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10.1016/j.ijpsycho.2018.12.009

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

Int J Psychophysiol

Temporal dynamics of hedonic and eudaimonic reward processing: An event-related potentials (ERPs) study.

Reward or pleasure can be achieved from a hedonic approach (pleasure attainment) or eudaimonic approach (meaning and self-realization). However, the neurodynamics of hedonic and eudaimonic reward processing remain unclear. By operationalizing hedonic reward as "win money for oneself" and eudaimonic reward as "win money for charity", the current study used the monetary incentive delay task to parse hedonic and eudaimonic reward dynamics into the anticipatory and consummatory stages while event-related potentials (ERPs) were recorded. 24 participants (12 women) were recruited in this study. The results showed that in the anticipatory stage, the amplitudes evoked by hedonic and eudaimonic reward did not differ during early cue recognition (P2, N2), but they separated during late cue elaboration (cue-P3). In the consummatory stage, hedonic reward elicited a larger FRN effect, but eudaimonic reward elicited a larger fb-P3 effect. In addition, we also used the neural indices of hedonic and eudaimonic reward processing to predict participants' longitudinal changes in well-being (depression and positive emotion) across 6 months as exploratory in nature. Preliminary regression evidence suggested that greater differential amplitude of cue-P3 elicited by eudaimonic reward anticipation versus neutral anticipation positively predicted longitudinal increases in positive emotion. The findings elucidated specific substages of hedonic and eudaimonic reward processing and explored their potential roles in longitudinal changes in well-being.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsy116

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

A key role for stimulus-specific updating of the sensory cortices in the learning of stimulus-reward associations.

Successful adaptive behavior requires the learning of associations between stimulus-specific choices and rewarding outcomes. Most research on the mechanisms underlying such processes has focused on subcortical reward-processing regions, in conjunction with frontal circuits. Given the extensive stimulus-specific coding in the sensory cortices, we hypothesized they would play a key role in the learning of stimulus-specific reward associations. We recorded electrical brain activity (using electroencephalogram) during a learning-based decision-making gambling task where, on each trial, participants chose between a face and a house and then received feedback (gain or loss). Within each 20-trial set, either faces or houses were more likely to predict a gain. Results showed that early feedback processing (~200-1200 ms) was independent of the choice made. In contrast, later feedback processing (~1400-1800 ms) was stimulus-specific, reflected by decreased alpha power (reflecting increased cortical activity) over face-selective regions, for winning-vs-losing after a face choice but not after a house choice. Finally, as the reward association was learned in a set, there was an increasingly stronger attentional bias towards the more likely winning stimulus, reflected by increasing attentional orienting-related brain activity and increasing likelihood of choosing that stimulus. These results delineate the processes underlying the updating of stimulus-reward associations during feedback-guided learning, which then guide future attentional allocation and decision-making.

CognitiveConstruct

RewardProcessing

10.1016/j.appet.2018.12.017

Appetite

Appetite

Food vs money? Effects of hunger on mood and behavioral reactivity to reward in anorexia nervosa.

Previous studies using neuroimaging and behavioral measures reported altered reward processing in anorexia nervosa (AN). In addition, anhedonia states are frequently reported in AN, potentially due to the physiological stress produced by the permanent starvation. We investigated the effect of fasting and satiety on mood and reaction times to monetary rewards in AN patients and healthy controls. Twenty-four participants with acute AN (BMI 14.4 (11.9-15.5) Kg/m) and 17 age and gender matched healthy, normal weight subjects (HW) (BMI 21.8 (18.9-24.9) Kg/m) performed a reward task (the wheel of fortune) involving uncertain (50/50 probability of winning high and low rewards), safe and risky (30/70 and 10/90 probabilities) categories in fasted (after an 8-h fasting period) and fed (after intake of a standardized meal) states. Data analysis was done with linear mixed models. AN reacted slower than HW when maximum uncertainty (50/50) was involved. Positive mood in response to winning was higher when fasting especially for HW, while negative mood in response to not winning was higher in the fed state for both groups. Still, HW were more reactive than AN to not winning a highly predictable monetary reward (10/90 safe). The data on the reaction times indicate an impaired motor response to uncertainty in AN. Mood reactivity to winning a monetary reward does not seem to be impaired in AN, however, our results suggest that negative mood in response to not winning is less adaptive in AN. Implications to clinical psychotherapy are discussed.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2018.00643

Frontiers in psychiatry

Front Psychiatry

Deformation-based Morphometry MRI Reveals Brain Structural Modifications in Living Mu Opioid Receptor Knockout Mice.

Mu opioid receptor (MOR) activation facilitates reward processing and reduces pain, and brain networks underlying these effects are under intense investigation. Mice lacking the MOR gene (MOR KO mice) show lower drug and social reward, enhanced pain sensitivity and altered emotional responses. Our previous neuroimaging analysis using Resting-state (Rs) functional Magnetic Resonance Imaging (fMRI) showed significant alterations of functional connectivity (FC) within reward/aversion networks in these mice, in agreement with their behavioral deficits. Here we further used a structural MRI approach to determine whether volumetric alterations also occur in MOR KO mice. We acquired anatomical images using a 7-Tesla MRI scanner and measured deformation-based morphometry (DBM) for each voxel in subjects from MOR KO and control groups. Our analysis shows marked anatomical differences in mutant animals. We observed both local volumetric contraction (striatum, nucleus accumbens, bed nucleus of the stria terminalis, hippocampus, hypothalamus and periacqueducal gray) and expansion (prefrontal cortex, amygdala, habenula, and periacqueducal gray) at voxel level. Volumetric modifications occurred mainly in MOR-enriched regions and across reward/aversion centers, consistent with our prior FC findings. Specifically, several regions with volume differences corresponded to components showing highest FC changes in our previous Rs-fMRI study, suggesting a possible function-structure relationship in MOR KO-related brain differences. In conclusion, both Rs-fMRI and volumetric MRI in live MOR KO mice concur to disclose functional and structural whole-brain level mechanisms that likely drive MOR-controlled behaviors in animals, and may translate to MOR-associated endophenotypes or disease in humans.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2018.00640

Frontiers in psychiatry

Front Psychiatry

Systemic Administration of Orexin a Loaded Liposomes Potentiates Nucleus Accumbens Shell Dopamine Release by Sucrose Feeding.

Orexin neurons originate in the lateral and dorsomedial hypothalamus and perifornical area and produce two different neuropeptides: orexin A (OxA) and orexin B (OxB), which activate OxR1 and OxR2 receptors. In the lateral hypothalamus (LH) orexin neurons are involved in behavior motivated by natural rewards such as palatable food (sugar, high-fat food) and it has been demonstrated similarly that the orexin signaling in the ventral tegmental area (VTA) is implicated in the intake of high-fat food. The VTA is an important area involved in reward processing. Given the involvement of nucleus accumbens (NAc) shell dopamine (DA) in motivation for food, we intended to investigate the effect of OxA on the basal and feeding-activated DA transmission in the NAc shell. OxA is a large peptide and does not cross the blood-brain barrier and for this reason was loaded on two kinds of liposomes: anti-transferrin-monoclonal antibodies (OX26-mAb) and lactoferrin-modified stealth liposomes. The effect of IV administration of both OxA liposomes on NAc shell DA was studied by microdialysis in freely moving rats. OxA, administered using both kinds of liposomes, produced a delayed and transitory increase in dialysate DA in the NAc shell, strongly and lastingly potentiated the increase in dialysate DA elicited by sucrose pellet consumption and increased the number of eaten pellets. These effects of OxA on DA transmission and feeding were prevented by the OxR1 antagonist SB 334867. Hence, OxA acting on VTA OxR1 can facilitate sucrose-stimulated NAc shell DA transmission directly by increasing the basal activity of VTA DA neurons that send their projections to the NAc shell.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.0250-18.2018

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

J Neurosci

Sleep Deprivation Selectively Upregulates an Amygdala-Hypothalamic Circuit Involved in Food Reward.

Sleep loss is associated with increased obesity risk, as demonstrated by correlations between sleep duration and change in body mass index or body fat percentage. Whereas previous studies linked this weight gain to disturbed endocrine parameters after sleep deprivation or restriction, neuroimaging studies revealed upregulated neural processing of food rewards after sleep loss in reward-processing areas such as the anterior cingulate cortex, ventral striatum, and insula. To address this ongoing debate between hormonal versus hedonic factors underlying sleep-loss-associated weight gain, we rigorously tested the association between sleep deprivation and food cue processing using high-resolution fMRI and assessment of hormones. After taking blood samples from 32 lean, healthy, human male participants, they underwent fMRI while performing a neuroeconomic, value-based decision-making task with snack food and trinket rewards following a full night of habitual sleep and a night of sleep deprivation in a repeated-measures crossover design. We found that des-acyl ghrelin concentrations were increased after sleep deprivation compared with habitual sleep. Despite similar hunger ratings due to fasting in both conditions, participants were willing to spend more money on food items only after sleep deprivation. Furthermore, fMRI data paralleled this behavioral finding, revealing a food-reward-specific upregulation of hypothalamic valuation signals and amygdala-hypothalamic coupling after a single night of sleep deprivation. Behavioral and fMRI results were not significantly correlated with changes in acyl, des-acyl, or total ghrelin concentrations. Our results suggest that increased food valuation after sleep loss might be due to hedonic rather than hormonal mechanisms. Epidemiological studies suggest an association between overweight and reduced nocturnal sleep, but the relative contributions of hedonic and hormonal factors to overeating after sleep loss are a matter of ongoing controversy. Here, we tested the association between sleep deprivation and food cue processing in a repeated-measures crossover design using fMRI. We found that willingness to pay increased for food items only after sleep deprivation. fMRI data paralleled this behavioral finding, revealing a food-reward-specific upregulation of hypothalamic valuation signals and amygdala-hypothalamic coupling after a single night of sleep deprivation. However, there was no evidence for hormonal modulations of behavioral or fMRI findings. Our results suggest that increased food valuation after sleep loss is due to hedonic rather than hormonal mechanisms.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2018.00884

Frontiers in neuroscience

Front Neurosci

Invasive and Non-invasive Stimulation of the Obese Human Brain.

Accumulating evidence suggests that non-invasive and invasive brain stimulation may reduce food craving and calorie consumption rendering these techniques potential treatment options for obesity. Non-invasive transcranial direct current stimulation (tDCS) or repetitive transcranial magnet stimulation (rTMS) are used to modulate activity in superficially located executive control regions, such as the dorsolateral prefrontal cortex (DLPFC). Modulation of the DLPFC's activity may alter executive functioning and food reward processing in interconnected dopamine-rich regions such as the striatum or orbitofrontal cortex. Modulation of reward processing can also be achieved by invasive deep brain stimulation (DBS) targeting the nucleus accumbens. Another target for DBS is the lateral hypothalamic area potentially leading to improved energy expenditure. To date, available evidence is, however, restricted to few exceptional cases of morbid obesity. The vagal nerve plays a crucial role in signaling the homeostatic demand to the brain. Invasive or non-invasive vagal nerve stimulation (VNS) is thus assumed to reduce appetite, rendering VNS another possible treatment option for obesity. Based on currently available evidence, the U.S. Food and Drug Administration recently approved VNS for the treatment of obesity. This review summarizes scientific evidence regarding these techniques' efficacy in modulating food craving and calorie intake. It is time for large controlled clinical trials that are necessary to translate currently available research discoveries into patient care.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsycho.2018.12.008

Biological psychology

Biol Psychol

A potential mechanistic role for neuroinflammation in reward processing impairments in autism spectrum disorder.

Accumulating evidence suggests that autism spectrum disorder (ASD) may be conceptualized within a framework of reward processing impairments. The Social Motivation Theory of Autism posits that reduced motivation to interact with people and decreased pleasure derived from social interactions may derail typical social development and contribute to the emergence of core social communication deficits in ASD. Neuroinflammation may disrupt the development of mesolimbic dopaminergic systems that are critical for optimal functioning of social reward processing systems. This neuroinflammation-induced disturbance of mesolimbic dopaminergic functioning has been substantiated using maternal immune activation rodent models whose offspring show aberrant dopaminergic corticostriatal function, as well as behavioral characteristics of ASD model systems. Preclinical findings are in turn supported by clinical evidence of increased mesolimbic neuroinflammatory responses in individuals with ASD. This review summarizes evidence for reward processing deficits and neuroinflammatory impairments in ASD and examines how immune inflammatory dysregulation may impair the development of dopaminergic mesolimbic circuitry in ASD. Finally, future research directions examining neuroinflammatory effects on reward processing in ASD are proposed.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2018.00458

Frontiers in human neuroscience

Front Hum Neurosci

Can Your DNA Influence Your Bet-Placing? The Impact of Cannabinoid Receptor 1 Gene on Gambling Tasks.

Are we placing a bet by ourselves or has our DNA already made the decision for us? Previous research has suggested that some genes related to dopamine or serotonin can influence our non-bet-placing decision-making, but little is known about whether cannabinoid-related genes can impact how much people bet. To investigate this issue, we focused on rs1049353, a single-nucleotide polymorphism of the cannabinoid receptor 1 (), because it is related to addictive behavior and reward processing. In this study ( = 377), we used a modified Cambridge gambling task to test the effect of polymorphism on how much people bet. We found that participants who are homozygous for C allele placed significantly larger bets than C/T carriers [(1,371) = 7.805, = 0.005]. We further studied the gene expression map in human brains and found that the gene is overexpressed in striatum, amygdala, and hippocampus. These brain structures are known to underpin reward and risk processing. Our findings suggest that, to some extent, high-level social decision-making even like bet-placing could be influenced by a single genetic locus variation in healthy volunteers. In addition, such effects were likely to be mediated by key brain regions in the reward- and risk-processing networks.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2018.12.011

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

Exploring the potential role of mesocorticolimbic circuitry in motivation for and adherence to chronic pain self-management interventions.

Adherence to pain self-management strategies is associated with favorable psychobehavioral outcomes among individuals with chronic pain. Substantive adherence to treatments teaching these adaptive skills often proves challenging, resulting in poor individual and societal outcomes. Evidence demonstrates motivation for behavior change as a key predictor of treatment adherence. Despite behavioral techniques that target motivation, however, nonadherence persists as a barrier to positive clinical outcomes in chronic pain. Understanding the neurobiological mechanisms underlying treatment motivation might highlight novel avenues for augmentative therapies. The purpose of this review is to present theory and evidence that the mesocorticolimbic system (i.e., brain circuitry associated with reward processing and motivation) contributes to treatment motivation among chronic pain patients, ultimately influencing adherence. We review evidence for motivation as a key adherence determinant, detail neuroimaging findings relating mesocorticolimbic circuitry and motivation, and discuss data supporting mesocorticolimbic dysfunction among chronic pain patients. We propose a neurobehavioral model for adherence to pain self-management interventions, listing testable hypotheses. Finally, we discuss potential research and intervention implications from the proposed model.

CognitiveConstruct

RewardProcessing

10.1007/s11065-018-9393-5

Neuropsychology review

Neuropsychol Rev

Efficacy of Invasive and Non-Invasive Brain Modulation Interventions for Addiction.

It is important to find new treatments for addiction due to high relapse rates despite current interventions and due to expansion of the field with non-substance related addictive behaviors. Neuromodulation may provide a new type of treatment for addiction since it can directly target abnormalities in neurocircuits. We review literature on five neuromodulation techniques investigated for efficacy in substance related and behavioral addictions: transcranial direct current stimulation (tDCS), (repetitive) transcranial magnetic stimulation (rTMS), EEG, fMRI neurofeedback and deep brain stimulation (DBS) and additionally report on effects of these interventions on addiction-related cognitive processes. While rTMS and tDCS, mostly applied at the dorsolateral prefrontal cortex, show reductions in immediate craving for various addictive substances, placebo-responses are high and long-term outcomes are understudied. The lack in well-designed EEG-neurofeedback studies despite decades of investigation impedes conclusions about its efficacy. Studies investigating fMRI neurofeedback are new and show initial promising effects on craving, but future trials are needed to investigate long-term and behavioral effects. Case studies report prolonged abstinence of opioids or alcohol with ventral striatal DBS but difficulties with patient inclusion may hinder larger, controlled trials. DBS in neuropsychiatric patients modulates brain circuits involved in reward processing, extinction and negative-reinforcement that are also relevant for addiction. To establish the potential of neuromodulation for addiction, more randomized controlled trials are needed that also investigate treatment duration required for long-term abstinence and potential synergy with other addiction interventions. Finally, future advancement may be expected from tailoring neuromodulation techniques to specific patient (neurocognitive) profiles.

CognitiveConstruct

RewardProcessing

10.3758/s13415-018-00680-1

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Differential impact of ventromedial prefrontal cortex damage on "hot" and "cold" decisions under risk.

The ventromedial prefrontal cortex (vmPFC) is known to play a key role in reward processing and decision making. However, its relative contribution to affect-rich ("hot") and affect-poor ("cold") decisions is not fully understood. Damage to vmPFC is associated with impaired performance on laboratory tasks of decision making under ambiguity and risk. In the current study, we tested the hypothesis that vmPFC is critical for adaptive risk taking under "hot" conditions specifically. Participants included patients with focal lesions in vmPFC, patient controls with damage in regions not including vmPFC, and healthy controls. They completed hot and cold versions of a dynamic risk-taking task, the Columbia Card Task (CCT). Relative to healthy controls and patient controls, vmPFC patients showed a strong overall increase in risk taking in the hot version of the CCT, despite preserved sensitivity to trial-level variation in risk. In the cold version, overall risk taking was similar among all three groups, even though vmPFC patients showed reduced sensitivity to trial-level variation in risk. Sensitivity to gain and loss magnitudes did not differ significantly among the groups, in either the hot or the cold CCT. These findings lend novel support to the hypothesis that the vmPFC is critical for adaptive decision making under affect-rich conditions.

CognitiveConstruct

RewardProcessing

10.1016/j.physbeh.2018.12.006

Physiology & behavior

Physiol Behav

Effects of chronic cannabinoid exposure during adolescence on reward preference and mPFC activation in adulthood.

Cannabis is one of the most commonly used drugs among adolescents, with initial use beginning between the ages of 12 to 17. Although often perceived as a 'soft drug', both short- and long-term use have been associated with numerous adverse outcomes, including cognitive impairment, increased risk of substance abuse, and heightened risk of psychosis or schizophrenia in individuals with a predisposition. Further, the severity of these impairments is closely linked to initiation of use, i.e. earlier use increases risk. It has been suggested that adolescent vulnerability to the adverse consequences of cannabis use is due to ongoing brain development occurring during this time. Indeed, the adolescent brain continues to be remodeled well into adolescence and early adulthood, particularly in the prefrontal cortex (PFC). The medial prefrontal cortex (mPFC) has been implicated in reward processing and decision-making and alterations in mPFC development due to adolescent cannabis exposure could impair these functions. To model the effects of cannabis on mPFC function, we administered the synthetic cannabinoid WIN 55, 212-2 (WIN) to male and female rats from postnatal day 30-60. Once animals reached adulthood, we used a Probabilistic Reward (PR) choice task to elicit PFC activity and measure how patterns of activity to task-related events were modulated by adolescent WIN-treatment. Adult animals showed subtle effects of WIN-treatment on choice patterns. During task performance, mPFC activity elicited by lever press at the time of choices and reward delivery following choices were reduced in WIN-treated animals. This lasting effect of WIN suggests an impairment of the maturation of excitatory-inhibitory balance of signals in mPFC during adolescence, which may alter executive function into adulthood.

CognitiveConstruct

RewardProcessing

10.1016/j.neuron.2018.11.021

Neuron

Neuron

Fractionating Blunted Reward Processing Characteristic of Anhedonia by Over-Activating Primate Subgenual Anterior Cingulate Cortex.

Anhedonia is a core symptom of depression, but the underlying neurobiological mechanisms are unknown. Correlative neuroimaging studies implicate dysfunction within ventromedial prefrontal cortex, but the causal roles of specific subregions remain unidentified. We addressed these issues by combining intracerebral microinfusions with cardiovascular and behavioral monitoring in marmoset monkeys to show that over-activation of primate subgenual anterior cingulate cortex (sgACC, area 25) blunts appetitive anticipatory, but not consummatory, arousal, whereas manipulations of adjacent perigenual ACC (pgACC, area 32) have no effect. sgACC/25 over-activation also reduces the willingness to work for reward. F-FDG PET imaging reveals over-activation induced metabolic changes in circuits involved in reward processing and interoception. Ketamine treatment ameliorates the blunted anticipatory arousal and reverses associated metabolic changes. These results demonstrate a causal role for primate sgACC/25 over-activity in selective aspects of impaired reward processing translationally relevant to anhedonia, and ketamine's modulation of an affective network to exert its action.

CognitiveConstruct

RewardProcessing

10.1016/j.neulet.2018.11.043

Neuroscience letters

Neurosci Lett

Dopaminergic modulation of pain signals in the medial prefrontal cortex: Challenges and perspectives.

Chronic pain is a massive socieoeconomic burden and is often refractory to treatment. To devise novel therapeutic interventions, it is important to understand in detail the processing of pain signals in the brain. Recent studies have revealed shared features between the brain's reward and pain systems. Dopamine (DA) is a key neuromodulator in the mesocorticolimbic system that has been implicated not only in motivated behaviours, reinforcement learning and reward processing, but also in the pain axis. The medial prefrontal cortex (mPFC) is an important region for mediating executive functions including attention, judgement, and learning. Studies have revealed that the mPFC undergoes plasticity during the development of chronic pain. The mPFC receives dopaminergic input from the ventral tegmental area (VTA), and stimulation of these inputs has been shown to modulate the plasticity of the mPFC and anxiety and aversive behaviour. Here, we review the role of the mPFC and its dopaminergic modulation in chronic pain.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0205085

PloS one

PLoS One

Neurobiology of social reward valuation in adults with a history of anorexia nervosa.

Anorexia nervosa (AN) is a disorder characterized by atypical patterns of reward valuation (e.g. positive valuation of hunger). Atypical reward processing may extend into social domains. If so, such findings would be of prognostic significance as impaired social functioning predicts worse outcome. We explore neural circuits implicated in social reward processing in individuals with a history of AN who are weight-restored relative to controls and examine the effects of illness course on the experience of social value. 20 weight-restored individuals with a history of AN (AN-WR) and 24 healthy control (HC) participants were assessed using fMRI tasks that tapped social reward: smiling faces and full human figures that varied in attractiveness and weight. AN-WR differed from HC in attractiveness ratings by weight (negatively correlated in AN-WR). While there were no significant differences when viewing smiling faces, viewing full figures resulted in decreased activation in regions implicated in reward valuation (the right caudate) for AN-WR and this region was negatively correlated with a sustained course of the disorder. Exploratory whole brain analyses revealed reduced activation in regions associated with social reward, self-referential processing, and cognitive reappraisal (e.g., medial prefrontal cortex, striatum, and nucleus accumbens) with sustained disorder course. The rewarding value of full body images decreases with a sustained disorder course. This may reflect an extension of atypical reward processing documented in AN-WR, perhaps as a function of starvation dampening visceral motivational signals; the deployment of cognitive strategies that lessen the experience of reward; and/or the nature of the stimuli themselves as provocative of eating disorder symptoms (e.g., thin bodies). These findings did not extend to smiling face stimuli. Advances in technology (e.g., virtual avatars, text messaging) may provide novel means to build relationships, including therapeutic relationships, to support improved social connections without threats to symptom provocation.

CognitiveConstruct

RewardProcessing

10.1016/j.psyneuen.2018.11.024

Psychoneuroendocrinology

Psychoneuroendocrinology

Inflammation and dimensions of reward processing following exposure to the influenza vaccine.

Alterations in reward processing are a central feature of depression and may be influenced by inflammation. Indeed, inflammation is associated with deficits in reward-related processes in animal models and with dysregulation in reward-related neural circuitry in humans. However, the downstream behavioral manifestations of such impairments are rarely examined in humans. The influenza vaccination was used to elicit a mild inflammatory response in 41 healthy young adults (age range: 18-22, 30 female). Participants provided blood samples and completed behavioral measures of three key aspects of reward-reward motivation, reward learning, and reward sensitivity-before and 1 day after receiving the influenza vaccine. The influenza vaccine led to mild but significant increases in circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) (p <  .001). Consistent with hypotheses, increases in IL-6 predicted lower reward motivation (p =  .029). However, contrary to hypotheses, increases in IL-6 predicted increased performance on a reward learning task (p =  .043) and were not associated with changes in reward sensitivity (p's > .288). These findings contribute to an emerging literature on the nuanced associations between inflammation and reward and demonstrate that even mild alterations in inflammation are associated with multiple facets of reward processing.

CognitiveConstruct

RewardProcessing

10.1037/abn0000389

Journal of abnormal psychology

J Abnorm Psychol

Aberrant striatal tracking of reward magnitude in youth with current or past-year depression.

Reward dysfunction is often present in youth with major depressive disorder (MDD), but the specific neurobiological bases underlying reward valuation deficits remain unclear. The current study examined whether adolescents and young adults with MDD track brain and behavioral responses according to relative reward magnitude-a neurocognitive valuation process known as magnitude tracking. Female adolescents and young adults ages 15-20 years (n = 56 with current or past-year MDD; n = 26 healthy controls [HCs]) completed a task during functional neuroimaging in which they could win or lose money at high stakes (+$1/-50¢) and low stakes (+20¢/-10¢). Behaviorally, HC accelerated button press responses on high stakes compared to low-stakes trials, whereas MDD did not alter response speed across stakes. Neurally, HC increased recruitment of the ventral and dorsal striatum, canonical reward-processing regions, for high-magnitude versus low-magnitude rewards. However, the MDD group did not exhibit striatal magnitude tracking for low versus high rewards-an effect independent of MDD recency, MDD symptom severity, comorbid anxiety and substance use disorders, and psychiatric medication use. In contrast, striatal recruitment for overall reward reactivity, measured by comparing striatal activity for reward and loss feedback, was similar in the MDD and HC groups. However, reward reactivity was negatively correlated with current depression symptom severity in the MDD group. Taken together, these findings suggest that whereas reward reactivity may vary with current depression severity, reward magnitude tracking may represent an important aberrant valuation process in youth with depression-independent of symptom severity and recency. This valuation deficit may have implications for maladaptive motivation and learning observed in youth with MDD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

CognitiveConstruct

RewardProcessing

10.1017/S0033291718003446

Psychological medicine

Psychol Med

From laboratory to life: associating brain reward processing with real-life motivated behaviour and symptoms of depression in non-help-seeking young adults.

Depression has been associated with abnormalities in neural underpinnings of Reward Learning (RL). However, inconsistencies have emerged, possibly owing to medication effects. Additionally, it remains unclear how neural RL signals relate to real-life behaviour. The current study, therefore, examined neural RL signals in young, mildly to moderately depressed - but non-help-seeking and unmedicated - individuals and how these signals are associated with depressive symptoms and real-life motivated behaviour. Individuals with symptoms along the depression continuum (n = 87) were recruited from the community. They performed an RL task during functional Magnetic Resonance Imaging and were assessed with the Experience Sampling Method (ESM), completing short questionnaires on emotions and behaviours up to 10 times/day for 15 days. Q-learning model-derived Reward Prediction Errors (RPEs) were examined in striatal areas, and subsequently associated with depressive symptoms and an ESM measure capturing (non-linearly) how anticipation of reward experience corresponds to actual reward experience later on. Significant RPE signals were found in the striatum, insula, amygdala, hippocampus, frontal and occipital cortices. Region-of-interest analyses revealed a significant association between RPE signals and (a) self-reported depressive symptoms in the right nucleus accumbens (b = -0.017, p = 0.006) and putamen (b = -0.013, p = .012); and (b) the quadratic ESM variable in the left (b = 0.010, p = .010) and right (b = 0.026, p = 0.011) nucleus accumbens and right putamen (b = 0.047, p < 0.001). Striatal RPE signals are disrupted along the depression continuum. Moreover, they are associated with reward-related behaviour in real-life, suggesting that real-life coupling of reward anticipation and engagement in rewarding activities might be a relevant target of psychological therapies for depression.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2018.00546

Frontiers in psychiatry

Front Psychiatry

Ventral Striatal Reactivity in Compulsive Sexual Behaviors.

Compulsive Sexual Behaviors (CSB) are a reason to seek treatment. Given this reality, the number of studies on CSB has increased substantially in the last decade and the World Health Organization (WHO) included CSB in its proposal for the upcoming ICD-11. Sixty percent of the neuroimaging studies on CSB published since 2014 aimed to examine similarities and differences between brain mechanisms underlying CSB, gambling disorder, and substance use disorders. One of the crucial brain circuits involved in addiction is the reward system involving the ventral striatum (including nucleus accumbens). There are two distinct theories describing ventral striatal activity in addictions: Incentive Salience Theory (IST) and Reward Deficiency Syndrome (RDS). IST describes increased ventral striatal activations during the anticipation of addiction-related reward, while RDS describes decreased ventral striatal reactivity both during the anticipation of the reward and during the reward processing. Here, we aim to investigate how the findings on ventral striatal reactivity in CSB support each of these two addiction frameworks. For this purpose, we conducted a systematic review of neuroimaging studies on CSB available in Pubmed, EBSCO, and Google Scholar between 2005 and 2018. We found nine relevant research papers. Only four of these studies directly investigated processing of erotic cues and/or rewards and reported findings related to ventral striatum activations. Three of these studies indicate increased ventral striatal reactivity for erotic stimuli, which is consistent with IST and does not support predictions based on RDS. Therefore, the current state of this data suggest that CSB is related to increased ventral striatal reactivity during the anticipation of erotic stimuli.

CognitiveConstruct

RewardProcessing

10.1016/j.euroneuro.2018.10.002

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Eur Neuropsychopharmacol

Daily-life stress differentially impacts ventral striatal dopaminergic modulation of reward processing in first-degree relatives of individuals with psychosis.

Emerging evidence shows that stress can impair the ability to learn from and pursue rewards, which in turn has been linked to motivational impairments characteristic of the psychotic disorder. Ventral striatal dopaminergic neurotransmission has been found to modulate reward processing, and appears to be disrupted by exposure to stress. We investigated the hypothesis that stress experienced in the everyday life has a blunting effect on reward-induced dopamine release in the ventral striatum of 16 individuals at a familial risk for psychosis compared to 16 matched control subjects. Six days of ecological momentary assessments quantified the amount of daily-life stress prior to [F]fallypride PET imaging while performing a probabilistic reinforcement learning task. Relative to the controls, individuals at a familial risk for psychosis who encountered more daily-life stress showed significantly diminished extent of reward-induced dopamine release in the right ventral striatum, as well as poorer performance on the reward task. These findings provide the first neuromolecular evidence for stress-related deregulation of reward processing in familial predisposition to psychosis. The implication of daily-life stress in compromised modulation of reward function may facilitate the design of targeted neuropharmacological and ecological interventions.

CognitiveConstruct

RewardProcessing

10.1177/1550059418814987

Clinical EEG and neuroscience

Clin EEG Neurosci

Event-Related Potentials Are Associated With Unexpected Gain and Loss: Using a Gambling Paradigm.

Previous neuroimaging studies have described altered activity in brain areas associated with reward processing following reward or punishment. This study examines the extent to which feedback-based experience of gain and loss is associated with electrophysiological correlates. Twenty-nine healthy participants used a gambling task that focused on actual nonpredictable gains and losses. During the task, an electroencephalography recording was performed in order to assess reward processing. Event-related potentials were analyzed when participants were receiving gain/loss feedback. Event-related potentials revealed higher feedback-related negativity for both overall gain and loss compared with a neutral condition in fronto-centro-parietal electrodes. P3 potentials were significantly increased for high gains/losses compared to neutral and small gains/losses. These results indicate that the paradigm is suitable to evoke specific patterns of reward-related electrophysiological responses. The wavelet analysis showed that electroencephalography frequency variations depended on the amount of gains/losses. This gambling paradigm is appropriate to measure aspects of feedback processing and could help analyze disease-specific alterations of the reward system in patients.

CognitiveConstruct

RewardProcessing

10.1017/S1092852918001335

CNS spectrums

CNS Spectr

Reward systems and cognitions in Major Depressive Disorder.

A lack of motivation and anhedonia represent frequent and pervasive symptoms in depression, although with poor specificity. Historically described as a response bias, reward-related impairments in depression may account for the important aspects of the cognitive impairments associated with diagnosis of major depressive disorder. Reward processing is a broad psychological construct that can be parsed into 3 distinct components known as "reinforcement learning" (learning), "reward responsiveness" (liking), and "motivation to obtain a reward" (wanting). Depressed patients respond hyposensitively to reward and maladaptively to punishment: this pattern is related to a dysfunction in the frontostriatal systems modulated by the monoamine systems; seems to be observed in medicated and unmedicated patients with depression and in healthy individuals with high levels of anhedonia; and could be observed in patients with a history of depression, even when in full remission. Considered to be cognitive impairments, reward-related-impairments may also constitute part of an underlying neurobiological vulnerability to major depressive disorder (MDD). For example, the reward-related impairment is state dependent and, more or less, correlated with symptom severity in some studies but has also been proposed as being trait like, with endophenotype characteristics, possibly contributing to the persistence of the disease or treatment resistance. The 3 core aspects of reward processing have specific neurobiological correlates that involve the ventral and dorsal striatum, lateral habenula, ventral tegmental area, orbitofrontal cortex, anterior cingulate cortex, and ventromedial and dorsolateral prefrontal cortex. These structures underline the important role of the dopaminergic mesolimbic pathway, but glutamate and serotonin could also have an important role, at least in some aspects of reward-related impairments.

CognitiveConstruct

RewardProcessing

10.1016/bs.pmbts.2018.07.008

Progress in molecular biology and translational science

Prog Mol Biol Transl Sci

Effects of Estrogens on Central Nervous System Neurotransmission: Implications for Sex Differences in Mental Disorders.

Nearly one of every five US individuals aged 12 years old or older lives with certain types of mental disorders. Men are more likely to use various types of substances, while women tend to be more susceptible to mood disorders, addiction, and eating disorders, all of which are risks associated with suicidal attempts. Fundamental sex differences exist in multiple aspects of the functions and activities of neurotransmitter-mediated neural circuits in the central nervous system (CNS). Dysregulation of these neural circuits leads to various types of mental disorders. The potential mechanisms of sex differences in the CNS neural circuitry regulating mood, reward, and motivation are only beginning to be understood, although they have been largely attributed to the effects of sex hormones on CNS neurotransmission pathways. Understanding this topic is important for developing prevention and treatment of mental disorders that should be tailored differently for men and women. Studies using animal models have provided important insights into pathogenesis, mechanisms, and new therapeutic approaches of human diseases, but some concerns remain to be addressed. The purpose of this chapter is to integrate human and animal studies involving the effects of the sex hormones, estrogens, on CNS neurotransmission, reward processing, and associated mental disorders. We provide an overview of existing evidence for the physiological, behavioral, cellular, and molecular actions of estrogens in the context of controlling neurotransmission in the CNS circuits regulating mood, reward, and motivation and discuss related pathology that leads to mental disorders.

CognitiveConstruct

RewardProcessing

10.1038/s41386-018-0262-y

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Sex-dependent regulation of social reward by oxytocin receptors in the ventral tegmental area.

Social reward is critical for social relationships, and yet we know little about the characteristics of social interactions that are rewarding or the neural mechanisms underlying that reward. Here, we investigate the sex-dependent role of oxytocin receptors within the ventral tegmental area (VTA) in mediating the magnitude and valence of social reward. Operant and classical conditioning tests were used to measure social reward associated with same-sex social interactions. The effects of oxytocin, selective oxytocin receptor agonists, antagonists, and vehicle injected into the VTA on social reward was determined in male and female Syrian hamsters. The colocalization of FOS and oxytocin in sites that project to the VTA following social interaction was also determined. Females find same-sex social interactions more rewarding than males and activation of oxytocin receptors in the VTA is critical for social reward in females, as well as males. These studies provide support for the hypothesis that there is an inverted U relationship between the duration of social interaction and social reward, mediated by oxytocin; and that in females the dose-response relationship is initiated at lower doses compared with males. Same-sex social interaction is more rewarding in females than in males, and an inverted U relationship mediated by oxytocin may have a critical role in assigning positive and negative valence to social stimuli. Understanding these sex differences in social reward processing may be essential for understanding the sex differences in the prevalence of many psychiatric disorders and the development of gender-specific treatments of neuropsychiatric disorders.

CognitiveConstruct

RewardProcessing

10.1080/1028415X.2018.1537169

Nutritional neuroscience

Nutr Neurosci

An intermittent hypercaloric diet alters gut microbiota, prefrontal cortical gene expression and social behaviours in rats.

Excessive consumption of high fat and high sugar (HFHS) diets alters reward processing, behaviour, and changes gut microbiota profiles. Previous studies in gnotobiotic mice also provide evidence that these gut microorganisms may influence social behaviour. To further investigate these interactions, we examined the impact of the intermittent access to a HFHS diet on social behaviour, gene expression and microbiota composition in adolescent rats. Male rats were permitted intermittent daily access (2 h / day) to a palatable HFHS chow diet for 28 days across adolescence. Social interaction, social memory and novel object recognition were assessed during this period. Following testing, RT-PCR was conducted on hippocampal and prefrontal cortex (PFC) samples. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa in faecal samples. We observed reduced social interaction behaviours, impaired social memory and novel object recognition in HFHS diet rats compared to chow controls. RT-PCR revealed reduced levels of monoamine oxidase A (), catechol-O-methyltransferase () and brain derived neurotrophic factor () mRNA in the PFC of HFHS diet rats. Faecal microbiota analysis demonstrated that the relative abundance of a number of specific bacterial taxa differed significantly between the two diet groups, in particular, and bacteria. Intermittent HFHS diet consumption evoked physiological changes to the brain, particularly expression of mRNA associated with reward and neuroplasticity, and gut microbiome. These changes may underpin the observed alterations to social behaviours.

CognitiveConstruct

RewardProcessing

10.9758/cpn.2018.16.4.449

Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology

Clin Psychopharmacol Neurosci

Dysfunctional Social Reinforcement Processing in Disruptive Behavior Disorders: An Functional Magnetic Resonance Imaging Study.

Prior functional magnetic resonance imaging (fMRI) work has revealed that children/adolescents with disruptive behavior disorders (DBDs) show dysfunctional reward/non-reward processing of non-social reinforcements in the context of instrumental learning tasks. Neural responsiveness to reinforcements during instrumental learning, despite the importance of this for socialization, has not yet been previously investigated. Twenty-nine healthy children/adolescents and 19 children/adolescents with DBDs performed the fMRI social/non-social reinforcement learning task. Participants responded to random fractal image stimuli and received social and non-social rewards/non-rewards according to their accuracy. Children/adolescents with DBDs showed significantly reduced responses within the caudate and posterior cingulate cortex (PCC) to non-social (financial) rewards and social non-rewards (the distress of others). Connectivity analyses revealed that children/adolescents with DBDs have decreased positive functional connectivity between the ventral striatum (VST) and the ventromedial prefrontal cortex (vmPFC) seeds and the lateral frontal cortex in response to reward relative to non-reward, irrespective of its sociality. In addition, they showed decreased positive connectivity between the vmPFC seed and the amygdala in response to non-reward relative to reward. These data indicate compromised reinforcement processing of both non-social rewards and social non-rewards in children/adolescents with DBDs within core regions for instrumental learning and reinforcement-based decision- making (caudate and PCC). In addition, children/adolescents with DBDs show dysfunctional interactions between the VST, vmPFC, and lateral frontal cortex in response to rewarded instrumental actions potentially reflecting disruptions in attention to rewarded stimuli.

CognitiveConstruct

RewardProcessing

10.3389/fnana.2018.00084

Frontiers in neuroanatomy

Front Neuroanat

Cell-Type-Specific Afferent Innervation of the Nucleus Accumbens Core and Shell.

The nucleus accumbens (NAc) is clearly implicated in reward processing and drug addiction, as well as in numerous neurological and psychiatric disorders; nevertheless, the circuit mechanisms underlying the diverse functions of the NAc remain poorly understood. Here, we characterized the whole-brain and monosynaptic inputs to two main projection cell types - D1 dopamine receptor expressing medium spiny neurons (D1R-MSNs) and D2 dopamine receptor expressing medium spiny neurons (D2R-MSNs) - within the NAc core and NAc shell by rabies-mediated trans-synaptic tracing. We discovered that D1R-MSNs and D2R-MSNs in both NAc subregions receive similar inputs from diverse sources. Inputs to the NAc core are broadly scattered, whereas inputs to the NAc shell are relatively concentrated. Furthermore, we identified numerous brain areas providing important contrasting inputs to different NAc subregions. The anterior cortex preferentially innervates the NAc core for both D1R-MSNs and D2R-MSNs, whereas the lateral hypothalamic area (LH) preferentially targets D1R-MSNs in the NAc shell. Characterizing the cell-type-specific connectivity of different NAc subregions lays a foundation for studying how diverse functions of the NAc are mediated by specific pathways.

CognitiveConstruct

RewardProcessing

10.1016/j.ynstr.2018.10.002

Neurobiology of stress

Neurobiol Stress

Diminished positive affect and traumatic stress: A biobehavioral review and commentary on trauma affective neuroscience.

Post-traumatic stress manifests in disturbed affect and emotion, including exaggerated severity and frequency of negative valence emotions, e.g., fear, anxiety, anger, shame, and guilt. However, another core feature of common post-trauma psychopathologies, i.e. post-traumatic stress disorder (PTSD) and major depression, is diminished positive affect, or reduced frequency and intensity of positive emotions and affective states such as happiness, joy, love, interest, and desire/capacity for interpersonal affiliation. There remains a stark imbalance in the degree to which the neuroscience of each affective domain has been probed and characterized in PTSD, with our knowledge of post-trauma diminished positive affect remaining comparatively underdeveloped. This remains a prominent barrier to realizing the clinical breakthroughs likely to be afforded by the increasing availability of neuroscience assessment and intervention tools. In this review and commentary, the author summarizes the modest extant neuroimaging literature that has probed diminished positive affect in PTSD using reward processing behavioral paradigms, first briefly reviewing and outlining the neurocircuitry implicated in reward and positive emotion and its interrelationship with negative emotion and negative valence circuitry. Specific research guidelines are then offered to best and most efficiently develop the knowledge base in this area in a way that is clinically translatable and will exert a positive impact on routine clinical care. The author concludes with the prediction that the development of an integrated, bivalent theoretical and predictive model of how trauma impacts affective neurocircuitry to promote post-trauma psychopathology will ultimately lead to breakthroughs in how trauma treatments are conceptualized mechanistically and developed pragmatically.

CognitiveConstruct

RewardProcessing

10.1016/j.ynstr.2018.09.005

Neurobiology of stress

Neurobiol Stress

A review of nonhuman primate models of early life stress and adolescent drug abuse.

Adolescence represents a developmental stage in which initiation of drug use typically occurs and is marked by dynamic neurobiological changes. These changes present a sensitive window during which perturbations to normative development lead to alterations in brain circuits critical for stress and emotional regulation as well as reward processing, potentially resulting in an increased susceptibility to psychopathologies. The occurrence of early life stress (ELS) is related to a greater risk for the development of substance use disorders (SUD) during adolescence. Studies using nonhuman primates (NHP) are ideally suited to examine how ELS may alter the development of neurobiological systems modulating the reinforcing effects of drugs, given their remarkable neurobiological, behavioral, and developmental homologies to humans. This review examines NHP models of ELS that have been used to characterize its effects on sensitivity to drug reinforcement, and proposes future directions using NHP models of ELS and drug abuse in an effort to develop more targeted intervention and prevention strategies for at risk clinical populations.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2018.09.027

Drug and alcohol dependence

Drug Alcohol Depend

Greater tolerance to losses in sensation seeking: Evidence from probability and delay discounting.

Sensation seeking is a behavioral endophenotype of substance use and is associated with abnormalities in financial reward processing. Previous research suggests that high sensation seekers (HSS) relative to low sensation seekers (LSS) show either an enhanced sensitivity to financial rewards or a reduced sensitivity to financial punishments. However, there are few studies investigating the valuation of financial rewards and punishments as a function of delivery probability and delay, two important aspects of reward processing that influence the valuation. We administrated a probability discounting task and a delay discounting task to 56 HSS and 57 LSS selected from a large sample. Each task was crossed with two factors: valence (gain vs. loss) and amount (Ұ1000 vs. Ұ50000). For the probability discounting task, HSS discounted probabilistic losses but not gains more steeply than LSS, irrespective of the amount of outcome. For the delay discounting task, HSS discounted delayed losses more steeply than LSS, for the large but not small amount condition. In contrast, both groups exhibited comparable discounting rates for gains across the two amount conditions. These results remained significant when impulsivity levels were controlled for. Together, our data strengthen the argument that the dysfunctional valuation in sensation seeking is valence specific, which may be driven by a weaker avoidance system, rather than by a stronger approach system.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2018.00776

Frontiers in neuroscience

Front Neurosci

Power of Feedback-Induced Beta Oscillations Reflect Omission of Rewards: Evidence From an EEG Gambling Study.

The functional role of high beta oscillations (20-35 Hz) during feedback processing has been suggested to reflect unexpected gains. Using a novel gambling task that separates gains and losses across blocks and directly compares reception of monetary rewards to a 'no-reward/punishment' condition with equal probability we aimed to further investigate the role of beta oscillations. When contrasting different feedback conditions across rewards, we found that a late low beta component (12-20 Hz) had increased in power during the omission of rewards relative to the reception of rewards, while no differences were observed during the loss domain. These findings may indicate that late low beta oscillations in the context of feedback processing may respond to omission of gains relative to other potential outcomes. We speculate that late low beta oscillations may operate as a learning mechanism that signals the brain to make future adequate decisions. Overall, our study provides new insights for the role of late low beta oscillations in reward processing.

CognitiveConstruct

RewardProcessing

10.1093/chemse/bjy071

Chemical senses

Chem Senses

Brain Responses to Anticipation and Consumption of Beer with and without Alcohol.

Beer is a popular alcoholic beverage worldwide. Nonalcoholic beer (NA-beer) is increasingly marketed. Brain responses to beer and NA-beer have not been compared. It could be that the flavor of beer constitutes a conditioned stimulus associated with alcohol reward. Therefore, we investigated whether oral exposure to NA-beer with or without alcohol elicits similar brain responses in reward-related areas in a context where regular alcoholic beer is expected. Healthy men (n = 21) who were regular beer drinkers were scanned using functional MRI. Participants were exposed to word cues signaling delivery of a 10-mL sip of chilled beer or carbonated water (control) and subsequent sips of NA-beer with or without alcohol or water (control). Beer alcohol content was not signaled. The beer cue elicited less activation than the control cue in the primary visual cortex, supplementary motor area (reward-related region) and bilateral inferior frontal gyrus/frontal operculum. During tasting, there were no significant differences between the 2 beers. Taste activation after swallowing was significantly greater for alcoholic than for NA-beer in the inferior frontal gyrus/anterior insula and dorsal prefrontal cortex (superior frontal gyrus). This appears to be due to sensory stimulation by ethanol rather than reward processing. In conclusion, we found no differences in acute brain reward upon consumption of NA-beer with and without alcohol, when presented in a context where regular alcoholic beer is expected. This suggests that in regular consumers, beer flavor rather than the presence of alcohol is the main driver of the consumption experience.

CognitiveConstruct

RewardProcessing

10.1186/s40337-018-0217-z

Journal of eating disorders

J Eat Disord

What can food-image tasks teach us about anorexia nervosa? A systematic review.

A salient feature of anorexia nervosa (AN) is the persistent and severe restriction of food, such that dietary intake is inadequate to maintain a healthy body weight. Experimental tasks and paradigms have used illness-relevant stimuli, namely food images, to study the eating-specific neurocognitive mechanisms that promote food avoidance. This systematic review, completed in accordance with PRISMA guidelines, identified and critically evaluated paradigms involving images of food that have been used to study AN. There were 50 eligible studies, published before March 10 2018, identified from Medline and PsychINFO searches, and reference screening. Studies using food image-based paradigms were categorised into three methodologic approaches: neuropsychology, neurophysiology, and functional magnetic resonance imaging (fMRI). Paradigms were reviewed with a focus on how well they address phenomena central to AN. Across tasks, differences between individuals with AN and healthy peers have been identified, with the most consistent findings in the area of reward processing. Measuring task performance alongside actual eating behaviour, and using experimental manipulations to probe causality, may advance understanding of the mechanisms of illness in AN.

CognitiveConstruct

RewardProcessing

10.1016/j.bpsc.2017.10.008

Biological psychiatry. Cognitive neuroscience and neuroimaging

Biol Psychiatry Cogn Neurosci Neuroimaging

Anhedonia in Trauma-Exposed Individuals: Functional Connectivity and Decision-Making Correlates.

Reward processing deficits have been increasingly associated with trauma exposure and are a core feature of posttraumatic stress disorder (PTSD). While altered resting-state functional connectivity (rsFC) of ventral striatal regions, including the nucleus accumbens (NAcc), has been associated with anhedonia in some stress-related disorders, relationships between NAcc rsFC and anhedonia have not previously been investigated in trauma-exposed individuals. Additionally, relationships between anhedonia and reward-related decision making remain unexplored in relation to trauma exposure. We hypothesized that elevated anhedonia would be associated with altered rsFC between NAcc and default mode network regions and with increased delay discounting. The sample included 51 participants exposed to a DSM-IV PTSD Criterion A event related to community trauma. Participants completed the Clinician Administered PTSD Scale, the Snaith-Hamilton Pleasure Scale, the Beck Depression Inventory, a computerized delay discounting paradigm, and resting-state functional magnetic resonance imaging. rsFC data were analyzed in SPM12 and CONN. Higher levels of anhedonia were associated with increased rsFC between seed regions of bilateral NAcc and areas of right dorsomedial prefrontal cortex. This relationship remained significant after accounting for Clinician Administered PTSD Scale total scores, Beck Depression Inventory total scores, or diagnostic group in the regression. Additionally, anhedonia was associated with elevated (increased) delay discounting. Greater anhedonia was related to higher positive connectivity between NAcc and right dorsomedial prefrontal cortex and to increased delay discounting, i.e., greater preference for smaller immediate versus larger delayed rewards. These findings contribute to a growing body of literature emphasizing the importance of anhedonia in trauma-exposed individuals.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsy098

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Contextual valence modulates the effect of choice on incentive processing.

Previous research has demonstrated that reward-related neural activity is enhanced for choice relative to no-choice opportunities in the gain context. The current event-related potential study examined whether this modulatory effect of choice can be observed in both the gain and the loss contexts across anticipatory and consummatory phases of incentive processing. Thirty-two participants performed a simple choice task during which choices were made either by themselves (a choice condition) or by a computer (a no-choice condition) during a gain context (gain vs nongain) and a loss context (nonloss vs loss). Behaviorally, participants reported a higher level of perceived control in the choice than the no-choice condition as well as in the gain than loss context. During the anticipatory phase, the choice relative to the no-choice condition elicited an increased cue-P3 in the loss context and an enhanced stimulus-preceding negativity in the gain context. During the consummatory phase, the choice condition elicited a larger reward positivity (ΔRewP) than the no-choice condition in the gain relative to the loss context but a comparable feedback P3 across contexts. These findings demonstrate that the crucial role of voluntary choice in reward processing is contingent upon contextual valence.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2018.09.013

Drug and alcohol dependence

Drug Alcohol Depend

Reward and executive control network resting-state functional connectivity is associated with impulsivity during reward-based decision making for cocaine users.

Cocaine addiction is related to impulsive decision making that is mediated by brain circuitry involved in reward processing and executive functions, such as cognitive control and attentional salience. Resting-state functional connectivity between reward and executive control circuitry is altered among cocaine users, with concomitant deficits in impulsivity and learning. Prior research has examined how select brain regions interact to influence impulsive decision making for drug users; however, research examining interactions between large-scale brain networks and impulsive behavior is limited. The current study compared reward and executive control network resting-state functional connectivity and its relationship to impulsive decision making between cocaine users (n = 37) and non-cocaine using control participants (n = 35). Participants completed computerized decision-making tasks and a separate resting-state functional magnetic resonance imaging scan. Data underwent independent component, dual regression, and linear regression moderation analyses. Higher impulsivity on the Balloon Analogue Risk Task (BART) was associated with inverse resting-state connectivity between the left cognitive control and subgenual anterior cingulate extended reward networks for cocaine users, while the opposite was found for controls. Less impulsivity on the monetary choice questionnaire was associated with stronger positive resting-state connectivity between the attentional salience and striatal core reward networks for controls, while cocaine users showed no association between impulsivity and resting-state connectivity of these networks. Cocaine users show aberrant associations between reward-executive control resting-state network coupling and impulsive decision making. The findings support the conclusion that an imbalance between reward and executive control circuitry contributes to impulsivity in drug use.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2018.10.083

NeuroImage

Neuroimage

Oscillatory signatures of reward prediction errors in declarative learning.

Reward prediction errors (RPEs) are crucial to learning. Whereas these mismatches between reward expectation and reward outcome are known to drive procedural learning, their role in declarative learning remains underexplored. Earlier work from our lab addressed this, and consistently found that signed reward prediction errors (SRPEs; "better-than-expected" signals) boost declarative learning. In the current EEG study, we sought to explore the neural signatures of SRPEs. Participants studied 60 Dutch-Swahili word pairs while RPE magnitudes were parametrically manipulated. Behaviorally, we replicated our previous findings that SRPEs drive declarative learning, with increased recognition for word pairs accompanied by large, positive RPEs. In the EEG data, at the start of reward feedback processing, we found an oscillatory (theta) signature consistent with unsigned reward prediction errors (URPEs; "different-than-expected" signals). Slightly later during reward feedback processing, we observed oscillatory (high-beta and high-alpha) signatures for SRPEs during reward feedback, similar to SRPE signatures during procedural learning. These findings illuminate the time course of neural oscillations in processing reward during declarative learning, providing important constraints for future theoretical work.

CognitiveConstruct

RewardProcessing

10.1021/acschemneuro.8b00437

ACS chemical neuroscience

ACS Chem Neurosci

Local μ-Opioid Receptor Antagonism Blunts Evoked Phasic Dopamine Release in the Nucleus Accumbens of Rats.

μ-opioid receptors (MORs) in the nucleus accumbens (NAc) can regulate reward-related behaviors that are dependent on mesolimbic dopamine, but the precise mechanism of this MOR regulation is unknown. We hypothesized that MORs within the NAc core regulate dopamine release. Specifically, we infused the MOR antagonist CTAP (d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2) into the NAc core while dopamine release was evoked by electrical stimulation of the ventral tegmental area and measured by fast-scan cyclic voltammetry. We report that CTAP dose-dependently inhibited evoked dopamine release, with full blockade achieved with the 8 μg infusion. In contrast, evoked dopamine release increased after nomifensine infusion and was unchanged after vehicle infusion. These findings demonstrate profound local control of dopamine release by MORs within the NAc core, which has implications for regulation of reward processing.

CognitiveConstruct

RewardProcessing

10.3758/s13415-018-0638-9

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Substance use is associated with reduced devaluation sensitivity.

Substance use has been linked to impairments in reward processing and decision-making, yet empirical research on the relationship between substance use and devaluation of reward in humans is limited. We report findings from two studies that tested whether individual differences in substance use behavior predicted reward learning strategies and devaluation sensitivity in a nonclinical sample. Participants in Experiment 1 (N = 66) and Experiment 2 (N = 91) completed subscales of the Externalizing Spectrum Inventory and then performed a two-stage reinforcement learning task that included a devaluation procedure. Spontaneous eye blink rate was used as an indirect proxy for dopamine functioning. In Experiment 1, correlational analysis revealed a negative relationship between substance use and devaluation sensitivity. In Experiment 2, regression modeling revealed that while spontaneous eyeblink rate moderated the relationship between substance use and reward learning strategies, substance use alone was related to devaluation sensitivity. These results suggest that once reward-action associations are established during reinforcement learning, substance use predicted reduced sensitivity to devaluation independently of variation in eyeblink rate. Thus, substance use is not only related to increased habit formation but also to difficulty disengaging from learned habits. Implications for the role of the dopaminergic system in habitual responding in individuals with substance use problems are discussed.

CognitiveConstruct

RewardProcessing

10.1007/s11427-018-9371-4

Science China. Life sciences

Sci China Life Sci

An overview of energy and metabolic regulation.

The physiology and behaviors related to energy balance are monitored by the nervous and humoral systems. Because of the difficulty in treating diabetes and obesity, elucidating the energy balance mechanism and identifying critical targets for treatment are important research goals. Therefore, the purpose of this article is to describe energy regulation by the central nervous system (CNS) and peripheral humoral pathway. Homeostasis and rewarding are the basis of CNS regulation. Anorexigenic or orexigenic effects reflect the activities of the POMC/CART or NPY/AgRP neurons within the hypothalamus. Neurotransmitters have roles in food intake, and responsive brain nuclei have different functions related to food intake, glucose monitoring, reward processing. Peripheral gut- or adipose-derived hormones are the major source of peripheral humoral regulation systems. Nutrients or metabolites and gut microbiota affect metabolism via a discrete pathway. We also review the role of peripheral organs, the liver, adipose tissue, and skeletal muscle in peripheral regulation. We discuss these topics and how the body regulates metabolism.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0206421

PloS one

PLoS One

Social stress during adolescence activates long-term microglia inflammation insult in reward processing nuclei.

The experience of social stress during adolescence is associated with higher vulnerability to drug use. Increases in the acquisition of cocaine self-administration, in the escalation of cocaine-seeking behavior, and in the conditioned rewarding effects of cocaine have been observed in rodents exposed to repeated social defeat (RSD). In addition, prolonged or severe stress induces a proinflammatory state with microglial activation and increased cytokine production. The aim of the present work was to describe the long-term effects induced by RSD during adolescence on the neuroinflammatory response and synaptic structure by evaluating different glial and neuronal markers. In addition to an increase in the conditioned rewarding effects of cocaine, our results showed that RSD in adolescence produced inflammatory reactivity in microglia that is prolonged into adulthood, affecting astrocytes and neurons of two reward-processing areas of the brain (the prelimbic cortex, and the nucleus accumbens core). Considered as a whole these results suggest that social stress experience modulates vulnerability to suffer a loss of glia-supporting functions and neuronal functional synaptic density due to drug consumption in later life.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2018.00490

Frontiers in psychiatry

Front Psychiatry

Does Cognitive Dysfunction in Bipolar Disorder Qualify as a Diagnostic Intermediate Phenotype?-A Perspective Paper.

The present perspective paper addresses and discusses whether cognitive dysfunction in bipolar disorder qualifies as a diagnostic intermediate phenotype using the Robin and Guze criteria of diagnostic validity. The paper reviews current data within (1) delineation of the clinical intermediate phenotype, (2) associations of the intermediate phenotype with para-clinical data such as brain imaging and blood-based data, (3) associations to family history / genetics, (4) characteristics during long-term follow-up, and (5) treatment effects on cognition. In this way, the paper identifies knowledge gaps and suggests recommendations for future research within each of the five areas. Based on the current state of knowledge, we conclude that cognitive dysfunction does not qualify as a diagnostic intermediate phenotype or endophenotype for bipolar disorder, although promising new evidence points to emotion and reward processing abnormalities as possible putative endophenotypes.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2018.07.004

Developmental cognitive neuroscience

Dev Cogn Neurosci

What lies beneath peer acceptance in adolescence? Exploring the role of Nucleus Accumbens responsivity to self-serving and vicarious rewards.

Peer relationships play an important role in adolescent social development. Adolescence is also a sensitive period for reward-related processing where Nucleus Accumbens (NAcc) shows peak levels of activity. To investigate the role of reward-related neural processes in peer relationships, we scanned 31 adolescents (16 boys, 15 girls) from 12 to 17 years old and had their classmates rate their likability and dislikability. Using these ratings, we calculated levels of peer acceptance (i.e., likability minus dislikability scores). Participants played a social gambling paradigm in the scanner where we examined NAcc responses to winning for self and winning for best friends. We showed that acceptance by peers was related negatively to activation patterns in the NAcc when winning money for self. Peer acceptance was not related to NAcc activity during vicarious reward processing where participants won money for their best friend. These results point in the direction of an underlying neural mechanism indicating that peer interactions of well-liked adolescents are characterized by a lower focus on benefits for self.

CognitiveConstruct

RewardProcessing

10.3389/fphys.2018.01378

Frontiers in physiology

Front Physiol

Fractal Analysis of BOLD Time Series in a Network Associated With Waiting Impulsivity.

Fractal phenomena can be found in numerous scientific areas including neuroscience. Fractals are structures, in which the whole has the same shape as its parts. A specific structure known as (also called fractal or 1/f noise) is one key fractal manifestation, exhibits both stability and adaptability, and can be addressed via the Hurst exponent (). FMRI studies using on regional fMRI time courses used fractality as an important characteristic to unravel neural networks from artificial noise. In this fMRI-study, we examined 103 healthy male students at rest and while performing the 5-choice serial reaction time task. We addressed fractality in a network associated with waiting impulsivity using the adaptive fractal analysis (AFA) approach to determine . We revealed the fractal nature of the impulsivity network. Furthermore, fractality was influenced by individual impulsivity in terms of decreasing fractality with higher impulsivity in regions of top-down control (left middle frontal gyrus) as well as reward processing (nucleus accumbens and anterior cingulate cortex). We conclude that fractality as determined via is a promising marker to quantify deviations in network functions at an early stage and, thus, to be able to inform preventive interventions before the manifestation of a disorder.

CognitiveConstruct

RewardProcessing

10.1037/abn0000369

Journal of abnormal psychology

J Abnorm Psychol

Effects of reward on spatial working memory in schizophrenia.

Reward processing and cognition are disrupted in schizophrenia (SCZ), yet how these processes interface is unknown. In SCZ, deficits in reward representation may affect motivated, goal-directed behaviors. To test this, we examined the effects of monetary reward on spatial working memory (WM) performance in patients with SCZ. To capture complimentary effects, we tested biophysically grounded computational models of neuropharmacologic manipulations onto a canonical fronto-parietal association cortical microcircuit capable of WM computations. Patients with SCZ (n = 33) and healthy control subjects (HCS; n = 32) performed a spatial WM task with 2 reward manipulations: reward cues presented prior to each trial, or contextually prior to a block of trials. WM performance was compared with cortical circuit models of WM subjected to feed-forward glutamatergic excitation, feed-forward GABAergic inhibition, or recurrent modulation strengthening local connections. Results demonstrated that both groups improved WM performance to reward cues presented prior to each trial (HCS d = -0.62; SCZ d = -1.0), with percent improvement correlating with baseline WM performance (r = .472, p < .001). However, rewards presented contextually before a block of trials did not improve WM performance in patients with SCZ (d = 0.01). Modeling simulations achieved improved WM precision through strengthened local connections via neuromodulation, or feed-forward inhibition. Taken together, this work demonstrates that patients with SCZ can improve WM performance to short-term, but not longer-term rewards-thus, motivated behaviors may be limited by strength of reward representation. A potential mechanism for transiently improved WM performance may be strengthening of local fronto-parietal microcircuit connections via neuromodulation or feed-forward inhibitory drive. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.0457-18.2018

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

J Neurosci

How the Level of Reward Awareness Changes the Computational and Electrophysiological Signatures of Reinforcement Learning.

The extent to which subjective awareness influences reward processing, and thereby affects future decisions, is currently largely unknown. In the present report, we investigated this question in a reinforcement learning framework, combining perceptual masking, computational modeling, and electroencephalographic recordings (human male and female participants). Our results indicate that degrading the visibility of the reward decreased, without completely obliterating, the ability of participants to learn from outcomes, but concurrently increased their tendency to repeat previous choices. We dissociated electrophysiological signatures evoked by the reward-based learning processes from those elicited by the reward-independent repetition of previous choices and showed that these neural activities were significantly modulated by reward visibility. Overall, this report sheds new light on the neural computations underlying reward-based learning and decision-making and highlights that awareness is beneficial for the trial-by-trial adjustment of decision-making strategies. The notion of reward is strongly associated with subjective evaluation, related to conscious processes such as "pleasure," "liking," and "wanting." Here we show that degrading reward visibility in a reinforcement learning task decreases, without completely obliterating, the ability of participants to learn from outcomes, but concurrently increases subjects' tendency to repeat previous choices. Electrophysiological recordings, in combination with computational modeling, show that neural activities were significantly modulated by reward visibility. Overall, we dissociate different neural computations underlying reward-based learning and decision-making, which highlights a beneficial role of reward awareness in adjusting decision-making strategies.

CognitiveConstruct

RewardProcessing

10.1016/j.tins.2018.09.008

Trends in neurosciences

Trends Neurosci

From Stress to Anhedonia: Molecular Processes through Functional Circuits.

Converging evidence across species highlights the contribution of environmental stress to anhedonia (loss of pleasure and/or motivation). However, despite a clear link between stress and the emergence of anhedonic-like behavior in both human and animal models, the underlying biological pathways remain elusive. Here, we synthesize recent findings across multiple levels, from molecular signaling pathways through whole-brain networks, to discuss mechanisms through which stress may influence anhedonia. Recent work suggests the involvement of diverse systems that converge on the mesolimbic reward pathway, including medial-prefrontal cortical circuitry, neuroendocrine stress responses, homeostatic energy regulation systems, and inflammation. We conclude by emphasizing the need to disentangle the influences of key dimensions of stress on specific aspects of reward processing, taking into account individual differences that could moderate this relationship.

CognitiveConstruct

RewardProcessing

10.1177/0145445518805682

Behavior modification

Behav Modif

Reward Network Modulation as a Mechanism of Change in Behavioral Activation.

Behavioral Activation (BA) is a contemporary third-wave psychosocial treatment approach that emphasizes helping individuals become more active in ways that are meaningful to them as a means of improving mood and quality of life. BA has been designated as a well-established, validated treatment for depression by the American Psychological Association following several decades of accumulated empirical support demonstrating that BA techniques successfully reduce depression symptoms and produce other desirable outcomes across a variety of populations and contexts. The purported mechanism of change underlying BA treatment lies in increasing activation, which in turn increases contact with positive reinforcement thereby reversing the cycle of depression. Current studies are further investigating how increasing activation and subsequent contact with mood reinforcers can influence mood and behavior. Specifically, there is growing evidence that BA modifies function of reward-related networks in the brain, and that these changes are associated with clinical improvement. Herein, we provide a brief history of BA, describe the primary components of BA treatment, and describe BA's purported mechanisms of change at behavioral, neural, and subjective activation levels. We present limitations as well as gaps in the current state of knowledge regarding mechanisms of action of BA.

CognitiveConstruct

RewardProcessing

10.1016/bs.irn.2018.07.030

International review of neurobiology

Int Rev Neurobiol

Molecular Imaging of Addictive Behavior in Idiopathic Parkinson's Disease.

Parkinson's disease (PD) is commonly associated with motor symptoms, however cognitive and neurobehavioral complications are increasingly recognized and contribute to long-term disability. Dopamine replacement therapy is effective for motor symptoms, but can also lead to motor side-effects and addictive behavior such as impulse control disorders. Molecular imaging is advancing our knowledge of the mechanisms involved in the development of behavioral addictions. This chapter will discuss potential risk factors and associations with the development of addictive behavior in PD including the role of dopaminergic medication and genetic predisposition. We further will describe the common neurobiology and similarities of addictive behavior in PD to addiction, particularly the neuroanatomy of reward processing and its alteration in substance and behavioral addictions. Finally, we will discuss molecular imaging approaches which are helping to delineate the structure as well as the dynamic interactions between different components involving neurotransmitters, transporters, and receptors.

CognitiveConstruct

RewardProcessing

10.1016/bs.pbr.2018.07.009

Progress in brain research

Prog Brain Res

Potential roles for opioid receptors in motivation and major depressive disorder.

Deficits in motivation are at the core of many neuropsychiatric disorders, including major depressive disorder (MDD). Research in MDD has been heavily focused on anhedonia and depression or negative/positive symptoms of depression, with less research attention focused on the dysregulation of motivational processes. Opioid receptors are widely distributed throughout the brain, particularly in areas implicated in motivation, especially the striatum, nucleus accumbens, medial prefrontal cortex, hippocampus, ventral tegmental area, hypothalamus, and amygdala. Mu, kappa, and delta opioid receptors (MOR, KOR, and DOR, respectively) and their endogenous ligands play an essential role in the regulation of mood, reward processing, and motivated behavior. This review will highlight the impact of opioids in motivational behavior with a particular focus on depression. An understanding of the neurobiology and neural circuits subserving motivational behavior will facilitate treatment of disorders that comprise reward deficits.

CognitiveConstruct

RewardProcessing

10.1016/j.physbeh.2018.10.005

Physiology & behavior

Physiol Behav

High-intensity interval exercise impairs neuroelectric indices of reinforcement-learning.

A single bout of high-intensity interval exercise (HIIE) improves behavioural measures of cognitive function; however, investigations using event-related potentials (ERPs) to examine the systems that underlie these cognitive improvements are lacking. The reward positivity is a positive-going ERP component that indexes reward processing evoked by 'win' feedback and is a candidate marker of an underlying human reinforcement learning system. While HIIE improves behavioural measures of learning, it is unknown how HIIE affects the amplitude of the reward positivity. Therefore, the purpose of this study was to investigate how HIIE affects reward positivity amplitude in response to reward feedback in university students. Using a single-group randomly assigned counterbalance crossover design, 25 healthy university students performed HIIE and control visits on separate days. Electroencephalographic data was recorded before (pre-intervention) and 10 min after (post-intervention) the intervention period while participants played a novel gambling task. The HIIE intervention consisted of 4 separate body-weight exercises totaling 11 min in duration, including rest. The control visit intervention consisted of quietly watching a nature documentary for 11 min. Heart rate (HR) was measured at the same time intervals in both trials. Analysis revealed that HIIE significantly diminished the amplitude of the reward positivity whereas it remained unaffected in the control condition. HR was significantly higher following HIIE compared to control during post-intervention testing. These findings suggest that mechanisms of reinforcement learning are impaired shortly after HIIE cessation, possibly due to persistent, suboptimal arousal as evidenced by elevated HR post-HIIE.

CognitiveConstruct

RewardProcessing

10.1016/j.spen.2018.03.005

Seminars in pediatric neurology

Semin Pediatr Neurol

A Developmental Social Neuroscience Model for Understanding Pathways to Substance Use Disorders During Adolescence.

Adolescence is a transitional period of development characterized by critical changes in physical, neural, cognitive, affective, and social functions. Studies investigating the underlying mechanisms of substance use at levels of self-report, brain response, and behavioral data are generally consistent with suggestions from dual-process model that differential growth rates of frontally mediated control and striato-frontal reward processing are related to a heightened risk of substance use during adolescence. However, social theories highlight the important role of social context and environment in which adolescents grow up and suggest that growing up in an unfavorable environment and in particular exposure to adverse childhood experiences play a huge role in how this vulnerability is translated into actual risk. In this review, we provide a summary of recent theories that examine a number of key individual and social and environmental risk factors underlying risk for early initiation and escalation of substance misuse. We also present a model that expands the dual-process model to incorporate the role of negative self-concept and negative affect associated with growing up in an unfavorable environment and their interactions with cognitive control and inhibition to further explain vulnerability to early initiation and development of substance misuse in adolescents.

CognitiveConstruct

RewardProcessing

10.1016/j.neulet.2018.10.003

Neuroscience letters

Neurosci Lett

A preliminary examination of the relation between neural sensitivity to reward and history of alcohol use disorder among adults with internalizing psychopathologies.

Decreased reward responsiveness, as demonstrated utilizing the event-related potential (ERP) component the reward positivity (RewP), is an established correlate of internalizing psychopathologies (IPs), such as depressive and anxiety disorders. Although IPs are highly comorbid with alcohol use disorders (AUDs) and despite evidence that AUDs are also characterized by aberrant reward processing styles, no studies have examined how AUD history impacts the RewP among adults with IPs. The current preliminary study sought to examine this question in a sample of 65 adults with 1) current IPs (i.e., depression, social anxiety, and/or generalized anxiety, 2) current IPs with a history of an AUD (IP + Past AUD), and 3) no history of a DSM-IV disorder. Participants completed a guessing reward task while electroencephalogram (EEG) was recorded. Results indicated that participants in the IP group exhibited a more attenuated RewP relative to IP + Past AUD and healthy control individuals. Findings from this study highlight the importance of examining diagnostic subgroups among adults with anxiety and depressive disorders, and suggest that a history of AUD may enhance reward reactivity at the neural level in individuals with IPs.

CognitiveConstruct

RewardProcessing

10.1021/acschemneuro.8b00272

ACS chemical neuroscience

ACS Chem Neurosci

Real-Time Accumbal Dopamine Response to Negative Stimuli: Effects of Ethanol.

Activity in the mesolimbic dopamine (DA) pathway is known to have a role in reward processing and related behaviors. The mesolimbic DA response to reward has been well-examined, while the response to aversive or negative stimuli has been studied to a lesser extent and produced inconclusive results. However, a brief increase in the DA concentration in terminals during nociceptive activation has become an established but not well-characterized phenomenon. Consequently, the interpretation of the significance of this neurochemical response is still elusive. The present study was designed to further explore these increases in subsecond DA dynamics triggered by negative stimuli using voltammetry in anesthetized rats. Our experiments revealed that repeated exposure to a tail pinch resulted in more efficacious DA release in rat nucleus accumbens. This fact may suggest a protective nature of immediate DA efflux. Furthermore, a sensitized DA response to a neutral stimulus, such as a touch, was discovered following several noxious pinches, while a touch applied before these pinches did not trigger DA release. Finally, it was found that the pinch-evoked DA efflux was significantly decreased by ethanol acutely administrated at an analgesic dose. Taken together, these results support the hypothesis that subsecond DA release in the nucleus accumbens may serve as an endogenous antinociceptive signal.

CognitiveConstruct

RewardProcessing

10.1002/hbm.24345

Human brain mapping

Hum Brain Mapp

Shifted balance of dorsal versus ventral striatal communication with frontal reward and regulatory regions in cannabis-dependent males.

The transition from voluntary to addictive behavior is characterized by a loss of regulatory control in favor of reward driven behavior. Animal models indicate that this process is neurally underpinned by a shift in ventral-dorsal striatal control of behavior; however, this shift has not been directly examined in humans. The present resting state functional magnetic resonance imaging (fMRI) study employed a two-step approach to: (a) precisely map striatal alterations using a novel, data-driven network classification strategy combining intrinsic connectivity contrast with multivoxel pattern analysis and, (b) to determine whether a ventral to dorsal striatal shift in connectivity with reward and regulatory control regions can be observed in abstinent (28 days) male cannabis-dependent individuals (n = 24) relative to matched controls (n = 28). Network classification revealed that the groups can be reliably discriminated by global connectivity profiles of two striatal regions that mapped onto the ventral (nucleus accumbens) and dorsal striatum (caudate). Subsequent functional connectivity analysis demonstrated a relative shift between ventral and dorsal striatal communication with fronto-limbic regions that have been consistently involved in reward processing (rostral anterior cingulate cortex [ACC]) and executive/regulatory functions (dorsomedial prefrontal cortex [PFC]). Specifically, in the cannabis-dependent subjects, connectivity between the ventral striatum with the rostral ACC increased, whereas both striatal regions were uncoupled from the regulatory dorsomedial PFC. Together, these findings suggest a shift in the balance between dorsal and ventral striatal control in cannabis dependence. Similar changes have been observed in animal models and may promote the loss of control central to addictive behavior.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2018.07.044

Drug and alcohol dependence

Drug Alcohol Depend

Amygdala-orbitofrontal functional connectivity mediates the relationship between sensation seeking and alcohol use among binge-drinking adults.

Decreased amygdala-orbitofrontal cortex (OFC) neural functional connectivity (FC) positively predicts alcohol use among adolescents. Low amygdala-OFC FC is also associated with poor emotion regulation, a trait robustly linked to alcohol use. Thus, decreased amygdala-OFC connectivity may represent a risk factor for the development of alcohol use disorder (AUD) via impaired emotion regulation or reward processing. In this study, we examined amygdala-OFC FC among young adult binge drinkers at high risk for AUD. We also tested if amygdala-OFC FC mediates the relationship between externalizing personality traits and alcohol use. Healthy male and female (n = 39) binge drinkers completed a resting state fMRI scan and the Eysenck Impulsive Personality questionnaire. We utilized seed-based connectivity of the left and right amygdala to prefrontal regions as well as mediation analysis. Individuals with higher weekly alcohol use displayed decreased right amygdala-OFC FC. Furthermore, high trait venturesomeness, but not impulsivness, was associated with decreased right amygdala-OFC FC. Finally, right amygdala-OFC FC mediated the relationship between trait venturesomeness and weekly drinking; individuals with high trait venturesomeness displayed decreased right amygdala-OFC FC, which in turn predicted greater weekly drinking. Our findings corroborate and extend the adolescent literature by showing that decreased amygdala-OFC FC is associated with higher alcohol consumption among adults at elevated risk for AUD. This study also demonstrates for the first time that this neural profile reflects a tendency to sensation seeking. In sum, our findings suggest that amygdala-OFC FC may be an objective neural target for alcohol use prevention and intervention.

CognitiveConstruct

RewardProcessing

10.1016/j.psyneuen.2018.09.027

Psychoneuroendocrinology

Psychoneuroendocrinology

Childhood maltreatment moderates the influence of genetic load for obesity on reward related brain structure and function in major depression.

Obesity is a clinically relevant and highly prevalent somatic comorbidity of major depression (MDD). Genetic predisposition and history of childhood trauma have both independently been demonstrated to act as risk factors for obesity and to be associated with alterations in reward related brain structure and function. We therefore aimed to investigate the influence of childhood maltreatment and genetic risk for obesity on structural and functional imaging correlates associated with reward processing in MDD. 161 MDD patients underwent structural and functional MRI during a frequently used card guessing paradigm. Main and interaction effects of a polygenic risk score for obesity (PRS) and childhood maltreatment experiences as assessed using the Childhood Trauma Questionnaire (CTQ) were investigated. We found that maltreatment experiences and polygenic risk for obesity significantly interacted on a) body mass index b) gray matter volume of the orbitofrontal cortex as well as on c) BOLD response in the right insula during reward processing. While polygenic risk for obesity was associated with elevated BMI as well as with decreased OFC gray matter and increased insular BOLD response in non-maltreated patients, these associations were absent in patients with a history of childhood trauma. No significant main effect of PRS or maltreatment on gray matter or BOLD response could be detected at the applied thresholds. The present study suggests that childhood maltreatment moderates the influence of genetic load for obesity on BMI as well as on altered brain structure and function in reward related brain circuits in MDD.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2018.09.059

NeuroImage

Neuroimage

Disentangling common from specific processing across tasks using task potency.

When an individual engages in a task, the associated evoked activities build upon already ongoing activity, shaped by an underlying functional connectivity baseline (Fox et al., 2009; Smith et al., 2009; Tavor et al., 2016). Building on the idea that rest represents the brain's full functional repertoire, we here incorporate the idea that task-induced functional connectivity modulations ought to be task-specific with respect to their underlying resting state functional connectivity. Various metrics such as clustering coefficient or average path length have been proposed to index processing efficiency, typically from single fMRI session data. We introduce a framework incorporating task potency, which provides direct access to task-specificity by enabling direct comparison between task paradigms. In particular, to study functional connectivity modulations related to cognitive involvement in a task we define task potency as the amplitude of a connectivity modulation away from its baseline functional connectivity architecture as observed during a resting state acquisition. We demonstrate the use of our framework by comparing three tasks (visuo-spatial working memory, reward processing, and stop signal task) available within a large cohort. Using task potency, we demonstrate that cognitive operations are supported by a set of common within-network interactions, supplemented by connections between large-scale networks in order to solve a specific task.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2018.00437

Frontiers in psychiatry

Front Psychiatry

Role of Frontostriatal Connectivity in Adolescents With Excessive Smartphone Use.

As smartphone use has grown rapidly over recent decade, it has been a growing interest in the potential negative impact of excessive smartphone use. In this study, we aim to identify altered brain connectivity associated with excessive smartphone use, and to investigate correlations between withdrawal symptoms, cortisol concentrations, and frontostriatal connectivity. We focused on investigating functional connectivity in frontostriatal regions, including the orbitofrontal cortex (OFC), midcingulate cortex (MCC), and nucleus accumbens (NAcc), which is related to reward processing and cognitive control. We analyzed data from 38 adolescents with excessive smartphone use (SP) and 42 healthy controls (HC). In the SP group compared with HC, we observed lower functional connectivity between the right OFC and NAcc, and between the left OFC and MCC. Moreover, functional connectivity between the MCC and NAcc was greater in SP compared with HC. Subsequently, we examined the relationship between Internet use withdrawal symptoms, cortisol concentrations, and functional connectivity between the OFC and NAcc in SP and HC. We observed that more severe withdrawal symptoms were associated with higher cortisol concentrations in adolescents with excessive smartphone use. The most interesting finding was that we observed a negative correlation between OFC connectivity with the NAcc and both withdrawal symptoms and cortisol concentrations. The functional connectivity between the OFC and NAcc, and between the OFC and MCC are related to cognitive control of emotional stimuli including reward. The current study suggests that adolescents with SP had reduced functional connectivity in these regions related to cognitive control. Furthermore, Internet use withdrawal symptoms appear to elicit cortisol secretion, and this psychophysiological change may affect frontostriatal connectivity. Our findings provide important clues to understanding the effects of excessive use of smartphones on brain functional connectivity in adolescence.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsy087

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Early maternal care may counteract familial liability for psychopathology in the reward circuitry.

Reward processing is altered in various psychopathologies and has been shown to be susceptible to genetic and environmental influences. Here, we examined whether maternal care may buffer familial risk for psychiatric disorders in terms of reward processing. Functional magnetic resonance imaging during a monetary incentive delay task was acquired in participants of an epidemiological cohort study followed since birth (N = 172, 25 years). Early maternal stimulation was assessed during a standardized nursing/playing setting at the age of 3 months. Parental psychiatric disorders (familial risk) during childhood and the participants' previous psychopathology were assessed by diagnostic interview. With high familial risk, higher maternal stimulation was related to increasing activation in the caudate head, the supplementary motor area, the cingulum and the middle frontal gyrus during reward anticipation, with the opposite pattern found in individuals with no familial risk. In contrast, higher maternal stimulation was associated with decreasing caudate head activity during reward delivery and reduced levels of attention deficit hyperactivity disorder (ADHD) in the high-risk group. Decreased caudate head activity during reward anticipation and increased activity during delivery were linked to ADHD. These findings provide evidence of a long-term association of early maternal stimulation on both adult neurobiological systems of reward underlying externalizing behavior and ADHD during development.

CognitiveConstruct

RewardProcessing

10.1007/s11065-018-9385-5

Neuropsychology review

Neuropsychol Rev

The Neural Substrate of Reward Anticipation in Health: A Meta-Analysis of fMRI Findings in the Monetary Incentive Delay Task.

The monetary incentive delay task breaks down reward processing into discrete stages for fMRI analysis. Here we look at anticipation of monetary gain and loss contrasted with neutral anticipation. We meta-analysed data from 15 original whole-brain group maps (n = 346) and report extensive areas of relative activation and deactivation throughout the whole brain. For both anticipation of gain and loss we report robust activation of the striatum, activation of key nodes of the putative salience network, including anterior cingulate and anterior insula, and more complex patterns of activation and deactivation in the central executive and default networks. On between-group comparison, we found significantly greater relative deactivation in the left inferior frontal gyrus associated with incentive valence. This meta-analysis provides a robust whole-brain map of a reward anticipation network in the healthy human brain.

CognitiveConstruct

RewardProcessing

10.1002/hbm.24377

Human brain mapping

Hum Brain Mapp

Reward-related regions form a preferentially coupled system at rest.

Neuroimaging studies have implicated a set of striatal and orbitofrontal cortex (OFC) regions that are commonly activated during reward processing tasks. Resting-state functional connectivity (RSFC) studies have demonstrated that the human brain is organized into several functional systems that show strong temporal coherence in the absence of goal-directed tasks. Here we use seed-based and graph-theory RSFC approaches to characterize the systems-level organization of putative reward regions of at rest. Peaks of connectivity from seed-based RSFC patterns for the nucleus accumbens (NAcc) and orbitofrontal cortex (OFC) were used to identify candidate reward regions which were merged with a previously used set of regions (Power et al., 2011). Graph-theory was then used to determine system-level membership for all regions. Several regions previously implicated in reward-processing (NAcc, lateral and medial OFC, and ventromedial prefrontal cortex) comprised a distinct, preferentially coupled system. This RSFC system is stable across a range of connectivity thresholds and shares strong overlap with meta-analyses of task-based reward studies. This reward system shares between-system connectivity with systems implicated in cognitive control and self-regulation, including the fronto-parietal, cingulo-opercular, and default systems. Differences may exist in the pathways through which control systems interact with reward system components. Whereas NAcc is functionally connected to cingulo-opercular and default systems, OFC regions show stronger connectivity with the fronto-parietal system. We propose that future work may be able to interrogate group or individual differences in connectivity profiles using the regions delineated in this work to explore potential relationships to appetitive behaviors, self-regulation failure, and addiction.

CognitiveConstruct

RewardProcessing

10.1016/j.psyneuen.2018.09.007

Psychoneuroendocrinology

Psychoneuroendocrinology

The corticosteroid prednisolone increases amygdala and insula reactivity to food approach signals in healthy young men.

Short- and long-term treatment with glucocorticoids is widely used in clinical practice and frequently induces features of iatrogenic Cushing syndrome, such as abdominally centered weight gain. Despite decades of glucocorticoids usage, the mechanisms underlying these side effects are still only partly understood. One possibility is that glucocorticoids impact subcortical (hypothalamus, amygdala, insula) and cortical (orbitofrontal and cingulate cortex) brain regions involved in appetite regulation and reward processing. In the present study, we used functional magnetic resonance imaging (fMRI) to study the acute effects of a prednisolone infusion on reactivity of brain reward systems to food stimuli. Twenty healthy normal-weight men were tested in a randomized, double-blind, cross-over study. After an overnight fast and infusion of either 250 mg prednisolone or placebo (always administered between 8 and 9 A M), fMRI scans were taken while presenting food and object pictures in a Go/NoGo (GNG) task. At home, participants were asked to register what they had eaten. On the following morning they came back to the lab and had a supervised ad libitum breakfast at a standardized buffet. Food-Go in contrast to Object-Go pictures yielded increased blood oxygen level dependent (BOLD) activity in hippocampus, amygdala, orbitofrontal cortex, insula and anterior cingulate cortex. Prednisolone increased activation in the bilateral amygdala and right insula for approach-associated food pictures. The buffet test did not reveal significant differences in calorie consumption or preferences of different macronutrients. However, prednisolone-induced insula reactivity to Food-Go images was associated with greater caloric intake, both at home and in the standardized buffet. In sum, we observed a specific effect of prednisolone on the BOLD response of the amygdala and insula to approach-associated food stimuli. As these brain areas have previously been implicated in hedonic eating, the present pattern of results may reflect an increased anticipated reward value of food modulated by glucocorticoids. These effects might potentially drive increased food intake and weight gain under prolonged glucocorticoid treatment.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2018.09.051

NeuroImage

Neuroimage

Increased responses of the reward circuitry to positive task feedback following acute stress in healthy controls but not in siblings of schizophrenia patients.

Acute stress is known to affect the way we process rewards. For example, during, or directly after stress, activity within key brain areas of the reward circuitry is reduced when a reward is presented. Generally, the effects of stress on the brain are time-dependent, changing neural and cognitive processing in the aftermath of stress to aid recovery. Such a dynamic response to stress is important for resilience on the longer term. However, relatively little is known about reward processing during the recovery phase of stress and whether this is changed in individuals at increased risk for stress-related psychopathology. Healthy male individuals (N = 40) and unaffected siblings of schizophrenia patients (N = 40) were randomized to either an acute stress task (Trier Social Stress Test) or a no-stress task. Neural responses during reward anticipation and reward feedback (monetary gain or no gain) were examined 50 min later using an fMRI monetary incentive delay task. The ventral striatum and orbitofrontal cortex (OFC) were used as predefined hypothesis-driven regions of interest. Neural responses following stress differed between controls and siblings during reward feedback (group × stress interaction OFC p = 0.003, ventral striatum p = 0.031), showing increased ventral striatum and OFC responses following stress in healthy controls only. Exploratory analyses revealed that this effect was most pronounced during hit trials (compared to when a reward was omitted), and independent of monetary value. Stress did not affect subsequent reward processing in siblings of schizophrenia patients. We found no significant differences between controls and siblings in ventral striatum and OFC responses during reward anticipation following stress. This study shows that ventral striatum and OFC responses to positive task feedback are increased in the aftermath of stress in healthy male controls, regardless of monetary value. This indicates a dynamic shift from previously reported reduced responses in the striatum and OFC to reward feedback directly after stress to increased responses to both reward and non-reward feedback during the recovery phase of stress. These increased neural responses following stress were absent in siblings of schizophrenia patients. Together, these findings indicate that stress recovery is affected in this at-risk group, particularly in responses to positive feedback following stress.

CognitiveConstruct

RewardProcessing

10.1038/s41398-018-0247-y

Translational psychiatry

Transl Psychiatry

Back-translating behavioral intervention for autism spectrum disorders to mice with blunted reward restores social abilities.

The mu opioid receptor (MOR) plays a critical role in modulating social behavior in humans and animals. Accordingly, MOR null mice display severe alterations in their social repertoire as well as multiple other behavioral deficits, recapitulating core and secondary symptoms of autism spectrum disorder (ASD). Such behavioral profile suggests that MOR dysfunction, and beyond this, altered reward processes may contribute to ASD etiopathology. Interestingly, the only treatments that proved efficacy in relieving core symptoms of ASD, early behavioral intervention programs, rely principally on positive reinforcement to ameliorate behavior. The neurobiological underpinnings of their beneficial effects, however, remain poorly understood. Here we back-translated applied behavior analysis (ABA)-based behavioral interventions to mice lacking the MOR (Oprm1), as a model of autism with blunted reward processing. By associating a positive reinforcement, palatable food reward, to daily encounter with a wild-type congener, we were able to rescue durably social interaction and preference in Oprm1 mice. Along with behavioral improvements, the expression of marker genes of neuronal activity and plasticity as well as genes of the oxytocin/vasopressin system were remarkably normalized in the reward/social circuitry. Our study provides further evidence for a critical involvement of reward processes in driving social behavior and opens new perspectives regarding therapeutic intervention in ASD.

CognitiveConstruct

RewardProcessing

10.1002/hbm.24370

Human brain mapping

Hum Brain Mapp

Mapping adolescent reward anticipation, receipt, and prediction error during the monetary incentive delay task.

The functional neuroanatomy and connectivity of reward processing in adults are well documented, with relatively less research on adolescents, a notable gap given this developmental period's association with altered reward sensitivity. Here, a large sample (n = 1,510) of adolescents performed the monetary incentive delay (MID) task during functional magnetic resonance imaging. Probabilistic maps identified brain regions that were reliably responsive to reward anticipation and receipt, and to prediction errors derived from a computational model. Psychophysiological interactions analyses were used to examine functional connections throughout reward processing. Bilateral ventral striatum, pallidum, insula, thalamus, hippocampus, cingulate cortex, midbrain, motor area, and occipital areas were reliably activated during reward anticipation. Bilateral ventromedial prefrontal cortex and bilateral thalamus exhibited positive and negative activation, respectively, during reward receipt. Bilateral ventral striatum was reliably active following prediction errors. Previously, individual differences in the personality trait of sensation seeking were shown to be related to individual differences in sensitivity to reward outcome. Here, we found that sensation seeking scores were negatively correlated with right inferior frontal gyrus activity following reward prediction errors estimated using a computational model. Psychophysiological interactions demonstrated widespread cortical and subcortical connectivity during reward processing, including connectivity between reward-related regions with motor areas and the salience network. Males had more activation in left putamen, right precuneus, and middle temporal gyrus during reward anticipation. In summary, we found that, in adolescents, different reward processing stages during the MID task were robustly associated with distinctive patterns of activation and of connectivity.

CognitiveConstruct

RewardProcessing

10.1093/ijnp/pyy081

The international journal of neuropsychopharmacology

Int J Neuropsychopharmacol

Circuit Mechanisms of Reward, Anhedonia, and Depression.

Pleasure and motivation are important factors for goal-directed behavior and well-being in both animals and humans. Intact hedonic capacity requires an undisturbed interplay between a number of different brain regions and transmitter systems. Concordantly, dysfunction of networks encoding for reward have been shown in depression and other psychiatric disorders. The development of technological possibilities to investigate connectivity on a functional level in humans and to directly influence networks in animals using optogenetics among other techniques has provided new important insights in this field of research.In this review, we aim to provide an overview on the neurobiological substrates of anhedonia on a network level. For this purpose, definition of anhedonia and the involved reward components are described first, then current data on reward networks in healthy individuals and in depressed patients are summarized, and the roles of different neurotransmitter systems involved in reward processing are specified. Based on this information, the impact of different therapeutic approaches on reward processing is described with a particular focus on deep brain stimulation (DBS) as a possibility for a direct modulation of human brain structures in vivo.Overall, results of current studies emphasize the importance of anhedonia in psychiatric disorders and the relevance of targeting this phenotype for a successful psychiatric treatment. However, more data incorporating these results for the refinement of methodological approaches are needed to be able to develop individually tailored therapeutic concepts based on both clinical and neurobiological profiles of patients.

CognitiveConstruct

RewardProcessing

10.1007/s11682-018-9959-0

Brain imaging and behavior

Brain Imaging Behav

Neural correlates of apathy in patients with neurodegenerative disorders: an activation likelihood estimation (ALE) meta-analysis.

Apathy is commonly reported in Alzheimer's Disease (AD), Fronto-Temporal Dementia (FTD) and Parkinson's Disease (PD). In our meta-analysis we analysed a total of 41 studies to identify brain patterns associated with apathy. For these purposes we used activation likelihood estimation meta-analyses. Our main overall analysis showed that apathy is associated to hypometabolism and a decreased gray matter volume in the left inferior frontal gyrus (BA 45, 46). Disorder-specific analyses, not performed by means of meta-analysis, because of the small number of studies, but by means a label-based review, revealed an altered brain perfusion and decreased gray matter volume in anterior cingulate cortex (BA 24, 32) in AD patients and a decreased gray matter volume in inferior frontal gyrus (BA 44, 45) and parietal cortex (BA 40) in FTD patients. These findings suggest that apathy is mainly associated with a cortical dysfunction of areas involved in executive-cognitive processing (i.e. action planning) and emotional regulation (auto-activation and reward processing). Knowledge about the neural underpinnings of apathy is crucial for understanding its clinical characteristics in neurodegenerative diseases and for developing novel strategies of treatment in clinical practice.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2018.00404

Frontiers in psychiatry

Front Psychiatry

Editorial: Neural Mechanisms Underlying Internet Gaming Disorder.

CognitiveConstruct

RewardProcessing

10.1007/s12402-018-0269-6

Attention deficit and hyperactivity disorders

Atten Defic Hyperact Disord

The impact of successful learning of self-regulation on reward processing in children with ADHD using fMRI.

Neurofeedback (NF) is a non-pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) that is targeting self-regulation, is efficacious when standard protocols are used and induces partly specific neurophysiological changes in the inhibitory network. However, its effects on reward processing, which is also considered an important aspect of ADHD and has been linked to neurophysiological deficits, remain unknown. Children with ADHD (N = 15, mean age 11.8, SD 1.52) were randomly assigned to either slow cortical potential NF (n = 8) or EMG biofeedback control training (n = 7) and received 20 sessions of training under comparable conditions. Learning was defined as the slope of successful training runs across all transfer sessions. Whole brain analysis, region-of-interest analysis of anticipatory ventral striatal (VS) activation, and analysis of behavioral data were performed. Clinically, the NF group improved more than the EMG group. Whole brain analysis indicated increased activation in the left superior frontal gyrus in the control group only, and in medial prefrontal cortex and dorsolateral prefrontal gyrus (DLPFC) after treatment across all groups. Only successful learners of self-regulation (n = 8) showed increased left inferior frontal gyrus and DLPFC activation after treatment. Left VS activation was increased after treatment and showed a significant time*medication-status interaction. Specific treatment effects were found in left frontal regions for the control treatment and successful learners. Also, unmedicated participants, irrespective of treatment type or successful learning, showed treatment-induced improvement in reward processing. The results suggest no prominent specific effect of NF on reward processing. However, cautious interpretation is warranted due to the small sample.

CognitiveConstruct

RewardProcessing

10.1073/pnas.1805573115

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

Proc Natl Acad Sci U S A

Effects of self-transcendence on neural responses to persuasive messages and health behavior change.

Self-transcendence refers to a shift in mindset from focusing on self-interests to the well-being of others. We offer an integrative neural model of self-transcendence in the context of persuasive messaging by examining the mechanisms of self-transcendence in promoting receptivity to health messages and behavior change. Specifically, we posited that focusing on values and activities that transcend the self can allow people to see that their self-worth is not tied to a specific behavior in question, and in turn become more receptive to subsequent, otherwise threatening health information. To test whether inducing self-transcendent mindsets before message delivery would help overcome defensiveness and increase receptivity, we used two priming tasks, affirmation and compassion, to elicit a transcendent mindset among 220 sedentary adults. As preregistered, those who completed a self-transcendence task before health message exposure, compared with controls, showed greater increases in objectively logged levels of physical activity throughout the following month. In the brain, self-transcendence tasks up-regulated activity in a region of the ventromedial prefrontal cortex, chosen for its role in positive valuation and reward processing. During subsequent health message exposure, self-transcendence priming was associated with increased activity in subregions of the ventromedial prefrontal cortex, implicated in self-related processing and positive valuation, which predicted later decreases in sedentary behavior. The present findings suggest that having a positive self-transcendent mindset can increase behavior change, in part by increasing neural receptivity to health messaging.

CognitiveConstruct

RewardProcessing

10.1111/gbb.12519

Genes, brain, and behavior

Genes Brain Behav

Systems genetics of sensation seeking.

Sensation seeking is a multifaceted, heritable trait which predicts the development of substance use and abuse in humans; similar phenomena have been observed in rodents. Genetic correlations among sensation seeking and substance use indicate shared biological mechanisms, but the genes and networks underlying these relationships remain elusive. Here, we used a systems genetics approach in the BXD recombinant inbred mouse panel to identify shared genetic mechanisms underlying substance use and preference for sensory stimuli, an intermediate phenotype of sensation seeking. Using the operant sensation seeking (OSS) paradigm, we quantified preference for sensory stimuli in 120 male and 127 female mice from 62 BXD strains and the C57BL/6J and DBA/2J founder strains. We used relative preference for the active and inactive levers to dissociate preference for sensory stimuli from locomotion and exploration phenotypes. We identified genomic regions on chromosome 4 (155.236-155.742 Mb) and chromosome 13 (72.969-89.423 Mb) associated with distinct behavioral components of OSS. Using publicly available behavioral data and mRNA expression data from brain regions involved in reward processing, we identified (a) genes within these behavioral QTL exhibiting genome-wide significant cis-eQTL and (b) genetic correlations among OSS phenotypes, ethanol phenotypes and mRNA expression. From these analyses, we nominated positional candidates for behavioral QTL associated with distinct OSS phenotypes including Gnb1 and Mef2c. Genetic covariation of Gnb1 expression, preference for sensory stimuli and multiple ethanol phenotypes suggest that heritable variation in Gnb1 expression in reward circuitry partially underlies the widely reported relationship between sensation seeking and substance use.

CognitiveConstruct

RewardProcessing

10.1016/j.cub.2018.07.045

Current biology : CB

Curr Biol

Encoding of Multiple Reward-Related Computations in Transient and Sustained High-Frequency Activity in Human OFC.

Human orbitofrontal cortex (OFC) has long been implicated in value-based decision making. In recent years, convergent evidence from human and model organisms has further elucidated its role in representing reward-related computations underlying decision making. However, a detailed description of these processes remains elusive due in part to (1) limitations in our ability to observe human OFC neural dynamics at the timescale of decision processes and (2) methodological and interspecies differences that make it challenging to connect human and animal findings or to resolve discrepancies when they arise. Here, we sought to address these challenges by conducting multi-electrode electrocorticography (ECoG) recordings in neurosurgical patients during economic decision making to elucidate the electrophysiological signature, sub-second temporal profile, and anatomical distribution of reward-related computations within human OFC. We found that high-frequency activity (HFA) (70-200 Hz) reflected multiple valuation components grouped in two classes of valuation signals that were dissociable in temporal profile and information content: (1) fast, transient responses reflecting signals associated with choice and outcome processing, including anticipated risk and outcome regret, and (2) sustained responses explicitly encoding what happened in the immediately preceding trial. Anatomically, these responses were widely distributed in partially overlapping networks, including regions in the central OFC (Brodmann areas 11 and 13), which have been consistently implicated in reward processing in animal single-unit studies. Together, these results integrate insights drawn from human and animal studies and provide evidence for a role of human OFC in representing multiple reward computations.

CognitiveConstruct

RewardProcessing

10.1017/S0033291718002441

Psychological medicine

Psychol Med

Early change in reward and punishment sensitivity as a predictor of response to antidepressant treatment for major depressive disorder: a CAN-BIND-1 report.

In an effort to optimize patient outcomes, considerable attention is being devoted to identifying patient characteristics associated with major depressive disorder (MDD) and its responsiveness to treatment. In the current study, we extend this work by evaluating whether early change in these sensitivities is associated with response to antidepressant treatment for MDD. Participants included 210 patients with MDD who were treated with 8 weeks of escitalopram and 112 healthy comparison participants. Of the original 210 patients, 90 non-responders received adjunctive aripiprazole for an additional 8 weeks. Symptoms of depression and anhedonia were assessed at the beginning of treatment and 8 weeks later in both samples. Reward and punishment sensitivity were assessed using the BIS/BAS scales measured at the initiation of treatment and 2 weeks later. Individuals with MDD exhibited higher punishment sensitivity and lower reward sensitivity compared with healthy comparison participants. Change in reward sensitivity during the first 2 weeks of treatment was associated with improved depressive symptoms and anhedonia following 8 weeks of treatment with escitalopram. Similarly, improvement in reward responsiveness during the first 2 weeks of adjunctive therapy with aripiprazole was associated with fewer symptoms of depression at post-treatment. Findings highlight the predictive utility of early change in reward sensitivity during antidepressant treatment for major depression. In a clinical setting, a lack of change in early reward processing may signal a need to modify a patient's treatment plan with alternative or augmented treatment approaches.

CognitiveConstruct

RewardProcessing

10.1016/j.neulet.2018.09.016

Neuroscience letters

Neurosci Lett

Acute morphine administration alters the power of local field potentials in mesolimbic pathway of freely moving rats: Involvement of dopamine receptors.

Increasing number of evidence support the role of ventral tegmental area (VTA) and nucleus accumbens (NAc) in mediating the opiate effects as the two critical components of brain reward pathway. It is believed that VTA to NAC dopaminergic projections mediate the reinforcing effects induced by opioid drugs. Although numerous studies have investigated mechanisms of reward processing in these brain regions, alterations of local field potentials (LFPs), as an index of total synaptic currents, has not been previously addressed. In the present study, thin metal electrodes were implanted in both VTA and shell sub-region of NAc to simultaneously record the spontaneous LFPs in freely moving rats. After one week recovery period, a single dose of morphine was systemically administered and the LFP recording was performed 15, 30, 45 and 60 post-injection. Also, in order to assess the role of dopamine system, two groups of animals were pre-treated by selective antagonists of dopamine type-1 and type-2 receptors 15 min prior to morphine injection. The obtained results indicated that in VTA, acute morphine administration potentiates the power of all LFP frequency bands (i.e. delta, theta, alpha, beta and gamma). However, in NAc shell, theta wave was significantly attenuated by morphine and other components were not affected. In addition, pre-treatment with both antagonists prevented the observed effect of morphine on LFP power suggesting the involvement of dopamine receptors in this process. Future studies should address mechanisms of dopamine-morphine interactions. It is also valuable to focus on acute and chronic effects of morphine on LFP power and assessment of the observed effects following naloxone challenge.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2018.00178

Frontiers in behavioral neuroscience

Front Behav Neurosci

A Novel Role for the Periaqueductal Gray in Consummatory Behavior.

The periaqueductal gray (PAG) has a well-established role in pain processing, autonomic function and behavioral responses to fear. Anatomical work suggests the PAG may mediate food intake and reward processing as it has extensive reciprocal connections within brain circuits that mediate appetitive processes and consummatory behaviors such as prefrontal cortex, hypothalamus, amygdala, parabrachial nucleus (PBN) and ventral tegmental area (Kelley et al., 2005). Therefore, we investigated if the PAG of hungry rats has a functional role in appetitive and consummatory behaviors. To address this, PAG was pharmacologically inactivated during a spatial working memory task with muscimol (0.1-0.3 μg), a GABA agonist via intracranial infusion. Inactivation of PAG led to reduced intake of food rewards and increased errors on this task. To focus on the specific effects PAG inactivation had on food consumption, PAG was inactivated during two separate food intake tasks in a separate group of rats. Again, PAG inactivation resulted in a significant decrease in food consumption, as well as an increased latency to consume food. We next investigated PAG neural responses to reward encounters. A different group of rats performed the same task used in Experiment 1 while the activity of PAG neurons was recorded. In a subset of PAG neurons, reward encounters elicited phasic excitation. A separate subset of PAG neurons were inhibited during reward encounters. These responses scaled with the size of the reward, with sustained excitation or inhibition in response to large rewards compared to small. Our data also show that separate groups of PAG neurons in awake behaving animals display either increased and decreased neural responses to reward encounters. Additionally, a proportion of neurons were modulated by the animals' velocity. This study is the first to show that PAG neurons process reward-related information, perhaps to mediate consummatory behaviors related to food consumption.

CognitiveConstruct

RewardProcessing

10.1038/s41398-018-0241-4

Translational psychiatry

Transl Psychiatry

Increased inflammation and brain glutamate define a subtype of depression with decreased regional homogeneity, impaired network integrity, and anhedonia.

Combined increases in peripheral inflammation and brain glutamate may identify a subtype of depression with distinct neuroimaging signatures. Two contrasting subgroups of depressed subjects-with and without combined elevations in plasma C-reactive protein (CRP) and basal ganglia glutamate (high and low CRP-Glu, respectively) were identified by hierarchical clustering using plasma CRP (indexing peripheral inflammation) and magnetic resonance spectroscopy (MRS)-based measurement of left basal ganglia glutamate. High CRP-Glu group status was associated with greater severity of anhedonia and cognitive and motor slowing. Local- and network-level measures of functional integrity were determined using brain oxygen level-dependent (BOLD)-oscillatory activity and graph theory. Greater decreases in concordance of oscillatory activity between neighboring voxels (Regional Homogeneity 'ReHo', p < 0.01) within the MRS volume-of-interest was associated with the High CRP-Glu subgroup. Using brain-wide, CRP-Glu ReHo contrast maps, a covariance network of 41 regions-of-interest (ROIs) with similar ReHo decreases was identified in the High CRP-Glu group and was located to brain structures previously implicated in depression. The 41-ROI network was further decomposed into four subnetworks. ReHo decreases within Subnetwork4-comprised of reward processing regions -was associated with anhedonia. Subnetwork4 ReHo also predicted decreased network integrity, which mediated the link between local ReHo and anhedonia in the Low but not High CRP-Glu group. These findings suggest that decreased ReHo and related disruptions in network integrity may reflect toxic effects of inflammation-induced increases in extrasynaptic glutamate signaling. Moreover, local BOLD oscillatory activity as reflected in ReHo might be a useful measure of target-engagement in the brain for treatment of inflammation-induced behaviors.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2018.09.006

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation.

A wealth of evidence has implicated inflammation in the development of depression. Yet, the heterogeneous nature of depression has impeded efforts to understand, prevent, and treat the disease. The purpose of this integrative review is to summarize the connections between inflammation and established core features of depression that exhibit more homogeneity than the syndrome itself: exaggerated reactivity to negative information, altered reward processing, decreased cognitive control, and somatic syndrome. For each core feature, we first provide a brief overview of its relevance to depression and neurobiological underpinnings, and then review evidence investigating a potential role of inflammation. We focus primarily on findings from experimental paradigms of exogenously-induced inflammation. We conclude that inflammation likely plays a role in exaggerated reactivity to negative information, altered reward reactivity, and somatic symptoms. There is less evidence supporting an effect of inflammation on cognitive control as assessed by standard neuropsychological measures. Finally, we discuss implications for future research and recommendationsfor how to test the role of inflammation in the pathogenesis of heterogeneous psychiatric disorders.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2018.08.057

Journal of affective disorders

J Affect Disord

Preliminary support for the role of reward relevant effort and chronotype in the depression/insomnia comorbidity.

The presence of insomnia in the context of depression is linked to a number of poor outcomes including reduced treatment response, increased likelihood of relapse, and greater functional impairment. Given the frequent co-occurrence of depression and insomnia, research into systems and processes relevant to both disorders, specifically reward processing and circadian rhythm disruption, may help parse this complex comorbidity. A pilot study was conducted on a sample of 10 veterans with clinically significant depression and insomnia symptoms. Participants completed objective (actigraphy) and subjective (sleep diary) assessments of sleep, self-reports of chronotype, and behavioral tasks assessing reward relevant effort before and after 6 sessions of Cognitive Behavioral Therapy for Insomnia. Insomnia and depression significantly improved following CBT-I. Subjective sleep parameters significantly improved with large effect sizes. Actigraphy results were nonsignificant, but effect sizes for sleep efficiency and onset latency were in the medium range. Chronotype shifted significantly toward morningness following CBT-I, and an earlier chronotype at baseline was associated with increased reward effort following treatment. Changes in chronotype, depression and insomnia were not associated with changes in effort. Findings are limited by small sample size and lack of randomized control group. Findings should be interpreted as hypothesis generating in the service of furthering research aimed at uncovering potential mechanisms underlying the depression/insomnia comorbidity. Analyses of sleep data in extant datasets of reward processing impairments in depression as well as original projects aimed at exploring potential sleep, circadian rhythm, and reward interactions in depression are encouraged.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2018.00371

Frontiers in psychiatry

Front Psychiatry

Internet Game Overuse Is Associated With an Alteration of Fronto-Striatal Functional Connectivity During Reward Feedback Processing.

Internet gaming disorder is associated with abnormal reward processing in the reward circuit, which is known to interact with other brain regions during feedback learning. Kim et al. (1) observed that individuals with internet game overuse (IGO) exhibit altered behavior and neural activity for non-monetary reward, but not for monetary reward. Here, we extend our analysis of IGO to the functional connectivity of the reward network. Functional MRI data were obtained during a stimulus-response association learning task from 18 young males with IGO and 20 age-matched controls, where either monetary or non-monetary rewards were given as positive feedback for a correct response. Group differences in task-dependent functional connectivity were examined for the ventromedial prefrontal cortex (vmPFC) and ventral striatum (VS), which are known for reward evaluation and hedonic response processing, respectively, using a generalized form of the psychophysiological interaction approach. For non-monetary reward processing, no differences in functional connectivity were found. In contrast, for monetary reward, connectivity of the vmPFC with the left caudate nucleus was weaker for the IGO group relative to controls, while vmPFC connectivity with the right nucleus accumbens (NAcc) was elevated. The strength of vmPFC-NAcc functional connectivity appeared to be behaviorally relevant, because individuals with stronger vmPFC-NAcc connectivity showed lower learning rates for monetary reward. In addition, the IGO group showed weaker ventral striatum functional connectivity with various brain regions, including the right ventrolateral prefrontal cortex, dorsal anterior cingulate regions, and left pallidum. Thus, for monetary reward, the IGO group exhibited stronger functional connectivity within the brain regions involved in motivational salience, whereas they showed reduced functional connectivity the widely distributed brain areas involved in learning or attention. These differences in functional connectivity of reward networks, along with related behavioral impairments of reward learning, suggest that internet gaming disorder is associated with the increased incentive salience or "wanting" of addiction disorders, and may serve as the neurobiological mechanisms underlying the impaired goal-directed behavior.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2018.09.001

NeuroImage

Neuroimage

Alteration of functional brain architecture in 22q11.2 deletion syndrome - Insights into susceptibility for psychosis.

The 22q11.2 deletion is one of the most common copy number variants in humans. Carriers of the deletion have a markedly increased risk for neurodevelopmental brain disorders, including schizophrenia, autism spectrum disorders, and attention deficit hyperactivity disorder. The high risk of psychiatric disorders associated with 22q11.2 deletion syndrome offers a unique possibility to identify the functional abnormalities that precede the emergence of psychosis. Carriers of a 22q11.2 deletion show a broad range of sensory processing and cognitive abnormalities similar as in schizophrenia, such as auditory and visual sensory processing, response inhibition, working memory, social cognition, reward processing and arithmetic processing. All these processes have a significant negative impact on daily life if impaired and have been studied extensively in schizophrenia using task-based functional neuroimaging. Here, we review task-related functional brain mapping studies that have used electroencephalography or functional magnetic resonance imaging to identify functional alterations in carriers with 22q11.2 deletion syndrome within the above mentioned cognitive and sensory domains. We discuss how the identification of functional changes at the brain system level can advance the general understanding of which neurobiological alterations set the frame for the emergence of neurodevelopmental disorders in the human brain. The task-based functional neuroimaging literature shows conflicting results in many domains. Nevertheless, consistent similarities between 22q11.2 deletion syndrome and schizophrenia have been found for sensory processing, social cognition and working memory. We discuss these functional brain alterations in terms of potential biomarkers of increased risk for psychosis in the general population.

CognitiveConstruct

RewardProcessing

10.1093/schbul/sby109

Schizophrenia bulletin

Schizophr Bull

Reduced Neural Sensitivity to Social vs Nonsocial Reward in Schizophrenia.

Human beings find social stimuli rewarding, which is thought to facilitate efficient social functioning. Although reward processing has been extensively studied in schizophrenia, a few studies have examined neural processes specifically involved in social reward processing. This study examined neural sensitivity to social and nonsocial rewards in schizophrenia. Twenty-seven patients with schizophrenia and 25 community controls completed a One-Armed Bandit Task, an implicit reinforcement learning task, in the scanner. There were 2 conditions with an identical trial structure, one with social rewards and the other with nonsocial rewards. The data were analyzed using a region of interest (ROI) approach, focusing on the ventral striatum, ventromedial prefrontal cortex, and anterior cingulate cortex. Across all 3 ROIs, patients showed reduced activation for social rewards compared to controls. However, the 2 groups showed comparable levels of activation for nonsocial rewards. Within the patient group, levels of neural activation in these ROIs during the social reward condition were associated with better performance. This study found reduced neural sensitivity in patients with schizophrenia in key reward-processing regions for social but not for nonsocial rewards. These findings suggest a relatively specific social reward-processing deficit in schizophrenia during an implicit reinforcement learning task.

CognitiveConstruct

RewardProcessing

10.1097/FBP.0000000000000424

Behavioural pharmacology

Behav Pharmacol

Dopamine and reward: a view from the prefrontal cortex.

The prefrontal cortex (PFC) is a heterogeneous area that is critical to reward-based decision-making. In particular, the dorsal anterior cingulate cortex, ventromedial PFC and orbitofrontal cortex are frequently implicated in different aspects of choice behaviour. These regions receive projections from midbrain dopamine (DA) neurons and, in turn, project to other key dopaminergic regions such as the striatum. However, our current understanding of the role of DA in reward-based processes is based mainly on studies of midbrain dopaminergic neurons and striatal DA release from nonhuman animal models. An important gap in the literature surrounds the precise functions of DA release in the PFC, particularly in humans. A priority for future research will be to integrate, both computationally and biologically, the seemingly disparate value representations across different nodes within the reward-processing network. Such models should aim to define the functional interactions between the PFC and basal ganglia, through which dopaminergic neurotransmission guides reward-based behaviour.

CognitiveConstruct

RewardProcessing

10.3389/fncel.2018.00260

Frontiers in cellular neuroscience

Front Cell Neurosci

Dichotomous Dopaminergic Control of Ventral Pallidum Neurons.

The ventral pallidum (VP) is crucially involved in reward processing. Dopaminergic afferents reach the VP from the ventral tegmental area (VTA). Recent studies suggest dopamine application increase the firing in the VP. However, little is known about the cellular effects of dopamine within the VP. We aimed to address this paucity of data using brain slices containing the VP and multi-electrode array recordings. Dopamine significantly affected firing in 86% of spontaneously active VP neurons. Among the affected neurons, 84% were excited, while 16% were inhibited. The selective D1-like receptor agonist SKF81297 also had modulatory effects on the majority of VP neurons, but its effects were universally excitatory. On the other hand, the D2-like receptor agonist quinpirole had modulatory effects on 87% of VP neurons studied. It caused significant inhibitory effects in 33% of the cases and excitatory effects in the remaining 67%. The effects of D1-like receptor activation were presynaptic as blocking synaptic transmission with low Ca abolished the effects of SKF81297 application. Furthermore, SKF81297 effects were abolished by blocking ionotropic glutamate receptors, suggesting that D1-like receptors boost glutamate release, which in turn excites VP neurons through postsynaptic glutamate receptors. Effects caused by D2-like receptor activation were found to involve pre and postsynaptic mechanisms, as low Ca abolished the excitatory effects of quinpirole but not the inhibitory ones. Increases in firing frequency (ff) to quinpirole application were abolished by a group 2/3 mGluR antagonist, suggesting that D2-like receptors cause presynaptic inhibition of glutamate release, resulting in reduced postsynaptic activation of inhibitory mGluRs. Conversely, the inhibitory effects of quinpirole persisted in low Ca and therefore can be attributed to postsynaptic D2-like receptor activation. VP neurons excited by dopamine had shorter spike half-widths and are excited by D1-like receptors (presynaptically) and by D2-like receptors (postsynaptically). VP neurons inhibited by dopamine have longer spike half-widths and while D1-like receptor activation has a presynaptic excitatory influence on them, D2-like receptor activation has a postsynaptic inhibitory effect that prevails, on balance. These data provide novel insights into the cellular mechanisms by which dopamine controls information processing within the VP.

CognitiveConstruct

RewardProcessing

10.1007/s00415-018-9024-3

Journal of neurology

J Neurol

Neural correlates of changes in sexual function in frontotemporal dementia: implications for reward and physiological functioning.

Frontotemporal dementia (FTD) is characterised by changes in behaviour including alterations in sexual function. While hypersexual behaviour is commonly thought to predominate, emerging evidence suggests that hyposexual behaviour is in fact most prevalent. The underlying mechanisms driving these behavioural changes remain unclear; however, likely reflect interactions between cognitive, emotional, reward processing and physiological functioning. We aimed to systematically quantify changes in sexual behaviour in behavioural variant FTD (bvFTD) and semantic dementia (SD) in contrast with Alzheimer's disease (AD) and to elucidate the neural correlates of these changes using whole-brain voxel-based morphometry. Carers of 62 dementia patients (30 bvFTD, 12 SD, 20 AD) were interviewed using the Sexual Behaviour and Intimacy Questionnaire, which assesses changes in sexual function. Voxel-based morphometry analysis of structural MRI brain scans was used to determine the association between changes in grey matter intensity and the presence of hyposexual, hypersexual, and inappropriate sexual behaviour across groups. Widespread attenuation of sexual drive, intimacy and the display of affection were evident irrespective of dementia subtype. In contrast, hypersexual and inappropriate sexual behaviour was present in only a small proportion of patients. Neuroimaging analyses revealed an association between hyposexual behaviour and atrophy of the right supramarginal gyrus, middle frontal gyrus and thalamus, whilst hypersexual behaviour was associated with cerebellar atrophy. Counter to the prevailing view, younger-onset dementia syndromes predominantly display an attenuation in sexual drive. Changes in sexual function likely reflect the degeneration of cortical and subcortical neural circuits implicated in reward, autonomic function, empathy, and emotional processing.

CognitiveConstruct

RewardProcessing

10.1002/cne.24526

The Journal of comparative neurology

J Comp Neurol

The tree shrew cerebellum atlas: Systematic nomenclature, neurochemical characterization, and afferent projections.

The cerebellum is involved in the control of movement, emotional responses, and reward processing. The tree shrew is the closest living relative of primates. However, little is known not only about the systematic nomenclature for the tree shrew cerebellum but also about the detailed neurochemical characterization and afferent projections. In this study, Nissl staining and acetylcholinesterase histochemistry were used to reveal anatomical features of the cerebellum of tree shrews (Tupaia belangeri chinensis). The cerebellar cortex presented a laminar structure. The morphological characteristics of the cerebellum were comprehensively described in the coronal, sagittal, and horizontal sections. Moreover, distributive maps of calbindin-immunoreactive (-ir) cells in the Purkinje cell layer of the cerebellum of tree shrews were depicted using coronal, sagittal, and horizontal schematics. In addition, 5th cerebellar lobule (5Cb)-projecting neurons were present in the pontine nuclei, reticular nucleus, spinal vestibular nucleus, ventral spinocerebellar tract, and inferior olive of the tree shrew brain. The anterior part of the paramedian lobule of the cerebellum (PMa) received mainly strong innervation from the lateral reticular nucleus, inferior olive, pontine reticular nucleus, spinal trigeminal nucleus, pontine nuclei, and reticulotegmental nucleus of the pons. The present results provide the first systematic nomenclature, detailed atlas of the whole cerebellum, and whole-brain mapping of afferent projections to the 5Cb and PMa in tree shrews. Our findings provide morphological support for tree shrews as an alternative model for studies of human cerebellar pathologies.

CognitiveConstruct

RewardProcessing

10.1007/s12035-018-1319-y

Molecular neurobiology

Mol Neurobiol

Astrocytic Mechanisms Involving Kynurenic Acid Control Δ-Tetrahydrocannabinol-Induced Increases in Glutamate Release in Brain Reward-Processing Areas.

The reinforcing effects of Δ-tetrahydrocannabinol (THC) in rats and monkeys, and the reinforcement-related dopamine-releasing effects of THC in rats, can be attenuated by increasing endogenous levels of kynurenic acid (KYNA) through systemic administration of the kynurenine 3-monooxygenase inhibitor, Ro 61-8048. KYNA is a negative allosteric modulator of α7 nicotinic acetylcholine receptors (α7nAChRs) and is synthesized and released by astroglia, which express functional α7nAChRs and cannabinoid CB1 receptors (CB1Rs). Here, we tested whether these presumed KYNA autoreceptors (α7nAChRs) and CB1Rs regulate glutamate release. We used in vivo microdialysis and electrophysiology in rats, RNAscope in situ hybridization in brain slices, and primary culture of rat cortical astrocytes. Acute systemic administration of THC increased extracellular levels of glutamate in the nucleus accumbens shell (NAcS), ventral tegmental area (VTA), and medial prefrontal cortex (mPFC). THC also reduced extracellular levels of KYNA in the NAcS. These THC effects were prevented by administration of Ro 61-8048 or the CB1R antagonist, rimonabant. THC increased the firing activity of glutamatergic pyramidal neurons projecting from the mPFC to the NAcS or to the VTA in vivo. These effects were averted by pretreatment with Ro 61-8048. In vitro, THC elicited glutamate release from cortical astrocytes (on which we demonstrated co-localization of the CB1Rs and α7nAChR mRNAs), and this effect was prevented by KYNA and rimonabant. These results suggest a key role of astrocytes in interactions between the endocannabinoid system, kynurenine pathway, and glutamatergic neurotransmission, with ramifications for the pathophysiology and treatment of psychiatric and neurodegenerative diseases.

CognitiveConstruct

RewardProcessing

10.1016/j.addbeh.2018.08.019

Addictive behaviors

Addict Behav

Individual differences in learning from probabilistic reward and punishment predicts smoking status.

The ability to update reward and punishment contingencies is a fundamental aspect of effective decision-making, requiring the ability to successfully adapt to the changing demands of one's environment. In the case of nicotine addiction, research has predominantly focused on reward- and punishment-based learning processes among current smokers relative to non-smokers, whereas less is known about these processes in former smokers. In a total sample of 105 students, we used the Probabilistic Selection Task to examine differences in reinforcement learning among 41 current smokers, 29 ex-smokers, and 35 non-smokers. The PST was comprised of a training and test phase that allowed for the comparison of learning from positive versus negative feedback. The test phase of the Probabilistic Selection Task significantly predicted smoking status. Current and non-smokers were classified with moderate accuracy, whereas ex-smokers were typically misclassified as smokers. Lower rates of learning from rewards were associated with an increased likelihood of being a smoker or an ex-smoker compared with being a non-smoker. Higher rates of learning from punishment were associated with an increased likelihood of being a smoker relative to non-smoker. However, learning from punishment did not predict ex-smoker status. Current smokers and ex-smokers were less likely to learn from rewards, supporting the hypothesis that deficient reward processing is a feature of chronic addiction. In addition, current smokers were more sensitive to punishment than ex-smokers, contradicting some recent findings.

CognitiveConstruct

RewardProcessing

10.1007/s00213-018-5007-4

Psychopharmacology

Psychopharmacology (Berl)

Investigating dopamine and glucocorticoid systems as underlying mechanisms of anhedonia.

Anhedonia, a deficit in reward processing, is an endophenotype of several neuropsychiatric conditions. Despite its prevalence and debilitating effects, treatments for anhedonia are lacking, primarily because its underlying mechanisms are poorly understood. Dopamine (DA) has been implicated in anhedonia through its role in reward-related learning; glucocorticoid systems may also be involved in that anhedonia is often preceded by chronic stress. This study investigated DA and glucocorticoid systems in anhedonia using a rat version of the probabilistic reward task (PRT). Adult male Wistar rats were trained on the PRT and then tested following: (1) activation or inhibition of DA activity induced by amphetamine (AMPH) or pramipexole (PRAMI) injections, (2) chronic mild stress (CMS), or (3) glucocorticoid system activation (dexamethasone (DEX)) or inhibition (mifepristone (MIFE)). AMPH increased and PRAMI decreased response bias, pointing to enhanced and diminished reward responsiveness with DA agonism and antagonism, respectively. CMS reduced response bias but only in a subpopulation of rats. DEX also decreased response bias, suggesting that glucocorticoid processes contribute to anhedonia, although glucocorticoid inhibition (MIFE) had no effect. None of the manipulations altered the ability to detect and respond to reward-paired stimuli. These results confirm a role of DA in anhedonia and elucidate the contribution of the glucocorticoid system to this effect. In addition, chronic stress may interfere with normal DA functioning, leading to impaired reward-related learning in some animals. These findings may direct future treatment of anhedonia by targeting DA and glucocorticoid systems, as well as a possible interaction between the two.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2018.08.038

NeuroImage

Neuroimage

Connectome-based individualized prediction of temperament trait scores.

Temperament consists of multi-dimensional traits that affect various domains of human life. Evidence has shown functional connectome-based predictive models are powerful predictors of cognitive abilities. Putatively, individuals' innate temperament traits may be predictable by unique patterns of brain functional connectivity (FC) as well. However, quantitative prediction for multiple temperament traits at the individual level has not yet been studied. Therefore, we were motivated to realize the individualized prediction of four temperament traits (novelty seeking [NS], harm avoidance [HA], reward dependence [RD] and persistence [PS]) using whole-brain FC. Specifically, a multivariate prediction framework integrating feature selection and sparse regression was applied to resting-state fMRI data from 360 college students, resulting in 4 connectome-based predictive models that enabled prediction of temperament scores for unseen subjects in cross-validation. More importantly, predictive models for HA and NS could be successfully generalized to two relevant personality traits for unseen individuals, i.e., neuroticism and extraversion, in an independent dataset. In four temperament trait predictions, brain connectivities that show top contributing power commonly concentrated on the hippocampus, prefrontal cortex, basal ganglia, amygdala, and cingulate gyrus. Finally, across independent datasets and multiple traits, we show person's temperament traits can be reliably predicted using functional connectivity strength within frontal-subcortical circuits, indicating that human social and behavioral performance can be characterized by specific brain connectivity profile.

CognitiveConstruct

RewardProcessing

10.1097/MCO.0000000000000504

Current opinion in clinical nutrition and metabolic care

Curr Opin Clin Nutr Metab Care

The dynamic nature of food reward processing in the brain.

The dominant view in the literature is that increased neural reactivity to high-caloric palatable foods in the mesocorticolimbic system is a stable-specific characteristic of obese people. In this review, we argue that this viewpoint may not be justified, and we propose that the neural response to food stimuli is dynamic, and in synchrony with the current motivational and cognitive state of an individual. We will further motivate why a clear mental task in the scanner is a necessity for drawing conclusions from neural activity, and why multivariate approaches to functional MRI (fMRI) data-analysis may carry the field forward. From the reviewed literature we draw the conclusions that: neural food-cue reactivity depends strongly on cognitive factors such as the use of cognitive regulation strategies, task demands, and focus of attention; neural activity in the mesocorticolimbic system is not proportionate to the hedonic value of presented food stimuli; and multivariate approaches to fMRI data-analysis have shown that hedonic value can be decoded from multivoxel patterns of neural activity. Future research should take the dynamic nature of food-reward processing into account and take advantage from state-of-the-art multivariate approaches to fMRI data-analysis.

CognitiveConstruct

RewardProcessing

10.1017/ipm.2017.78

Irish journal of psychological medicine

Ir J Psychol Med

Attending to adult ADHD: a review of the neurobiology behind adult ADHD.

Attention deficit hyperactivity disorder (ADHD) is a common disorder in childhood, which progresses to adulthood in about a fifth of cases. For various reasons, adult ADHD is a disorder not comprehensively assessed by psychiatrists, not least because the biological underpinnings are only recently being unmasked.AimsThis selective review targets psychiatrists without a background in neuroscience and aims to describe the neurobiological basis of ADHD. In total, 40 articles from a PubMed search were selected for inclusion based on sample population and methodology (neuroimaging studies). Studies focussing on adult participants were selected preferentially for inclusion. Seminal articles relevant to childhood populations were included for the purpose of understanding general concepts around ADHD. The neuropathology of ADHD is not rooted in a single anatomical area, but in multiple parallel and intersecting pathways, which have demonstrated impaired functional connectivity in ADHD brains. Dysfunction in executive function, reward processing, attention networks and default networks play major roles in the neuropathology of this condition. Biological findings vary between individuals, with some showing greater dysfunction at cortical levels and others at subcortical levels, which is in keeping with its clinical heterogeneity. Improved symptomatology in adulthood is linked to a number of factors. Maturation of the prefrontal cortex in early adulthood contributes to symptom attenuation in many cases, meaning that individuals with cortical dysfunction are more likely to grow out of symptoms, whereas individuals with subcortical dysfunction may be less likely to do so. There is emerging evidence for a similar but distinct disorder arising de novo in adulthood.

CognitiveConstruct

RewardProcessing

10.1016/j.cobeha.2018.05.001

Current opinion in behavioral sciences

Curr Opin Behav Sci

Rat models of reward deficits in psychiatric disorders.

Loss of interest in rewarding activities is a hallmark of many psychiatric disorders and may be relevant for neurodegenerative disorders and patients suffering from brain injury. There is increasing evidence that deficits in reward-related behaviour are more complex than previously described. The traditional view of anhedonia as 'the inability to experience pleasure' may be too limited to fully encompass the types of reward deficit observed in these patients. Developments in methods to measure different aspects of reward processing in humans and animals are starting to provide insights into the complexity of this behaviour. In this article we consider the rodent models which have traditionally been used to study reward deficits in psychiatric disorders and consider their limitations relative to clinical findings. We then discuss work where methods derived from human neuropsychological tests are providing insights into the complexity of reward-related behaviour. Specifically, we consider tasks which investigate different aspects of reward-related behaviour focusing on learning and memory as well as decision-making and consider what these may mean in terms of how we model reward deficits in rodents.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2018.07.005

Biological psychiatry

Biol Psychiatry

Structural Brain Connectivity in Childhood Disruptive Behavior Problems: A Multidimensional Approach.

Studies of white matter connectivity in children with disruptive behavior have yielded inconsistent results, possibly owing to the trait's heterogeneity, which comprises diverse symptoms like physical aggression, irritability, and delinquency. This study examined associations of global and specific white matter connectivity with childhood disruptive behavior problems, while accounting for their complex multidimensionality. In a large cross-sectional population-based study of 10-year-old preadolescents (n = 2567), we assessed four previously described empirically derived dimensions of disruptive behavior problems using the Child Behavior Checklist: physical aggression, irritability, disobedient behavior, and delinquent behavior. Global and specific white matter microstructure was assessed by diffusion tensor imaging. Global fractional anisotropy and mean diffusivity were not associated with broad measures of disruptive behavior, e.g., Child Behavior Checklist externalizing problems scale. Global fractional anisotropy was negatively associated with delinquent behavior (β = -.123, p = .028) and global mean diffusivity was positively associated with delinquent behavior (β = .205, p < 0.001), suggesting reduced white matter microstructure in preadolescents with higher levels of delinquent behavior. Lower white matter microstructure in the inferior longitudinal fasciculus, superior longitudinal fasciculus, cingulum, and uncinate underlie these associations. Global white matter microstructure was not associated with physical aggression, irritability, or disobedient behavior. Delinquent behavior, a severe manifestation of childhood disruptive behavior, was associated with lower white matter microstructure in tracts connecting frontal and temporal lobes. These brain regions are involved in decision making, reward processing, and emotion regulation. This study demonstrated that incorporating the multidimensional nature of childhood disruptive behavior traits shows promise in advancing the search for elucidating neurobiological correlates of disruptive behavior.

CognitiveConstruct

RewardProcessing

10.1101/lm.046748.117

Learning & memory (Cold Spring Harbor, N.Y.)

Learn Mem

Cannabinoid disruption of learning mechanisms involved in reward processing.

The increasing use of cannabis, its derivatives, and synthetic cannabinoids for medicinal and recreational purposes has led to burgeoning interest in understanding the addictive potential of this class of molecules. It is estimated that ∼10% of marijuana users will eventually show signs of dependence on the drug, and the diagnosis of cannabis use disorder (CUD) is increasing in the United States. The molecule that sustains the use of cannabis is Δ-tetrahydrocannabinol (Δ-THC), and our knowledge of its effects, and those of other cannabinoids on brain function has expanded rapidly in the past two decades. Additionally, the identification of endogenous cannabinoid (endocannabinoid) systems in brain and their roles in physiology and behavior, demonstrate extensive involvement of these lipid signaling molecules in regulating CNS function. Here, we examine roles for endogenous cannabinoids in shaping synaptic activity in cortical and subcortical brain circuits, and we discuss mechanisms in which exogenous cannabinoids, such as Δ-THC, interact with endocannabinoid systems to disrupt neuronal network oscillations. We then explore how perturbation of the interaction of this activity within brain reward circuits may lead to impaired learning. Finally, we propose that disruption of cellular plasticity mechanisms by exogenous cannabinoids in cortical and subcortical circuits may explain the difficulty in establishing viable cannabinoid self-administration models in animals.

CognitiveConstruct

RewardProcessing

10.1007/s11682-018-9934-9

Brain imaging and behavior

Brain Imaging Behav

Striato-nigro-striatal tract dispersion abnormalities in patients with chronic schizophrenia.

The white matter connections between the midbrain dopamine neurons and the striatum are part of a neural system involved in reward-based learning, a process that is impaired in patients with schizophrenia. The striato-nigro-striatal (SNS) tract, which participates in this process, has not as yet been explored. The present study aimed to use diffusion MRI (dMRI) to delineate the SNS tract, and to compare the application of two dMRI measures, Tract Dispersion (TD), an index of white matter morphology, and Fractional Anisotropy (FA), an index of white matter integrity, to detect group differences between patients with chronic schizophrenia (CSZ) and healthy controls (HC). dMRI scans were acquired in 22 male patients with CSZ and 23 age-matched HC. Two-tensor tractography was used in addition to manually-delineated regions of interest to extract the SNS tract. A mixed-model analysis of variance was used to investigate differences in TD and FA between CSZ patients and HC. The associations between TD and behavioral measures were also explored. Patients and controls differed significantly in TD (P = 0.04), but not in FA (P = 0.69). The group differences in TD were driven by a higher TD in the right hemisphere in the CSZ group. Higher TD correlated significantly with poorer performance in the Iowa Gambling Task (IGT) when combining the scores of both groups. The findings suggest that dysconnectiviy of the SNS tract which is associated with schizophrenia, could arise from abnormalities in white matter morphology. These abnormalities may potentially reflect irregularities in brain development.

CognitiveConstruct

RewardProcessing

10.1016/j.physbeh.2018.08.003

Physiology & behavior

Physiol Behav

Enhanced neural responses to monetary rewards in methamphetamine use disordered individuals compared to healthy controls.

Converging evidence supports that addiction involves the pathological usurpation of normal reward processes. However, the nature and direction of reward processing dysfunction in substance abusers remain unclear. The current study explored the electrophysiological responses associated with different stages of reward processing in methamphetamine (MA) use disordered individuals. Electroencephalography recording was used to compare responses of 21 MA use disordered individuals and 22 healthy controls (HC) while participants engaged in a simple gambling task. Compared to HC, MA use disordered individuals made more risky choices following a loss outcome on a previous trial. During the reward anticipatory stage, MA use disordered individuals showed an enhanced stimulus-preceding negativity (SPN), as compared to HC. During the reward outcome stage, MA use disordered individuals showed an enhanced feedback-related negativity (FRN) for the losses versus gains as compared to HC. Furthermore, an enhanced P300 was observed under the gain condition, but not under the loss condition, in MA use disordered individuals as compared to HC. These findings provide further evidence that MA use disordered individuals have a sensitized neural response to non-drug rewards and support the impulsivity and incentive sensitization theories in MA use disordered individuals. The current study helps to elucidate the neural mechanisms of reward processing in MA use disordered individuals.

CognitiveConstruct

RewardProcessing

10.1016/j.euroneuro.2018.07.101

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Eur Neuropsychopharmacol

A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response.

The TTC12-ANKK1-DRD2 gene-cluster has been implicated in adult smoking. Here, we investigated the contribution of individual genes in the TTC12-ANKK1-DRD2 cluster in smoking and their association with smoking-associated reward processing in adolescence. A meta-analysis of TTC12-ANKK1-DRD2 variants and self-reported smoking behaviours was performed in four European adolescent cohorts (N = 14,084). The minor G-allele of rs2236709, mapping TTC12, was associated with self-reported smoking (p = 5.0 × 10) and higher plasma cotinine levels (p = 7.0 × 10). This risk allele was linked to an increased ventral-striatal blood-oxygen level-dependent (BOLD) response during reward anticipation (n = 1,263) and with higher DRD2 gene expression in the striatum (p = 0.013), but not with TTC12 or ANKK gene expression. These data suggest a role for the TTC12-ANKK1-DRD2 gene-cluster in adolescent smoking behaviours, provide evidence for the involvement of DRD2 in the early stages of addiction and support the notion that genetically-driven inter-individual differences in dopaminergic transmission mediate reward sensitivity and risk to smoking.

CognitiveConstruct

RewardProcessing

10.1111/cdev.13126

Child development

Child Dev

Early Childhood Parenting Predicts Late Childhood Brain Functional Connectivity During Emotion Perception and Reward Processing.

Seventy-nine 3-year olds and their mothers participated in a laboratory-based task to assess maternal hostility. Mothers also reported their behavioral regulation of their child. Seven years later, functional magnetic resonance imaging data were acquired while viewing emotional faces and completing a reward processing task. Maternal hostility predicted more negative amygdala connectivity during exposure to sad relative to neutral faces with frontal and parietal regions as well as more negative left ventral striatal connectivity during monetary gain relative to loss feedback with the right posterior orbital frontal cortex and right inferior frontal gyrus. In contrast, maternal regulation predicted enhanced cingulo-frontal connectivity during monetary gain relative to loss feedback. Results suggest parenting is associated with alterations in emotion and reward processing circuitry 7-8 years later.

CognitiveConstruct

RewardProcessing