390/nu13062091

Nutrients

Nutrients

Alpha-Glycerylphosphorylcholine Increases Motivation in Healthy Volunteers: A Single-Blind, Randomized, Placebo-Controlled Human Study.

Alpha-glycerylphosphorylcholine (αGPC) is a precursor of acetylcholine and can increase acetylcholine concentration in the brain. In addition, αGPC has a role in cholinergic function as well as monoaminergic transmission, including dopaminergic and serotonergic systems. These monoaminergic systems are related to feelings and emotions, including motivation, reward processing, anxiety, and depression. However, the precise effects of αGPC on human feelings and emotions remain to be elucidated. In this study, we investigated changes in the subjective feelings of healthy volunteers using the KOKORO scale before and after administering αGPC. Thirty-nine volunteers participated in a single-blind, placebo-controlled design. Participants completed a KOKORO scale test to quantify self-reported emotional states, three times each day for two weeks preceding treatment and then for a further two weeks while self-administering treatment. αGPC treatment show a tendency to increase motivation during the intervention period. Furthermore, motivation at night was significantly higher in the αGPC group than in the placebo group ( < 0.05). However, αGPC did not show any effects on anxiety. These data suggest that αGPC can be used to increase motivation in healthy individuals.

CognitiveConstruct

RewardProcessing

10.3390/ijms22115994

International journal of molecular sciences

Int J Mol Sci

Role of Lateral Hypothalamus in Acupuncture Inhibition of Cocaine Psychomotor Activity.

Acupuncture modulates the mesolimbic dopamine (DA) system; an area implicated in drug abuse. However, the mechanism by which peripheral sensory afferents, during acupuncture stimulation, modulate this system needs further investigation. The lateral hypothalamus (LH) has been implicated in reward processing and addictive behaviors. To investigate the role of the LH in mediating acupuncture effects, we evaluated the role of LH and spinohypothalamic neurons on cocaine-induced psychomotor activity and NAc DA release. Systemic injection of cocaine increased locomotor activity and 50 kHz ultrasonic vocalizations (USVs), which were attenuated by mechanical stimulation of needles inserted into HT7 but neither ST36 nor LI5. The acupuncture effects were blocked by chemical lesions of the LH or mimicked by activation of LH neurons. Single-unit extracellular recordings showed excitation of LH and spinohypothalamic neurons following acupuncture. Our results suggest that acupuncture recruits the LH to suppress the mesolimbic DA system and psychomotor responses following cocaine injection.

CognitiveConstruct

RewardProcessing

10.2147/NDT.S282554

Neuropsychiatric disease and treatment

Neuropsychiatr Dis Treat

Exploring Neural Mechanisms Related to Cognitive Control, Reward, and Affect in Eating Disorders: A Narrative Review of FMRI Studies.

Studies using functional magnetic resonance imaging (fMRI) have contributed to our understanding of possible neural abnormalities among individuals with eating disorders. Many of these studies have focused on three domains: 1) cognitive control, 2) reward processing, and 3) affective processing. This review attempts to summarize the recent fMRI findings across these domains among the most well-characterized eating disorders: anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Though the literature is a bit murky, a few major themes have emerged. Cognitive control systems are affected among individuals across eating disorder diagnoses, but effects seem least pronounced in AN. Specifically, individuals with all eating disorders appear to show decreased prefrontal activation during cognitive control, but there is less evidence in AN linking decreased prefrontal activation with behavior. There is some evidence that the reinforcing value of food is reduced in AN, but individuals with BN and BED show hyperactivation to rewarding food-related stimuli, suggesting the reinforcing value of food may be enhanced. However, more complex reward processing paradigms show that individuals with BN and BED exhibit hypoactivation to reward anticipation and provide mixed results with regards to reward receipt. There are fewer neuroimaging findings related to affective processing, yet behavioral findings suggest affective processing is important in understanding eating disorders. Though the extant literature is complicated, these studies represent a foundation from which to build and provide insight into potential neurobiological mechanisms that may contribute to the pathophysiology of eating disorders.

CognitiveConstruct

RewardProcessing

10.1016/j.cortex.2021.05.013

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

Cortex

Avoiding monetary loss: A human habenula functional MRI ultra-high field study.

A number of convergent human neuroimaging and animal studies suggest that habenula neurons fire in anticipation of non-rewarding outcomes, and suppress their firing in anticipation of rewarding outcomes. This normative function of the habenula appears disrupted in depression, and may be critical to the anti-depressant effects of ketamine. However, studying habenula functionality in humans using standard 3 T MRI is inherently limited by its small size. We employed ultra-high field (7 T) fMRI to investigate habenular activity in eighteen healthy volunteers during a Monetary Incentive Delay Task, focussing on loss avoidance, monetary loss and neutral events. We assessed neural activation in the field of view (FOV) in addition to ROI-based habenula-specific activity and generalized task-dependent functional connectivity. Whole FOV results indicated substantial neural differences between monetary loss and neutral outcomes, as well as between loss avoidance and neutral outcomes. Habenula-specific analyses showed bilateral deactivation during loss avoidance, compared to other outcomes. This first investigation into the habenula's role during loss avoidance revealed that the left habenula further differentiated between loss avoidance and monetary loss. Functional connectivity between the right habenula and the ipsilateral hippocampus and subcallosal cingulate (regions implicated in memory and depression pathophysiology) was enhanced when anticipating potential losses compared to anticipating neutral outcomes. Our findings suggest that the human habenula responds most strongly to outcomes of loss avoidance when compared to neutral and monetary losses, suggesting a role for the habenula in both reward and aversive processing. This has critical relevance to understanding the pathophysiology of habenula function in mood and other neuropsychiatric disorders, as well as the mechanism of action of habenula-targeting antidepressants such as ketamine.

CognitiveConstruct

RewardProcessing

10.1016/j.bpsc.2021.05.010

Biological psychiatry. Cognitive neuroscience and neuroimaging

Biol Psychiatry Cogn Neurosci Neuroimaging

Reward Processing in Psychiatric Inpatients With Depression.

Previous neuroimaging studies have investigated reward-processing dysfunction in major depressive disorder and have led to the common finding that major depressive disorder is associated with reduced reward responses within the reward circuit. Yet it is unclear whether such reward-processing dysfunction is specifically associated with the severity of depressive symptoms in major depressive disorder or is associated with common comorbidities. We investigated reward-processing differences using a classic juice-delivery functional magnetic resonance imaging experiment to compare psychiatric patients with severe depressive symptoms (DEPs) to both psychiatric control subjects (PCs) and healthy control subjects. In this study, the DEPs (n = 108) were matched to healthy control subjects (n = 62) for demographic characteristics and to the PCs (n = 108) for demographics and comorbid psychiatric diagnoses. An a priori region of interest, the left putamen, was selected using previous studies. An exploratory whole-brain analysis was performed to explore for nonhypothesized regions. Relative to the PCs and healthy control subjects, the DEP group showed smaller responses to reward stimulus in the left putamen. Whole-brain exploratory analysis revealed that DEPs had significantly lower responses to reward stimulus in the bilateral dorsal striatum (putamen and caudate), middle frontal gyrus, left precentral gyrus, and middle cingulate cortex than PCs. Our findings suggest that DEPs may have a lesser ability to modulate behavior as a function of reward, especially in those individuals who experience the most severe depressive symptoms. In both DEPs and PCs, the severity of depressive symptoms was related to reduced reward responses in the left putamen.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsab081

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Confirmation of Interpersonal Expectations is Intrinsically Rewarding.

People want to interact successfully with other individuals, and they invest significant efforts in attempting to do so. Decades of research have demonstrated that to simplify the dauntingly complex task of interpersonal communication, perceivers predict the responses of individuals in their environment using stereotypes and other sources of prior knowledge. Here, we show that these top-down expectations can also shape the subjective value of expectation-consistent and expectation-violating targets. Specifically, in two neuroimaging experiments (n = 58), we observed increased activation in brain regions associated with reward processing-including the nucleus accumbens-when perceivers observed information consistent with their social expectations. In two additional behavioral experiments (n = 704), we observed that perceivers were willing to forgo money to encounter an expectation-consistent target and avoid an expectation-violating target. Together, these findings suggest that perceivers value having their social expectations confirmed, much like food or monetary rewards.

CognitiveConstruct

RewardProcessing

10.1017/S0007114521002312

The British journal of nutrition

Br J Nutr

Overview of the central amygdala role in feeding behaviour.

The neural regulation of feeding behaviour, as an essential factor for survival, is an important research area today. Feeding behaviour and other lifestyle habits play a major role in optimising health and obesity control. Feeding behaviour is physiologically controlled through processes associated with energy and nutrient needs. Different brain nuclei are involved in the neural regulation of feeding behaviours. Therefore, understanding the function of these brain nuclei helps develop feeding control methods. Among important brain nuclei, there is scant literature on the central amygdala (CeA) nucleus and feeding behaviour. The CeA is one of the critical brain regions that play a significant role in various physiological and behavioural responses, such as emotional states, reward processing, energy balance and feeding behaviour. It contains γ-aminobutyric acid neurons. Also, it is the major output region of the amygdaloidal complex. Moreover, the CeA is also involved in multiple molecular and biochemical factors and has extensive connections with other brain nuclei and their neurotransmitters, highlighting its role in feeding behaviour. This review aims to highlight the significance of the CeA nucleus on food consumption by its interaction with the performance of reward, digestive and emotional systems.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2021.102700

NeuroImage. Clinical

Neuroimage Clin

The functional neural architecture of dysfunctional reward processing in autism.

Functional imaging studies have found differential neural activation patterns during reward-paradigms in patients with autism spectrum disorder (ASD) compared to neurotypical controls. However, publications report conflicting results on the directionality and location of these aberrant activations. We here quantitatively summarized relevant fMRI papers in the field using the anatomical likelihood estimation (ALE) algorithm. Patients with ASD consistently showed hypoactivations in the striatum across studies, mainly in the right putamen and accumbens. These regions are functionally involved in the processing of rewards and are enrolled in extensive neural networks involving limbic, cortical, thalamic and mesencephalic regions. The striatal hypo-activations found in our ALE meta-analysis, which pooled over contrasts derived from the included studies on reward-processing in ASD, highlight the role of the striatum as a key neural correlate of impaired reward processing in autism. These changes were present for studies using social and non-social stimuli alike. The involvement of these regions in extensive networks associated with the processing of both positive and negative emotion alike might hint at broader impairments of emotion processing in the disorder.

CognitiveConstruct

RewardProcessing

10.1556/2006.2021.00040

Journal of behavioral addictions

J Behav Addict

Motivated attention to stimuli related to social networking sites: A cue-reactivity study.

It has been argued that similar to addictive behaviors, problematic Social Network sites use (PSNSU) is characterized by sensitized reward processing and cue-reactivity. However, no study to our knowledge has yet investigated cue-reactivity in PSNSU. The present study aims at investigating cue-reactivity to Social Network sites (i.e., Facebook)-related visual cues in individuals identified as problematic vs. non-problematic Facebook users by the Problematic Facebook Use Scale. The Event-Related Potentials (ERPs) were recorded during the passive viewing of Facebook-related, pleasant, unpleasant, and neutral pictures in 27 problematic and 26 non-problematic users. Moreover, craving for Facebook usage was collected using a Likert scale. Despite problematic users were more likely to endorse higher craving than non-problematic ones, Facebook-related cues elicited larger ERP positivity (400-600 ms) than neutral, and comparable to unpleasant stimuli, in all Facebook users. Only in problematic users we found larger positivity (600-800 ms) to pleasant than unpleasant cues and higher craving to be related with lower later positivity (800-1,000 ms) to pleasant and unpleasant cues. Regardless of whether Facebook usage is problematic or non-problematic, Facebook-related cues seem to be motivationally relevant stimuli that capture attentional resources in the earlier stages of "motivated" attentional allocation. Moreover, our results support the view that in higher-craving problematic users, reduced abilities to experience emotions would be the result of defective emotion regulation processes that allow craving states to capture more motivational/attentional resources at the expense of other emotional states.

CognitiveConstruct

RewardProcessing

10.1016/j.addbeh.2021.107015

Addictive behaviors

Addict Behav

Problematic smartphone use: The role of reward processing, depressive symptoms and self-control.

The widespread adoption of smartphones has been associated with the emergence of problematic smartphone use. Problematic smartphone use is consistently associated with increased levels of depression and lower self-control, and pathological technology use more generally may be associated with reduced activity in the reward system, an effect that is also observed in depression and with poor self-control. The current study sought to examine the association between problematic smartphone use and event-related potentials (ERPs) related to reward processing, and to determine whether reward processing, depressive symptoms and self-control have shared or unique influences on problematic smartphone use. The sample was drawn from a university student population (N = 94, age M = 19.34, SD = 1.23 years, 67 female, 25 male, 1 gender non-conforming, 1 unidentified). Participants performed a gambling task while EEG was recorded and completed measures of smartphone pathology, depressive symptoms and self-control. The ERP data revealed that increasing problematic smartphone use was associated with reduced ERP amplitude for gains and losses when individuals were the agent of choice, but not when the computer chose. This may reflect a selective association between problematic smartphone use and neural prediction errors. Regression analyses revealed that reward processing, depressive symptoms and self-control were predictors of problematic smartphone use, possibly revealing multiple pathways to problematic smartphone use.

CognitiveConstruct

RewardProcessing

10.1002/jnr.24900

Journal of neuroscience research

J Neurosci Res

Prenatal androgen influences on the brain: A review, critique, and illustration of research on congenital adrenal hyperplasia.

Sex hormones, especially androgens, contribute to sex and gender differences in the brain and behavior. Organizational effects are particularly important because they are thought to be permanent, reflecting hormone exposure during sensitive periods of development. In human beings, they are often studied with natural experiments in which sex hormones are dissociated from other biopsychosocial aspects of development, such as genes and experiences. Indeed, the greatest evidence for organizational effects on sex differences in human behavior comes from studies of females with congenital adrenal hyperplasia (CAH), who have heightened prenatal androgen exposure, female-typical rearing, and masculinized toy play, activity and career interests, spatial skills, and some personal characteristics. Interestingly, however, neuroimaging studies of females with CAH have revealed few neural mechanisms underlying these hormone-behavior links, with the exception of emotion processing; studies have instead shown reduced gray matter volumes and reduced white matter integrity most consistent with other disease-related processes. The goals of this narrative review are to: (a) describe methods for studying prenatal androgen influences, while offering a brief overview of behavioral outcomes; (b) provide a critical methodological review of neuroimaging research on females with CAH; (c) present an illustrative analysis that overcomes methodological limitations of previous work, focusing on person-specific neural reward networks (and their associations with sensation seeking) in women with CAH and their unaffected sisters in order to inform future research questions and approaches that are most likely to reveal organizational hormone effects on brain structure and function.

CognitiveConstruct

RewardProcessing

10.1038/s41537-021-00163-2

NPJ schizophrenia

NPJ Schizophr

Interaction of schizophrenia and chronic cannabis use on reward anticipation sensitivity.

Chronic cannabis use and schizophrenia are both thought to affect reward processing. While behavioural and neural effects on reward processing have been investigated in both conditions, their interaction has not been studied, although chronic cannabis use is common among these patients. In the present study eighty-nine participants divided into four groups (control chronic cannabis users and non-users; schizophrenia patient cannabis users and non-users) performed a two-choice decision task, preceded by monetary cues (high/low reward/punishment or neutral), while being scanned using functional magnetic resonance imaging. Reward and punishment anticipation resulted in activation of regions of interest including the thalamus, striatum, amygdala and insula. Chronic cannabis use and schizophrenia had opposing effects on reward anticipation sensitivity. More specifically control users and patient non-users showed faster behavioural responses and increased activity in anterior/posterior insula for high magnitude cues compared to control non-users and patient users. The same interaction pattern was observed in the activation of the right thalamus for reward versus punishment cues. This study provided evidence for interaction of chronic cannabis use and schizophrenia on reward processing and highlights the need for future research addressing the significance of this interaction for the pathophysiology of these conditions and its clinical consequences.

CognitiveConstruct

RewardProcessing

10.5334/joc.167

Journal of cognition

J Cogn

Examining Social Cognition with Embodied Robots: Does Prior Experience with a Robot Impact Feedback-associated Learning in a Gambling Task?

Social agents rely on the ability to use feedback to learn and modify their behavior. The extent to which this happens in social contexts depends on motivational, cognitive and/or affective parameters. For instance, feedback-associated learning occurs at different rates when the outcome of an action (e.g., winning or losing in a gambling task) affects oneself ("Self") versus another human ("Other"). Here, we examine whether similar context effects on feedback-associated learning can also be observed when the "other" is a social robot (here: Cozmo). We additionally examine whether a "hybrid" version of the gambling paradigm, where participants are free to engage in a dynamic interaction with a robot, then move to a controlled screen-based experiment can be used to examine social cognition in human-robot interaction. This hybrid method is an alternative to current designs where researchers examine the effect of the interaction on social cognition during the interaction with the robot. For that purpose, three groups of participants (n total = 60) interacted with Cozmo over different time periods (no interaction vs. a single 20 minute interaction in the lab vs. daily 20 minute interactions over five consecutive days at home) before performing the gambling task in the lab. The results indicate that prior interactions impact the degree to which participants benefit from feedback during the gambling task, with overall worse learning immediately after short-term interactions with the robot and better learning in the "Self" versus "Other" condition after repeated interactions with the robot. These results indicate that "hybrid" paradigms are a suitable option to investigate social cognition in human-robot interaction when a fully dynamic implementation (i.e., interaction and measurement dynamic) is not feasible.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2021.05.093

Journal of affective disorders

J Affect Disord

Neural correlates of irritability in a community sample of children.

Irritability has been associated with aberrant patterns of neural activation, yet little is known about structural brain correlates of irritability. As such, we aimed to investigate associations between irritability and gray matter volume (GMV) in a community sample of children enriched for irritability. The sample comprised children (n=162) aged 9-11 years with and without Attention-Deficit/Hyperactivity Disorder (ADHD), participating in a cohort study with magnetic resonance imaging data available. Mixed effects linear regression analyses tested the associations between irritability symptoms and regional GMV (extracted using Freesurfer). Irritability was associated with smaller gray matter volume across multiple brain regions implicated in executive functioning, and emotion and reward processing including frontal regions and the cingulate.

CognitiveConstruct

RewardProcessing

10.1016/j.bpsc.2021.05.009

Biological psychiatry. Cognitive neuroscience and neuroimaging

Biol Psychiatry Cogn Neurosci Neuroimaging

Ketamine Modulates the Neural Correlates of Reward Processing in Unmedicated Patients in Remission from Depression.

Ketamine as an antidepressant improves anhedonia as early as 2h post-infusion. These drug effects are thought to be exerted via actions on reward-related brain areas-yet, these actions remain largely unknown. Our study investigates ketamine's effects during the anticipation and receipt of an expected reward, after the psychotomimetic effects of ketamine have passed, when early antidepressant effects are reported. We examined ketamine's effects during the anticipation and receipt of expected rewards on pre-defined brain areas, namely the dorsal and ventral striatum, the ventral tegmental area, the amygdala and the insula. We have recruited 37 male and female participants who remitted from depression and were free from symptoms and antidepressant treatments at the time of the scan. Participants were scanned, 2h after drug administration, in a double-blind cross over design (ketamine:0.5mg/kg and placebo) while performing a monetary reward task. A significant main effect of ketamine, across all ROIs, was observed during the anticipation and feedback phases of win and no-win trials. The drug effects were particularly prominent in the nucleus accumbens and putamen, which showed increased activation upon the receipt of smaller rewards compared to neutral. The levels of (2R,6R)-HNK, 2h post-infusion, significantly correlated with the activation observed in the ventral tegmental area for that contrast. These findings demonstrate that ketamine can produce detectable changes in reward-related brain areas, 2h after infusion, which occur without symptom changes and support the idea that ketamine might improve reward-related symptoms via modulation of response to feedback.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2021.559401

Frontiers in psychiatry

Front Psychiatry

Reward Processing and Circuit Dysregulation in Posttraumatic Stress Disorder.

Past decades have witnessed substantial progress in understanding of neurobiological mechanisms that contribute to generation of various PTSD symptoms, including intrusive memories, physiological arousal and avoidance of trauma reminders. However, the neurobiology of anhedonia and emotional numbing in PTSD, that have been conceptualized as reward processing deficits - reward wanting (anticipation of reward) and reward liking (satisfaction with reward outcome), respectively, remains largely unexplored. Empirical evidence on reward processing in PTSD is rather limited, and no studies have examined association of reward processing abnormalities and neurocircuitry-based models of PTSD pathophysiology. The manuscript briefly summarizes "state of the science" of both human reward processing, and of PTSD implicated neurocircuitry, as well as empirical evidence of reward processing deficits in PTSD. We then summarize current gaps in the literature and outline key future directions, further illustrating it by the example of two alternative explanations of PTSD pathophysiology potentially affecting reward processing via different neurobiological pathways. Studying reward processing in PTSD will not only advance the understanding of their link, but also could enhance current treatment approaches by specifically targeting anhedonia and emotional symptoms in PTSD patients.

CognitiveConstruct

RewardProcessing

10.1017/S003329172100204X

Psychological medicine

Psychol Med

Reduced willingness to expend effort for rewards is associated with risk for conversion and negative symptom severity in youth at clinical high-risk for psychosis.

Schizophrenia (SZ) is typically preceded by a prodromal (i.e. pre-illness) period characterized by attenuated positive symptoms and declining functional outcome. Negative symptoms are prominent among individuals at clinical high-risk (CHR) for psychosis (i.e. those with prodromal syndromes) and predictive of conversion to illness. Mechanisms underlying negative symptoms are unclear in the CHR population. The current study evaluated whether CHR participants demonstrated deficits in the willingness to expend effort for rewards and whether these impairments are associated with negative symptoms and greater risk for conversion. Participants included 44 CHR participants and 32 healthy controls (CN) who completed the Effort Expenditure for Reward Task (EEfRT). Compared to CN, CHR participants displayed reduced likelihood of exerting high effort for high probability and magnitude rewards. Among CHR participants, reduced effort expenditure was associated with greater negative symptom severity and greater probability of conversion to a psychotic disorder on a cross-sectional risk calculator. Findings suggest that effort-cost computation is a marker of illness liability and a transphasic mechanism underlying negative symptoms in the SZ spectrum.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2021.645048

Frontiers in human neuroscience

Front Hum Neurosci

Brain Networks Underlying Strategy Execution and Feedback Processing in an Efficient Functional Magnetic Resonance Imaging Neurofeedback Training Performed in a Parallel or a Serial Paradigm.

Neurofeedback (NF) is a complex learning scenario, as the task consists of trying out mental strategies while processing a feedback signal that signifies activation in the brain area to be self-regulated and acts as a potential reward signal. In an attempt to dissect these subcomponents, we obtained whole-brain networks associated with efficient self-regulation in two paradigms: parallel, where the task was performed concurrently, combining feedback with strategy execution; and serial, where the task was performed consecutively, separating feedback processing from strategy execution. Twenty participants attempted to control their anterior midcingulate cortex (aMCC) using functional magnetic resonance imaging (fMRI) NF in 18 sessions over 2 weeks, using cognitive and emotional mental strategies. We analyzed whole-brain fMRI activations in the NF training runs with the largest aMCC activation for the serial and parallel paradigms. The equal length of the strategy execution and the feedback processing periods in the serial paradigm allows a description of the two task subcomponents with equal power. The resulting activation maps were spatially correlated with functionally annotated intrinsic connectivity brain maps (BMs). Brain activation in the parallel condition correlates with the basal ganglia (BG) network, the cingulo-opercular network (CON), and the frontoparietal control network (FPCN); brain activation in the serial strategy execution condition with the default mode network (DMN), the FPCN, and the visual processing network; while brain activation in the serial feedback processing condition predominantly with the CON, the DMN, and the FPCN. Additional comparisons indicate that BG activation is characteristic to the parallel paradigm, while supramarginal gyrus (SMG) and superior temporal gyrus (STG) activations are characteristic to the serial paradigm. The multifaceted view of the subcomponents allows describing the cognitive processes associated with strategy execution and feedback processing independently in the serial feedback task and as combined processes in the multitasking scenario of the conventional parallel feedback task.

CognitiveConstruct

RewardProcessing

10.1016/j.cobeha.2021.03.019

Current opinion in behavioral sciences

Curr Opin Behav Sci

Mindful Positive Emotion Regulation as a Treatment for Addiction: From Hedonic Pleasure to Self-Transcendent Meaning.

Chronic drug use is theorized to induce cortico-striatal neuroplasticity, driving an allostatic process marked by increased sensitivity to drug-related cues and decreased sensitivity to natural rewards that results in anhedonia and a dearth of positive affect. As such, positive emotion regulation represents a key mechanistic target for addictions treatment. This paper provides a conceptual model detailing how mindfulness may synergize a range of positive affective mechanisms to reduce addictive behavior, from savoring the hedonic pleasure derived from natural rewards, to self-generating interoceptive reward responses, and ultimately to cultivating self-transcendent meaning. These therapeutic processes may restructure reward processing from over-valuation of drug-related rewards back to valuation of natural rewards, and hypothetically, "reset" the default mode network dysfunction that undergirds addiction.

CognitiveConstruct

RewardProcessing

10.1038/s41598-021-91227-x

Scientific reports

Sci Rep

Connectivity adaptations in dopaminergic systems define the brain maturity of investors.

Investment decisions rely on perceptions from external stimuli along with the integration of inner brain-body signals, all of which are shaped by experience. As experience is capable of molding both the structure and function of the human brain, we have used a novel neuroimaging connectomic-genetic approach to investigate the influence of investment work experience on brain anatomy. We found that senior investors display higher gray matter volume and increased structural brain connectivity in dopamine-related pathways, as well as a set of genes functionally associated with adrenaline and noradrenaline biosynthesis (SLC6A3, TH and SLC18A2), which is seemingly involved in reward processing and bodily stress responses during financial trading. These results suggest the key role of catecholamines in the way senior investors harness their emotions while raising bodily awareness as they grow in investment maturity.

CognitiveConstruct

RewardProcessing

10.1177/0271678X211019827

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

J Cereb Blood Flow Metab

Functional dynamics of dopamine synthesis during monetary reward and punishment processing.

The assessment of dopamine release with the PET competition model is thoroughly validated but entails disadvantages for the investigation of cognitive processes. We introduce a novel approach incorporating 6-[F]FDOPA uptake as index of the dynamic regulation of dopamine synthesis enzymes by neuronal firing. The feasibility of this approach is demonstrated by assessing widely described sex differences in dopamine neurotransmission. Reward processing was behaviorally investigated in 36 healthy participants, of whom 16 completed fPET and fMRI during the monetary incentive delay task. A single 50 min fPET acquisition with 6-[F]FDOPA served to quantify task-specific changes in dopamine synthesis. In men monetary gain induced stronger increases in ventral striatum dopamine synthesis than loss. Interestingly, the opposite effect was discovered in women. These changes were further associated with reward (men) and punishment sensitivity (women). As expected, fMRI showed robust task-specific neuronal activation but no sex difference. Our findings provide a neurobiological basis for known behavioral sex differences in reward and punishment processing, with important implications in psychiatric disorders showing sex-specific prevalence, altered reward processing and dopamine signaling. The high temporal resolution and magnitude of task-specific changes make fPET a promising tool to investigate functional neurotransmitter dynamics during cognitive processing and in brain disorders.

CognitiveConstruct

RewardProcessing

10.1186/s40337-021-00417-5

Journal of eating disorders

J Eat Disord

Adapting a neuroscience-informed intervention to alter reward mechanisms of anorexia nervosa: a novel direction for future research.

Accumulating psychobiological data implicate reward disturbances in the persistence of anorexia nervosa (AN). Evidence suggests that individuals with AN demonstrate decision-making deficits similar to those with mood and anxiety disorders that cause them to under-respond to many conventionally rewarding experiences (e.g., eating, interacting socially). In contrast, unlike individuals with other psychiatric disorders, individuals with AN simultaneously over-respond to rewards associated with eating-disorder behaviors (e.g., restrictive eating, exercising). This pattern of reward processing likely perpetuates eating-disorder symptoms, as the rewards derived from eating-disorder behaviors provide temporary relief from the anhedonia associated with limited responsivity to other rewards. Positive Affect Treatment (PAT) is a cognitive-behavioral intervention designed to target reward deficits that contribute to anhedonia in mood and anxiety disorders, including problems with reward anticipation, experiencing, and learning. PAT has been found to promote reward responsivity and clinical improvement in mood and anxiety disorders. This manuscript will: (1) present empirical evidence supporting the promise of PAT as an intervention for AN; (2) highlight nuances in the maintaining processes of AN that necessitate adaptations of PAT for this population; and (3) suggest future directions in research on PAT and other reward-based treatments that aim to enhance clinical outcomes for AN.

CognitiveConstruct

RewardProcessing

10.1038/s41380-021-01165-3

Molecular psychiatry

Mol Psychiatry

Hippocampal neurogenesis promotes preference for future rewards.

Adult hippocampal neurogenesis has been implicated in a number of disorders where reward processing is disrupted but whether new neurons regulate specific aspects of reward-related decision making remains unclear. Given the role of the hippocampus in future-oriented cognition, here we tested whether adult neurogenesis regulates preference for future, advantageous rewards in a delay discounting paradigm for rats. Indeed, blocking neurogenesis caused a profound aversion for delayed rewards, and biased choice behavior toward immediately available, but smaller, rewards. Consistent with a role for the ventral hippocampus in impulsive decision making and future-thinking, neurogenesis-deficient animals displayed reduced activity in the ventral hippocampus. In intact animals, delay-based decision making restructured dendrites and spines in adult-born neurons and specifically activated adult-born neurons in the ventral dentate gyrus, relative to dorsal activation in rats that chose between immediately-available rewards. Putative developmentally-born cells, located in the superficial granule cell layer, did not display task-specific activity. These findings identify a novel and specific role for neurogenesis in decisions about future rewards, thereby implicating newborn neurons in disorders where short-sighted gains are preferred at the expense of long-term health.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2021.100963

Developmental cognitive neuroscience

Dev Cogn Neurosci

Reward-related neural correlates of early life stress in school-aged children.

Early life stress likely contributes to dysfunction in neural reward processing systems. However, studies to date have focused almost exclusively on adolescents and adults, measured early life stress retrospectively, and have often failed to control for concurrent levels of stress. The current study examined the contribution of prospectively measured cumulative life stress in preschool-age children on reward-related neural activation and connectivity in school-age children. Children (N = 46) and caregivers reported children's exposure to early life stress between birth and preschool age (mean = 4.8 years, SD = 0.80). At follow-up (mean age = 7.52 years, SD = .78), participants performed a child-friendly monetary incentive delay task during functional magnetic resonance imaging. Children with higher levels of cumulative early life stress, controlling for concurrent stressful life events, exhibited aberrant patterns of neural activation and connectivity in reward- and emotion-related regions (e.g., prefrontal cortex, temporal pole, culmen), depending on the presence of a potential reward and whether or not the target was hit or missed. Findings suggest that stress exposure during early childhood may impact neural reward processing systems earlier in development than has previously been demonstrated. Understanding how early life stress relates to alterations in reward processing could guide earlier, more mechanistic interventions.

CognitiveConstruct

RewardProcessing

10.1016/j.cpr.2021.102035

Clinical psychology review

Clin Psychol Rev

Neural reward circuit dysfunction as a risk factor for bipolar spectrum disorders and substance use disorders: A review and integration.

Bipolar spectrum disorders (BSDs) and substance use disorders (SUDs) are associated with neural reward dysfunction. However, it is unclear what pattern of neural reward function underlies pre-existing vulnerability to BSDs and SUDs, or whether neural reward function explains their high co-occurrence. The current paper provides an overview of the separate literatures on neural reward sensitivity in BSDs and SUDs. We provide a systematic review of 35 studies relevant to identifying neural reward function vulnerability to BSDs and SUDs. These studies include those examining neural reward processing on a monetary reward task with prospective designs predicting initial onset of SUDs, familial risk studies that examine unaffected offspring or first-degree relatives of family members with BSDs or SUDs, and studies that examine individuals with BSDs or SUDs who are not currently in an episode of the disorder. Findings from the review highlight that aberrant responding and connectivity across neural regions associated with reward and cognitive control confers risk for the development of BSDs and SUDs. Discussion focuses on limitations of the extant literature. We conclude with an integration and theoretical model for understanding how aberrant neural reward responding may constitute a vulnerability to the development of both BSDs and SUDs.

CognitiveConstruct

RewardProcessing

10.1007/s00702-021-02352-w

Journal of neural transmission (Vienna, Austria : 1996)

J Neural Transm (Vienna)

Neural correlates of RDoC-specific cognitive processes in a high-functional autistic patient: a statistically validated case report.

The level of functioning of individuals with autism spectrum disorder (ASD) varies widely. To better understand the neurobiological mechanism associated with high-functioning ASD, we studied the rare case of a female patient with an exceptional professional career in the highly competitive academic field of Mathematics. According to the Research Domain Criteria (RDoC) approach, which proposes to describe the basic dimensions of functioning by integrating different levels of information, we conducted four fMRI experiments targeting the (1) social processes domain (Theory of mind (ToM) and face matching), (2) positive valence domain (reward processing), and (3) cognitive domain (N-back). Patient's data were compared to data of 14 healthy controls (HC). Additionally, we assessed the subjective experience of our case during the experiments. The patient showed increased response times during face matching and achieved a higher total gain in the Reward task, whereas her performance in N-back and ToM was similar to HC. Her brain function differed mainly in the positive valence and cognitive domains. During reward processing, she showed reduced activity in a left-hemispheric frontal network and cortical midline structures but increased connectivity within this network. During the working memory task patients' brain activity and connectivity in left-hemispheric temporo-frontal regions were elevated. In the ToM task, activity in posterior cingulate cortex and temporo-parietal junction was reduced. We suggest that the high level of functioning in our patient is rather related to the effects in brain connectivity than to local cortical information processing and that subjective report provides a fruitful framework for interpretation.

CognitiveConstruct

RewardProcessing

10.1016/j.pnpbp.2021.110354

Progress in neuro-psychopharmacology & biological psychiatry

Prog Neuropsychopharmacol Biol Psychiatry

Maternal serotonin transporter genotype and offsprings' clinical and cognitive measures of ADHD and ASD.

Serotonin (5-HT) is an important factor for prenatal neurodevelopment whereby its neurotrophic actions can be regulated through maternal-fetal interactions. We explored if maternal 5-HTTLPR genotype is associated with clinical and cognitive measures of attention-deficit/hyperactivity disorder (ADHD) and comorbid autism spectrum disorder (ASD) in typically-developing and ADHD-diagnosed offspring, beyond classical inheritance and environmental- and comorbidity-mediators/confounders. Family-based variance decomposition analyses were performed incorporating 6-31 year-old offsprings' as well as parental genotypes of 462 ADHD and control families from the NeuroIMAGE cohort. Dependent measures were offsprings' ADHD symptom- and ASD trait-scores and cognitive measures including executive functioning (including response inhibition and cognitive flexibility), sustained attention, reward processing, motor control, and emotion recognition. Offsprings' stereotyped behavior was predicted by an interaction between maternal 5-HTTLPR genotype and offsprings' sex. Furthermore, offspring of mothers with low-expressing genotypes demonstrated larger reward-related reductions in reaction time. While specifically adult male offspring of these mothers reported a faster reversal learning with less errors, specifically young female offspring of these mothers were more accurate in identifying happy faces. Adult offspring from the mothers with low-expressing 5-HTTLPR genotypes were also slower in identifying happy faces. However, this association seemed to be mediated by offsprings' high anxiety levels. In sum, we found some support for a role of the maternal 5-HT system in modulating fetal brain development and behavior. Offsprings' cognitive measures might be more sensitive to small alterations within the maternal 5-HT system than their ADHD and ASD clinical phenotypes. Further studies are needed to specify the association between maternal genotype and risk for neurodevelopmental disorders.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0251700

PloS one

PLoS One

The effects of the form of sugar (solid vs. beverage) on body weight and fMRI activation: A randomized controlled pilot study.

To test if sugar sweetened beverages (SSBs) and sugar sweetened solids (SSSs) have differential effects on body weight and reward processing in the brain. In a single blind randomized controlled pilot trial (RCT), twenty participants with BMI between 20 and 40 kg/m2 were randomized to consume a 20 fluid ounce soda (SSB, 248 kcal) or the equivalent in solid form (SSS; similar to thick gelatin or gummy candy) daily. At baseline and day 28, fasting body weight and fed-state BOLD fMRI of the brain were assessed. Differences in fMRI signals between views of low-fat (LF (<30%)) high sugar (HS (>30%)) food, and non-food images were calculated in brain regions implicated in energy homeostasis, taste, and reward. All participants in the SSB (6F 4M; 8 Caucasian; 36±14 y, 28.2±5.5 kg/m2; Mean±SD) and SSS (3F 7M; 6 Caucasian; 39±12; 26.3±4.4) groups completed the study. Weight change was 0.27±0.78 kg between SSB and SSS participants. Changes in the fMRI response to LF/HS foods in reward, homeostatic and taste regions tended to not be different between the groups over the four weeks. However, activation of the right substantia nigra increased following the SSB but decreased activation following the SSS in response to LF/HS foods over 28 days (-0.32±0.12). Ratings of wanting for LF/HS foods were correlated with activation in several brain regions, including the OFC. Change in weight was modest between the groups in this study. Daily consumption of a SSB over 28 days led to mixed responses to LF/HS foods in areas of the brain associated with reward. Ratings of wanting are correlated with fMRI activation inside an MRI scanner.

CognitiveConstruct

RewardProcessing

10.1080/10253890.2021.1929164

Stress (Amsterdam, Netherlands)

Stress

Acute stress reduces reward-related neural activity: Evidence from the reward positivity.

Stress and blunted reward processing are risk factors for Major Depressive Disorder (MDD). The experience of acute stress reduces fMRI correlates of reward-related neural activity; however, few studies have examined how acute stress impacts measures of reward derived from event-related potentials (ERPs). The current study examined the impact of an acute stressor on the Reward Positivity (RewP), an ERP that indexes reward sensitivity, in twenty-six college students. Participants completed a monetary reward task while they placed their left hand in cold water set at 13 °C (i.e. acute stress condition) and again while their hand was placed in room temperature water (i.e. control condition). These conditions were separated by one week and performed in a counter-balanced order across participants. The results revealed that the RewP amplitude was blunted in the acute stress condition compared to the control condition. Moreover, there was a trend toward this effect interacting with self-reported depressive symptoms: the RewP was reduced only among individuals who reported low depressive symptoms. The current study suggests that an acute stressor reduces the RewP, and that this effect might be moderated by current depressive symptoms. Future studies might examine the temporal association between reward processing and stress, and how they interact to predict depressive symptoms.LAY SUMMARYThe current study examined the impact of acute stress on the brain's reward system. The results indicated that acute stress reduced activity within the brain's reward system, particularly among individuals with low depressive symptoms.

CognitiveConstruct

RewardProcessing

10.1007/s00429-021-02288-7

Brain structure & function

Brain Struct Funct

Characterization of basal forebrain glutamate neurons suggests a role in control of arousal and avoidance behavior.

The basal forebrain (BF) is involved in arousal, attention, and reward processing but the role of individual BF neuronal subtypes is still being uncovered. Glutamatergic neurons are the least well-understood of the three main BF neurotransmitter phenotypes. Here we analyzed the distribution, size, calcium-binding protein content and projections of the major group of BF glutamatergic neurons expressing the vesicular glutamate transporter subtype 2 (vGluT2) and tested the functional effect of activating them. Mice expressing Cre recombinase under the control of the vGluT2 promoter were crossed with a reporter strain expressing the red fluorescent protein, tdTomato, to generate vGluT2-cre-tdTomato mice. Immunohistochemical staining for choline acetyltransferase and a cross with mice expressing green fluorescent protein selectively in GABAergic neurons confirmed that cholinergic, GABAergic and vGluT2+ neurons represent distinct BF subpopulations. Subsets of BF vGluT2+ neurons expressed the calcium-binding proteins calbindin or calretinin, suggesting that multiple subtypes of BF vGluT2+ neurons exist. Anterograde tracing using adeno-associated viral vectors expressing channelrhodopsin2-enhanced yellow fluorescent fusion proteins revealed major projections of BF vGluT2+ neurons to neighboring BF cholinergic and parvalbumin neurons, as well as to extra-BF areas involved in the control of arousal or aversive/rewarding behavior such as the lateral habenula and ventral tegmental area. Optogenetic activation of BF vGluT2+ neurons elicited a striking avoidance of the area where stimulation was given, whereas stimulation of BF parvalbumin or cholinergic neurons did not. Together with previous optogenetic findings suggesting an arousal-promoting role, our findings suggest that BF vGluT2 neurons play a dual role in promoting wakefulness and avoidance behavior.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2021.03.002

Biological psychiatry

Biol Psychiatry

Distinct Roles of the Human Subthalamic Nucleus and Dorsal Pallidum in Parkinson's Disease Impulsivity.

Impulsivity and impulse control disorders are common in Parkinson's disease and lead to increased morbidity and reduced quality of life. Impulsivity is thought to arise from aberrant reward processing and inhibitory control, but it is unclear why deep brain stimulation of either the subthalamic nucleus (STN) or globus pallidus internus (GPi) affects levels of impulsivity. Our aim was to assess the role of the STN and GPi in impulsivity using invasive local field potential (LFP) recordings from deep brain stimulation electrodes. We measured LFPs during a simple rewarding Go/NoGo paradigm in 39 female and male human patients with Parkinson's disease manifesting variable amounts of impulsivity who were undergoing unilateral deep brain stimulation of either the STN (18 nuclei) or GPi (28 nuclei). We identified reward-specific LFP event-related potentials and correlated them to impulsivity severity. LFPs in both structures modulated during reward-specific Go and NoGo stimulus evaluation, reward feedback, and loss feedback. Motor and limbic functions were anatomically separable in the GPi but not in the STN. Across participants, LFP reward processing responses in the STN and GPi uniquely depended on the severity of impulsivity. This study establishes LFP correlates of impulsivity within the STN and GPi regions. We propose a model for basal ganglia reward processing that includes the bottom-up role of the GPi in reward salience and the top-down role of the STN in cognitive control.

CognitiveConstruct

RewardProcessing

10.1016/j.xpro.2021.100454

STAR protocols

STAR Protoc

Quantifying anhedonia-like symptoms in marmosets using appetitive Pavlovian conditioning.

Blunted reward responsivity is associated with anhedonia in humans and is a core feature of depression. This protocol describes how to train the common marmoset, , on an appetitive Pavlovian conditioning paradigm to measure behavioral and cardiovascular correlates of anticipatory and consummatory phases of reward processing. We describe how to use intracerebral infusions to manipulate brain regions whose activity is relevant to impaired reward processing in depression and how the paradigm can be used to test antidepressant efficacy. For complete details on the use and execution of this protocol, please refer to Alexander et al. (2019).

CognitiveConstruct

RewardProcessing

10.1016/j.neulet.2021.135946

Neuroscience letters

Neurosci Lett

Blockade of orexin receptors in the hippocampal dentate gyrus reduced the extinction latency of morphine-induced place preference in male rats.

Relapse to drugs such as opioids is a major challenge in addiction therapy. It has been known that the orexinergic system has a significant role in mediating reward processing and addiction, as shown by the conditioned place preference (CPP). The dentate gyrus (DG) of the hippocampus receives orexinergic projections from the lateral hypothalamus that has been approved as a critical area arbitrating the maintenance of drug-seeking behavior following the extinction. The present study aimed to investigate the effects of intra-DG administration of the orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R) antagonists on the extinction of morphine-induced CPP in male rats. Animals received different doses of SB334867 (as OX1R antagonist) or TCS OX2 29 (as OX2R antagonist) (0.5, 2.5, and 12.5 nM/0.5 μl DMSO 12 %) bilaterally into the DG during the extinction phase, after CPP had been induced by subcutaneous injection of morphine (5 mg/kg) during a 3-day conditioning phase. The conditioning scores were recorded during the test. The results demonstrated that intra-DG administration of the highest dose of OX1R antagonist (12.5 nM/0.5 μl DMSO 12 %) shortened the extinction latency of morphine-CPP compared to the DMSO group, while the OX2R antagonist did not significantly alter the latency. Findings imply that the blockade of OX1R, but not OX2R, within the DG facilitates the extinction of morphine-induced reward. In conclusion, the OX1R antagonist might be kept in mind as a convenient therapeutic factor in repressing drug-seeking behaviors in an optimum amount of treatment considering the low dose-treatments applied.

CognitiveConstruct

RewardProcessing

10.1080/10253890.2021.1923690

Stress (Amsterdam, Netherlands)

Stress

Reward anticipation buffers neuroendocrine and cardiovascular responses to acute psychosocial stress in healthy young adults.

Research over the last 10 years suggests that the brain's reward system plays a crucial role in stress resilience. Notably, reward processing includes both an anticipatory (cue-triggered "wanting") phase and a consummatory ("liking") phase. However, previous studies manipulated rewards via direct reward administration, which makes it difficult to isolate the buffering effect of anticipating the reward stimulus. In the current study, we designed a paradigm to manipulate participants into generating reward anticipation or not and investigated whether reward anticipation can buffer psychological, neuroendocrine, and cardiovascular responses to psychosocial stress. A sample of 78 healthy young adults underwent the Trier Social Stress Test or placebo-Trier Social Stress Test after a reward anticipation task. Results showed that reward anticipation relieved subjective stress feelings, as well as the overall cortisol secretion and the increased heart rate induced by psychosocial stress. Taken together, these findings expanded our understanding of the role the reward system plays in stress resilience, and the possible psychological mechanism of the buffering effect for future stress study was also discussed.HIGHLIGHTSReward processing includes both an anticipatory and consummatory phasesThe buffering effect of anticipating the reward stimulus requires elucidationWe examined if said anticipation buffers varied responses to psychosocial stressReward anticipation relieved subjective stress, cortisol secretion, and heart rateWe clarified the role of the reward system in stress resilience.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2021.657371

Frontiers in psychiatry

Front Psychiatry

A Mini-Review of Relationships Between Cannabis Use and Neural Foundations of Reward Processing, Inhibitory Control and Working Memory.

Cannabis is commonly used, and use may be increasing in the setting of increasing legalization and social acceptance. The scope of the effects of cannabis products, including varieties with higher or lower levels of Δ9-tetrahydrocannabinol (THC) or cannabidiol (CBD), on domains related to addictive behavior deserves attention, particularly as legalization continues. Cannabis use may impact neural underpinnings of cognitive functions linked to propensities to engage in addictive behaviors. Here we consider these neurocognitive processes within the framework of the dual-process model of addictions. In this mini-review, we describe data on the relationships between two main constituents of cannabis (THC and CBD) and neural correlates of reward processing, inhibitory control and working memory.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroscience.2021.04.029

Neuroscience

Neuroscience

Social and Non-social Brain Areas in Risk Behaviour: The Role of Social Context.

The human brain contains social areas that become active when interacting with another human. These are located in the ventral prefrontal and mediodorsal cortices, adjacent to areas involved in reward processing and cognitive control. Human behaviour is strongly influenced by the social context. This is particularly evident when observing greater risk propensity in the presence of a peer, particularly during adolescence and emerging adulthood. We explored the widely held view that enhanced risk propensity is the consequence of weak cognitive control. We used brain activity, estimated from EEG recordings in a sample of 114 emerging adult dyads whilst performing a risk perception task, to predict risk behaviour in a subsequent driving simulation task. Being with a peer reduced the ability to discriminate riskiness in images of traffic scenes, biased responses towards the perception of no-risk, and increased the rate of accidents in the driving simulation. Risk perception involved three sets of clusters showing activity only when being with a peer, only when being alone, and in both social contexts. Functional connectivity between the clusters accounted for the later driving simulation performance depending on the peer's presence. In the light of our findings, greater risk-taking, when a peer is present, seems to be triggered by the activation of a different, less efficient brain network for risk-processing.

CognitiveConstruct

RewardProcessing

10.1017/S0954579420002059

Development and psychopathology

Dev Psychopathol

Identifying intervention strategies for preventing the mental health consequences of childhood adversity: A modified Delphi study.

Exposure to childhood adversity is a powerful risk factor for psychopathology. Despite extensive efforts, we have not yet identified effective or scalable interventions that prevent the emergence of mental health problems in children who have experienced adversity. In this modified Delphi study, we identified intervention strategies for effectively targeting both the neurodevelopmental mechanisms linking childhood adversity and psychopathology - including heightened emotional reactivity, difficulties with emotion regulation, blunted reward processing, and social information processing biases, as well as a range of psychopathology symptoms. We iteratively synthesized information from experts in the field and relevant meta-analyses through three surveys, first with experts in intervention development, prevention, and childhood adversity (n = 32), and then within our study team (n = 8). The results produced increasing stability and good consensus on intervention strategy recommendations for specific neurodevelopmental mechanisms and symptom presentations and on strength of evidence ratings of intervention strategies targeting youth and parents. More broadly, our findings highlight how intervention decision making can be informed by meta-analyses, enhanced by aggregate group feedback, saturated before consensus, and persistently subjective or even contradictory. Ultimately, the results converged on several promising intervention strategies for prevention programming with adversity-exposed youth, which will be tested in an upcoming clinical trial.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2021.04.033

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

Reward processing as a common diathesis for chronic pain and depression.

Pain disorders and psychiatric illness are strongly comorbid, particularly in the context of Major Depressive Disorder (MDD). While these disorders account for a significant amount of global disability, the mechanisms of their overlap remain unclear. Understanding these mechanisms is of vital importance to developing prevention strategies and interventions that target both disorders. Of note, brain reward processing may be relevant to explaining how the comorbidity arises, given pain disorders and MDD can result in maladaptive reward responsivity that limits reward learning, appetitive approach behaviours and consummatory response. In this review, we discuss this research and explore the possibility of reward processing deficits as a common diathesis to explain the manifestation of pain disorders and MDD. Specifically, we hypothesize that contextual physical or psychological events (e.g. surgery, divorce) in the presence of a reward impairment diathesis worsens symptoms and results in a negative feedback loop that increases the chronicity and probability of developing the other disorder. We also highlight the implications for treatment and provide a framework for future research.

CognitiveConstruct

RewardProcessing

10.3758/s13415-021-00904-x

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Selective Devaluation Affects the Processing of Preferred Rewards.

The present study investigated whether the representation of subjective preferences in the event-related potential is manipulable through selective devaluation, i.e., the consumption of a specific food item until satiety. Thirty-four participants completed a gambling task in which they chose between virtual doors to find one of three snack items, representing a high, medium, or low preference outcome as defined by individual desire-to-eat ratings. In one of two test sessions, they underwent selective devaluation of the high preference outcome. In the other, they completed the task on an empty stomach. Consistent with previous findings, averaged across sessions, amplitudes were increased for more preferred rewards in the time windows of P2, late FRN, and P300. As hypothesised, we also found a selective devaluation effect for the high preference outcome in the P300 time window, reflected in a decrease in amplitude. The present results provide evidence for modulations of reward processing not only by individual factors, such as subjective preferences, but also by the current motivational state. Importantly, the present data suggest that selective devaluation effects in the P300 may be a promising tool to further characterise altered valuation of food rewards in the context of eating disorders and obesity.

CognitiveConstruct

RewardProcessing

10.3390/jpm11040315

Journal of personalized medicine

J Pers Med

Early Life Stress and Risks for Opioid Misuse: Review of Data Supporting Neurobiological Underpinnings.

A robust body of research has shown that traumatic experiences occurring during critical developmental periods of childhood when neuronal plasticity is high increase risks for a spectrum of physical and mental health problems in adulthood, including substance use disorders. However, until recently, relatively few studies had specifically examined the relationships between early life stress (ELS) and opioid use disorder (OUD). Associations with opioid use initiation, injection drug use, overdose, and poor treatment outcome have now been demonstrated. In rodents, ELS has also been shown to increase the euphoric and decrease antinociceptive effects of opioids, but little is known about these processes in humans or about the neurobiological mechanisms that may underlie these relationships. This review aims to establish a theoretical model that highlights the mechanisms by which ELS may alter opioid sensitivity, thereby contributing to future risks for OUD. Alterations induced by ELS in mesocorticolimbic brain circuits, and endogenous opioid and dopamine neurotransmitter systems are described. The limited but provocative evidence linking these alterations with opioid sensitivity and risks for OUD is presented. Overall, the findings suggest that better understanding of these mechanisms holds promise for reducing vulnerability, improving prevention strategies, and prescribing guidelines for high-risk individuals.

CognitiveConstruct

RewardProcessing

10.1016/j.pnpbp.2021.110333

Progress in neuro-psychopharmacology & biological psychiatry

Prog Neuropsychopharmacol Biol Psychiatry

A review of effort-based decision-making in eating and weight disorders.

Effort-based decision-making provides a framework to understand the mental computations estimating the amount of work ("effort") required to obtain a reward. The aim of the current review is to systematically synthesize the available literature on effort-based decision-making across the spectrum of eating and weight disorders. More specifically, the current review summarises the literature examining whether 1) individuals with eating disorders and overweight/obesity are willing to expend more effort for rewards compared to healthy controls, 2) if particular components of effort-based decision-making (i.e. risk, discounting) relate to specific binge eating conditions, and 3) how individual differences in effort and reward -processing measures relate to eating pathology and treatment measures. A total of 96 studies were included in our review, following PRISMA guidelines. The review suggests that individuals with binge eating behaviours 1) are more likely to expend greater effort for food rewards, but not monetary rewards, 2) demonstrate greater decision-making impairments under risk and uncertainty, 3) prefer sooner rather than delayed rewards for both food and money, and 4) demonstrate increased implicit 'wanting' for high fat sweet foods. Finally, individual differences in effort and reward -processing measures relating to eating pathology and treatment measures are also discussed.

CognitiveConstruct

RewardProcessing

10.1016/j.brat.2021.103860

Behaviour research and therapy

Behav Res Ther

Changes in neural reward processing following Amplification of Positivity treatment for depression and anxiety: Preliminary findings from a randomized waitlist controlled trial.

Positive valence system (PVS) deficits are increasingly recognized as important treatment targets for depression and anxiety. Emerging behavioral treatments designed to upregulate the PVS show initial promise; however, neural mechanisms underlying these approaches remain unknown. This study investigated neural reward-processing-related changes following Amplification of Positivity (AMP)-a treatment designed to enhance positive thinking, emotions and behaviors through positive activity interventions (Clinicaltrials.gov: NCT02330627). Individuals with depression and/or anxiety (N = 29) were randomized to 10 sessions of AMP (n = 16) or waitlist (WL; n = 13). Participants completed a monetary incentive delay task during fMRI at baseline and post-assessment. Hypothesis-driven region of interest (ventral striatum, insula, anterior cingulate) and exploratory whole-brain activation and connectivity analyses evaluated pre-to-post changes for AMP vs. WL when anticipating potential monetary gain or loss. No between-group brain activation changes emerged in regions of interest or whole-brain analyses. Increased neural connectivity from pre-to-post-treatment was observed in AMP vs. WL, including ventral striatum, anterior insula, and anterior cingulate connectivity with prefrontal, limbic, occipital and parietal regions-predominantly during loss anticipation. This preliminary study is the first to examine neural mechanisms of positive activity interventions in depression and anxiety and suggests that AMP may strengthen brain connectivity in reward processing, attention, and emotion regulation networks.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2021.01.011

Biological psychiatry

Biol Psychiatry

Reward Processing in Novelty Seekers: A Transdiagnostic Psychiatric Imaging Biomarker.

Dysfunctional reward processing is implicated in multiple mental disorders. Novelty seeking (NS) assesses preference for seeking novel experiences, which is linked to sensitivity to reward environmental cues. A subset of 14-year-old adolescents (IMAGEN) with the top 20% ranked high-NS scores was used to identify high-NS-associated multimodal components by supervised fusion. These features were then used to longitudinally predict five different risk scales for the same and unseen subjects (an independent dataset of subjects at 19 years of age that was not used in predictive modeling training at 14 years of age) (within IMAGEN, n ≈1100) and even for the corresponding symptom scores of five types of patient cohorts (non-IMAGEN), including drinking (n = 313), smoking (n = 104), attention-deficit/hyperactivity disorder (n = 320), major depressive disorder (n = 81), and schizophrenia (n = 147), as well as to classify different patient groups with diagnostic labels. Multimodal biomarkers, including the prefrontal cortex, striatum, amygdala, and hippocampus, associated with high NS in 14-year-old adolescents were identified. The prediction models built on these features are able to longitudinally predict five different risk scales, including alcohol drinking, smoking, hyperactivity, depression, and psychosis for the same and unseen 19-year-old adolescents and even predict the corresponding symptom scores of five types of patient cohorts. Furthermore, the identified reward-related multimodal features can classify among attention-deficit/hyperactivity disorder, major depressive disorder, and schizophrenia with an accuracy of 87.2%. Adolescents with higher NS scores can be used to reveal brain alterations in the reward-related system, implicating potential higher risk for subsequent development of multiple disorders. The identified high-NS-associated multimodal reward-related signatures may serve as a transdiagnostic neuroimaging biomarker to predict disease risks or severity.

CognitiveConstruct

RewardProcessing

10.1016/j.bpsc.2021.04.005

Biological psychiatry. Cognitive neuroscience and neuroimaging

Biol Psychiatry Cogn Neurosci Neuroimaging

Persistence, Reward Dependence, and Sensitivity to Reward Are Associated With Unexpected Salience Response in Girls but Not in Adult Women: Implications for Psychiatric Vulnerabilities.

Adolescence is a critical period for the development of not only personality but also psychopathology. These processes may be specific to sex, and brain reward circuits may have a role. Here, we studied how reward processing and temperament associations differ across adolescent and adult females. A total of 29 adolescent girls and 41 adult women completed temperament assessments and performed a classical taste conditioning paradigm during brain imaging. Data were analyzed for the dopamine-related prediction error response. In addition, unexpected stimulus receipt or omission and expected receipt response were also analyzed. Heat maps identified cortical-subcortical brain response associations. Adolescents showed stronger prediction error and unexpected receipt and omission responses (partial η = 0.063 to 0.166; p = .001 to .043) in insula, orbitofrontal cortex (OFC), and striatum than adults. Expected stimulus receipt response was similar between groups. In adolescents versus adults, persistence was more strongly positively related to prediction error (OFC, insula, striatum; Fisher's z = 1.704 to 3.008; p = .001 to .044) and unexpected stimulus receipt (OFC, insula; Fisher's z = 1.843 to 2.051; p = .014 to .033) and negatively with omission (OFC, insula, striatum; Fisher's z = -1.905 to -3.069; p = .001 to .028). Reward sensitivity and reward dependence correlated more positively with unexpected stimulus receipt and more negatively with stimulus omission response in adolescents. Adolescents showed significant correlations between the striatum and FC for unexpected stimulus receipt and omission that correlated with persistence but were absent in adults. Associations between temperamental traits and brain reward response may provide neurotypical markers that contribute to developing adaptive or maladaptive behavior patterns when transitioning from adolescence to adulthood.

CognitiveConstruct

RewardProcessing

10.1016/j.cortex.2021.02.029

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

Cortex

Apathy is associated with parietal cortical-subcortical dysfunction in ALS.

Apathy is the core behavioural feature of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS). Initiation and emotional manifestations of apathy significantly affect patients and carers, particularly in terms of quality of life. As such, the primary aim of the present study was to investigate the prevalence and neural correlates of initiation, and emotional subtypes of apathy in ALS. A total of 109 participants were recruited from a specialised, tertiary referral ALS/FTD clinic. Overall rates of apathy, including cognitive, initiation and emotion subtypes as assessed by the Dimensional Apathy Scale (DAS), were examined and correlated with brain volumes, including voxel-based morphometry on high resolution MRI. Clinically significant apathy ranged between 49% (patient-rated DAS) and 64% (carer-rated DAS), with the most common apathy subtypes being initiation (84-96%) and emotional (74-75%) apathy. The results of the two-way repeated measures ANOVA revealed significant differences across the DAS executive, emotional and initiation subscales (p = .0001). Multivariate analysis using a logistic regression model showed that only initiation; (odds ratio = 3.08, p = .004) and emotional (odds ratio = 2.40, p = .008) apathy were predictive of clinically significant apathy, controlling for education and depression. Increased initiation apathy correlated with reduced grey matter within bilateral superior frontal gyrus and increased emotional apathy correlated with reduced grey matter in prefrontal cortices and right anterior cingulate, previously implicated in apathy. Additional correlations were identified including the angular gyrus (or the temporo-parietal junction), important in reward valuation and subsequent goal-directed behaviour. Taken together, results from the present series highlight the frequency and multi-dimensionality of apathy in ALS. The pathophysiological mechanisms of apathy in ALS may be critically underpinned by neurodegeneration across a distributed brain network, with key roles in task initiation, emotion, reward processing and subsequent goal-directed behaviour.

CognitiveConstruct

RewardProcessing

10.1016/j.appet.2021.105258

Appetite

Appetite

Binge sucrose-induced neuroadaptations: A focus on the endocannabinoid system.

Binge eating, the defining feature of binge eating disorder (BED), is associated with a number of adverse health outcomes as well as a reduced quality of life. Animals, like humans, selectively binge on highly palatable food suggesting that the behaviour is driven by hedonic, rather than metabolic, signals. Given the links to both reward processing and food intake, this study examined the contribution of the endocannabinoid system (ECS) to binge-like eating in rats. Separate groups were given intermittent (12 h) or continuous (24 h) access to 10% sucrose and food over 28 days, with only the 12 h access group displaying excessive sucrose intake within a discrete period of time (i.e., binge eating). Importantly, this group also exhibited alterations in ECS transcripts and endocannabinoid levels in brain reward regions, including an increase in cannabinoid receptor 1 (CB1R) mRNA in the nucleus accumbens as well as changes in endocannabinoid levels in the prefrontal cortex and hippocampus. We then tested whether different doses (1 and 3 mg/kg) of a CB1R antagonist, Rimonabant, modify binge-like intake or the development of a conditioned place preference (CPP) to sucrose. CB1R blockade reduced binge-like intake of sucrose and blocked a sucrose CPP, but only in rats that had undergone 28 days of sucrose consumption. These findings indicate that sucrose bingeing alters the ECS in reward-related areas, modifications that exacerbate the effect of CB1R blockade on sucrose reward. Overall, our results broaden the understanding of neural alterations associated with bingeing eating and demonstrate an important role for CB1R mechanisms in reward processing. In addition, these findings have implications for understanding substance abuse, which is also characterized by excessive and maladaptive intake, pointing towards addictive-like properties of palatable food.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2021.100948

Developmental cognitive neuroscience

Dev Cogn Neurosci

Multimodal brain predictors of current weight and weight gain in children enrolled in the ABCD study ®.

Multimodal neuroimaging assessments were utilized to identify generalizable brain correlates of current body mass index (BMI) and predictors of pathological weight gain (i.e., beyond normative development) one year later. Multimodal data from children enrolled in the Adolescent Brain Cognitive Development Study® at 9-to-10-years-old, consisted of structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), resting state (rs), and three task-based functional (f) MRI scans assessing reward processing, inhibitory control, and working memory. Cross-validated elastic-net regression revealed widespread structural associations with BMI (e.g., cortical thickness, surface area, subcortical volume, and DTI), which explained 35% of the variance in the training set and generalized well to the test set (R = 0.27). Widespread rsfMRI inter- and intra-network correlations were related to BMI (R = 0.21; R = 0.14), as were regional activations on the working memory task (R = 0.20; (R = 0.16). However, reward and inhibitory control tasks were unrelated to BMI. Further, pathological weight gain was predicted by structural features (Area Under the Curve (AUC) = 0.83; AUC = 0.83, p < 0.001), but not by fMRI nor rsfMRI. These results establish generalizable brain correlates of current weight and future pathological weight gain. These results also suggest that sMRI may have particular value for identifying children at risk for pathological weight gain.

CognitiveConstruct

RewardProcessing

10.1016/j.ibneur.2020.11.001

IBRO neuroscience reports

IBRO Neurosci Rep

Region- and receptor-specific effects of chronic social stress on the central serotonergic system in mice.

Serotonin (5-HT), via its receptors expressed in discrete brain regions, modulates aversion and reward processing and is implicated in various psychiatric disorders including depression. Stressful experiences affect central serotonergic activity and act as a risk factor for depression; this can be modelled preclinically. In adult male C57BL/6J mice, 15-day chronic social stress (CSS) leads to depression-relevant behavioural states, including increased aversion and reduced reward sensitivity. Based on this evidence, here we investigated CSS effects on 5-HT1A, 5-HT2A, and 5-HT2C receptor binding in discrete brain regions using in vitro quantitative autoradiography with selective radioligands. In addition, mRNA expression of and (5-HT transporter) was measured by quantitative PCR. Relative to controls, the following effects were observed in CSS mice: 5-HT1A receptor binding was markedly increased in the dorsal raphe nucleus (136%); mRNA expression was increased in raphe nuclei (19%), medial prefrontal cortex (35%), and hypothalamic para- and periventricular nuclei (21%) and ventral medial nucleus (38%). 5-HT2A receptor binding was decreased in the amygdala (48%) and ventral tegmental area (60%); mRNA expression was increased in the baso-lateral amygdala (116%). 5-HT2C receptor binding was decreased in the dorsal raphe nucleus (42%). mRNA expression was increased in the raphe (59%). The present findings add to the translational evidence that chronic social stress impacts on the central serotonergic system in a region- and receptor-specific manner, and that this altered state of the serotonergic system contributes to stress-induced dysfunctions in emotional processing.

CognitiveConstruct

RewardProcessing

10.1007/s11920-021-01247-7

Current psychiatry reports

Curr Psychiatry Rep

Social and Nonsocial Reward Anticipation in Typical Development and Autism Spectrum Disorders: Current Status and Future Directions.

While there has been sustained interest in understanding the role of reward processing in autism spectrum disorder (ASD), researchers are just beginning to focus on the anticipation phase of reward processing in this population. This review aimed to briefly summarize recent advancements in functional imaging studies of anticipatory social and nonsocial reward processing in individuals with and without ASD and provide suggestions for avenues of future research. Reward salience and activation of the complex network of brain regions supporting reward anticipation vary across development and by important demographic characteristics, such as sex assigned at birth. Current research comparing social and nonsocial reward anticipation may possess confounds related to the mismatch in tangibility and salience of social and nonsocial experimental stimuli. Growing evidence suggests individuals with ASD demonstrate aberrant generalized reward anticipation that is not specific to social reward. Future research should carefully match social and nonsocial reward stimuli and consider employing a longitudinal design to disentangle the complex processes contributing to the development of reward anticipation. It may be useful to conceptualize differences in reward anticipation as a transdiagnostic factor, rather than an ASD-specific deficit.

CognitiveConstruct

RewardProcessing

10.1093/ntr/ntab072

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco

Nicotine Tob Res

Genetic and depressive traits moderate the reward-enhancing effects of acute nicotine in young light smokers.

Rates of light smoking have increased in recent years and are associated with adverse health outcomes. Reducing light smoking is a challenge because it is unclear why some but not others, progress to heavier smoking. Nicotine has profound effects on brain reward systems and individual differences in nicotine's reward-enhancing effects may drive variability in smoking trajectories. Therefore, we examined whether a genetic risk factor and personality traits known to moderate reward processing, also moderate the reward-enhancing effects of nicotine. Light smokers (n=116) performed a Probabilistic Reward Task to assess reward responsiveness after receiving either nicotine or placebo (order counterbalanced). Individuals were classified as nicotine dependence 'risk' allele carriers (rs16969968 A-allele carriers) or non-carriers (non-A-allele carriers), and self-reported negative affective traits were also measured. Across the whole sample, reward responsiveness was greater following nicotine compared to placebo (p=0.045). For Caucasian A-allele carriers but not non-A-allele carriers, nicotine enhanced reward responsiveness compared to placebo for those who received the placebo first (p=0.010). Furthermore, for A-allele carriers but not non-A-allele carriers who received nicotine first, the enhanced reward responsiveness in the nicotine condition carried over to the placebo condition (p<0.001). Depressive traits also moderated the reward-enhancing effects of nicotine (p=0.010) and were associated with more blunted reward responsiveness following placebo but enhanced reward responsiveness following nicotine. These findings suggest that individual differences in a genetic risk factor and depressive traits alter nicotine's effect on reward responsiveness in light smokers and may be important factors underpinning variability in smoking trajectories in this growing population.

CognitiveConstruct

RewardProcessing

10.1007/978-981-33-6044-0_6

Advances in experimental medicine and biology

Adv Exp Med Biol

Development of Neuroimaging-Based Biomarkers in Major Depression.

A leading goal in the field of biological psychiatry for depression is to find a promising diagnostic biomarker and selection of specific psychiatric treatment mode that is most likely to benefit patients with depression. Recent neuroimaging studies have characterized the pathophysiology of major depressive disorder (MDD) with functional and structural alterations in the neural circuitry involved in emotion or reward processing. Particularly, structural and functional magnetic resonance imaging (MRI) studies have reported that the brain structures deeply involved in emotion regulation or reward processing including the amygdala, prefrontal cortex (PFC), anterior cingulate cortex (ACC), ventral striatum, and hippocampus are key regions that provide useful information about diagnosis and treatment outcome prediction in MDD. For example, it has been consistently reported that elevated activity of the ACC is associated with better antidepressant response in patients with MDD. This chapter will discuss a growing body of evidence that suggests that diagnosis or prediction of outcome for specific treatment can be assisted by a neuroimaging-based biomarker in MDD.

CognitiveConstruct

RewardProcessing

10.7759/cureus.13718

Cureus

Cureus

Reinforcement and Compensatory Mechanisms in Attention-Deficit Hyperactivity Disorder: A Systematic Review of Case-Control Studies.

Attention-deficit hyperactivity disorder (ADHD) is a neuropsychological disorder that causes inattentiveness, hyperactivity, and impulsiveness in patients. Ventral striatal hypo-responsiveness, orbitofrontal cortex, and dopaminergic status in the brain are related to the pathogenesis of ADHD. Reinforcement tasks by monetary incentive delay (MID) was shown to produce more responsiveness in patients. In this study, we reviewed how reinforcement interventions and compensatory mechanisms affect the behavior of ADHD patients. This systematic review was undertaken as per the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, and PubMed database was used for literature search. The quality appraisal was completed using the Newcastle-Ottawa scale, and nine case-control studies were included in this systematic review. A total of 976 participants were included, with 493 cases and 330 controls. The studies included discuss reinforcement, attention networks, and compensatory mechanisms. Our review concludes that reinforcement improves responsiveness to gain and loss of rewards in ADHD patients. Reward processing is selectively associated with the salience network. While ADHD, predominantly the inattentive type, is insensitive to stimuli, ADHD combined type and controls showed similar responsiveness. The right visual cortex may also be related to compensatory mechanisms in ADHD. As we only included case-control studies from the last eight years, in the English language, we might have missed some relevant studies related to this research. Because the included studies have a relatively small sample size, we recommend future studies to explore larger cohorts of patients to improve the reliability of findings pertinent to this field.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2021.03.043

Journal of affective disorders

J Affect Disord

Trauma-related dysfunction in the fronto-striatal reward circuit.

Reduced reactivity to pleasurable stimulation is a defining symptom of post-traumatic stress disorder (PTSD), but trauma exposure also increases the severity of many anxiety and mood disorders, including depression, social anxiety, and panic disorder, suggesting that reward system dysfunction might be pervasive in the internalizing disorders. The ventromedial prefrontal cortex (vmPFC) and ventral striatum are core components of the reward circuit and the current study assesses functional activity and connectivity in this circuit during emotional picture viewing in anxiety and mood disorder patients. Functional brain activity (fMRI) and functional connectivity in the fronto-striatal circuit were measured in a large sample of patients diagnosed with anxiety and mood disorders (n=155) during affective scene viewing as it varied with trauma exposure and temperament. In women, but not men, blunted fronto-striatal connectivity was associated with increased posttraumatic anhedonic symptoms, whereas the amplitude of functional activity was not related to trauma exposure. In both men and women, reduced fronto-striatal connectivity was associated with decreases in temperamental positive affect. When predicting fronto-striatal connectivity, temperament and posttraumatic symptomology accounted for independent proportions of variance. In this civilian sample of anxiety disorder patients, men reported very little trauma-related symptomology. Because dysfunctional reward processing due to trauma and temperament is pervasive across the internalizing disorder spectrum, assessing the integrity of the fronto-striatal reward circuit could provide important information in diagnostic and treatment protocols.

CognitiveConstruct

RewardProcessing

10.1556/2006.2021.00018

Journal of behavioral addictions

J Behav Addict

Sexual incentive delay in the scanner: Sexual cue and reward processing, and links to problematic porn consumption and sexual motivation.

The use of pornography, while unproblematic for the majority, can grow into addiction-like behavior which in its extreme form is labeled as compulsive sexual behavioral disorder in the ICD-11 (WHO, 2018). The aim of this study was to investigate the addiction-specific reactivity to cues in order to better understand underlying mechanisms in the development of this disorder. We have used an optimized Sexual Incentive Delay Task to study brain activity in reward associated brain areas during an anticipation phase (with cues predicting pornographic videos, control videos or no videos) and a corresponding delivery phase in healthy men. Correlations to indicators of problematic pornography use, the time spent on pornography use, and trait sexual motivation were analyzed. The results of 74 men showed that reward-related brain areas (amygdala, dorsal cingulate cortex, orbitofrontal cortex, nucleus accumbens, thalamus, putamen, caudate nucleus, and insula) were significantly more activated by both the pornographic videos and the pornographic cues than by control videos and control cues, respectively. However, we found no relationship between these activations and indicators of problematic pornography use, time spent on pornography use, or with trait sexual motivation. The activity in reward-related brain areas to both visual sexual stimuli as well as cues indicates that optimization of the Sexual Incentive Delay Task was successful. Presumably, associations between reward-related brain activity and indicators for problematic or pathological pornography use might only occur in samples with increased levels and not in a rather healthy sample used in the present study.

CognitiveConstruct

RewardProcessing

10.1080/17470919.2021.1911843

Social neuroscience

Soc Neurosci

Neural responses to implicit forms of peer influence in young adults.

Young adults are acutely sensitive to peer influences. Differences have been found in neural sensitivity to peer influences, such as seeing peer ratings on social media. The present study aimed to identify patterns of neural sensitivity to peer influences, which involve more subtle cues that shape preferences and behaviors. Participants were 43 young adults ( = 19.2 years; 24 males) who underwent functional magnetic resonance imaging while completing a task used to assess neural responses to implicitly "socially tagged" symbols (previously judged by peers as liked vs. not liked, thus differing in apparent popularity) vs. novel symbols that carried no social meaning (not judged by peers). Results indicated greater activity in brain regions involved in salience detection (e.g., anterior cingulate cortex) and reward processing (e.g., caudate) to socially tagged vs. novel symbols, and particularly to unpopular symbols. Greater self-reported susceptibility to peer influence was related to more activity in the insula and caudate when viewing socially tagged vs. novel symbols. These results suggest that the brain is sensitive to even subtle cues varying in level of peer endorsement and neural sensitivity differed by the tendency to conform to peers' behaviors particularly in regions implicated in social motivation.

CognitiveConstruct

RewardProcessing

10.1027/0269-8803/a000253

Journal of psychophysiology

J Psychophysiol

Social Feedback Valence Differentially Modulates the Reward Positivity, P300, and Late Positive Potential.

Abnormal social or reward processing is associated with several mental disorders. Although most studies examining reward processing have focused on monetary rewards, recent research also has tested neural reactivity to social rewards (e.g., positive social feedback). However, the majority of these studies only include two feedback valences (e.g., acceptance, rejection). Yet, social evaluation is rarely binary (positive vs. negative) and people often give 'on the fence' or neutral evaluations of others. Processing of this type of social feedback may be ambiguous and impacted by factors such as psychopathology, self-esteem, and prior experiences of rejection. Thus, the present study probed the reward positivity (RewP), P300, and late positive potential (LPP) following acceptance, rejection, and "one the fence" [between acceptance and rejection] feedback in undergraduate students ( = 45). Results indicated that the RewP showed more positive amplitudes following acceptance compared to both rejection and "on the fence" feedback, and the RewP was larger (i.e., more positive) following rejection relative to "on the fence" feedback. In contrast, the P300 did not differ between rejection and "on the fence" feedback, and both were reduced compared to acceptance. The LPP was blunted in response to rejection relative to acceptance and "on the fence" feedback (which did not differ from each other). Exploratory analyses demonstrated that greater self-reported rejection sensitivity was associated with a reduced LPP to acceptance. Taken together, these findings suggest that the neural systems underlying the RewP, P300, and LPP may evaluate "on the fence" social feedback differently, and that individuals high on rejection sensitivity may exhibit reduced attention toward and elaborative processing of social acceptance.

CognitiveConstruct

RewardProcessing

10.1111/jopy.12637

Journal of personality

J Pers

Online betting intensity is linked with Extraversion and Conscientiousness.

Extraversion and Conscientiousness are well-studied personality traits associated with reward processing and goal prioritization, respectively, and bear on individual differences in financial risk-taking. Using unique large datasets, we investigated the link between these traits and male online gamblers' actual betting participation and intensity. We combined datasets containing online horse betting data (during 2015-2016) from the Finnish monopoly betting company, administrative registry data from Statistics Finland, and personality trait measures from the Finnish Defence Forces corresponding to Extraversion and Conscientiousness as defined in the five-factor model. We modelled associations between these traits and betting participation (n = 471,968) and intensity (n = 11,217) among male horse bettors (age = 36-53). Controlling for demographics and IQ, individuals scoring high on Conscientiousness (or Extraversion) were less (or more) likely to bet and less (or more) intensive bettors-even when personality was measured 16-34 years before betting occurred. One SD personality score increase represented an annual decrease (Conscientiousness) or increase (Extraversion) of €570-754 in spending. Extraversion and Conscientiousness are implicated in real-life financial behavior with tangible consequences for individuals. These effects are stronger than for many known demographic variables used in gambling studies and persist up to 34 years after personality has been measured.

CognitiveConstruct

RewardProcessing

10.1016/j.jpsychires.2021.03.029

Journal of psychiatric research

J Psychiatr Res

The impact of overweight/obesity on monetary reward processing: A systematic review.

Converging evidence suggests abnormalities in monetary reward processing may underlie the shared pathophysiology between major depressive disorder and obesity. As such, there is a need to parse deficits in specific subcomponents of monetary reward functioning (i.e., valuation, learning and anticipation). PsycINFO, Google Scholar and PubMed databases were searched for English-language articles published between database inception to June 6th, 2020. Studies were identified using the following medical search heading (MeSH) terms and search strings: (reward (valuation OR motivation OR anticipation OR learning OR functioning OR decision-making OR reinforcement)) AND ((obesity OR overweight OR obese). Findings were reviewed from 11 studies evaluating the association between obesity and monetary reward processing. Four studies found significant differences in reward learning in individuals with obesity compared to normal-weight participants. Five studies found body mass index (BMI) to be predictive of willingness to expend effort (i.e., valuation) for a monetary reward. Three studies found changes in neural activations in the ventral striatum during anticipatory phases preceding receipt of a monetary reward in participants with obesity. Participants with obesity demonstrated significantly poorer performance in task-based measures of reward learning, valuation, and anticipation, resulting in lower monetary reward outcomes across all studies compared to healthy controls. Notably, participants with obesity and comorbid depression performed worse than participants with no comorbid depression. There persists heterogeneity between studies with regards to inclusion of mood disorder populations and exclusion of psychiatric comorbidities in groups with obesity.

CognitiveConstruct

RewardProcessing

10.1002/jnr.24835

Journal of neuroscience research

J Neurosci Res

Larger bilateral amygdalar volumes are associated with affective loss experiences.

Affective loss (AL) (i.e., bereavement, relationship breakup) is a stressful life event leading to a heightened risk of developing a psychiatric disorder, for example, depression and anxiety disorder. These disorders have been associated with altered subcortical brain volumes. Little is known though, how AL in healthy subjects is linked to subcortical volumes. In a study with 196 healthy young adults, we probed the association between AL across the individual entire life span, assessed via the List of Threatening Experiences Questionnaire, and magnetic resonance imaging brain gray matter volumes (a priori selected: bilateral amygdalae, hippocampi, thalami; exploratory analyses: nuclei accumbens, caudate, putamina), segmented by use of volBrain. AL was defined as death of a first-degree relative/spouse, close relative/friend, and breakup of a marriage or steady relationship. AL was associated with larger bilateral amygdalar volumes and, after taking into account the total number of ALs, with smaller right hippocampal volumes, both irrespective of sex. Exploratory analyses of striatal volumes yielded an association of AL with larger right nucleus accumbens volumes in men, and increased caudate volumes after the loss of a first-degree relative irrespective of sex. Our data suggest that AL engenders alterations in limbic structures that likely involve processes of chronic stress and amygdala- and hippocampus-dependent fear conditioning, and resemble those observed in general anxiety disorder, childhood maltreatment, and major depressive disorder. Our exploratory findings of striatal volume alterations hint at a modulation of reward processing by AL.

CognitiveConstruct

RewardProcessing

10.1097/WNR.0000000000001616

Neuroreport

Neuroreport

Thalamic shape abnormalities in patients with multiple sclerosis-related fatigue.

Thalamus plays an important role in the pathogenesis of multiple sclerosis-related fatigue (MSrF). However, the thalamus is a heterogeneous structure and the specific thalamic subregions that are involved in this condition are unclear. Here, we used thalamic shape analysis for the detailed localization of thalamic abnormalities in MSrF. Using the Modified Fatigue Impact Scale, we measured fatigue in 42 patients with relapsing-remitting multiple sclerosis (MS). The thalamic shape was extracted from T1w images using an automated pipeline. We investigated the association of thalamic surface deviations with the severity of global fatigue and its cognitive, physical and psychosocial subdomains. Cognitive fatigue was correlated with an inward deformity of the left anteromedial thalamic surface, but no other localized shape deviation was observed in correlation with global, physical or psychosocial fatigue. Our findings indicate that the left anteromedial thalamic subregions are implicated in cognitive fatigue, possibly through their role in reward processing and cognitive and executive functions.

CognitiveConstruct

RewardProcessing

10.1016/bs.irn.2020.11.012

International review of neurobiology

Int Rev Neurobiol

Reward signaling by the rodent medial frontal cortex.

The anatomical relevance and functional significance of medial parts of the rodent frontal cortex have been intensely debated over the modern history of neuroscience. Early studies emphasized common functions among medial frontal regions in rodents and the dorsolateral prefrontal cortex of primates. Behavioral tasks emphasized memory-guided performance and persistent neural activity as a marker of working memory. Over time, it became clear that long-standing concerns about cross-species homology were justified and the view emerged that rodents are useful for understanding medial parts of the frontal cortex in primates, and not the dorsolateral prefrontal cortex. Here, we summarize a series of studies on the rodent medial frontal cortex that began with an interest in studying working memory in the perigenual prelimbic area and ended up studying reward processing in the medial orbital region. Our experiments revealed a role for a 4-8Hz "theta" rhythm in tracking engagement in the consumption of rewarding fluids and denoting the value of a given reward. Evidence for a functional differentiation between the rostral and caudal medial frontal cortex and its relationship to other frontal cortical areas is also discussed with the hope of motivating future work on this part of the cerebral cortex.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2021.113258

Behavioural brain research

Behav Brain Res

Influence of anhedonic symptom severity on reward circuit connectivity in PTSD.

Anhedonia, marked by deficits in reward processing, is a prominent symptom of several psychiatric conditions and has been shown to influence functional connectivity between reward-related regions. However, the unique influence of anhedonia severity on reward circuit connectivity in posttraumatic stress disorder (PTSD) remains unclear. To address this, we examined resting-state functional connectivity (rsFC) of the ventral striatum as a function of anhedonia for individuals with PTSD. Resting-state functional MRI scans and behavioral assessments were collected for 71 women diagnosed with PTSD. Seed-based voxelwise rsFC analyses for left and right nucleus accumbens (NAcc) seed regions of interest were performed. Voxelwise regression analyses were conducted to examine the relationship between anhedonia severity and rsFC of left and right NAcc. Results indicated that greater anhedonia severity was associated with reduced rsFC between the left NAcc and a cluster in the left caudate extending to the thalamus. This relationship between anhedonia and rsFC remained significant after controlling for PTSD symptom severity or depression severity. Our findings suggest that reward circuit dysfunction at rest is associated with anhedonia in PTSD. These results further contribute to our understanding of the neural correlates of anhedonia in psychiatric conditions.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroscience.2021.03.018

Neuroscience

Neuroscience

Structural Brain Correlates of the Externalizing Spectrum in Young Adults.

The externalizing spectrum, including traits and behaviors such as aggression, reduced inhibitiory control and substance abuse, is associated with altered prefrontal brain morphology. However, the degree to which different manifestations of the externalizing spectrum are associated with distinct or overlapping variations in individual brain morphology is unclear. Here, we therefore used structural magnetic resonance imaging, self-report assessment, and a response inhibition task in a sample of 59 young adults to examine how cortical thickness in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex (DLPFC) relate to four different manifestations of the externalizing spectrum: disinhibition, callous aggression, substance abuse, and behavioral inhibitory control. Using Bayesian linear regression models controlling for age, gender, and years of education, we found that the different manifestations of the externalizing spectrum were associated with both distinct and overlapping morphology variations. Specifically, both callous aggression and inhibitory control was associated with increased cortical thickness of the OFC, a region involved in reward processing, decision-making, and regulation of anxiety and fear. Both disinhibition and substance abuse were associated with DLPFC thickness, although with opposite association patterns, possibly reflecting processes related to inhibitory control, working memory and attention. Moreover, disinhibition, but not callous aggression or substance abuse, was associated with behavioral inhibitory control. Our results provide further support for the link between externalizing behaviors and prefrontal brain morphology, while identifying distinct prefrontal areas associated with different clinically relevant manifestations. These findings may help guide further research aimed at developing novel treatment and intervention strategies for externalizing behaviors and disorders.

CognitiveConstruct

RewardProcessing

10.1007/s10071-021-01506-3

Animal cognition

Anim Cogn

2D or not 2D? An fMRI study of how dogs visually process objects.

Given humans' habitual use of screens, they rarely consider potential differences when viewing two-dimensional (2D) stimuli and real-world versions of dimensional stimuli. Dogs also have access to many forms of screens and touchpads, with owners even subscribing to dog-directed content. Humans understand that 2D stimuli are representations of real-world objects, but do dogs? In canine cognition studies, 2D stimuli are almost always used to study what is normally 3D, like faces, and may assume that both 2D and 3D stimuli are represented in the brain the same way. Here, we used awake fMRI in 15 dogs to examine the neural mechanisms underlying dogs' perception of two- and three-dimensional objects after the dogs were trained on either two- or three-dimensional versions of the objects. Activation within reward processing regions and parietal cortex of the dog brain to 2D and 3D versions of objects was determined by their training experience, as dogs trained on one dimensionality showed greater differential activation within the dimension on which they were trained. These results show that dogs do not automatically generalize between two- and three-dimensional versions of object stimuli and suggest that future research consider the implicit assumptions when using pictures or videos.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2021.117970

NeuroImage

Neuroimage

The NIMH Intramural Longitudinal Study of the Endocrine and Neurobiological Events Accompanying Puberty: Protocol and rationale for methods and measures.

Delineating the relationship between human neurodevelopment and the maturation of the hypothalamic-pituitary-gonadal (HPG) axis during puberty is critical for investigating the increase in vulnerability to neuropsychiatric disorders that is well documented during this period. Preclinical research demonstrates a clear association between gonadal production of sex steroids and neurodevelopment; however, identifying similar associations in humans has been complicated by confounding variables (such as age) and the coactivation of two additional endocrine systems (the adrenal androgenic system and the somatotropic growth axis) and requires further elucidation. In this paper, we present the design of, and preliminary observations from, the ongoing NIMH Intramural Longitudinal Study of the Endocrine and Neurobiological Events Accompanying Puberty. The aim of this study is to directly examine how the increase in sex steroid hormone production following activation of the HPG-axis (i.e., gonadarche) impacts neurodevelopment, and, additionally, to determine how gonadal development and maturation is associated with longitudinal changes in brain structure and function in boys and girls. To disentangle the effects of sex steroids from those of age and other endocrine events on brain development, our study design includes 1) selection criteria that establish a well-characterized baseline cohort of healthy 8-year-old children prior to the onset of puberty (e.g., prior to puberty-related sex steroid hormone production); 2) temporally dense longitudinal, repeated-measures sampling of typically developing children at 8-10 month intervals over a 10-year period between the ages of eight and 18; 3) contemporaneous collection of endocrine and other measures of gonadal, adrenal, and growth axis function at each timepoint; and 4) collection of multimodal neuroimaging measures at these same timepoints, including brain structure (gray and white matter volume, cortical thickness and area, white matter integrity, myelination) and function (reward processing, emotional processing, inhibition/impulsivity, working memory, resting-state network connectivity, regional cerebral blood flow). This report of our ongoing longitudinal study 1) provides a comprehensive review of the endocrine events of puberty; 2) details our overall study design; 3) presents our selection criteria for study entry (e.g., well-characterized prepubertal baseline) along with the endocrinological considerations and guiding principles that underlie these criteria; 4) describes our longitudinal outcome measures and how they specifically relate to investigating the effects of gonadal development on brain development; and 5) documents patterns of fMRI activation and resting-state networks from an early, representative subsample of our cohort of prepubertal 8-year-old children.

CognitiveConstruct

RewardProcessing

10.1177/2167702620933570

Clinical psychological science : a journal of the Association for Psychological Science

Clin Psychol Sci

Reward processing modulates the association between trauma exposure and externalizing psychopathology.

Childhood adversity is common and strongly associated with risk for psychopathology. Identifying factors that buffer children from experiencing psychopathology following adversity is critical for developing more effective intervention approaches. The present study examined several behavioral metrics of reward processing reflecting global approach motivation for reward and the degree to which reward responses scaled with reward value (i.e., behavioral sensitivity to reward value) as potential moderators of the association of multiple dimensions of adversity-including trauma, caregiver neglect, and food insecurity-with depression and externalizing psychopathology in a sample of youth aged 8-16 years (n = 132). Trauma exposure and externalizing problems were positively associated at low and moderate levels of reward reactivity, but this association became non-significant at high levels of reward reactivity. Our findings extend prior work, suggesting that high behavioral sensitivity to reward value may buffer against externalizing problems following exposure to trauma.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2021.102618

NeuroImage. Clinical

Neuroimage Clin

Reward-related neural correlates in adolescents with excess body weight.

The functional and connectivity reward processing in adults with excessive body weight is well documented, though is relatively less researched during adolescence. Given that reward and inhibition may be highly malleable during adolescence, it is unknown how impulsive behaviors, potentially stemming from impaired inhibitory control and heightened sensitivity to rewarding cues, relate to increases in body weight in adolescents. Adolescents (N = 76; mean age = 14.10 years, SD = 1.92) with varied body mass index (BMI) performed a child-friendly monetary incentive delay task during functional magnetic resonance imaging, to study reward processing during the anticipation of rewards (cue) and reactions to feedback about rewards (feedback). Our results show that adolescents with greater BMI z-score show neural activation and ventral striatum connectivity alterations in networks implicated in reward, salience detection, and inhibitory control. These bottom-up reward and top-down inhibitory control networks, as well as interactions between these networks were prevalent during the anticipation period (when the cue is presented) as well as when receiving feedback about whether one has received a reward. Specifically, our results were mainly driven by failure to receive a reward in the feedback period, and the anticipation of a potential reward in the anticipation period. Overall, we provide evidence for heightened reward salience as well as inhibitory control deficits that, in combination, may contribute to the impulsive behaviors that lead to higher BMI in adolescents.

CognitiveConstruct

RewardProcessing

10.1038/s41598-021-85027-6

Scientific reports

Sci Rep

Processing of increased frequency of social interaction in social anxiety disorder and borderline personality disorder.

We investigated how patients with social anxiety disorder (SAD) and patients with borderline personality disorder (BPD) process an increase in the frequency of social interaction. We used an EEG-compatible version of the online ball-tossing game Cyberball to induce an increase in the frequency of social interaction. In the first condition, each player received the ball equally often (inclusion: 33% ball reception). In the following condition, the frequency of the ball reception was increased (overinclusion: 45% ball reception). The main outcome variable was the event-related potential P2, an indicator for social reward processing. Moreover, positive emotions were assessed. Twenty-eight patients with SAD, 29 patients with BPD and 28 healthy controls (HCs) participated. As expected, HCs and patients with BPD, but not patients with SAD, showed an increase in the P2 amplitude from the inclusion to the overinclusion condition. Contrary to our expectations, positive emotions did not change from the inclusion to the overinclusion condition. EEG results provide preliminary evidence that patients with BPD and HCs, but not patients with SAD, process an increase in the frequency of social interaction as rewarding.

CognitiveConstruct

RewardProcessing

10.1002/brb3.2093

Brain and behavior

Brain Behav

Interactions between methodological and interindividual variability: How Monetary Incentive Delay (MID) task contrast maps vary and impact associations with behavior.

Phenomena related to reward responsiveness have been extensively studied in their associations with substance use and socioemotional functioning. One important task in this literature is the Monetary Incentive Delay (MID) task. By cueing and delivering performance-contingent reward, the MID task has been demonstrated to elicit robust activation of neural circuits involved in different phases of reward responsiveness. However, systematic evaluations of common MID task contrasts have been limited to between-study comparisons of group-level activation maps, limiting their ability to directly evaluate how researchers' choice of contrasts impacts conclusions about individual differences in reward responsiveness or brain-behavior associations. In a sample of 104 participants (Age Mean = 19.3, SD = 1.3), we evaluate similarities and differences between contrasts in: group- and individual-level activation maps using Jaccard's similarity index, region of interest (ROI) mean signal intensities using Pearson's r, and associations between ROI mean signal intensity and psychological measures using Bayesian correlation. Our findings demonstrate more similarities than differences between win and loss cues during the anticipation contrast, dissimilarity between some win anticipation contrasts, an apparent deactivation effect in the outcome phase, likely stemming from the blood oxygen level-dependent undershoot, and behavioral associations that are less robust than previously reported. Consistent with recent empirical findings, this work has practical implications for helping researchers interpret prior MID studies and make more informed a priori decisions about how their contrast choices may modify results.

CognitiveConstruct

RewardProcessing

10.1016/j.pnpbp.2021.110298

Progress in neuro-psychopharmacology & biological psychiatry

Prog Neuropsychopharmacol Biol Psychiatry

Do comorbid personality disorders in cocaine dependence exacerbate neuroanatomical alterations? A structural neuroimaging study.

Cocaine dependence (CD) is highly comorbid with personality disorders, with implications for poorer treatment response. The neurobiological mechanisms of this comorbidity are unclear. We aimed to test the role of comorbid personality disorders in the neuroanatomy of CD. We examined 4 groups using high-resolution structural neuroimaging, psychological questionnaires and cognitive tests: CD (n = 19), CD and personality disorder type B (CD + B, n = 21), CD and personality disorder C (CD + C, n = 13) and 21 controls. We compared groups in neuroanatomy and hypothesised that (i) CD would show altered striatal areas ascribed to reward processing (i.e., accumbens, caudate and putamen), (ii) CD + B and CD + C would show altered areas supporting emotional regulation/social valuation and anxiety/avoidance (i.e., OFC and amygdala). The CD + B group had larger caudate volumes than CD (p = .01, d = 0.94) and reduced lateral OFC thickness than CD + C (p = .056, d = 0.71). Exploratory correlations showed that altered neural integrity of the OFC and of the caudate nucleus in these groups exacerbated with worse personality disorder severity and impulsivity scores. CD with and without comorbid personality disorders may have partially distinct underlying mechanisms and targets for treatment.

CognitiveConstruct

RewardProcessing

10.1080/14728214.2021.1898588

Expert opinion on emerging drugs

Expert Opin Emerg Drugs

Efficacy of dextromethorphan for the treatment of depression: a systematic review of preclinical and clinical trials.

The large percentage of adults with major depressive disorder (MDD) insufficiently responding and/or tolerating conventional monoamine-based antidepressants invites the need for mechanistically novel treatments. Convergent evidence implicates glutamatergic signaling as a potential therapeutic target in MDD. The synthesis herein of preclinical and clinical studies indicates that dextromethorphan (DXM) is well tolerated and exhibits clinically significant antidepressant effects; DXM combined with bupropion has demonstrated replicated and relatively rapid onset efficacy in adults with MDD. DXM efficacy has been preliminarily reported in adults with bipolar depression. The combination of DXM and bupropion represents a pharmacokinetic and pharmacodynamic synergy which may account for the rapidity of action in MDD. The combination of DXM and bupropion is a safe, well tolerated and efficacious treatment option in adults with MDD. Priority questions are whether DXM/bupropion is uniquely effective across discrete domains of psychopathology (e.g. anhedonia, reward processing, general cognitive systems) and/or whether it is able to significantly improve patient-reported outcomes (e.g. quality of life, psychosocial functioning). The availability of ketamine/esketamine and DXM/bupropion instantiates the relevance of glutamate as a treatment target in MDD. Studies in bipolar depression with DXM/bupropion are warranted as well as in MDD with suicidality.

CognitiveConstruct

RewardProcessing