Datasets:

morteza

/

cogtext

like 0

Acta scientific neurology

Acta Sci Neurol

Should We Embrace the Incorporation of Genetically Guided "Dopamine Homeostasis" in the Treatment of Reward Deficiency Syndrome (RSD) as a Frontline Therapeutic Modality?

In 2019, the US Center for Disease Control and Prevention provided vital statistics related to drug overdoses in the United State1. They concluded that in the USA the number of deaths at almost 72,000 was due to 66.6% of opioid overdoses. In fact, the rate is alarming and increasing yearly. To make 2021 even more scary is the daunting effect on increased drug usage due to COVID 19 as a pandemic, albeit the new vaccines. Specifically, in 2020, the death rate from opioid overdoses rose to 13% nationally and in some sates 30%. The common neuromodulating aspects of neurotransmission, and its disruption via chronic exposure of drugs and behavioral addictions, requires further intense research focus on developing novel strategies to combat these unwanted genetic and epigenic infractions as accomplished with heroin addiction by our group. The take home message is the plausible acceptance of the well-established evidence for hypodopaminergia, a blunted reward processing system, reduced resting state functional connectivity, genetic antecedents, anti- reward symptomatology, poor compliance with MAT, and generalized RDS. With this evidence it is conceivable that pursuit through intensive future research should involve an approach that incorporates "dopamine homeostasis". This required paradigm shift may consist of many beneficial modalities including but not limited to: exercise, pro-dopamine regulation, nutrigenomics, cognitive behavioral therapy, hedonic hot spot targets brain, rTMRS, deep brain stimulation, diet, genetic edits, genetic guided therapeutics, epigenetic repair, amongst others. It is our opinion that nutrigenomics may assist the millions of people of getting out of a" hypodopaminergic ditch" WC 250.

CognitiveConstruct

RewardProcessing

10.1016/j.bpsc.2020.12.005

Biological psychiatry. Cognitive neuroscience and neuroimaging

Biol Psychiatry Cogn Neurosci Neuroimaging

Failure to Identify Robust Latent Variables of Positive or Negative Valence Processing Across Units of Analysis.

The heterogeneous nature of mood and anxiety disorders highlights a need for dimensionally based descriptions of psychopathology that inform better classification and treatment approaches. Following the Research Domain Criteria approach, this investigation sought to derive constructs assessing positive and negative valence domains across multiple units of analysis. Adults with clinically impairing mood and anxiety symptoms (N = 225) completed comprehensive assessments across several units of analysis. Self-report assessments included nine questionnaires that assess mood and anxiety symptoms and traits reflecting the negative and positive valence systems. Behavioral assessments included emotional reactivity and distress tolerance tasks, during which skin conductance and heart rate were measured. Neuroimaging assessments included fear conditioning and a reward processing task. The latent variable structure underlying these measures was explored using sparse Bayesian group factor analysis. Group factor analysis identified 11 latent variables explaining 31.2% of the variance across tasks, none of which loaded across units of analysis or tasks. Instead, variance was best explained by individual latent variables for each unit of analysis within each task. Post hoc analyses 1) showed associations with small effect sizes between latent variables that were derived separately from functional magnetic resonance imaging and self-report data and 2) showed that some latent variables are not directly related to individual valence system constructs. The lack of latent structure across units of analysis highlights challenges of the Research Domain Criteria approach and suggests that while dimensional analyses work well to reveal within-task features, more targeted approaches are needed to reveal latent cross-modal relationships that could illuminate psychopathology.

CognitiveConstruct

RewardProcessing

10.1016/j.neulet.2021.135798

Neuroscience letters

Neurosci Lett

Differences in basic psychological needs-related resting-state functional connectivity between individuals with high and low life satisfaction.

Basic psychological needs including autonomy, competence, and relatedness can be affected by the level of life satisfaction. The current research aimed to elucidate differences in the association of these needs and functional connectivity of reward processing and emotion regulation between individuals with high and low life satisfaction. A total of 83 young adults were divided into the high life satisfaction (HLS) and low life satisfaction (LLS) groups and were scanned for 5-min resting-state fMRI. A seed-to-voxel analysis was performed using the seeds of the nucleus accumbens (NAcc), medial orbitofrontal cortex, subgenual anterior cingulate cortex (sgACC), insula, and amygdala. Analysis of covariance was conducted to test differences in the association of basic psychological needs and functional connectivity between the two groups. Connectivity strengths between the NAcc and right ventromedial prefrontal cortex and between the sgACC and left ventromedial prefrontal cortex were higher in the HLS group as the autonomy and relatedness scores increased, respectively, whereas in the LLS group as they decreased. Connectivity strengths between the NAcc and right midcingulate cortex and between the sgACC and left fusiform gyrus were higher in the HLS group as the competence and relatedness scores decreased, respectively, but in the LLS group as they increased. These findings suggest that individuals' perceived life satisfaction affects the relationship between the neural mechanism for reward processing and emotion regulation and basic psychological needs support. Psychological need satisfactions seem to have an emotional impact by acting as a contradictory brain mechanism between individuals with high and low life satisfaction.

CognitiveConstruct

RewardProcessing

10.1016/j.tins.2021.02.001

Trends in neurosciences

Trends Neurosci

Modulating the Neuromodulators: Dopamine, Serotonin, and the Endocannabinoid System.

Dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT), and endocannabinoids (ECs) are key neuromodulators involved in many aspects of motivated behavior, including reward processing, reinforcement learning, and behavioral flexibility. Among the longstanding views about possible relationships between these neuromodulators is the idea of DA and 5-HT acting as opponents. This view has been challenged by emerging evidence that 5-HT supports reward seeking via activation of DA neurons in the ventral tegmental area. Adding an extra layer of complexity to these interactions, the endocannabinoid system is uniquely placed to influence dopaminergic and serotonergic neurotransmission. In this review we discuss how these three neuromodulatory systems interact at the cellular and circuit levels. Technological advances that facilitate precise identification and control of genetically targeted neuronal populations will help to achieve a better understanding of the complex relationship between these essential systems, and the potential relevance for motivated behavior.

CognitiveConstruct

RewardProcessing

10.3390/ijms22052405

International journal of molecular sciences

Int J Mol Sci

Oxytocin and Addiction: Potential Glutamatergic Mechanisms.

Recently, oxytocin (OXT) has been investigated for its potential therapeutic role in addiction. OXT has been found to diminish various drug-seeking and drug-induced behaviors. Although its behavioral effects are well-established, there is not much consensus on how this neuropeptide exerts its effects. Previous research has given thought to how dopamine (DA) may be involved in oxytocinergic mechanisms, but there has not been as strong of a focus on the role that glutamate (Glu) has. The glutamatergic system is critical for the processing of rewards and the disruption of glutamatergic projections produces the behaviors seen in drug addicts. We introduce the idea that OXT has direct effects on Glu transmission within the reward processing pathway. Thus, OXT may reduce addictive behaviors by restoring abnormal drug-induced changes in the glutamatergic system and in its interactions with other neurotransmitters. This review offers insight into the mechanisms through which a potentially viable therapeutic target, OXT, could be used to reduce addiction-related behaviors.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2021.108638

Drug and alcohol dependence

Drug Alcohol Depend

A neuroimaging investigation into the role of peripheral metabolic biomarkers in the anticipation of reward in alcohol use.

The relationship between alcohol use and metabolism has focused on the effects of alcohol use on metabolic factors. Metabolic factors, such as triglycerides, cholesterol, and glucose, have been shown to be associated with increased risk for heavy alcohol consumption and alcohol use disorder (AUD). It's been suggested that changes in metabolic factors may play a role in reward seeking behaviors and pathways. Studies on feeding behavior and obesity revealed the role of triglycerides in neural response to food cues in neurocircuitry regulating reward and feeding behaviors. This study aimed to explore the relationship of peripheral metabolism, alcohol use, and reward processing in individuals that use alcohol. Ninety participants from a previously collected dataset were included in the analysis. Participants were treatment seeking, detoxified individuals with AUD and healthy individuals without AUD, with the following metabolic biomarkers: triglyceride, glucose, high- and low-density cholesterol, and HbA1c levels. Participants completed a neuroimaging version of the Monetary Incentive Delay task (MID). Correlations on peripheral metabolic biomarkers, alcohol use, and neural activity during reward anticipation and outcome during the MID task were not significant. Mediation models revealed triglycerides and high-density cholesterol had significant effects on left anterior insula during anticipation of potential monetary loss and this effect was not mediated by alcohol use. Limbic recruitment by anticipation of monetary rewards revealed an independent relationship with peripheral metabolism and was not affected by individual differences in alcohol use, despite the effects of alcohol use on metabolic markers and reward processing neural circuitry.

CognitiveConstruct

RewardProcessing

10.1002/da.23143

Depression and anxiety

Depress Anxiety

Family history of depression is associated with alterations in task-dependent connectivity between the cerebellum and ventromedial prefrontal cortex.

A family history of major depressive disorder (MDD) increases the likelihood of a future depressive episode, which itself poses a significant risk for disruptions in reward processing and social cognition. However, it is unclear whether a family history of MDD is associated with alterations in the neural circuitry underlying reward processing and social cognition. We subdivided 279 participants from the Human Connectome Project into three groups: 71 with a lifetime history of MDD, 103 with a family history (FH) of MDD, and 105 healthy controls (HCs). We then evaluated task-based functional magnetic resonance imaging data on a social cognition and a reward processing task and found a region of the ventromedial prefrontal cortex (vmPFC) that responded to both tasks, independent of the group. To investigate whether the vmPFC shows alterations in functional connectivity between groups, we conducted psychophysiological interaction analyses using the vmPFC as a seed region. We found that FH (relative to HC) was associated with increased sadness scores, and MDD (relative to both FH and HC) was associated with increased sadness and MDD symptoms. Additionally, the FH group had increased vmPFC functional connectivity within the nucleus accumbens, left dorsolateral PFC, and subregions of the cerebellum relative to HC during the social cognition task. These findings suggest that aberrant neural mechanisms among those with a familial risk of MDD may underlie vulnerability to altered social cognition.

CognitiveConstruct

RewardProcessing

10.1002/hbm.25400

Human brain mapping

Hum Brain Mapp

The effect of risperidone on reward-related brain activity is robust to drug-induced vascular changes.

Dopamine (DA) mediated brain activity is intimately linked to reward-driven cerebral responses, while aberrant reward processing has been implicated in several psychiatric disorders. fMRI has been a valuable tool in understanding the mechanism by which DA modulators alter reward-driven responses and how they may exert their therapeutic effect. However, the potential effects of a pharmacological compound on aspects of neurovascular coupling may cloud the interpretability of the BOLD contrast. Here, we assess the effects of risperidone on reward driven BOLD signals produced by reward anticipation and outcome, while attempting to control for potential drug effects on regional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). Healthy male volunteers (n = 21) each received a single oral dose of either 0.5 mg, 2 mg of risperidone or placebo in a double-blind, placebo-controlled, randomised, three-period cross-over study design. Participants underwent fMRI scanning while performing the widely used Monetary Incentive Delay (MID) task to assess drug impact on reward function. Measures of CBF (Arterial Spin Labelling) and breath-hold challenge induced BOLD signal changes (as a proxy for CVR) were also acquired and included as covariates. Risperidone produced divergent, dose-dependent effects on separate phases of reward processing, even after controlling for potential nonneuronal influences on the BOLD signal. These data suggest the D2 antagonist risperidone has a wide-ranging influence on DA-mediated reward function independent of nonneuronal factors. We also illustrate that assessment of potential vascular confounds on the BOLD signal may be advantageous when investigating CNS drug action and advocate for the inclusion of these additional measures into future study designs.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2021.02.030

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

Dopamine and the interdependency of time perception and reward.

Time is a fundamental dimension of our perception of the world and is therefore of critical importance to the organization of human behavior. A corpus of work - including recent optogenetic evidence - implicates striatal dopamine as a crucial factor influencing the perception of time. Another stream of literature implicates dopamine in reward and motivation processes. However, these two domains of research have remained largely separated, despite neurobiological overlap and the apothegmatic notion that "time flies when you're having fun". This article constitutes a review of the literature linking time perception and reward, including neurobiological and behavioral studies. Together, these provide compelling support for the idea that time perception and reward processing interact via a common dopaminergic mechanism.

CognitiveConstruct

RewardProcessing

10.1007/s10571-021-01064-9

Cellular and molecular neurobiology

Cell Mol Neurobiol

The Roles of Serotonin in Neuropsychiatric Disorders.

The serotonergic system extends throughout the central nervous system (CNS) and the gastrointestinal (GI) tract. In the CNS, serotonin (5-HT, 5-hydroxytryptamine) modulates a broad spectrum of functions, including mood, cognition, anxiety, learning, memory, reward processing, and sleep. These processes are mediated through 5-HT binding to 5-HT receptors (5-HTRs), are classified into seven distinct groups. Deficits in the serotonergic system can result in various pathological conditions, particularly depression, schizophrenia, mood disorders, and autism. In this review, we outlined the complexity of serotonergic modulation of physiologic and pathologic processes. Moreover, we provided experimental and clinical evidence of 5-HT's involvement in neuropsychiatric disorders and discussed the molecular mechanisms that underlie these illnesses and contribute to the new therapies.

CognitiveConstruct

RewardProcessing

10.1002/brb3.2090

Brain and behavior

Brain Behav

The role of chronotype and reward processing in understanding social hierarchies in adolescence.

Circadian rhythms shift toward an evening preference during adolescence, a developmental period marked by greater focus on the social domain and salience of social hierarchies. The circadian system influences maturation of cognitive architecture responsible for motivation and reward, and observation of responses to reward cues has provided insights into neurocognitive processes that underpin adolescent social development. The objective was to investigate whether circadian phase of entrainment (chronotype) predicted both reward-related response inhibition and social status, and to explore whether mediator and moderator relationships existed between chronotype, reward processing, and social status outcomes. Participants were 75 adolescents aged 13-14 years old (41 females) who completed an eye tracking paradigm that involved an inhibitory control task (antisaccade task) within a nonsocial reward (Card Guessing Game) and a social reward (Cyberball Game) context. Chronotype was calculated from weekend midsleep and grouped into early, intermediate, and later terciles. Participants indicated subjective social status compared with peers in seven domains. An intermediate and later chronotype predicted improved inhibitory control in the social versus nonsocial reward context. Chronotype also predicted higher perceived social status in two domains (powerful, troublemaker). Intermediate chronotypes reported higher "Powerful" status whereas later chronotypes were higher on "Troublemaker." Improved social reward-related performance predicted only the higher powerful scores and chronotype moderated this relationship. Improved inhibitory control to social reward predicted higher subjective social status in the intermediate and later chronotype group, an effect that was absent in the early group. This behavioral study found evidence that changes toward a later phase of entrainment predicts social facilitation effects on inhibitory control and higher perceived power among peers. It is proposed here that circadian delayed phase in adolescence is linked to approach-related motivation, and the social facilitation effects could reflect a social cognitive capacity involved in the drive to achieve social rank.

CognitiveConstruct

RewardProcessing

10.1111/psyp.13789

Psychophysiology

Psychophysiology

The reward positivity reflects the integrated value of temporally threefold-layered decision outcomes.

In reinforcement learning, adaptive behavior depends on the ability to predict future outcomes based on previous decisions. The Reward Positivity (RewP) is thought to encode reward prediction errors in the anterior midcingulate cortex (aMCC) whenever these predictions are violated. Although the RewP has been extensively studied in the context of simple binary (win vs. loss) reward processing, recent studies suggest that the RewP scales complex feedback in a fine graded fashion. The aim of this study was to replicate and extend previous findings that the RewP reflects the integrated sum of instantaneous and delayed consequences of a singular outcome by increasing the feedback information content by a third temporal dimension. We used a complex reinforcement-learning task where each option was associated with an immediate, intermediate and delayed monetary outcome and analyzed the RewP in the time domain as well as fronto-medial theta power in the time-frequency domain. To test if the RewP sensitivity to the three outcome dimensions reflect stable trait-like individual differences in reward processing, a retesting session took place 3 months later. The results confirm that the RewP reflects the integrated value of complex temporally extended consequences in a stable manner, albeit there was no relation to behavioral choice. Our findings indicate that the medial frontal cortex receives fine graded information about complex action outcomes that, however, may not necessarily translate to cognitive or behavioral control processes.

CognitiveConstruct

RewardProcessing

10.1007/s00213-021-05801-2

Psychopharmacology

Psychopharmacology (Berl)

Cannabinoids, reward processing, and psychosis.

Evidence suggests that an overlap exists between the neurobiology of psychotic disorders and the effects of cannabinoids on neurocognitive and neurochemical substrates involved in reward processing. We investigate whether the psychotomimetic effects of delta-9-tetrahydrocannabinol (THC) and the antipsychotic potential of cannabidiol (CBD) are underpinned by their effects on the reward system and dopamine. This narrative review focuses on the overlap between altered dopamine signalling and reward processing induced by cannabinoids, pre-clinically and in humans. A systematic search was conducted of acute cannabinoid drug-challenge studies using neuroimaging in healthy subjects and those with psychosis RESULTS: There is evidence of increased striatal presynaptic dopamine synthesis and release in psychosis, as well as abnormal engagement of the striatum during reward processing. Although, acute THC challenges have elicited a modest effect on striatal dopamine, cannabis users generally indicate impaired presynaptic dopaminergic function. Functional MRI studies have identified that a single dose of THC may modulate regions involved in reward and salience processing such as the striatum, midbrain, insular, and anterior cingulate, with some effects correlating with the severity of THC-induced psychotic symptoms. CBD may modulate brain regions involved in reward/salience processing in an opposite direction to that of THC. There is evidence to suggest modulation of reward processing and its neural substrates by THC and CBD. Whether such effects underlie the psychotomimetic/antipsychotic effects of these cannabinoids remains unclear. Future research should address these unanswered questions to understand the relationship between endocannabinoid dysfunction, reward processing abnormalities, and psychosis.

CognitiveConstruct

RewardProcessing

10.1016/j.brainres.2021.147393

Brain research

Brain Res

What happens when right means wrong? The impact of conflict arising from competing feedback responses.

Humans often rely on feedback to learn. Indeed, in learning the difference between feedback and an expected outcome is computed to inform future actions. Further, recent work has found that reward and feedback have a unique role in modulating conflict processing and cognitive control. However, it is still not clear how conflict, especially concerning the processing and evaluation of feedback, impacts learning. To address this, we examined the effects of feedback competition on feedback evaluation in a reinforcement learning task. Specifically, we had participants play a simple two-choice gambling game while electroencephalographic (EEG) data were recorded. On half of the experiment blocks, we reversed the meaning of performance feedback for each trial from its prepotent meaning to induce response conflict akin to the Stroop effect (e.g., '✓' meant incorrect). Behaviourally, we found that participants' accuracy was reduced as a result of incongruent feedback. Paralleling this, an analysis of our EEG revealed that incongruent feedback resulted in a reduction in amplitude of the reward positivity and the P300, components of the human event-related brain potential implicated in reward processing. Our results demonstrate the negative impact of conflict on feedback evaluation and the impact of this on subsequent performance.

CognitiveConstruct

RewardProcessing

10.1017/S003329172100026X

Psychological medicine

Psychol Med

Associations between insomnia and reward learning in clinical depression.

Depression and insomnia commonly co-occur. Yet, little is known about the mechanisms through which insomnia influences depression. Recent research and theory highlight reward system dysfunction as a potential mediator of the relationship between insomnia and depression. This study is the first to examine the impact of insomnia on reward learning, a key component of reward system functioning, in clinical depression. The sample consisted of 72 veterans with unipolar depression who endorsed sleep disturbance symptoms. Participants completed the Structured Clinical Interview for DSM-IV, self-report measures of insomnia, depression, and reward processing, and a previously validated signal detection task (Pizzagalli et al., 2005, Biological Psychiatry, 57(4), 319-327). Trial-by-trial response bias (RB) estimates calculated for each of the 200 task trials were examined using linear mixed-model analyses to investigate change in reward learning. Findings demonstrated diminished rate and magnitude of reward learning in the Insomnia group relative to the Hypersomnia/Mixed Symptom group across the task. Within the Insomnia group, participants with more severe insomnia evidenced the lowest rates of reward learning, with increased RB across the task with decreasing insomnia severity. Among individuals with depression, insomnia is associated with decreased ability to learn associations between neutral stimuli and rewarding outcomes and/or modify behavior in response to differential receipt of reward. This attenuated reward learning may contribute to clinically meaningful decreases in motivation and increased withdrawal in this comorbid group. Results extend existing theory by highlighting impairments in reward learning specifically as a potential mediator of the association between insomnia and depression.

CognitiveConstruct

RewardProcessing

10.1016/j.pnpbp.2021.110289

Progress in neuro-psychopharmacology & biological psychiatry

Prog Neuropsychopharmacol Biol Psychiatry

Anhedonia as a central factor in depression: Neural mechanisms revealed from preclinical to clinical evidence.

Anhedonia is one of the core symptoms of major depressive disorder (MDD), which is often inadequately treated by traditional antidepressants. The modern framework of anhedonia extends the definition from impaired consummatory pleasure or interest in rewards to a broad spectrum of deficits that impact functions such as reward anticipation, approach motivation, effort expenditure, reward valuation, expectation, and reward-cue association learning. Substantial preclinical and clinical research has explored the neural basis of reward deficits in the context of depression, and has implicated mesocorticolimbic reward circuitry comprising the nucleus accumbens, ventral pallidum, ventral tegmental area, amygdala, hippocampus, anterior cingulate, insula, orbitofrontal cortex, and other prefrontal cortex regions. Dopamine modulates several reward facets including anticipation, motivation, effort, and learning. As well, serotonin, norepinephrine, opioids, glutamate, Gamma aminobutyric acid (GABA), and acetylcholine are also involved in anhedonia, and medications targeting these systems may also potentially normalize reward processing in depression. Unfortunately, whereas reward anticipation and reward outcome are extensively explored by both preclinical and clinical studies, translational gaps remain in reward motivation, effort, valuation, and learning, where clinical neuroimaging studies are in the early stages. This review aims to synthesize the neurobiological mechanisms underlying anhedonia in MDD uncovered by preclinical and clinical research. The translational difficulties in studying the neural basis of reward are also discussed.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.1869-20.2021

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

J Neurosci

Chronic Stress Prevents Cortico-Accumbens Cue Encoding and Alters Conditioned Approach.

Chronic stress impairs the function of multiple brain regions and causes severe hedonic and motivational deficits. One brain region known to be susceptible to these effects is the PFC. Neurons in this region, specifically neuronal projections from the prelimbic region (PL) to the nucleus accumbens core (NAcC), have a significant role in promoting motivated approach. However, little is known about how activity in this pathway changes during associative learning to encode cues that promote approach. Less is known about how activity in this pathway may be altered by stress. In this study, an intersectional fiber photometry approach was used in male Sprague Dawley rats engaged in a Pavlovian autoshaping design to characterize the involvement of the PL-NAcC pathway in the typical acquisition of learned approach (directed at both the predictive cue and the goal), and its potential alteration by stress. Specifically, the hypothesis that neural activity in PL-NAcC would encode a Pavlovian approach cue and that prior exposure to chronic stress would disrupt both the nature of conditioned approach and the encoding of a cue that promotes approach was tested. Results of the study demonstrated that the rapid acquisition of conditioned approach was associated with cue-induced PL-NAcC activity. Prior stress both reduced cue-directed behavior and impaired the associated cortical activity. These findings demonstrate that prior stress diminishes the task-related activity of a brain pathway that regulates approach behavior. In addition, the results support the interpretation that stress disrupts reward processing by altering the incentive value of associated cues. Chronic stress causes hedonic and motivational deficits and disrupts the function of the PFC. A specific projection from the prelimbic region of the PFC to the nucleus accumbens core (PL-NAcC) promotes approach behavior and is a strong candidate for contributing to stress-induced disruptions in motivation. However, it is not known how activity in this pathway encodes cues that promote approach, and how this encoding may be altered by stress. Here we show that the rapid acquisition of conditioned approach is associated with cue-induced activity in the PL-NAcC pathway. Prior stress both reduces cue-directed behavior and impairs the associated cortical activity. These findings demonstrate that stress diminishes task-related activity in a brain pathway that regulates approach behavior.

CognitiveConstruct

RewardProcessing

10.1111/cogs.12941

Cognitive science

Cogn Sci

Individual Differences in Reward-Based Learning Predict Fluid Reasoning Abilities.

The ability to reason and problem-solve in novel situations, as measured by the Raven's Advanced Progressive Matrices (RAPM), is highly predictive of both cognitive task performance and real-world outcomes. Here we provide evidence that RAPM performance depends on the ability to reallocate attention in response to self-generated feedback about progress. We propose that such an ability is underpinned by the basal ganglia nuclei, which are critically tied to both reward processing and cognitive control. This hypothesis was implemented in a neurocomputational model of the RAPM task, which was used to derive novel predictions at the behavioral and neural levels. These predictions were then verified in one neuroimaging and two behavioral experiments. Furthermore, an effective connectivity analysis of the neuroimaging data confirmed a role for the basal ganglia in modulating attention. Taken together, these results suggest that individual differences in a neural circuit related to reward processing underpin human fluid reasoning abilities.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2021.100936

Developmental cognitive neuroscience

Dev Cogn Neurosci

Hormonal and neural correlates of prosocial conformity in adolescents.

The dual hormone hypothesis, which centers on the interaction between testosterone and cortisol on social behavior, offers a compelling framework for examining the role of hormones on the neural correlates of adolescent peer conformity. Expanding on this hypothesis, the present study explored the interaction between testosterone and cortisol via hair concentrations on adolescents' conformity to peers. During fMRI, 136 adolescents (51 % female) ages 11-14 years (M = 12.32; SD = 0.6) completed a prosocial decision-making task. Participants chose how much of their time to donate to charity before and after observing a low- or high-prosocial peer. Conformity was measured as change in behavior pre- to post-observation. High testosterone with low cortisol was associated with greater conformity to high-prosocial peers but not low prosocial peers. Focusing on high prosocial peers, whole-brain analyses indicated greater activation post- vs. pre-observation as a function of high testosterone and low cortisol in regions implicated in social cognition, salience detection, and reward processing: pSTS/TPJ, insula, OFC, and caudate nucleus. Results highlight the relevance of hormones for understanding the neural correlates of adolescents' conformity to prosocial peers.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2021.117872

NeuroImage

Neuroimage

The longitudinal stability of fMRI activation during reward processing in adolescents and young adults.

The use of functional neuroimaging has been an extremely fruitful avenue for investigating the neural basis of human reward function. This approach has included identification of potential neurobiological mechanisms of psychiatric disease and examination of environmental, experiential, and biological factors that may contribute to disease risk via effects on the reward system. However, a central and largely unexamined assumption of much of this research is that neural reward function is an individual difference characteristic that is relatively stable and trait-like over time. In two independent samples of adolescents and young adults studied longitudinally (Ns = 145 & 139, 100% female and 100% male, ages 15-21 and 20-22, 2-4 scans and 2 scans respectively), we tested within-person stability of reward-task BOLD activation, with a median of 1 and 2 years between scans. We examined multiple commonly used contrasts of active states and baseline in both the anticipation and feedback phases of a card-guessing reward task. We examined the effects of cortical parcellation resolution, contrast, network (reward regions and resting-state networks), region-size, and activation strength and variability on the stability of reward-related activation. In both samples, contrasts of an active state relative to a baseline were more stable (ICC: intra-class correlation; e.g., Win>Baseline; mean ICC = 0.13 - 0.33) than contrasts of two active states (e.g., Win>Loss; mean ICC = 0.048 - 0.05). Additionally, activation in reward regions was less stable than in many non-task networks (e.g., dorsal attention), and activation in regions with greater between-subject variability showed higher stability in both samples. These results show that some contrasts from functional neuroimaging activation during a card guessing reward task have partially trait-like properties in adolescent and young adult samples over 1-2 years. Notably, results suggest that contrasts intended to map cognitive function and show robust group-level effects (i.e. Win > Loss) may be less effective in studies of individual differences and disease risk. The robustness of group-level activation should be weighed against other factors when selecting regions of interest in individual difference fMRI studies.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2021.117874

NeuroImage

Neuroimage

Electrophysiological investigation of reward anticipation and outcome evaluation during slot machine play.

Slot machines are a popular form of gambling, offering a tractable way to experimentally model reward processes. This study used a 3-reel slot paradigm to assess psychologically distinct phases of reward processing, reflecting anticipation, and early- and late-stage outcome processing. EEG measures of winning, nearly missing (a losing outcome revealed at the final, third reel), and "totally" missing (a losing outcome revealed earlier, at the second reel) were collected from healthy adults (n=54). Condition effects were evaluated in: i) event-related potential (ERP) components reflecting anticipatory attention (stimulus preceding negativity, SPN) and outcome processing (reward positivity, RewP and late-positive potential, LPP) and ii) total power and phase synchrony of theta and delta band oscillations. Behaviorally, trial initiation was fastest after a near miss outcome and slowest after a winning outcome. As expected, a significant SPN was observed for possible wins (AA) vs. total misses (AB), consistent with reward anticipation. Larger win (AAA) vs. near miss (AAB) amplitudes were observed for the RewP; LPP amplitudes were largest for wins (AAA), intermediate for near misses (AAB), and smallest for total misses (ABC), reflecting significant early (RewP) and late-stage (LPP) outcome processing effects. There was an effect of reel position on the RewP, with larger amplitude in the final reel (AAA-AAB) relative to the 2-reel locked difference waves (AA-AB). Across all outcomes, near misses elicited the largest and most phase-synchronized theta responses, while wins elicited larger and more phase-synchronized delta responses than total misses, with delta band measures not distinguishing between near misses and wins. . Phase locking measures contrasting win vs. near miss delta and theta synchronization, within time windows corresponding to ERP measurements, covaried with RewP, but not SPN or LPP, amplitude. Lastly, EEG measures showed differential relationships with age and self-reported consummatory pleasure. In the context of slot machine play, where reward anticipation and attainment place minimal demands on effort and skill, ERP and time-frequency methods capture distinct neurophysiological signatures of reward anticipation and outcome processing.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropharm.2021.108500

Neuropharmacology

Neuropharmacology

Promising vulnerability markers of substance use and misuse: A review of human neurobehavioral studies.

Substance use often begins, and noticeably escalates, during adolescence. Identifying predictive neurobehavioral vulnerability markers of substance use and related problems may improve targeted prevention and early intervention initiatives. This review synthesizes 44 longitudinal studies and explores the utility of developmental imbalance models and neurobehavioral addiction frameworks in predicting neural and cognitive patterns that are associated with prospective substance use initiation and escalation among young people. A total of 234 effect sizes were calculated and compared. Findings suggest that aberrant neural structure and function of regions implicated in reward processing, cognitive control, and impulsivity can predate substance use initiation, escalation, and disorder. Functional vulnerability markers of substance use include hyperactivation during reward feedback and risk evaluation in prefrontal and ventral striatal regions, fronto-parietal hypoactivation during working memory, distinctive neural patterns during successful (fronto-parietal hyperactivation) and failed response inhibition (frontal hypoactivation), and related cognitive deficits. Structurally, smaller fronto-parietal and amygdala volume and larger ventral striatal volume predicts prospective substance misuse. Taken together, the findings of this review suggest that neurobehavioral data can be useful in predicting future substance use behaviors. Notably, little to no research has empirically tested the underlying assumptions of widely used theoretical frameworks. To improve the reliability and utility of neurobehavioral data in predicting future substance use behaviors, recommendations for future research are provided. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'

CognitiveConstruct

RewardProcessing

10.1177/2470547020984732

Chronic stress (Thousand Oaks, Calif.)

Chronic Stress (Thousand Oaks)

Applying Reinforcement Learning to Rodent Stress Research.

Rodent models are an invaluable tool for studying the pathophysiological mechanisms underlying stress and depressive disorders. However, the widely used behavioral assays to measure depressive-like states in rodents have serious limitations. In this commentary, we suggest that learning tasks, particularly those that can be analyzed with the framework of reinforcement learning, are ideal for assaying reward processing deficits relevant to depression. The key advantages of these tasks are their repeatable, quantifiable nature and the link to clinical studies. By optimizing the behavioral readout of stress-induced phenotypes in rodents, a reinforcement learning-based approach may help bridge the translational gap and advance antidepressant discovery.

CognitiveConstruct

RewardProcessing

10.14348/molcells.2021.0006

Molecules and cells

Mol Cells

Functional Dissection of Glutamatergic and GABAergic Neurons in the Bed Nucleus of the Stria Terminalis.

The bed nucleus of the stria terminalis (BNST)-a key part of the extended amygdala-has been implicated in the regulation of diverse behavioral states, ranging from anxiety and reward processing to feeding behavior. Among the host of distinct types of neurons within the BNST, recent investigations employing cell type- and projection-specific circuit dissection techniques (such as optogenetics, chemogenetics, deep-brain calcium imaging, and the genetic and viral methods for targeting specific types of cells) have highlighted the key roles of glutamatergic and GABAergic neurons and their axonal projections. As anticipated from their primary roles in excitatory and inhibitory neurotransmission, these studies established that the glutamatergic and GABAergic subpopulations of the BNST oppositely regulate diverse behavioral states. At the same time, these studies have also revealed unexpected functional specificity and heterogeneity within each subpopulation. In this Minireview, we introduce the body of studies that investigated the function of glutamatergic and GABAergic BNST neurons and their circuits. We also discuss unresolved questions and future directions for a more complete understanding of the cellular diversity and functional heterogeneity within the BNST.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2021.628933

Frontiers in psychiatry

Front Psychiatry

Monetary Reward Discounting, Inhibitory Control, and Trait Impulsivity in Young Adults With Internet Gaming Disorder and Nicotine Dependence.

Internet Gaming Disorder (IGD) has been considered a potential behavioral or non-substance addiction that requires further investigation. Recognition of the commonalities between IGD and Substance Use disorders (SUD) would be of great help to better understand the basic mechanisms of addictive behaviors and excessive Internet gaming. However, little research has targeted a straightforward contrast between IGD and SUD on neuropsychological aspects. The present study thus aimed to explore the associations of reward processing and inhibitory control with IGD and nicotine dependence (ND) in young adults. Fifty-eight IGD and 53 ND individuals, as well as 57 age- and gender-matched healthy controls, were assessed with a series of measurements including the Delay-discounting Test (DDT), Probability Discounting Test (PDT), the Stroop Color-Word Task, a revised Go/No Go Task, and the Barratt Impulsiveness Scale (BIS-11). Multivariate analysis of variance (mANOVA) models revealed that both IGD and ND groups scored higher than healthy controls on the BIS-11 attentional, motor, and non-planning impulsiveness (Cohen's = 0.41-1.75). Higher degrees of delay discounting on the DDT were also found in IGD and ND groups compared to healthy controls (Cohen's = 0.53-0.69). Although IGD group did not differ from healthy controls on the PDT, ND group had a lower degree of probability discounting than healthy controls (Cohen's = 0.55), suggesting a reduction in risk aversion. Furthermore, ND subjects showed a lower correct accuracy in the incongruent trials of the Stroop task than healthy controls (Cohen's = 0.61). On the Go/No Go task, both IGD and ND groups had a lower correct accuracy in the No-Go trials than healthy controls (Cohen's = 1.35-1.50), indicating compromised response inhibition. These findings suggested that IGD was linked to both anomalous reward discounting and dysfunctional inhibitory control, which was comparable with one typical SUD category (i.e., ND). This study might promote a better understanding of the pathogenesis of IGD as a potential addictive disorder similar to SUD.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2020.563475

Frontiers in psychiatry

Front Psychiatry

Increased Reward-Related Activation in the Ventral Striatum During Stress Exposure Associated With Positive Affect in the Daily Life of Young Adults With a Family History of Depression. Preliminary Findings.

Being the offspring of a parent with major depression disorder (MDD) is a strong predictor for developing MDD. Blunted striatal responses to reward were identified in individuals with MDD and in asymptomatic individuals with family history of depression (FHD). Stress is a major etiological factor for MDD and was also reported to reduce the striatal responses to reward. The stress-reward interactions in FHD individuals has not been explored yet. Extending neuroimaging results into daily-life experience, self-reported ambulatory measures of positive affect (PA) were shown to be associated with striatal activation during reward processing. A reduction of self-reported PA in daily life is consistently reported in individuals with current MDD. Here, we aimed to test (1) whether increased family risk of depression is associated with blunted neural and self-reported reward responses. (2) the stress-reward interactions at the neural level. We expected a stronger reduction of reward-related striatal activation under stress in FHD individuals compared to HC. (3) the associations between fMRI and daily life self-reported data on reward and stress experiences, with a specific interest in the striatum as a crucial region for reward processing. Participants were 16 asymptomatic young adults with FHD and 16 controls (HC). They performed the Fribourg Reward Task with and without stress induction, using event-related fMRI. We conducted whole-brain analyses comparing the two groups for the main effect of reward (rewarded > not-rewarded) during reward feedback in control (no-stress) and stress conditions. Beta weights extracted from significant activation in this contrast were correlated with self-reported PA and negative affect (NA) assessed over 1 week. Under stress induction, the reward-related activation in the ventral striatum (VS) was higher in the FHD group than in the HC group. Unexpectedly, we did not find significant group differences in the self-reported daily life PA measures. During stress induction, VS reward-related activation correlated positively with PA in both groups and negatively with NA in the HC group. As expected, our results indicate that increased family risk of depression was associated with specific striatum reactivity to reward in a stress condition, and support previous findings that ventral striatal reward-related response is associated with PA. A new unexpected finding is the negative association between NA and reward-related ventral striatal activation in the HC group.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2020.613378

Frontiers in neuroscience

Front Neurosci

The Role of Affectionate Caregiver Touch in Early Neurodevelopment and Parent-Infant Interactional Synchrony.

Though rarely included in studies of parent-infant interactions, affectionate touch plays a unique and vital role in infant development. Previous studies in human and rodent models have established that early and consistent affectionate touch from a caregiver confers wide-ranging and holistic benefits for infant psychosocial and neurophysiological development. We begin with an introduction to the neurophysiological pathways for the positive effects of touch. Then, we provide a brief review of how affectionate touch tunes the development of infant somatosensory, autonomic (stress regulation), and immune systems. Affective touch also plays a foundational role in the establishment of social affiliative bonds and early psychosocial behavior. These touch-related bonding effects are known to be mediated primarily by the oxytocin system, but touch also activates mesocorticolimbic dopamine and endogenous opioid systems which aid the development of social cognitive processes such as social learning and reward processing. We conclude by proposing a unique role for affectionate touch as an essential pathway to establishing and maintaining parent-infant interactional synchrony at behavioral and neural levels. The limitations of the current understanding of affectionate touch in infant development point to fruitful avenues for future research.

CognitiveConstruct

RewardProcessing

10.1007/s00429-021-02231-w

Brain structure & function

Brain Struct Funct

A probabilistic atlas of the human ventral tegmental area (VTA) based on 7 Tesla MRI data.

Functional magnetic resonance imaging (fMRI) BOLD signal is commonly localized by using neuroanatomical atlases, which can also serve for region of interest analyses. Yet, the available MRI atlases have serious limitations when it comes to imaging subcortical structures: only 7% of the 455 subcortical nuclei are captured by current atlases. This highlights the general difficulty in mapping smaller nuclei deep in the brain, which can be addressed using ultra-high field 7 Tesla (T) MRI. The ventral tegmental area (VTA) is a subcortical structure that plays a pivotal role in reward processing, learning and memory. Despite the significant interest in this nucleus in cognitive neuroscience, there are currently no available, anatomically precise VTA atlases derived from 7 T MRI data that cover the full region of the VTA. Here, we first provide a protocol for multimodal VTA imaging and delineation. We then provide a data description of a probabilistic VTA atlas based on in vivo 7 T MRI data.

CognitiveConstruct

RewardProcessing

10.1556/2006.2021.00003

Journal of behavioral addictions

J Behav Addict

Enhanced neural responses in specific phases of reward processing in individuals with Internet gaming disorder.

Internet gaming disorder (IGD) has become a global health problem. The self-regulation model noted that a shift to reward system, whether due to overwhelming reward-seeking or impaired control, can lead to self-regulation failures, e.g., addiction. The present study focused on the reward processing of IGD, aiming to provide insights into the etiology of IGD. Reward processing includes three phases: reward anticipation, outcome monitoring and choice evaluation. However, it is not clear which phases of reward processing are different between individuals with IGD and healthy controls (HC). To address this issue, the present study asked 27 individuals with IGD and 26 HC to complete a roulette task during a functional MRI scan. Compared with HC, individuals with IGD preferred to take risks in pursuit of high rewards behaviorally and showed exaggerated brain activity in the striatum (nucleus accumbens and caudate) during the reward anticipation and outcome monitoring but not during the choice evaluation. These results reveal that the oversensitivity of the reward system to potential and positive rewards in college students with IGD drives them to approach risky options more frequently although they are able to assess the risk values of options and the correctness of decisions properly as HC do. These findings provide partial support for the application of the self-regulation model to the IGD population. Moreover, this study enriches this model from the perspective of three phases of reward processing and provides specific targets for future research regarding effective treatment of IGD.

CognitiveConstruct

RewardProcessing

10.1111/jnc.15321

Journal of neurochemistry

J Neurochem

The neurochemistry of social reward during development: What have we learned from rodent models?

Social rewards are fundamental to survival and overall health. Several studies suggest that adequate social stimuli during early life are critical for developing appropriate socioemotional and cognitive skills, whereas adverse social experiences negatively affect the proper development of brain and behavior, by increasing the susceptibility to develop neuropsychiatric conditions. Therefore, a better understanding of the neural mechanisms underlying social interactions, and their rewarding components in particular, is an important challenge of current neuroscience research. In this context, preclinical research has a crucial role: Animal models allow to investigate the neurobiological aspects of social reward in order to shed light on possible neurochemical alterations causing aberrant social reward processing in neuropsychiatric diseases, and they allow to test the validity and safety of innovative therapeutic strategies. Here, we discuss preclinical research that has investigated the rewarding properties of two forms of social interaction that occur in different phases of the lifespan of mammals, that is, mother-infant interaction and social interactions with peers, by focusing on the main neurotransmitter systems mediating their rewarding components. Together, the research performed so far helped to elucidate the mechanisms of social reward and its psychobiological components throughout development, thus increasing our understanding of the neurobiological substrates sustaining social functioning in health conditions and social dysfunction in major psychiatric disorders.

CognitiveConstruct

RewardProcessing

10.1016/j.tins.2021.01.002

Trends in neurosciences

Trends Neurosci

The Raphe Dopamine System: Roles in Salience Encoding, Memory Expression, and Addiction.

Dopamine (DA) neurons of the dorsal raphe nucleus (DRN) were traditionally viewed as an extension of the ventral tegmental area (VTA) DA population. While the VTA DA population is known to play important roles in reward processing, emerging evidence now supports the view that DRN DA neurons are a specialized midbrain DA subsystem that performs distinct functions in parallel to the VTA DA population. Recent studies have shed new light on the roles of DRN DA neurons in encoding incentive salience and in regulating memory expression and arousal. Here, we review recent findings using mouse models about the physiology and behavioral functions of DRN DA neurons, highlight the engagement of DRN DA neurons and their upstream circuits in opioid addiction, and discuss emerging lines of investigation that reveal multifaceted heterogeneity among DRN DA neurons.

CognitiveConstruct

RewardProcessing

10.1016/j.jns.2021.117326

Journal of the neurological sciences

J Neurol Sci

Modulatory effects of cognitive exertion on regional functional connectivity of the salience network in women with ME/CFS: A pilot study.

A common symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is post-exertional malaise (PEM). Various brain abnormalities have been observed in patients with ME/CFS, especially in insular and limbic areas, but their link with ME/CFS symptoms is still unclear. This pilot study aimed at investigating the association between PEM in ME/CFS and changes in functional connectivity (FC) of two main networks: the salience network (SN) and the default-mode network (DMN). A total of 16 women, 6 with and 10 without ME/CFS, underwent clinical and MRI assessment before and after cognitive exertion. Resting-state FC maps of 7 seeds (3 for the SN and 4 for the DMN) and clinical measures of fatigue, pain and cognition were analysed with repeated-measure models. FC-symptom change associations were also investigated. Exertion induced increases in fatigue and pain in patients with ME/CFS compared to the control group, while no changes were found in cognitive performance. At baseline, patients showed altered FC between some DMN seeds and frontal areas and stronger FC between all SN seeds and left temporal areas and the medulla. Significantly higher FC increases in patients than in controls were found only between the right insular seed and frontal and subcortical areas; these increases correlated with worsening of symptoms. Cognitive exertion can induce worsening of ME/CFS-related symptoms. These changes were here associated with strengthening of FC of the right insula with areas involved in reward processing and cognitive control.

CognitiveConstruct

RewardProcessing

10.1016/j.expneurol.2021.113637

Experimental neurology

Exp Neurol

The convergence of aversion and reward signals in individual neurons of the mice lateral habenula.

The lateral habenula (LHb) and ventral tegmental area (VTA) are two structures closely connected, and they serve as aversion and reward junction of the brain, respectively. This study investigated whether single neurons in the LHb/VTA respond to both aversion and reward stimuli and how these neurons regulate aversion and reward processing. Using optogenetic combined with multi-channel recording of LHb / VTA neuronal discharge, we found that most single neurons in the LHb/ VTA respond to both aversion and reward stimuli. Interestingly, majority of neurons in LHb were aversion-activated and reward-inhibited neurons, consisting mainly of glutamatergic neurons, while most neurons in VTA were reward-activated and aversion-inhibited neurons, which inhibited by glutamatergic neurons in the LHb. Furthermore, optogenetic activation or inhibition of glutamatergic neurons in LHb and their terminals in VTA could induce aversive or reward behaviors. These results indicate that identical neurons in the LHb and VTA have different responses to reward and aversion stimuli. The aversion behaviors induced by activating LHb glutamatergic neurons may be due to its inhibition on reward-activated neurons in VTA. This study suggests that interplay between the LHb and VTA neurons may play a key role in regulating reward and aversion behaviors.

CognitiveConstruct

RewardProcessing

10.1037/abn0000618

Journal of abnormal psychology

J Abnorm Psychol

Neuroticism and reward-related ventral striatum activity: Probing vulnerability to stress-related depression.

Elevated neuroticism may confer vulnerability to the depressogenic effects of stressful life events (SLEs). However, the mechanisms underlying this susceptibility remain poorly understood. Accumulating evidence suggests that stress-related disruptions in neural reward processing might undergird links between stress and depression. Using data from the Saint Louis Personality and Aging Network (SPAN) study and Duke Neurogenetics Study (DNS), we examined whether neuroticism moderates links between stressful life events (SLE) and depression as well as SLEs and ventral striatum (VS) response to reward. In the longitudinal SPAN sample ( = 971 older adults), SLEs prospectively predicted future depressive symptoms, especially among those reporting elevated neuroticism, even after accounting for prior depressive symptoms and previous SLE exposure (NxSLE interaction: = .016, Δ² = 0.003). Cross-sectional analyses of the DNS, a young adult college sample with neuroimaging data, replicated this interaction ( = 1,343: NxSLE interaction: = .019, Δ² = 0.003) and provided evidence that neuroticism moderates the association between SLEs and reward-related VS response ( = 1,195, NxSLE: = .017, Δ² = 0.0048). Blunted left VS response to reward was associated with a lifetime depression diagnosis, = -0.07, = .02, but not current depressive symptoms, = -0.003, = .93. These data suggest that neuroticism may promote vulnerability to stress-related depression and that sensitivity to stress-related reductions in VS response may be a potential neural mechanism underlying vulnerability to clinically significant depression. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

CognitiveConstruct

RewardProcessing

10.1037/abn0000662

Journal of abnormal psychology

J Abnorm Psychol

Intergenerational transmission of depression risk: Mothers' neural response to reward and history of depression are associated with daughters' neural response to reward across adolescence.

Impaired reward responsiveness, a construct of the RDoC positive valence systems (PVS), prospectively predicts depression onset and may therefore represent an important marker of risk. Neural structures implicated in reward processing undergo substantial change during adolescence, a period of heightened risk for depression, particularly for those with a family history of the disorder. However, it is not clear whether familial transmission of PVS functioning also changes across adolescence, nor whether a family history of depression influences normative development of the PVS. To address these questions, mothers and their adolescent daughters each completed a monetary reward guessing task while an electroencephalogram was recorded (N = 109 dyads). Daughters' pubertal status significantly moderated the association between mothers' and daughters' reward processing in the delta frequency, such that there was a negative association for daughters in early puberty that shifted toward a positive association in later puberty. Furthermore, for never-depressed daughters without a maternal history of depression, more advanced pubertal development was associated with increased reward-related power in the delta frequency, whereas, for daughters with a maternal history of depression, more advanced pubertal development was associated with reduced power in the delta frequency. These data indicate that biomarkers of risk for psychopathology may differ as a function of both familial risk and developmental status. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2020.11.017

Biological psychiatry

Biol Psychiatry

Trauma Affects Prospective Relationships Between Reward-Related Ventral Striatal and Amygdala Activation and 1-Year Future Hypo/Mania Trajectories.

Trauma exposure is associated with a more severe, persistent course of affective and anxiety symptoms. Markers of reward neural circuitry function, specifically activation to reward prediction error (RPE), are impacted by trauma and predict the future course of affective symptoms. This study's purpose was to determine how lifetime trauma exposure influences relationships between reward neural circuitry function and the course of future affective and anxiety symptoms in a naturalistic, transdiagnostic observational context. A total of 59 young adults aged 18-25 (48 female and 11 male participants, mean ± SD = 21.5 ± 2.0 years) experiencing psychological distress completed the study. Participants were evaluated at baseline, 6, and 12 months. At baseline, the participants reported lifetime trauma events and completed a monetary reward functional magnetic resonance imaging task. Affective and anxiety symptoms were reported at each visit, and trajectories were calculated using MPlus. Neural activation during RPE and other phases of reward processing were determined using SPM8. Trauma and reward neural activation were entered as predictors of symptom trajectories. Trauma exposure moderated prospective relationships between left ventral striatum (β = -1.29, p = .02) and right amygdala (β = 0.58, p = .04) activation to RPE and future hypo/mania severity trajectory: the interaction between greater trauma and greater left ventral striatum activation to RPE was associated with a shallower increase in hypo/mania severity, whereas the interaction between greater trauma and greater right amygdala activation to RPE was associated with increasing hypo/mania severity. Trauma exposure affects prospective relationships between markers of reward circuitry function and affective symptom trajectories. Evaluating trauma exposure is thus crucial in naturalistic and treatment studies aiming to identify neural predictors of future affective symptom course.

CognitiveConstruct

RewardProcessing

10.1016/j.neurobiolaging.2020.12.017

Neurobiology of aging

Neurobiol Aging

Reward motivation and cognitive flexibility in tau null-mutation mice.

The reduction of tau or hyperphosphorylated tau (p-tau) has been proposed as a therapeutic strategy for Alzheimer's disease (AD) and frontotemporal dementia (FTD). Cognitive decline and sleep-wake dysregulation seen in AD and FTD patients are mimicked in transgenic and null-mutation mouse models of tauopathy. Alterations in the reward system are additional symptoms of AD and FTD. However, the role of tau in reward processes is not well understood. The present study aimed to examine reward and reward-motivated cognitive processes in male and female tau knockout (tau) and wild-type mice using progressive ratio and reversal learning tasks. Tau mice were heavier, ate more in the home cage, and reached criterion in operant lever training faster than wild-type mice. Tau mice had a higher breakpoint in progressive ratio but were unimpaired in reversal learning or reward sensitivity. These data indicate that tau loss of function alters reward processing. This may help to explain aberrant reward-related behaviors in tauopathy patients and highlights a potentially important area for consideration in the development of anti-tau therapies.

CognitiveConstruct

RewardProcessing

10.1016/j.bpsc.2020.11.001

Biological psychiatry. Cognitive neuroscience and neuroimaging

Biol Psychiatry Cogn Neurosci Neuroimaging

The Relationship Between Depression Symptoms and Adolescent Neural Response During Reward Anticipation and Outcome Depends on Developmental Timing: Evidence From a Longitudinal Study.

Blunted neural reward responsiveness (RR) is observed in youth depression. However, it is unclear whether symptoms of depression experienced early in development relate to adolescent RR beyond current symptoms and, further, whether such relationships with RR differ during two key components of reward processing: anticipation and outcome. Within a prospective longitudinal study oversampled for early depression, children and caregivers completed semiannual diagnostic assessments beginning in preschool. In later adolescence, mean age = 16.49 years (SD = 0.94), youths' (N = 100) neurophysiological responses to cues signaling likely win and loss and these outcomes were assessed. Longitudinally assessed dimensional depression and externalizing symptoms (often comorbid with depression as well as associated with RR) experienced at different developmental periods (preschool [age 3-5.11 years], school age [6-9.11 years], early adolescence [10-14.11 years], current) were used as simultaneous predictors of event-related potentials indexing anticipatory cue processing (cue-P3) and outcome processing (reward positivity/feedback negativity and feedback-P3). Blunted motivated attention to cues signaling likely win (cue-P3) was specifically predicted by early-adolescent depression symptoms. Blunted initial response to win (reward positivity) and loss (feedback negativity) outcomes was specifically predicted by preschool depression symptoms. Blunted motivational salience of win and loss outcomes (feedback-P3) was predicted by cumulative depression, not specific to any developmental stage. Although blunted anticipation and outcome RR is a common finding in depression, specific deficits related to motivated attention to cues and initial outcome processing may map onto the developmental course of these symptoms.

CognitiveConstruct

RewardProcessing

10.1016/j.psyneuen.2021.105148

Psychoneuroendocrinology

Psychoneuroendocrinology

Novelty seeking is associated with increased body weight and orbitofrontal grey matter volume reduction.

Novelty seeking (NS) has previously been identified as a personality trait that is associated with elevated body mass index (BMI) and obesity. Of note, both obesity and reduced impulse control - a core feature of NS - have previously been associated with grey matter volume (GMV) reductions in the orbitofrontal cortex (OFC). Yet, it remains unknown, if body weight-related grey matter decline in the OFC might be explained by higher levels of NS. To address this question, we studied associations between NS, BMI and brain structure in 355 healthy subjects. Brain images were pre-processed using voxel-based morphometry (VBM). BMI was calculated from self-reported height and weight. The Tridimensional Personality Questionnaire (TPQ) was used to assess NS. NS and BMI were associated positively (r = .137, p = .01) with NS being a significant predictor of BMI (B = 0.172; SE B = 0.05; ß = 0.184; p = 0.001). Significant associations between BMI and GMV specifically in the OFC (x = -44, y = 56, z = -2, t(350) = 4.34, k = 5, p = 0.011) did not uphold when correcting for NS in the model. In turn, a significant negative association between NS and OFC GMV was found independent of BMI (x = -2, y = 48, z = -10, t(349) = 4.42, k = 88, p = 0.008). Body mass-related grey matter decrease outside the OFC could not be attributed to NS. Our results suggest that body-weight-related orbitofrontal grey matter reduction can at least partly be linked to higher levels of NS. Given the pivotal role of the OFC in overweight as well as cognitive domains such as impulse inhibition, executive control and reward processing, its association with NS seems to provide a tenable neurobiological correlate for future research.

CognitiveConstruct

RewardProcessing

10.1038/s41598-021-81966-2

Scientific reports

Sci Rep

Social isolation enhances cued-reinstatement of sucrose and nicotine seeking, but this is reversed by a return to social housing.

Physical or perceived (i.e. loneliness) social isolation is increasing in Western cultures. Unfortunately, social isolation is associated with a range of negative physical and mental health outcomes, including increased incidence of obesity and smoking. Here we monitored the impact of social isolation on a range of physical measures, and then tested whether social isolation in adult rats changes how reward-related stimuli motivate sucrose- or nicotine-seeking. Socially isolated rats showed elevated baseline CORT, gained significantly less weight across the study, were more active in response to a novel or familiar environment. Isolated rats also acquired nose-poking for a food pellet more rapidly, and showed increased susceptibility to cue-, but not reward-induced reinstatement. Notably, these effects are partially mitigated by a return to group housing, suggesting that they are not necessarily permanent, and that a return to a social setting can quickly reverse any deficits or changes associated with social isolation. This study advances our understanding of altered reward-processing in socially isolated individuals and reiterates the importance of socialisation in the treatment of disorders such as overeating and addiction.

CognitiveConstruct

RewardProcessing

10.1016/j.bbi.2021.01.016

Brain, behavior, and immunity

Brain Behav Immun

Elevated peripheral inflammation is associated with attenuated striatal reward anticipation in major depressive disorder.

Major depressive disorder (MDD) is the leading cause of years lived with disability worldwide, and up to 40% of individuals with MDD do not respond to current treatments. Studies suggest that peripheral inflammation plays an important role in the striatal mesolimbic dopamine pathway and corticostriatal reward circuitry in MDD. Although MDD patients show blunted striatal responses to reward, the link between degree of inflammation and attenuation of reward processing is unclear. We investigated whether MDD patients with elevated peripheral inflammation exhibit attenuated reward responses to enhance our understanding of MDD pathophysiology and develop more effective treatments for current non-responders. MDD subjects varying on serum C-reactive protein (CRP) concentrations (MDD-High CRP, >3 mg/L, n = 44; MDD-Low CRP, <3 mg/L, n = 44) and healthy comparisons (HC, n = 44) completed a monetary incentive delay (MID) task and provided blood samples to measure inflammation-related markers. MDD-High and MDD-Low were propensity score-matched on age, sex, body mass index (BMI), smoking status, exercise and MID task head motion. Percent change in blood oxygen level-dependent (BOLD) signal during anticipation of wins and losses was extracted from bilateral nucleus accumbens, dorsal caudate and dorsolateral putamen regions of interest (ROIs). A linear mixed-effects model was used to test group (MDD-High, MDD-Low and HC), condition (large-win, small-win and no win), and their interaction for these ROIs as well as whole-brain voxelwise data. Analyses also tested group differences in inflammatory mediators. Correlations were used to explore the relationship between inflammatory mediators and brain regions showing differences between MDD-High and MDD-Low. MDD-High exhibited: (a) lower BOLD signal change in dorsal caudate, thalamus, left insula and left precuneus during anticipation of small wins than MDD-Low; and (b) higher serum soluble intercellular adhesion molecule 1 (sICAM-1) and interleukin 6 (IL-6) concentrations than MDD-Low and HC. MDD as a whole, regardless of CRP-based inflammation, exhibited: (a) lower precuneus BOLD signal change to large wins than HC; and (b) higher Interleukin 1 receptor antagonist (IL-1ra), macrophage-derived chemokine (MDC) and macrophage inflammatory protein-1 alpha (MIP-1α) concentrations than HC. Higher serum sICAM-1 concentrations were associated with lower caudate BOLD signal change to small wins only within the MDD-High group. Within MDD patients, high inflammation (CRP, sICAM-1) was linked to reduced striatal activation recruited to discriminate intermediate reward magnitudes. These findings support an association between levels of peripheral inflammation and the degree of reward-related activation in individuals with MDD. The ClinicalTrials.gov identifier for the clinical protocol associated with data published in this current paper is NCT02450240, "Latent Structure of Multi-level Assessments and Predictors of Outcomes in Psychiatric Disorders."

CognitiveConstruct

RewardProcessing

10.3389/fnins.2020.579702

Frontiers in neuroscience

Front Neurosci

To Reveal or Not to Reveal? Observation of Social Outcomes Facilitates Reward Processing.

Motivation is a key topic that comprises considerable theoretical and practical implications, and its study is gaining increasing traction in recent years. Employing both behavioral and neural techniques, previous studies examined the extent to which intrinsic and extrinsic motivations collectively shape individual decision making. Investigations found that both processes play indispensable and interactive roles in choice behavior. However, despite its importance, little is known respecting the role of extrinsic social factors in contributing to individual variations in intrinsic motivation. Toward elucidating the role of extrinsic social factors in motivated decision making, the current study implements the stop watch task, combined with hyper-recording electrophysiological measurements. With the electrophysiological toolkit, our goal is to bring to light how extrinsic social signals impact intrinsic motivation and shape the reward processing over success and failure at the succeeding stage. Empirically, we show that, following social outcome presentation, there is an increased divergent feedback-related negativity (FRN), which reflects the failure/success discrepancy at the outcome stage of choice behavior. In summary, this study demonstrates the saliency of social information in intrinsic motivational processes that underpin success-failure outcomes.

CognitiveConstruct

RewardProcessing

10.1038/s41593-020-00772-7

Nature neuroscience

Nat Neurosci

Ventral arkypallidal neurons inhibit accumbal firing to promote reward consumption.

The nucleus accumbens shell (NAcSh) and the ventral pallidum (VP) are critical for reward processing, although the question of how coordinated activity within these nuclei orchestrates reward valuation and consumption remains unclear. Inhibition of NAcSh firing is necessary for reward consumption, but the source of this inhibition remains unknown. Here, we report that a subpopulation of VP neurons, the ventral arkypallidal (vArky) neurons, project back to the NAcSh, where they inhibit NAcSh neurons in vivo in mice. Consistent with this pathway driving reward consumption via inhibition of the NAcSh, calcium activity of vArky neurons scaled with reward palatability (which was dissociable from reward seeking) and predicted the subsequent drinking behavior during a free-access paradigm. Activation of the VP-NAcSh pathway increased ongoing reward consumption while amplifying hedonic reactions to reward. These results establish a pivotal role for vArky neurons in the promotion of reward consumption through modulation of NAcSh firing in a value-dependent manner.

CognitiveConstruct

RewardProcessing

10.1016/j.psyneuen.2021.105143

Psychoneuroendocrinology

Psychoneuroendocrinology

Weight gain and neuroadaptations elicited by high fat diet depend on fatty acid composition.

Overconsumption of food is a major health concern in the western world. Palatable food has been shown to alter the activity of neural circuits, and obesity has been linked to alterations in the connectivity between the hypothalamus and cortical regions involved in decision-making and reward processing, putatively modulating the incentive value of food. Outlining neurophysiological adaptations induced by dietary intake of high fat diets (HFD) is thus valuable to establish how the diet by itself may promote overeating. To this end, C57BL/6 mice were fed HFD rich in either saturated fatty acids (HFD-S) or polyunsaturated fatty acids (HFD-P), or a low-fat control diet (LFD) for four weeks. Food and energy intake were monitored and ex vivo electrophysiology was employed to assess neuroadaptations in lateral hypothalamus (LH) and corticostriatal circuits, previously associated with food intake. In addition, the effects of dietary saturated and polyunsaturated fatty acids on the gene expression of NMDA, AMPA and GABA receptor subunits in the hypothalamus were investigated. Our data shows that mice fed HFD-P had increased daily food and energy intake compared with mice fed HFD-S or LFD. However, this increase in energy intake had no obesogenic effects. Electrophysiological recordings demonstrated that HFD-P had a selective effect on glutamatergic neurotransmission in the LH, which was concomitant with a change in mRNA expression of AMPA receptor subtypes Gria1, Gria3 and Gria4, with no effect on the mRNA expression of NMDA receptor subtypes or GABA receptor subtypes. Furthermore, while synaptic output from corticostriatal subregions was not significantly modulated by diet, synaptic plasticity in the form of long-term depression (LTD) was impaired in the dorsomedial striatum of mice fed HFD-S. In conclusion, this study suggests that the composition of fatty acids in the diet not only affects weight gain, but may also modulate neuronal function and plasticity in brain regions involved in food intake.

CognitiveConstruct

RewardProcessing

10.1146/annurev-clinpsy-081219-114309

Annual review of clinical psychology

Annu Rev Clin Psychol

Clinical Neuroscience of Addiction: What Clinical Psychologists Need to Know and Why.

The last three decades in psychological research have been marked by interdisciplinary science. Addiction represents a prime example of a disorder marked by a complex interaction among psychosocial and biological factors. This review highlights critical findings in the basic neuroscience of addiction and translates them into clinical language that can inform clinical psychologists in their research, teaching, and practice. From mechanisms of reward processing, learning and memory, allostasis, incentive-sensitization, withdrawal, tolerance, goal-directed decision making, habit learning, genetics, inflammation, and the microbiome, the common theme of this review is to illustrate the clinical utility of basic neuroscience research and to identify opportunities for clinical science. The thoughtful integration of basic and clinical science provides a powerful tool to fulfill the scientific mission of improving health care. Clinical psychologists have a crucial role to play in the translational science of addiction.

CognitiveConstruct

RewardProcessing

10.1002/hbm.25148

Human brain mapping

Hum Brain Mapp

Upward and downward comparisons across monetary and status domains.

The ability to accurately infer one's place with respect to others is crucial for social interactions. Individuals tend to evaluate their own actions and outcomes by comparing themselves to others in either an upward or downward direction. We performed two fMRI meta-analyses on monetary (n = 39; 1,231 participants) and status (n = 23; 572 participants) social comparisons to examine how domain and the direction of comparison can modulate neural correlates of social hierarchy. Overall, both status and monetary downward comparisons activated regions associated with reward processing (striatum) while upward comparisons yielded loss-related activity. These findings provide partial support for the common currency hypothesis in that downward and upward comparisons from both monetary and status domains resemble gains and losses, respectively. Furthermore, status upward and monetary downward comparisons revealed concordant orbitofrontal cortical activity, an area associated with evaluating the value of goals and decisions implicated in both lesion and empirical fMRI studies investigating social hierarchy. These findings may offer new insight into how people relate to individuals with higher social status and how these social comparisons deviate across monetary and social status domains.

CognitiveConstruct

RewardProcessing

10.1002/dev.22090

Developmental psychobiology

Dev Psychobiol

Neural mechanisms of reward processing in adolescent irritability.

Irritability is impairing and prevalent across pediatric psychiatric disorders and typical development, yet its neural mechanisms are largely unknown. This study evaluated the relation between adolescent irritability and reward-related brain function as a candidate neural mechanism. Adolescents from intervention-seeking families in the community (N = 52; mean age = 13.80, SD = 1.94) completed a monetary incentive delay task to assess reward anticipation and feedback (reward receipt and omission) during fMRI acquisition. Whole-brain analyses, controlling for age, examined brain activation and striatal and amygdala connectivity in relation to irritability. Irritability was measured using the parent- and youth-reported Affective Reactivity Index. Irritability was associated with altered reward processing-related activation and connectivity in multiple networks during reward anticipation and feedback, including increased striatal activation and altered ventral striatum connectivity with prefrontal areas. Our findings suggest that irritability is associated with altered neural patterns during reward processing and that aberrant prefrontal cortex-mediated top-down control may be related to irritability. These findings inform our understanding of the etiology of youth irritability and the development of mechanism-based interventions.

CognitiveConstruct

RewardProcessing

10.1038/s41591-020-01173-w

Nature medicine

Nat Med

High-frequency neuromodulation improves obsessive-compulsive behavior.

Nearly one billion people worldwide suffer from obsessive-compulsive behaviors, yet our mechanistic understanding of these behaviors is incomplete, and effective therapeutics are unavailable. An emerging perspective characterizes obsessive-compulsive behaviors as maladaptive habit learning, which may be associated with abnormal beta-gamma neurophysiology of the orbitofrontal-striatal circuitry during reward processing. We target the orbitofrontal cortex with alternating current, personalized to the intrinsic beta-gamma frequency of the reward network, and show rapid, reversible, frequency-specific modulation of reward- but not punishment-guided choice behavior and learning, driven by increased exploration in the setting of an actor-critic architecture. Next, we demonstrate that chronic application of the procedure over 5 days robustly attenuates obsessive-compulsive behavior in a non-clinical population for 3 months, with the largest benefits for individuals with more severe symptoms. Finally, we show that convergent mechanisms underlie modulation of reward learning and reduction of obsessive-compulsive symptoms. The results contribute to neurophysiological theories of reward, learning and obsessive-compulsive behavior, suggest a unifying functional role of rhythms in the beta-gamma range, and set the groundwork for the development of personalized circuit-based therapeutics for related disorders.

CognitiveConstruct

RewardProcessing

10.1038/s41398-020-01192-8

Translational psychiatry

Transl Psychiatry

Multimethod investigation of the neurobiological basis of ADHD symptomatology in children aged 9-10: baseline data from the ABCD study.

Attention deficit/hyperactivity disorder is associated with numerous neurocognitive deficits, including poor working memory and difficulty inhibiting undesirable behaviors that cause academic and behavioral problems in children. Prior work has attempted to determine how these differences are instantiated in the structure and function of the brain, but much of that work has been done in small samples, focused on older adolescents or adults, and used statistical approaches that were not robust to model overfitting. The current study used cross-validated elastic net regression to predict a continuous measure of ADHD symptomatology using brain morphometry and activation during tasks of working memory, inhibitory control, and reward processing, with separate models for each MRI measure. The best model using activation during the working memory task to predict ADHD symptomatology had an out-of-sample R = 2% and was robust to residualizing the effects of age, sex, race, parental income and education, handedness, pubertal status, and internalizing symptoms from ADHD symptomatology. This model used reduced activation in task positive regions and reduced deactivation in task negative regions to predict ADHD symptomatology. The best model with morphometry alone predicted ADHD symptomatology with an R = 1% but this effect dissipated when including covariates. The inhibitory control and reward tasks did not yield generalizable models. In summary, these analyses show, with a large and well-characterized sample, that the brain correlates of ADHD symptomatology are modest in effect size and captured best by brain morphometry and activation during a working memory task.

CognitiveConstruct

RewardProcessing

10.1016/j.euroneuro.2020.12.010

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Eur Neuropsychopharmacol

Reward processing in major depressive disorder and prediction of treatment response - Neuropharm study.

Major depressive disorder (MDD) is a prevalent brain disorder for which anhedonia is a core symptom, indicating aberrations in the neural processing of reward. The striatum, medial prefrontal cortex (mPFC) and anterior insula (AI) are core reward processing regions. Here we used a reward-related, card-guessing functional magnetic resonance imaging (fMRI) paradigm to assay brain responses to reward in 90 MDD individuals and 58 healthy controls. We evaluated group differences in task-responsive, reward-related striatal, mPFC, and AI reactivity and whether baseline reactivity predicted an eight-week escitalopram antidepressant treatment response in MDD individuals. Thirty-eight MDD individuals also completed the reward paradigm after treatment and we evaluated antidepressant effects on reward reactivity estimates. Multivariate statistical analysis of task-responsive striatum, mPFC and AI brain responses did not reveal statistically significant differences between MDD and HC individuals (p>0.23). Logistic regression models (five-fold cross-validation, statistical significance assessed with permutation testing) also did not support that baseline reward-related brain responses significantly predicted antidepressant treatment response (p>0.39). Finally, reward-related brain responses were not statistically significantly changed over the course of treatment (p>0.27). Our findings in a comparatively large MDD cohort do not support that these reward-related fMRI brain responses are informative biomarkers of MDD or antidepressant treatment response to escitalopram.

CognitiveConstruct

RewardProcessing

10.1038/s41386-020-00940-0

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Schizophrenia and bipolar disorder are associated with opposite brain reward anticipation-associated response.

Blunted and exaggerated neuronal response to rewards are hypothesized to be core features of schizophrenia spectrum disorders (SZ) and bipolar disorder (BD), respectively. Nonetheless, direct tests of this hypothesis, in which response between SZ and BD is compared in the same study, are lacking. Here we examined the functional correlates of reward processing during the Incentivized Control Engagement Task (ICE-T) using 3T fMRI. Reward-associated activation was examined in 49 healthy controls (HCs), 52 recent-onset individuals with SZ, and 22 recent-onset individuals with Type I BD using anterior cingulate (ACC), anterior insula, and ventral striatal regions of interest. Significant group X reward condition (neutral vs. reward) interactions were observed during reward anticipation in the dorsal ACC (F(2,120) = 4.21, P = 0.017) and right insula (F(2,120) = 4.77, P = 0.010). The ACC interaction was driven by relatively higher activation in the BD group vs. HCs (P = 0.007) and vs. individuals with SZ (P = 0.010). The insula interaction was driven by reduced activation in the SZ group relative to HCs (P = 0.018) and vs. people with BD (P = 0.008). A composite of reward anticipation-associated response across all associated ROIs also differed significantly by diagnosis (F(1,120) = 5.59, P = 0.02), BD > HC > SZ. No effects of group or group X reward interactions were observed during reward feedback. These results suggest that people with SZ and BD have opposite patterns of activation associated with reward anticipation but not reward receipt. Implications of these findings in regard to Research Domain Criteria-based classification of illness and the neurobiology of reward in psychosis are discussed.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsab006

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Shared and unique neural circuitry underlying temporally unpredictable threat and reward processing.

Temporally unpredictable stimuli influence behavior across species, as previously demonstrated for sequences of simple threats and rewards with fixed or variable onset. Neuroimaging studies have identified a specific frontolimbic circuit that may become engaged during the anticipation of temporally unpredictable threat (U-threat). However, the neural mechanisms underlying processing of temporally unpredictable reward (U-reward) are incompletely understood. It is also unclear whether these processes are mediated by overlapping or distinct neural systems. These knowledge gaps are noteworthy given that disruptions within these neural systems may lead to maladaptive response to uncertainty. Here, using functional magnetic resonance imaging data from a sample of 159 young adults, we showed that anticipation of both U-threat and U-reward elicited activation in the right anterior insula, right ventral anterior nucleus of the thalamus and right inferior frontal gyrus. U-threat also activated the right posterior insula and dorsal anterior cingulate cortex, relative to U-reward. In contrast, U-reward elicited activation in the right fusiform and left middle occipital gyrus, relative to U-threat. Although there is some overlap in the neural circuitry underlying anticipation of U-threat and U-reward, these processes appear to be largely mediated by distinct circuits. Future studies are needed to corroborate and extend these preliminary findings.

CognitiveConstruct

RewardProcessing

10.1111/psyp.13764

Psychophysiology

Psychophysiology

Differentiating stages of reward responsiveness: Neurophysiological measures and associations with facets of the behavioral activation system.

The Research Domain Criteria (RDoC) positive valence systems domain include multiple aspects of reward responsiveness with potential to elucidate the understanding of motivational and hedonic deficits in psychological disorders. There is a need for reliable and valid methods to delineate behavioral and biological processes underlying stages of reward responsiveness. Event-related potentials (ERPs) offer a promising method for examining the temporal dynamics of reward processing, but the literature has mainly focused on the feedback stage and often single components. We investigated the electrophysiological aspects of reward anticipation and initial response to reward using an ERP monetary incentive delay task in 114 emerging adults. Principal component analysis was used to derive temporally and spatially distinct ERP components sensitive to reward processing. Components that reflect initial engagement toward a cue indicating potential reward (cue-P3) and anticipation of possible reward feedback (stimulus-preceding negativity; SPN) emerged in the anticipatory stage. In the initial response to reward stage, a reward positivity (RewP) was found. We further tested the association between ERPs and self-reported facets of the behavioral activation system. Greater self-reported reward responsiveness was associated with heightened response in the anticipatory stage (i.e., cue-P3, SPN). Self-reported drive was positively associated with RewP, but fun-seeking was negatively associated with RewP. Additional components were observed beyond those identified in prior work, warranting future research on temporal dynamics of reward processing across stages. Furthermore, examination of a broader range of reward-related ERPs in clinical populations has the potential to more precisely characterize alterations in positive valence systems in psychopathology.

CognitiveConstruct

RewardProcessing

10.1016/j.bpsc.2020.11.002

Biological psychiatry. Cognitive neuroscience and neuroimaging

Biol Psychiatry Cogn Neurosci Neuroimaging

Reward Processing Abnormalities and Promising New Directions for Understanding Suicide Vulnerability.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2020.12.131

Journal of affective disorders

J Affect Disord

Decreased sensitivity to risk levels in ventral stratum in major depressive disorder during risky decision-making.

Reduced decision-making ability in depressive people has been observed both in daily life and experimental behavioral studies. However, the neurobiology of dysfunction in decision-making among depressive people is still unclear. The study included 63 patients with major depressive disorder (MDD) and 49 healthy controls (HCs). The balloon analog risk task (BART), a risky decision-making paradigm, was used in a functional magnetic resonance imaging experiment to evaluate how brain activation was modulated by different levels of risk. No significant difference in behavioral performance was found. In prespecified brain regions, the activation of the left ventral stratum (VS) in MDD patients showed reduced modulation by risk levels compared with HCs. No significant group difference was found in prespecified dorsal anterior cingulate cortex (dACC) and right dorsal lateral prefrontal cortex (DLPFC). BART did not isolate stages of making a choice and experiencing the outcome of the choice. The left VS was less sensitive to risk levels in MDD patients compared with HCs, indicating inefficient reward processing in risky decision-making in MDD.

CognitiveConstruct

RewardProcessing

10.1093/cercor/bhaa369

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

Cereb Cortex

Resting State Hypoconnectivity of Reward Networks in Binge Eating Disorder.

The clinical presentation of binge eating disorder (BED) and data emerging from task-based functional neuroimaging research suggests that this disorder may be associated with alterations in reward processing. However, there is a dearth of research investigating the functional organization of brain networks that mediate reward in BED. To address this gap, 27 adults with BED and 21 weight-matched healthy controls (WMC) completed a multimodel assessment consisting of a resting functional magnetic resonance imaging scan, behavioral tasks measuring reward-based decision-making (i.e., delay discounting and reversal learning), and self-report assessing clinical symptoms. A seed-based approach was employed to examine the resting state functional connectivity (rsFC) of the striatum (nucleus accumbens [NAcc] and ventral and dorsal caudate), a collection of regions implicated in reward processing. Compared with WMC, the BED group exhibited lower rsFC of striatal seeds, with frontal regions mediating executive functioning (e.g., superior frontal gyrus [SFG]) and posterior, parietal, and temporal regions implicated in emotional processing. Lower NAcc-SFG rsFC was associated with more difficulties with reversal learning and binge eating frequency in the BED group. Results suggest that hypoconnectivity of striatal networks that integrate self-regulation and reward processing may promote the clinical phenomenology of BED. Interventions for BED may benefit from targeting these circuit-based disturbances.

CognitiveConstruct

RewardProcessing

10.1177/1073110520979419

The Journal of law, medicine & ethics : a journal of the American Society of Law, Medicine & Ethics

J Law Med Ethics

A Behavioral Addiction Model of Revenge, Violence, and Gun Abuse.

Data from multiple sources point to the desire for revenge in response to grievances or perceived injustices as a root cause of violence, including firearm violence. Neuroscience and behavioral studies are beginning to reveal that the desire for revenge in response to grievances activates the same neural reward-processing circuitry as that of substance addiction, suggesting that grievances trigger powerful cravings for revenge in anticipation of experiencing pleasure. Based on this evidence, the authors argue that a behavioral addiction framework may be appropriate for understanding and addressing violent behavior. Such an approach could yield significant benefits by leveraging scientific and public health-oriented drug abuse prevention and treatment strategies that target drug cravings to spur development of scientific and public-health-oriented "gun abuse" prevention and treatment strategies targeting the revenge cravings that lead to violence. An example of one such "motive control" strategy is discussed. Approaching revenge-seeking, violence, and gun abuse from the perspective of compulsion and addiction would have the added benefit of avoiding the stigmatization as violent of individuals with mental illness while also acknowledging the systemic, social, and cultural factors contributing to grievances that lead to violent acts.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2020.102492

NeuroImage. Clinical

Neuroimage Clin

Reward processing electrophysiology in schizophrenia: Effects of age and illness phase.

Reward processing abnormalities may underlie characteristic pleasure and motivational impairments in schizophrenia. Some neural measures of reward processing show age-related modulation, highlighting the importance of considering age effects on reward sensitivity. We compared event-related potentials (ERPs) reflecting reward anticipation (stimulus-preceding negativity, SPN) and evaluation (reward positivity, RewP; late positive potential, LPP) across individuals with schizophrenia (SZ) and healthy controls (HC), with an emphasis on examining the effects of chronological age, brain age (i.e., predicted age based on neurobiological measures), and illness phase. Subjects underwent EEG while completing a slot-machine task for which rewards were not dependent on performance accuracy, speed, or response preparation. Slot-machine task EEG responses were compared between 54 SZ and 54 HC individuals, ages 19 to 65. Reward-related ERPs were analyzed with respect to chronological age, categorically-defined illness phase (early; ESZ versus chronic schizophrenia; CSZ), and were used to model brain age relative to chronological age. Illness phase-focused analyses indicated there were no group differences in average SPN or RewP amplitudes. However, a group × reward outcome interaction revealed that ESZ differed from HC in later outcome processing, reflected by greater LPP responses following loss versus reward (a reversal of the HC pattern). While brain age estimates did not differ among groups, depressive symptoms in SZ were associated with older brain age estimates while controlling for negative symptoms. ESZ and CSZ did not differ from HC in reward anticipation or early outcome processing during a cognitively undemanding reward task, highlighting areas of preserved functioning. However, ESZ showed altered later reward outcome evaluation, pointing to selective reward deficits during the early illness phase of schizophrenia. Further, an association between ERP-derived brain age and depressive symptoms in SZ extends prior findings linking depression with reward-related ERP blunting. Taken together, both illness phase and age may impact reward processing among SZ, and brain aging may offer a promising, novel marker of reward dysfunction that warrants further study.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2020.100909

Developmental cognitive neuroscience

Dev Cogn Neurosci

Early childhood stress is associated with blunted development of ventral tegmental area functional connectivity.

Early life stress increases risk for later psychopathology, due in part to changes in dopaminergic brain systems that support reward processing and motivation. Work in animals has shown that early life stress has a profound impact on the ventral tegmental area (VTA), which provides dopamine to regions including nucleus accumbens (NAcc), anterior hippocampus, and medial prefrontal cortex (mPFC), with cascading effects over the course of development. However, little is known about how early stress exposure shifts the developmental trajectory of mesocorticolimbic circuitry in humans. In the current study, 88 four- to nine-year-old children participated in resting-state fMRI. Parents completed questionnaires on their children's chronic stress exposure, including socioeconomic status (SES) and adverse childhood experiences (ACEs). We found an age x SES interaction on VTA connectivity, such that children from higher SES backgrounds showed a positive relationship between age and VTA-mPFC connectivity. Similarly, we found an age x ACEs exposure interaction on VTA connectivity, such that children with no ACEs exposure showed a positive relationship between age and VTA-mPFC connectivity. Our findings suggest that early stress exposure relates to the blunted maturation of VTA connectivity in young children, which may lead to disrupted reward processing later in childhood and beyond.

CognitiveConstruct

RewardProcessing

10.7717/peerj.10520

PeerJ

PeerJ

Peripheral-physiological and neural correlates of the flow experience while playing video games: a comprehensive review.

The flow state is defined by intense involvement in an activity with high degrees of concentration and focused attention accompanied by a sense of pleasure. Video games are effective tools for inducing flow, and keeping players in this state is considered to be one of the central goals of game design. Many studies have focused on the underlying physiological and neural mechanisms of flow. Results are inconsistent when describing a unified mechanism underlying this mental state. This paper provides a comprehensive review of the physiological and neural correlates of flow and explains the relationship between the reported physiological and neural markers of the flow experience. Despite the heterogeneous results, it seems possible to establish associations between reported markers and the cognitive and experiential aspects of flow, particularly regarding arousal, attention control, reward processing, automaticity, and self-referential processing.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2020.603232

Frontiers in behavioral neuroscience

Front Behav Neurosci

Oxytocin Attenuates Expression, but Not Acquisition, of Sucrose Conditioned Place Preference in Rats.

Maladaptation of reward processing for natural rewards, such as sucrose or sugar, may play a role in the development of diseases such as obesity and diabetes. Furthermore, uncovering mechanisms to disrupt or reverse maladaptation of reward-seeking behaviors for natural reinforcers can provide insight into treatment of such diseases, as well as disorders such as addiction. As such, studying the effects of potential pharmacotherapeutics on maladaptive sugar-seeking behavior offers valuable clinical significance. Sucrose conditioned place preference (CPP) paradigms can offer insight into aspects of reward processes as it provides a way to assess acquisition and expression of context-reward associations. The present study examined the effect of peripheral oxytocin injections on sucrose CPP in rats. Oxytocin, when administered prior to CPP test, attenuated expression of sucrose CPP. However, oxytocin, when administered during sucrose conditioning, did not affect subsequent place preference. These findings suggest oxytocin sufficiently attenuates expression of sucrose-associated place preference.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2020.100903

Developmental cognitive neuroscience

Dev Cogn Neurosci

Social experience calibrates neural sensitivity to social feedback during adolescence: A functional connectivity approach.

The adaptive calibration model suggests exposure to highly stressful or highly supportive early environments sensitizes the brain to later environmental input. We examined whether family and peer experiences predict neural sensitivity to social cues in 85 adolescent girls who completed a social feedback task during a functional brain scan and an interview assessing adversity. Whole-brain functional connectivity (FC) analyses revealed curvilinear associations between social experiences and FC between the ventral striatum and regions involved in emotion valuation, social cognition, and salience detection (e.g., insula, MPFC, dACC, dlPFC) during social reward processing, such that stronger FC was found at both very high and very low levels of adversity. Moreover, exposure to adversity predicted stronger FC between the amygdala and regions involved in salience detection, social cognition, and emotional memory (e.g., sgACC, precuneus, lingual gyrus, parahippocampal gyrus) during social threat processing. Analyses also revealed some evidence for blunted FC (VS-PCC for reward; amygdala-parahippocampal gyrus for threat) at very high and low levels of adversity. Overall, results suggest social experiences may play a critical role in shaping neural sensitivity to social feedback during adolescence. Future work will need to elucidate the implications of these patterns of neural function for the development of psychopathology.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2020.560423

Frontiers in behavioral neuroscience

Front Behav Neurosci

Increased Endocannabinoid Signaling Reduces Social Motivation in Intact Rats and Does Not Affect Animals Submitted to Early-Life Seizures.

The early life (SE) causes high anxiety and chronic socialization abnormalities, revealed by a low preference for social novelty and deficit in social discrimination. This study investigated the involvement of the endocannabinoid system on the sociability in this model, due to its role in social motivation regulation. Male Wistar rats at postnatal day 9 were subjected to pilocarpine-induced neonatal SE and controls received saline. From P60 the groups received vehicle or JZL195 2 h before each behavioral test to increase endocannabinoids availability. In the sociability test, animals subjected to neonatal SE exhibited impaired sociability, characterized by social discrimination deficit, which was unaffected by the JZL195 treatment. In contrast, JZL195-treated control rats showed low sociability and impaired social discrimination. The negative impact of JZL195 over the sociability in control rats and the lack of effect in animals subjected to neonatal SE was confirmed in the social memory paradigm. In this paradigm, as expected for vehicle-treated control rats, the investigation toward the same social stimulus decreased with the sequential exposition and increased toward a novel stimulus. In animals subjected to neonatal SE, regardless of the treatment, as well as in JZL195-treated control rats, the investigation toward the same social stimulus was significantly reduced with no improvement toward a novel stimulus. Concerning the locomotion, the JZL195 increased it only in control rats. After behavioral tests, brain tissues of untreated animals were used for CB1 receptor quantification by Elisa and for gene expression by RT-PCR: no difference between control and experimental animals was noticed. The results reinforce the evidence that the early causes chronic socialization abnormalities, revealed by the low social interest for novelty and impaired social discrimination. The dual FAAH/MAGL inhibitor (JZL195) administration before the social encounter impaired the social interaction in intact rats with no effect in animals subjected to early-life seizures.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2020.108485

Drug and alcohol dependence

Drug Alcohol Depend

Novel circuit biomarker of impulsivity and craving in male heroin-dependent individuals.

The striatum mediates reward processing in addiction, and previous fMRI (functional Magnetic Resonance Imaging) studies have revealed abnormal striatofrontal functional connectivity in heroin addiction. However, little is known about whether there is abnormal structural connectivity of the striatal circuit in heroin addiction. This study investigated the structural connectivity of striatal circuits in abstinent heroin-dependent individuals (HDIs) without methadone treatment. Forty-three (age: 38.8 ± 7.1) male HDIs and twenty-one (age: 42.4 ± 7.9) matched healthy controls underwent high-resolution T1 and whole-brain diffusion tensor imaging (64 directions) magnetic resonance imaging. Connectivity-based seed classification probabilistic tractography was used to detect the tract strengths of striatal circuits with 10 a priori target masks. Tract strengths were compared between groups and correlated with impulsivity behavior, evaluated using the Barratt Impulsivity Scale (BIS), and craving, measured on visual analogue scale (VAS). HDIs showed significantly weaker tract strength of the left striatum-medial orbitofrontal cortex (mOFC) (Bonferroni corrected, p < 0.05/20 = 0.0025) and significantly higher BIS total, attention, motor, and non-planning scores (Bonferroni corrected, p < 0.05/4 = 0.0125) than controls. In HDIs, negative correlations were observed between the left striatum- mOFC tract strengths and the BIS total, attention and non-planning scores (r=-0.410, p = 0.005; r=-0.432, p = 0.003; r=-0.506, p<0.001) and between the right striatum-posterior cingulate cortex (PCC) tract strengths and craving scores (r=-0.433, p = 0.009) in HDIs. HDIs displayed decreased structural connectivity of the striatum-mOFC circuit and higher impulsivity. Higher impulsive behavior was associated with decreased left striatal circuit connectivity. These findings suggest that the striatal circuit tract strengths might be a novel potential biomarker in heroin and, potentially, general opioid addiction.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2020.117656

NeuroImage

Neuroimage

The effort-doors task: Examining the temporal dynamics of effort-based reward processing using ERPs.

Aberrant reward processing is a cardinal feature of various forms of psychopathology. However, recent research indicates that aberrant reward processing may manifest at temporally distinct substages and involve interdependent subcomponents of reward processing. To improve our understanding of both the temporal dynamics and distinct subcomponents of reward processing, we added an effort manipulation to the "doors" reward-task paradigm, to derive behavioral and event-related potential (ERP) measures of effort-based reward processing. Behavioral measures consisting of reaction time, response rate, and response rate change were used to index effort expenditure, and ERP measures were used to index attention allocated toward effort-completion cues, anticipation of reward, valuation of reward, and attention toward monetary feedback. Reduced response rate and slowing of response were evident during the high effort versus the low effort condition. ERP findings indicated increased attention to signals of high- compared to low-effort completion cues-as well as reduced anticipation of rewards, and reduced attention toward feedback information following high effort expenditure. Participants showing the most response-rate slowing evidenced the greatest reward devaluation following high versus low effort. Findings demonstrate that the addition of an effort expenditure manipulation to the doors reward paradigm produced reliable ERP and behavioral measures of effort-based reward processing, providing opportunities for future researchers to utilize the effort-doors task to parse the temporal dynamics of both anticipatory and consummatory reward processing components.

CognitiveConstruct

RewardProcessing

10.1016/j.jaac.2020.12.018

Journal of the American Academy of Child and Adolescent Psychiatry

J Am Acad Child Adolesc Psychiatry

Editorial: Heavy Adolescent Alcohol Use: An Accelerant of Impulsivity?

It has been difficult to disentangle factors conferring vulnerability to substance use disorders (SUDs) from the consequences of substance use. Reward sensitivity and impulsivity have been identified as adolescent risk factors that confer vulnerability for later problematic substance use. Studies also suggest, however, that substance use itself affects brain development and behavior and that some of the same risk factors that predispose youth to SUD (eg, reward sensitivity and impulsivity) may be brought on or worsened by the neurotoxicity of drugs of abuse. Studies examining neural and behavioral correlates of SUDs commonly include youth with varying degrees of substance exposure; thus development of vulnerabilities to substance abuse are difficult to separate from the effects of substance use. In this issue of JACC, Ivanov et al. advance our field's knowledge in this area by leveraging longitudinal data from the European IMAGEN dataset (n = 2,200) in order to characterize predictors of alcohol use at age 16 as well as trajectories of impulsivity. This design allows investigation into whether alcohol drinking in adolescence may actually be related to worsening impulsivity. The authors followed a subset of the IMAGEN sample, 304 substance-naïve 14-year-olds over 2 years. Reward system function in the brain was assessed at baseline by collecting functional magnetic resonance imaging scans during a Monetary Incentive Delay (MID) task which assessed neural response to reward anticipation and outcome. Impulsivity and delay discounting, the propensity to select smaller immediate rewards versus larger, delayed rewards, were also assessed at baseline and follow-up. Linear regression was used to evaluate longitudinal associations among the frequency of alcohol use at age 16 and impulsivity, delay discounting, and reward system function at age 14. Reward system function was measured by activation in medial orbitofrontal cortex (mOFC) and ventral striatum regions of interest during the highest versus the lowest reward levels on the MID task. These regions are involved in key aspects of reward processing, including valuation of rewarding stimuli and outcomes..

CognitiveConstruct

RewardProcessing

10.1370/afm.2591

Annals of family medicine

Ann Fam Med

When Physical and Social Pain Coexist: Insights Into Opioid Therapy.

The US opioid epidemic challenges us to rethink our understanding of the function of opioids and the nature of chronic pain. We have neatly separated opioid use and abuse as well as physical and social pain in ways that may not be consistent with the most recent neuroscientific and epidemiological research. Physical injury and social rejection activate similar brain centers. Many of the patients who use opioid medications long term for the treatment of chronic pain have both physical and social pain, but these medications may produce a state of persistent opioid dependence that suppresses the endogenous opioid system that is essential for human socialization and reward processing. Recognition of the social aspects of chronic pain and opioid action can improve our treatment of chronic pain and our use of opioid medications.

CognitiveConstruct

RewardProcessing

10.1017/pen.2020.11

Personality neuroscience

Personal Neurosci

An fMRI investigation of the relations between Extraversion, internalizing psychopathology, and neural activation following reward receipt in the Human Connectome Project sample.

Quantitative models of psychopathology (i.e., HiTOP) propose that personality and psychopathology are intertwined, such that the various processes that characterize personality traits may be useful in describing and predicting manifestations of psychopathology. In the current study, we used data from the Human Connectome Project (N = 1050) to investigate neural activation following receipt of a reward during an fMRI task as one shared mechanism that may be related to the personality trait Extraversion (specifically its sub-component Agentic Extraversion) and internalizing psychopathology. We also conducted exploratory analyses on the links between neural activation following reward receipt and the other Five-Factor Model personality traits, as well as separate analyses by gender. No significant relations ( < .005) were observed between any personality trait or index of psychopathology and neural activation following reward receipt, and most effect sizes were null to very small in nature (i.e., < |.05|). We conclude by discussing the appropriate interpretation of these null findings, and provide suggestions for future research that spans psychological and neurobiological levels of analysis.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2020.599141

Frontiers in psychiatry

Front Psychiatry

Altered Reward Processing System in Internet Gaming Disorder.

Converging evidence indicates that addiction involves impairment in reward processing systems. However, the patterns of dysfunction in different stages of reward processing in internet gaming addiction remain unclear. In previous studies, individuals with internet gaming disorder were found to be impulsive and risk taking, but there is no general consensus on the relation between impulsivity and risk-taking tendencies in these individuals. The current study explored behavioral and electrophysiological responses associated with different stages of reward processing among individuals with internet gaming disorders (IGDs) with a delayed discounting task and simple gambling tasks. Compared to the healthy control (HC) group, the IGD group discounted delays more steeply and made more risky choices, irrespective of the outcome. As for the event-related potential (ERP) results, during the reward anticipation stage, IGDs had the same stimulus-preceding negativity (SPN) for both large and small choices, whereas HCs exhibited a higher SPN in large vs. small choices. During the outcome evaluation stage, IGDs exhibited a blunted feedback-related negativity for losses vs. gains. The results indicate impairment across different stages of reward processing among IGDs. Moreover, we found negative correlation between impulsivity indexed by BIS-11 and reward sensitivity indexed by SPN amplitude during anticipation stage only, indicating different neural mechanisms at different stages of reward processing. The current study helps to elucidate the behavioral and neural mechanisms of reward processing in internet gaming addiction.

CognitiveConstruct

RewardProcessing

10.1038/s41598-020-79247-5

Scientific reports

Sci Rep

Exploring the dog-human relationship by combining fMRI, eye-tracking and behavioural measures.

Behavioural studies revealed that the dog-human relationship resembles the human mother-child bond, but the underlying mechanisms remain unclear. Here, we report the results of a multi-method approach combining fMRI (N = 17), eye-tracking (N = 15), and behavioural preference tests (N = 24) to explore the engagement of an attachment-like system in dogs seeing human faces. We presented morph videos of the caregiver, a familiar person, and a stranger showing either happy or angry facial expressions. Regardless of emotion, viewing the caregiver activated brain regions associated with emotion and attachment processing in humans. In contrast, the stranger elicited activation mainly in brain regions related to visual and motor processing, and the familiar person relatively weak activations overall. While the majority of happy stimuli led to increased activation of the caudate nucleus associated with reward processing, angry stimuli led to activations in limbic regions. Both the eye-tracking and preference test data supported the superior role of the caregiver's face and were in line with the findings from the fMRI experiment. While preliminary, these findings indicate that cutting across different levels, from brain to behaviour, can provide novel and converging insights into the engagement of the putative attachment system when dogs interact with humans.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2020.09.021

Biological psychiatry

Biol Psychiatry

The Influence of Cannabis and Nicotine Co-use on Neuromaturation: A Systematic Review of Adolescent and Young Adult Studies.

Accumulating evidence suggests that the use of cannabis and nicotine and tobacco-related products (NTPs) during the adolescent years has harmful effects on the developing brain. Yet, few studies have focused on the developing brain as it relates to the co-administration of cannabis and NTPs, despite the high prevalence rates of co-use in adolescence. This review aims to synthesize the existing literature on neurocognitive, structural neuroimaging, and functional neuroimaging outcomes associated with cannabis and NTP co-use. A systematic search of peer-reviewed articles resulted in a pool of 1107 articles. Inclusion criteria were 1) data-based study; 2) age range of 13 to 35 years or, for preclinical studies, nonadult subjects; 3) cannabis and NTP group jointly considered; and 4) neurocognitive, structural neuroimaging, or functional neuroimaging as an outcome measure. Twelve studies met inclusion criteria. Consistent with the literature, cannabis and nicotine were found to have independent effects on cognition. The available research on the co-use of cannabis and NTPs demonstrates a potential nicotine-related masking effect on cognitive deficits associated with cannabis use, yet there is little research on co-use and associations with neuroimaging indices. In neuroimaging studies, there is preliminary evidence for hippocampal volume differences in co-users and a lack of evidence for co-use differences related to nucleus accumbens activity during reward processing. Notably, no structural neuroimaging studies were found to examine the combined effects of nicotine and cannabis in adolescent-only populations. Further research, including longitudinal studies, is warranted to investigate the influence of cannabis and NTP co-use on maturation.

CognitiveConstruct

RewardProcessing

10.1111/jne.12923

Journal of neuroendocrinology

J Neuroendocrinol

Unchanged food approach-avoidance behaviour of healthy men after oxytocin administration.

The oxytocinergic system has been assumed to contribute to food intake, possibly via interactions with dopamine. However, so far, it is unknown whether oxytocin influences the underlying motivational behaviour towards food. In the present study, we used a food-based approach-avoidance task (AAT) in a randomised, placebo-controlled, double-blind, cross-over design to compare intranasal oxytocin with a placebo. In the AAT, participants pushed or pulled a joystick when images of foods with a high or low craving rating were presented, where differences in response times typically reflect approach and avoidance motivational biases towards positively and negatively valence stimuli, respectively. Thirty-three healthy male participants (age = 25.12 ± 3.51 years; body mass index = 24.25 ± 2.48 kg/m ) completed the two-session study, one with placebo and the other with oxytocin. We used mixed-effects models to investigate effects of treatment (oxytocin, placebo), response type (approach, avoid) and stimulus (high, low craving). The results showed that both approach and avoid responses tended to be faster for foods higher in craving compared to foods lower in craving. Most importantly, we did not observe any significant effects of oxytocin compared to placebo in motivational behaviour towards food. Our study demonstrates a general response bias towards foods with different craving values, which could have implications for future studies investigating food-related behaviour. We discuss possible explanations for the null effects of oxytocin and suggest further investigation of the relationship between oxytocin, dopamine and food-reward processing.

CognitiveConstruct

RewardProcessing

10.1002/brb3.1987

Brain and behavior

Brain Behav

Neural correlates of reward processing: Functional dissociation of two components within the ventral striatum.

Rewarding and punishing stimuli elicit BOLD responses in the affective division of the striatum. The responses typically traverse from the affective to the associative division of the striatum, suggesting an involvement of associative processes during the modulation of stimuli valance. In this study, we hypothesized that fMRI responses to rewards versus punishments in a guessing card game can be disassociated into two functional component processes that reflect the convergence of limbic and associative functional networks in the ventral striatum. We used fMRI data of 175 (92 female) subjects from the human connectome project´s gambling task, working memory task, and resting-state scans. A reward > punish contrast identified a ventral striatum cluster from which voxelwise GLM parameter estimates were entered into a k-means clustering algorithm. The k-means analysis supported separating the cluster into two spatially distinct components. These components were used as seeds to investigate their functional connectivity profile. GLM parameter estimates were extracted and compared from the task contrasts reward > punish and 2-back > 0-back from two ROIs in the ventral striatum and one ROI in hippocampus. The analyses converged to show that a superior striatal component, coupled with the ventral attention and frontal control networks, was responsive to both a modulation of cognitive control in working memory and to rewards, whereas the most inferior part of the ventral striatum, coupled with the limbic and default mode networks including the hippocampus, was selectively responsive to rewards. We show that the fMRI response to rewards in the ventral striatum reflects a mixture of component processes of reward. An inferior ventral striatal component and hippocampus are part of an intrinsically coupled network that responds to reward-based processing during gambling. The more superior ventral striatal component is intrinsically coupled to networks involved with executive functioning and responded to both reward and cognitive control demands.

CognitiveConstruct

RewardProcessing

10.1016/j.pneurobio.2020.101969

Progress in neurobiology

Prog Neurobiol

An amylin and calcitonin receptor agonist modulates alcohol behaviors by acting on reward-related areas in the brain.

Alcohol causes stimulatory behavioral responses by activating reward-processing brain areas including the laterodorsal (LDTg) and ventral tegmental areas (VTA) and the nucleus accumbens (NAc). Systemic administration of the amylin and calcitonin receptor agonist salmon calcitonin (sCT) attenuates alcohol-mediated behaviors, but the brain sites involved in this process remain unknown. Firstly, to identify potential sCT sites of action in the brain, we used immunohistochemistry after systemic administration of fluorescent-labeled sCT. We then performed behavioral experiments to explore how infused sCT into the aforementioned reward-processing brain areas affects acute alcohol-induced behaviors in mice and chronic alcohol consumption in rats. We show that peripheral sCT crosses the blood brain barrier and is detected in all the brain areas studied herein. sCT infused into the LDTg attenuates alcohol-evoked dopamine release in the NAc shell in mice and reduces alcohol intake in rats. sCT into the VTA blocks alcohol-induced locomotor stimulation and dopamine release in the NAc shell in mice and decreases alcohol intake in rats. Lastly, sCT into the NAc shell prevents alcohol-induced locomotor activity in mice. Our data suggest that central sCT modulates the ability of alcohol to activate reward-processing brain regions.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2020.11.027

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

The neural basis of gambling disorder: An activation likelihood estimation meta-analysis.

Previous imaging studies suggested that impairments of prefrontal-striatal and limbic circuits are correlated to excessive gambling. However, the neural underpinnings of gambling disorder (GD) continue to be the topic of debate. The present study aimed to identify structural changes in GD and differentiate the specific brain activity patterns associated with decision-making and reward-processing. We performed a systematic review complemented by Activation likelihood estimation (ALE) meta-analyses on morphometric and functional studies on neural correlates of GD. The ALE meta-analysis on structural studies revealed that patients with GD showed significant cortical grey-matter thinning in the right ventrolateral and ventromedial prefrontal cortex compared to healthy subjects. The ALE meta-analyses on functional studies revealed that patients with GD showed a significant hyperactivation in the medial prefrontal cortex and in the right ventral striatum during decision-making and gain processing compared to healthy subjects. These findings suggest that GD is related to an alteration of brain mechanisms underlying top-down control and appraisal of gambling-related stimuli and provided indications to develop new interventions in clinical practice.

CognitiveConstruct

RewardProcessing

10.3758/s13415-020-00851-z

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Executive functioning moderates neural reward processing in youth.

Although executive functioning has traditionally been studied in "cool" settings removed from emotional contexts, it is highly relevant in "hot" emotionally salient settings such as reward processing. Furthermore, brain structures related to "cool" executive functioning and "hot" reward-related processes develop simultaneously, yet little is known about how executive functioning modulates neural processes related to reward processing during adolescence, a period of time when these systems are still developing. The present study examined how performance on "cool" behavioral executive functioning measures moderates neural reward processing. Youths (N = 43, M = 13.74 years, SD = 1.81 years) completed a child-friendly monetary incentive delay task during fMRI acquisition that captures neural responses to reward anticipation and to reward receipt and omission. Performance on inhibitory control and cognitive flexibility measures, captured outside the scanner, was used to predict brain activation and seed-based connectivity (ventral striatum and amygdala). Across analyses, we found that executive functioning moderated youths' neural responses during both reward anticipation and performance feedback, predominantly with respect to amygdala connectivity with prefrontal/frontal and temporal structures, supporting previous theoretical models of brain development during adolescence. Overall, youths with worse executive functioning had more pronounced differences in neural activation and connectivity between task conditions compared with youths with better executive functioning. This study contributes to elucidating the relationship between "cool" and "hot" processes and our findings demonstrate that simple executive functioning skills moderate more complex processes that involve incorporation of numerous skills in an emotionally salient context, such as reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.clinthera.2020.10.014

Clinical therapeutics

Clin Ther

The Neurobiology of Binge-eating Disorder Compared with Obesity: Implications for Differential Therapeutics.

Emerging work indicates divergence in the neurobiologies of binge-eating disorder (BED) and obesity despite their frequent co-occurrence. This review highlights specific distinguishing aspects of BED, including elevated impulsivity and compulsivity possibly involving the mesocorticolimbic dopamine system, and discusses implications for differential therapeutics for BED. This narrative review describes epidemiologic, clinical, genetic, and preclinical differences between BED and obesity. Subsequently, this review discusses human neuroimaging work reporting differences in executive functioning, reward processing, and emotion reactivity in BED compared with obesity. Finally, on the basis of the neurobiology of BED, this review identifies existing and new therapeutic agents that may be most promising given their specific targets based on putative mechanisms of action relevant specifically to BED. BED is characterized by elevated impulsivity and compulsivity compared with obesity, which is reflected in divergent neurobiological characteristics and effective pharmacotherapies. Therapeutic agents that influence both reward and executive function systems may be especially effective for BED. Greater attention to impulsivity/compulsivity-related, reward-related, and emotion reactivity-related processes may enhance conceptualization and treatment approaches for patients with BED. Consideration of these distinguishing characteristics and processes could have implications for more targeted pharmacologic treatment research and interventions.

CognitiveConstruct

RewardProcessing

10.1371/journal.pcbi.1008410

PLoS computational biology

PLoS Comput Biol

Dopamine release, diffusion and uptake: A computational model for synaptic and volume transmission.

Computational modeling of dopamine transmission is challenged by complex underlying mechanisms. Here we present a new computational model that (I) simultaneously regards release, diffusion and uptake of dopamine, (II) considers multiple terminal release events and (III) comprises both synaptic and volume transmission by incorporating the geometry of the synaptic cleft. We were able to validate our model in that it simulates concentration values comparable to physiological values observed in empirical studies. Further, although synaptic dopamine diffuses into extra-synaptic space, our model reflects a very localized signal occurring on the synaptic level, i.e. synaptic dopamine release is negligibly recognized by neighboring synapses. Moreover, increasing evidence suggests that cognitive performance can be predicted by signal variability of neuroimaging data (e.g. BOLD). Signal variability in target areas of dopaminergic neurons (striatum, cortex) may arise from dopamine concentration variability. On that account we compared spatio-temporal variability in a simulation mimicking normal dopamine transmission in striatum to scenarios of enhanced dopamine release and dopamine uptake inhibition. We found different variability characteristics between the three settings, which may in part account for differences in empirical observations. From a clinical perspective, differences in striatal dopaminergic signaling contribute to differential learning and reward processing, with relevant implications for addictive- and compulsive-like behavior. Specifically, dopaminergic tone is assumed to impact on phasic dopamine and hence on the integration of reward-related signals. However, in humans DA tone is classically assessed using PET, which is an indirect measure of endogenous DA availability and suffers from temporal and spatial resolution issues. We discuss how this can lead to discrepancies with observations from other methods such as microdialysis and show how computational modeling can help to refine our understanding of DA transmission.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2020.536112

Frontiers in psychiatry

Front Psychiatry

Optimizing Behavioral Paradigms to Facilitate Development of New Treatments for Anhedonia and Reward Processing Deficits in Schizophrenia and Major Depressive Disorder: Study Protocol.

Behavioral tasks focusing on different subdomains of reward processing may provide more objective and quantifiable measures of anhedonia and impaired motivation compared with clinical scales. Typically, single tasks are used in relatively small studies to compare cases and controls in one indication, but they are rarely included in larger multisite trials. This is due to limited systematic standardization as well as the challenges of deployment in international studies and stringent adherence to the high regulatory requirements for data integrity. The Reward Task Optimization Consortium (RTOC) was formed to facilitate operational implementation of reward processing tasks, making them suitable for use in future large-scale, international, multisite drug development studies across multiple indications. The RTOC clinical study aims to conduct initial optimization of a set of tasks in patients with major depressive disorder (MDD) or schizophrenia (SZ). We will conduct a multicenter study across four EU countries. Participants (MDD = 37, SZ = 37, with ≤80 age- and gender-matched healthy volunteers) will attend a study visit comprising screening, self-report and clinically rated assessments of anhedonia and symptom severity, and three reward processing tasks; specifically, the Grip Strength Effort task, the Doors task, and the Reinforcement Learning Working Memory task. The Grip Strength Effort and Doors tasks include simultaneous electroencephalography/event-related potential recordings. Outcomes will be compared using a two-way group design of MDD and SZ with matched controls, respectively. Further analyses will include anhedonia assessment scores as covariates. Planned analyses will assess whether our findings replicate previously published data, and multisite deployment will be evaluated through assessments of quality and conduct. A subset of participants will complete a second visit, to assess test-retest reliability of the task battery. This study will evaluate the operational deployment of three reward processing tasks to the regulatory standards required for use in drug development trials. We will explore the potential of these tasks to differentiate patients from controls and to provide a quantitative marker of anhedonia and/or impaired motivation, establishing their usefulness as endpoints in multisite clinical trials. This study should demonstrate where multifaceted reward deficits are similar or divergent across patient populations. : ClinicalTrials.gov (NCT04024371).

CognitiveConstruct

RewardProcessing

10.1016/j.appet.2020.105055

Appetite

Appetite

Hierarchical integrated processing of reward-related regions in obese males: A graph-theoretical-based study.

Abnormal activities in reward-related regions are associated with overeating or obesity. Preliminary studies have shown that changes in neural activity in obesity include not only regional reward regions abnormalities but also impairments in the communication between reward-related regions and multiple functional areas. A recent study has shown that the transitions between different neural networks are nonrandom and hierarchical, and that activation of particular brain networks is more likely to occur after other brain networks. The aims of this study were to investigate the key nodes of reward-related regions in obese males and explore the hierarchical integrated processing of key nodes. Twenty-four obese males and 24 normal-weight male controls of similar ages were recruited. The fMRI data were acquired using 3.0 T MRI. The fMRI data preprocessing was performed in DPABI and SPM 12. Degree centrality analyses were conducted using GRETNA toolkit, and Granger causality analyses were calculated using DynamicBC toolbox. Decreased degree centrality was observed in left ventral medial prefrontal cortex (vmPFC) and right parahippocampal/hippocampal gyrus in group with obesity. The group with obesity demonstrated increased effective connectivity between left vmPFC and several regions (left inferior temporal gyrus, left supplementary motor area, right insular cortex, right postcentral gyrus, right paracentral lobule and bilateral fusiform gyrus). Increased effective connectivity was observed between right parahippocampal/hippocampal gyrus and left precentral/postcentral gyrus. Decreased effective connectivity was found between right parahippocampal/hippocampal gyrus and left inferior parietal lobule. This study identified the features of hierarchical interactions between the key reward nodes and multiple function networks. These findings may provide more evidence for the existing view of hierarchical organization in reward processing.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2020.565815

Frontiers in neuroscience

Front Neurosci

Cortical Patterns of Pleasurable Musical Chills Revealed by High-Density EEG.

Music has the capacity to elicit strong positive feelings in humans by activating the brain's reward system. Because group emotional dynamics is a central concern of social neurosciences, the study of emotion in natural/ecological conditions is gaining interest. This study aimed to show that high-density EEG (HD-EEG) is able to reveal patterns of cerebral activities previously identified by fMRI or PET scans when the subject experiences pleasurable musical chills. We used HD-EEG to record participants (11 female, 7 male) while listening to their favorite pleasurable chill-inducing musical excerpts; they reported their subjective emotional state from low pleasure up to chills. HD-EEG results showed an increase of theta activity in the prefrontal cortex when arousal and emotional ratings increased, which are associated with orbitofrontal cortex activation localized using source localization algorithms. In addition, we identified two specific patterns of chills: a decreased theta activity in the right central region, which could reflect supplementary motor area activation during chills and may be related to rhythmic anticipation processing, and a decreased theta activity in the right temporal region, which may be related to musical appreciation and could reflect the right superior temporal gyrus activity. The alpha frontal/prefrontal asymmetry did not reflect the felt emotional pleasure, but the increased frontal beta to alpha ratio (measure of arousal) corresponded to increased emotional ratings. These results suggest that EEG may be a reliable method and a promising tool for the investigation of group musical pleasure through musical reward processing.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsaa155

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Neural Indicators Of Food Cue Reactivity, Regulation, And Valuation And Their Associations With Body Composition And Daily Eating Behavior.

Exposure to food cues activates the brain's reward system and undermines efforts to regulate impulses to eat. During explicit regulation, lateral prefrontal cortex activates and modulates activity in reward regions and decreases food cravings. However, it is unclear the extent to which between-person differences in recruitment of regions associated with reward processing, subjective valuation, and regulation during food cue exposure-absent instructions to regulate-predict body composition and daily eating behaviors. In this preregistered study, we pooled data from five fMRI samples (N = 262) to examine whether regions associated with reward, valuation, and regulation, as well as whole-brain pattern expression indexing these processes, were recruited during food cue exposure and associated with body composition and real-world eating behavior. Regression models for a single a priori analytic path indicated that univariate and multivariate measures of reward and valuation were associated with individual differences in BMI and enactment of daily food cravings. Specification curve analyses further revealed reliable associations between univariate and multivariate neural indicators of reactivity, regulation, and valuation, and all outcomes. These findings highlight the utility of these methods to elucidate brain-behavior associations and suggest that multiple processes are implicated in proximal and distal markers of eating behavior.

CognitiveConstruct

RewardProcessing

10.1111/jcpp.13347

Journal of child psychology and psychiatry, and allied disciplines

J Child Psychol Psychiatry

Heightened sensitivity to the caregiving environment during adolescence: implications for recovery following early-life adversity.

Adolescence has been proposed to be a period of heightened sensitivity to environmental influence. If true, adolescence may present a window of opportunity for recovery for children exposed to early-life adversity. Recent evidence supports adolescent recalibration of stress response systems following early-life adversity. However, it is unknown whether similar recovery occurs in other domains of functioning in adolescence. We use data from the Bucharest Early Intervention Project - a randomized controlled trial of foster care for children raised in psychosocially depriving institutions - to examine the associations of the caregiving environment with reward processing, executive functioning, and internalizing and externalizing psychopathology at ages 8, 12, and 16 years, and evaluate whether these associations change across development. Higher quality caregiving in adolescence was associated with greater reward responsivity and lower levels of internalizing and externalizing symptoms, after covarying for the early-life caregiving environment. The associations of caregiving with executive function and internalizing and externalizing symptoms varied by age and were strongest at age 16 relative to ages 8 and 12 years. This heightened sensitivity to caregiving in adolescence was observed in both children with and without exposure to early psychosocial neglect. Adolescence may be a period of heightened sensitivity to the caregiving environment, at least for some domains of functioning. For children who experience early psychosocial deprivation, this developmental period may be a window of opportunity for recovery of some functions. Albeit correlational, these findings suggest that it may be possible to reverse or remediate some of the lasting effects of early-life adversity with interventions that target caregiving during adolescence.

CognitiveConstruct

RewardProcessing

10.20900/jpbs.20200024

Journal of psychiatry and brain science

J Psychiatr Brain Sci

The Role of Social Reward and Corticostriatal Connectivity in Substance Use.

This report describes an ongoing R03 grant that explores the links between trait reward sensitivity, substance use, and neural responses to social and nonsocial reward. Although previous research has shown that trait reward sensitivity and neural responses to reward are linked to substance use, whether this relationship is impacted by how people process social stimuli remains unclear. We are investigating these questions via a neuroimaging study with college-aged participants, using individual difference measures that examine the relation between substance use, social context, and trait reward sensitivity with tasks that measure reward anticipation, strategic behavior, social reward consumption, and the influence of social context on reward processing. We predict that substance use will be tied to distinct patterns of striatal dysfunction. Specifically, reward hyposensitive individuals will exhibit blunted striatal responses to social and non-social reward and enhanced connectivity with the orbitofrontal cortex; in contrast, reward hypersensitive individuals will exhibit enhanced striatal responses to social and non-social reward and blunted connectivity with the orbitofrontal cortex. We also will examine the relation between self-reported reward sensitivity, substance use, and striatal responses to social reward and social context. We predict that individuals reporting the highest levels of substance use will show exaggerated striatal responses to social reward and social context, independent of self-reported reward sensitivity. Examining corticostriatal responses to reward processing will help characterize the relation between reward sensitivity, social context and substance use while providing a foundation for understanding risk factors and isolating neurocognitive mechanisms that may be targeted to increase the efficacy of interventions.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0242573

PloS one

PLoS One

Game-based learning environments affect frontal brain activity.

Inclusion of game elements in learning environments to increase motivation and learning outcome is becoming increasingly popular. However, underlying mechanisms of game-based learning have not been studied sufficiently yet. In the present study, we investigated effects of game-based learning environments on a neurofunctional level. In particular, 59 healthy adults completed a game-based version (including game elements such as a narrative and virtual incentives) as well as a non-game-based version of a number line estimation task, to improve fractional knowledge, while their brain activity was monitored using near-infrared spectroscopy. Behavioral performance was comparable across the two versions, although there was a tendency that less errors were made in the game-based version. However, subjective user experience differed significantly between versions. Participants rated the game-based version as more attractive, novel, and stimulating but less efficient than the non-game-based version. Additionally, positive affect was reported to be higher while engaging in the game-based as compared to the non-game-based task version. Corroborating these user reports, we identified increased brain activation in areas associated with emotion and reward processing while playing the game-based version, which might be driven by rewarding elements of the game-based version. Moreover, frontal areas associated with attention were also more activated in the game-based version of the task. Hence, we observed converging evidence on a user experience and neurofunctional level indicating that the game-based version was more rewarding as well as emotionally and attentionally engaging. These results underscore the potential of game-based learning environments to promote more efficient learning by means of attention and reward up-tuning.

CognitiveConstruct

RewardProcessing

10.1038/s41598-020-76934-1

Scientific reports

Sci Rep

Experimental sleep disruption attenuates morphine analgesia: findings from a randomized trial and implications for the opioid abuse epidemic.

Preclinical studies demonstrate that sleep disruption diminishes morphine analgesia and modulates reward processing. We sought to translate these preclinical findings to humans by examining whether sleep disruption alters morphine's analgesic and hedonic properties. We randomized 100 healthy adults to receive morphine versus placebo after two nights of undisturbed sleep (US) and two nights of forced awakening (FA) sleep disruption. Sleep conditions were counterbalanced, separated by a two-week washout. The morning after both sleep conditions, we tested cold pressor pain tolerance before and 40-min after double-blind injection of .08 mg/kg morphine or placebo. The primary outcome was the analgesia index, calculated as the change in cold pressor hand withdrawal latency (HWL) before and after drug injection. Secondary outcomes were ratings of feeling "high," drug "liking," and negative drug effects. We found a significant sleep condition by drug interaction on the analgesia index (95% CI - 0.57, - 0.001). After US, subjects receiving morphine demonstrated significantly longer HWL compared to placebo (95% CI 0.23, 0.65), but not after FA (95% CI - 0.05, 0.38). Morphine analgesia was diminished threefold under FA, relative to US. After FA, females (95% CI - 0.88, - 0.05), but not males (95% CI - 0.23, 0.72), reported decreased subjective "high" effects compared to US. After FA, females (95% CI 0.05, 0.27), but not males (95% CI - 0.10, 0.11), administered morphine reported increased negative drug effects compared to US. These data demonstrate that sleep disruption attenuates morphine analgesia in humans and suggest that sleep disturbed males may be at greatest risk for problematic opioid use.

CognitiveConstruct

RewardProcessing

10.1176/appi.ajp.2020.20050635

The American journal of psychiatry

Am J Psychiatry

Association of Inflammatory Activity With Larger Neural Responses to Threat and Reward Among Children Living in Poverty.

Children exposed to severe, chronic stress are vulnerable to mental and physical health problems across the lifespan. To explain how these problems develop, the neuroimmune network hypothesis suggests that early-life stress initiates a positive feedback loop between peripheral inflammatory cells and networked brain regions involved in threat and reward processing. The authors sought to test this hypothesis by studying a sample of urban children from diverse socioeconomic backgrounds. The authors examined the basic predictions of the neuroimmune network hypothesis in 207 children (mean age=13.9 years, 63% female; 33% Black; 30% Hispanic), focusing on poverty as a stressor. The children had fasting blood drawn to quantify five inflammatory biomarkers-C-reactive protein, tumor necrosis factor-α, and interleukins-6, -8, and -10-which were averaged to form a composite score. Children also completed two functional MRI tasks, which measured amygdala responsivity to angry facial expressions and ventral striatum responsivity to monetary rewards. Poverty status and neural responsivity interacted statistically to predict inflammation. Among children living in poverty, amygdala threat responsivity was positively associated with inflammation, and the same was true for ventral striatum responsivity to reward. As children's socioeconomic conditions improved, these brain-immune associations became weaker. In sensitivity analyses, these patterns were robust to alternative measures of socioeconomic status and were independent of age, sex, racial and ethnic identity, and pubertal status. The associations were also condition specific; no interactions were apparent for amygdala responsivity to neutral faces, or striatal responsivity to monetary losses. These findings suggest that childhood poverty is associated with accentuated neural-immune signaling, consistent with the neuroimmune network hypothesis.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2020.11.004

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

Using pharmacological manipulations to study the role of dopamine in human reward functioning: A review of studies in healthy adults.

Dopamine (DA) plays a key role in reward processing and is implicated in psychological disorders such as depression, substance use, and schizophrenia. The role of DA in reward processing is an area of highly active research. One approach to this question is drug challenge studies with drugs known to alter DA function. These studies provide good experimental control and can be performed in parallel in laboratory animals and humans. This review aimed to summarize results of studies using pharmacological manipulations of DA in healthy adults. 'Reward' is a complex process, so we separated 'phases' of reward, including anticipation, evaluation of cost and benefits of upcoming reward, execution of actions to obtain reward, pleasure in response to receiving a reward, and reward learning. Results indicated that i) DAergic drugs have different effects on different phases of reward; ii) the relationship between DA and reward functioning appears unlikely to be linear; iii) our ability to detect the effects of DAergic drugs varies depending on whether subjective, behavioral, imaging measures are used.

CognitiveConstruct

RewardProcessing

10.1016/j.jpsychires.2020.11.008

Journal of psychiatric research

J Psychiatr Res

Frontoparietal hyperconnectivity during cognitive regulation in obsessive-compulsive disorder followed by reward valuation inflexibility.

Obsessive-compulsive disorder (OCD) is characterized by cognitive deficits and altered reward processing systems. An imbalance between cognitive and reward pathways may explain the lack of control over obsessions followed by rewarding compulsive behaviors. While the processes of emotional cognitive regulation are widely studied in OCD, the mechanisms of cognitive regulation of reward are poorly described. Our goal was to investigate the OCD impact on cognitive regulation of reward at behavioral and neural functioning levels. OCD and control participants performed a functional magnetic resonance imaging task where they cognitively modulated their craving for food pictures under three cognitive regulation conditions: indulge/increase craving, distance/decrease craving, and natural/no regulation of craving. After regulation, the participants gave each picture a monetary value. We found that OCD patients had fixed food valuation scores while the control group modulated these values accordingly to the regulation conditions. Moreover, we observed frontoparietal hyperconnectivity during cognitive regulation. Our results suggest that OCD is characterized by deficits in cognitive regulation of internal states associated with inflexible behavior during reward processing. These findings bring new insights into the nature of compulsive behaviors in OCD.

CognitiveConstruct

RewardProcessing

10.1038/s41386-020-00896-1

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Effects of substance misuse on reward-processing in patients with attention-deficit/hyperactivity disorder.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use Disorder (SUD) often co-occur and are associated with treatment resistance. Both disorders are characterized by similar reward-processing deficits with decreased striatal responses to reward anticipation, though literature is inconsistent. It is unclear whether substance misuse exaggerates reward-processing deficits observed in ADHD. The aim of this study was to examine substance misuse effects on reward-processing in ADHD. Functional MRI data in a Monetary Incentive Delay (MID) task from a multi-site study were compared across ADHD groups with and without substance misuse (ADHD + SM and ADHD-only, respectively) and healthy controls (n = 40/group, 74 males and 46 females, aged 13.7-25.9 years). Substance misuse was defined as misuse of alcohol, nicotine, or drugs. Groups were matched with presence/absence of parental SUD to avoid interference with SUD trait effects. Compared to ADHD-only and controls, ADHD + SM showed hyperactivation in putamen during reward anticipation. Compared to controls, the ADHD groups showed hypoactivation in motor/sensory cortices and hyperactivation in frontal pole and OFC during reward outcome. ADHD + SM also showed hyperactivation in frontal pole during neutral outcome. Moreover, ADHD + SM patients showed higher callous-unemotional (CU) traits that were positively correlated with putamen responses to reward anticipation. Our results show distinct condition-independent neural activation profile for ADHD + SM compared to ADHD-only and controls. Effects of comorbid substance misuse and variability of its prevalence across ADHD studies might have contributed to inconsistencies in ADHD literature. Contrasted with findings for reward-processing in SUD literature, results potentially suggest distinct underlying mechanisms for SUD subgroups with different characteristics, like antisocial/psychopathic traits.

CognitiveConstruct

RewardProcessing

10.3390/diagnostics10110930

Diagnostics (Basel, Switzerland)

Diagnostics (Basel)

Cognitive Fatigue Is Associated with Altered Functional Connectivity in Interoceptive and Reward Pathways in Multiple Sclerosis.

Cognitive fatigue is common and debilitating among persons with multiple sclerosis (pwMS). Neural mechanisms underlying fatigue are not well understood, which results in lack of adequate treatment. The current study examined cognitive fatigue-related functional connectivity among 26 pwMS and 14 demographically matched healthy controls (HCs). Participants underwent functional magnetic resonance imaging (fMRI) scanning while performing a working memory task (n-back), with two conditions: one with higher cognitive load (2-back) to induce fatigue and one with lower cognitive load (0-back) as a control condition. Task-independent residual functional connectivity was assessed, with seeds in brain regions previously implicated in cognitive fatigue (dorsolateral prefrontal cortex (DLPFC), ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), insula, and striatum). Cognitive fatigue was measured using the Visual Analogue Scale of Fatigue (VAS-F). Results indicated that as VAS-F scores increased, HCs showed increased residual functional connectivity between the striatum and the vmPFC (crucial in reward processing) during the 2-back condition compared to the 0-back condition. In contrast, pwMS displayed increased residual functional connectivity from interoceptive hubs-the insula and the dACC-to the striatum. In conclusion, pwMS showed a hyperconnectivity within the interoceptive network and disconnection within the reward circuitry when experiencing cognitive fatigue.

CognitiveConstruct

RewardProcessing

10.1177/1352458520972279

Multiple sclerosis (Houndmills, Basingstoke, England)

Mult Scler

Fatigue, depression, and pain in multiple sclerosis: How neuroinflammation translates into dysfunctional reward processing and anhedonic symptoms.

Fatigue, depression, and pain affect the majority of multiple sclerosis (MS) patients, which causes a substantial burden to patients and society. The pathophysiology of these symptoms is not entirely clear, and current treatments are only partially effective. Clinically, these symptoms share signs of anhedonia, such as reduced motivation and a lack of positive affect. In the brain, they are associated with overlapping structural and functional alterations in areas involved in reward processing. Moreover, neuroinflammation has been shown to directly impede monoaminergic neurotransmission that plays a key role in reward processing. Here, we review recent neuroimaging and neuroimmunological findings, which indicate that dysfunctional reward processing might represent a shared functional mechanism fostering the symptom cluster of fatigue, depression, and pain in MS. We propose a framework that integrates these findings with a focus on monoaminergic neurotransmission and discuss its therapeutic implications, limitations, and perspectives.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2020.590528

Frontiers in behavioral neuroscience

Front Behav Neurosci

Heterogeneity in the Paraventricular Thalamus: The Traffic Light of Motivated Behaviors.

The paraventricular thalamic nucleus (PVT) is highly interconnected with brain areas that control reward-seeking behavior. Despite this known connectivity, broad manipulations of PVT often lead to mixed, and even opposing, behavioral effects, clouding our understanding of how PVT precisely contributes to reward processing. Although the function of PVT in influencing reward-seeking is poorly understood, recent studies show that forebrain and hypothalamic inputs to, and nucleus accumbens (NAc) and amygdalar outputs from, PVT are strongly implicated in PVT responses to conditioned and appetitive or aversive stimuli that determine whether an animal will approach or avoid specific rewards. These studies, which have used an array of chemogenetic, optogenetic, and calcium imaging technologies, have shown that activity in PVT input and output circuits is highly heterogeneous, with mixed activity patterns that contribute to behavior in highly distinct manners. Thus, it is important to perform experiments in precisely defined cell types to elucidate how the PVT network contributes to reward-seeking behaviors. In this review, we describe the complex heterogeneity within PVT circuitry that appears to influence the decision to seek or avoid a reward and point out gaps in our understanding that should be investigated in future studies.

CognitiveConstruct

RewardProcessing

10.3389/fnsys.2020.562154

Frontiers in systems neuroscience

Front Syst Neurosci

Differential Expression of DeltaFosB in Reward Processing Regions Between Binge Eating Prone and Resistant Female Rats.

Binge eating (BE) is characterized by the consumption of large amounts of palatable food in a discrete period and compulsivity. Even though BE is a common symptom in bulimia nervosa (BN), binge eating disorder (BED), and some cases of other specified feeding or eating disorders, little is known about its pathophysiology. We aimed to identify brain regions and neuron subtypes implicated in the development of binge-like eating in a female rat model. We separated rats into binge eating prone (BEP) and binge eating resistant (BER) phenotypes based on the amount of sucrose they consumed following foot-shock stress. We quantified deltaFosB (ΔFosB) expression, a stably expressed Fos family member, in different brain regions involved in reward, taste, or stress processing, to assess their involvement in the development of the phenotype. The number of ΔFosB-expressing neurons was: (1) higher in BEP than BER rats in reward processing areas [medial prefrontal cortex (mPFC), nucleus accumbens (Acb), and ventral tegmental area (VTA)]; (2) similar in taste processing areas [insular cortex, IC and parabrachial nucleus (PBN)]; and (3) higher in the paraventricular nucleus of BEP than BER rats, but not different in the locus coeruleus (LC), which are stress processing structures. To study subtypes of ΔFosB-expressing neurons in the reward system, we performed hybridization for glutamate decarboxylase 65 and tyrosine hydroxylase (TH) mRNA after ΔFosB immunohistochemistry. In the mPFC and Acb, the proportions of γ-aminobutyric acidergic (GABAergic) and non-GABAergic ΔFosB-expressing neurons were similar in BER and BEP rats. In the VTA, while the proportion of dopaminergic ΔFosB-expressing neurons was similar in both phenotypes, the proportion of GABAergic ΔFosB-expressing neurons was higher in BER than BEP rats. Our results suggest that reward processing brain regions, particularly the VTA, are important for the development of binge-like eating.

CognitiveConstruct

RewardProcessing

10.1152/jn.00495.2020

Journal of neurophysiology

J Neurophysiol

The tubular striatum and nucleus accumbens distinctly represent reward-taking and reward-seeking.

The ventral striatum regulates motivated behaviors that are essential for survival. The ventral striatum contains both the nucleus accumbens (NAc), which is well established to contribute to motivated behavior, and the adjacent tubular striatum (TuS), which is poorly understood in this context. We reasoned that these ventral striatal subregions may be uniquely specialized in their neural representation of goal-directed behavior. To test this, we simultaneously examined TuS and NAc single-unit activity as male mice engaged in a sucrose self-administration task, which included extinction and cue-induced reinstatement sessions. Although background levels of activity were comparable between regions, more TuS neurons were recruited upon reward-taking, and among recruited neurons, TuS neurons displayed greater changes in their firing during reward-taking and extinction than those in the NAc. Conversely, NAc neurons displayed greater changes in their firing during cue-reinstated reward-seeking. Interestingly, at least in the context of this behavioral paradigm, TuS neural activity predicted reward-seeking, whereas NAc activity did not. Together, by directly comparing their dynamics in several behavioral contexts, this work reveals that the NAc and TuS ventral striatum subregions distinctly represent reward-taking and reward-seeking. The ventral striatum, considered the reward circuitry "hub," is composed of two regions: the NAc, which is well established for its role in reward processing, and the TuS, which has been largely excluded from such studies. This study provides a first step in directly contextualizing the TuS's activity in relation to that in the NAc and, by doing so, establishes a critical framework for future research seeking to better understand the brain basis for drug addiction.

CognitiveConstruct

RewardProcessing

10.1007/s11065-020-09459-z

Neuropsychology review

Neuropsychol Rev

A Systematic Review of the Positive Valence System in Autism Spectrum Disorder.

This review synthesized current literature of behavioral and cognitive studies targeting reward processing in autism spectrum disorder (ASD). The National Institute of Mental Health's Research Domain Criteria (RDoC) Positive Valence System (PVS) domain was used as an overarching framework. The objectives were to determine which component operations of reward processing may be atypical in ASD and consequently postulate a heuristic model of reward processing in ASD that could be evaluated with future research. 34 studies were identified from the Embase, PubMed, PsycINFO, and Web of Science databases and included in the review using guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (also known as PRISMA guidelines). The extant literature suggested potential relationships between social symptoms of ASD and PVS sub-constructs of reward anticipation, probabilistic and reinforcement learning, reward prediction error, reward (probability), delay, and effort as well as between restricted and repetitive behaviors and interests (RRBIs) and PVS-sub constructs of initial response to reward, reward anticipation, reward (probability), delay, and effort. However, these findings are limited by a sparse and mixed literature for some sub-constructs. We put forward a developmentally informed heuristic model that posits how these component reward processes may be implicated in early ASD behaviors as well as later emerging and more intransigent symptoms. Future research is needed to comprehensively evaluate the proposed model.

CognitiveConstruct

RewardProcessing

10.1111/bph.15319

British journal of pharmacology

Br J Pharmacol

Chronic fluoxetine treatment impairs motivation and reward learning by affecting neuronal plasticity in the central amygdala.

The therapeutic effects of fluoxetine are believed to be due to increasing neuronal plasticity and reversing some learning deficits. Nevertheless, a growing amount of evidence shows adverse effects of this drug on cognition and some forms of neuronal plasticity. To study the effects of chronic fluoxetine treatment, we combine an automated assessment of motivation and learning in mice with an investigation of neuronal plasticity in the central amygdala and basolateral amygdala. We use immunohistochemistry to visualize neuronal types and perineuronal nets, along with DI staining to assess dendritic spine morphology. Gel zymography is used to test fluoxetine's impact on matrix metalloproteinase-9, an enzyme involved in synaptic plasticity. We show that chronic fluoxetine treatment in non-stressed mice increases perineuronal nets-dependent plasticity in the basolateral amygdala, while impairing MMP-9-dependent plasticity in the central amygdala. Further, we illustrate how the latter contributes to anhedonia and deficits of reward learning. Behavioural impairments are accompanied by alterations in morphology of dendritic spines in the central amygdala towards an immature state, most likely reflecting animals' inability to adapt. We strengthen the link between the adverse effects of fluoxetine and its influence on MMP-9 by showing that behaviour of MMP-9 knockout animals remains unaffected by the drug. Chronic fluoxetine treatment differentially affects various forms of neuronal plasticity, possibly explaining its opposing effects on brain and behaviour. These findings are of immediate clinical relevance since reported side effects of fluoxetine pose a potential threat to patients.

CognitiveConstruct

RewardProcessing

10.1002/da.23104

Depression and anxiety

Depress Anxiety

Multimodal structural neuroimaging markers of risk and recovery from posttrauma anhedonia: A prospective investigation.

Anhedonic symptoms of posttraumatic stress disorder (PTSD) reflect deficits in reward processing that have significant functional consequences. Although recent evidence suggests that disrupted integrity of fronto-limbic circuitry is related to PTSD development, including anhedonic PTSD symptoms (posttrauma anhedonia [PTA]), little is known about potential structural biomarkers of long-term PTA as well as structural changes in fronto-limbic pathways associated with recovery from PTA over time. We investigated associations between white matter microstructure, gray matter volume, and PTA in 75 recently traumatized individuals, with a subset of participants (n = 35) completing follow-up assessment 12 months after trauma exposure. Deterministic tractography and voxel-based morphometry were used to assess changes in white and gray matter structure associated with changes in PTA. Reduced fractional anisotropy (FA) of the uncinate fasciculus at around the time of trauma predicted greater PTA at 12-months posttrauma. Further, increased FA of the fornix over time was associated with lower PTA between 1 and 12-months posttrauma. Increased gray matter volume of the ventromedial prefrontal cortex and precuneus over time was also associated with reduced PTA. The microstructure of the uncinate fasciculus, an amygdala-prefrontal white matter connection, may represent a biomarker of vulnerability for later PTA. Conversely, development and recovery from PTA appear to be facilitated by white and gray matter structural changes in a major hippocampal pathway, the fornix. The present findings shed new light on neuroanatomical substrates of recovery from PTA and characterize white matter biomarkers of risk for posttraumatic dysfunction.

CognitiveConstruct

RewardProcessing

10.4103/psychiatry.IndianJPsychiatry_103_20

Indian journal of psychiatry

Indian J Psychiatry

Integrated intervention program for alcoholism improves impulsiveness and disadvantageous reward processing/risk-taking.

Impulsivity and aberrant reward processing are the core features of substance use disorders, including alcoholism. The present study examined the effects of an Integrated Intervention Program for Alcoholism (IIPA) on impulsiveness and disadvantageous reward processing/risk-taking in persons with alcoholism. The study adopted age- and education-matched (±1 year) randomized control design with the pre-post comparison. The sample comprised 50 persons with alcoholism. They were allotted randomly into two groups, the intervention (IIPA) group and treatment as usual (TAU) group ( = 25 in each). Participants were assessed at pre-intervention on impulsivity (Barratt's Impulsiveness Scale) and decision-making task, which reflects reward processing deficits (modified Iowa gambling task [mIGT]). The TAU group received usual treatment for alcoholism (i.e., pharmacotherapy; three sessions in a week group therapy on relapse prevention and six sessions in week yoga) for 18 days. The intervention group received IIPA along with usual treatment (except yoga). Outcome assessment was repeated after 18 days of intervention. Both groups were comparable at pre-intervention (baseline). However, the intervention (IIPA) group showed a significant reduction in impulsivity and selection from disadvantageous decks on mIGT at post-intervention, while the TAU group had no significant change. The findings suggest that IIPA could improve impulsivity and disadvantageous reward processing/risk-taking in persons with alcoholism. These are core features of substance use disorders and could pose a high chance for relapse after treatment. Further studies may examine improving these characteristics with IIPA and its impact on treatment outcomes such as relapse rate and maintaining sobriety.

CognitiveConstruct

RewardProcessing

10.1097/WNR.0000000000001545

Neuroreport

Neuroreport

Glucagon-like peptide-1 receptors modulate the binge-like feeding induced by µ-opioid receptor stimulation of the nucleus accumbens in the rat.

Neuropeptides and peptide hormones affect food-directed motivation, in part, through actions on brain regions associated with reward processing. For instance, previous reports have shown that stimulating glucagon-like peptide-1 (GLP-1) receptors in the nucleus accumbens (NAc), an area that directs motivational processes towards food and drugs of abuse, has an anorectic effect. In contrast, µ-opioid receptor activation of the NAc increases feeding, particularly on highly palatable diets. While both neurotransmitters act within the NAc to impact food intake, it is not clear if and how they might interact to affect feeding. Therefore, these experiments tested the effects of NAc injections of the GLP-1 receptor agonist Exendin 4 (EX4) or antagonist Exendin 9 (EX9) on the consumption of a sweetened fat diet, with and without simultaneous µ-opioid receptor stimulation. Male Sprague-Dawley rats (n = 8/group, EX4 or EX9) underwent surgery to place bilateral cannula above the NAc core. After recovery, animals were tested following NAc injections of saline or the µ-opioid agonist [D-Ala, N-MePhe, Gly-ol]-enkephalin (DAMGO) (0.025 µg/side), combined with varying doses of EX4 (0, 0.05, or 0.10 µg/side) or EX9 (0, 2.5, 5.0 µg/side), counterbalanced across 6 testing days. Food and water intake, along with locomotor activity, was monitored for 2 h. Mu-opioid receptor stimulation significantly increased feeding, and this effect was reduced by GLP-1 receptor stimulation. In contrast, GLP-1 antagonism with EX9 altered the dynamics of DAMGO-induced binge-like feeding, extending µ-opioid-induced binging, and increasing food consumption. These findings are the first to demonstrate an interaction between NAc µ-opioid and GLP-1 receptors on palatable food intake.

CognitiveConstruct

RewardProcessing