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10.1371/journal.pone.0097651

PloS one

PLoS One

Ghrelin modulates the fMRI BOLD response of homeostatic and hedonic brain centers regulating energy balance in the rat.

The orexigenic gut-brain peptide, ghrelin and its G-protein coupled receptor, the growth hormone secretagogue receptor 1a (GHS-R1A) are pivotal regulators of hypothalamic feeding centers and reward processing neuronal circuits of the brain. These systems operate in a cooperative manner and receive a wide array of neuronal hormone/transmitter messages and metabolic signals. Functional magnetic resonance imaging was employed in the current study to map BOLD responses to ghrelin in different brain regions with special reference on homeostatic and hedonic regulatory centers of energy balance. Experimental groups involved male, ovariectomized female and ovariectomized estradiol-replaced rats. Putative modulation of ghrelin signaling by endocannabinoids was also studied. Ghrelin-evoked effects were calculated as mean of the BOLD responses 30 minutes after administration. In the male rat, ghrelin evoked a slowly decreasing BOLD response in all studied regions of interest (ROI) within the limbic system. This effect was antagonized by pretreatment with GHS-R1A antagonist JMV2959. The comparison of ghrelin effects in the presence or absence of JMV2959 in individual ROIs revealed significant changes in the prefrontal cortex, nucleus accumbens of the telencephalon, and also within hypothalamic centers like the lateral hypothalamus, ventromedial nucleus, paraventricular nucleus and suprachiasmatic nucleus. In the female rat, the ghrelin effects were almost identical to those observed in males. Ovariectomy and chronic estradiol replacement had no effect on the BOLD response. Inhibition of the endocannabinoid signaling by rimonabant significantly attenuated the response of the nucleus accumbens and septum. In summary, ghrelin can modulate hypothalamic and mesolimbic structures controlling energy balance in both sexes. The endocannabinoid signaling system contributes to the manifestation of ghrelin's BOLD effect in a region specific manner. In females, the estradiol milieu does not influence the BOLD response to ghrelin.

CognitiveConstruct

RewardProcessing

10.1111/acer.12393

Alcoholism, clinical and experimental research

Alcohol Clin Exp Res

Contingency learning in alcohol dependence and pathological gambling: learning and unlearning reward contingencies.

Patients with alcohol dependence (AD) and pathological gambling (PG) are characterized by dysfunctional reward processing and their ability to adapt to alterations of reward contingencies is impaired. However, most neurocognitive tasks investigating reward processing involve a complex mix of elements, such as working memory, immediate and delayed rewards, and risk-taking. As a consequence, it is not clear whether contingency learning is altered in AD or PG. Therefore, the current study aimed to examine performance in a deterministic contingency learning task, investigating discrimination, reversal, and extinction learning. Thirty-three alcohol-dependent patients (ADs), 28 pathological gamblers (PGs), and 18 healthy controls (HCs) performed a contingency learning task in which they learned stimulus-reward associations that were first reversed and later extinguished while receiving deterministic feedback throughout. Accumulated points, number of perseverative errors and trials required to reach a criterion in each learning phase were compared between groups using nonparametric Kruskal-Wallis rank-sum tests. Regression analyses were performed to compare learning curves. PGs and ADs did not differ from HCs in discrimination learning, reversal learning, or extinction learning, on the nonparametric tests. Regression analyses, however, showed differences in the initial speed of learning: PGs were significantly faster in discrimination learning compared to ADs, and both PGs and ADs learned slower than HCs in the reversal learning and extinction phases of the task. Learning rates for reversal and extinction were slower for the alcohol-dependent group and PG group compared to HCs, suggesting that reversing and extinguishing learned contingencies require more effort in ADs and PGs. This implicates a diminished flexibility to overcome previously learned contingencies.

CognitiveConstruct

RewardProcessing

10.1016/j.appet.2014.04.028

Appetite

Appetite

Cognitive and behavioural effects of sugar consumption in rodents. A review.

The pronounced global rise in sugar consumption in recent years has been driven largely by increased consumption of sugar-sweetened beverages. Although high sugar intakes are recognised to increase the risk of obesity and related metabolic disturbances, less is known about how sugar might also impair cognition and learned behaviour. This review considers the effects of sugar in rodents on measures of learning and memory, reward processing, anxiety and mood. The parallels between sugar consumption and addictive behaviours are also discussed. The available evidence clearly indicates that sugar consumption can induce cognitive dysfunction. Deficits have been found most consistently on tasks measuring spatial learning and memory. Younger animals appear to be particularly sensitive to the effects of sugar on reward processing, yet results vary according to what reward-related behaviour is assessed. Sugar does not appear to produce long-term effects on anxiety or mood. Importantly, cognitive impairments have been found when intake approximates levels of sugar consumption in people and without changes to weight gain. There remain several caveats when extrapolating from animal models to putative effects of sugar on cognitive function in people. These issues are discussed in conjunction with potential underlying neural mechanisms and directions for future research.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22540

Human brain mapping

Hum Brain Mapp

Reward anticipation in the adolescent and aging brain.

Processing of reward is the basis of adaptive behavior of the human being. Neural correlates of reward processing seem to be influenced by developmental changes from adolescence to late adulthood. The aim of this study is to uncover these neural correlates during a slot machine gambling task across the lifespan. Therefore, we used functional magnetic resonance imaging to investigate 102 volunteers in three different age groups: 34 adolescents, 34 younger adults, and 34 older adults. We focused on the core reward areas ventral striatum (VS) and ventromedial prefrontal cortex (VMPFC), the valence processing associated areas, anterior cingulate cortex (ACC) and insula, as well as information integration associated areas, dorsolateral prefrontal cortex (DLPFC), and inferior parietal lobule (IPL). Results showed that VS and VMPFC were characterized by a hyperactivation in adolescents compared with younger adults. Furthermore, the ACC and insula were characterized by a U-shape pattern (hypoactivation in younger adults compared with adolescents and older adults), whereas the DLPFC and IPL were characterized by a J-shaped form (hyperactivation in older adults compared with younger groups). Furthermore, a functional connectivity analysis revealed an elevated negative functional coupling between the inhibition-related area rIFG and VS in younger adults compared with adolescents. Results indicate that lifespan-related changes during reward anticipation are characterized by different trajectories in different reward network modules and support the hypothesis of an imbalance in maturation of striatal and prefrontal cortex in adolescents. Furthermore, these results suggest compensatory age-specific effects in fronto-parietal regions.

CognitiveConstruct

RewardProcessing

10.1016/j.cortex.2014.02.023

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

Cortex

Haloperidol blocks dorsal striatum activity but not analgesia in a placebo paradigm.

Although placebo analgesia has been associated with an engagement of the endogenous opioid system there is growing evidence from neuropharmacological studies for an involvement of additional neurotransmitter systems. An increased dopaminergic neurotransmission in the ventral basal ganglia that has been found during placebo analgesia suggests a role for the dopaminergic system (Scott et al., 2007). It is, however, unclear whether striatal dopaminergic activity is causally involved in this type of analgesia. This study aimed at exploring the functional role of the dopaminergic system in placebo analgesia. To this end, we investigated the effect of the dopamine D2/D3 receptor antagonist haloperidol on behavioral and neural measures of placebo analgesia using functional magnetic resonance imaging (fMRI) in healthy volunteers. We found that 2 mg haloperidol p.o. significantly reduced the correlation between dorsal striatum activity and the individual placebo response, but had no significant effect on placebo analgesia at the behavioral or neural level, as indexed by activity in sensory or pain-modulatory brain regions. Our study therefore suggests that dopaminergic neurotransmission might not be causally involved in placebo analgesia but is related to phenomena associated with placebo analgesia such as reward processing and learning.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2014.00331

Frontiers in psychology

Front Psychol

Stability of executive function and predictions to adaptive behavior from middle childhood to pre-adolescence.

The shift from childhood to adolescence is characterized by rapid remodeling of the brain and increased risk-taking behaviors. Current theories hypothesize that developmental enhancements in sensitivity to affective environmental cues in adolescence may undermine executive function (EF) and increase the likelihood of problematic behaviors. In the current study, we examined the extent to which EF in childhood predicts EF in early adolescence. We also tested whether individual differences in neural responses to affective cues (rewards/punishments) in childhood serve as a biological marker for EF, sensation-seeking, academic performance, and social skills in early adolescence. At age 8, 84 children completed a gambling task while event-related potentials (ERPs) were recorded. We examined the extent to which selections resulting in rewards or losses in this task elicited (i) the P300, a post-stimulus waveform reflecting the allocation of attentional resources toward a stimulus, and (ii) the SPN, a pre-stimulus anticipatory waveform reflecting a neural representation of a "hunch" about an outcome that originates in insula and ventromedial PFC. Children also completed a Dimensional Change Card-Sort (DCCS) and Flanker task to measure EF. At age 12, 78 children repeated the DCCS and Flanker and completed a battery of questionnaires. Flanker and DCCS accuracy at age 8 predicted Flanker and DCCS performance at age 12, respectively. Individual differences in the magnitude of P300 (to losses vs. rewards) and SPN (preceding outcomes with a high probability of punishment) at age 8 predicted self-reported sensation seeking (lower) and teacher-rated academic performance (higher) at age 12. We suggest there is stability in EF from age 8 to 12, and that childhood neural sensitivity to reward and punishment predicts individual differences in sensation seeking and adaptive behaviors in children entering adolescence.

CognitiveConstruct

RewardProcessing

10.1016/j.npep.2014.04.003

Neuropeptides

Neuropeptides

Blockade of orexin-1 receptors in the ventral tegmental area could attenuate the lateral hypothalamic stimulation-induced potentiation of rewarding properties of morphine.

The orexins (hypocretins) are lateral hypothalamic (LH) neuropeptides that have been implicated in a variety of behaviors ranging from feeding to sleep and arousal. Evidence from animal models suggests a role for orexins in reward processing and drug addiction. In the present study, we investigated the direct effect of an orexin antagonist in the ventral tegmental area (VTA) on acquisition and expression of morphine conditioned place preference (CPP) induced by concurrent stimulation of the LH. Eighty-one adult male Wistar rats weighing 220-280 g were unilaterally implanted by two separate cannulae into the LH and VTA. The CPP paradigm was done; conditioning score and locomotor activity were recorded by Ethovision software. The animals received SB334867 as a selective orexin-1 receptor antagonist (0.1, 1 and 10 nmol/0.3 μl DMSO) in the VTA, just 5 min prior to intra-LH administration of ineffective dose of carbachol as a cholinergic agonist (62.5 nmol/0.5 μl saline) that stimulates orexin neurons in the LH and ineffective dose of morphine (1 mg/kg, subcutaneously) concurrently during conditioning phase (acquisition experiments) or post-conditioning phase (expression experiments). Data showed that the blockade of orexin-1 receptors in the VTA could inhibit the acquisition (development) but not expression of LH stimulation-induced morphine CPP in the rats. Our findings suggest that the orexinergic projections from the LH to the VTA are involved in the development of the LH stimulation-induced potentiation of morphine rewarding properties and orexin-1 receptors in the VTA have a substantial role in this phenomenon.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2014.03.031

Drug and alcohol dependence

Drug Alcohol Depend

Pretreatment measures of brain structure and reward-processing brain function in cannabis dependence: an exploratory study of relationships with abstinence during behavioral treatment.

Cannabis is widely abused, and efficacies of therapeutics for cannabis dependence remain suboptimal. Magnetic resonance imaging (MRI) may aid in the identification of biological markers for successful treatment outcomes (i.e., abstinence). Twenty men with cannabis dependence and twenty non-substance-using healthy comparison (HC) men underwent MRI scanning. Cannabis-dependent individuals then participated in a 12-week randomized clinical trial of behavioral treatments (contingency management (CM), cognitive behavioral therapy (CBT) or both). Pretreatment functional and structural data were compared between the cannabis-dependent and HC participants. In addition, individuals with cannabis dependence were subdivided based on the successful achievement of 21 days of consecutive abstinence during treatment to assess whether abstinent versus non-abstinent cannabis-dependent participants displayed different pretreatment functional and structural characteristics when compared to HC participants. In comparison to HC participants, cannabis-dependent participants demonstrated greater ventral striatal activation during the receipt of losing outcomes and smaller putamenal volumes. Cannabis-dependent participants who did not subsequently achieve 21 days of consecutive abstinence had increased activity within the striatum during the receipt of losing outcomes, relative to HC participants. Cannabis-dependent participants who did not achieve 21 days of abstinence had decreased bilateral putamen volumes prior to treatment, relative to HC participants. Individual differences in pretreatment striatal function and structure may relate to individual differences in treatment responses for cannabis dependence. While mechanisms underlying these associations require further exploration, the striatum might mediate treatment responses via its role in associative reward-learning (e.g., through skills training in CBT or reinforcement of abstinence in CM).

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2014.04.024

Behavioural brain research

Behav Brain Res

Individual differences in impulsive and risky choice: effects of environmental rearing conditions.

The present experiment investigated early-rearing environment modulation of individual differences in impulsive and risky choice. Rats were reared in an isolated condition (IC; n=12), in which they lived alone without novel stimuli, or an enriched condition (EC; n=11), in which they lived among conspecifics with novel stimuli. The impulsive choice task involved choices between smaller-sooner (SS) versus larger-later (LL) rewards. The risky choice task involved choices between certain-smaller (C-S) versus uncertain-larger (U-L) rewards. Following choice testing, incentive motivation to work for food was measured using a progressive ratio task and correlated with choice behavior. HPLC analyses were conducted to determine how monoamine concentrations within the prefrontal cortex (PFC) and nucleus accumbens (NAC) related to behavior in different tasks. IC rats were more impulsive than EC rats, but they did not differ in risky choice behavior. However, choice behavior across tasks was significantly correlated (i.e., the more impulsive rats were also riskier). There were no group differences in monoamine levels, but noradrenergic and serotonergic concentrations were significantly correlated with impulsive and risky choice. Furthermore, serotonin and norepinephrine concentrations in the NAC significantly correlated with incentive motivation and the timing of the reward delays within the choice tasks. These results suggest a role for domain general processes in impulsive and risky choice and indicate the importance of the NAC and/or PFC in timing, reward processing, and choice behavior.

CognitiveConstruct

RewardProcessing

10.1007/s00213-014-3573-7

Psychopharmacology

Psychopharmacology (Berl)

Opposing neural effects of naltrexone on food reward and aversion: implications for the treatment of obesity.

Opioid antagonism reduces the consumption of palatable foods in humans but the neural substrates implicated in these effects are less well understood. The aim of the present study was to examine the effects of the opioid antagonist, naltrexone, on neural response to rewarding and aversive sight and taste stimuli. We used functional magnetic resonance imaging (fMRI) to examine the neural responses to the sight and taste of pleasant (chocolate) and aversive (mouldy strawberry) stimuli in 20 healthy volunteers who received a single oral dose of naltrexone (50 mg) and placebo in a double-blind, repeated-measures cross-over, design. Relative to placebo, naltrexone decreased reward activation to chocolate in the dorsal anterior cingulate cortex and caudate, and increased aversive-related activation to unpleasant strawberry in the amygdala and anterior insula. These findings suggest that modulation of key brain areas involved in reward processing, cognitive control and habit formation such as the dorsal anterior cingulate cortex (dACC) and caudate might underlie reduction in food intake with opioid antagonism. Furthermore we show for the first time that naltrexone can increase activations related to aversive food stimuli. These results support further investigation of opioid treatments in obesity.

CognitiveConstruct

RewardProcessing

10.1016/j.cortex.2014.02.022

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

Cortex

Conceptualizing neuropsychiatric diseases with multimodal data-driven meta-analyses - the case of behavioral variant frontotemporal dementia.

Uniform coordinate systems in neuroimaging research have enabled comprehensive systematic and quantitative meta-analyses. Such approaches are particularly relevant for neuropsychiatric diseases, the understanding of their symptoms, prediction and treatment. Behavioral variant frontotemporal dementia (bvFTD), a common neurodegenerative syndrome, is characterized by deep alterations in behavior and personality. Investigating this 'nexopathy' elucidates the healthy social and emotional brain. Here, we combine three multimodal meta-analyses approaches - anatomical and activation likelihood estimates and behavioral domain profiles - to identify neural correlates of bvFTD in 417 patients and 406 control subjects and to extract mental functions associated with this disease by meta-analyzing functional activation studies in the comprehensive probabilistic functional brain atlas of the BrainMap database. The analyses identify the frontomedian cortex, basal ganglia, anterior insulae and thalamus as most relevant hubs, with a regional dissociation between atrophy and hypometabolism. Neural networks affected by bvFTD were associated with emotion and reward processing, empathy and executive functions (mainly inhibition), suggesting these functions as core domains affected by the disease and finally leading to its clinical symptoms. In contrast, changes in theory of mind or mentalizing abilities seem to be secondary phenomena of executive dysfunctions. The study creates a novel conceptual framework to understand neuropsychiatric diseases by powerful data-driven meta-analytic approaches that shall be extended to the whole neuropsychiatric spectrum in the future.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.2152-13.2014

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

J Neurosci

Valence-specific effects of BDNF Val66Met polymorphism on dopaminergic stress and reward processing in humans.

Brain-derived neurotrophic factor (BDNF) levels in dopaminergic (DA) cells within the ventral tegmental area (VTA)/nucleus accumbens (NAc) circuitry appear to be a candidate mechanism for the neuroadaptive changes that follow stress and reward responses in animal models. However, the role of the BDNF gene variants in responses to salient cues through DA neurotransmission in humans remains unexplored. Here, we studied the effect of the common functional BDNF Val(66)Met (rs6265) polymorphism on rewarding experiences in the striatum and DA-mediated responses to stress. Seventy-two healthy controls were genotyped for the BDNF Val(66)Met polymorphism and underwent the monetary incentive delay task during an functional magnetic resonance imaging (fMRI) session. Forty-nine of them also underwent a sustained pain challenge with and without placebo administration with potential analgesic properties during PET measures of DA D2/3-receptor-mediated neurotransmission. Neuroimaging results revealed a significant effect of BDNF (Met(66) carriers > Val/Val) on brain responses during the anticipation of monetary losses, baseline D2/3 receptor availability, and pain-stress-induced DA release in the NAc. Conversely, BDNF Met(66) carriers showed no activation in response to monetary gains and a blunted DA response to the analgesic placebo in the NAc. These results provide initial human evidence regarding the effect of the BDNF Val(66)Met polymorphism on DA-mediated responses to stress, its cognitive regulation by positive expectations, and the anticipatory responses to monetary gains and losses in the VTA-NAc pathway. Our results are of relevance to the neurobiology of stress and reward interactions and the pathophysiology of stress-related disorders.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0094300

PloS one

PLoS One

Brain signature of chronic orofacial pain: a systematic review and meta-analysis on neuroimaging research of trigeminal neuropathic pain and temporomandibular joint disorders.

Brain neuroimaging has been widely used to investigate the bran signature of chronic orofacial pain, including trigeminal neuropathic pain (TNP) and pain related to temporomandibular joint disorders (TMD). We here systematically reviewed the neuroimaging literature regarding the functional and structural changes in the brain of TNP and TMD pain patients, using a computerized search of journal articles via PubMed. Ten TNP studies and 14 TMD studies were reviewed. Study quality and risk of bias were assessed based on the criteria of patient selection, the history of medication, the use of standardized pain/psychological assessments, and the model and statistics of imaging analyses. Qualitative meta-analysis was performed by examining the brain regions which showed significant changes in either brain functions (including the blood-oxygen-level dependent signal, cerebral blood flow and the magnetic resonance spectroscopy signal) or brain structure (including gray matter and white matter anatomy). We hypothesized that the neuroimaging findings would display a common pattern as well as distinct patterns of brain signature in the disorders. This major hypothesis was supported by the following findings: (1) TNP and TMD patients showed consistent functional/structural changes in the thalamus and the primary somatosensory cortex, indicating the thalamocortical pathway as the major site of plasticity. (2) The TNP patients showed more alterations at the thalamocortical pathway, and the two disorders showed distinct patterns of thalamic and insular connectivity. Additionally, functional and structural changes were frequently reported in the prefrontal cortex and the basal ganglia, suggesting the role of cognitive modulation and reward processing in chronic orofacial pain. The findings highlight the potential for brain neuroimaging as an investigating tool for understanding chronic orofacial pain.

CognitiveConstruct

RewardProcessing

10.1111/adb.12144

Addiction biology

Addict Biol

Pathological gambling and alcohol dependence: neural disturbances in reward and loss avoidance processing.

Pathological gambling (PG) shares clinical characteristics such as craving and loss of control with substance use disorders and is thus considered a behavioral addiction. While functional alterations in the mesolimbic reward system have been correlated with craving and relapse in substance use disorders, only a few studies have examined this brain circuit in PG, and no direct comparison has been conducted so far. Thus, we investigated the neuronal correlates of reward processing in PG in contrast to alcohol-dependent (AD) patients and healthy subjects. Eighteen PG patients, 15 AD patients and 17 controls were investigated with a monetary incentive delay task, in which visual cues predict the consequence (monetary gain, avoidance of loss, none) of a fast response to a subsequent target stimulus. Functional magnetic resonance imaging data were analyzed to account for possible confounding factors such as local gray matter volume. Activity in the right ventral striatum during loss anticipation was increased in PG patients compared with controls and AD patients. Moreover, PG patients showed decreased activation in the right ventral striatum and right medial prefrontal cortex during successful loss avoidance compared with controls, which was inversely associated with severity of gambling behavior. Thus, despite neurobiological similarities to substance use disorders in reward processing, as reported by previous studies, we found relevant differences with respect to the anticipation of loss as well as its avoidance (negative reinforcement), which further contributes to the understanding of PG.

CognitiveConstruct

RewardProcessing

10.1177/0963721412474460

Current directions in psychological science

Curr Dir Psychol Sci

Parsing Anhedonia: Translational Models of Reward-Processing Deficits in Psychopathology.

The term has long been used in the psychiatric literature to describe reward-processing dysfunction in psychopathology, especially depression and schizophrenia. Although anhedonia literally describes a lack of pleasurable experiences in everyday life, recent advances in both the basic science and clinical literatures indicate that reward deficits in these disorders are much broader than hedonic responses. In this article, we summarize some of the recent theoretical and empirical advances in understanding deficits in reward processing and their neurobehavioral mechanisms, with a particular focus on the neural underpinnings of motivation and effort-based decision making. We also highlight the potential of translational neuroscience to enhance diagnostic clarity by defining clinical symptoms in terms of underlying pathophysiology.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2014.03.024

Drug and alcohol dependence

Drug Alcohol Depend

Changes in resting functional connectivity during abstinence in stimulant use disorder: a preliminary comparison of relapsers and abstainers.

Previously identified resting functional connectivity (FC) differences in individuals with stimulant use disorder (SUD) suggest an imbalance in neural regions that mediate behavioral aspects relevant to addiction such as emotion regulation and reward processing. There is a need to further investigate these differences across time between those that relapse and those that do not. This is the first longitudinal study of recently abstinent SUD (SUD-RA) that identifies specific FC changes in subsequent relapsers (vs abstainers). We hypothesized that (1) subsequent relapsers (vs abstainers) will show lower FC of emotion regulation regions and higher FC of reward processing regions and (2) FC differences would be more evident across time. We examined resting FC in 18 SUD-RAs (8 females, age: M=22.05 ± 2.64) and 15 non-substance abusing controls (NSAC; 5 females, age: M=24.21 ± 5.76) at Time 1 (abstinent ∼5 weeks). Fourteen NSAC and 12 SUD-RAs were re-examined at Time 2 (abstinent ∼13 weeks). With seed-based FC measures, we examined FC differences between SUD-RAs that abstained or relapsed over the subsequent 6 months. Relapsers (vs abstainers) had higher FC between (1) nucleus accumbens (NAcc) and left frontopolar cortex (FPC), (2) NAcc and posterior cingulate gyrus and (3) subgenual anterior cingulate and left FPC at Time 1. Relapsers (vs abstainers) showed larger reduction in FC strength within these regions across time. Resting FC reduction found in relapsers (vs. abstainers) from 5 to 13 weeks of abstinence may be a biological marker of relapse vulnerability. These preliminary findings require replication with larger sample sizes.

CognitiveConstruct

RewardProcessing

10.3758/s13415-014-0273-z

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Reward speeds up and increases consistency of visual selective attention: a lifespan comparison.

Children and older adults often show less favorable reward-based learning and decision making, relative to younger adults. It is unknown, however, whether reward-based processes that influence relatively early perceptual and attentional processes show similar lifespan differences. In this study, we investigated whether stimulus-reward associations affect selective visual attention differently across the human lifespan. Children, adolescents, younger adults, and older adults performed a visual search task in which the target colors were associated with either high or low monetary rewards. We discovered that high reward value speeded up response times across all four age groups, indicating that reward modulates attentional selection across the lifespan. This speed-up in response time was largest in younger adults, relative to the other three age groups. Furthermore, only younger adults benefited from high reward value in increasing response consistency (i.e., reduction of trial-by-trial reaction time variability). Our findings suggest that reward-based modulations of relatively early and implicit perceptual and attentional processes are operative across the lifespan, and the effects appear to be greater in adulthood. The age-specific effect of reward on reducing intraindividual response variability in younger adults likely reflects mechanisms underlying the development and aging of reward processing, such as lifespan age differences in the efficacy of dopaminergic modulation. Overall, the present results indicate that reward shapes visual perception across different age groups by biasing attention to motivationally salient events.

CognitiveConstruct

RewardProcessing

10.1093/brain/awu075

Brain : a journal of neurology

Brain

Anatomical correlates of reward-seeking behaviours in behavioural variant frontotemporal dementia.

Behavioural variant frontotemporal dementia is characterized by abnormal responses to primary reward stimuli such as food, sex and intoxicants, suggesting abnormal functioning of brain circuitry mediating reward processing. The goal of this analysis was to determine whether abnormalities in reward-seeking behaviour in behavioural variant frontotemporal dementia are correlated with atrophy in regions known to mediate reward processing. Review of case histories in 103 patients with behavioural variant frontotemporal dementia identified overeating or increased sweet food preference in 80 (78%), new or increased alcohol or drug use in 27 (26%), and hypersexuality in 17 (17%). For each patient, a primary reward-seeking score of 0-3 was created with 1 point given for each target behaviour (increased seeking of food, drugs, or sex). Voxel-based morphometry performed in 91 patients with available imaging revealed that right ventral putamen and pallidum atrophy correlated with higher reward-seeking scores. Each of the reward-related behaviours involved partially overlapping right hemisphere reward circuit regions including putamen, globus pallidus, insula and thalamus. These findings indicate that in some patients with behavioural variant frontotemporal dementia, low volume of subcortical reward-related structures is associated with increased pursuit of primary rewards, which may be a product of increased thalamocortical feedback.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2014.04.019

NeuroImage

Neuroimage

Resting state functional connectivity of the basal nucleus of Meynert in humans: in comparison to the ventral striatum and the effects of age.

The basal nucleus of Meynert (BNM) provides the primary cholinergic inputs to the cerebral cortex. Loss of neurons in the BNM is linked to cognitive deficits in Alzheimer's disease and other degenerative conditions. Numerous animal studies described cholinergic and non-cholinergic neuronal responses in the BNM; however, work in humans has been hampered by the difficulty of defining the BNM anatomically. Here, on the basis of a previous study that delineated the BNM of post-mortem human brains in a standard stereotaxic space, we sought to examine functional connectivity of the BNM, as compared to the nucleus accumbens (or ventral striatum, VS), in a large resting state functional magnetic resonance imaging data set. The BNM and VS shared but also showed a distinct pattern of cortical and subcortical connectivity. Compared to the VS, the BNM showed stronger positive connectivity with the putamen, pallidum, thalamus, amygdala and midbrain, as well as the anterior cingulate cortex, supplementary motor area and pre-supplementary motor area, a network of brain regions that respond to salient stimuli and orchestrate motor behavior. In contrast, compared to the BNM, the VS showed stronger positive connectivity with the ventral caudate and medial orbitofrontal cortex, areas implicated in reward processing and motivated behavior. Furthermore, the BNM and VS each showed extensive negative connectivity with visual and lateral prefrontal cortices. Together, the distinct cerebral functional connectivities support the role of the BNM in arousal, saliency responses and cognitive motor control and the VS in reward related behavior. Considering the importance of BNM in age-related cognitive decline, we explored the effects of age on BNM and VS connectivities. BNM connectivity to the visual and somatomotor cortices decreases while connectivity to subcortical structures including the midbrain, thalamus, and pallidum increases with age. These findings of age-related changes of cerebral functional connectivity of the BNM may facilitate research of the neural bases of cognitive decline in health and illness.

CognitiveConstruct

RewardProcessing

10.1016/j.bandc.2014.03.015

Brain and cognition

Brain Cogn

Show me the Money: the impact of actual rewards and losses on the feedback negativity.

The feedback negativity (FN) is an event-related potential component which is typically conceptualized as a negativity in response to losses that is absent in response to gains. However, there is also evidence that variation in the FN reflects the neural response to gains. The present study sought to explore these possibilities by manipulating the context in which loss and gain feedback was presented in a straightforward gambling task. In half the blocks, participants could win or lose money (Value condition), and in half the blocks, participants could not win or lose any money (No Value condition). The degree to which losses and gains were differentiated from one another (i.e., the ΔFN) was greater in the Value condition than in the No Value condition. Furthermore, though the responses to loss feedback and gain feedback were each enhanced in the Value condition relative to the No-Value condition, the effect of the monetary manipulation was substantially larger for the positivity to gains than the negativity to losses. This is consistent with the notion that the FN might reflect two independent processes, but that variation in the FN depends more upon the response to rewards than losses.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2014.00056

Frontiers in neuroscience

Front Neurosci

Neural evidence for description dependent reward processing in the framing effect.

Human decision making can be influenced by emotionally valenced contexts, known as the framing effect. We used event-related brain potentials to investigate how framing influences the encoding of reward. We found that the feedback related negativity (FRN), which indexes the "worse than expected" negative prediction error in the anterior cingulate cortex (ACC), was more negative for the negative frame than for the positive frame in the win domain. Consistent with previous findings that the FRN is not sensitive to "better than expected" positive prediction error, the FRN did not differentiate the positive and negative frame in the loss domain. Our results provide neural evidence that the description invariance principle which states that reward representation and decision making are not influenced by how options are presented is violated in the framing effect.

CognitiveConstruct

RewardProcessing

10.1002/eat.22204

The International journal of eating disorders

Int J Eat Disord

A pilot study linking reduced fronto-Striatal recruitment during reward processing to persistent bingeing following treatment for binge-eating disorder.

The primary purpose of this study was to examine neurobiological underpinnings of reward processing that may relate to treatment outcome for binge-eating disorder (BED). Prior to starting treatment, 19 obese persons seeking treatment for BED performed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Analyses examined how the neural correlates of reward processing related to binge-eating status after 4-months of treatment. Ten individuals continued to report binge-eating (BEpost-tx ) following treatment and 9 individuals did not (NBEpost-tx ). The groups did not differ in body mass index. The BEpost-tx group relative to the NBEpost-tx group showed diminished recruitment of the ventral striatum and the inferior frontal gyrus during the anticipatory phase of reward processing and reduced activity in the medial prefrontal cortex during the outcome phase of reward processing. These results link brain reward circuitry to treatment outcome in BED and suggest that specific brain regions underlying reward processing may represent important therapeutic targets in BED.

CognitiveConstruct

RewardProcessing

10.1016/j.bbi.2014.04.001

Brain, behavior, and immunity

Brain Behav Immun

Obesity and neuroinflammation: a pathway to cognitive impairment.

Obesity is a growing problem worldwide and is associated with a range of comorbidities, including cognitive dysfunction. In this review we will address the evidence that obesity and high fat feeding can lead to cognitive dysfunction. We will also examine the idea that obesity-associated systemic inflammation leads to inflammation within the brain, particularly the hypothalamus, and that this is partially responsible for these negative cognitive outcomes. Thus, obesity, and high fat feeding, lead to systemic inflammation and excess circulating free fatty acids. Circulating cytokines, free fatty acids and immune cells reach the brain at the level of the hypothalamus and initiate local inflammation, including microglial proliferation. This local inflammation likely causes synaptic remodeling and neurodegeneration within the hypothalamus, altering internal hypothalamic circuitry and hypothalamic outputs to other brain regions. The result is disruption to cognitive function mediated by regions such as hippocampus, amygdala, and reward-processing centers. Central inflammation is also likely to affect these regions directly. Thus, central inflammation in obesity leads not just to disruption of hypothalamic satiety signals and perpetuation of overeating, but also to negative outcomes on cognition.

CognitiveConstruct

RewardProcessing

10.1038/npp.2014.86

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

The CB1 receptor as an important mediator of hedonic reward processing.

The endocannabinoid (ECB) system has emerged recently as a key mediator for reward processing. It is well known that cannabinoids affect appetitive learning processes and can induce reinforcing and rewarding effects. However, the involvement of the ECB system in hedonic aspects of reward-related behavior is not completely understood. With the present study, we investigated the modulatory role of the ECB system on hedonic perception, measured by the pleasure attenuated startle (PAS) paradigm for a palatable food reward. Here, a conditioned odor is thought to induce a pleasant affective state that attenuates an aversive reflex-the acoustic startle response. Modulatory effects of the CB1 receptor antagonist/inverse agonist SR1411716 and the cannabinoid agonist WIN 55 212-2 on PAS were examined in rats. PAS was also measured in CB1 receptor knockout (KO) and wild-type (WT) mice. Pharmacological inhibition as well as the absence of CB1 receptors was found to reduce PAS, whereas WIN 55 212-2 administration increased PAS. Finally, presentation of a conditioned reward cue was found to induce striatal FosB/ΔFosB expression in WT mice, but not in KO mice, indicating a reduced stimulation of reward-related brain regions in conditioned KO mice by odor presentation. We here show that in addition to our previous studies in rats, PAS may also serve as a valuable and suitable measure to assess hedonic processing in mice. Our data further indicate that the ECB system, and in particular CB1 receptor signaling, appears to be highly important for the mediation of hedonic aspects of reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2014.03.077

NeuroImage

Neuroimage

P300 amplitude variation is related to ventral striatum BOLD response during gain and loss anticipation: an EEG and fMRI experiment.

The anticipation of favourable or unfavourable events is a key component in our daily life. However, the temporal dynamics of anticipation processes in relation to brain activation are still not fully understood. A modified version of the monetary incentive delay task was administered during separate functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) sessions in the same 25 participants to assess anticipatory processes with a multi-modal neuroimaging set-up. During fMRI, gain and loss anticipation were both associated with heightened activation in ventral striatum and reward-related areas. EEG revealed most pronounced P300 amplitudes for gain anticipation, whereas CNV amplitudes distinguished neutral from gain and loss anticipation. Importantly, P300, but not CNV amplitudes, were correlated to neural activation in the ventral striatum for both gain and loss anticipation. Larger P300 amplitudes indicated higher ventral striatum blood oxygen level dependent (BOLD) response. Early stimulus evaluation processes indexed by EEG seem to be positively related to higher activation levels in the ventral striatum, indexed by fMRI, which are usually associated with reward processing. The current results, however, point towards a more general motivational mechanism processing salient stimuli during anticipation.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0093955

PloS one

PLoS One

Amphetamine sensitization alters reward processing in the human striatum and amygdala.

Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS) has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD) signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.

CognitiveConstruct

RewardProcessing

10.1038/npp.2014.83

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

DRD2/ANKK1 polymorphism modulates the effect of ventral striatal activation on working memory performance.

Motivation is important for learning and cognition. Although dopaminergic (D2) transmission in the ventral striatum (VS) is associated with motivation, learning, and cognition are more strongly associated with function of the dorsal striatum, including activation in the caudate nucleus. A recent study found an interaction between intrinsic motivation and the DRD2/ANKK1 polymorphism (rs1800497), suggesting that A-carriers of rs1800497 are significantly more sensitive to motivation in order to improve during working memory (WM) training. Using data from the two large-scale imaging genetic data sets, IMAGEN (n=1080, age 13-15 years) and BrainChild (n∼300, age 6-27), we investigated whether rs1800497 is associated with WM. In the IMAGEN data set, we tested whether VS/caudate activation during reward anticipation was associated with WM performance and whether rs1800497 and VS/caudate activation interact to affect WM performance. We found that rs1800497 was associated with WM performance in IMAGEN and BrainChild. Higher VS and caudate activation during reward processing were significantly associated with higher WM performance (p<0.0001). An interaction was found between the DRD2/ANKK1 polymorphism rs1800497 and VS activation during reward anticipation on WM (p<0.01), such that carriers of the minor allele (A) showed a significant correlation between VS activation and WM, whereas the GG-homozygotes did not, suggesting that the effect of VS BOLD on WM is modified by inter-individual genetic differences related to D2 dopaminergic transmission.

CognitiveConstruct

RewardProcessing

10.1007/s00429-014-0760-6

Brain structure & function

Brain Struct Funct

A new window to understanding individual differences in reward sensitivity from attentional networks.

Existing evidence suggests that the presence of reward cues modifies the activity in attentional networks, however, the nature of these influences remains poorly understood. Here, we performed independent component analysis (ICA) in two fMRI datasets corresponding to two incentive delay tasks, which compared the response to reward (money and erotic pictures) and neutral cues, and yielded activations in the ventral striatum using a general linear model approach. Across both experiments, ICA revealed that both the right frontoparietal network and default mode network time courses were positively and negatively modulated by reward cues, respectively. Moreover, this dual neural response pattern was enhanced in individuals with strong reward sensitivity. Therefore, ICA may be a complementary tool to investigate the relevant role of attentional networks on reward processing, and to investigate reward sensitivity in normal and pathological populations.

CognitiveConstruct

RewardProcessing

10.3791/51281

Journal of visualized experiments : JoVE

J Vis Exp

Studying food reward and motivation in humans.

A key challenge in studying reward processing in humans is to go beyond subjective self-report measures and quantify different aspects of reward such as hedonics, motivation, and goal value in more objective ways. This is particularly relevant for the understanding of overeating and obesity as well as their potential treatments. In this paper are described a set of measures of food-related motivation using handgrip force as a motivational measure. These methods can be used to examine changes in food related motivation with metabolic (satiety) and pharmacological manipulations and can be used to evaluate interventions targeted at overeating and obesity. However to understand food-related decision making in the complex food environment it is essential to be able to ascertain the reward goal values that guide the decisions and behavioral choices that people make. These values are hidden but it is possible to ascertain them more objectively using metrics such as the willingness to pay and a method for this is described. Both these sets of methods provide quantitative measures of motivation and goal value that can be compared within and between individuals.

CognitiveConstruct

RewardProcessing

10.1007/s00213-014-3499-0

Psychopharmacology

Psychopharmacology (Berl)

Modafinil augments brain activation associated with reward anticipation in the nucleus accumbens.

The nucleus accumbens (NAc) works as a key brain structure of the reward system, in which reward-related neural activity is well correlated with dopamine release from mesolimbic dopaminergic neurons. Since modafinil can modulate dopaminergic transmission through re-uptake inhibition of dopamine, we investigated whether modafinil affects the reward-related brain activity in the NAc in healthy subjects. Twenty healthy participants underwent two series of functional magnetic resonance imaging while performing monetary incentive delay task in which they were cued to anticipate and respond to a rapidly presented target to gain or avoid losing varying amounts of money, under modafinil or placebo condition. Blood oxygenation-level dependent (BOLD) activation signals during gain and loss anticipations were analyzed in the NAc as an a priori region of interest as well as the whole brain. Modafinil significantly changed subjective feelings toward positive ones. The activation of BOLD signals was observed during gain anticipation under the placebo and modafinil conditions in the left and bilateral NAc, respectively. The modafinil condition showed significantly higher BOLD signal change at the highest gain (+¥500) cue compared to the placebo condition. The present study showed that modafinil affects reward processing in the NAc in healthy subjects through enhancing more positive anticipation, and it may provide a basis for the use of this drug for treating anhedonia observed in psychiatric disorders.

CognitiveConstruct

RewardProcessing

10.1037/a0035223

Journal of abnormal psychology

J Abnorm Psychol

Neural activity to positive expressions predicts daily experience of schizophrenia-spectrum symptoms in adults with high social anhedonia.

Social anhedonia (SA), the diminished pleasure from social relationships, is a prominent characteristic of the vulnerability and manifestation of schizophrenia disorder. However, SA can develop for multiple reasons and little is known about its neural basis; these 2 issues hinder the utility and sensitivity of SA as a marker of schizophrenia pathology. This study investigated whether lateral prefrontal cortex (LPFC) deficits in social reward processing are associated with both SA and other schizophrenia-spectrum symptoms. During functional MRI (fMRI), a community sample of healthy adults (N = 30) with high and low SA viewed positive, negative, and neutral facial expressions. Afterward, participants completed an online daily diary in which they rated schizophrenia-spectrum symptoms and occurrence of interpersonal conflict each day for 21 days. Compared with low SA, high SA participants had less ventral (V)LPFC activity to positive versus neutral expressions. In addition, participants with a combination of high SA and low VLPFC activity to positive versus neutral expressions had worse daily diary ratings of schizophrenia-spectrum symptoms, including worse cognition, paranoia, motivation/productivity, and vigor/positive affect (i.e., psychomotor activation). Finally, among high SA participants, VLPFC activity predicted the daily relationship between distress from interpersonal conflict and symptom-severity; specifically, high SA participants with low VLPFC activity had worse paranoia on days of high conflict distress. These findings indicate that VLPFC deficits in positive emotion are associated with both SA and other schizophrenia-spectrum symptoms and that understanding the interaction of SA, VLPFC function, and social stress could facilitate the use of SA in the prevention and treatment of schizophrenia.

CognitiveConstruct

RewardProcessing

10.1111/pcn.12182

Psychiatry and clinical neurosciences

Psychiatry Clin Neurosci

Cognitive neuroscience of social emotions and implications for psychopathology: examining embarrassment, guilt, envy, and schadenfreude.

Social emotions are affective states elicited during social interactions and integral for promoting socially appropriate behaviors and discouraging socially inappropriate ones. Social emotion-processing deficits significantly impair interpersonal relationships, and play distinct roles in the manifestation and maintenance of clinical symptomatology. Elucidating the neural correlates of discrete social emotions can serve as a window to better understanding and treating neuropsychiatric disorders. Moral cognition and social emotion-processing broadly recruit a fronto-temporo-subcortical network, supporting empathy, perspective-taking, self-processing, and reward-processing. The present review specifically examines the neural correlates of embarrassment, guilt, envy, and schadenfreude. Embarrassment and guilt are self-conscious emotions, evoked during negative evaluation following norm violations and supported by a fronto-temporo-posterior network. Embarrassment is evoked by social transgressions and recruits greater anterior temporal regions, representing conceptual social knowledge. Guilt is evoked by moral transgressions and recruits greater prefrontal regions, representing perspective-taking and behavioral change demands. Envy and schadenfreude are fortune-of-other emotions, evoked during social comparison and supported by a prefronto-striatal network. Envy represents displeasure in others' fortunes, and recruits increased dorsal anterior cingulate cortex, representing cognitive dissonance, and decreased reward-related striatal regions. Schadenfreude represents pleasure in others' misfortunes, and recruits reduced empathy-related insular regions and increased reward-related striatal regions. Implications for psychopathology and treatment design are discussed.

CognitiveConstruct

RewardProcessing

10.1007/s00213-014-3518-1

Psychopharmacology

Psychopharmacology (Berl)

Varenicline effects on drinking, craving and neural reward processing among non-treatment-seeking alcohol-dependent individuals.

The α4β2 nicotinic acetylcholine receptor partial agonist varenicline has been reported to reduce drinking among both heavy-drinking smokers and primary alcoholics, and this effect may be related to varenicline-mediated reduction of alcohol craving. Among smokers, varenicline has been reported to modulate cigarette cue-elicited brain activation in several reward-related areas. This pilot study tested varenicline's effects on drinking, alcohol craving, and alcohol cue-elicited activation of reward-related brain areas among non-treatment-seeking alcohol-dependent individuals. Thirty-five such individuals (mean age = 30, 57 % male, 76 % heavy drinking days in the past month, 15 smokers) were randomized to either varenicline (titrated to 2 mg) or placebo for 14 days, and were administered an alcohol cue reactivity fMRI task on day 14. A priori regions of interest (ROIs) were bilateral and medial orbitofrontal cortex (OFC), right ventral striatum (VS), and medial prefrontal cortex (mPFC). Despite good medication adherence, varenicline did not reduce heavy drinking days or other drinking parameters. It did, however, increase self-reported control over alcohol-related thoughts and reduced cue-elicited activation bilaterally in the OFC, but not in other brain areas. These data indicate that varenicline reduces alcohol craving and some of the neural substrates of alcohol cue reactivity. However, varenicline effects on drinking mediated by cue-elicited brain activation and craving might be best observed among treatment-seekers motivated to reduce their alcohol consumption.

CognitiveConstruct

RewardProcessing

10.1007/s11682-014-9298-8

Brain imaging and behavior

Brain Imaging Behav

Altered regional brain volumes in elderly carriers of a risk variant for drug abuse in the dopamine D2 receptor gene (DRD2).

Dopamine D2 receptors mediate the rewarding effects of many drugs of abuse. In humans, several polymorphisms in DRD2, the gene encoding these receptors, increase our genetic risk for developing addictive disorders. Here, we examined one of the most frequently studied candidate variant for addiction in DRD2 for association with brain structure. We tested whether this variant showed associations with regional brain volumes across two independent elderly cohorts, totaling 1,032 subjects. We first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI1). We hypothesized that this addiction-related polymorphism would be associated with structural brain differences in regions previously implicated in familial vulnerability for drug dependence. Then, we assessed the generalizability of our findings by testing this polymorphism in a non-overlapping replication sample of 294 elderly subjects from a continuation of the first ADNI project (ADNI2) to minimize the risk of reporting false positive results. In both cohorts, the minor allele-previously linked with increased risk for addiction-was associated with larger volumes in various brain regions implicated in reward processing. These findings suggest that neuroanatomical phenotypes associated with familial vulnerability for drug dependence may be partially mediated by DRD2 genotype.

CognitiveConstruct

RewardProcessing

10.1016/j.psychres.2014.01.036

Psychiatry research

Psychiatry Res

The road not taken: social vs. private comparisons in Asperger׳s syndrome and high functioning autism.

Evaluation of the outcomes of our decisions may instigate comparisons of our actual outcome with those of others (social comparisons) or comparisons with alternative outcomes of choices not made (private comparisons). Previous research has suggested a deficit in attention to social information among individuals with autism spectrum disorders. As social comparison involves the processing of social information, here we investigated the orientation towards and sensitivity to social vs. private comparisons in individuals with autism spectrum disorders. We compared the sensitivity to social vs. private comparisons among individuals diagnosed with Asperger's Syndrome (AS) or High Functioning Autism, using a task that entailed monetary rewards. Results showed that while individuals with AS generally demonstrate comparable sensitivity to absolute and relative rewards, they show less sensitivity to social comparison as compared to controls. Furthermore, they are characterized by a higher sensitivity to private rather than social comparison. These results suggest that low sensitivity to social comparisons is an important factor to consider in autism spectrum disorders.

CognitiveConstruct

RewardProcessing

10.1176/appi.ajp.2014.13081008

The American journal of psychiatry

Am J Psychiatry

A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and a road map for future research.

In this critical review, the authors appraise neuroimaging findings in bipolar disorder in emotion-processing, emotion-regulation, and reward-processing neural circuitry in order to synthesize the current knowledge of the neural underpinnings of bipolar disorder and provide a neuroimaging research road map for future studies. The authors examined findings from all major studies in bipolar disorder that used functional MRI, volumetric analysis, diffusion imaging, and resting-state techniques, integrating findings to provide a better understanding of larger-scale neural circuitry abnormalities in bipolar disorder. Bipolar disorder can be conceptualized, in neural circuitry terms, as parallel dysfunction in prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion-processing and emotion-regulation circuits bilaterally, together with an "overactive" left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward-processing circuitry, resulting in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation, and heightened reward sensitivity. A potential structural basis for these functional abnormalities is gray matter volume decreases in the prefrontal and temporal cortices, the amygdala, and the hippocampus and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions. Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuits supporting emotion processing, emotion regulation, and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in youths with bipolar disorder or at risk for bipolar disorder; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful individual-level data. Such studies will help identify clinically relevant biomarkers to guide diagnosis and treatment decision making for individuals with bipolar disorder.

CognitiveConstruct

RewardProcessing

10.3389/fnsys.2014.00024

Frontiers in systems neuroscience

Front Syst Neurosci

Impact of appetitive and aversive outcomes on brain responses: linking the animal and human literatures.

Decision-making is motivated by the possibility of obtaining reward and/or avoiding punishment. Though many have investigated behavior associated with appetitive or aversive outcomes, few have examined behaviors that rely on both. Fewer still have addressed questions related to how anticipated appetitive and aversive outcomes interact to alter neural signals related to expected value, motivation, and salience. Here we review recent rodent, monkey, and human research that address these issues. Further development of this area will be fundamental to understanding the etiology behind human psychiatric diseases and cultivating more effective treatments.

CognitiveConstruct

RewardProcessing

10.1007/s00221-014-3887-z

Experimental brain research

Exp Brain Res

Statistical and perceptual updating: correlated impairments in right brain injury.

It has been hypothesized that many of the cognitive impairments commonly seen after right brain damage (RBD) can be characterized as a failure to build or update mental models. We (Danckert et al. in Neglect as a disorder of representational updating. NOVA Open Access, New York, 2012a; Cereb Cortex 22:2745-2760, 2012b) were the first to directly assess the association between RBD and updating and found that RBD patients were unable to exploit a strongly biased play strategy in their opponent in the children's game rock, paper, scissors. Given that this game required many other cognitive capacities (i.e., working memory, sustained attention, reward processing), RBD patients could have failed this task for various reasons other than a failure to update. To assess the generality of updating deficits after RBD, we had RBD, left brain-damaged (LBD) patients and healthy controls (HCs) describe line drawings that evolved gradually from one figure (e.g., rabbit) to another (e.g., duck) in addition to the RPS updating task. RBD patients took significantly longer to alter their perceptual report from the initial object to the final object than did LBD patients and HCs. Although both patient groups performed poorly on the RPS task, only the RBD patients showed a significant correlation between the two, very different, updating tasks. We suggest these data indicate a general deficiency in the ability to update mental representations following RBD.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2014.00052

Frontiers in behavioral neuroscience

Front Behav Neurosci

The effect of age on neural processing of pleasant soft touch stimuli.

Tactile interactions with our environment stimulate afferent fibers within the skin, which deliver information about sensations of pain, texture, itch and other feelings to the brain as a comprehensive sense of self. These tactile interactions can stimulate brain regions involved in interoception and reward processing. This study examined subjective, behavioral, and neural processing as a function of age during stimulation of A-beta (Aβ) and C tactile (CT) afferents using a soft brush stroke task. 16 adolescents (ages 15-17), 22 young adults (ages 20-28), and 20 mature adults (ages 29-55) underwent a simple continuous performance task while periodically anticipating and experiencing a soft touch to the palm or forearm, during functional magnetic resonance imaging (fMRI). fMRI results showed that adolescents displayed greater bilateral posterior insula activation than young and mature adults across all conditions and stimulus types. Adolescents also demonstrated greater bilateral posterior insula activation than young and mature adults specifically in response to the soft touch condition. Adolescents also exhibited greater activation than mature adults in bilateral inferior frontal gyrus and striatum during the soft touch condition. However, mature adults showed greater striatum activation than adolescents and young adults during anticipation. In the left anterior cingulate cortex, mature adults exhibited greater activation than adolescents and young adults when anticipating the upcoming touch. These results support the hypothesis that adolescents show an exaggerated neural response to pleasant stimulation of afferents, which may have profound effects on how they approach or avoid social and risky situations. In particular, heightened interoceptive reactivity to pleasant stimuli might cause adolescents to seek experiences that are associated with pleasant stimulation.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2014.00048

Frontiers in behavioral neuroscience

Front Behav Neurosci

The oxytocin paradox.

CognitiveConstruct

RewardProcessing

10.1007/s00213-014-3504-7

Psychopharmacology

Psychopharmacology (Berl)

Effects of Mindfulness-Oriented Recovery Enhancement on reward responsiveness and opioid cue-reactivity.

Dysregulated reward processing is a hallmark feature of drug addiction; however, scant research has evaluated restructuring reward processing in the context of addiction treatment. We examined effects of Mindfulness-Oriented Recovery Enhancement (MORE) on reward responsiveness (RR) and opioid cue-reactivity in a sample of chronic pain patients with opioid use problems. We previously reported that MORE decreased pain, opioid misuse, and craving relative to a social support control group (SG). Here, we examined whether these outcomes were linked to changes in RR in a subset of participants. Participants were chronic pain patients (71 % women, age 46.6 ± 13.9) who received MORE (n = 20) or SG (n = 29). RR was measured before and after 8 weeks of treatment via heart rate (HR) and heart rate variability (HRV) responses during a dot probe task that included opioid-related, pain-related, and natural reward stimuli, as well as craving ratings. The MORE group, who reported decreased opioid misuse and opioid craving during treatment, evidenced less subjective opioid cue-reactivity, greater HR decelerations, and greater increases in HRV to all cues after treatment compared to the SG; HR and HRV effects were most pronounced for natural reward cues. Within the MORE group, HR deceleration to natural reward cues was correlated with increased subjective arousal to the cues, whereas HR deceleration to opioid cues was correlated with decreased subjective arousal. Effects of MORE on craving were mediated by enhanced RR. Results suggest that during treatment with MORE, cardiac-autonomic responsiveness to non-drug reward increases, while reactivity to opioid reward decreases. Studies are needed to discern whether changes in RR were a result or a determinant of reductions in opioid misuse and craving. RR may play a role in addiction treatment.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0089129

PloS one

PLoS One

Abnormal striatal BOLD responses to reward anticipation and reward delivery in ADHD.

Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22496

Human brain mapping

Hum Brain Mapp

Placebo analgesia and reward processing: integrating genetics, personality, and intrinsic brain activity.

Our expectations about an event can strongly shape our subjective evaluation and actual experience of events. This ability, applied to the modulation of pain, has the potential to affect therapeutic analgesia substantially and constitutes a foundation for non-pharmacological pain relief. A typical example of such modulation is the placebo effect. Studies indicate that placebo may be regarded as a reward, and brain activity in the reward system is involved in this modulation process. In the present study, we combined resting-state functional magnetic resonance imaging (rs-fMRI) measures, genotype at a functional COMT polymorphism (Val158Met), and personality measures in a model to predict the magnitude of placebo conditioning effect indicated by subjective pain rating reduction to calibrated noxious stimuli. We found that the regional homogeneity (ReHo), an index of local neural coherence, in the ventral striatum, was significantly associated with conditioning effects on pain rating changes. We also found that the number of Met alleles at the COMT polymorphism was linearly correlated to the suppression of pain. In a fitted regression model, we found the ReHo in the ventral striatum, COMT genotype, and Openness scores accounted for 59% of the variance in the change in pain ratings. The model was further tested using a separate data set from the same study. Our findings demonstrate the potential of combining resting-state connectivity, genetic information, and personality to predict placebo effect.

CognitiveConstruct

RewardProcessing

10.1038/npp.2014.21

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Temporal difference error prediction signal dysregulation in cocaine dependence.

Cocaine dependence impacts drug-related, dopamine-dependent reward processing, yet its influence on non-drug reward processing is unclear. Here, we investigated cocaine-mediated effects on reward learning using a natural food reinforcer. Cocaine-dependent subjects (N = 14) and healthy controls (N = 14) learned to associate a visual cue with a juice reward. In subsequent functional imaging sessions they were exposed to trials where juice was received as learned, withheld (negative temporal difference error (NTDE)), or received unexpectedly (positive temporal difference error (PTDE)). Subjects were scanned twice in sessions that were identical, except that cocaine-dependent participants received cocaine or saline 10 min before task onset. In the insula, precentral and postcentral gyri NTDE signals were greater, and PTDE-related function was reduced in cocaine-dependent subjects. Compared with healthy controls, in the cocaine-dependent group PTDE signals were also reduced in medial frontal gyrus and reward-related function, irrespective of predictability, was reduced in the putamen. Group differences in error-related activity were predicted by the time as last self-administered cocaine use, but TDE function was not influenced by acute cocaine. Thus, cocaine dependence seems to engender increased responsiveness to unexpected negative outcomes and reduced sensitivity to positive events in dopaminergic reward regions. Although it remains to be established if these effects are a consequence of or antecedent to cocaine dependence, they likely have implications for the high-cocaine use recidivism rates by contributing to the drive to consume cocaine, perhaps via influence on dopamine-related reward computations. The fact that these effects do not acquiesce to acute cocaine administration might factor in binge-related escalated consumption.

CognitiveConstruct

RewardProcessing

10.1016/j.rasd.2013.12.003

Research in autism spectrum disorders

Res Autism Spectr Disord

Intact Hedonic Responses to Sweet Tastes in Autism Spectrum Disorder.

The Sweet Taste Test (STT) is a standardized measure designed to index the ability to detect differences in sweet tastes (sweet taste sensitivity) and hedonic responses to sweet tastes (sweet taste liking). Profiles of response on the STT suggest enhanced hedonic responses to sweet tastes in psychiatric disorders characterized by dysfunctional reward processing systems, including binge-eating disorders and substance use disorders, and a putative mechanism governing STT responses is the brain opioid system. The present study examined STT responses in 20 adults with autism spectrum disorder (ASD) and 38 healthy control adults. There were no differences in sweet taste sensitivity or hedonic response to sweet tastes between the ASD and control groups. Within the ASD sample, ASD symptom severity was associated with sweet taste sensitivity, but not hedonic response to sweet taste. Results may ultimately shed light on brain opioid system functioning in ASD.

CognitiveConstruct

RewardProcessing

10.1016/j.physbeh.2014.02.026

Physiology & behavior

Physiol Behav

Dopamine signaling in the amygdala, increased by food ingestion and GLP-1, regulates feeding behavior.

Mesolimbic dopamine plays a critical role in food-related reward processing and learning. The literature focuses primarily on the nucleus accumbens as the key dopaminergic target in which enhanced dopamine signaling is associated with reward. Here, we demonstrate a novel neurobiological mechanism by which dopamine transmission in the amygdala regulates food intake and reward. We show that food intake was associated with increased dopamine turnover in the amygdala. Next, we assess the impact of direct intra-amygdala D1 and D2 receptor activation on food intake and sucrose-driven progressive ratio operant conditioning in rats. Amygdala D2 receptor activation reduced food intake and operant behavior for sucrose, whereas D2 receptor blockade increased food intake but surprisingly reduced operant behavior. In contrast, D1 receptor stimulation or blockade did not alter feeding or operant conditioning for food. The glucagon-like peptide 1 (GLP-1) system, a target for type 2 diabetes treatment, in addition to regulating glucose homeostasis, also reduces food intake. We found that central GLP-1R receptor activation is associated with elevated dopamine turnover in the amygdala, and that part of the anorexic effect of GLP-1 is mediated by D2 receptor signaling in the amygdala. Our findings indicate that amygdala dopamine signaling is activated by both food intake and the anorexic brain-gut peptide GLP-1 and that amygdala D2 receptor activation is necessary and sufficient to change feeding behavior. Collectively these studies indicate a novel mechanism by which the dopamine system affects feeding-oriented behavior at the level of the amygdala.

CognitiveConstruct

RewardProcessing

10.3758/s13415-014-0261-3

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Antipsychotic dose modulates behavioral and neural responses to feedback during reinforcement learning in schizophrenia.

Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2014.00046

Frontiers in psychology

Front Psychol

Two systems drive attention to rewards.

How options are framed can dramatically influence choice preference. While salience of information plays a central role in this effect, precisely how it is mediated by attentional processes remains unknown. Current models assume a simple relationship between attention and choice, according to which preference should be uniformly biased towards the attended item over the whole time-course of a decision between similarly valued items. To test this prediction we considered how framing alters the orienting of gaze during a simple choice between two options, using eye movements as a sensitive online measure of attention. In one condition participants selected the less preferred item to discard and in the other, the more preferred item to keep. We found that gaze gravitates towards the item ultimately selected, but did not observe the effect to be uniform over time. Instead, we found evidence for distinct early and late processes that guide attention according to preference in the first case and task demands in the second. We conclude that multiple time-dependent processes govern attention during choice, and that these may contribute to framing effects in different ways.

CognitiveConstruct

RewardProcessing

10.1007/s00429-014-0725-9

Brain structure & function

Brain Struct Funct

Midbrain volume predicts fMRI and ERP measures of reward reactivity.

Ventral striatal activation measured with functional magnetic resonance imaging (fMRI) and feedback negativity amplitude measured with event-related potentials (ERPs) are each enhanced during reward processing. Recent research has found that these two neural measures of reward processing are also related to one another, such that increases in ventral striatal activity are accompanied by increases in the amplitude of the feedback negativity. Although there is a long history of research implicating the midbrain dopamine system in reward processing, there has been little research into the possibility that structural variability in the midbrain may be linked to functional variability in reward reactivity. Here, we used structural MRI to measure midbrain volumes in addition to fMRI and ERP measures of functional neural reactivity to rewards in a simple gambling task. The results suggest that as midbrain volumes increase, fMRI reward reactivity in the ventral striatum and medial prefrontal cortex also increases. A similar relationship exists between midbrain structure and the amplitude of the feedback negativity; further, this relationship is mediated specifically by activity in the ventral striatum. These data demonstrate convergence between neuroanatomical, hemodynamic, and electrophysiological measures. Thus, structural variability in the midbrain relates to variability in fMRI and ERP measures of functional reward reactivity, which may play a critical role in reward-related psychopathologies and the treatment of these disorders.

CognitiveConstruct

RewardProcessing

10.1038/npp.2014.39

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Disturbed anterior prefrontal control of the mesolimbic reward system and increased impulsivity in bipolar disorder.

Bipolar disorder (BD) is characterized by recurrent mood episodes ranging from severe depression to acute full-blown mania. Both states of this severe psychiatric disorder have been associated with alterations of reward processing in the brain. Here, we present results of a functional magnetic resonance imaging (fMRI) study on the neural correlates and functional interactions underlying reward gain processing and reward dismissal in favor of a long-term goal in bipolar patients. Sixteen medicated patients diagnosed with bipolar I disorder, euthymic to mildly depressed, and sixteen matched healthy controls performed the 'desire-reason dilemma' (DRD) paradigm demanding rejection of priorly conditioned reward stimuli to successfully pursue a superordinate goal. Both groups exhibited significant activations in reward-related brain regions, particularly in the mesolimbic reward system. However, bipolar patients showed reduced neural responses of the ventral striatum (vStr) when exploiting a reward stimulus, and exhibited a decreased suppression of the reward-related activation of the mesolimbic reward system while having to reject immediate reward in favor of the long-term goal. Further, functional interaction between the anteroventral prefrontal cortex and the vStr in the 'DRD' was significantly impaired in the bipolar group. These findings provide evidence for a reduced responsivity of the vStr to reward stimuli in BD, possibly related to clinical features like anhedonia. The disturbed top-down control of mesolimbic reward signals by prefrontal brain regions in BD can be interpreted in terms of a disease-related enhanced impulsivity, a trait marker of BD.

CognitiveConstruct

RewardProcessing

10.1007/s00213-014-3466-9

Psychopharmacology

Psychopharmacology (Berl)

Ghrelin receptor antagonism of morphine-induced accumbens dopamine release and behavioral stimulation in rats.

Ghrelin, an orexigenic (appetite stimulating) peptide activates binding sites in the ventral tegmental area (a structure linked with the neural reward system) allowing it to participate in reward-seeking behavior. 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. The aim of the present study was to ascertain whether a ghrelin antagonist (JMV2959) was able to inhibit markers of morphine-induced activation of the neural reward system, namely morphine-induced increase of dopamine in the nucleus accumbens and behavioral changes in rats. We used in vivo microdialysis to determine changes of dopamine and its metabolites in the nucleus accumbens shell in rats following morphine (MO, 5, 10 mg/kg s.c.) administration with and without ghrelin antagonist pretreatment (JMV2959, 3, 6 mg/kg i.p., 20 min before MO). Induced behavioral changes were simultaneously monitored. JMV2959 significantly and dose dependently reduced MO-induced dopamine release in the nucleus accumbens shell and affected concentration of by-products associated with dopamine metabolism: 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA). JMV2959 pretreatment also significantly reduced MO-induced behavioral stimulation, especially stereotyped behavior. Ghrelin secretagogue receptors (GHS-R1A) appear to be involved in the opioid-induced changes in the mesolimbic dopaminergic system associated with the reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2014.01.021

Neuropsychologia

Neuropsychologia

Differential representation of feedback and decision in adolescents and adults.

It is widely accepted that brain maturation from adolescence to adulthood contributes to substantial behavioural changes. Despite this, however, knowledge of the precise mechanisms is still sparse. We used fMRI to investigate developmental differences between healthy adolescents (age range 14-15) and adults (age range 20-39) in feedback-related decision making using a probabilistic reversal learning task. Conventionally groups are compared based on continuous values of blood oxygen level dependent (BOLD) percentage signal change. In contrast, we transformed these values into discrete states and used the pattern of these states to compare groups. We focused our analysis on anterior cingulate cortex (ACC), ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC) as their functions have been shown to be critical in feedback related decision making. Discretisation of continuous BOLD values revealed differential patterns of activity as compared to conventional statistical methods. Results showed differential representation of feedback and decision in ACC and vmPFC between adolescents and adults but no difference in VS. We argue that the pattern of activity of ACC, vmPFC and VS in adolescents resulted in several drawbacks in decision making such as redundant and imprecise representation of decision and subsequently poorer performance in terms of the number of system changes (change of contingencies). This method can be effectively used to infer group differences from within-group analysis rather than studying the differences by direct between-group comparisons.

CognitiveConstruct

RewardProcessing

10.1016/j.bandc.2013.10.005

Brain and cognition

Brain Cogn

A cross-sectional and longitudinal analysis of reward-related brain activation: effects of age, pubertal stage, and reward sensitivity.

Neurobiological models suggest that adolescents are driven by an overactive ventral striatum (VS) response to rewards that may lead to an adolescent increase in risk-taking behavior. However, empirical studies showed mixed findings of adolescents' brain response to rewards. In this study, we aimed to elucidate the relationship between reward-related brain activation and risky decision-making. In addition, we examined effects of age, puberty, and individuals' reward sensitivity. We collected two datasets: Experiment 1 reports cross-sectional brain data from 75 participants (ages 10-25) who played a risky decision task. Experiment 2 presents a longitudinal extension in which a subset of these adolescents (n=33) was measured again 2years later. Results showed that (1) a reward-related network including VS and medial PFC was consistently activated over time, (2) the propensity to choose the risky option was related to increased reward-related activation in VS and medial PFC, and (3) longitudinal comparisons indicated that self-reported reward sensitivity was specifically related to VS activation over time. Together, these results advance our insights in the brain circuitry underlying reward processing across adolescence.

CognitiveConstruct

RewardProcessing

10.1016/j.bandc.2014.01.007

Brain and cognition

Brain Cogn

Pubertal status associations with reward and threat sensitivities and subcortical brain volumes during adolescence.

Adolescence is characterized by complex developmental processes that impact behavior, biology, and social functioning. Two such adolescence-specific processes are puberty and increases in reward sensitivity. Relations between these processes are poorly understood. The present study focused on examining unique effects of puberty, age, and sex on reward and threat sensitivities and volumes of subcortical brain structures relevant for reward/threat processing in a healthy sample of 9-18year-olds. Unlike age, pubertal status had a significant unique positive relationship with reward sensitivity. In addition, there was a trend for adolescent females to exhibit higher threat sensitivity with more advanced pubertal development and higher reward and threat sensitivity with older age. Similarly, there were significant puberty by sex interaction effects on striatal volumes, i.e., left nucleus accumbens and right pallidum. The present pattern of results suggests that pubertal development, independent of chronological age, is uniquely associated with reward hypersensitivity and with structural differences in striatal regions implicated in reward processing.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22474

Human brain mapping

Hum Brain Mapp

Neural correlates of substance abuse: reduced functional connectivity between areas underlying reward and cognitive control.

Substance use disorders (SUD) have been associated with dysfunction in reward processing, habit formation, and cognitive-behavioral control. Accordingly, neurocircuitry models of addiction highlight roles for nucleus accumbens, dorsal striatum, and prefrontal/anterior cingulate cortex. However, the precise nature of the disrupted interactions between these brain regions in SUD, and the psychological correlates thereof, remain unclear. Here we used magnetic resonance imaging to measure rest-state functional connectivity of three key striatal nuclei (nucleus accumbens, dorsal caudate, and dorsal putamen) in a sample of 40 adult male prison inmates (n = 22 diagnosed with SUD; n = 18 without SUD). Relative to the non-SUD group, the SUD group exhibited significantly lower functional connectivity between the nucleus accumbens and a network of frontal cortical regions involved in cognitive control (dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and frontal operculum). There were no group differences in functional connectivity for the dorsal caudate or dorsal putamen. Moreover, the SUD group exhibited impairments in laboratory measures of cognitive-behavioral control, and individual differences in functional connectivity between nucleus accumbens and the frontal cortical regions were related to individual differences in measures of cognitive-behavioral control across groups. The strength of the relationship between functional connectivity and cognitive control did not differ between groups. These results indicate that SUD is associated with abnormal interactions between subcortical areas that process reward (nucleus accumbens) and cortical areas that govern cognitive-behavioral control.

CognitiveConstruct

RewardProcessing

10.1016/j.brainres.2014.02.003

Brain research

Brain Res

Serotonergic modulation of reward and punishment: evidence from pharmacological fMRI studies.

Until recently, the bulk of research on the human reward system was focused on studying the dopaminergic and opioid neurotransmitter systems. However, extending the initial data from animal studies on reward, recent pharmacological brain imaging studies on human participants bring a new line of evidence on the key role serotonin plays in reward processing. The reviewed research has revealed how central serotonin availability and receptor specific transmission modulates the neural response to both appetitive (rewarding) and aversive (punishing) stimuli in putative reward-related brain regions. Thus, serotonin is suggested to be involved in behavioral control when there is a prospect of reward or punishment. The new findings may have implications in understanding psychiatric disorders such as major depression which is characterized by abnormal serotonergic function and reward-related processing and may also provide a neural correlated for the emotional blunting observed in the clinical treatment of psychiatric disorders with selective serotonin reuptake inhibitors. Given the unique profile of action of each serotonergic receptor subtype, future pharmacological studies may favor receptor specific investigations to complement present research mainly focused on global serotonergic manipulations.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroscience.2014.01.058

Neuroscience

Neuroscience

Differential effects of acute stress on anticipatory and consummatory phases of reward processing.

Anhedonia is one of the core symptoms of depression and has been linked to blunted responses to rewarding stimuli in striatal regions. Stress, a key vulnerability factor for depression, has been shown to induce anhedonic behavior, including reduced reward responsiveness in both animals and humans, but the brain processes associated with these effects remain largely unknown in humans. Emerging evidence suggests that stress has dissociable effects on distinct components of reward processing, as it has been found to potentiate motivation/'wanting' during the anticipatory phase but reduce reward responsiveness/'liking' during the consummatory phase. To examine the impact of stress on reward processing, we used a monetary incentive delay (MID) task and an acute stress manipulation (negative performance feedback) in conjunction with functional magnetic resonance imaging (fMRI). Fifteen healthy participants performed the MID task under no-stress and stress conditions. We hypothesized that stress would have dissociable effects on the anticipatory and consummatory phases in reward-related brain regions. Specifically, we expected reduced striatal responsiveness during reward consumption (mirroring patterns previously observed in clinical depression) and increased striatal activation during reward anticipation consistent with non-human findings. Supporting our hypotheses, significant Phase (Anticipation/Consumption)×Stress (Stress/No-stress) interactions emerged in the putamen, nucleus accumbens, caudate and amygdala. Post hoc tests revealed that stress increased striatal and amygdalar activation during anticipation but decreased striatal activation during consumption. Importantly, stress-induced striatal blunting was similar to the profile observed in clinical depression under baseline (no-stress) conditions in prior studies. Given that stress is a pivotal vulnerability factor for depression, these results offer insight to better understand the etiology of this prevalent disorder.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0088188

PloS one

PLoS One

Relationships between reward sensitivity, risk-taking and family history of alcoholism during an interactive competitive fMRI task.

Individuals with a positive family history for alcoholism (FHP) have shown differences from family-history-negative (FHN) individuals in the neural correlates of reward processing. FHP, compared to FHN individuals, demonstrate relatively diminished ventral striatal activation during anticipation of monetary rewards, and the degree of ventral striatal activation shows an inverse correlation with specific impulsivity measures in alcohol-dependent individuals. Rewards in socially interactive contexts relate importantly to addictive propensities, yet have not been examined with respect to how their neural underpinnings relate to impulsivity-related measures. Here we describe impulsivity measures in FHN and FHP individuals as they relate to a socially interactive functional magnetic resonance imaging (fMRI) task. Forty FHP and 29 FHN subjects without histories of Axis-I disorders completed a socially interactive Domino task during functional magnetic resonance imaging and completed self-report and behavioral impulsivity-related assessments. FHP compared to FHN individuals showed higher scores (p = .004) on one impulsivity-related factor relating to both compulsivity (Padua Inventory) and reward/punishment sensitivity (Sensitivity to Punishment/Sensitivity to Reward Questionnaire). Multiple regression analysis within a reward-related network revealed a correlation between risk-taking (involving another impulsivity-related factor, the Balloon Analog Risk Task (BART)) and right ventral striatum activation under reward >punishment contrast (p<0.05 FWE corrected) in the social task. Behavioral risk-taking scores may be more closely associated with neural correlates of reward responsiveness in socially interactive contexts than are FH status or impulsivity-related self-report measures. These findings suggest that risk-taking assessments be examined further in socially interactive settings relevant to addictive behaviors.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsu001

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Future planning: default network activity couples with frontoparietal control network and reward-processing regions during process and outcome simulations.

We spend much of our daily lives imagining how we can reach future goals and what will happen when we attain them. Despite the prevalence of such goal-directed simulations, neuroimaging studies on planning have mainly focused on executive processes in the frontal lobe. This experiment examined the neural basis of process simulations, during which participants imagined themselves going through steps toward attaining a goal, and outcome simulations, during which participants imagined events they associated with achieving a goal. In the scanner, participants engaged in these simulation tasks and an odd/even control task. We hypothesized that process simulations would recruit default and frontoparietal control network regions, and that outcome simulations, which allow us to anticipate the affective consequences of achieving goals, would recruit default and reward-processing regions. Our analysis of brain activity that covaried with process and outcome simulations confirmed these hypotheses. A functional connectivity analysis with posterior cingulate, dorsolateral prefrontal cortex and anterior inferior parietal lobule seeds showed that their activity was correlated during process simulations and associated with a distributed network of default and frontoparietal control network regions. During outcome simulations, medial prefrontal cortex and amygdala seeds covaried together and formed a functional network with default and reward-processing regions.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0085978

PloS one

PLoS One

Humor as a reward mechanism: event-related potentials in the healthy and diseased brain.

Humor processing involves distinct processing stages including incongruity detection, emotional response, and engagement of mesolimbic reward regions. Dysfunctional reward processing and clinical symptoms in response to humor have been previously described in both hypocretin deficient narcolepsy-cataplexy (NC) and in idiopathic Parkinson disease (PD). For NC patients, humor is the strongest trigger for cataplexy, a transient loss of muscle tone, whereas dopamine-deficient PD-patients show blunted emotional responses to humor. To better understand the role of reward system and the various contributions of hypocretinergic and dopaminergic mechanisms to different stages of humor processing we examined the electrophysiological response to humorous and neutral pictures when given as reward feedback in PD, NC and healthy controls. Humor compared to neutral feedback demonstrated modulation of early ERP amplitudes likely corresponding to visual processing stages, with no group differences. At 270 ms post-feedback, conditions showed topographical and amplitudinal differences for frontal and left posterior electrodes, in that humor feedback was absent in PD patients but increased in NC patients. We suggest that this effect relates to a relatively early affective response, reminiscent of increased amygdala response reported in NC patients. Later ERP differences, corresponding to the late positive potential, revealed a lack of sustained activation in PD, likely due to altered dopamine regulation in reward structures in these patients. This research provides new insights into the temporal dynamics and underlying mechanisms of humor detection and appreciation in health and disease.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0087277

PloS one

PLoS One

Relationship between personality traits and brain reward responses when playing on a team.

Cooperation is an integral part of human social life and we often build teams to achieve certain goals. However, very little is currently understood about emotions with regard to cooperation. Here, we investigated the impact of social context (playing alone versus playing on a team) on emotions while winning or losing a game. We hypothesized that activity in the reward network is modulated by the social context and that personality characteristics might impact team play. We conducted an event-related functional magnetic resonance imaging experiment that involved a simple game of dice. In the team condition, the participant played with a partner against another two-person team. In the single-player condition, the participant played alone against another player. Our results revealed that reward processing in the right amygdala was modulated by the social context. The main effect of outcome (gains versus losses) was associated with increased responses in the reward network. We also found that differences in the reward-related neural response due to social context were associated with specific personality traits. When playing on a team, increased activity in the amygdala during winning was a unique function of openness, while decreased activity in the ventromedial prefrontal cortex and ventral striatum during losing was associated with extraversion and conscientiousness, respectively. In conclusion, we provide evidence that working on a team influences the affective value of a negative outcome by attenuating the negative response associated with it in the amygdala. Our results also show that brain reward responses in a social context are affected by personality traits related to teamwork.

CognitiveConstruct

RewardProcessing

10.1007/s00213-013-3393-1

Psychopharmacology

Psychopharmacology (Berl)

Reducing substance use during adolescence: a translational framework for prevention.

Most substance use is initiated during adolescence when substantial development of relevant brain circuitry is still rapidly maturing. Developmental differences in reward processing, behavioral flexibility, and self-regulation lead to changes in resilience or vulnerability to drugs of abuse depending on exposure to risk factors. Intervention and prevention approaches to reducing addiction in teens may be able to capitalize on malleable brain systems in a predictable manner. This review will highlight what is known about how factors that increase vulnerability to addiction, including developmental stage, exposure to early life adversity (ranging from abuse, neglect, and bullying), drug exposure, and genetic predisposition, impact the development of relevant systems. Appropriate, early intervention may restore the normal course of an abnormal trajectory and reduce the likelihood of developing a substance use disorder (SUD) later in life. A considerable amount is known about the functional neuroanatomy and/or pharmacology of risky behaviors based on clinical and preclinical studies, but relatively little has been directly translated to reduce their impact on addiction in high-risk children or teenagers. An opportunity exists to effectively intervene before adolescence when substance use is likely to emerge.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2013.12.007

NeuroImage. Clinical

Neuroimage Clin

Ventral striatum gray matter density reduction in patients with schizophrenia and psychotic emotional dysregulation.

Substantial heterogeneity remains across studies investigating changes in gray matter in schizophrenia. Differences in methodology, heterogeneous symptom patterns and symptom trajectories may contribute to inconsistent findings. To address this problem, we recently proposed to group patients by symptom dimensions, which map on the language, the limbic and the motor systems. The aim of the present study was to investigate whether patients with prevalent symptoms of emotional dysregulation would show structural neuronal abnormalities in the limbic system. 43 right-handed medicated patients with schizophrenia were assessed with the Bern Psychopathology Scale (BPS). The patients and a control group of 34 healthy individuals underwent structural imaging at a 3T MRI scanner. Whole brain voxel-based morphometry (VBM) was compared between patient subgroups with different severity of emotional dysregulation. Group comparisons (comparison between patients with severe emotional dysregulation, patients with mild emotional dysregulation, patients with no emotional dysregulation and healthy controls) were performed using a one way ANOVA and ANCOVA respectively. Patients with severe emotional dysregulation had significantly decreased gray matter density in a large cluster including the right ventral striatum and the head of the caudate compared to patients without emotional dysregulation. Comparing patients with severe emotional dysregulation and healthy controls, several clusters of significant decreased GM density were detected in patients, including the right ventral striatum, head of the caudate, left hippocampus, bilateral thalamus, dorsolateral prefrontal and orbitofrontal cortex. The significant effect in the ventral striatum was lost when patients with and without emotional dysregulation were pooled and compared with controls. Decreased gray matter density in a large cluster including the right ventral striatum was associated with severe symptoms of emotional dysregulation in patients with schizophrenia. The ventral striatum is an important part of the limbic system, and was indicated to be involved in the generation of incentive salience and psychotic symptoms. Only patients with severe emotional dysregulation had decreased gray matter in several brain structures associated with emotion and reward processing compared to healthy controls. The results support the hypothesis that grouping patients according to specific clinical symptoms matched to the limbic system allows identifying patient subgroups with structural abnormalities in the limbic network.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2013.11.009

NeuroImage. Clinical

Neuroimage Clin

Functional brain imaging studies of youth depression: a systematic review.

There is growing interest in understanding the neurobiology of major depressive disorder (MDD) in youth, particularly in the context of neuroimaging studies. This systematic review provides a timely comprehensive account of the available functional magnetic resonance imaging (fMRI) literature in youth MDD. A literature search was conducted using PubMED, PsycINFO and Science Direct databases, to identify fMRI studies in younger and older youth with MDD, spanning 13-18 and 19-25 years of age, respectively. Twenty-eight studies focusing on 5 functional imaging domains were identified, namely emotion processing, cognitive control, affective cognition, reward processing and resting-state functional connectivity. Elevated activity in "extended medial network" regions including the anterior cingulate, ventromedial and orbitofrontal cortices, as well as the amygdala was most consistently implicated across these five domains. For the most part, findings in younger adolescents did not differ from those in older youth; however a general comparison of findings in both groups compared to adults indicated differences in the domains of cognitive control and affective cognition. Youth MDD is characterized by abnormal activations in ventromedial frontal regions, the anterior cingulate and amygdala, which are broadly consistent with the implicated role of medial network regions in the pathophysiology of depression. Future longitudinal studies examining the effects of neurodevelopmental changes and pubertal maturation on brain systems implicated in youth MDD will provide a more comprehensive neurobiological model of youth depression.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2013.00173

Frontiers in psychiatry

Front Psychiatry

Mindfulness training targets neurocognitive mechanisms of addiction at the attention-appraisal-emotion interface.

Prominent neuroscience models suggest that addictive behavior occurs when environmental stressors and drug-relevant cues activate a cycle of cognitive, affective, and psychophysiological mechanisms, including dysregulated interactions between bottom-up and top-down neural processes, that compel the user to seek out and use drugs. Mindfulness-based interventions (MBIs) target pathogenic mechanisms of the risk chain linking stress and addiction. This review describes how MBIs may target neurocognitive mechanisms of addiction at the attention-appraisal-emotion interface. Empirical evidence is presented suggesting that MBIs ameliorate addiction by enhancing cognitive regulation of a number of key processes, including: clarifying cognitive appraisal and modulating negative emotions to reduce perseverative cognition and emotional arousal; enhancing metacognitive awareness to regulate drug-use action schema and decrease addiction attentional bias; promoting extinction learning to uncouple drug-use triggers from conditioned appetitive responses; reducing cue-reactivity and increasing cognitive control over craving; attenuating physiological stress reactivity through parasympathetic activation; and increasing savoring to restore natural reward processing. Treatment and research implications of our neurocognitive framework are presented. We conclude by offering a temporally sequenced description of neurocognitive processes targeted by MBIs through a hypothetical case study. Our neurocognitive framework has implications for the optimization of addiction treatment with MBIs.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.4389-13.2014

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

J Neurosci

Reward-related activity in ventral striatum is action contingent and modulated by behavioral relevance.

Multiple features of the environment are often imbued with motivational significance, and the relative importance of these can change across contexts. The ability to flexibly adjust evaluative processes so that currently important features of the environment alone drive behavior is critical to adaptive routines. We know relatively little about the neural mechanisms involved, including whether motivationally significant features are obligatorily evaluated or whether current relevance gates access to value-sensitive regions. We addressed these questions using functional magnetic resonance imaging data and a task design where human subjects had to choose whether to accept or reject an offer indicated by visual and auditory stimuli. By manipulating, on a trial-by-trial basis, which stimulus determined the value of the offer, we show choice activity in the ventral striatum solely reflects the value of the currently relevant stimulus, consistent with a model wherein behavioral relevance modulates the impact of sensory stimuli on value processing. Choice outcome signals in this same region covaried positively with wins on accept trials, and negatively with wins on reject trials, consistent with striatal activity at feedback reflecting correctness of response rather than reward processing per se. We conclude that ventral striatum activity during decision making is dynamically modulated by behavioral context, indexed here by task relevance and action selection.

CognitiveConstruct

RewardProcessing

10.1111/add.12494

Addiction (Abingdon, England)

Addiction

Strategic and non-strategic problem gamblers differ on decision-making under risk and ambiguity.

To analyse problem gamblers' decision-making under conditions of risk and ambiguity, investigate underlying psychological factors associated with their choice behaviour and examine whether decision-making differed in strategic (e.g., sports betting) and non-strategic (e.g., electronic gaming machine) problem gamblers. Cross-sectional study. Out-patient treatment centres and university testing facilities in Victoria, Australia. Thirty-nine problem gamblers and 41 age, gender and estimated IQ-matched controls. Decision-making tasks included the Iowa Gambling Task (IGT) and a loss aversion task. The Prospect Valence Learning (PVL) model was used to provide an explanation of cognitive, motivational and response style factors involved in IGT performance. Overall, problem gamblers performed more poorly than controls on both the IGT (P = 0.04) and the loss aversion task (P = 0.01), and their IGT decisions were associated with heightened attention to gains (P = 0.003) and less consistency (P = 0.002). Strategic problem gamblers did not differ from matched controls on either decision-making task, but non-strategic problem gamblers performed worse on both the IGT (P = 0.006) and the loss aversion task (P = 0.02). Furthermore, we found differences in the PVL model parameters underlying strategic and non-strategic problem gamblers' choices on the IGT. Problem gamblers demonstrated poor decision-making under conditions of risk and ambiguity. Strategic (e.g. sports betting, poker) and non-strategic (e.g. electronic gaming machines) problem gamblers differed in decision-making and the underlying psychological processes associated with their decisions.

CognitiveConstruct

RewardProcessing

10.1073/pnas.1317090111

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

Proc Natl Acad Sci U S A

Functional changes of the reward system underlie blunted response to social gaze in cocaine users.

Social interaction deficits in drug users likely impede treatment, increase the burden of the affected families, and consequently contribute to the high costs for society associated with addiction. Despite its significance, the neural basis of altered social interaction in drug users is currently unknown. Therefore, we investigated basal social gaze behavior in cocaine users by applying behavioral, psychophysiological, and functional brain-imaging methods. In study I, 80 regular cocaine users and 63 healthy controls completed an interactive paradigm in which the participants' gaze was recorded by an eye-tracking device that controlled the gaze of an anthropomorphic virtual character. Valence ratings of different eye-contact conditions revealed that cocaine users show diminished emotional engagement in social interaction, which was also supported by reduced pupil responses. Study II investigated the neural underpinnings of changes in social reward processing observed in study I. Sixteen cocaine users and 16 controls completed a similar interaction paradigm as used in study I while undergoing functional magnetic resonance imaging. In response to social interaction, cocaine users displayed decreased activation of the medial orbitofrontal cortex, a key region of reward processing. Moreover, blunted activation of the medial orbitofrontal cortex was significantly correlated with a decreased social network size, reflecting problems in real-life social behavior because of reduced social reward. In conclusion, basic social interaction deficits in cocaine users as observed here may arise from altered social reward processing. Consequently, these results point to the importance of reinstatement of social reward in the treatment of stimulant addiction.

CognitiveConstruct

RewardProcessing

10.1098/rstb.2012.0468

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

Philos Trans R Soc Lond B Biol Sci

Timing in reward and decision processes.

Sensitivity to time, including the time of reward, guides the behaviour of all organisms. Recent research suggests that all major reward structures of the brain process the time of reward occurrence, including midbrain dopamine neurons, striatum, frontal cortex and amygdala. Neuronal reward responses in dopamine neurons, striatum and frontal cortex show temporal discounting of reward value. The prediction error signal of dopamine neurons includes the predicted time of rewards. Neurons in the striatum, frontal cortex and amygdala show responses to reward delivery and activities anticipating rewards that are sensitive to the predicted time of reward and the instantaneous reward probability. Together these data suggest that internal timing processes have several well characterized effects on neuronal reward processing.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22442

Human brain mapping

Hum Brain Mapp

Attenuated serotonin transporter association between dorsal raphe and ventral striatum in major depression.

Suffering from anhedonia, patients with major depressive disorder (MDD) exhibit alterations in several parts of the serotonergic neurotransmitter system, which are in turn involved in reward processing. However, previous investigations of the serotonin transporter (SERT) focused on regional differences with varying results depending on the clinical syndrome. Here, we aimed to describe the serotonergic system of MDD patients on a network level by evaluating SERT associations across brain regions. Twenty medication free patients with major depression and 20 healthy controls underwent positron emission tomography using the radioligand [(11) C]DASB. SERT binding potentials (BPND ) were quantified voxel-wise with the multilinear reference tissue model 2. In addition, SERT BPND was extracted from the dorsal raphe nucleus (DRN) as an indicator of midbrain serotonergic neurotransmission. Whole-brain linear regression analysis was applied to evaluate the association of DRN SERT bindings to those in projection areas, which was followed by ANCOVA to assess differences in interregional relationships between patients and controls. Although both groups showed widespread positive correlations, group differences were restricted to decreased SERT associations between the DRN and the ventral striatum (right and left respectively: t=5.85, P<0.05 corrected and t=5.07, P<0.1 corrected) when comparing MDD patients (R(2)=0.11 and 0.24) to healthy subjects (R(2)=0.72 and 0.66, P<0.01 and 0.05 corrected). Adjusting for age and sex did not change these findings. This study indicates a disturbed regulation between key regions involved in reward processing via the SERT. Our interregional approach highlights the importance of evaluating pathophysiological alterations on a network level to gain complementary information in addition to regional investigations.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2013.12.004

Psychiatry research

Psychiatry Res

Resting state functional connectivity of the nucleus accumbens in youth with a family history of alcoholism.

Adolescents with a family history of alcoholism (FHP) are at heightened risk for developing alcohol use disorders (AUDs). The nucleus accumbens (NAcc), a key brain region for reward processing, is implicated in the development of AUDs. Thus, functional connectivity of the NAcc may be an important marker of risk in FHP youth. Resting state functional magnetic resonance imaging (rs-fcMRI) was used to examine the intrinsic connectivity of the NAcc in 47 FHP and 50 family history negative (FHN) youth, ages 10-16 years old. FHP and FHN adolescents showed significant group differences in resting state synchrony between the left NAcc and bilateral inferior frontal gyri and the left postcentral gyrus (PG). Additionally, FHP youth differed from FHN youth in right NAcc functional connectivity with the left orbitofrontal cortex (OFC), left superior temporal gyrus, right cerebellum, left PG, and right occipital cortex. These results indicate that FHP youth have less segregation between the NAcc and executive functioning brain regions, and less integration with reward-related brain areas, such as the OFC. The findings of the current study highlight that premorbid atypical connectivity of appetitive systems, in the absence of heavy alcohol use, may be a risk marker in FHP adolescents.

CognitiveConstruct

RewardProcessing

10.1002/wcs.1266

Wiley interdisciplinary reviews. Cognitive science

Wiley Interdiscip Rev Cogn Sci

The social brain and reward: social information processing in the human striatum.

In the highly social life of humans, rewards that are sought and experienced are intertwined with social relationships and interactions between people. Just as we value nonsocial rewards such as food or money, we also value social outcomes (e.g., praise from a superior). We use social information to evaluate and form expectations of others and to make decisions involving others. Here we review research demonstrating how the neural circuitry of reward, particularly the striatum, is also involved in processing social information and making decisions in social situations. This research provides an understanding of the neural basis for social behavior from the perspective of how we evaluate social experiences and how our social interactions and decisions are motivated. We review research addressing the common neural systems underlying evaluation of social and nonsocial rewards. The human striatum, known to play a key role in reward processing, displays signals related to a broad spectrum of social functioning, including evaluating social rewards, making decisions influenced by social factors, learning about social others, cooperating, competing, and following social norms. WIREs Cogn Sci 2014, 5:61-73. doi: 10.1002/wcs.1266 Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website.

CognitiveConstruct

RewardProcessing

10.1210/en.2013-1831

Endocrinology

Endocrinology

The temporal pattern of cfos activation in hypothalamic, cortical, and brainstem nuclei in response to fasting and refeeding in male mice.

In this study we examined fasted and refed cfos activation in cortical, brainstem, and hypothalamic brain regions associated with appetite regulation. We examined a number of time points during refeeding to gain insight into the temporal pattern of neuronal activation and changes in endocrine parameters associated with fasting and refeeding. In response to refeeding, blood glucose and plasma insulin returned to basal levels within 30 minutes, whereas plasma nonesterified fatty acids and leptin returned to basal levels after 1 and 2 hours, respectively. Within the hypothalamic arcuate nucleus (ARC), fasting increased cfos activation in ∼25% of neuropeptide Y neurons, which was terminated 1 hour after refeeding. Fasting had no effect on cfos activation in pro-opiomelanocortin neurons; however, 1 and 2 hours of refeeding significantly activated ∼20% of ARC pro-opiomelanocortin neurons. Acute refeeding (30, 60, and 120 minutes), but not fasting, increased cfos activation in the nucleus accumbens, the cingulate cortex (but not the insular cortex), the medial and lateral parabrachial nucleus, the nucleus of the solitary tract, the area postrema, the dorsal raphe, and the ventromedial nucleus of the hypothalamus. After 6 hours of refeeding, cfos activity was reduced in the majority of these regions compared with that at earlier time points. Our data indicate that acute refeeding, rather than long-term fasting, activates cortical, brainstem, and hypothalamic neural circuits associated with appetite regulation and reward processing. Although the hypothalamic ARC remains a critical sensory node detecting changes in the metabolic state and feedback during fasting and acute refeeding, our results also reveal the temporal pattern in cfos activation in cortical and brainstem areas implicated in the control of appetite and body weight regulation.

CognitiveConstruct

RewardProcessing

10.1080/13554794.2013.873063

Neurocase

Neurocase

Reward processing in neurodegenerative disease.

Representation of reward value involves a distributed network including cortical and subcortical structures. Because neurodegenerative illnesses target specific anatomic networks that partially overlap with the reward circuit, they would be predicted to have distinct impairments in reward processing. This review presents the existing evidence of reward processing changes in neurodegenerative diseases including mild cognitive impairment (MCI), Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis (ALS), Parkinson's disease, and Huntington's disease, as well as in healthy aging. Carefully distinguishing the different aspects of reward processing (primary rewards, secondary rewards, reward-based learning, and reward-based decision-making) and using tasks that differentiate the stages of processing reward will lead to improved understanding of this fundamental process and clarify a contributing cause of behavioral change in these illnesses.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2013.00259

Frontiers in neuroscience

Front Neurosci

How social cognition can inform social decision making.

Social decision-making is often complex, requiring the decision-maker to make inferences of others' mental states in addition to engaging traditional decision-making processes like valuation and reward processing. A growing body of research in neuroeconomics has examined decision-making involving social and non-social stimuli to explore activity in brain regions such as the striatum and prefrontal cortex, largely ignoring the power of the social context. Perhaps more complex processes may influence decision-making in social vs. non-social contexts. Years of social psychology and social neuroscience research have documented a multitude of processes (e.g., mental state inferences, impression formation, spontaneous trait inferences) that occur upon viewing another person. These processes rely on a network of brain regions including medial prefrontal cortex (MPFC), superior temporal sulcus (STS), temporal parietal junction, and precuneus among others. Undoubtedly, these social cognition processes affect social decision-making since mental state inferences occur spontaneously and automatically. Few studies have looked at how these social inference processes affect decision-making in a social context despite the capability of these inferences to serve as predictions that can guide future decision-making. Here we review and integrate the person perception and decision-making literatures to understand how social cognition can inform the study of social decision-making in a way that is consistent with both literatures. We identify gaps in both literatures-while behavioral economics largely ignores social processes that spontaneously occur upon viewing another person, social psychology has largely failed to talk about the implications of social cognition processes in an economic decision-making context-and examine the benefits of integrating social psychological theory with behavioral economic theory.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2013.12.003

Developmental cognitive neuroscience

Dev Cogn Neurosci

Girls' challenging social experiences in early adolescence predict neural response to rewards and depressive symptoms.

Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC), striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence.

CognitiveConstruct

RewardProcessing

10.1177/0956797613514589

Psychological science

Psychol Sci

The value of exercising control over monetary gains and losses.

Using functional MRI, we examined how the affective experience of choice, the means by which individuals exercise control, is modulated by the valence of potential outcomes (gains, losses). When trials involved potential gains, participants reported liking cues predicting a choice opportunity better than cues predicting no choice opportunity--an effect that corresponded with blood-oxygen-level-dependent (BOLD) increases in ventral striatum (VS) activity. Surprisingly, no differences were observed between choice and no-choice cues when participants anticipated potential losses. Individual differences in subjective choice preference in the loss condition, however, corresponded to choice-related BOLD activity in VS. We conducted a second experiment to examine whether monetary losses were perceived differently in the context of simultaneous gains. When losses occurred in the absence of gains, participants showed an increased affective experience of choice--they reported greater liking of choice than no-choice trials, and VS activity was greater for choice than for no-choice cues. Collectively, the findings suggest that the affective experience of choice involves reward-processing circuitry when people anticipate appetitive and aversive outcomes, but the choice experience may be sensitive to context and individual differences.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0084044

PloS one

PLoS One

Sex differences in the neural processing of aversive interoceptive events: the benefit of relief.

Do men and women process and experience unpleasant bodily states differently? We used fMRI to determine brain processing before, during and after an aversive respiratory stimulation. No sex difference emerged during anticipation or stimulation. However, after the offset of the stimulation, men but not women showed enhanced activation of brain regions that are important for interoception and reward processing. Moreover, this activation was highest in those males who rated the preceding stimulation as most unpleasant. These results indicate that men are particularly sensitive to reward associated with the termination of an aversive event, which may signal relief.

CognitiveConstruct

RewardProcessing

10.1038/npp.2013.351

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Serotonin depletion induces 'waiting impulsivity' on the human four-choice serial reaction time task: cross-species translational significance.

Convergent results from animal and human studies suggest that reducing serotonin neurotransmission promotes impulsive behavior. Here, serotonin depletion was induced by the dietary tryptophan depletion procedure (TD) in healthy volunteers to examine the role of serotonin in impulsive action and impulsive choice. We used a novel translational analog of a rodent 5-choice serial reaction time task (5-CSRTT)-- the human 4-CSRTT--and a reward delay-discounting questionnaire to measure effects on these different forms of 'waiting impulsivity'. There was no effect of TD on impulsive choice as indexed by the reward delay-discounting questionnaire. However, TD significantly increased 4-CSRTT premature responses (or impulsive action), which is remarkably similar to the previous findings of effect of serotonin depletion on rodent 5-CSRTT performance. Moreover, the increased premature responding in TD correlated significantly with individual differences on the motor impulsivity subscale of the Barratt Impulsivity Scale. TD also improved the accuracy of performance and speeded responding, possibly indicating enhanced attention and reward processing. The results suggest: (i) the 4-CSRTT will be a valuable addition to the tests already available to measure impulsivity in humans in a direct translational analog of a test extensively used in rodents; (ii) TD in humans produces a qualitatively similar profile of effects to those in rodents (ie, enhancing premature responding), hence supporting the conclusion that TD in humans exerts at least some of its effects on central serotonin; and (iii) this manipulation of serotonin produces dissociable effects on different measures of impulsivity, suggesting considerable specificity in its modulatory role.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22433

Human brain mapping

Hum Brain Mapp

Cognitive strategies regulate fictive, but not reward prediction error signals in a sequential investment task.

Computational models of reward processing suggest that foregone or fictive outcomes serve as important information sources for learning and augment those generated by experienced rewards (e.g. reward prediction errors). An outstanding question is how these learning signals interact with top-down cognitive influences, such as cognitive reappraisal strategies. Using a sequential investment task and functional magnetic resonance imaging, we show that the reappraisal strategy selectively attenuates the influence of fictive, but not reward prediction error signals on investment behavior; such behavioral effect is accompanied by changes in neural activity and connectivity in the anterior insular cortex, a brain region thought to integrate subjective feelings with high-order cognition. Furthermore, individuals differ in the extent to which their behaviors are driven by fictive errors versus reward prediction errors, and the reappraisal strategy interacts with such individual differences; a finding also accompanied by distinct underlying neural mechanisms. These findings suggest that the variable interaction of cognitive strategies with two important classes of computational learning signals (fictive, reward prediction error) represent one contributing substrate for the variable capacity of individuals to control their behavior based on foregone rewards. These findings also expose important possibilities for understanding the lack of control in addiction based on possibly foregone rewarding outcomes.

CognitiveConstruct

RewardProcessing

10.3389/fncom.2013.00175

Frontiers in computational neuroscience

Front Comput Neurosci

Linking reward processing to behavioral output: motor and motivational integration in the primate subthalamic nucleus.

The expectation and detection of motivationally relevant events is a major determinant of goal-directed behavior and there is a strong interest in the contribution of basal ganglia in the integration of motivational processes into behavioral output. Recent research has focused on the role of the subthalamic nucleus (STN) in the motivational control of action, but it remains to be determined how information about reward is encoded in this nucleus. We recorded the activity of single neurons in the STN of two behaving monkeys to examine whether activity was influenced by the delivery of reward in an instrumental task, a Pavlovian stimulus-reward association, or outside of a task context. We confirmed preliminary findings indicating that STN neurons were sensitive not only to rewards obtained during task performance, but also to the expectation of reward when its delivery was delayed in time. Most of the modulations at the onset of reaching movement were combined with modulations following reward delivery, suggesting the convergence of signals related to the animal's movement and its outcome in the same neurons. Some neurons were also influenced by the visuomotor contingencies of the task, i.e., target location and/or movement direction. In addition, modulations were observed under conditions where reward delivery was not contingent on an instrumental response, even in the absence of a reward predictive cue. Taken as a whole, these results demonstrate a potential contribution of the STN to motivational control of behavior in the non-human primate, although problems in distinguishing neuronal signals related to reward from those related to motor behavior should be considered. Characterizing the specificity of reward processing in the STN remains challenging and could have important implications for understanding the influence of this key component of basal ganglia circuitry on emotional and motivated behaviors under normal and pathological conditions.

CognitiveConstruct

RewardProcessing

10.1016/j.appet.2013.12.017

Appetite

Appetite

Influence of feeding state on neurofunctional differences between individuals who are obese and normal weight: a meta-analysis of neuroimaging studies.

Obesity is a complex disorder associated with serious health risks. Examining differences in brain activity between normal weight and obese populations in response to food cues may help researchers and clinicians understand the underlying causes of overeating and obesity and help prevent them. Multiple neuroimaging studies have investigated weight differences in functional activity to food cues but have found varying results. We performed six meta-analyses of functional neuroimaging studies of weight differences in response to food images and isolated differences in processing between normal weight and obese participants. Within this study, 7 papers and 3 sets of unpublished data on functional activation to food images were analyzed using an Activation Likelihood Estimation meta-analytic approach. These analyses also addressed how feeding state impacts functional activity between weight groups. Feeding state affected weight related differences in neurofunctional activity triggered by visual food cues. In the premeal state, greater activation in the amygdala/hippocampus was found in obese participants compared to normal weight participants and, in the postmeal state, obese individuals had greater activation in the caudate and medial prefrontal cortex (MPFC) as compared to normal weight individuals. Regions of the brain associated with caloric evaluation, arousal, and memory were more active in the obese before eating, while less activity was found in an area linked to interoceptive processing. In the postmeal state, greater activity was found in the obese in areas related to risk vs. reward evaluation and reward processing. These findings may help researchers and clinicians understand and treat obesity related behaviors by identifying the altered functional regions that lead to obesity, providing a guide for future research on which neural regions need to be the target of further investigation.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0083414

PloS one

PLoS One

Relationship between oscillatory neuronal activity during reward processing and trait impulsivity and sensation seeking.

The processing of reward and punishment stimuli in humans appears to involve brain oscillatory activity of several frequencies, probably each with a distinct function. The exact nature of associations of these electrophysiological measures with impulsive or risk-seeking personality traits is not completely clear. Thus, the aim of the present study was to investigate event-related oscillatory activity during reward processing across a wide spectrum of frequencies, and its associations with impulsivity and sensation seeking in healthy subjects. During recording of a 32-channel EEG 22 healthy volunteers were characterized with the Barratt Impulsiveness and the Sensation Seeking Scale and performed a computerized two-choice gambling task comprising different feedback options with positive vs. negative valence (gain or loss) and high or low magnitude (5 vs. 25 points). We observed greater increases of amplitudes of the feedback-related negativity and of activity in the theta, alpha and low-beta frequency range following loss feedback and, in contrast, greater increase of activity in the high-beta frequency range following gain feedback. Significant magnitude effects were observed for theta and delta oscillations, indicating greater amplitudes upon feedback concerning large stakes. The theta amplitude changes during loss were negatively correlated with motor impulsivity scores, whereas alpha and low-beta increase upon loss and high-beta increase upon gain were positively correlated with various dimensions of sensation seeking. The findings suggest that the processing of feedback information involves several distinct processes, which are subserved by oscillations of different frequencies and are associated with different personality traits.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0083029

PloS one

PLoS One

Orexinergic input to dopaminergic neurons of the human ventral tegmental area.

The mesolimbic reward pathway arising from dopaminergic (DA) neurons of the ventral tegmental area (VTA) has been strongly implicated in reward processing and drug abuse. In rodents, behaviors associated with this projection are profoundly influenced by an orexinergic input from the lateral hypothalamus to the VTA. Because the existence and significance of an analogous orexigenic regulatory mechanism acting in the human VTA have been elusive, here we addressed the possibility that orexinergic neurons provide direct input to DA neurons of the human VTA. Dual-label immunohistochemistry was used and orexinergic projections to the VTA and to DA neurons of the neighboring substantia nigra (SN) were analyzed comparatively in adult male humans and rats. Orexin B-immunoreactive (IR) axons apposed to tyrosine hydroxylase (TH)-IR DA and to non-DA neurons were scarce in the VTA and SN of both species. In the VTA, 15.0±2.8% of TH-IR perikarya in humans and 3.2±0.3% in rats received orexin B-IR afferent contacts. On average, 0.24±0.05 and 0.05±0.005 orexinergic appositions per TH-IR perikaryon were detected in humans and rats, respectively. The majority (86-88%) of randomly encountered orexinergic contacts targeted the dendritic compartment of DA neurons. Finally, DA neurons of the SN also received orexinergic innervation in both species. Based on the observation of five times heavier orexinergic input to TH-IR neurons of the human, compared with the rat, VTA, we propose that orexinergic mechanism acting in the VTA may play just as important roles in reward processing and drug abuse in humans, as already established well in rodents.

CognitiveConstruct

RewardProcessing

10.1093/schbul/sbt197

Schizophrenia bulletin

Schizophr Bull

A review of reward processing and motivational impairment in schizophrenia.

This article reviews and synthesizes research on reward processing in schizophrenia, which has begun to provide important insights into the cognitive and neural mechanisms associated with motivational impairments. Aberrant cortical-striatal interactions may be involved with multiple reward processing abnormalities, including: (1) dopamine-mediated basal ganglia systems that support reinforcement learning and the ability to predict cues that lead to rewarding outcomes; (2) orbitofrontal cortex-driven deficits in generating, updating, and maintaining value representations; (3) aberrant effort-value computations, which may be mediated by disrupted anterior cingulate cortex and midbrain dopamine functioning; and (4) altered activation of the prefrontal cortex, which is important for generating exploratory behaviors in environments where reward outcomes are uncertain. It will be important for psychosocial interventions targeting negative symptoms to account for abnormalities in each of these reward processes, which may also have important interactions; suggestions for novel behavioral intervention strategies that make use of external cues, reinforcers, and mobile technology are discussed.

CognitiveConstruct

RewardProcessing

10.1007/s10567-013-0159-6

Clinical child and family psychology review

Clin Child Fam Psychol Rev

Antisocial behavior, psychopathic features and abnormalities in reward and punishment processing in youth.

A better understanding of what leads youth to initially engage in antisocial behavior (ASB) and more importantly persist with such behaviors into adulthood has significant implications for prevention and intervention efforts. A considerable number of studies using behavioral and neuroimaging techniques have investigated abnormalities in reward and punishment processing as potential causal mechanisms underlying ASB. However, this literature has yet to be critically evaluated, and there are no comprehensive reviews that systematically examine and synthesize these findings. The goal of the present review is twofold. The first aim is to examine the extent to which youth with ASB are characterized by abnormalities in (1) reward processing; (2) punishment processing; or (3) both reward and punishment processing. The second aim is to evaluate whether aberrant reward and/or punishment processing is specific to or most pronounced in a subgroup of antisocial youth with psychopathic features. Studies utilizing behavioral methods are first reviewed, followed by studies using functional magnetic resonance imaging. An integration of theory and research across multiple levels of analysis is presented in order to provide a more comprehensive understanding of reward and punishment processing in antisocial youth. Findings are discussed in terms of developmental and contextual considerations, proposed future directions and implications for intervention.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2013.00814

Frontiers in human neuroscience

Front Hum Neurosci

Age related changes in striatal resting state functional connectivity in autism.

Characterizing the nature of developmental change is critical to understanding the mechanisms that are impaired in complex neurodevelopment disorders such as autism spectrum disorder (ASD) and, pragmatically, may allow us to pinpoint periods of plasticity when interventions are particularly useful. Although aberrant brain development has long been theorized as a characteristic feature of ASD, the neural substrates have been difficult to characterize, in part due to a lack of developmental data and to performance confounds. To address these issues, we examined the development of intrinsic functional connectivity, with resting state fMRI from late childhood to early adulthood (8-36 years), using a seed based functional connectivity method with the striatal regions. Overall, we found that both groups show decreases in cortico-striatal circuits over age. However, when controlling for age, ASD participants showed increased connectivity with parietal cortex and decreased connectivity with prefrontal cortex relative to typically developed (TD) participants. In addition, ASD participants showed aberrant age-related connectivity with anterior aspects of cerebellum, and posterior temporal regions (e.g., fusiform gyrus, inferior and superior temporal gyri). In sum, we found prominent differences in the development of striatal connectivity in ASD, most notably, atypical development of connectivity in striatal networks that may underlie cognitive and social reward processing. Our findings highlight the need to identify the biological mechanisms of perturbations in brain reorganization over development, which may also help clarify discrepant findings in the literature.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2013.11.013

Biological psychiatry

Biol Psychiatry

Dissociated effects of anticipating smoking versus monetary reward in the caudate as a function of smoking abstinence.

Theories of addiction suggest that chronic smoking may be associated with both hypersensitivity to smoking and related cues and hyposensitivity to alternative reinforcers. However, neural responses to smoking and nonsmoking rewards are rarely evaluated within the same paradigm, leaving the extent to which both processes operate simultaneously uncertain. Behavioral evidence and theoretical models suggest that dysregulated reward processing may be more pronounced during deprivation from nicotine, but neuroimaging evidence on the effects of deprivation on reward processing is limited. The current study examined the impact of deprivation from smoking on neural processing of both smoking and monetary rewards. Two separate functional magnetic resonance imaging scans were performed in 38 daily smokers, one after smoking without restriction and one following 24 hours of abstinence. A rewarded guessing task was conducted during each scan to evaluate striatal blood oxygen level-dependent response during anticipation of both smoking and monetary rewards. A significant reward type by abstinence interaction was observed in the bilateral caudate and medial prefrontal cortex during reward anticipation. The blood oxygen level-dependent response to anticipation of smoking reward was significantly higher and anticipation of monetary rewards was significantly lower during abstinence compared with nonabstinence. Attenuation of monetary reward-related activation during abstinence was significantly correlated with abstinence-induced increases in craving and withdrawal. These results provide the first direct evidence of dissociated effects of smoking versus monetary rewards as a function of abstinence. The findings suggest an important neural pathway that may underlie the choice to smoke in lieu of alternative reinforcement during a quit attempt.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2013.12.012

Behavioural brain research

Behav Brain Res

Chronic wheel running affects cocaine-induced c-Fos expression in brain reward areas in rats.

Emerging evidence from human and animal studies suggests that exercise is a highly effective treatment for drug addiction. However, most work has been done in behavioral models, and the effects of exercise on the neurobiological substrates of addiction have not been identified. Specifically, it is unknown whether prior exercise exposure alters neuronal activation of brain reward circuitry in response to drugs of abuse. To investigate this hypothesis, rats were given 21 days of daily access to voluntary wheel running in a locked or unlocked running wheel. Subsequently, they were challenged with a saline or cocaine (15 mg/kg, i.p.) injection and sacrificed for c-Fos immunohistochemistry. The c-Fos transcription factor is a measure of cellular activity and was used to quantify cocaine-induced activation of reward-processing areas of the brain: nucleus accumbens (NAc), caudate putamen (CPu), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). The mean fold change in cocaine-induced c-Fos cell counts relative to saline-induced c-Fos cell counts was significantly higher in exercising compared to control rats in the NAc core, dorsomedial and dorsolateral CPu, the prelimbic area, and the OFC, indicating differential cocaine-specific cellular activation of brain reward circuitry between exercising and control animals. These results suggest neurobiological mechanisms by which voluntary wheel running attenuates cocaine-motivated behaviors and provide support for exercise as a novel treatment for drug addiction.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0082534

PloS one

PLoS One

The neural circuitry of reward processing in complex social comparison: evidence from an event-related FMRI study.

In this study, Functional magnetic resonance imaging (fMRI) was conducted to investigate the mechanisms by which the brain activity in a complex social comparison context. One true subject and two pseudo-subjects were asked to complete a simple number estimate task at the same time which including upward and downward comparisons. Two categories of social comparison rewards (fair and unfair rewards distributions) were mainly presented by comparing the true subject with other two pseudo-subjects. Particularly, there were five conditions of unfair distribution when all the three subjects were correct but received different rewards. Behavioral data indicated that the ability to self-regulate was important in satisfaction judgment when the subject perceived an unfair reward distribution. fMRI data indicated that the interaction between the ventral striatum and the prefrontal cortex was important in self-regulation under specific conditions in complex social comparison, especially under condition of reward processing when there were two different reward values and the subject failed to exhibit upward comparison.

CognitiveConstruct

RewardProcessing

10.1111/add.12403

Addiction (Abingdon, England)

Addiction

Striatum and insula dysfunction during reinforcement learning differentiates abstinent and relapsed methamphetamine-dependent individuals.

Individuals with methamphetamine dependence (MD) exhibit dysfunction in brain regions involved in goal maintenance and reward processing when compared with healthy individuals. We examined whether these characteristics also reflect relapse vulnerability within a sample of MD patients. Longitudinal, with functional magnetic resonance imaging (fMRI) and clinical interview data collected at baseline and relapse status collected at 1-year follow-up interview. Keck Imaging Center, University of California San Diego, USA. MD patients (n = 60) enrolled into an in-patient drug treatment program at baseline. MD participants remaining abstinent at 1-year follow-up (abstinent MD group; n = 42) were compared with MD participants who relapsed within this period (relapsed MD group; n = 18). Behavioral and neural responses to a reinforcement learning (paper-scissors-rock) paradigm recorded during an fMRI session at time of treatment. The relapsed MD group exhibited greater bilateral inferior frontal gyrus (IFG) and right striatal activation than the abstinent MD group during the learning of reward contingencies (Cohen's d range: 0.60-0.83). In contrast, the relapsed MD group displayed lower bilateral striatum, bilateral insula, left IFG and left anterior cingulate activation than the abstinent MD group (Cohen's d range: 0.90-1.23) in response to winning, tying and losing feedback. Methamphetamine-dependent individuals who achieve abstinence and then relapse show greater inferior frontal gyrus activation during learning, and relatively attenuated striatal, insular and frontal activation in response to feedback, compared with methamphetamine-dependent people who remain abstinent.

CognitiveConstruct

RewardProcessing

10.1073/pnas.1312011110

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

Proc Natl Acad Sci U S A

Working-memory capacity protects model-based learning from stress.

Accounts of decision-making have long posited the operation of separate, competing valuation systems in the control of choice behavior. Recent theoretical and experimental advances suggest that this classic distinction between habitual and goal-directed (or more generally, automatic and controlled) choice may arise from two computational strategies for reinforcement learning, called model-free and model-based learning. Popular neurocomputational accounts of reward processing emphasize the involvement of the dopaminergic system in model-free learning and prefrontal, central executive-dependent control systems in model-based choice. Here we hypothesized that the hypothalamic-pituitary-adrenal (HPA) axis stress response--believed to have detrimental effects on prefrontal cortex function--should selectively attenuate model-based contributions to behavior. To test this, we paired an acute stressor with a sequential decision-making task that affords distinguishing the relative contributions of the two learning strategies. We assessed baseline working-memory (WM) capacity and used salivary cortisol levels to measure HPA axis stress response. We found that stress response attenuates the contribution of model-based, but not model-free, contributions to behavior. Moreover, stress-induced behavioral changes were modulated by individual WM capacity, such that low-WM-capacity individuals were more susceptible to detrimental stress effects than high-WM-capacity individuals. These results enrich existing accounts of the interplay between acute stress, working memory, and prefrontal function and suggest that executive function may be protective against the deleterious effects of acute stress.

CognitiveConstruct

RewardProcessing

10.1007/s00213-013-3363-7

Psychopharmacology

Psychopharmacology (Berl)

Specific impairments in instrumental learning following chronic intermittent toluene inhalation in adolescent rats.

Inhalant abuse is prevalent in adolescent populations, with chronic use resulting in neurobiological and cognitive abnormalities in adulthood. However, the nature and persistence of cognitive dysfunction, particularly following adolescent inhalant abuse, remain equivocal. The present study assessed specific cognitive processes beginning in late adolescence and adulthood following adolescent inhalation of toluene, a main component of many compounds readily abused. Adolescent male Wistar rats (postnatal day (PN) 27) were exposed to chronic intermittent inhaled toluene (10,000 ppm) for 1 h/day, 3 days/week for 4 weeks (PN 27-52) to mimic the patterns observed in human adolescent inhalant abusers. Following toluene exposure, motor and cognitive function was assessed. Adolescent toluene exposure did not alter motor learning in the Rotarod task (PN 58) or acquisition, reversal, or retention of spatial learning in the Morris water maze (PN 55-64). In contrast, it delayed acquisition of instrumental responding for sucrose (5 % w/v) and impaired operant reversal learning and cue-induced reinstatement of sucrose seeking in adulthood (PN 57-100). This study demonstrates that exposure to toluene at an abuse concentration during adolescence results in specific impairments in aspects of instrumental learning, without altering motor function and spatial learning in late adolescence/early adulthood. Our data imply that persistent alterations in reward processing may occur following adolescent inhalant misuse.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2013.11.023

Neuropsychologia

Neuropsychologia

The influence of anhedonia on feedback negativity in major depressive disorder.

Anhedonia is associated with reward-processing deficits of the dopamine system, which may increase the risk of depression. Nevertheless, few previous studies have examined the influence of hedonic tone on event-related potential (ERP) measures of reward processing in major depressive disorder. A simple gambling task was used to elicit feedback negativity (FN), an ERP component elicited by feedback indicating gain versus loss, in 27 patients with major depression and 27 healthy participants. We found that participants with depression were characterized by reduced FN responses, especially towards monetary gains, but not losses, compared with healthy individuals. In addition, the amplitude of FN to gain feedback in participants with depression was related to anhedonia severity and depressive symptoms. These findings indicate an association between low hedonic capacity and reduction in FN. As a neural measure of reward sensitivity, FN may be generated in part by reward-related activity.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2013.11.045

Behavioural brain research

Behav Brain Res

I endeavor to make it: effort increases valuation of subsequent monetary reward.

Although it is commonly accepted that the amount of effort we put into accomplishing a task would exert an influence on subsequent reward processing and outcome evaluation, whether effort is incorporated as a cost or it would increase the valuation of concomitant reward is still under debate. In this study, EEGs were recorded while subjects performed calculation tasks that required different amount of effort, correct responses of which were followed by either no reward or fixed compensation. Results showed that high effort induced larger differentiated FRN responses to the reward and non-reward discrepancy across two experimental conditions. Furthermore, P300 manifested valence effect during reward feedback, with more positive amplitudes for reward than for non-reward only in the high effort condition. These results suggest that effort might increase subjective evaluation toward subsequent reward.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22383

Human brain mapping

Hum Brain Mapp

Attentional modulation of reward processing in the human brain.

Although neural signals of reward anticipation have been studied extensively, the functional relationship between reward and attention has remained unclear: Neural signals implicated in reward processing could either reflect attentional biases towards motivationally salient stimuli, or proceed independently of attentional processes. Here, we sought to disentangle reward and attention-related neural processes by independently modulating reward value and attentional task demands in a functional magnetic resonance imaging study in healthy human participants. During presentation of a visual reward cue that indicated whether monetary reward could be obtained in a subsequent reaction time task, participants either attended to the reward cue or performed an unrelated attention-demanding task at two different levels of difficulty. In ventral striatum and ventral tegmental area, neural responses were modulated by reward anticipation irrespective of attentional demands, thus indicating attention-independent processing of reward cues. By contrast, additive effects of reward and attention were observed in visual cortex. Critically, reward-related activations in right anterior insula strongly depended on attention to the reward cue. Dynamic causal modelling revealed that the attentional modulation of reward processing in insular cortex was mediated by enhanced effective connectivity from ventral striatum to anterior insula. Our results provide evidence for distinct functional roles of the brain regions involved in the processing of reward-indicating information: While subcortical structures signal the motivational salience of reward cues even when attention is fully engaged elsewhere, reward-related responses in anterior insula depend on available attentional resources, likely reflecting the conscious evaluation of sensory information with respect to motivational value.

CognitiveConstruct

RewardProcessing

10.1016/j.cct.2013.11.007

Contemporary clinical trials

Contemp Clin Trials

Neuroimaging studies of factors related to exercise: rationale and design of a 9 month trial.

The prevalence of obesity is high resulting from chronic imbalances between energy intake and expenditure. On the expenditure side, regular exercise is associated with health benefits, including enhanced brain function. The benefits of exercise are not immediate and require persistence to be realized. Brain regions associated with health-related decisions, such as whether or not to exercise or controlling the impulse to engage in immediately rewarding activities (e.g., sedentary behavior), include reward processing and cognitive control regions. A 9 month aerobic exercise study will be conducted in 180 sedentary adults (n = 90 healthy weight [BMI = 18.5 to 26.0 kg/m(2)]; n = 90 obese [BMI = 29.0 to 41.0 kg/m(2)) to examine the brain processes underlying reward processing and impulse control that may affect adherence in a new exercise regimen. The primary aim is to use functional magnetic resonance imaging (fMRI) to examine reward processing and impulse control among participants that adhere (exercise >80% of sessions) and those that do not adhere to a nine-month exercise intervention with secondary analyses comparing sedentary obese and sedentary healthy weight participants. Our results will provide valuable information characterizing brain activation underlying reward processing and impulse control in sedentary obese and healthy weight individuals. In addition, our results may identify brain activation predictors of adherence and success in the exercise program along with measuring the effects of exercise and improved fitness on brain activation.

CognitiveConstruct

RewardProcessing

10.1037/a0035179

Journal of experimental psychology. General

J Exp Psychol Gen

System justification and electrophysiological responses to feedback: support for a positivity bias.

Conservatives, compared to liberals, are consistently found to exhibit physiological sensitivity to aversive stimuli. However, it remains unknown whether conservatives are also sensitive to salient positively valenced stimuli. We therefore used event-related potentials to determine the relationship between system justification (SJ), a fundamental component of conservative political ideology, and neural processing of negative and positive feedback. Participants (N = 29) filled out questionnaire assessments of SJ. Feedback-related negativity (FRN), an event-related potential component thought to index activity in neural regions associated with reward processing, was assessed in response to positive and negative feedback on a time estimation task. A significant interaction was noted between SJ and feedback type in predicting FRN. Simple effects tests suggested that SJ predicted greater FRN in response to positive but not to negative feedback. Conservatives may experience salient positive information with a heightened intensity.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2013.11.020

Behavioural brain research

Behav Brain Res

Focal lesions within the ventral striato-pallidum abolish attraction for male chemosignals in female mice.

In rodents, socio-sexual behaviour is largely mediated by chemosensory cues, some of which are rewarding stimuli. Female mice display an innate attraction towards male chemosignals, dependent on the vomeronasal system. This behaviour likely reflects the hedonic value of sexual chemosignals. The anteromedial aspect of the olfactory tubercle, along with its associated islands of Calleja, receives vomeronasal inputs and sexually-dimorphic vasopressinergic innervation. Thus, we hypothesised that this portion of the ventral striato-pallidum, known to be involved in reward processing, might be important for sexual odorant-guided behaviours. In this study, we demonstrate that lesions of this region, but not of regions in the posterolateral striato-pallidum, abolish the attraction of female mice for male chemosignals, without affecting significantly their preference for a different natural reward (a sucrose solution). These results show that, at least in female mice, the integrity of the anterior aspect of the medioventral striato-pallidum, comprising a portion of the olfactory tubercle and associated islands of Calleja, is necessary for the attraction for male chemosignals. We suggest that this region contributes to the processing of the hedonic properties of biologically significant odorants.

CognitiveConstruct

RewardProcessing

10.1002/eat.22223

The International journal of eating disorders

Int J Eat Disord

Differential impairments underlying decision making in anorexia nervosa and bulimia nervosa: a cognitive modeling analysis.

This study examined the underlying processes of decision-making impairments in individuals with anorexia nervosa (AN) and bulimia nervosa (BN). We deconstructed their performance on the widely used decision task, the Iowa Gambling Task (IGT) into cognitive, motivational, and response processes using cognitive modeling analysis. We hypothesized that IGT performance would be characterized by impaired memory functions and heightened punishment sensitivity in AN, and by elevated sensitivity to reward as opposed to punishment in BN. We analyzed trial-by-trial data of IGT obtained from 224 individuals: 94 individuals with AN, 63 with BN, and 67 healthy comparison individuals (HC). The prospect valence learning model was used to assess cognitive, motivational, and response processes underlying IGT performance. Individuals with AN showed marginally impaired IGT performance compared to HC. Their performance was characterized by impairments in memory functions. Individuals with BN showed significantly impaired IGT performance compared to HC. They showed greater relative sensitivity to gains as opposed to losses than HC. Memory functions in AN were positively correlated with body mass index. This study identified differential impairments underlying IGT performance in AN and BN. Findings suggest that impaired decision making in AN might involve impaired memory functions. Impaired decision making in BN might involve altered reward and punishment sensitivity.

CognitiveConstruct

RewardProcessing