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10.3758/s13415-018-0569-5

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Peers influence adolescent reward processing, but not response inhibition.

Most adolescent risk taking occurs in the presence of peers. Prior research suggests that peers alter adolescents' decision making by increasing reward sensitivity and the engagement of regions involved in the processing of rewards, primarily the striatum. However, the potential influence of peers on the capacity for impulse control, and the associated recruitment of the brain's control circuitry, has not yet been adequately examined. In the current study, adolescents underwent functional neuroimaging while they completed interleaved rounds of risk-taking and response-inhibition tasks. Social context was manipulated such that the participants believed they were either playing alone and unobserved, or watched by an anonymous peer. Compared to those who completed the tasks alone, adolescents in the peer condition took more risks during the risk-taking task and exhibited relatively heightened activation of the striatum. Activity within this striatal region also predicted individual differences in overall risk taking. In contrast, the presence of peers had no effect on behavioral response inhibition and had minimal impact on the engagement of typical cognitive control regions. In a subregion of the anterior insula engaged mutually by both tasks, activity was again found to be sensitive to social context during the risk-taking task, but not during the response-inhibition task. These findings extend the evidence that the presence of peers biases adolescents towards risk taking by increasing reward sensitivity rather than disrupting cognitive control.

CognitiveConstruct

RewardProcessing

10.1097/HRP.0000000000000179

Harvard review of psychiatry

Harv Rev Psychiatry

Ketamine-Associated Brain Changes: A Review of the Neuroimaging Literature.

Major depressive disorder (MDD) is one of the most prevalent conditions in psychiatry. Patients who do not respond to traditional monoaminergic antidepressant treatments have an especially difficult-to-treat type of MDD termed treatment-resistant depression. Subanesthetic doses of ketamine-a glutamatergic modulator-have shown great promise for rapidly treating patients with the most severe forms of depression. As such, ketamine represents a promising probe for understanding the pathophysiology of depression and treatment response. Through neuroimaging, ketamine's mechanism may be elucidated in humans. Here, we review 47 articles of ketamine's effects as revealed by neuroimaging studies. Some important brain areas emerge, especially the subgenual anterior cingulate cortex. Furthermore, ketamine may decrease the ability to self-monitor, may increase emotional blunting, and may increase activity in reward processing. Further studies are needed, however, to elucidate ketamine's mechanism of antidepressant action.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2018.02.002

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

Int J Psychophysiol

Beyond the FRN: Broadening the time-course of EEG and ERP components implicated in reward processing.

Most reward-related electroencephalogram (EEG) studies focus exclusively on the feedback-related negativity (FRN, also known as feedback negativity or FN, medial-frontal negativity or MFN, feedback error-related negativity or fERN, and reward positivity or RewP). This component is usually measured approximately 200-300 ms post-feedback at a single electrode in the frontal-central area (e.g., Fz or FCz). The present review argues that this singular focus on the FRN fails to leverage EEG's greatest strength, its temporal resolution, by underutilizing the rich variety of event-related potential (ERP) and EEG time-frequency components encompassing the wider temporal heterogeneity of reward processing. The primary objective of this review is to provide a comprehensive understanding of often overlooked ERP and EEG correlates beyond the FRN in the context of reward processing with the secondary goal of guiding future research toward multistage experimental designs and multicomponent analyses that leverage the temporal power of EEG. We comprehensively review reward-related ERPs (including the FRN, readiness potential or RP, stimulus-preceding negativity or SPN, contingent-negative variation or CNV, cue-related N2 and P3, Feedback-P3, and late-positive potential or LPP/slow-wave), and reward-related EEG time-frequency components (changes in power at alpha, beta, theta, and delta bands). These electrophysiological signatures display distinct time-courses, scalp topographies, and reflect independent psychological processes during anticipatory and/or outcome stages of reward processing. Special consideration is given to the time-course of each component and factors that significantly contribute to component variation. Concluding remarks identify current limitations along with recommendations for potential important future directions.

CognitiveConstruct

RewardProcessing

10.1093/ijnp/pyy011

The international journal of neuropsychopharmacology

Int J Neuropsychopharmacol

Human Striatal Response to Reward Anticipation Linked to Hippocampal Glutamate Levels.

Dysfunctional reward processing is associated with a number of psychiatric disorders, such as addiction and schizophrenia. It is thought that reward is regulated mainly by dopamine transmission in the ventral striatum. Contemporary animal models suggest that striatal dopamine concentrations and associated behaviors are related to glutamatergic functioning in the ventral hippocampus. However, in humans the association between reward-related ventral striatal response and hippocampal glutamate levels is unclear. Nineteen healthy participants were studied using proton magnetic resonance spectroscopy to measure hippocampal glutamate levels, and functional magnetic resonance imaging to assess striatal activation and functional connectivity during performance of a monetary incentive delay task. We found that ventral striatal activation related to reward processing was correlated with hippocampal glutamate levels. In addition, context-dependent functional coupling was demonstrated between the ventral striatum and both the lingual gyrus and hippocampus during reward anticipation. Elevated hippocampal glutamate levels were inversely related to context-dependent functional connectivity between the ventral striatum and the anterior hippocampus while anticipating reward. These findings indicate that human striatal responses to reward are influenced by hippocampal glutamate levels. This may be relevant for psychiatric disorders associated with abnormal reward processing such as addiction and schizophrenia.

CognitiveConstruct

RewardProcessing

10.1017/S0033291718000041

Psychological medicine

Psychol Med

Differential neural reward mechanisms in treatment-responsive and treatment-resistant schizophrenia.

The significant proportion of schizophrenia patients refractory to treatment, primarily directed at the dopamine system, suggests that multiple mechanisms may underlie psychotic symptoms. Reinforcement learning tasks have been employed in schizophrenia to assess dopaminergic functioning and reward processing, but these have not directly compared groups of treatment-refractory and non-refractory patients. In the current functional magnetic resonance imaging study, 21 patients with treatment-resistant schizophrenia (TRS), 21 patients with non-treatment-resistant schizophrenia (NTR), and 24 healthy controls (HC) performed a probabilistic reinforcement learning task, utilizing emotionally valenced face stimuli which elicit a social bias toward happy faces. Behavior was characterized with a reinforcement learning model. Trial-wise reward prediction error (RPE)-related neural activation and the differential impact of emotional bias on these reward signals were compared between groups. Patients showed impaired reinforcement learning relative to controls, while all groups demonstrated an emotional bias favoring happy faces. The pattern of RPE signaling was similar in the HC and TRS groups, whereas NTR patients showed significant attenuation of RPE-related activation in striatal, thalamic, precentral, parietal, and cerebellar regions. TRS patients, but not NTR patients, showed a positive relationship between emotional bias and RPE signal during negative feedback in bilateral thalamus and caudate. TRS can be dissociated from NTR on the basis of a different neural mechanism underlying reinforcement learning. The data support the hypothesis that a favorable response to antipsychotic treatment is contingent on dopaminergic dysfunction, characterized by aberrant RPE signaling, whereas treatment resistance may be characterized by an abnormality of a non-dopaminergic mechanism - a glutamatergic mechanism would be a possible candidate.

CognitiveConstruct

RewardProcessing

10.1038/s41598-018-20963-4

Scientific reports

Sci Rep

Oxytocin curbs calorie intake via food-specific increases in the activity of brain areas that process reward and establish cognitive control.

The hypothalamic neurohormone oxytocin decreases food intake via largely unexplored mechanisms. We investigated the central nervous mediation of oxytocin's hypophagic effect in comparison to its impact on the processing of generalized rewards. Fifteen fasted normal-weight, young men received intranasal oxytocin (24 IU) or placebo before functional magnetic resonance imaging (fMRI) measurements of brain activity during exposure to food stimuli and a monetary incentive delay task (MID). Subsequently, ad-libitum breakfast intake was assessed. Oxytocin compared to placebo increased activity in the ventromedial prefrontal cortex, supplementary motor area, anterior cingulate, and ventrolateral prefrontal cortices in response to high- vs. low-calorie food images in the fasted state, and reduced calorie intake by 12%. During anticipation of monetary rewards, oxytocin compared to placebo augmented striatal, orbitofrontal and insular activity without altering MID performance. We conclude that during the anticipation of generalized rewards, oxytocin stimulates dopaminergic reward-processing circuits. In contrast, oxytocin restrains food intake by enhancing the activity of brain regions that exert cognitive control, while concomitantly increasing the activity of structures that process food reward value. This pattern points towards a specific role of oxytocin in the regulation of eating behaviour in humans that might be of relevance for potential clinical applications.

CognitiveConstruct

RewardProcessing

10.1093/sleep/zsy022

Sleep

Sleep

Bright environmental light ameliorates deficient subjective 'liking' in insomnia: an experience sampling study.

Altered comfort sensing and reduced gray matter volume in the orbitofrontal cortex of the brain in people suffering from insomnia disorder (ID) suggest compromised processes of motivation and hedonia. The experience sampling (ES) method was used to evaluate whether, in naturalistic conditions, people with ID differ from those without sleep complaints with respect to subjective Wanting and Liking, two major dimensions of the reward system. Since light affects brain circuits involved in affect and reward, ES was combined with ambulatory monitoring of light intensity fluctuations to evaluate their effect on subjective Wanting and Liking. Participants with ID (n = 17, 12 females, 56.8 ± 6.5 mean ± standard deviation years of age) and matched controls without sleep complaints (n = 18, 12 females, 57.0 ± 8.6 years of age) were probed by a smartphone alarm to log their subjective Wanting, Liking, and mood nine times a day for 7 days. Using an ambulatory light recorder, light intensity exposure was sampled simultaneously and averaged over the intervals between subsequent ES alarms. Mixed-effect models were used to evaluate how ID and varying light intensity affected subjective assessments. The results indicated significantly lower subjective Liking and Wanting in people suffering from ID, particularly at low environmental light intensity. Wanting and Liking, rather than more commonly used mood adjectives, showed an increased sensitivity to detect deficient hedonic and reward processing in insomnia during everyday life. Deficient Liking may in part be rescued by exposure to bright environmental light.

CognitiveConstruct

RewardProcessing

10.1186/s13229-018-0189-5

Molecular autism

Mol Autism

Oscillatory rhythm of reward: anticipation and processing of rewards in children with and without autism.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, and multiple theories have emerged concerning core social deficits. While the social motivation hypothesis proposes that deficits in the social reward system cause individuals with ASD to engage less in social interaction, the overly intense world hypothesis (sensory over-responsivity) proposes that individuals with ASD find stimuli to be too intense and may have hypersensitivity to social interaction, leading them to avoid these interactions. EEG was recorded during reward anticipation and reward processing. Reward anticipation was measured using alpha asymmetry, and post-feedback theta was utilized to measure reward processing. Additionally, we calculated post-feedback alpha suppression to measure attention and salience. Participants were 6- to 8-year-olds with ( = 20) and without ( = 23) ASD. Children with ASD showed more left-dominant alpha suppression when anticipating rewards accompanied by nonsocial stimuli compared to social stimuli. During reward processing, children with ASD had less theta activity than typically developing (TD) children. Alpha activity after feedback showed the opposite pattern: children with ASD had greater alpha suppression than TD children. Significant correlations were observed between behavioral measures of autism severity and EEG activity in both the reward anticipation and reward processing time periods. The findings provide evidence that children with ASD have greater approach motivation prior to nonsocial (compared to social) stimuli. Results after feedback suggest that children with ASD evidence less robust activity thought to reflect evaluation and processing of rewards (e.g., theta) compared to TD children. However, children with ASD evidence greater alpha suppression after feedback compared to TD children. We hypothesize that post-feedback alpha suppression reflects general cognitive engagement-which suggests that children with ASD may experience feedback as overly intense. Taken together, these results suggest that aspects of both the social motivation hypothesis and the overly intense world hypothesis may be occurring simultaneously.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2018.02.003

Neuropsychologia

Neuropsychologia

Neural responses during the anticipation and receipt of olfactory reward and punishment in human.

Pleasure experience is an important part of normal healthy life and is essential for general and mental well-being. Many neuroimaging studies have investigated the underlying neural processing of verbal and visual modalities of reward. However, how the brain processes rewards in the olfactory modality is not fully understood. This study aimed to examine the neural basis of olfactory rewards in 25 healthy participants using functional magnetic resonance imaging (fMRI). We developed an Olfactory Incentive Delay (OLID) imaging task distinguishing between the anticipation and receipt of olfactory rewards and punishments. We found that the pallidum was activated during the anticipation of both olfactory rewards and punishments. The bilateral insula was activated independently from the odours' hedonic valence during the receipt phase. In addition, right caudate activation during the anticipation of unpleasant odours was correlated with self-reported anticipatory hedonic traits, whereas bilateral insular activation during the receipt of pleasant odours was correlated with self-reported consummatory hedonic traits. These findings suggest that activity in the insula and the caudate may be biomarkers of anhedonia. These findings also highlight a useful and valid paradigm to study the neural circuitry underlying reward processing in people with anhedonia.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropharm.2018.01.035

Neuropharmacology

Neuropharmacology

Bupropion and naltrexone combination alters high fructose corn syrup self-administration and gene expression in rats.

Contrave is an adjunct pharmacotherapy for obesity that contains bupropion (BUP) and naltrexone (NTX). To further explore the psychopharmacology of this drug combination, male Sprague-Dawley rats were implanted with subcutaneous osmotic mini-pumps releasing: 40 mg/kg/day BUP, 4 mg/kg/day NTX, or 40 + 4 mg/kg/day BUP and NTX (BN). During 12 days of exposure, the animals were tested on operant intraoral self-administration (IOSA) of high fructose corn syrup (HFCS) on continuous (FR1) and progressive ratio (PR) schedules, on home cage drinking of HFCS, and on HFCS taste reactivity. Locomotion activity was also assessed. At the conclusion of the study, mRNA expression of genes involved in reward processing, appetite and mood were quantified. It was found that BN produced effects that could largely be ascribed to either BUP or NTX independently. More specifically, BN-induced reductions of HFCS IOSA on a FR1 schedule and home cage drinking, as well as alterations of MOR and POMC mRNA in the nucleus accumbens core and hypothalamus respectively, were attributable to NTX; while alterations of hippocampal BDNF mRNA was attributable to BUP. But, there was also some evidence of drug synergy: only BN caused persistent reductions of HFCS IOSA and drinking; BN produced the least gain of body weight; and only BN-treated rats displayed altered D2R mRNA in the caudate-putamen. Taken together, these observations support the use of BUP + NTX as a mean to alter consumption of sugars and reducing their impact on brain systems involved in reward, appetite and mood.

CognitiveConstruct

RewardProcessing

10.1016/j.addbeh.2018.01.021

Addictive behaviors

Addict Behav

Cognitive deficits in individuals with methamphetamine use disorder: A meta-analysis.

Methamphetamine has long been considered as a neurotoxic substance causing cognitive deficits. Recently, however, the magnitude and the clinical significance of the cognitive effects associated with methamphetamine use disorder (MUD) have been debated. To help clarify this controversy, we performed a meta-analysis of the cognitive deficits associated with MUD. A literature search yielded 44 studies that assessed cognitive dysfunction in 1592 subjects with MUD and 1820 healthy controls. Effect size estimates were calculated using the Comprehensive Meta-Analysis, for the following 12 cognitive domains: attention, executive functions, impulsivity/reward processing, social cognition, speed of processing, verbal fluency/language, verbal learning and memory, visual learning and memory, visuo-spatial abilities and working memory. Findings revealed moderate impairment across most cognitive domains, including attention, executive functions, language/verbal fluency, verbal learning and memory, visual memory and working memory. Deficits in impulsivity/reward processing and social cognition were more prominent, whereas visual learning and visuo-spatial abilities were relatively spared cognitive domains. A publication bias was observed. These results show that MUD is associated with broad cognitive deficits that are in the same range as those associated with alcohol and cocaine use disorder, as recently shown by way of meta-analysis. The prominent effects of MUD on social cognition and impulsivity/reward processing are based on a small number of studies, and as such, these results will need to be replicated. The functional consequences (social and occupational) of the cognitive deficits of methamphetamine will also need to be determined.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2017.00297

Frontiers in psychiatry

Front Psychiatry

Influences of Dietary Added Sugar Consumption on Striatal Food-Cue Reactivity and Postprandial GLP-1 Response.

Sugar consumption in the United States exceeds recommendations from the American Heart Association. Overconsumption of sugar is linked to risk for obesity and metabolic disease. Animal studies suggest that high-sugar diets alter functions in brain regions associated with reward processing, including the dorsal and ventral striatum. Human neuroimaging studies have shown that these regions are responsive to food cues, and that the gut-derived satiety hormones, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY), suppress striatal food-cue responsivity. We aimed to determine the associations between dietary added sugar intake, striatal responsivity to food cues, and postprandial GLP-1 and PYY levels. Twenty-two lean volunteers underwent a functional magnetic resonance imaging (fMRI) scan during which they viewed pictures of food and non-food items after a 12-h fast. Before scanning, participants consumed a glucose drink. A subset of 19 participants underwent an additional fMRI session in which they consumed water as a control condition. Blood was sampled for GLP-1, and PYY levels and hunger ratings were assessed before and ~75 min after drink consumption. In-person 24-h dietary recalls were collected from each participant on three to six separate occasions over a 2-month period. Average percent calories from added sugar were calculated using information from 24-h dietary recalls. A region-of-interest analysis was performed to compare the blood oxygen level-dependent (BOLD) response to food vs. non-food cues in the bilateral dorsal striatum (caudate/putamen) and ventral striatum (nucleus accumbens). The relationships between added sugar, striatal responses, and hormone changes after drink consumption were assessed using Spearman's correlations. We observed a positive correlation between added sugar intake and BOLD response to food cues in the dorsal striatum and a similar trend in the nucleus accumbens after glucose, but not water, consumption. Added sugar intake was negatively associated with GLP-1 response to glucose. analysis revealed a negative correlation between GLP-1 response to glucose and BOLD response to food cues in the dorsal striatum. Our findings suggest that habitual added sugar intake is related to increased striatal response to food cues and decreased GLP-1 release following glucose intake, which could contribute to susceptibility to overeating.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2018.01.011

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

Int J Psychophysiol

Psychometric properties of neural responses to monetary and social rewards across development.

Reward-related event-related potentials (ERPs) are often used to index individual differences that signal the presence or predict the onset of psychopathology. However, relatively little research has explored the psychometric properties of reward-related ERPs. Without understanding their psychometric properties, the value of using ERPs as biomarkers for psychopathology is limited. The present study, therefore, sought to establish the internal consistency reliability and convergent validity of the reward positivity (RewP) and feedback negativity (FN) elicited by two types of incentives commonly used in individual differences research - monetary and social rewards. A large, developmentally-diverse sample completed a forced-choice guessing task in which they won or lost money, as well as a social interaction task in which they received acceptance and rejection feedback. Data were analyzed at both Cz and at a frontocentral region of interest (ROI) using techniques derived from classical test theory and generalizability theory. Results demonstrated good to excellent internal consistency of the RewP and FN within 20 trials in both tasks, in addition to convergent validity between the two tasks. Results from a regression-based approach to isolating activity specific to a single response demonstrated acceptable to good internal consistency within 20 trials in both tasks, while a subtraction-based approach (∆RewP) did not achieve acceptable internal consistency in either task. Internal consistency was not moderated by age and did not differ between Cz and the frontocentral ROI; however, the magnitudes of the RewP and FN were significantly associated with age at Cz but not at the ROI. This work replicates previous studies demonstrating good psychometric properties of the monetary RewP/FN and provides novel information about the psychometric properties of the social RewP/FN. These data support the use of reward-related ERPs elicited by multiple reward types in studies of biomarkers of psychopathology.

CognitiveConstruct

RewardProcessing

10.1038/s41398-017-0080-8

Translational psychiatry

Transl Psychiatry

A systematic review of the role of the nociceptin receptor system in stress, cognition, and reward: relevance to schizophrenia.

Schizophrenia is a debilitating neuropsychiatric illness that is characterized by positive, negative, and cognitive symptoms. Research over the past two decades suggests that the nociceptin receptor system may be involved in domains affected in schizophrenia, based on evidence aligning it with hallmark features of the disorder. First, aberrant glutamatergic and striatal dopaminergic function are associated with psychotic symptoms, and the nociceptin receptor system has been shown to regulate dopamine and glutamate transmission. Second, stress is a critical risk factor for first break and relapse in schizophrenia, and evidence suggests that the nociceptin receptor system is also directly involved in stress modulation. Third, cognitive deficits are prevalent in schizophrenia, and the nociceptin receptor system has significant impact on learning and working memory. Last, reward processing is disrupted in schizophrenia, and nociceptin signaling has been shown to regulate reward cue salience. These findings provide the foundation for the involvement of the nociceptin receptor system in the pathophysiology of schizophrenia and outline the need for future research into this system.

CognitiveConstruct

RewardProcessing

10.1523/ENEURO.0136-17.2017

eNeuro

eNeuro

Transcranial Alternating Current Stimulation Modulates Risky Decision Making in a Frequency-Controlled Experiment.

In this study, we investigated the effect of transcranial alternating current stimulation (tACS) on voluntary risky decision making and executive control in humans. Stimulation was delivered online at 5 Hz (θ), 10 Hz (α), 20 Hz (β), and 40 Hz (γ) on the left and right frontal area while participants performed a modified risky decision-making task. This task allowed participants to voluntarily select between risky and certain decisions associated with potential gains or losses, while simultaneously measuring the cognitive control component (voluntary switching) of decision making. The purpose of this experimental design was to test whether voluntary risky decision making and executive control can be modulated with tACS in a frequency-specific manner. Our results revealed a robust effect of a 20-Hz stimulation over the left prefrontal area that significantly increased voluntary risky decision making, which may suggest a possible link between risky decision making and reward processing, underlined by β-oscillatory activity.

CognitiveConstruct

RewardProcessing

10.1038/s41598-017-18784-y

Scientific reports

Sci Rep

Dopamine genes are linked to Extraversion and Neuroticism personality traits, but only in demanding climates.

Cross-national differences in personality have long been recognized in the behavioural sciences. However, the origins of such differences are debated. Building on reinforcement sensitivity theories and gene-by-environment interactions, we predict that personality trait phenotypes linked to dopaminergic brain functions (centrally involved in reward processing) diverge most strongly in climatically stressful environments, due to shifts in perceived rewards vs risks. Individuals from populations with a highly efficient dopamine system are biased towards behavioural approach traits (Extraversion and Emotional Stability) due to higher perceived reward values, whereas individuals from populations with a less efficient dopaminergic system are biased towards risk avoidance. In temperate climates, we predict smaller phenotypic differences due to overall weakened reward and risk ratios. We calculated a population-level index of dopamine functioning using 9 commonly investigated genetic polymorphisms encoding dopamine transporters and receptors, derived from a meta-analysis with data from 805 independent samples involving 127,685 participants across 73 societies or territories. We found strong support for the dopamine gene by climatic stress interaction: Population genetic differences in dopamine predicted personality traits at the population level in demanding climates, but not in temperate, less demanding climates, even when controlling for known correlates of personality including wealth and parasite stress.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2017.02134

Frontiers in psychology

Front Psychol

The Neural Basis of Social Influence in a Dictator Decision.

Humans tend to reduce inequitable distributions. Previous neuroimaging studies have shown that inequitable decisions are related to brain regions that associated with negative emotion and signaling conflict. In the highly complex human social environment, our opinions and behaviors can be affected by social information. In current study, we used a modified dictator game to investigate the effect of social influence on making an equitable decision. We found that the choices of participants in present task was influenced by the choices of peers. However, participants' decisions were influenced by equitable rather than inequitable group choices. fMRI results showed that brain regions that related to norm violation and social conflict were related to the inequitable social influence. The neural responses in the dorsomedial prefrontal cortex, rostral cingulate zone, and insula predicted subsequent conforming behavior in individuals. Additionally, psychophysiological interaction analysis revealed that the interconnectivity between the dorsal striatum and insula was elevated in advantageous inequity influence versus no-social influence conditions. We found decreased functional connectivity between the medial prefrontal cortex and insula, supplementary motor area, posterior cingulate gyrus and dorsal anterior cingulate cortex in the disadvantageous inequity influence versus no-social influence conditions. This suggests that a disadvantageous inequity influence may decrease the functional connectivity among brain regions that are related to reward processes. Thus, the neural mechanisms underlying social influence in an equitable decision may be similar to those implicated in social norms and reward processing.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2017.00639

Frontiers in human neuroscience

Front Hum Neurosci

Allostatic Load Is Linked to Cortical Thickness Changes Depending on Body-Weight Status.

Overweight (body mass index or BMI ≥ 25 kg/m) and stress interact with each other in complex ways. Overweight promotes chronic low-inflammation states, while stress is known to mediate caloric intake. Both conditions are linked to several avoidable health problems and to cognitive decline, brain atrophy, and dementia. Since it was proposed as a framework for the onset of mental illness, the allostatic load model has received increasing attention. Although changes in health and cognition related to overweight and stress are well-documented separately, the association between allostatic load and brain integrity has not been addressed in depth, especially among overweight subjects. Thirty-four healthy overweight-to-obese and 29 lean adults underwent blood testing, neuropsychological examination, and magnetic resonance imaging to assess the relationship between cortical thickness and allostatic load, represented as an index of 15 biomarkers (this is, systolic and diastolic arterial tension, glycated hemoglobin, glucose, creatinine, total cholesterol, HDL and LDL cholesterol, triglycerides, c-reactive protein, interleukin-6, insulin, cortisol, fibrinogen, and leptin). Allostatic load indexes showed widespread positive and negative significant correlations ( < 0.01) with cortical thickness values depending on body-weight status. The increase of allostatic load is linked to changes in the gray matter composition of regions monitoring behavior, sensory-reward processing, and general cognitive function.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsy006

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

A comparison of the electrocortical response to monetary and social reward.

Affective science research on reward processing has primarily focused on monetary rewards. There has been a growing interest in evaluating the neural basis of social decision-making and reward processing. The present study employed a within-subject design and compared the reward positivity (RewP), an event-related potential component that is present following favorable feedback and absent or reduced following unfavorable feedback, during monetary and social reward tasks. Specifically, 114 participants (75 females) completed a monetary reward task and a novel social reward task that were matched on trial structure, timing, and feedback stimuli in a counterbalanced order. Results indicated that the monetary and social RewP were of similar magnitude, positively correlated and demonstrated comparable psychometric properties, including reliability and dependability. Across both the monetary and social tasks, women demonstrated a greater RewP compared with men. This study provides a novel methodological approach toward examining the electrocortical response to social reward that is comparable to monetary reward.

CognitiveConstruct

RewardProcessing

10.1007/s00426-018-0979-6

Psychological research

Psychol Res

Intertwining personal and reward relevance: evidence from the drift-diffusion model.

In their seminal paper 'Is our self nothing but reward', Northoff and Hayes (Biol Psychiatry 69(11):1019-1025, Northoff, Hayes, Biological Psychiatry 69(11):1019-1025, 2011) proposed three models of the relationship between self and reward and opened a continuing debate about how these different fields can be linked. To date, none of the proposed models received strong empirical support. The present study tested common and distinct effects of personal relevance and reward values by de-componenting different stages of perceptual decision making using a drift-diffusion approach. We employed a recently developed associative matching paradigm where participants (N = 40) formed mental associations between five geometric shapes and five labels referring personal relevance in the personal task, or five shape-label pairings with different reward values in the reward task and then performed a matching task by indicating whether a displayed shape-label pairing was correct or incorrect. We found that common effects of personal relevance and monetary reward were manifested in the facilitation of behavioural performance for high personal relevance and high reward value as socially important signals. The differential effects between personal and monetary relevance reflected non-decisional time in a perceptual decision process, and task-specific prioritization of stimuli. Our findings support the parallel processing model (Northoff & Hayes, Biol Psychiatry 69(11):1019-1025, Northoff, Hayes, Biological Psychiatry 69(11):1019-1025, 2011) and suggest that self-specific processing occurs in parallel with high reward processing. Limitations and further directions are discussed.

CognitiveConstruct

RewardProcessing

10.1098/rstb.2017.0028

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

Philos Trans R Soc Lond B Biol Sci

The thalamus in drug addiction: from rodents to humans.

Impairments in response inhibition and salience attribution (iRISA) have been proposed to underlie the clinical symptoms of drug addiction as mediated by cortico-striatal-thalamo-cortical networks. The bulk of evidence supporting the iRISA model comes from neuroimaging research that has focused on cortical and striatal influences with less emphasis on the role of the thalamus. Here, we highlight the importance of the thalamus in drug addiction, focusing on animal literature findings on thalamic nuclei in the context of drug-seeking, structural and functional changes of the thalamus as measured by imaging studies in human drug addiction, particularly during drug cue and non-drug reward processing, and response inhibition tasks. Findings from the animal literature suggest that the paraventricular nucleus of the thalamus, the lateral habenula and the mediodorsal nucleus may be involved in the reinstatement, extinction and expression of drug-seeking behaviours. In support of the iRISA model, the human addiction imaging literature demonstrates enhanced thalamus activation when reacting to drug cues and reduced thalamus activation during response inhibition. This pattern of response was further associated with the severity of, and relapse in, drug addiction. Future animal studies could widen their field of focus by investigating the specific role(s) of different thalamic nuclei in different phases of the addiction cycle. Similarly, future human imaging studies should aim to specifically delineate the structure and function of different thalamic nuclei, for example, through the application of advanced imaging protocols at higher magnetic fields (7 Tesla).This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.

CognitiveConstruct

RewardProcessing

10.1111/sltb.12418

Suicide & life-threatening behavior

Suicide Life Threat Behav

Adolescents' Reward-related Neural Activation: Links to Thoughts of Nonsuicidal Self-Injury.

Adolescence is a critical developmental period marked by an increase in risk behaviors, including nonsuicidal self-injury (NSSI). Heightened reward-related brain activation and relatively limited recruitment of prefrontal regions contribute to the initiation of risky behaviors in adolescence. However, neural reward processing has not been examined among adolescents who are at risk for future engagement for NSSI specifically, but who have yet to actually engage in this behavior. In the current fMRI study (N = 71), we hypothesized that altered reward processing would be associated with adolescents' thoughts of NSSI. Results showed that NSSI youth exhibited heightened activation in the bilateral putamen in response to a monetary reward. This pattern of findings suggests that heightened neural sensitivity to reward is associated with thoughts of NSSI in early adolescence. Implications for prevention are discussed.

CognitiveConstruct

RewardProcessing

10.1002/hbm.23948

Human brain mapping

Hum Brain Mapp

Test-retest reliability and longitudinal analysis of automated hippocampal subregion volumes in healthy ageing and Alzheimer's disease populations.

The hippocampal formation is a complex brain structure that is important in cognitive processes such as memory, mood, reward processing and other executive functions. Histological and neuroimaging studies have implicated the hippocampal region in neuropsychiatric disorders as well as in neurodegenerative diseases. This highly plastic limbic region is made up of several subregions that are believed to have different functional roles. Therefore, there is a growing interest in imaging the subregions of the hippocampal formation rather than modelling the hippocampus as a homogenous structure, driving the development of new automated analysis tools. Consequently, there is a pressing need to understand the stability of the measures derived from these new techniques. In this study, an automated hippocampal subregion segmentation pipeline, released as a developmental version of Freesurfer (v6.0), was applied to T1-weighted magnetic resonance imaging (MRI) scans of 22 healthy older participants, scanned on 3 separate occasions and a separate longitudinal dataset of 40 Alzheimer's disease (AD) patients. Test-retest reliability of hippocampal subregion volumes was assessed using the intra-class correlation coefficient (ICC), percentage volume difference and percentage volume overlap (Dice). Sensitivity of the regional estimates to longitudinal change was estimated using linear mixed effects (LME) modelling. The results show that out of the 24 hippocampal subregions, 20 had ICC scores of 0.9 or higher in both samples; these regions include the molecular layer, granule cell layer of the dentate gyrus, CA1, CA3 and the subiculum (ICC > 0.9), whilst the hippocampal fissure and fimbria had lower ICC scores (0.73-0.88). Furthermore, LME analysis of the independent AD dataset demonstrated sensitivity to group and individual differences in the rate of volume change over time in several hippocampal subregions (CA1, molecular layer, CA3, hippocampal tail, fissure and presubiculum). These results indicate that this automated segmentation method provides a robust method with which to measure hippocampal subregions, and may be useful in tracking disease progression and measuring the effects of pharmacological intervention.

CognitiveConstruct

RewardProcessing

10.1177/0269881117744995

Journal of psychopharmacology (Oxford, England)

J Psychopharmacol

Neuroimaging meta-analysis of cannabis use studies reveals convergent functional alterations in brain regions supporting cognitive control and reward processing.

Lagging behind rapid changes to state laws, societal views, and medical practice is the scientific investigation of cannabis's impact on the human brain. While several brain imaging studies have contributed important insight into neurobiological alterations linked with cannabis use, our understanding remains limited. Here, we sought to delineate those brain regions that consistently demonstrate functional alterations among cannabis users versus non-users across neuroimaging studies using the activation likelihood estimation meta-analysis framework. In ancillary analyses, we characterized task-related brain networks that co-activate with cannabis-affected regions using data archived in a large neuroimaging repository, and then determined which psychological processes may be disrupted via functional decoding techniques. When considering convergent alterations among users, decreased activation was observed in the anterior cingulate cortex, which co-activated with frontal, parietal, and limbic areas and was linked with cognitive control processes. Similarly, decreased activation was observed in the dorsolateral prefrontal cortex, which co-activated with frontal and occipital areas and linked with attention-related processes. Conversely, increased activation among users was observed in the striatum, which co-activated with frontal, parietal, and other limbic areas and linked with reward processing. These meta-analytic outcomes indicate that cannabis use is linked with differential, region-specific effects across the brain.

CognitiveConstruct

RewardProcessing

10.1016/j.cpr.2018.01.001

Clinical psychology review

Clin Psychol Rev

Intolerance of uncertainty: Neural and psychophysiological correlates of the perception of uncertainty as threatening.

Intolerance of uncertainty (IU) reflects the perception of uncertainty as threatening, regardless of the true probability of threat. IU is elevated in various forms of psychopathology, uniquely associated with anxiety and depression symptoms after controlling for related constructs, and prospectively predicts symptoms. Given the ubiquity of uncertainty in daily life and the clinical implications of IU, recent work has begun to investigate the neural and psychophysiological correlates of IU. This review summarizes the existing literature and integrates findings within a mechanistic neural model of responding to uncertainty. IU is associated with heightened reactivity to uncertainty reflected in greater activity of the anterior insula and amygdala, alterations in neural responses to rewards and errors evident in event-related potentials, a mixed pattern of startle responses to uncertain threat, and deficiencies in safety learning indexed by startle and skin conductance responding. These findings provide evidence of disruptions in several domains of responding to uncertainty, threat, and reward associated with IU that may confer risk for the development of psychopathology. Significant attention is devoted to recommendations for future research, including consideration of the complex interplay of IU with emotion regulation, cognitive control, and reward processing.

CognitiveConstruct

RewardProcessing

10.1038/s41398-017-0068-4

Translational psychiatry

Transl Psychiatry

Preliminary evidence for genetic overlap between body mass index and striatal reward response.

The reward-processing network is implicated in the aetiology of obesity. Several lines of evidence suggest obesity-linked genetic risk loci (such as DRD2 and FTO) may influence individual variation in body mass index (BMI) through neuropsychological processes reflected in alterations in activation of the striatum during reward processing. However, no study has tested the broader hypotheses that (a) the relationship between BMI and reward-related brain activation (measured through the blood oxygenation-dependent (BOLD) signal) may be observed in a large population study and (b) the overall genetic architecture of these phenotypes overlap, an assumption critical for the progression of imaging genetic studies in obesity research. Using data from the Human Connectome Project (N = 1055 healthy, young individuals: average BMI = 26.4), we first establish a phenotypic relationship between BMI and ventral striatal (VS) BOLD during the processing of rewarding (monetary) stimuli (β = 0.44, P = 0.013), accounting for potential confounds. BMI and VS BOLD were both significantly influenced by additive genetic factors (H2r = 0.57; 0.12, respectively). Further decomposition of this variance suggested that the relationship was driven by shared genetic (ρ  = 0.47, P = 0.011), but not environmental (ρ  = -0.07, P = 0.29) factors. To validate the assumption of genetic pleiotropy between BMI and VS BOLD, we further show that polygenic risk for higher BMI is also associated with increased VS BOLD response to appetitive stimuli (calorically high food images), in an independent sample (N = 81; P  < 0.005). Together, these observations suggest that the genetic factors link risk to obesity to alterations within key nodes of the brain's reward circuity. These observations provide a basis for future work exploring the mechanistic role of genetic loci that confer risk for obesity using the imaging genetics approach.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2017.00611

Frontiers in human neuroscience

Front Hum Neurosci

Effect of Explicit Evaluation on Neural Connectivity Related to Listening to Unfamiliar Music.

People can experience different emotions when listening to music. A growing number of studies have investigated the brain structures and neural connectivities associated with perceived emotions. However, very little is known about the effect of an explicit act of judgment on the neural processing of emotionally-valenced music. In this study, we adopted the novel consensus clustering paradigm, called binarisation of consensus partition matrices (Bi-CoPaM), to study whether and how the conscious aesthetic evaluation of the music would modulate brain connectivity networks related to emotion and reward processing. Participants listened to music under three conditions - one involving a non-evaluative judgment, one involving an explicit evaluative aesthetic judgment, and one involving no judgment at all (passive listening only). During non-evaluative attentive listening we obtained auditory-limbic connectivity whereas when participants were asked to decide explicitly whether they liked or disliked the music excerpt, only two clusters of intercommunicating brain regions were found: one including areas related to auditory processing and action observation, and the other comprising higher-order structures involved with visual processing. Results indicate that explicit evaluative judgment has an impact on the neural auditory-limbic connectivity during affective processing of music.

CognitiveConstruct

RewardProcessing

10.1016/j.neuron.2017.12.022

Neuron

Neuron

Nucleus Accumbens Subnuclei Regulate Motivated Behavior via Direct Inhibition and Disinhibition of VTA Dopamine Subpopulations.

Mesolimbic dopamine (DA) neurons play a central role in motivation and reward processing. Although the activity of these mesolimbic DA neurons is controlled by afferent inputs, little is known about the circuits in which they are embedded. Using retrograde tracing, electrophysiology, optogenetics, and behavioral assays, we identify principles of afferent-specific control in the mesolimbic DA system. Neurons in the medial shell subdivision of the nucleus accumbens (NAc) exert direct inhibitory control over two separate populations of mesolimbic DA neurons by activating different GABA receptor subtypes. In contrast, NAc lateral shell neurons mainly synapse onto ventral tegmental area (VTA) GABA neurons, resulting in disinhibition of DA neurons that project back to the NAc lateral shell. Lastly, we establish a critical role for NAc subregion-specific input to the VTA underlying motivated behavior. Collectively, our results suggest a distinction in the incorporation of inhibitory inputs between different subtypes of mesolimbic DA neurons.

CognitiveConstruct

RewardProcessing

10.1016/j.parkreldis.2017.12.024

Parkinsonism & related disorders

Parkinsonism Relat Disord

Reward processing dysfunction in ventral striatum and orbitofrontal cortex in Parkinson's disease.

Parkinson's disease is a growing concern as the longevity of the world's population steadily increases. Both ageing and Parkinson's disease have an impact on dopamine neurotransmission. It is therefore important to investigate their relative impact on the fronto-striatal reward system. There has been little investigation of reward processing in terms of anticipation and reward outcome in Parkinson's disease. Abnormal responses during reward processing have previously been demonstrated in whole-brain analysis of Parkinson's patients with mild lateralized disease, but the exact impact in regions specific to reward processing is still unknown. Here we aim to investigate the impact of Parkinson's disease on the orbitofrontal ventral striatal reward system in patients with moderate to severe clinical symptoms. We utilized a monetary incentive delay (MID) task in 17 Parkinson's patients who were compared to two control groups stratified by age. The MID paradigm reliably activates the ventral striatum during reward anticipation and the orbitofrontal cortex during reward outcome processing. Relative to the two control groups, Parkinson's disease patients had abnormal task related activity during both reward anticipation in the ventral striatum and reward outcome in the orbitofrontal cortex. There were no effects of ageing. These findings demonstrate abnormalities in anticipatory as well as reward outcome processing while treated primarily with levodopa. The orbitofrontal dysfunction during reward outcome processing may have specificity in Parkinson's disease, as it has been shown to be relatively unaffected by normal ageing.

CognitiveConstruct

RewardProcessing

10.1097/PRA.0000000000000268

Journal of psychiatric practice

J Psychiatr Pract

Reward Dysfunction in the Manic Spectrum: Unable to Win? The Use of Biographical Information to Refine Neurobiological Modeling.

The manic spectrum is thought to be characterized by a hypersensitive biobehavioral reward system, the behavioral activation system. Evidence for this framework comes from questionnaire-based, self-report data collected in cross-sectional and prospective studies of mania, mania in remission, and proneness to hypomania, and from functional neuroimaging investigations of brain reward circuit activity during incentivized choice protocols. Although heightened reward anticipation is consistently documented, the status of later goal attainment activity, hedonic responses, and satiety reactions is less clear. This report examines the status of such reward receipt processes as they operate in the manic spectrum. A case report of a typical subject with bipolar II disorder with a hyperthymic temperament is presented using longitudinal, biographical data. Diminished reward receipt, pleasure, and satiety were demonstrated indicating impaired hedonic processing in hyperthymic temperament. This impairment indicates a dissociation between early, intensified reward pursuit processes and later, blunted, reward attainment activity. The experience and neural correlates of hedonic processing may be impaired in the manic spectrum. Possible mechanisms for this impairment and its dissociation from the earlier stage of reward processing characterized by hyperactive reward pursuit are considered. Clinical reports and longitudinal, life-based follow-up can provide important data to supplement more experimentally based neurobiological models of reward dysfunction in bipolar disorders.

CognitiveConstruct

RewardProcessing

10.1097/PRA.0000000000000267

Journal of psychiatric practice

J Psychiatr Pract

Reward Dysfunction in the Manic Spectrum: Unable to Win? The Use of Biographical Information to Refine Neurobiological Modeling.

The manic spectrum is thought to be characterized by a hypersensitive biobehavioral reward system, the behavioral activation system. Evidence for this framework comes from questionnaire-based, self-report data collected in cross-sectional and prospective studies of mania, mania in remission, and proneness to hypomania, and from functional neuroimaging investigations of brain reward circuit activity during incentivized choice protocols. Although heightened reward anticipation is consistently documented, the status of later goal attainment activity, hedonic responses, and satiety reactions is less clear. This report examines the status of such reward receipt processes as they operate in the manic spectrum. A case report of a typical subject with bipolar II disorder with a hyperthymic temperament is presented using longitudinal, biographical data. Diminished reward receipt, pleasure, and satiety were demonstrated indicating impaired hedonic processing in hyperthymic temperament. This impairment indicates a dissociation between early, intensified reward pursuit processes and later, blunted, reward attainment activity. The experience and neural correlates of hedonic processing may be impaired in the manic spectrum. Possible mechanisms for this impairment and its dissociation from the earlier stage of reward processing characterized by hyperactive reward pursuit are considered. Clinical reports and longitudinal, life-based follow-up can provide important data to supplement more experimentally based neurobiological models of reward dysfunction in bipolar disorders.

CognitiveConstruct

RewardProcessing

Dialogues in clinical neuroscience

Dialogues Clin Neurosci

Minding the brain: the role of pharmacotherapy in substance-use disorder treatment.

With its medicalization as a brain-based disease, addiction has come to be regarded as amenable to biomedical treatment approaches, most commonly pharmacotherapy. Various vulnerabilities are recognized to contribute to maladaptive substance use, and have been linked to diverse neurobiological alterations that may be targeted with pharmacotherapy: withdrawal, craving and cue reactivity, and aberrant reward processing are the most significant. Here, we summarize current thinking regarding pharmacotherapy for substance-use disorders, grouping medications by the type of vulnerability they propose to address and providing insight into their neurobiological mechanisms. We also examine the limitations of the brain-based disease model in addiction treatment, especially as these shortcomings pertain to the place of pharmacotherapy in recovery. We conclude by sketching a framework whereby medications might be integrated fruitfully with other interventions, such as behavioral, existential, or peer-based treatments, targeting aspects of addiction beyond neurobiological deficits.

CognitiveConstruct

RewardProcessing

10.1007/s11682-017-9786-8

Brain imaging and behavior

Brain Imaging Behav

Altered monetary loss processing and reinforcement-based learning in individuals with obesity.

Individuals with obesity are often characterized by alterations in reward processing. This may affect how new information is used to update stimulus values during reinforcement-based learning. Here, we investigated obesity-related changes in non-food reinforcement processing, their impact on learning performance as well as the neural underpinnings of reinforcement-based learning in obesity. Nineteen individuals with obesity (BMI > = 30 kg/m, 10 female) and 23 lean control participants (BMI 18.5-24.9 kg/m, 11 female) performed a probabilistic learning task during functional magnetic resonance imaging (fMRI), in which they learned to choose between advantageous and disadvantageous choice options in separate monetary gain, loss, and neutral conditions. During learning individuals with obesity made a significantly lower number of correct choices and accumulated a significantly lower overall monetary outcome than lean control participants. FMRI analyses revealed aberrant medial prefrontal cortex responses to monetary losses in individuals with obesity. There were no significant group differences in the regional representation of prediction errors. However, we found evidence for increased functional connectivity between the ventral striatum and insula in individuals with obesity. The present results suggest that obesity is associated with aberrant value representations for monetary losses, alterations in functional connectivity during the processing of learning outcomes, as well as a decresased reinforcement-based learning performance. This may affect how new information is incorporated to adjust dysfunctional behavior and could be a factor contributing to the maintenance of dysfunctional eating behavior in obesity.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2017.12.004

NeuroImage. Clinical

Neuroimage Clin

Altered task-based and resting-state amygdala functional connectivity following real-time fMRI amygdala neurofeedback training in major depressive disorder.

We have previously shown that in participants with major depressive disorder (MDD) trained to upregulate their amygdala hemodynamic response during positive autobiographical memory (AM) recall with real-time fMRI neurofeedback (rtfMRI-nf) training, depressive symptoms diminish. Here, we assessed the effect of rtfMRI-nf on amygdala functional connectivity during both positive AM recall and rest. The current manuscript consists of a secondary analysis on data from our published clinical trial of neurofeedback. Patients with MDD completed two rtfMRI-nf sessions (18 received amygdala rtfMRI-nf, 16 received control parietal rtfMRI-nf). One-week prior-to and following training participants also completed a resting-state fMRI scan. A GLM-based functional connectivity analysis was applied using a seed ROI in the left amygdala. We compared amygdala functional connectivity changes while recalling positive AMs from the baseline run to the final transfer run during rtfMRI-nf training, as well during rest from the baseline to the one-week follow-up visit. Finally, we assessed the correlation between change in depression scores and change in amygdala connectivity, as well as correlations between amygdala regulation success and connectivity changes. Following training, amygdala connectivity during positive AM recall increased with widespread regions in the frontal and limbic network. During rest, amygdala connectivity increased following training within the fronto-temporal-limbic network. During both task and resting-state analyses, amygdala-temporal pole connectivity decreased. We identified increased amygdala-precuneus and amygdala-inferior frontal gyrus connectivity during positive memory recall and increased amygdala-precuneus and amygdala-thalamus connectivity during rest as functional connectivity changes that explained significant variance in symptom improvement. Amygdala-precuneus connectivity changes also explain a significant amount of variance in neurofeedback regulation success. Neurofeedback training to increase amygdala hemodynamic activity during positive AM recall increased amygdala connectivity with regions involved in self-referential, salience, and reward processing. Results suggest future targets for neurofeedback interventions, particularly interventions involving the precuneus.

CognitiveConstruct

RewardProcessing

10.1016/j.peptides.2017.12.017

Peptides

Peptides

Role of orexin-1 receptors in the dorsal hippocampus (CA1 region) in expression and extinction of the morphine-induced conditioned place preference in the rats.

Orexinergic system is involved in reward processing and drug addiction. Objectives here, we investigated the effect of intra-hippocampal CA1 administration of orexin-1 receptor (OX1r) antagonist on the expression, and extinction of morphine-induced place preference in rats. Conditioned place preference (CPP) was induced by subcutaneous injection of morphine (5 mg/kg) during a 3-day conditioning phase. Two experimental plots were designed; SB334867 as a selective OX1r antagonist was dissolved in 12% DMSO, prepared in solutions with different concentrations (3, 30, and 300 nM), and microinjected into the CA1 and some neighboring regions (0.5 μl/side), bilaterally. CPP score and locomotor activity were recorded during the CPP test. Results demonstrated that intra-CA1 administration of the OX1r antagonist attenuates the expression of morphine-induced CPP. Furthermore, higher concentrations of SB334867 facilitated the extinction period of morphine-induced CPP and reduced its latency. Nevertheless, solely administration of DMSO did not have any influence on the CPP scores and locomotion in both phases. Our findings suggest that OX1rs in the CA1 region of the hippocampus are involved in the expression of morphine CPP. Moreover, blockade of OX1rs could facilitate extinction and may extinguish the ability of drug-related cues. It seems that the antagonist might be considered as a propitious therapeutic agent in suppressing drug-seeking behaviors.

CognitiveConstruct

RewardProcessing

10.1111/cdev.13011

Child development

Child Dev

Differential Associations of Distinct Forms of Childhood Adversity With Neurobehavioral Measures of Reward Processing: A Developmental Pathway to Depression.

Childhood adversity is associated with altered reward processing, but little is known about whether this varies across distinct types of adversity. In a sample of 94 children (6-19 years), we investigated whether experiences of material deprivation, emotional deprivation, and trauma have differential associations with reward-related behavior and white matter microstructure in tracts involved in reward processing. Material deprivation (food insecurity), but not emotional deprivation or trauma, was associated with poor reward performance. Adversity-related influences on the integrity of white matter microstructure in frontostriatal tracts varied across childhood adversity types, and reductions in frontostriatal white matter integrity mediated the association of food insecurity with depressive symptoms. These findings document distinct behavioral and neurodevelopmental consequences of specific forms of adversity that have implications for psychopathology risk.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0189771

PloS one

PLoS One

Differences in reward processing between putative cell types in primate prefrontal cortex.

Single-unit studies in monkeys have demonstrated that neurons in the prefrontal cortex predict the reward type, reward amount or reward availability associated with a stimulus. To examine contributions of pyramidal cells and interneurons in reward processing, single-unit activity was extracellularly recorded in prefrontal cortices of four monkeys performing a reward prediction task. Based on their shapes of spike waveforms, prefrontal neurons were classified into broad-spike and narrow-spike units that represented putative pyramidal cells and interneurons, respectively. We mainly observed that narrow-spike neurons showed higher firing rates but less bursty discharges than did broad-spike neurons. Both narrow-spike and broad-spike cells selectively responded to the stimulus, reward and their interaction, and the proportions of each type of selective neurons were similar between the two cell classes. Moreover, the two types of cells displayed equal reliability of reward or stimulus discrimination. Furthermore, we found that broad-spike and narrow-spike cells showed distinct mechanisms for encoding reward or stimulus information. Broad-spike neurons raised their firing rate relative to the baseline rate to represent the preferred reward or stimulus information, whereas narrow-spike neurons inhibited their firing rate lower than the baseline rate to encode the non-preferred reward or stimulus information. Our results suggest that narrow-spike and broad-spike cells were equally involved in reward and stimulus processing in the prefrontal cortex. They utilized a binary strategy to complementarily represent reward or stimulus information, which was consistent with the task structure in which the monkeys were required to remember two reward conditions and two visual stimuli.

CognitiveConstruct

RewardProcessing

10.1002/bdr2.1176

Birth defects research

Birth Defects Res

Convergent neurobiological predictors of emergent psychopathology during adolescence.

The adolescent brain undergoes significant structural and functional development. Through the use of magnetic resonance imaging in adolescents, it has been demonstrated that the prefrontal cortex, pertinent for executive control, demonstrates protracted development compared to limbic structures, active during emotion and reward processing. This asynchronous development creates a sensitive window during adolescence, in which many psychopathological disorders (i.e., mental health and substance use) emerge. This review outlines longitudinal studies that use magnetic resonance imaging to identify neurobiological predictors of emergent psychopathology (depression, anxiety, and substance use), during adolescence. Studies identifying neurobiological markers that predict onset and escalation of these disorders, as well as those that predict successful treatment outcomes are explored. An emphasis is placed on frontolimbic brain structures, a convergent neurobiological target for both emergent mental health issues and emergent substance use. The literature reviewed herein suggests that reduced volume and cortical thickness in frontolimbic regions, as well as reduced functional activation (particularly during task involving reward or emotional stimuli) in these regions, may serve as a neurobiological predictors of emergent psychopathology in adolescence. This knowledge is crucial, as it may be used to develop neurobiologically targeted prevention and intervention strategies for youth who are at-risk for developing these psychopathologies.

CognitiveConstruct

RewardProcessing

10.1002/bdr2.1173

Birth defects research

Birth Defects Res

The impact of junk foods on the adolescent brain.

Adolescence is a significant period of physical, social, and emotional development, and is characterized by prominent neurobiological changes in the brain. The maturational processes that occur in brain regions responsible for cognitive control and reward seeking may underpin excessive consumption of palatable high fat and high sugar "junk" foods during adolescence. Recent studies have highlighted the negative impact of these foods on brain function, resulting in cognitive impairments and altered reward processing. The increased neuroplasticity during adolescence may render the brain vulnerable to the negative effects of these foods on cognition and behavior. In this review, we describe the mechanisms by which junk food diets influence neurodevelopment during adolescence. Diet can lead to alterations in dopamine-mediated reward signaling, and inhibitory neurotransmission controlled by γ-aminobutyric acid (GABA), two major neurotransmitter systems that are under construction across adolescence. We propose that poor dietary choices may derail the normal adolescent maturation process and influence neurodevelopmental trajectories, which can predispose individuals to dysregulated eating and impulsive behaviors.

CognitiveConstruct

RewardProcessing

10.1007/s11682-017-9811-y

Brain imaging and behavior

Brain Imaging Behav

Neural processing of food and monetary rewards is modulated by metabolic state.

In humans, food is considered a powerful primary reinforcer, whereas money is a secondary reinforcer, as it gains a value through learning experience. Here, we aimed to identify the neural regions supporting the processing of food-related reinforcers, relate it to the neural underpinnings of monetary reinforcers, and explore their modulation by metabolic state (hunger vs satiety). Twenty healthy male participants were tested in two experimental sessions, once hungry and once satiated, using functional magnetic resonance imaging. Participants performed an associative learning task, receiving food or monetary rewards (in the form of images) on separate blocks. Irrespective of incentive type, both food and monetary rewards engaged ventral striatum, medial orbitofrontal cortex and amygdala, regions that have been previously associated with reward processing. Food incentives additionally engaged the opercular part of the inferior frontal gyrus and the insula, collectively known as a primary gustatory cortex. Moreover, in response to negative feedback (here, reward omission), robust activation was observed in anterior insula, supplementary motor area and lateral parts of the prefrontal cortex, including middle and inferior frontal gyrus. Furthermore, the interaction between metabolic state and incentive type resulted in supramarginal gyrus (SMG) activity, among other motor and sensory-related regions. Finally, functional connectivity analysis showed correlation in the hungry state between the SMG and mesolimbic regions, including the hippocampus, midbrain and cingulate areas. Also, the interaction between metabolic state and incentive type revealed coupling between SMG and ventral striatum. Whereas general purpose reward-related regions process incentives of different kinds, the current results suggest that the SMG might play a key role in integrating the information related to current metabolic state and available incentive type.

CognitiveConstruct

RewardProcessing

10.1007/s40429-017-0164-9

Current addiction reports

Curr Addict Rep

Neural Correlates of Social Influence on Risk Taking and Substance Use in Adolescents.

Adolescents often engage in elevated levels of risk taking that gives rise to substance use. Family and peers constitute the primary contextual risk factors for adolescent substance use. This report reviews how families and peers influence adolescent neurocognitive development to inform their risk taking and subsequent substance use. Developmental neuroscience using functional magnetic resonance imaging (fMRI) has identified regions of the brain involved in social cognition, cognitive control, and reward processing that are integrally linked to social influence on adolescent risk taking. These neural mechanisms play a role in how peer and family influence (e.g., physical presence, relationship quality, rejection) translates into adolescent substance use. Peers and families can independently, and in tandem, contribute to adolescent substance use, for better or for worse. We propose that future work utilize fMRI to investigate the neural mechanisms involved in different aspects of peer and family influence, and how these contexts uniquely and interactively influence adolescent substance use initiation and escalation across development.

CognitiveConstruct

RewardProcessing

10.1017/S0033291717003476

Psychological medicine

Psychol Med

Intact striatal dopaminergic modulation of reward learning and daily-life reward-oriented behavior in first-degree relatives of individuals with psychotic disorder.

Abnormalities in reward learning in psychotic disorders have been proposed to be linked to dysregulated subcortical dopaminergic (DA) neurotransmission, which in turn is a suspected mechanism for predisposition to psychosis. We therefore explored the striatal dopaminergic modulation of reward processing and its behavioral correlates in individuals at familial risk for psychosis. We performed a DA D2/3 receptor [18F]fallypride positron emission tomography scan during a probabilistic reinforcement learning task in 16 healthy first-degree relatives of patients with psychosis and 16 healthy volunteers, followed by a 6-day ecological momentary assessment study capturing reward-oriented behavior in the everyday life. We detected significant reward-induced DA release in bilateral caudate, putamen and ventral striatum of both groups, with no group differences in its magnitude nor spatial extent. In both groups alike, greater extent of reward-induced DA release in all regions of interest was associated with better performance in the task, as well as in greater tendency to be engaged in reward-oriented behavior in the daily life. These findings suggest intact striatal dopaminergic modulation of reinforcement learning and reward-oriented behavior in individuals with familial predisposition to psychosis. Furthermore, this study points towards a key link between striatal reward-related DA release and pursuit of ecologically relevant rewards.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2017.11.011

Developmental cognitive neuroscience

Dev Cogn Neurosci

Assessing age-dependent multi-task functional co-activation changes using measures of task-potency.

It is being hypothesised that the developing adolescent brain is increasingly enlisting long-range connectivity, allowing improved communication between spatially distant brain regions. The developmental trajectories of such maturational changes remain elusive. Here, we aim to study how the brain engages in multiple tasks (working memory, reward processing, and inhibition) at the network-level and evaluate how effects of age across these tasks are related to each other. We characterise how the brain departs from its functional baseline architecture towards task-induced functional connectivity modulations using a novel measure called task potency, allowing direct comparison between tasks by defining sensitivity to one or multiple tasks. By applying this method in a sample of healthy participants (N = 218) aged 8-30 years, we demonstrate maturational changes in task-dependent functional co-activation over and above baseline connectivity maturation. Our results provide evidence for task-specific maturational windows with different cognitive systems probed by different tasks displaying specific age-range dependencies of strongest developmental change. Our results highlight the use of task potency for modelling developmental trajectories and the impact of differential maturation across tasks. This enables better characterisation of cognitive processes disrupted in neurodevelopmental disorders and may explain the increased level of heterogeneity observed in adolescent population studies.

CognitiveConstruct

RewardProcessing

10.1016/j.janxdis.2017.11.001

Journal of anxiety disorders

J Anxiety Disord

Impulsive responding in threat and reward contexts as a function of PTSD symptoms and trait disinhibition.

We examined current posttraumatic stress disorder (PTSD) symptoms, trait disinhibition, and affective context as contributors to impulsive and self-destructive behavior in 94 trauma-exposed Veterans. Participants completed an affective Go/No-Go task (GNG) with different emotional contexts (threat, reward, and a multidimensional threat/reward condition) and current PTSD, trait disinhibition, and risky/self-destructive behavior measures. PTSD interacted with trait disinhibition to explain recent engagement in risky/self-destructive behavior, with Veterans scoring high on trait disinhibition and current PTSD symptoms reporting the highest levels of these behaviors. On the GNG task, commission errors were also associated with the interaction of PTSD symptoms and trait disinhibition. Specifically, PTSD symptoms were associated with greater commission errors in threat vs. reward contexts for individuals who were low on trait disinhibition. In contrast, veterans high on PTSD and trait disinhibition exhibited the greatest number of commission errors in the multidimensional affective context that involved both threat and reward processing. Results highlight the interactive effects of PTSD and disinhibited personality traits, as well as threat and reward systems, as risk factors for impulsive and self-destructive behavior in trauma-exposed groups. Findings have clinical implications for understanding heterogeneity in the expression of PTSD and its association with disinhibited behavior.

CognitiveConstruct

RewardProcessing

10.3758/s13415-017-0553-5

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Elaborative feedback: Engaging reward and task-relevant brain regions promotes learning in pseudoword reading aloud.

Although much is known about the cognitive and neural basis of establishing letter-sound mappings in learning word forms, relatively little is known about what makes for the most effective feedback during this process. We sought to determine the neural basis by which elaborative feedback (EF), which contains both reward-related and content-specific information, may be more helpful than feedback containing only one kind of information (simple positive feedback, PF) or the other (content feedback, CF) in learning orthography-phonology (spelling-sound) mappings for novel letter strings. Compared to CF, EF activated the ventromedial prefrontal cortex, implicated in reward processing. Compared to PF, EF activated the posterior middle temporal, superior temporal, and supramarginal gyri-regions implicated in orthography-phonology conversion. In the same comparison, EF also activated the left fusiform gyrus/visual word form area-implicated in orthographic processing. Also EF, but not CF or PF, modulated activity in the caudate nucleus. In a postscan questionnaire, EF and PF were rated as more pleasant than CF, suggesting that modulation of the caudate for EF may be due to the coupling of reward and skill content. These findings suggest the enhanced effectiveness of EF may be due to concurrent activation of reward-related and task-relevant brain regions.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2017.11.017

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

Int J Psychophysiol

Feedback information and the reward positivity.

The reward positivity is a component of the event-related brain potential (ERP) sensitive to neural mechanisms of reward processing. Multiple studies have demonstrated that reward positivity amplitude indices a reward prediction error signal that is fundamental to theories of reinforcement learning. However, whether this ERP component is also sensitive to richer forms of performance information important for supervised learning is less clear. To investigate this question, we recorded the electroencephalogram from participants engaged in a time estimation task in which the type of error information conveyed by feedback stimuli was systematically varied across conditions. Consistent with our predictions, we found that reward positivity amplitude decreased in relation to increasing information content of the feedback, and that reward positivity amplitude was unrelated to trial-to-trial behavioral adjustments in task performance. By contrast, a series of exploratory analyses revealed frontal-central and posterior ERP components immediately following the reward positivity that related to these processes. Taken in the context of the wider literature, these results suggest that the reward positivity is produced by a neural mechanism that motivates task performance, whereas the later ERP components apply the feedback information according to principles of supervised learning.

CognitiveConstruct

RewardProcessing

10.1073/pnas.1708791114

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

Proc Natl Acad Sci U S A

Early childhood stress exposure, reward pathways, and adult decision making.

Individuals who have experienced chronic and high levels of stress during their childhoods are at increased risk for a wide range of behavioral problems, yet the neurobiological mechanisms underlying this association are poorly understood. We measured the life circumstances of a community sample of school-aged children and then followed these children for a decade. Those from the highest and lowest quintiles of childhood stress exposure were invited to return to our laboratory as young adults, at which time we reassessed their life circumstances, acquired fMRI data during a reward-processing task, and tested their judgment and decision making. Individuals who experienced high levels of early life stress showed lower levels of brain activation when processing cues signaling potential loss and increased responsivity when actually experiencing losses. Specifically, those with high childhood stress had reduced activation in the posterior cingulate/precuneus, middle temporal gyrus, and superior occipital cortex during the anticipation of potential rewards; reduced activation in putamen and insula during the anticipation of potential losses; and increased left inferior frontal gyrus activation when experiencing an actual loss. These patterns of brain activity were associated with both laboratory and real-world measures of individuals' risk taking in adulthood. Importantly, these effects were predicated only by childhood stress exposure and not by current levels of life stress.

CognitiveConstruct

RewardProcessing

10.1186/s13063-017-2328-2

Trials

Trials

Does motivation matter in upper-limb rehabilitation after stroke? ArmeoSenso-Reward: study protocol for a randomized controlled trial.

Fifty percent of all stroke survivors remain with functional impairments of their upper limb. While there is a need to improve the effectiveness of rehabilitative training, so far no new training approach has proven to be clearly superior to conventional therapy. As training with rewarding feedback has been shown to improve motor learning in humans, it is hypothesized that rehabilitative arm training could be enhanced by rewarding feedback. In this paper, we propose a trial protocol investigating rewards in the form of performance feedback and monetary gains as ways to improve effectiveness of rehabilitative training. This multicentric, assessor-blinded, randomized controlled trial uses the ArmeoSenso virtual reality rehabilitation system to train 74 first-ever stroke patients (< 100 days post stroke) to lift their impaired upper limb against gravity and to improve the workspace of the paretic arm. Three sensors are attached to forearm, upper arm, and trunk to track arm movements in three-dimensional space while controlling for trunk compensation. Whole-arm movements serve as input for a therapy game. The reward group (n = 37) will train with performance feedback and contingent monetary reward. The control group (n = 37) uses the same system but without monetary reward and with reduced performance feedback. Primary outcome is the change in the hand workspace in the transversal plane. Standard clinical assessments are used as secondary outcome measures. This randomized controlled trial will be the first to directly evaluate the effect of rewarding feedback, including monetary rewards, on the recovery process of the upper limb following stroke. This could pave the way for novel types of interventions with significantly improved treatment benefits, e.g., for conditions that impair reward processing (stroke, Parkinson's disease). ClinicalTrials.gov, ID: NCT02257125 . Registered on 30 September 2014.

CognitiveConstruct

RewardProcessing

10.1111/jcpp.12843

Journal of child psychology and psychiatry, and allied disciplines

J Child Psychol Psychiatry

Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents.

Nociceptin is a key regulator linking environmental stress and alcohol drinking. In a genome-wide methylation analysis, we recently identified an association of a methylated region in the OPRL1 gene with alcohol-use disorders. Here, we investigate the biological basis of this observation by analysing psychosocial stressors, methylation of the OPRL1 gene, brain response during reward anticipation and alcohol drinking in 660 fourteen-year-old adolescents of the IMAGEN study. We validate our findings in marchigian sardinian (msP) alcohol-preferring rats that are genetically selected for increased alcohol drinking and stress sensitivity. We found that low methylation levels in intron 1 of OPRL1 are associated with higher psychosocial stress and higher frequency of binge drinking, an effect mediated by OPRL1 methylation. In individuals with low methylation of OPRL1, frequency of binge drinking is associated with stronger BOLD response in the ventral striatum during reward anticipation. In msP rats, we found that stress results in increased alcohol intake and decreased methylation of OPRL1 in the nucleus accumbens. Our findings describe an epigenetic mechanism that helps to explain how psychosocial stress influences risky alcohol consumption and reward processing, thus contributing to the elucidation of biological mechanisms underlying risk for substance abuse.

CognitiveConstruct

RewardProcessing

10.1007/s10072-017-3205-1

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

Neurol Sci

The alcoholic brain: neural bases of impaired reward-based decision-making in alcohol use disorders.

Neuroeconomics is providing insights into the neural bases of decision-making in normal and pathological conditions. In the neuropsychiatric domain, this discipline investigates how abnormal functioning of neural systems associated with reward processing and cognitive control promotes different disorders, and whether such evidence may inform treatments. This endeavor is crucial when studying different types of addiction, which share a core promoting mechanism in the imbalance between impulsive subcortical neural signals associated with immediate pleasurable outcomes and inhibitory signals mediated by a prefrontal reflective system. The resulting impairment in behavioral control represents a hallmark of alcohol use disorders (AUDs), a chronic relapsing disorder characterized by excessive alcohol consumption despite devastating consequences. This review aims to summarize available magnetic resonance imaging (MRI) evidence on reward-related decision-making alterations in AUDs, and to envision possible future research directions. We review functional MRI (fMRI) studies using tasks involving monetary rewards, as well as MRI studies relating decision-making parameters to neurostructural gray- or white-matter metrics. The available data suggest that excessive alcohol exposure affects neural signaling within brain networks underlying adaptive behavioral learning via the implementation of prediction errors. Namely, weaker ventromedial prefrontal cortex activity and altered connectivity between ventral striatum and dorsolateral prefrontal cortex likely underpin a shift from goal-directed to habitual actions which, in turn, might underpin compulsive alcohol consumption and relapsing episodes despite adverse consequences. Overall, these data highlight abnormal fronto-striatal connectivity as a candidate neurobiological marker of impaired choice in AUDs. Further studies are needed, however, to unveil its implications in the multiple facets of decision-making.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2017.11.013

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

Int J Psychophysiol

Dissociable effects of reward and expectancy during evaluative feedback processing revealed by topographic ERP mapping analysis.

Evaluative feedback provided during performance monitoring (PM) elicits either a positive or negative deflection ~250-300ms after its onset in the event-related potential (ERP) depending on whether the outcome is reward-related or not, as well as expected or not. However, it remains currently unclear whether these two deflections reflect a unitary process, or rather dissociable effects arising from non-overlapping brain networks. To address this question, we recorded 64-channel EEG in healthy adult participants performing a standard gambling task where valence and expectancy were manipulated in a factorial design. We analyzed the feedback-locked ERP data using a conventional ERP analysis, as well as an advanced topographic ERP mapping analysis supplemented with distributed source localization. Results reveal two main topographies showing opposing valence effects, and being differently modulated by expectancy. The first one was short-lived and sensitive to no-reward irrespective of expectancy. Source-estimation associated with this topographic map comprised mainly regions of the dorsal anterior cingulate cortex. The second one was primarily driven by reward, had a prolonged time-course and was monotonically influenced by expectancy. Moreover, this reward-related topographical map was best accounted for by intracranial generators estimated in the posterior cingulate cortex. These new findings suggest the existence of dissociable brain systems depending on feedback valence and expectancy. More generally, they inform about the added value of using topographic ERP mapping methods, besides conventional ERP measurements, to characterize qualitative changes occurring in the spatio-temporal dynamic of reward processing during PM.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.1647-17.2017

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

J Neurosci

Brainstem Pain-Control Circuitry Connectivity in Chronic Neuropathic Pain.

Preclinical investigations have suggested that altered functioning of brainstem pain-modulation circuits may be crucial for the maintenance of some chronic pain conditions. While some human psychophysical studies show that patients with chronic pain display altered pain-modulation efficacy, it remains unknown whether brainstem pain-modulation circuits are altered in individuals with chronic pain. The aim of the present investigation was to determine whether, in humans, chronic pain following nerve injury is associated with altered ongoing functioning of the brainstem descending modulation systems. Using resting-state functional magnetic resonance imaging, we found that male and female patients with chronic neuropathic orofacial pain show increased functional connectivity between the rostral ventromedial medulla (RVM) and other brainstem pain-modulatory regions, including the ventrolateral periaqueductal gray (vlPAG) and locus ceruleus (LC). We also identified an increase in RVM functional connectivity with the region that receives orofacial nociceptor afferents, the spinal trigeminal nucleus. In addition, the vlPAG and LC displayed increased functional connectivity strengths with higher brain regions, including the hippocampus, nucleus accumbens, and anterior cingulate cortex, in individuals with chronic pain. These data reveal that chronic pain is associated with altered ongoing functioning within the endogenous pain-modulation network. These changes may underlie enhanced descending facilitation of processing at the primary synapse, resulting in increased nociceptive transmission to higher brain centers. Further, our findings show that higher brain regions interact with the brainstem modulation system differently in chronic pain, possibly reflecting top-down engagement of the circuitry alongside altered reward processing in pain conditions. Experimental animal models and human psychophysical studies suggest that altered functioning of brainstem pain-modulation systems contributes to the maintenance of chronic pain. However, the function of this circuitry has not yet been explored in humans with chronic pain. In this study, we report that individuals with orofacial neuropathic pain show altered functional connectivity between regions within the brainstem pain-modulation network. We suggest that these changes reflect largely central mechanisms that feed back onto the primary nociceptive synapse and enhance the transfer of noxious information to higher brain regions, thus contributing to the constant perception of pain. Identifying the mechanisms responsible for the maintenance of neuropathic pain is imperative for the development of more efficacious therapies.

CognitiveConstruct

RewardProcessing

10.1016/j.euroneuro.2017.11.002

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Eur Neuropsychopharmacol

Fluoxetine, not donepezil, reverses anhedonia, cognitive dysfunctions and hippocampal proteome changes during repeated social defeat exposure.

While anhedonia is considered a core symptom of major depressive disorder (MDD), less attention has been paid to cognitive dysfunctions. We evaluated the behavioural and molecular effects of a selective serotonin re-uptake inhibitor (SSRI, fluoxetine) and an acetylcholinesterase inhibitor (AChEI, donepezil) on emotional-cognitive endophenotypes of depression and the hippocampal proteome. A chronic social defeat (SD) procedure was followed up by "reminder" sessions of direct and indirect SD. Anhedonia-related behaviour was assessed longitudinally by intracranial self-stimulation (ICSS). Cognitive dysfunction was analysed by an object recognition test (ORT) and extinction of fear memory. Tandem mass spectrometry (MS) and protein-protein-interaction (PPI) network modelling were used to characterise the underlying biological processes of SD and SSRI/AChEI treatment. Independent selected reaction monitoring (SRM) was conducted for molecular validation. Repeated SD resulted in a stable increase of anhedonia-like behaviour as measured by ICSS. Fluoxetine treatment reversed this phenotype, whereas donepezil showed no effect. Fluoxetine improved recognition memory and inhibitory learning in a stressor-related context, whereas donepezil only improved fear extinction. MS and PPI network analysis highlighted functional SD stress-related hippocampal proteome changes including reduced glutamatergic neurotransmission and learning processes, which were reversed by fluoxetine, but not by donepezil. SRM validation of molecular key players involved in these pathways confirmed the hypothesis that fluoxetine acts via increased AMPA receptor signalling and Ca-mediated neuroplasticity in the amelioration of stress-impaired reward processing and memory consolidation. Our study highlights molecular mediators of SD stress reversed by SSRI treatment, identifying potential viable future targets to improve cognitive dysfunctions in MDD patients.

CognitiveConstruct

RewardProcessing

10.1038/s41598-017-16544-6

Scientific reports

Sci Rep

Associating a product with a luxury brand label modulates neural reward processing and favors choices in materialistic individuals.

The present study investigated the extent to which luxury vs. non-luxury brand labels (i.e., extrinsic cues) randomly assigned to items and preferences for these items impact choice, and how this impact may be moderated by materialistic tendencies (i.e., individual characteristics). The main objective was to investigate the neural correlates of abovementioned effects using functional magnetic resonance imaging. Behavioural results showed that the more materialistic people are, the more they choose and like items labelled with luxury brands. Neuroimaging results revealed the implication of a neural network including the dorsolateral and ventromedial prefrontal cortex and the orbitofrontal cortex that was modulated by the brand label and also by the participants' preference. Most importantly, items with randomly assigned luxurious brand labels were preferentially chosen by participants and triggered enhanced signal in the caudate nucleus. This effect increased linearly with materialistic tendencies. Our results highlight the impact of brand-item association, although random in our study, and materialism on preference, relying on subparts of the brain valuation system for the integration of extrinsic cues, preferences and individual characteristics.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2017.11.007

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

Int J Psychophysiol

Event-related brain potentials and the study of reward processing: Methodological considerations.

There is growing interest in using electroencephalography and specifically the event-related brain potential (ERP) methodology to study human reward processing. Since the discovery of the feedback related negativity (Miltner et al., 1997) and the development of theories associating the feedback related negativity and more recently the reward positivity with reinforcement learning, midbrain dopamine function, and the anterior cingulate cortex (i.e., Holroyd and Coles, 2002) researchers have used the ERP methodology to probe the neural basis of reward learning in humans. However, examination of the feedback related negativity and the reward positivity cannot be done without an understanding of some key methodological issues that must be taken into account when using ERPs and examining these ERP components. For example, even the component name - the feedback related negativity - is a source of debate within the research community as some now strongly feel that the component should be named the reward positivity (Proudfit, 2015). Here, ten key methodological issues are discussed - confusion in component naming, the reward positivity, component identification, peak quantification and the use of difference waveforms, frequency (the N200) and component contamination (the P300), the impact of feedback timing, action, and task learnability, and how learning results in changes in the amplitude of the feedback-related negativity/reward positivity. The hope here is to not provide a definitive approach for examining the feedback related negativity/reward positivity, but instead to outline the key issues that must be taken into account when examining this component to assist researchers in their study of human reward processing with the ERP methodology.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2017.11.005

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

Int J Psychophysiol

Relevance and uncertainty jointly influence reward anticipation at the level of the SPN ERP component.

The stimulus-preceding negativity (SPN) component reflects the anticipatory phase of reward processing. Its amplitude is usually larger for informative compared to uninformative upcoming stimuli, as well as for uncertain relative to predictable ones. In this study, we sought to assess whether these two effects, when combined together, produced a synergistic effect or rather independent ones on the SPN during performance monitoring. Participants performed a speeded Go/NoGo task while 64-channel EEG was recorded concurrently. We focused on the SPN activity generated in anticipation of feedback, which was either positive (for correct and fast reactions) or negative (for correct but slow responses). Further, the feedback's informativeness about the satisfaction status of goals was alternated across blocks. When uncertainty about the action outcome was low (in conditions where positive feedback was either less or more frequent than negative feedback), the SPN amplitude (measured at fronto-central electrodes) did not vary as a function of feedback's relevance or valence. By comparison, when positive and negative feedback were equiprobable (uncertainty was high), the SPN was more pronounced for relevant compared to irrelevant feedback. Interestingly, in this condition, it was also larger at right fronto-central sites for positive than negative feedback. These ERP results suggest that both factors-relevance and uncertainty- combine and influence reward anticipation at the SPN level.

CognitiveConstruct

RewardProcessing

10.1080/10826084.2017.1325374

Substance use & misuse

Subst Use Misuse

The Effects of Smoking Abstinence on Incentivized Spatial Working Memory.

Reward processing and working memory (WM) underlie value-based decision-making; consequently, joint examination of these systems may further our understanding of why smokers choose to smoke again following a quit attempt (relapse). While previous studies have demonstrated altered reward and WM function associated with nicotine exposure, little is known about the effects of abstinence on the joint function of these systems. The current study aims to address this gap. Eighteen daily smokers were tested on a monetarily incentivized memory guided saccade (MGS) task on two separate, counterbalanced occasions, an abstinent and a non-abstinent session. The MGS task is a widely used metric of spatial working memory and enables precise quantification of the effects of rewards and nicotine exposure on behavior. During the non-abstinent session, participants showed increased accuracy of the initial saccade towards the remembered target location on reward vs. neutral trials. Participants also showed increased accuracy of the final saccade towards the target, across incentive types, only during the non-abstinent condition. Our observation that rewards improve the accuracy of the initial memory guided saccade during the non-abstinent but not abstinent condition extends a growing literature indicating reduced motivation towards monetary rewards during abstinence. Further, differences in the accuracy of the final corrective saccade during the non-abstinent but not the abstinent condition suggests smoking abstinence-related effects on WM precision beyond those related to incentive motivation (e.g., sustained attention). This work extends our fundamental understanding of smoking's effects on core affective and cognitive processes.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2017.01790

Frontiers in psychology

Front Psychol

Patterns of Joint Improvisation in Adults with Autism Spectrum Disorder.

Recent research on autism spectrum disorders (ASDs) suggests that individuals with autism may have a basic deficit in synchronizing with others, and that this difficulty may lead to more complex social and communicative deficits. Here, we examined synchronization during an open-ended joint improvisation (JI) paradigm, called the mirror game (MG). In the MG, two players take turns leading, following, and jointly improvising motion using two handles set on parallel tracks, while their motion tracks are recorded with high temporal and spatial resolution. A series of previous studies have shown that players in the MG attain moments of highly synchronized co-confident (CC) motion, in which there is no typical kinematic pattern of leader and reactive follower. It has been suggested that during these moments players act as a coupled unit and feel high levels of connectedness. Here, we aimed to assess whether participants with ASD are capable of attaining CC, and whether their MG performance relates to broader motor and social skills. We found that participants with ASD ( = 34) can indeed attain CC moments when playing with an expert improviser, though their performance was attenuated in several ways, compared to typically developing (TD) participants ( = 35). Specifically, ASD participants had lower rates of CC, compared with TD participants, which was most pronounced during the following rounds. In addition, the duration of their CC segments was shorter, across all rounds. When controlling for participants' motor skills (both on the MG console, and more broadly) some of the variability in MG performance was explained, but group differences remained. ASD participants' alexithymia further correlated with their difficulty following another's lead; though other social skills did not relate to MG performance. Participants' subjective reports of the game suggest that other cognitive and emotional factors, such as attention, motivation, and reward-processing, which were not directly measured in the experiment, may impact their performance. Together, these results show that ASD participants can attain moments of high motor synchronization with an expert improviser, even during an open-ended task. Future studies should examine the ways in which these skills may be further harnessed in clinical settings.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2017.11.001

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

Int J Psychophysiol

A longitudinal examination of event-related potentials sensitive to monetary reward and loss feedback from late childhood to middle adolescence.

Brain regions involved in reward processing undergo developmental changes from childhood to adolescence, and alterations in reward-related brain function are thought to contribute to the development of psychopathology. Event-related potentials (ERPs), such as the reward positivity (RewP) component, are valid measures of reward responsiveness that are easily assessed across development and provide insight into temporal dynamics of reward processing. Little work has systematically examined developmental changes in ERPs sensitive to reward. In this longitudinal study of 75 youth assessed 3 times across 6years, we used principal components analyses (PCA) to differentiate ERPs sensitive to monetary reward and loss feedback in late childhood, early adolescence, and middle adolescence. We then tested reliability of, and developmental changes in, ERPs. A greater number of ERP components differentiated reward and loss feedback in late childhood compared to adolescence, but components in childhood accounted for only a small proportion of variance. A component consistent with RewP was the only one to consistently emerge at each of the 3 assessments. RewP demonstrated acceptable reliability, particularly from early to middle adolescence, though reliability estimates varied depending on scoring approach and developmental period. The magnitude of the RewP component did not significantly change across time. Results provide insight into developmental changes in the structure of ERPs sensitive to reward, and indicate that RewP is a consistently observed and relatively stable measure of reward responsiveness, particularly across adolescence.

CognitiveConstruct

RewardProcessing

10.1038/npp.2017.277

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Neural Correlates of Impaired Reward-Effort Integration in Remitted Bulimia Nervosa.

The integration of reward magnitudes and effort costs is required for an effective behavioral guidance. This reward-effort integration was reported to be dependent on dopaminergic neurotransmission. As bulimia nervosa has been associated with a dysregulated dopamine system and catecholamine depletion led to reward-processing deficits in remitted bulimia nervosa, the purpose of this study was to identify the role of catecholamine dysfunction and its relation to behavioral and neural reward-effort integration in bulimia nervosa. To investigate the interaction between catecholamine functioning and behavioral, and neural responses directly, 17 remitted bulimic (rBN) and 21 healthy individuals (HC) received alpha-methyl-paratyrosine (AMPT) over 24 h to achieve catecholamine depletion in a randomized, crossover study design. We used functional magnetic resonance imaging (fMRI) and the monetary incentive delay (MID) task to assess reward-effort integration in relation to catecholaminergic neurotransmission at the behavioral and neural level. AMPT reduced the ability to integrate rewards and efforts effectively in HC participants. In contrast, in rBN participants, the reduced reward-effort integration was associated with illness duration in the sham condition and unrelated to catecholamine depletion. Regarding neural activation, AMPT decreased the reward anticipation-related neural activation in the anteroventral striatum. This decrease was associated with the AMPT-induced reduction of monetary earning in HC in contrast to rBN participants. Our findings contributed to the theory of a desensitized dopaminergic system in bulimia nervosa. A disrupted processing of reward magnitudes and effort costs might increase the probability of maintenance of bulimic symptoms.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2017.11.001

Neuropsychologia

Neuropsychologia

"Why don't they 'like' me more?": Comparing the time courses of social and monetary reward processing.

Humans possess a strong tendency towards social affiliation and interpersonal interaction. Yet, we know far less about how rewards in one's social environment affect functioning as we do with other types of rewards, presumably due to the inherent complexity of measuring social phenomena in laboratory settings. Here, we adapted a social reward paradigm (social incentive delay [SID]) for use in event-related potential (ERP) research, enabling a direct comparison of social and monetary reward processing. We found that social and monetary rewards elicit comparable ERP latencies and scalp topographies across several processing stages (reward cue, outcome anticipation, and outcome evaluation), highlighting the possibility of a common neural network. We also found evidence of latent reward sensitivity, as analogous monetary and social ERPs were correlated and associations were uniquely driven by reward signals. The SID is a promising and viable paradigm that is capable of disentangling multiple stages of social reward processing. The capacity to measure social processes will be critical as we broaden efforts to incorporate multiple contexts in reward sensitivity, which will enable us to gain important new insights into human functioning and dysfunction.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2017.08.020

Biological psychiatry

Biol Psychiatry

Amygdala Reward Reactivity Mediates the Association Between Preschool Stress Response and Depression Severity.

Research in adolescents and adults has suggested that altered neural processing of reward following early life adversity is a highly promising depressive intermediate phenotype. However, very little is known about how stress response, neural processing of reward, and depression are related in very young children. The present study examined the concurrent associations between cortisol response following a stressor, functional brain activity to reward, and depression severity in children 4 to 6 years old. Medication-naïve children 4 to 6 years old (N = 52) participated in a study using functional magnetic resonance imaging to assess neural reactivity to reward, including gain, loss, and neutral outcomes. Parent-reported child depression severity and child cortisol response following stress were also measured. Greater caudate and medial prefrontal cortex reactivity to gain outcomes and increased amygdala reactivity to salient (i.e., both gain and loss) outcomes were observed. Higher total cortisol output following a stressor was associated with increased depression severity and reduced amygdala reactivity to salient outcomes. Amygdala reactivity was also inversely associated with depression severity and was found to mediate the relationship between cortisol output and depression severity. Results suggest that altered neural processing of reward is already related to increased cortisol output and depression severity in preschoolers. These results also demonstrate an important role for amygdala function as a mediator of this relationship at a very early age. Our results further underscore early childhood as an important developmental period for understanding the neurobiological correlates of early stress and increased risk for depression.

CognitiveConstruct

RewardProcessing

10.1038/s41562-017-0226-y

Nature human behaviour

Nat Hum Behav

The dopaminergic reward system underpins gender differences in social preferences.

Women are known to have stronger prosocial preferences than men, but it remains an open question as to how these behavioural differences arise from differences in brain functioning. Here, we provide a neurobiological account for the hypothesized gender difference. In a pharmacological study and an independent neuroimaging study, we tested the hypothesis that the neural reward system encodes the value of sharing money with others more strongly in women than in men. In the pharmacological study, we reduced receptor type-specific actions of dopamine, a neurotransmitter related to reward processing, which resulted in more selfish decisions in women and more prosocial decisions in men. Converging findings from an independent neuroimaging study revealed gender-related activity in neural reward circuits during prosocial decisions. Thus, the neural reward system appears to be more sensitive to prosocial rewards in women than in men, providing a neurobiological account for why women often behave more prosocially than men.

CognitiveConstruct

RewardProcessing

10.1111/jcpp.12823

Journal of child psychology and psychiatry, and allied disciplines

J Child Psychol Psychiatry

Practitioner Review: Definition, recognition, and treatment challenges of irritability in young people.

Irritability is one of the most common reasons for referral to child and adolescent mental health services and is the main characteristic of the new diagnosis of disruptive mood dysregulation disorder (DMDD). However, the recognition and management of irritability presents a major challenge in clinical practice and may be partly responsible for the dramatic increase in antipsychotic prescribing in recent years. In this review, we provide up-to-date information on the definition and mechanisms underlying irritability, and its assessment in clinical practice. We aim to discuss the latest research on DMDD, and the presence of severe irritability in the context of other disorders, as well as to recommend a treatment algorithm. Severe irritability is associated with aberrant reward processing and bias toward threatening stimuli. Several measures are available to easily assess irritability. The recent diagnosis of DMDD captures children whose main problem is severe irritability and differ from those with bipolar disorder in longitudinal outcomes, family history, and behavioral and neural correlates. Treatment of irritability might depend on the context it appears. Indirect evidence suggests that parent management training (PMT) and cognitive behavioral therapy (CBT) are the most supported psychological treatments for irritability. Irritability, recognized as a mood problem rather than a purely behavioral manifestation, is a common condition for young people. Practitioners should not ignore irritability as it is associated with substantial morbidity and impairment. Although there are no trials with irritability as main outcome, clinicians can apply several existing pharmacological and psychological interventions for its treatment. Also, new promising approaches relying on pathophysiological findings, such as exposure-based cognitive behavioral therapy techniques and interpretation bias training (IBT), are being currently investigated.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2017.10.030

NeuroImage

Neuroimage

Hippocampal morphology mediates biased memories of chronic pain.

Experiences and memories are often mismatched. While multiple studies have investigated psychological underpinnings of recall error with respect to emotional events, the neurobiological mechanisms underlying the divergence between experiences and memories remain relatively unexplored in the domain of chronic pain. Here we examined the discrepancy between experienced chronic low back pain (CBP) intensity (twice daily ratings) and remembered pain intensity (n = 48 subjects) relative to psychometric properties, hippocampus morphology, memory capabilities, and personality traits related to reward. 77% of CBP patients exaggerated remembered pain, which depended on their strongest experienced pain and their most recent mood rating. This bias persisted over nearly 1 year and was related to reward memory bias and loss aversion. Shape displacement of a specific region in the left posterior hippocampus mediated personality effects on pain memory bias, predicted pain memory bias in a validation CBP group (n = 21), and accounted for 55% of the variance of pain memory bias. In two independent groups (n = 20/group), morphology of this region was stable over time and unperturbed by the development of chronic pain. These results imply that a localized hippocampal circuit, and personality traits associated with reward processing, largely determine exaggeration of daily pain experiences in chronic pain patients.

CognitiveConstruct

RewardProcessing

10.1007/s00702-017-1793-9

Journal of neural transmission (Vienna, Austria : 1996)

J Neural Transm (Vienna)

Reward and value coding by dopamine neurons in non-human primates.

Rewards are fundamental to everyday life. They confer pleasure, support learning, and mediate decisions. Dopamine-releasing neurons in the midbrain are critical for reward processing. These neurons receive input from more than 30 brain areas and send widespread projections to the basal ganglia and frontal cortex. Their phasic responses are tuned to rewards. Specifically, dopamine signals code reward prediction error, the difference between received and predicted rewards. Decades of research in awake, behaving non-human primates (NHP), have shown the importance of these neural signals for learning and decision making. In this review, we will provide an overview of the bedrock findings that support the reward prediction error hypothesis and examine evidence that this signal plays a role in learning and decision making. In addition, we will highlight some of the conceptual challenges in dopamine neurophysiology and identify future areas of research to address these challenges. Keeping with the theme of this special issue, we will focus on the role of NHP studies in understanding dopamine neurophysiology and make the argument that primate models are essential to this line of research.

CognitiveConstruct

RewardProcessing

10.1002/brb3.807

Brain and behavior

Brain Behav

Prosocial deficits in behavioral variant frontotemporal dementia relate to reward network atrophy.

Empathy and shared feelings of reward motivate individuals to share resources with others when material gain is not at stake. Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disease that affects emotion- and reward-relevant neural systems. Although there is diminished empathy and altered reward processing in bvFTD, how the disease impacts prosocial behavior is less well understood. A total of 74 participants (20 bvFTD, 15 Alzheimer's disease [AD], and 39 healthy controls) participated in this study. Inspired by token-based paradigms from animal studies, we developed a novel task to measure prosocial giving (the "Giving Game"). On each trial of the Giving Game, participants decided how much money to offer to the experimenter, and prosocial giving was the total amount that participants gave to the experimenter when it cost them nothing to give. Voxel-based morphometry was then used to identify brain regions that were associated with prosocial giving. Prosocial giving was lower in bvFTD than in healthy controls; prosocial giving in AD did not differ significantly from either of the other groups. Whereas lower prosocial giving was associated with atrophy in the right pulvinar nucleus of the thalamus, greater prosocial giving was associated with atrophy in the left ventral striatum. These findings suggest that simple acts of generosity deteriorate in bvFTD due to lateralized atrophy in reward-relevant neural systems that promote shared feelings of positive affect.

CognitiveConstruct

RewardProcessing

10.1093/ntr/ntx159

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

Nicotine Tob Res

The Acute Effects of a Dopamine D3 Receptor Preferring Agonist on Motivation for Cigarettes in Dependent and Occasional Cigarette Smokers.

Dopaminergic functioning is thought to play critical roles in both motivation and addiction. There is preliminary evidence that dopamine agonists reduce the motivation for cigarettes in smokers. However, the effects of pramipexole, a dopamine D3 receptor preferring agonist, have not been investigated. The aim of this study was to examine the effects of an acute dose of pramipexole on the motivation to earn cigarettes and nondrug rewards. Twenty dependent and 20 occasional smokers received 0.5 mg pramipexole using a double-blind, placebo-controlled crossover design. Motivation for cigarettes and consummatory nondrug rewards was measured using the DReaM-Choice task, in which participants earned, and later "consumed," cigarettes, music, and chocolate. Demand for cigarettes was measured using the Cigarette Purchase Task (CPT). Self-reported craving, withdrawal, and drug effects were also recorded. Dependent smokers chose (p < .001) and button-pressed for (p < .001) cigarettes more, and chose chocolate less (p < .001), than occasional smokers. Pramipexole did not affect the number of choices for or amount of button-pressing for any reward including cigarettes, which was supported by a Bayesian analysis. The dependent smokers had greater demand for cigarettes than occasional smokers across all CPT outcomes (ps < .021), apart from elasticity. Pramipexole did not affect demand for cigarettes, and this was supported by Bayesian analyses. Pramipexole produced greater subjective "feel drug" and "dislike drug" effects than placebo. Dependent and occasional cigarette smokers differed in their motivation for cigarettes but not for the nondrug rewards. Pramipexole did not acutely alter motivation for cigarettes. These findings question the role of dopamine D3 receptors in cigarette-seeking behavior in dependent and occasional smokers. This study adds to the growing literature about cigarette versus nondrug reward processing in nicotine dependence and the role of dopamine in cigarette-seeking behavior. Our results suggest nicotine dependence is associated with a hypersensitivity to cigarette rewards but not a hyposensitivity to nondrug rewards. Furthermore, our results question the importance of dopamine D3 receptors in motivational processing of cigarettes in occasional and dependent smokers.

CognitiveConstruct

RewardProcessing

10.1093/ntr/ntx217

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

Nicotine Tob Res

Nicotine Increases Activation to Anticipatory Valence Cues in Anterior Insula and Striatum.

Smoking is associated with significant morbidity and mortality. Understanding the neurobiology of the rewarding effects of nicotine promises to aid treatment development for nicotine dependence. Through its actions on mesolimbic dopaminergic systems, nicotine engenders enhanced responses to drug-related cues signaling rewards, a mechanism hypothesized to underlie the development and maintenance of nicotine addiction. We evaluated the effects of acute nicotine on neural responses to anticipatory cues signaling (nondrug) monetary reward or loss among 11 nonsmokers who had no prior history of tobacco smoking. In a double-blind, crossover design, participants completed study procedures while wearing nicotine or placebo patches at least 1 week apart. In each drug condition, participants underwent functional magnetic resonance imaging while performing the monetary incentive delay task and performed a probabilistic monetary reward task, probing reward responsiveness as measured by response bias toward a more frequently rewarded stimulus. Nicotine administration was associated with enhanced activation, compared with placebo, of right fronto-anterior insular cortex and striatal regions in response to cues predicting possible rewards or losses and to dorsal anterior cingulate for rewards. Response bias toward rewarded stimuli correlated positively with insular activation to anticipatory cues. Nicotinic enhancement of monetary reward-related brain activation in the insula and striatum in nonsmokers dissociated acute effects of nicotine from effects on reward processing due to chronic smoking. Reward responsiveness predicted a greater nicotinic effect on insular activation to salient stimuli. Previous research demonstrates that nicotine enhances anticipatory responses to rewards in regions targeted by midbrain dopaminergic systems. The current study provides evidence that nicotine also enhances responses to rewards and losses in the anterior insula. A previous study found enhanced insular activation to rewards and losses in smokers and ex-smokers, a finding that could be due to nicotine sensitization or factors related to current or past smoking. Our finding of enhanced anterior insula response after acute administration of nicotine in nonsmokers provides support for nicotine-induced sensitization of insular response to rewards and losses.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2017.10.002

Psychiatry research. Neuroimaging

Psychiatry Res Neuroimaging

Automatic processing of emotional facial expressions as a function of social anhedonia.

Anhedonia is an important feature of major depression and schizophrenia-spectrum disorders. Few neuroimaging studies have investigated neural alterations in high anhedonia, isolated from other psychopathological variables, by including only participants without clinical diagnoses. The present study examined healthy individuals scoring high (N = 18) vs. low (N = 19) in social anhedonia, who were carefully selected from a sample of N = 282 participants. To examine differences in automatic brain responses to social-affective stimuli between high vs. low social anhedonia participants, we used functional magnetic resonance imaging. To assess early, automatic stages of emotion processing, we administered a paradigm presenting brief (33ms), backward-masked happy, sad, and neutral facial expressions. Individuals high in social anhedonia demonstrated increased activation in the bilateral thalamus and left red nucleus in response to masked sad faces relative to individuals low in social anhedonia. No significant group differences in brain activation emerged in other regions known to be involved in emotion and reward processing, including the amygdala and nucleus accumbens. Our results suggest that high social anhedonia in otherwise healthy individuals is associated with exaggerated automatic reactivity in the thalamus, which is a brain structure that has been implicated in the mediation of attentional processes.

CognitiveConstruct

RewardProcessing

10.1016/j.jadohealth.2017.08.006

The Journal of adolescent health : official publication of the Society for Adolescent Medicine

J Adolesc Health

Associations Between Neural Reward Processing and Binge Eating Among Adolescent Girls.

Neuroimaging studies suggest that altered brain responses to food-related cues in reward-sensitive regions characterize individuals who experience binge-eating episodes. However, the absence of longitudinal data limits the understanding of whether reward-system alterations increase vulnerability to binge eating, as theorized in models of the development of this behavior. Adolescent girls (N = 122) completed a functional magnetic resonance imaging monetary reward task at age 16 years as part of an ongoing longitudinal study. Self-report of binge eating was assessed using the Eating Attitudes Test at ages 16 and 18 years. Regression analyses examined concurrent and longitudinal associations between the blood-oxygenation-level-dependent response to anticipating and winning monetary rewards and the severity of binge eating while controlling for age 16 depressive symptoms and socioeconomic status. Greater ventromedial prefrontal cortex and caudate responses to winning money were correlated with greater severity of binge eating concurrently but not prospectively. This study is the first to examine longitudinal associations between reward responding and binge eating in community-based, mostly low-socioeconomic status adolescent girls. Ventromedial prefrontal cortex response to reward outcome-possibly reflecting an enhanced subjective reward value-appears to be a state marker of binge-eating severity rather than a predictor of future severity.

CognitiveConstruct

RewardProcessing

10.1016/bs.pbr.2017.08.005

Progress in brain research

Prog Brain Res

Functional roles of orexin/hypocretin receptors in reward circuit.

Since its first discovery in 1998, it has become clear that the orexinergic system plays an important role in regulating a number of functions including food, sex, social connections, and most prominently reward-related behaviors. Orexinergic neurons in the lateral hypothalamus project extensively to other brain areas, two most important of which are the ventral tegmental area and the nucleus accumbens that are involved in reward processing. In this review, we have presented the work in our laboratory along with the work of others and have discussed the possible functions we can infer from the research. We discuss the anatomy of the orexinergic system and its components followed by a presentation of other connected brain areas. The second part of this review discusses observed results from the morphine conditioned place preference test that sheds light on the possible role of the involved areas in reward processing. The complex circuits involved in reward processing are only beginning to be understood and we need to deepen our understanding regarding the nature of the interactions between all brain areas involved.

CognitiveConstruct

RewardProcessing

10.1093/brain/awx259

Brain : a journal of neurology

Brain

Reward deficits in behavioural variant frontotemporal dementia include insensitivity to negative stimuli.

During reward processing individuals weigh positive and negative features of a stimulus to determine whether they will pursue or avoid it. Though patients with behavioural variant frontotemporal dementia display changes in their pursuit of rewards, such as food, alcohol, money, and sex, the basis for these shifts is not clearly established. In particular, it is unknown whether patients' behaviour results from excessive focus on rewards, insensitivity to punishment, or to dysfunction in a particular stage of reward processing, such as anticipation, consumption, or action selection. Our goal was to determine the nature of the reward deficit in behavioural variant frontotemporal dementia and its underlying anatomy. We devised a series of tasks involving pleasant, unpleasant, and neutral olfactory stimuli, designed to separate distinct phases of reward processing. In a group of 25 patients with behavioural variant frontotemporal dementia and 21 control subjects, diagnosis by valence interactions revealed that patients with behavioural variant frontotemporal dementia rated unpleasant odours as less aversive than did controls and displayed lower skin conductance responses when anticipating an upcoming aversive odour. Subjective pleasantness ratings and skin conductance responses did not differ between behavioural variant frontotemporal dementia and controls for pleasant or neutral smells. In a task designed to measure the effort subjects would expend to smell or avoid smelling a stimulus, patients with behavioural variant frontotemporal dementia were less motivated, and therefore less successful than control subjects, at avoiding what they preferred not to smell, but had equivalent success at obtaining stimuli they found rewarding. Voxel-based morphometry of patients with behavioural variant frontotemporal dementia revealed that the inability to subjectively differentiate the valence of pleasant and unpleasant odours correlated with atrophy in right ventral mid-insula and right amygdala. High pleasantness ratings of unpleasant stimuli correlated with left dorsal anterior insula and frontal pole atrophy. These findings indicate that insensitivity to negative information may be a key component of the reward-seeking behaviours in behavioural variant frontotemporal dementia, and may relate to degeneration of structures that are involved in representing the emotional salience of sensory information.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2017.00195

Frontiers in psychiatry

Front Psychiatry

Impaired Feedback Processing for Symbolic Reward in Individuals with Internet Game Overuse.

Reward processing, which plays a critical role in adaptive behavior, is impaired in addiction disorders, which are accompanied by functional abnormalities in brain reward circuits. Internet gaming disorder, like substance addiction, is thought to be associated with impaired reward processing, but little is known about how it affects learning, especially when feedback is conveyed by less-salient motivational events. Here, using both monetary (±500 KRW) and symbolic (Chinese characters "right" or "wrong") rewards and penalties, we investigated whether behavioral performance and feedback-related neural responses are altered in Internet game overuse (IGO) group. Using functional MRI, brain responses for these two types of reward/penalty feedback were compared between young males with problems of IGO (IGOs,  = 18, mean age = 22.2 ± 2.0 years) and age-matched control subjects (Controls,  = 20, mean age = 21.2 ± 2.1) during a visuomotor association task where associations were learned between English letters and one of four responses. No group difference was found in adjustment of error responses following the penalty or in brain responses to penalty, for either monetary or symbolic penalties. The IGO individuals, however, were more likely to fail to choose the response previously reinforced by symbolic (but not monetary) reward. A whole brain two-way ANOVA analysis for reward revealed reduced activations in the IGO group in the rostral anterior cingulate cortex/ventromedial prefrontal cortex (vmPFC) in response to both reward types, suggesting impaired reward processing. However, the responses to reward in the inferior parietal region and medial orbitofrontal cortex/vmPFC were affected by the types of reward in the IGO group. Unlike the control group, in the IGO group the reward response was reduced only for symbolic reward, suggesting lower attentional and value processing specific to symbolic reward. Furthermore, the more severe the Internet gaming overuse symptoms in the IGO group, the greater the activations of the ventral striatum for monetary relative to symbolic reward. These findings suggest that IGO is associated with bias toward motivationally salient reward, which would lead to poor goal-directed behavior in everyday life.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsx089

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Influence of DARPP-32 genetic variation on BOLD activation to happy faces.

Dopaminergic pathways play a crucial role in reward processing, and advanced age can modulate its efficiency. DARPP-32 controls dopaminergic function and is a chemical nexus of reward processing. In 61 younger (20-30 years) and older adults (54% ♀) (65-74 years), we examined how blood-oxygen-level dependent (BOLD) activation to emotional faces, vary over genotypes at three single nucleotide polymorphism (SNPs), coding for DARPP-32 (rs879606; rs907094; 3764352). We also assessed age-magnification of DARPP-32 effects on BOLD activation. We found that major homozygote G, T or A genotypes, with higher cortical expression of DARPP-32, higher dopamine receptor efficacy, and greater bias toward positive cues, had increased functional connectivity in cortical-subcortical circuits in response to happy faces, engaging the dorsal prefrontal cortex (DLPFC), fusiform gyrus (FG) and the midbrain (MB). Local BOLD response to happy faces in FG, and MB was age-dependent, so that older carriers of the major G, T or A alleles showed lesser activation than minor genotypes. These genetic variants of DARPP-32 did not modulate BOLD response to angry faces, or engagement of the inferior occipital gyrus, to happy or angry faces. Taken together our results lend support for a potential role of DARPP-32 genetic variants in neural response to potential reward triggering cues.

CognitiveConstruct

RewardProcessing

10.2174/1570159X15666171017111532

Current neuropharmacology

Curr Neuropharmacol

Neural Network Alterations Across Eating Disorders: A Narrative Review of fMRI Studies.

Functional magnetic resonance imaging (fMRI) has provided insight on how neural abnormalities are related to the symptomatology of the eating disorders (EDs): anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). More specifically, an increasingly growing number of brain imaging studies has shed light on how functionally connected brain networks contribute not only to disturbed eating behavior, but also to transdiagnostic alterations in body/interoceptive perception, reward processing and executive functioning. This narrative review aims to summarize recent advances in fMRI studies of patients with EDs by highlighting studies investigating network alterations that are shared across EDs. Findings on reward processing in both AN and BN patients point to the presence of altered sensitivity to salient food stimuli in striatal regions and to the possibility of hypothalamic inputs being overridden by top-down emotional-cognitive control regions. Additionally, innovative new lines of research suggest that increased activations in fronto-striatal circuits are strongly associated with the maintenance of restrictive eating habits in AN patients. Although significantly fewer studies have been carried out in patients with BN and BED, aberrant neural responses to both food cues and anticipated food receipt appear to occur in these populations. These altered responses, coupled with diminished recruitment of prefrontal cognitive control circuitry, are believed to contribute to the binge eating of palatable foods. Results from functional network connectivity studies are diverse, but findings tend to converge on indicating disrupted resting-state connectivity in executive networks, the default-mode network and the salience network across EDs.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0185146

PloS one

PLoS One

Individual differences in responsivity to social rewards: Insights from two eye-tracking tasks.

Humans generally prefer social over nonsocial stimuli from an early age. Reduced preference for social rewards has been observed in individuals with autism spectrum conditions (ASC). This preference has typically been noted in separate tasks that measure orienting toward and engaging with social stimuli. In this experiment, we used two eye-tracking tasks to index both of these aspects of social preference in in 77 typical adults. We used two measures, global effect and preferential looking time. The global effect task measures saccadic deviation toward a social stimulus (related to 'orienting'), while the preferential looking task records gaze duration bias toward social stimuli (relating to 'engaging'). Social rewards were found to elicit greater saccadic deviation and greater gaze duration bias, suggesting that they have both greater salience and higher value compared to nonsocial rewards. Trait empathy was positively correlated with the measure of relative value of social rewards, but not with their salience. This study thus elucidates the relationship of empathy with social reward processing.

CognitiveConstruct

RewardProcessing

10.1111/acer.13526

Alcoholism, clinical and experimental research

Alcohol Clin Exp Res

Dopamine Transporter Gene Methylation is Associated with Nucleus Accumbens Activation During Reward Processing in Healthy but not Alcohol-Dependent Individuals.

Alcohol's reinforcement is mediated by dopamine signaling in the ventral striatum, which is modulated by the dopamine transporter (DAT). We hypothesized that methylomic variation in the DAT gene (DAT1/SLC6A3) affects DAT expression, thus contributing to differences in brain reward circuitry in individuals with alcohol dependence (ALC). Blood from 45 recently detoxified ALC and 45 healthy control (HC) individuals was used to assess DNA methylation across 5 functional regions of SLC6A3. Participants completed the monetary incentive delay task in a 3-Tesla magnetic resonance imaging (MRI) scanner. Employing regression models, we examined effects of SLC6A3 methylation on nucleus accumbens (NAc) blood-oxygen-level dependent (BOLD) responses during anticipation of high/low reward/loss. Results showed that decreased methylation of the promoter region of SLC6A3 predicted NAc activation during high loss anticipation (p = 0.028) and low loss anticipation (at trend-level; p = 0.057) in HC but not in individuals with ALC. Specifically, percentage of methylation at 2 CpG sites, located -1,001 and -993 base pairs from the transcription start site, accounted for significant variability in NAc activation in the HC group during high (ps ≤ 0.010) and low (ps ≤ 0.006) loss anticipation. There was no effect on reward anticipation. Furthermore, promoter methylation was positively associated with age, which replicates previous findings. Our data suggest that methylation in the promoter region of SLC6A3 predicts NAc activation during the anticipation of monetary loss in HCs. However, this effect was not present in the ALC group, suggesting that epigenetic regulation of striatal DAT expression might be disrupted in ALC, which may contribute to previously reported differences in sensitivity to reward and punishment in this population. Alternatively, it is possible that a similar relationship in the ALC group remained undetected possibly due to methodological limitations inherent in functional MRI (e.g., poor spatial resolution, low signal-to-noise ratio) that generally restrict interpretations regarding mechanisms of epigenetic factors involved in group differences in BOLD responses. Future neuroimaging studies are needed to further elucidate the relationship between SLC6A3 methylation and NAc activation in ALC.

CognitiveConstruct

RewardProcessing

10.1007/s10899-017-9721-3

Journal of gambling studies

J Gambl Stud

The Brain's Reward Response Occurs Even Without Actual Reward!

What if the brain's response to reward occurs even when there is no reward? Wouldn't that be a further concern for people prone to problem gambling and other forms of addiction, like those related to eating? Electroencephalography was employed to investigate this possibility using probabilistic feedback manipulations and measures of known event-related potentials (ERPs) related to reward processing. We tested the hypothesis-that reward-based ERPs would occur even in the absence of a tangible reward and when manipulations on expectation are implicit. The well-known P300 response potential was a key focus, and was assessed in non-gambling volunteer undergraduates on a task involving experimentally-manipulated probabilities of positive or negative feedback comprising three trial types-80, 50, or 20% positive feedback. A feedback stimulus (F1) followed a guess response between two possible outcomes (implicit win/loss), and then a second feedback stimulus (F2) was presented to confirm an alleged 'win' or 'loss' (explicit win/loss). Results revealed that amplitude of the P300 in F1-locked data (implicit manipulation) was larger (more positive) on average for feedback outcomes that were manipulated to be less likely than expected. The effect is pronounced after increased time on task (later trials), even though the majority of participants were not explicitly aware of our probability manipulations. For the explicit effects in F2-locked data, no meaningful or significant effects were observed. These findings point to the existence of proposed success-response mechanisms that operate not only explicitly but also with implicit manipulations that do not involve any direct indication of a win or loss, and are not associated with tangible rewards. Thus, there seems to be a non-explicit form of perception (we call 'implicit') associated with an internal experience of wins/losses (in the absence of actual rewards or losses) that can be measured in associated brain processes. The potential significance of these findings is discussed in terms of implications for problem gambling.

CognitiveConstruct

RewardProcessing

10.1111/bdi.12560

Bipolar disorders

Bipolar Disord

Disrupted cortico-limbic connectivity during reward processing in remitted bipolar I disorder.

Bipolar disorder (BD) is associated with elevated reward sensitivity and persistent positive affect, yet the neural mechanisms underlying these patterns are not well understood. In the present study, we examined putative disruptions in communication within a well-known cortico-limbic reward circuit during reward processing as a potential contributing mechanism to these symptoms. The present investigation employed a within- and between-subjects design utilizing a monetary and social incentive delay task among adults with bipolar disorder type I (BD; N = 24) and a healthy non-psychiatric control group (HC; N = 25) during functional magnetic resonance imaging (fMRI). Participants in the BD group were remitted at the time of testing. Functional connectivity analyses revealed increased connectivity between the ventral striatum (VS) seed region and orbitofrontal cortex (OFC) as well as the amygdala during processing of reward receipt in the BD group. After omission of expected rewards, the BD group showed decreased functional connectivity between the VS and a medial frontopolar cortex (mFPC) region associated with consideration of behavioral alternatives. Follow-up analyses within the BD group showed that increased VS-OFC connectivity after reward receipt, and decreased VS-mFPC connected after reward omission, were associated with higher levels of subthreshold mania symptoms. Results point toward potential mechanisms implicated in elevated reward sensitivity in BD. Enhanced VS-OFC connectivity after reward receipt may be involved in elevated valuation of rewards whereas blunted VS-mFPC connectivity after reward omission may reflect a failure to consider behavioral alternatives to reward pursuit.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsx092

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

A common neural code for social and monetary rewards in the human striatum.

Although managing social information and decision making on the basis of reward is critical for survival, it remains uncertain whether differing reward type is processed in a uniform manner. Previously, we demonstrated that monetary reward and the social reward of good reputation activated the same striatal regions including the caudate nucleus and putamen. However, it remains unclear whether overlapping activations reflect activities of identical neuronal populations or two overlapping but functionally independent neuronal populations. Here, we re-analyzed the original data and addressed this question using multivariate-pattern-analysis and found evidence that in the left caudate nucleus and bilateral nucleus accumbens, social vs monetary reward were represented similarly. The findings suggest that social and monetary rewards are processed by the same population of neurons within these regions of the striatum. Additional findings demonstrated similar neural patterns when participants experience high social reward compared to viewing others receiving low social reward (potentially inducing schadenfreude). This is possibly an early indication that the same population of neurons may be responsible for processing two different types of social reward (good reputation and schadenfreude). These findings provide a supplementary perspective to previous research, helping to further elucidate the mechanisms behind social vs non-social reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.rasd.2017.01.011

Research in autism spectrum disorders

Res Autism Spectr Disord

Inter-trial Coherence of Medial Frontal Theta Oscillations Linked to Differential Feedback Processing in Youth and Young Adults with Autism.

Impairment in prediction and appreciation for choice outcomes could contribute to several core symptoms of ASD. We examined electroencephalography (EEG) oscillations in 27 youth and young adults diagnosed with autism spectrum disorder (ASD) and 22 IQ-matched neurotypical controls while they performed a chance-based reward prediction task. We re-analyzed our previously published ERP data (Larson et al., 2011) and examined theta band oscillations (4-8 Hz) at frontal midline sites, within a timing window that overlaps with the feedback-related negativity (FRN). We focused on event-related changes after presentation of feedback for reward (WIN) and punitive (LOSE) outcomes, both for spectral power and inter-trial phase coherence. In our reward prediction task, for both groups, medial frontal theta power and phase coherence were greater following LOSE compared to WIN feedback. However, compared to controls, inter-trial coherence of medial frontal theta was significantly lower overall (across both feedback types) for individuals with ASD. Our results indicate that while individuals with ASD are sensitive to the valence of reward feedback, comparable to their neurotypical peers, they have reduced synchronization of medial frontal theta activity during feedback processing. This finding are consistent with previous studies showing neural variability in ASD and suggest that the processes underlying decision-making and reinforcement learning may be atypical and less efficient in ASD.

CognitiveConstruct

RewardProcessing

10.1093/sleep/zsx125

Sleep

Sleep

The Effects of Experimental Manipulation of Sleep Duration on Neural Response to Food Cues.

Despite growing literature on neural food cue responsivity in obesity, little is known about how the brain processes food cues following partial sleep deprivation and whether short sleep leads to changes similar to those observed in obesity. We used functional magnetic resonance imaging (fMRI) to test the hypothesis that short sleep leads to increased reward-related and decreased inhibitory control-related processing of food cues.In a within-subject design, 30 participants (22 female, mean age = 36.7 standard deviation = 10.8 years, body mass index range 20.4-40.7) completed four nights of 6 hours/night time-in-bed (TIB; short sleep) and four nights of 9 hours/night TIB (long sleep) in random counterbalanced order in their home environments. Following each sleep condition, participants completed an fMRI scan while viewing food and nonfood images.A priori region of interest analyses revealed increased activity to food in short versus long sleep in regions of reward processing (eg, nucleus accumbens/putamen) and sensory/motor signaling (ie, right paracentral lobule, an effect that was most pronounced in obese individuals). Contrary to the hypothesis, whole brain analyses indicated greater food cue responsivity during short sleep in an inhibitory control region (right inferior frontal gyrus) and ventral medial prefrontal cortex, which has been implicated in reward coding and decision-making (false discovery rate corrected q = 0.05).These findings suggest that sleep restriction leads to both greater reward and control processing in response to food cues. Future research is needed to understand the dynamic functional connectivity between these regions during short sleep and whether the interplay between these neural processes determines if one succumbs to food temptation.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0185796

PloS one

PLoS One

Beta-arrestin 1 regulation of reward-motivated behaviors and glutamatergic function.

The two highly homologous non-visual arrestins, beta-arrestin 1 and 2, are ubiquitously expressed in the central nervous system, yet knowledge of their disparate roles is limited. While beta-arrestin 2 (βarr2) has been implicated in several aspects of reward-related learning and behavior, very little is known about the behavioral function of beta-arrestin 1 (βarr1). Using mice lacking βarr1, we focused on the role of this scaffolding and signal transduction protein in reward-motivated behaviors and in striatal glutamatergic function. We found that βarr1 KO mice were both slower in acquiring cocaine self-administration and in extinguishing this behavior. They also showed deficits in learning tasks supported by a natural food reward, suggesting a general alteration in reward processing. We then examined glutamatergic synaptic strength in WT and KO medium spiny neurons (MSNs) of the Nucleus Accumbens (NAc) shell in naïve animals, and from those that underwent cocaine self-administration. An increase in the AMPA/NMDA (A/N) ratio and a relative lack of GluN2B-enriched NMDARs was found in naïve KO vs WT MSNs. Applying Lim Domain Kinase (LIMK1), the kinase that phosphorylates and inactivates cofilin, to these cells, showed that both βarr1 and LIMK regulate the A/N ratio and GluN2B-NMDARs. Cocaine self-administration increased the A/N ratio and GluN2B-NMDARs in WT MSNs and, although the A/N ratio also increased in KO MSNs, this was accompanied by fewer GluN2B-NMDARs and an appearance of calcium-permeable AMPARs. Finally, to examine the consequences of reduced basal GluN2B-NMDARs in reward-processing seen in KO mice, we chronically infused ifenprodil, a GluN2B antagonist, into the NAc shell of WT mice. This intervention substantially reduced food-motivated behavior. Together these findings identify a previously unknown role of βarr1 in regulating specific reward-motivated behaviors and glutamatergic function.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2017.09.013

Psychiatry research. Neuroimaging

Psychiatry Res Neuroimaging

Structural characteristics of the brain reward circuit regions in patients with bipolar I disorder: A voxel-based morphometric study.

Bipolar I disorder (BD-I) is often misdiagnosed, leading to inadequate treatment and significant disability along with reduced quality of life. Recent neural models suggest that the reward circuitry is affected in bipolar disorder. The purpose of the present study was to identify structural abnormalities in the brain reward-processing neural circuitry among patients with BD-I. 21 patients with BD-I and 21 healthy controls (HC) participated in this study. Structural magnetic resonance imaging was performed. Region-of-interest (ROI) voxel-based morphometry analysis was applied to assess the presence of structural changes between the BD-I patient group and the control group. The results of the reward circuitry ROI analysis revealed lower gray matter volumes in the left ventromedial prefrontal cortex (VMPFC), left dorsomedial prefrontal cortex (DMPFC), and left ventrolateral prefrontal cortex (VLPFC) in patients with BD-I compared to HC. Our results suggest that abnormalities in the brain reward-processing neural circuitry, especially those in the left VMPFC, left DMPFC, and left VLPFC, may play an important role in the pathophysiology of BD-I.

CognitiveConstruct

RewardProcessing

10.1016/j.pnpbp.2017.09.021

Progress in neuro-psychopharmacology & biological psychiatry

Prog Neuropsychopharmacol Biol Psychiatry

How can the depressed mind extract and remember predictive relationships of the environment? Evidence from implicit probabilistic sequence learning.

A growing body of evidence suggests that emotion and cognition are fundamentally intertwined; impairments in explicit, more effortful and attention-dependent cognitive functions have widely been observed in negative mood. Here we aimed to test how negative mood affects implicit cognition that is less susceptible to motivational and attentional factors associated with negative mood. Therefore, we examined implicit learning and retention of predictive relationships in patients with major depressive episode (MDE). Additionally, we directly compared subgroups of patients with major depressive disorder (MDD) vs. bipolar disorder (BD) in order to gain a deeper understanding of how implicit cognition is affected by these conditions. Implicit probabilistic sequence learning was measured by the Alternating Serial Reaction Time Task. The acquired knowledge was retested after a 24-hour delay period. Consistent with the frontostriatal deficits frequently reported in depression, we found weaker learning in patients with MDE, with a more pronounced deficit in patients with MDD compared to BD. After the 24-hour delay, MDE patients (both subgroups) showed forgetting, while the controls retained the previously acquired knowledge. These results cannot be explained by alterations in motivation, attention and reward processing but suggest more profound impairments of implicit learning and retention of predictive relationships among neutral stimuli in depression. To the best of our knowledge, this is the first study investigating retention of implicitly acquired sequential knowledge and reporting deficits in this domain in MDE. Our findings not only contribute to a better understanding of the complex interplay between affect and cognition but can also help improve screening, diagnosis and treatment protocols of depression.

CognitiveConstruct

RewardProcessing

10.1016/j.neuint.2017.09.013

Neurochemistry international

Neurochem Int

Ghrelin receptor antagonism of morphine-induced conditioned place preference and behavioral and accumbens dopaminergic sensitization in rats.

An increasing number of studies over the past few years have demonstrated ghrelin's role in alcohol, cocaine and nicotine abuse. However, the role of ghrelin in opioid effects has rarely been examined. Recently we substantiated in rats that ghrelin growth hormone secretagogue receptors (GHS-R1A) appear to be involved in acute opioid-induced changes in the mesolimbic dopaminergic system associated with the reward processing. The aim of the present study was to ascertain whether a ghrelin antagonist (JMV2959) was able to inhibit morphine-induced biased conditioned place preference and challenge-morphine-induced accumbens dopaminergic sensitization and behavioral sensitization in adult male rats. In the place preference model, the rats were conditioned for 8 days with morphine (10 mg/kg s.c.). On the experimental day, JMV2959 (3 and 6 mg/kg i.p.) or saline were administered before testing. We used in vivo microdialysis to determine changes of dopamine and its metabolites in the nucleus accumbens in rats following challenge-morphine dose (5 mg/kg s.c.) with or without JMV2959 (3 and 6 mg/kg i.p.) pretreatment, administered on the 12th day of spontaneous abstinence from morphine repeated treatment (5 days, 10-40 mg/kg). Induced behavioral changes were simultaneously monitored. Pretreatment with JMV2959 significantly and dose dependently reduced the morphine-induced conditioned place preference and significantly and dose dependently reduced the challenge-morphine-induced dopaminergic sensitization and affected concentration of by-products associated with dopamine metabolism in the nucleus accumbens. JMV2959 pretreatment also significantly reduced challenge-morphine-induced behavioral sensitization. Our present data suggest that GHS-R1A antagonists deserve to be further investigated as a novel treatment strategy for opioid addiction.

CognitiveConstruct

RewardProcessing

10.1176/appi.ajp.2017.17040430

The American journal of psychiatry

Am J Psychiatry

Ventral Striatum Functional Connectivity as a Predictor of Adolescent Depressive Disorder in a Longitudinal Community-Based Sample.

Previous studies have implicated aberrant reward processing in the pathogenesis of adolescent depression. However, no study has used functional connectivity within a distributed reward network, assessed using resting-state functional MRI (fMRI), to predict the onset of depression in adolescents. This study used reward network-based functional connectivity at baseline to predict depressive disorder at follow-up in a community sample of adolescents. A total of 637 children 6-12 years old underwent resting-state fMRI. Discovery and replication analyses tested intrinsic functional connectivity (iFC) among nodes of a putative reward network. Logistic regression tested whether striatal node strength, a measure of reward-related iFC, predicted onset of a depressive disorder at 3-year follow-up. Further analyses investigated the specificity of this prediction. Increased left ventral striatum node strength predicted increased risk for future depressive disorder (odds ratio=1.54, 95% CI=1.09-2.18), even after excluding participants who had depressive disorders at baseline (odds ratio=1.52, 95% CI=1.05-2.20). Among 11 reward-network nodes, only the left ventral striatum significantly predicted depression. Striatal node strength did not predict other common adolescent psychopathology, such as anxiety, attention deficit hyperactivity disorder, and substance use. Aberrant ventral striatum functional connectivity specifically predicts future risk for depressive disorder. This finding further emphasizes the need to understand how brain reward networks contribute to youth depression.

CognitiveConstruct

RewardProcessing

10.1016/j.bpsc.2017.01.009

Biological psychiatry. Cognitive neuroscience and neuroimaging

Biol Psychiatry Cogn Neurosci Neuroimaging

Reward-Related Neural Correlates of Antisocial Behavior and Callous-Unemotional Traits in Young Men.

Individuals involved in antisocial behavior often engage in excessive reward-driven behavior even in the face of severe punishments including incarceration. However, the neural mechanisms of reward processing in antisocial behavior have not been examined while considering the heterogeneity of antisocial behavior and specific phases of reward and loss processing. In this study, we investigate the relationship between antisocial behavior, callous-unemotional traits, and neural activity during the anticipation and receipt of rewards and losses. A community sample of 144 low income, racially diverse, urban males at risk for antisocial behavior completed self-report measures, a clinical interview, and an fMRI scan at age 20. Neural response during the anticipation and receipt of monetary rewards and losses was linked to antisocial behavior and callous-unemotional traits using ventral striatum region of interest analyses and exploratory whole brain analyses. Antisocial behavior, but not callous-unemotional traits, was related to less ventral striatum response during reward anticipation. There were no significant relationships between neural reactivity and antisocial behavior or callous-unemotional traits during reward or loss outcomes. Antisocial behavior was also related to less ventrolateral prefrontal cortex reactivity during reward and loss anticipation. These findings support a hypo-reactivity model of reward and loss anticipation in antisocial behavior. Lower striatal reactivity to cues of reward and lower prefrontal-regulatory recruitment during reward and loss anticipation may contribute to maladaptive reward-related behavior found in antisocial behavior.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2017.01529

Frontiers in psychology

Front Psychol

Gender Differences in the Perception of Personalized Half-Nude Female Bodies.

In the current study, we investigated how the perception of half-nude female body representations is altered by framing with information about the presented person. Images from tabloid newspapers were presented to male and female observers, and rated according to their aesthetic appeal while neurofunctional correlates were assessed using functional magnetic resonance imaging. While a generally stronger appetitive response might be expected in men, our results show a significant interaction between framing condition and gender of the observer. Men rated female bodies as more pleasing when presented without personal information, whereas women expressed more aesthetic appeal when information was added. Neuroimaging data revealed gender differences in processing body representations with additional personal information. In women, there was a stronger involvement of the anterior cingulate cortex and adjacent ventromedial prefrontal cortex, and in male observers a higher engagement of the bilateral inferior parietal cortex, when compared to each other respectively. These gender differences in framing effects particularly highlight higher aesthetic appeal and reward processing in women when female bodies are personalized.

CognitiveConstruct

RewardProcessing

10.1016/j.neulet.2017.09.038

Neuroscience letters

Neurosci Lett

Elderly adults show higher ventral striatal activation in response to motor performance related rewards than young adults.

Feedback on motor performance activates the striatum and boosting ventral striatum activation with rewarding feedback during motor training supports the consolidation of the learned skill. Aging is associated with changes of the reward system, including striatal and extrastriatal loss of dopamine receptors. How these changes interact with the blood oxygenation level dependent (BOLD) response is, however, not yet fully understood. While it is known that reward prediction and reward-based decision-making differ between young and elderly healthy adults, the influence of age on the processing of rewarding feedback on motor performance have not been investigated so far. Nineteen young (26.42±2.84years) and 18 elderly (65.39±6.40years) healthy adults performed an arc-tracking task including performance feedback linked to a monetary reward after half of the trials, while undergoing functional magnetic resonance imaging (fMRI). The BOLD effect was compared in three predefined regions of interest: Ventral and dorsal striatum plus primary motor cortex. Our study demonstrates differences in the processing of motor performance related reward between young and elderly healthy adults. While both groups earned similar amounts of money linked to their own performance, the ventral striatal response to the rewarding feedback was higher in the older group. Deficient prediction about the rewarding feedback, a higher motivational status or compensation for a reduced number of dopamine receptors in the elderly might be possible explanations. How this interacts with the reward-induced improvement of motor skill consolidation, as observed in young subjects, has to be clarified.

CognitiveConstruct

RewardProcessing

10.1210/er.2016-1133

Endocrine reviews

Endocr Rev

Linking Stress and Infertility: A Novel Role for Ghrelin.

Infertility affects a remarkable one in four couples in developing countries. Psychological stress is a ubiquitous facet of life, and although stress affects us all at some point, prolonged or unmanageable stress may become harmful for some individuals, negatively impacting on their health, including fertility. For instance, women who struggle to conceive are twice as likely to suffer from emotional distress than fertile women. Assisted reproductive technology treatments place an additional physical, emotional, and financial burden of stress, particularly on women, who are often exposed to invasive techniques associated with treatment. Stress-reduction interventions can reduce negative affect and in some cases to improve in vitro fertilization outcomes. Although it has been well-established that stress negatively affects fertility in animal models, human research remains inconsistent due to individual differences and methodological flaws. Attempts to isolate single causal links between stress and infertility have not yet been successful due to their multifaceted etiologies. In this review, we will discuss the current literature in the field of stress-induced reproductive dysfunction based on animal and human models, and introduce a recently unexplored link between stress and infertility, the gut-derived hormone, ghrelin. We also present evidence from recent seminal studies demonstrating that ghrelin has a principal role in the stress response and reward processing, as well as in regulating reproductive function, and that these roles are tightly interlinked. Collectively, these data support the hypothesis that stress may negatively impact upon fertility at least in part by stimulating a dysregulation in ghrelin signaling.

CognitiveConstruct

RewardProcessing

10.1038/s41598-017-11558-6

Scientific reports

Sci Rep

Development of Monetary and Social Reward Processes.

The current study investigated monetary and social reward processing in children, adolescents and adults with adapted incentive-delay tasks and self-report questionnaires. Both tasks had three levels of reward magnitudes (no, low, and high). Qualified participants received 15 Chinese Yuan and an honor certificate as monetary and social rewards, respectively. The results indicated that both monetary and social rewards effectively speeded up responses for all three age groups as reward magnitude increased in the choice reaction time task. Among adolescents and adults, males exhibited faster responses in high reward than in low reward condition, while females responded equally fast in both conditions. Among children, girls responded faster to high reward than low reward condition. However, boys committed more errors than girls in low and high reward conditions, and they had exhibited more errors in high reward than that in no reward condition for social reward. Regarding the subjective ratings, both children and adolescents reported higher motivation for social reward than for monetary reward. These findings indicated that the males in the adolescent and adult groups were more sensitive to reward than were the females. Moreover, tangible and quantitative social reward had stronger incentive power than monetary reward among children and adolescents.

CognitiveConstruct

RewardProcessing

10.1016/j.npep.2017.08.003

Neuropeptides

Neuropeptides

Role of orexin receptors in the ventral tegmental area on acquisition and expression of morphine-induced conditioned place preference in the rats.

The orexins are hypothalamic neuropeptides and their role in reward processing and drug addiction has been demonstrated. The extent of involvement of each orexin receptor in the acquisition and expression of conditioned place preference (CPP) for morphine is still a matter of controversy. We investigated the functional differences between orexin-1 and -2 receptor blockade in the ventral tegmental area (VTA) on the acquisition and expression of morphine CPP. A total of 86 adult male Wistar rats weighing 250±30g (age 7-8weeks) received intra-VTA microinjection of either SB334867 (0.1, 1 and 10nM), a selective orexin-1 receptor (OX1R) antagonist, or TCS-OX2-29 (1, 5 and 25nM), a selective orexin-2 receptor (OX2R) antagonist. To measure the acquisition, the animals received each antagonist (SB334867 or TCS-OX2-29) 5min prior to subcutaneous injection of morphine (5mg/kg) during the conditioning phase. To measure the CPP expression, the animals received each antagonist on the post-conditioning phase. The CPP conditioning score was recorded by Ethovision software. Data showed that intra-VTA microinjection of OX1-R antagonist significantly attenuated morphine CPP acquisition, during the conditioning phase, and expression, during the post-conditioning phase. Intra-VTA microinjection of OX2-R antagonist also significantly attenuated morphine CPP acquisition and expression in the mentioned phases. Our results showed the orexin role in learning and memory and indicate that orexin receptors (OX1R and OX2R) function in the VTA is essential for both acquisition and expression of morphine reward in rats in the CPP model.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroscience.2017.08.051

Neuroscience

Neuroscience

Psychological Processes in Chronic Pain: Influences of Reward and Fear Learning as Key Mechanisms - Behavioral Evidence, Neural Circuits, and Maladaptive Changes.

In the understanding of chronic pain, hypotheses derived from psychological theories, together with insights from physiological assessments and brain imaging, highlight the importance of mechanistically driven approaches. Physical system changes, for example following injury, can result in alterations of psychological processes and are accompanied by changes in corticolimbic circuits, which have been shown to be essential in emotional learning and memory, as well as reward processing and related behavior. In the present review, we thus highlight the importance of motivational, reward/pain relief, and fear learning processes in the context of chronic pain and discuss the potential of a mechanistic understanding of chronic pain within a clinical perspective, for example for the development of therapeutic strategies. We argue that changes in these mechanisms are not only characteristic for chronic pain, reflecting consequences of the disorder, but are also critically involved in the transition from acute to chronic pain states.

CognitiveConstruct

RewardProcessing

10.3389/fendo.2017.00200

Frontiers in endocrinology

Front Endocrinol (Lausanne)

Arginine Vasopressin Effects on Subjective Judgments and Neural Responses to Same and Other-Sex Faces in Men and Women.

Arginine vasopressin (AVP) influences social and emotional behaviors across a wide range of species. In humans, intranasal AVP has been previously shown to alter physiological responses to and subjective judgments of same-sex faces in both men and women. The present study attempted to elucidate the neural mechanism for these effects by randomizing 40 healthy men and 40 healthy women to treatment with either 40 IU intranasal AVP or a saline placebo approximately 30 min before imaging their brain function with fMRI as they viewed same and other-sex faces. All subjects were also scanned a second time several days later with no treatment to evaluate the persistence of AVP effects over time. AVP acutely increased positive ratings of same-sex faces in women, with some evidence that these effects persisted until the second scan. While AVP had no acute effects on same-sex ratings in men, AVP increased positive ratings of same-sex faces several days later. On the other hand, AVP had no effect on other-sex face judgments in either sex. AVP modulation of brain function was focused on the nucleus accumbens (NAc) and the lateral septum, two reward processing areas involved in the formation of social bonds. AVP provoked acute increases in right NAc and bilateral lateral septum responses to female faces among men, with left lateral septum responses persisting over time while right NAc responses reversed over time. Finally, AVP modulated hypothalamic activation to faces in both men and women. The present study therefore indicates that intranasal AVP affects subjective ratings and neural responses to same and other-sex faces in men and women, with some effects persisting and others emerging over time. Future studies should investigate whether AVP effects are modulated by individual variables such as genotype, personality, or attachment style as previously reported for other nonapeptides.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2017.08.007

Developmental cognitive neuroscience

Dev Cogn Neurosci

Flexing dual-systems models: How variable cognitive control in children informs our understanding of risk-taking across development.

Prevailing models of the development of decision-making propose that peak risk-taking occurs in adolescence due to a neural imbalance between two processes: gradual, linearly developing cognitive control and rapid, non-linearly developing reward-processing. Though many studies have found neural evidence supporting this dual-systems imbalance model, its behavioral predictions have been surprisingly difficult to document. Most laboratory studies have not found adolescents to exhibit greater risk-taking than children, and public health data show everyday risk-taking to peak in late adolescence/early adulthood. Moreover, when adolescents are provided detailed information about decision options and consequences, they evince similar behavior to adults. Such findings point to a critical feature of the development of decision-making that is missed by imbalance models. Specifically, the engagement of cognitive control is context dependent, such that cognitive control and therefore advantageous decision-making increases when available information is high and decreases when available information is low. Furthermore, the context dependence of cognitive control varies across development, such that increased information availability benefits children more than adolescents, who benefit more than adults. This review advances a flexible dual-systems model that is only imbalanced under certain conditions; explains disparities between neural, behavioral, and public health findings; and provides testable hypotheses for future research.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0183509

PloS one

PLoS One

Gut microbiome in ADHD and its relation to neural reward anticipation.

Microorganisms in the human intestine (i.e. the gut microbiome) have an increasingly recognized impact on human health, including brain functioning. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with abnormalities in dopamine neurotransmission and deficits in reward processing and its underlying neuro-circuitry including the ventral striatum. The microbiome might contribute to ADHD etiology via the gut-brain axis. In this pilot study, we investigated potential differences in the microbiome between ADHD cases and undiagnosed controls, as well as its relation to neural reward processing. We used 16S rRNA marker gene sequencing (16S) to identify bacterial taxa and their predicted gene functions in 19 ADHD and 77 control participants. Using functional magnetic resonance imaging (fMRI), we interrogated the effect of observed microbiome differences in neural reward responses in a subset of 28 participants, independent of diagnosis. For the first time, we describe gut microbial makeup of adolescents and adults diagnosed with ADHD. We found that the relative abundance of several bacterial taxa differed between cases and controls, albeit marginally significant. A nominal increase in the Bifidobacterium genus was observed in ADHD cases. In a hypothesis-driven approach, we found that the observed increase was linked to significantly enhanced 16S-based predicted bacterial gene functionality encoding cyclohexadienyl dehydratase in cases relative to controls. This enzyme is involved in the synthesis of phenylalanine, a precursor of dopamine. Increased relative abundance of this functionality was significantly associated with decreased ventral striatal fMRI responses during reward anticipation, independent of ADHD diagnosis and age. Our results show increases in gut microbiome predicted function of dopamine precursor synthesis between ADHD cases and controls. This increase in microbiome function relates to decreased neural responses to reward anticipation. Decreased neural reward anticipation constitutes one of the hallmarks of ADHD.

CognitiveConstruct

RewardProcessing

10.1038/s41598-017-10926-6

Scientific reports

Sci Rep

Humans with latent toxoplasmosis display altered reward modulation of cognitive control.

Latent infection with Toxoplasma gondii has repeatedly been shown to be associated with behavioral changes that are commonly attributed to a presumed increase in dopaminergic signaling. Yet, virtually nothing is known about its effects on dopamine-driven reward processing. We therefore assessed behavior and event-related potentials in individuals with vs. without latent toxoplasmosis performing a rewarded control task. The data show that otherwise healthy young adults with latent toxoplasmosis show a greatly diminished response to monetary rewards as compared to their non-infected counterparts. While this selective effect eliminated a toxoplasmosis-induced speed advantage previously observed for non-rewarded behavior, Toxo-positive subjects could still be demonstrated to be superior to Toxo-negative subjects with respect to response accuracy. Event-related potential (ERP) and source localization analyses revealed that this advantage during rewarded behavior was based on increased allocation of processing resources reflected by larger visual late positive component (LPC) amplitudes and associated activity changes in the right temporo-parietal junction (BA40) and left auditory cortex (BA41). Taken together, individuals with latent toxoplasmosis show superior behavioral performance in challenging cognitive control situations but may at the same time have a reduced sensitivity towards motivational effects of rewards, which might be explained by the presumed increase in dopamine.

CognitiveConstruct

RewardProcessing

10.1016/j.brainres.2017.08.024

Brain research

Brain Res

Reduced brain response to a sweet taste in Hispanic young adults.

Hispanics have an increased risk for metabolic disorders, which evidence suggests may be due to interactions between lifespan biological, genetic, and lifestyle factors. Studies show the diet of many U.S. Hispanic groups have high sugar consumption, which has been shown to influence future preference for and consumption of high-sugar foods, and is associated with increased risk for insulin-related disorders and obesity. Taste is a primary determinant of food preference and selection. Differences in neural response to taste have been associated with obesity. Understanding brain response to sweet taste stimuli in healthy Hispanic adults is an important first step in characterizing the potential neural mechanisms for this behavior. We used fMRI to examine brain activation during the hedonic evaluation of sucrose as a function of ethnicity in Hispanic and non-Hispanic young adults. Taste stimuli were administered orally while subjects were scanned at 3T. Data were analyzed with AFNI via 3dROIstats and 3dMEMA, a mixed effects multi-level analysis of whole brain activation. The Hispanic group had significantly lower ROI activation in the left amygdala and significantly lower whole brain activation in regions critical for reward processing, and hedonic evaluation (e.g. frontal, orbitofrontal, and anterior cingulate cortices) than the non-Hispanic group. Differences in processing of sweet tastes have important clinical and public health implications, especially considering increased risk of metabolic syndrome and cognitive decline in Hispanic populations. Future research to better understanding relationships between health risk and brain function in Hispanic populations is warranted to better conceptualize and develop interventions for these populations.

CognitiveConstruct

RewardProcessing