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10.1016/j.yhbeh.2013.01.005

Hormones and behavior

Horm Behav

Variation in vasopressin receptor (Avpr1a) expression creates diversity in behaviors related to monogamy in prairie voles.

Polymorphisms in noncoding regions of the vasopressin 1a receptor gene (Avpr1a) are associated with a variety of socioemotional characteristics in humans, chimpanzees, and voles, and may impact behavior through a site-specific variation in gene expression. The socially monogamous prairie vole offers a unique opportunity to study such neurobiological control of individual differences in complex behavior. Vasopressin 1a receptor (V1aR) signaling is necessary for the formation of the pair bond in males, and prairie voles exhibit greater V1aR binding in the reward-processing ventral pallidum than do asocial voles of the same genus. Diversity in social behavior within prairie voles has been correlated to natural variation in neuropeptide receptor expression in specific brain regions. Here we use RNA interference to examine the causal relationship between intraspecific variation in V1aR and behavioral outcomes, by approximating the degree of naturalistic variation in V1aR expression. Juvenile male prairie voles were injected with viral vectors expressing shRNA sequences targeting Avpr1a mRNA into the ventral pallidum. Down-regulation of pallidal V1aR density resulted in a significant impairment in the preference for a mated female partner and a reduction in anxiety-like behavior in adulthood. No effect on alloparenting was detected. These data demonstrate that within-species naturalistic-like variation in V1aR expression has a profound effect on individual differences in social attachment and emotionality. RNA interference may prove to be a useful technique to unite the fields of behavioral ecology and neurogenetics to perform ethologically relevant studies of the control of individual variation and offer insight into the evolutionary mechanisms leading to behavioral diversity.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.2201-12.2013

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

J Neurosci

Bayesian prediction and evaluation in the anterior cingulate cortex.

The dorsal anterior cingulate cortex (dACC) has been implicated in a variety of cognitive control functions, among them the monitoring of conflict, error, and volatility, error anticipation, reward learning, and reward prediction errors. In this work, we used a Bayesian ideal observer model, which predicts trial-by-trial probabilistic expectation of stop trials and response errors in the stop-signal task, to differentiate these proposed functions quantitatively. We found that dACC hemodynamic response, as measured by functional magnetic resonance imaging, encodes both the absolute prediction error between stimulus expectation and outcome, and the signed prediction error related to response outcome. After accounting for these factors, dACC has no residual correlation with conflict or error likelihood in the stop-signal task. Consistent with recent monkey neural recording studies, and in contrast with other neuroimaging studies, our work demonstrates that dACC reports at least two different types of prediction errors, and beyond contexts that are limited to reward processing.

CognitiveConstruct

RewardProcessing

10.1038/mp.2012.195

Molecular psychiatry

Mol Psychiatry

Sharing pain and relief: neural correlates of physicians during treatment of patients.

Patient-physician interactions significantly contribute to placebo effects and clinical outcomes. While the neural correlates of placebo responses have been studied in patients, the neurobiology of the clinician during treatment is unknown. This study investigated physicians' brain activations during patient-physician interaction while the patient was experiencing pain, including a 'treatment', 'no-treatment' and 'control' condition. Here, we demonstrate that physicians activated brain regions previously implicated in expectancy for pain-relief and increased attention during treatment of patients, including the right ventrolateral and dorsolateral prefrontal cortices. The physician's ability to take the patients' perspective correlated with increased brain activations in the rostral anterior cingulate cortex, a region that has been associated with processing of reward and subjective value. We suggest that physician treatment involves neural representations of treatment expectation, reward processing and empathy, paired with increased activation in attention-related structures. Our findings further the understanding of the neural representations associated with reciprocal interactions between clinicians and patients; a hallmark for successful treatment outcomes.

CognitiveConstruct

RewardProcessing

10.1002/eat.22083

The International journal of eating disorders

Int J Eat Disord

White matter integrity is reduced in bulimia nervosa.

To investigate brain white matter (WM) functionality in bulimia nervosa (BN) in relation to anxiety. Twenty-one control women (CW, mean age 27 ± 7 years) and 20 BN women (mean age 25 ± 5 years) underwent brain diffusion tensor imaging to measure fractional anisotropy (FA; an indication of WM axon integrity) and the apparent diffusion coefficient (ADC; reflecting WM cell damage). FA was decreased in BN in the bilateral corona radiata extending into the posterior limb of the internal capsule, the corpus callosum, the right sub-insular WM, and right fornix. In CW but not BN, trait anxiety correlated negatively with fornix, corpus callosum, and left corona radiata FA. ADC was increased in BN compared with CW in the bilateral corona radiata, corpus callosum, inferior fronto-occipital, and uncinate fasciculus. Alterations in BN WM functionality were not due to structural brain alterations. WM integrity is disturbed in BN, especially in the corona radiata, which has been associated with taste and brain reward processing. Whether this is a premorbid condition or an effect from the illness is yet uncertain. The relationships between WM FA and trait anxiety in CW but not BN may suggest that altered WM functionality contributes to high anxious traits in BN.

CognitiveConstruct

RewardProcessing

10.1007/s00702-012-0962-0

Journal of neural transmission (Vienna, Austria : 1996)

J Neural Transm (Vienna)

CID: a valid incentive delay paradigm for children.

Despite several modifications and the wide use of the monetary incentive delay paradigm (MID; Knutson et al. in J Neurosci 21(16):RC159, 2001a) for assessing reward processing, evidence concerning its application in children is scarce. A first child-friendly MID modification has been introduced by Gotlib et al. (Arch Gen Psychiatry 67(4): 380-387, 2010); however, comparability in the results of different tasks and validity across different age groups remains unclear. We investigated the validity of a newly modified MID task for children (CID) using functional magnetic resonance imaging. The CID comprises the integration of a more age appropriate feedback phase. We focused on reward anticipation and their neural correlates. Twenty healthy young adults completed the MID and the CID. Additionally, 10 healthy children completed the CID. As expected, both paradigms elicited significant ventral and dorsal striatal activity in young adults during reward anticipation. No differential effects of the tasks on reaction times, accuracy rates or on the total amount of gain were observed. Furthermore, the CID elicited significant ventral striatal activity in healthy children. In conclusion, these findings demonstrate evidence for the validity of the CID paradigm. The CID can be recommended for the application in future studies on reward processing in children, adolescents, and in adults.

CognitiveConstruct

RewardProcessing

10.1038/mp.2012.179

Molecular psychiatry

Mol Psychiatry

Opioid receptor mu 1 gene, fat intake and obesity in adolescence.

Dietary preference for fat may increase risk for obesity. It is a complex behavior regulated in part by the amygdala, a brain structure involved in reward processing and food behavior, and modulated by genetic factors. Here, we conducted a genome-wide association study (GWAS) to search for gene loci associated with dietary intake of fat, and we tested whether these loci are also associated with adiposity and amygdala volume. We studied 598 adolescents (12-18 years) recruited from the French-Canadian founder population and genotyped them with 530 011 single-nucleotide polymorphisms. Fat intake was assessed with a 24-hour food recall. Adiposity was examined with anthropometry and bioimpedance. Amygdala volume was measured by magnetic resonance imaging. GWAS identified a locus of fat intake in the μ-opioid receptor gene (OPRM1, rs2281617, P=5.2 × 10(-6)), which encodes a receptor expressed in the brain-reward system and shown previously to modulate fat preference in animals. The minor OPRM1 allele appeared to have a 'protective' effect: it was associated with lower fat intake (by 4%) and lower body-fat mass (by ∼2 kg, P=0.02). Consistent with the possible amygdala-mediated inhibition of fat preference, this allele was additionally associated with higher amygdala volume (by 69 mm(3), P=0.02) and, in the carriers of this allele, amygdala volume correlated inversely with fat intake (P=0.02). Finally, OPRM1 was associated with fat intake in an independent sample of 490 young adults. In summary, OPRM1 may modulate dietary intake of fat and hence risk for obesity, and this effect may be modulated by subtle variations in the amygdala volume.

CognitiveConstruct

RewardProcessing

10.1016/B978-0-444-62604-2.00021-6

Progress in brain research

Prog Brain Res

The effect of novelty on reinforcement learning.

Recent research suggests that novelty has an influence on reward-related learning. Here, we showed that novel stimuli presented from a pre-familiarized category can accelerate or decelerate learning of the most rewarding category, depending on the condition. The extent of this influence depended on the individual trait of novelty seeking. Different reinforcement learning models were developed to quantify subjects' choices. We introduced a bias parameter to model explorative behavior toward novel stimuli and characterize individual variation in novelty response. The theoretical framework allowed us to test different assumptions, concerning the motivational value of novelty. The best fitting-model combined all novelty components and had a significant positive correlation with both the experimentally measured novelty bias and the independent novelty-seeking trait. Altogether, we have not only shown that novelty by itself enhances behavioral responses underlying reward processing, but also that novelty has a direct influence on reward-dependent learning processes, consistently with computational predictions.

CognitiveConstruct

RewardProcessing

10.2741/e615

Frontiers in bioscience (Elite edition)

Front Biosci (Elite Ed)

Rapid dopamine dynamics in the accumbens core and shell: learning and action.

The catecholamine dopamine (DA) has been implicated in a host of neural processes as diverse as schizophrenia, parkinsonism and reward encoding. Importantly, these distinct features of DA function are due in large part to separate neural circuits involving connections arising from different DA-releasing nuclei and projections to separate afferent targets. Emerging data has suggested that this same principle of separate neural circuits may be applicable within structural subregions, such as the core and shell of the nucleus accumbens (NAc). Further, DA may act selectively on smaller ensembles of cells (or, microcircuits) via differential DA receptor density and distinct inputs and outputs of the microcircuits, thus enabling new learning about Pavlovian cues, instrumental responses, subjective reward processing and decision-making. In this review, by taking advantage of studies using subsecond voltammetric techniques in behaving animals to study how rapid changes in DA levels affect behavior, we examine the spatial and temporal features of DA release and how it relates to both normal learning and similarities to pathological learning in the form of addiction.

CognitiveConstruct

RewardProcessing

10.2741/e612

Frontiers in bioscience (Elite edition)

Front Biosci (Elite Ed)

Improved techniques for examining rapid dopamine signaling with iontophoresis.

Dopamine is a neurotransmitter that is utilized in brain circuits associated with reward processing and motor activity. Advances in microelectrode techniques and cyclic voltammetry have enabled its extracellular concentration fluctuations to be examined on a subsecond time scale in the brain of anesthetized and freely moving animals. The microelectrodes can be attached to micropipettes that allow local drug delivery at the site of measurement. Drugs that inhibit dopamine uptake or its autoreceptors can be evaluated while only affecting the brain region directly adjacent to the electrode. The drugs are ejected by iontophoresis in which an electrical current forces the movement of molecules by a combination of electrical migration and electroosmosis. Using electroactive tracer molecules, the amount ejected can be measured with cyclic voltammetry. In this review we will give an introduction to the basic principles of iontophoresis, including a historical account on the development of iontophoresis. It will also include an overview of the use of iontophoresis to study neurotransmission of dopamine in the rat brain. It will close by summarizing the advantages of iontophoresis and how the development of quantitative iontophoresis will facilitate future studies.

CognitiveConstruct

RewardProcessing

EXCLI journal

EXCLI J

Changes in apoptotic factors in hypothalamus and hippocampus after acute and subchronic stress induction during conditioned place preference paradigm.

The hypothalamus (HYP) and hippocampus (HIP) are important regions involved in stress responses. These areas are also associated with reward processing. In this study, the effects of acute and subchronic stress on the changes in apoptotic factors (Bax/Bcl-2 ratio, caspase-3 activation and PARP degradation) in the HYP and HIP during conditioned place preference (CPP) paradigm were evaluated. Male Wistar rats were divided into two saline- and morphine-treated supergroups. Each supergroup contained control, acute stress (AS) and subchronic stress (SS) groups. In all groups, CPP paradigm was done and thereinafter alterations of apoptotic factors were measured by western blot. The results revealed that in the HYP, all mentioned factors increased significantly in saline- or morphine-treated animals during AS and SS. On the other hand, in the HIP, Bax/Bcl-2 ratio in saline-treated animals increased significantly during AS and SS, while in morphine-treated animals this ratio did not have any significant alteration during AS and was decreased during SS compared with morphine-control group. Caspase-3 and PARP increased during AS and SS in saline- or morphine-treated animals. For example, caspase-3 increased during AS and SS in morphine-treated animals by 2.4 folds and PARP (89 KDa) increased by 3.1 and 3.5 folds, respectively. Interestingly, the increase of apoptotic factors in morphine-treated animals was more considerable than that of saline-treated animals. These results strongly implied that AS and SS trigger apoptotic events in the HYP and HIP of saline- and/or morphine-treated animals as well as morphine reinforces the effect of stress on the induction of apoptosis.

CognitiveConstruct

RewardProcessing

10.1016/j.jaac.2012.10.004

Journal of the American Academy of Child and Adolescent Psychiatry

J Am Acad Child Adolesc Psychiatry

Reward processing in adolescents with bipolar I disorder.

Bipolar disorder (BD) is a debilitating psychiatric condition that commonly begins in adolescence, a developmental period that has been associated with increased reward seeking. Because youth with BD are especially vulnerable to negative risk-taking behaviors, understanding the neural mechanisms by which dysregulated affect interacts with the neurobehavioral processing of reward is clearly important. One way to clarify how manic symptoms evolve in BD is to "prime" the affect before presenting rewarding stimuli. The objective of this study was to investigate the neural effects of an affective priming task designed to positively induce mood before reward processing in adolescents with and without BD. Neural activity and behaviors during the anticipation of and response to monetary reward and loss after an affective prime were compared using functional magnetic resonance imaging in 13- to 18-year-old adolescents with a recent onset of BD-I (n = 24) and demographically matched healthy comparison youth (n = 24). Compared with the healthy control youth, youth with BD had speeded reaction times and showed decreased activation in the thalamus and inferior temporal gyrus while anticipating gains after priming but increased activations in the middle frontal gyrus and parietal cortices while anticipating losses after priming. Youth with BD also showed less activation in the inferior parietal lobule, thalamus, and superior frontal gyrus while receiving losses after priming. Aberrant prefrontal and subcortical activations during reward processing suggest mechanisms that may underlie disordered self-awareness during goal pursuit and motivation in BD. Longitudinal studies are needed to examine whether this pattern of neural activation predicts a poorer long-term outcome.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0051507

PloS one

PLoS One

GABA neurons in the ventral tegmental area responding to peripheral sensory input.

Dopamine (DA) neurons in the ventral tegmental area (VTA) not only participate in reward processing, but also respond to aversive stimuli. Although GABA neurons in this area are actively involved in regulating the firing of DA neurons, few data exist concerning the responses of these neurons to aversive sensory input. In this study, by employing extracellular single-unit recording and spectral analysis techniques in paralyzed and ventilated rats, we found that the firing pattern in 44% (47 of 106) of GABA cells in the VTA was sensitive to the sensory input produced by the ventilation, showing a significant ventilation-associated oscillation in the power spectra. Detailed studies revealed that most ventilation-sensitive GABA neurons (38 of 47) were excited by the stimuli, whereas most ventilation-sensitive DA neurons (11 of 14) were inhibited. When the animals were under anesthesia or the sensory pathways were transected, the ventilation-associated oscillation failed to appear. Systemic administration of non-competitive N-methyl-D-aspartase (NMDA) receptor antagonist MK-801 completely disrupted the association between the firing of GABA neurons and the ventilation. Interestingly, local MK-801 injection into the VTA dramatically enhanced the sensitivity of GABA neurons to the ventilation. Our data demonstrate that both GABA and DA neurons in the VTA can be significantly modulated by sensory input produced by the ventilation, which may indicate potential functional roles of VTA in processing sensation-related input.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0051416

PloS one

PLoS One

Deficits in cognitive control, timing and reward sensitivity appear to be dissociable in ADHD.

Recent neurobiological models of ADHD suggest that deficits in different neurobiological pathways may independently lead to symptoms of this disorder. At least three independent pathways may be involved: a dorsal frontostriatal pathway involved in cognitive control, a ventral frontostriatal pathway involved in reward processing and a frontocerebellar pathway related to temporal processing. Importantly, we and others have suggested that disruptions in these three pathways should lead to separable deficits at the cognitive level. Furthermore, if these truly represent separate biological pathways to ADHD, these cognitive deficits should segregate between individuals with ADHD. The present study tests these hypotheses in a sample of children, adolescents and young adults with ADHD and controls. 149 Subjects participated in a short computerized battery assessing cognitive control, timing and reward sensitivity. We used Principal Component Analysis to find independent components underlying the variance in the data. The segregation of deficits between individuals was tested using Loglinear Analysis. We found four components, three of which were predicted by the model: Cognitive control, reward sensitivity and timing. Furthermore, 80% of subjects with ADHD that had a deficit were deficient on only one component. Loglinear Analysis statistically confirmed the independent segregation of deficits between individuals. We therefore conclude that cognitive control, timing and reward sensitivity were separable at a cognitive level and that deficits on these components segregated between individuals with ADHD. These results support a neurobiological framework of separate biological pathways to ADHD with separable cognitive deficits.

CognitiveConstruct

RewardProcessing

10.1016/j.yhbeh.2012.11.018

Hormones and behavior

Horm Behav

Pubertal maturation and sex steroids are related to alcohol use in adolescents.

Adolescents often show risk-taking behavior, including experimentation with alcohol. Previous studies have shown that advanced pubertal maturation is related to increased alcohol use in adolescents, even when controlling for age. Little is known about the underlying mechanisms of this relation between pubertal maturation and alcohol use. The goal of the present study was twofold. In Experiment 1, we investigated whether advanced pubertal maturation is associated with higher levels of alcohol use, when controlling for age. To this end, questionnaires on pubertal development and alcohol use were administered to a large sample of 797 Dutch adolescents (405 boys) aged 11-16 years. In Experiment 2, we explored whether sex steroids contribute to this relation between pubertal maturation and alcohol use by examining the association between salivary sex steroid levels and alcohol use in 168 adolescents (86 boys). It was found that, when controlling for age, advanced pubertal maturation is related to increased alcohol use in adolescent boys and girls. Controlling for age, higher testosterone and estradiol levels correlated with the onset of alcohol use in boys. In addition, higher estradiol levels were associated with a larger quantity of alcohol use in boys. Correlations between sex steroids and alcohol use were not significant in girls. These findings show that advanced pubertal maturation is related to advanced alcohol use, and that higher sex steroid levels could be one of the underlying mechanisms of this relation in boys. Sex steroids might promote alcohol use by stimulating brain regions implicated in reward processing.

CognitiveConstruct

RewardProcessing

10.1093/scan/nss146

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Common and distinct neural features of social and non-social reward processing in autism and social anxiety disorder.

Autism spectrum disorders (ASDs) and social anxiety disorder (SAD) are both characterized by social dysfunction, but no study to date has compared neural responses to social rewards in ASDs and SAD. Neural responses during social and non-social reward anticipation and outcomes were examined in individuals with ASD (n = 16), SAD (n = 15) and a control group (n = 19) via functional magnetic resonance imaging. Analyses modeling all three groups revealed increased nucleus accumbens (NAc) activation in SAD relative to ASD during monetary reward anticipation, whereas both the SAD and ASD group demonstrated decreased bilateral NAc activation relative to the control group during social reward anticipation. During reward outcomes, the SAD group did not differ significantly from the other two groups in ventromedial prefrontal cortex activation to either reward type. Analyses comparing only the ASD and SAD groups revealed greater bilateral amygdala activation to social rewards in SAD relative to ASD during both anticipation and outcome phases, and the magnitude of left amygdala hyperactivation in the SAD group during social reward anticipation was significantly correlated with the severity of trait anxiety symptoms. Results suggest reward network dysfunction to both monetary and social rewards in SAD and ASD during reward anticipation and outcomes, but that NAc hypoactivation during monetary reward anticipation differentiates ASD from SAD.

CognitiveConstruct

RewardProcessing

10.3389/fneur.2012.00168

Frontiers in neurology

Front Neurol

Active Reward Processing during Human Sleep: Insights from Sleep-Related Eating Disorder.

In this paper, we present two carefully documented cases of patients with sleep-related eating disorder (SRED), a parasomnia which is characterized by involuntary compulsive eating during the night and whose pathophysiology is not known. Using video-polysomnography, a dream diary and psychometric examination, we found that both patients present elevated novelty seeking and increased reward sensitivity. In light of new evidence on the mesolimbic dopaminergic implication in compulsive eating disorders, our findings suggest a role of an active reward system during sleep in the manifestation of SRED.

CognitiveConstruct

RewardProcessing

10.1093/scan/nss147

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Effort increases sensitivity to reward and loss magnitude in the human brain.

It is ecologically adaptive that the amount of effort invested to achieve a reward increases the relevance of the resulting outcome. Here, we investigated the effect of effort on activity in reward and loss processing brain areas by using functional magnetic resonance imaging. In total, 28 subjects were endowed with monetary rewards of randomly varying magnitude after performing arithmetic calculations that were either difficult (high effort), easy (low effort) or already solved (no effort). Subsequently, a forced donation took place, where a varying part of the endowment was transferred to a charity organization, causing a loss for the subject. Results show that reward magnitude positively modulates activity in reward-processing brain areas (subgenual anterior cingulate cortex and nucleus accumbens) only in the high effort condition. Furthermore, anterior insular activity was positively modulated by loss magnitude only after high effort. The results strongly suggest an increasing relevance of outcomes with increasing previous effort.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2012.11.029

NeuroImage

Neuroimage

Cortical and subcortical responses to high and low effective placebo treatments.

The effectiveness of placebo treatments depends on the recipient's expectations, which are at least in part shaped by previous experiences. Thus, positive past experience together with an accordant verbal instruction should enhance outcome expectations and subsequently lead to higher placebo efficacy. This should be reflected in subjective valuation reports and in activation of placebo-related brain structures. We tested this hypothesis in a functional magnetic resonance imaging study, where subjects experienced different levels of pain relief and conforming information about price levels for two placebo treatments during a manipulation phase, thereby establishing a weak and a strong placebo. As expected, both placebos led to a significant pain relief and the strong placebo induced better analgesic efficacy. Individual placebo value estimates reflected treatment efficacy, i.e. subjects were willing to pay more money for the strong placebo even though pain stimulation was completed at this time. On the neural level, placebo effects were associated with activation of the rostral anterior cingulate cortex, the anterior insula, and the ventral striatum and deactivations in the thalamus and secondary somatosensory cortex. However, only placebo-related responses in rostral anterior cingulate cortex were consistent across both the anticipation of painful stimuli and their actual administration. Most importantly, rostral anterior cingulate cortex responses were higher for the strong placebo, thus mirroring the behavioral effects. These results directly link placebo analgesia to anticipatory activity in the ventral striatum, a region involved in reward processing, and highlight the role of the rostral anterior cingulate cortex, as its activity consistently scaled with increasing analgesic efficacy.

CognitiveConstruct

RewardProcessing

10.1016/j.jpsychires.2012.09.026

Journal of psychiatric research

J Psychiatr Res

Differential reward processing in subtypes of adult attention deficit hyperactivity disorder.

Abnormalities in reward processing have been found in adolescents and adults with ADHD using the 'Monetary Incentive Delay' (MID) task. However, ADHD groups in previous studies were heterogeneous regarding ADHD subtype, gender and, in part, drug treatment status. This study sought to compare neural activations in the ventral striatum (VS) and prefrontal regions during reward processing in homogenous ADHD subtype groups and healthy adults, using the MID task. In total, 24 drug-naïve, right-handed male adults with ADHD (12 subjects with combined type (ADHD-ct) and 12 subjects with predominantly inattentive (ADHD-it) type ADHD), and twelve healthy right-handed male control subjects were included. Compared to ADHD-ct and healthy subjects, ADHD-it subjects showed a bilateral ventral striatal deficit during reward anticipation. In contrast, ADHD-ct subjects showed orbitofrontal hyporesponsiveness to reward feedback when compared with ADHD-it and healthy subjects. This is the first fMRI study that delineates dysfunctional and subtype-divergent neural and behavioural reward processing in adults with ADHD.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2012.10.016

Drug and alcohol dependence

Drug Alcohol Depend

Dopaminergic involvement in effort-based but not impulsive reward processing in smokers.

A reduction in reward responsivity and an increase in temporal discounting of rewards are both evident in smokers during acute abstinence compared to satiation. However, it is not yet known whether these processes can be modulated pharmacologically in smokers, other than with nicotine or tobacco. A double-blind placebo controlled crossover design assessed the effects of 0.5 mg pramipexole, a dopamine D₂/D₃ agonist, in smokers following 2 h of abstinence. Reward responsivity was measured using an effort-based card sorting task. Temporal discounting of monetary reward was assessed using Area Under the Curve (AUC) analysis, and affective and subjective effects were indexed. On placebo, smokers showed an equivalent speed of card sorting when a financial incentive was provided compared to when it was not. Conversely, more cards were sorted under rewarded compared to non-rewarded trials after pramipexole, indicating an improvement in reward responsivity. Temporal discounting of monetary reward was not affected by pramipexole. Drug treatment also decreased positive affect and increased drowsiness. A single dose of pramipexole can enhance effort-based reward responsivity, but does not alter temporal discounting in smokers. These findings highlight pharmacological correlates of reward processing deficits in nicotine dependence and offer potential targets for their treatment.

CognitiveConstruct

RewardProcessing

10.1162/jocn_a_00326

Journal of cognitive neuroscience

J Cogn Neurosci

Enhanced striatal sensitivity to aversive reinforcement in adolescents versus adults.

Neurodevelopmental changes in mesolimbic regions are associated with adolescent risk-taking behavior. Numerous studies have shown exaggerated activation in the striatum in adolescents compared with children and adults during reward processing. However, striatal sensitivity to aversion remains elusive. Given the important role of the striatum in tracking both appetitive and aversive events, addressing this question is critical to understanding adolescent decision-making, as both positive and negative factors contribute to this behavior. In this study, human adult and adolescent participants performed a task in which they received squirts of appetitive or aversive liquid while undergoing fMRI, a novel approach in human adolescents. Compared with adults, adolescents showed greater behavioral and striatal sensitivity to both appetitive and aversive stimuli, an effect that was exaggerated in response to delivery of the aversive stimulus. Collectively, these findings contribute to understanding how neural responses to positive and negative outcomes differ between adolescents and adults and how they may influence adolescent behavior.

CognitiveConstruct

RewardProcessing

10.1162/jocn_a_00331

Journal of cognitive neuroscience

J Cogn Neurosci

Meaningful family relationships: neurocognitive buffers of adolescent risk taking.

Discordant development of brain regions responsible for cognitive control and reward processing may render adolescents susceptible to risk taking. Identifying ways to reduce this neural imbalance during adolescence can have important implications for risk taking and associated health outcomes. Accordingly, we sought to examine how a key family relationship-family obligation-can reduce this vulnerability. Forty-eight adolescents underwent an fMRI scan during which they completed a risk-taking and cognitive control task. Results suggest that adolescents with greater family obligation values show decreased activation in the ventral striatum when receiving monetary rewards and increased dorsolateral PFC activation during behavioral inhibition. Reduced ventral striatum activation correlated with less real-life risk-taking behavior and enhanced dorsolateral PFC activation correlated with better decision-making skills. Thus, family obligation may decrease reward sensitivity and enhance cognitive control, thereby reducing risk-taking behaviors.

CognitiveConstruct

RewardProcessing

10.1038/tp.2012.113

Translational psychiatry

Transl Psychiatry

Maternal interpersonal affiliation is associated with adolescents' brain structure and reward processing.

Considerable animal and human research has been dedicated to the effects of parenting on structural brain development, focusing on hippocampal and prefrontal areas. Conversely, although functional imaging studies suggest that the neural reward circuitry is involved in parental affection, little is known about mothers' interpersonal qualities in relation to their children's brain structure and function. Moreover, gender differences concerning the effect of maternal qualities have rarely been investigated systematically. In 63 adolescents, we assessed structural and functional magnetic resonance imaging as well as interpersonal affiliation in their mothers. This allowed us to associate maternal affiliation with gray matter density and neural responses during different phases of the well-established Monetary Incentive Delay task. Maternal affiliation was positively associated with hippocampal and orbitofrontal gray matter density. Moreover, in the feedback of reward hit as compared with reward miss, an association with caudate activation was found. Although no significant gender effects were observed in these associations, during reward feedback as compared with baseline, maternal affiliation was significantly associated with ventral striatal and caudate activation only in females. Our findings demonstrate that maternal interpersonal affiliation is related to alterations in both the brain structure and reward-related activation in healthy adolescents. Importantly, the pattern is in line with typical findings in depression and post-traumatic stress disorder, suggesting that a lack of maternal affiliation might have a role in the genesis of mental disorders.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2012.05.007

Psychiatry research

Psychiatry Res

A window into the invisible wound of war: functional neuroimaging of REM sleep in returning combat veterans with PTSD.

Relative regional cerebral metabolic rate of glucose in rapid eye movement (REM) sleep and wakefulness was explored in combat veterans with and without posttraumatic stress disorder PTSD, using positron emission tomography. Hypermetabolism in brain regions involved in arousal regulation, fear responses, and reward processing persist during REM sleep in combat veterans with PTSD.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2012.06.003

Psychiatry research

Psychiatry Res

Salience network-midbrain dysconnectivity and blunted reward signals in schizophrenia.

Theories of schizophrenia propose that abnormal functioning of the neural reward system is linked to negative and psychotic symptoms, by disruption of reward processing and promotion of context-independent false associations. Recently, it has been argued that an insula-anterior cingulate cortex (ACC) salience network system enables switching of brain states from the default mode to a task-related activity mode. Abnormal interaction between the insula-ACC system and reward processing regions may help explain abnormal reinforcer processing and symptoms. Here we use functional magnetic resonance imaging to assess the neural correlates of reward processing in schizophrenia. Furthermore, we investigated functional connectivity between the dopaminergic midbrain, a key region for the processing of reinforcers, and other brain regions. In response to rewards, controls activated task related regions (striatum, amygdala/hippocampus and midbrain) and the insula-ACC salience network. Patients similarly activated the insula-ACC salience network system but failed to activate task related regions. Reduced functional connectivity between the midbrain and the insula was found in schizophrenia, with the extent of this abnormality correlating with increased psychotic symptoms. The findings support the notion that reward processing is abnormal in schizophrenia and highlight the potential role of abnormal interactions between the insula-ACC salience network and reward regions.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2012.11.003

NeuroImage

Neuroimage

High and low sensation seeking adolescents show distinct patterns of brain activity during reward processing.

Previous research has shown that personality characteristics, such as sensation seeking (SS), are strong predictors of risk-taking behavior during adolescence. However, the relationship between levels of SS and brain response has not been studied during this time period. Given the prevalence of risky behavior during adolescence, it is important to understand neurobiological differences in reward sensitivity between youth with high and low SS personalities. To this end, we used functional magnetic resonance imaging (fMRI) to examine differences in brain activity in an adolescent sample that included 27 high (HSS) and 27 low sensation seekers (LSS), defined by the Impulsive Sensation Seeking scale of the Zuckerman-Kuhlman Personality Questionnaire (Zuckerman et al., 1993). In the scanner, participants played a modified Wheel of Fortune decision-making task (Cservenka and Nagel, 2012) that resulted in trials with monetary Wins or No Wins. We compared age- and sex-matched adolescent HSS and LSS (mean age=13.94±1.05) on brain activity by contrasting Win vs. No Win trials. Our findings indicate that HSS show greater bilateral insular and prefrontal cortex (PFC) brain response on Win vs. No Win compared to LSS. Analysis of simple effects showed that while LSS showed comparable brain activity in these areas during Wins and No Wins, HSS showed significant differences in brain response to winning (activation) vs. not winning (deactivation), with between-group comparison suggesting significant differences in brain response, largely to reward absence. Group differences in insular activation between reward receipt and absence may suggest weak autonomic arousal to negative outcomes in HSS compared with LSS. Additionally, since the PFC is important for goal-directed behavior and attention, the current results may reflect that HSS allocate fewer attentional resources to negative outcomes than LSS. This insensitivity to reward absence in HSS may lead to a greater likelihood of maladaptive choices when negative consequences are not considered, and may be an early neural marker of decreased loss sensitivity that has been seen in addiction. This neurobiological information may ultimately be helpful in establishing prevention strategies aimed at reducing youth risk-taking and suggests value in further examination of neural associations with personality characteristics during adolescence.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2012.00157

Frontiers in neuroscience

Front Neurosci

Acute stress influences neural circuits of reward processing.

People often make decisions under aversive conditions such as acute stress. Yet, less is known about the process in which acute stress can influence decision-making. A growing body of research has established that reward-related information associated with the outcomes of decisions exerts a powerful influence over the choices people make and that an extensive network of brain regions, prominently featuring the striatum, is involved in the processing of this reward-related information. Thus, an important step in research on the nature of acute stress' influence over decision-making is to examine how it may modulate responses to rewards and punishments within reward processing neural circuitry. In the current experiment, we employed a simple reward processing paradigm - where participants received monetary rewards and punishments - known to evoke robust striatal responses. Immediately prior to performing each of two task runs, participants were exposed to acute stress (i.e., cold pressor) or a no stress control procedure in a between-subjects fashion. No stress group participants exhibited a pattern of activity within the dorsal striatum and orbitofrontal cortex (OFC) consistent with past research on outcome processing - specifically, differential responses for monetary rewards over punishments. In contrast, acute stress group participants' dorsal striatum and OFC demonstrated decreased sensitivity to monetary outcomes and a lack of differential activity. These findings provide insight into how neural circuits may process rewards and punishments associated with simple decisions under acutely stressful conditions.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2012.10.004

Journal of affective disorders

J Affect Disord

Reduced hedonic capacity in euthymic bipolar subjects: a trait-like feature?

The aim of our study was to assess hedonic capacity in euthymic bipolar subjects, identifying possible differences compared to remitted unipolar depressed patients and healthy controls. 107 subjects with bipolar disorders, 86 with major depressive disorder and 106 healthy controls, homogeneous with respect to demographic characteristics, were enrolled. The following scales were administered: the Snaith-Hamilton pleasure scale (SHAPS), the subscale for 'anhedonia/asociality' of the scale for the assessment of negative symptoms (SANS) and the visual analogue scale (VAS) for hedonic capacity. Scores on SHAPS total, interests and social interactions, SANS 'anhedonia/asociality' and VAS were all significantly higher in affective disorder patients compared to healthy controls. No difference was found between clinical groups. 20.5% (n=22) of bipolar disorder subjects and 24.5% (n=21) of major depressed subjects showed a significant reduction in hedonic capacity (SHAPS total score ≥ 3), compared to 7.5% (n=8) of healthy controls (χ(2)=12.03; p=.002). Limitations include heterogeneity with respect to pharmacological status and longitudinal course (i.e., 'single' vs. 'recurrent' affective episodes). The major finding of our study is that euthymic bipolar patients and remitted major depressed patients display residual anhedonic symptoms. This suggests that, in affective disorder patients, altered hedonic capacity could represent an enduring trait and that, possibly, dysfunctions in the neurobiological mechanisms underlying hedonic response and reward processing persist, irrespective of mood state.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2012.10.056

NeuroImage

Neuroimage

Spatial smoothing systematically biases the localization of reward-related brain activity.

Neuroimaging methods with enhanced spatial resolution such as functional magnetic resonance imaging (FMRI) suggest that the subcortical striatum plays a critical role in human reward processing. Analysis of FMRI data requires several preprocessing steps, some of which entail tradeoffs. For instance, while spatial smoothing can enhance statistical power, it may also bias localization towards regions that contain more gray than white matter. In a meta-analysis and reanalysis of an existing dataset, we sought to determine whether spatial smoothing could systematically bias the spatial localization of foci related to reward anticipation in the nucleus accumbens (NAcc). An activation likelihood estimate (ALE) meta-analysis revealed that peak ventral striatal ALE foci for studies that used smaller spatial smoothing kernels (i.e. <6mm FWHM) were more anterior than those identified for studies that used larger kernels (i.e. >7mm FWHM). Additionally, subtraction analysis of findings for studies that used smaller versus larger smoothing kernels revealed a significant cluster of differential activity in the left relatively anterior NAcc (Talairach coordinates: -10, 9, -1). A second meta-analysis revealed that larger smoothing kernels were correlated with more posterior localizations of NAcc activation foci (p<0.015), but revealed no significant associations with other potentially relevant parameters (including voxel volume, magnet strength, and publication date). Finally, repeated analysis of a representative dataset processed at different smoothing kernels (i.e., 0-12mm) also indicated that smoothing systematically yielded more posterior activation foci in the NAcc (p<0.005). Taken together, these findings indicate that spatial smoothing can systematically bias the spatial localization of striatal activity. These findings have implications both for historical interpretation of past findings related to reward processing and for the analysis of future studies.

CognitiveConstruct

RewardProcessing

10.1007/s00221-012-3272-8

Experimental brain research

Exp Brain Res

A target sample of adolescents and reward processing: same neural and behavioral correlates engaged in common paradigms?

Adolescence is a transition period that is assumed to be characterized by increased sensitivity to reward. While there is growing research on reward processing in adolescents, investigations into the engagement of brain regions under different reward-related conditions in one sample of healthy adolescents, especially in a target age group, are missing. We aimed to identify brain regions preferentially activated in a reaction time task (monetary incentive delay (MID) task) and a simple guessing task (SGT) in a sample of 14-year-old adolescents (N = 54) using two commonly used reward paradigms. Functional magnetic resonance imaging was employed during the MID with big versus small versus no win conditions and the SGT with big versus small win and big versus small loss conditions. Analyses focused on changes in blood oxygen level-dependent contrasts during reward and punishment processing in anticipation and feedback phases. We found clear magnitude-sensitive response in reward-related brain regions such as the ventral striatum during anticipation in the MID task, but not in the SGT. This was also true for reaction times. The feedback phase showed clear reward-related, but magnitude-independent, response patterns, for example in the anterior cingulate cortex, in both tasks. Our findings highlight neural and behavioral response patterns engaged in two different reward paradigms in one sample of 14-year-old healthy adolescents and might be important for reference in future studies investigating reward and punishment processing in a target age group.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2012.10.035

NeuroImage

Neuroimage

Functional connectivity in obesity during reward processing.

Obesity is a health problem that has become a major focus of attention in recent years. There is growing evidence of an association between obesity and differences in reward processing. However, it is not known at present whether these differences are linked exclusively to food, or whether they can be detected in other rewarding stimuli. We compared responses to food, rewarding non-food and neutral pictures in 18 young adults with obesity and 19 normal-weight subjects using independent component analysis. Both groups modulated task-related activity in a plausible way. However, in response to both food and non-food rewarding stimuli, participants with obesity showed weaker connectivity in a network involving activation of frontal and occipital areas and deactivation of the posterior part of the default mode network. In addition, obesity was related with weaker activation of the default mode network and deactivation of frontal and occipital areas while viewing neutral stimuli. Together, our findings suggest that obesity is related to a different allocation of cognitive resources in a fronto-occipital network and in the default mode network.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2012.00148

Frontiers in neuroscience

Front Neurosci

Effects of direct social experience on trust decisions and neural reward circuitry.

The human striatum is integral for reward-processing and supports learning by linking experienced outcomes with prior expectations. Recent endeavors implicate the striatum in processing outcomes of social interactions, such as social approval/rejection, as well as in learning reputations of others. Interestingly, social impressions often influence our behavior with others during interactions. Information about an interaction partner's moral character acquired from biographical information hinders updating of expectations after interactions via top down modulation of reward circuitry. An outstanding question is whether initial impressions formed through experience similarly modulate the ability to update social impressions at the behavioral and neural level. We investigated the role of experienced social information on trust behavior and reward-related BOLD activity. Participants played a computerized ball-tossing game with three fictional partners manipulated to be perceived as good, bad, or neutral. Participants then played an iterated trust game as investors with these same partners while undergoing fMRI. Unbeknownst to participants, partner behavior in the trust game was random and unrelated to their ball-tossing behavior. Participants' trust decisions were influenced by their prior experience in the ball-tossing game, investing less often with the bad partner compared to the good and neutral. Reinforcement learning models revealed that participants were more sensitive to updating their beliefs about good and bad partners when experiencing outcomes consistent with initial experience. Increased striatal and anterior cingulate BOLD activity for positive versus negative trust game outcomes emerged, which further correlated with model-derived prediction error learning signals. These results suggest that initial impressions formed from direct social experience can be continually shaped by consistent information through reward learning mechanisms.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2012.10.013

NeuroImage

Neuroimage

Nucleus accumbens, thalamus and insula connectivity during incentive anticipation in typical adults and adolescents.

Reward neurocircuitry links motivation with complex behavioral responses. Studies of incentive processing have repeatedly demonstrated activation of nucleus accumbens (NAc), thalamus, and anterior insula, three key components of reward neurocircuitry. The contribution of the thalamus to this circuitry in humans has been relatively ignored, a gap that needs to be filled, given the central role of this structure in processing and filtering information. This study aimed to understand how these three regions function as a network during gain or loss anticipation in adults and youth. Towards this goal, functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) were used to examine effective connectivity among these three nodes in healthy adults and adolescents who performed the monetary incentive delay (MID) task. Seven connectivity models, based on anatomic connections, were tested. They were estimated for incentive anticipation and underwent Bayesian Model Selection (BMS) to determine the best-fit model for each adult and adolescent group. Connection strengths were extracted from the best-fit model and examined for significance in each group. These variables were then entered into a linear mixed model to test between-group effects on effective connectivity in reward neurocircuitry. The best-fit model for both groups included all possible anatomic connections. Three main findings emerged: (1) Across the task, thalamus and insula significantly influenced NAc; (2) A broader set of significant connections was found for the loss-cue condition than the gain-cue condition in both groups; (3) Finally, between-group comparisons of connectivity strength failed to detect statistical differences, suggesting that adults and adolescents use this incentive-processing network in a similar manner. This study demonstrates the way in which the thalamus and insula influence the NAc during incentive processing in humans. Specifically, this is the first study to demonstrate in humans the key role of thalamus projections onto the NAc in support of reward processing. Our results suggest that anticipation of gain/loss involves an 'alerting' signal (thalamus) that converges with interoceptive information (insula) to shape action selection programs in the ventral striatum.

CognitiveConstruct

RewardProcessing

10.1249/MSS.0b013e318275306f

Medicine and science in sports and exercise

Med Sci Sports Exerc

Acute exercise influences reward processing in highly trained and untrained men.

Physical activity activates brain regions and transmitter systems that represent the reward system (i.e., the ventral striatum [VS] and dopamine). To date, the effect of training status and acute exercise on reward processing has not been investigated systematically in humans. To address this issue, we examined highly trained (HT) physically inactive (PIA) men with a monetary incentive delay (MID) paradigm. We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of monetary incentive processing after acute exercise. HT and PIA subjects were randomized into two groups. Subjects in one group ran on a treadmill (T) for 30 min at 60%-70% of their maximal oxygen uptake (V˙O2max), whereas subjects in the other group performed placebo exercise (P). Approximately 1 h after exercise, the MID task was conducted. Mood was assessed using the Positive and Negative Affect Schedule before and after the exercise intervention. The psychological assessment showed that exercise significantly increased mood in HT and PIA men. During gain anticipation and gain feedback of the MID task, the VS was significantly stronger activated in the placebo group than in the treadmill group. No effect of training status and no interactions between training status and acute exercise were found. Acute exercise diminishes sensitivity to monetary rewards in humans. This finding is discussed concerning interactions between tonic and phasic dopamine in the VS.

CognitiveConstruct

RewardProcessing

10.1017/S1461145712000983

The international journal of neuropsychopharmacology

Int J Neuropsychopharmacol

Enhanced reward-facilitating effects of d-amphetamine in rats in the quinpirole model of obsessive-compulsive disorder.

The underlying neurobiology of addictive or repetitive behaviours, such as obsessive-compulsive disorder (OCD), involves dopaminergic dysregulation. While addictive behaviour depends strongly on mesolimbocortical dopaminergic responses, repetitive behaviours have been associated with dopaminergic dysregulation in the basal ganglia-thalamo-cortical circuitry. The present study investigates differences in brain stimulation reward in rats with quinpirole-induced compulsive checking behaviour, in order to examine if deficits in reward processing are also relevant for OCD. Rats were tested in the intracranial self-stimulation (ICSS) paradigm, which targets reward-related responses. After phenotype induction, animals were implanted with a monopolar stimulation electrode in the left medial forebrain bundle and trained to press a lever to self-administer electric stimulation of varying frequency. The curve-shift method was used to assess the reward-facilitating effects of d-amphetamine and the reward-attenuating effects of haloperidol (a D(2) antagonist). Thresholds for ICSS were estimated before and after drug/saline injection. The reward-facilitating effects of d-amphetamine were enhanced in quinpirole-treated rats in comparison to controls. This finding suggests that chronic quinpirole-treatment induces changes within the reward circuitry relevant for compulsive behaviour in the rat.

CognitiveConstruct

RewardProcessing

10.1101/cshperspect.a011924

Cold Spring Harbor perspectives in medicine

Cold Spring Harb Perspect Med

Optogenetic strategies to dissect the neural circuits that underlie reward and addiction.

Optogenetic strategies for perturbation of neural circuit function have begun to revolutionize systems neuroscience. Whereas optogenetics has proven to be a powerful approach for studying neural systems, the tools to conduct these experiments are still continuously evolving. Here we briefly summarize available hardware and reagents that can be used for studying behaviors related to reward and addiction. In addition, we discuss recent studies in which these strategies have been applied to study neural circuit function in brain slices as well as awake and behaving animals. Collectively, this work serves as a brief introduction to optogenetic techniques and highlights how these tools can be applied to elucidate the neural circuits that underlie reward processing and addiction.

CognitiveConstruct

RewardProcessing

10.1016/j.pneurobio.2012.09.005

Progress in neurobiology

Prog Neurobiol

The role of the neuropeptide S system in addiction: focus on its interaction with the CRF and hypocretin/orexin neurotransmission.

Recent behavioral, pharmacological and molecular findings have linked the NPS system to drug dependence. Most of the evidence supports the possibility that increased NPS activity may contribute to shaping vulnerability to addiction, especially relapse. However, data suggesting that the anxiolytic-like properties of NPS may have protective effects on addiction have been also published. In addition, evidence from conditioned place preference experiments, though not unequivocal, suggests that NPS per se is devoid of motivational properties. Intriguingly, several effects of NPS on drugs of abuse appear to be mediated by downstream activation of brain corticotrophin releasing factor (CRF) and hypocretin-1/orexin-A (Hcrt-1/Ox-A) systems. The major objective of the present article is to review the existing work on NPS and addiction. Particular attention is devoted to the interpretation of findings revealing complex neuroanatomical and functional interactions between NPS, CRF, and the Hcrt-1/Ox-A systems. Original data aimed at shedding light on the role of NPS in reward processing are also shown. Finally, existing findings are discussed within the framework of addiction theories, and the potential of the NPS system as a treatment target for addiction is analyzed.

CognitiveConstruct

RewardProcessing

10.1159/000341997

Neuro-degenerative diseases

Neurodegener Dis

Delay discounting of reward and caudate nucleus volume in individuals with α-synuclein gene duplication before and after the development of Parkinson's disease.

α-Synuclein (SNCA) may be a key factor in dopaminergic neurotransmission, reward processing, and neurodegeneration in Parkinson's disease (PD). We investigated delay discounting of reward and caudate volume in SNCA gene duplication carriers before and after the development of PD. Participants were 7 presymptomatic SNCA duplication carriers who later developed PD (follow-up period: 5.4 years) and 10 matched non-carrier controls. At the follow-up assessment, patients received levodopa (L-DOPA) therapy. Delay discounting of reward was assessed with the Kirby discounting questionnaire. We measured the volume of the caudate nucleus and cerebral cortex using structural MRI and FreeSurfer software. In the presymptomatic stage, carriers showed similar delay discounting and caudate volume to that of non-carrier controls. However, after the development of PD, we observed a significant elevation in delay discounting (impulsive decisions) and reduced caudate volume. There was no cortical atrophy. Impaired reward-related decision making and caudate volume loss are not detectable in the presymptomatic stage in SNCA duplication carriers. These behavioral and neuroanatomical alterations are observed after the development of clinical symptoms when there is extensive neurodegeneration. Study limitations include a small sample size as well as the potential confounding effect of general cognitive decline.

CognitiveConstruct

RewardProcessing

10.1038/npp.2012.195

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Interacting effects of naltrexone and OPRM1 and DAT1 variation on the neural response to alcohol cues.

Variation at a single nucleotide polymorphism in the μ-opioid receptor gene (OPRM1), A118G (Asn40Asp), may moderate naltrexone (NTX) effects in alcohol dependence. Both NTX and A118G variation have also been reported to affect alcohol cue-elicited brain activation. This study investigated whether sub-acute NTX treatment and A118G genotype interacted in their effects on cue-elicited activation of the ventral striatum (VS), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). Secondarily, variation at a variable number tandem repeat polymorphism in the dopamine transporter gene (DAT1/SLC6A3), which has been associated with increased reward-related activation in VS, was analyzed as a moderator of medication and A118G effects. Seventy-four non-treatment-seeking alcohol-dependent individuals, half preselected to carry at least one copy of the A118G G (Asp) allele, were randomized to NTX (50 mg) or placebo for 7 days, and performed an fMRI alcohol cue reactivity task on day 6. Region-of-interest analyses indicated no main effects of medication or A118G genotype. However, these factors interacted in their effects on OFC activation, such that, among NTX-treated individuals, G-allele carriers had less activation than A-allele homozygotes. DAT1 variation also moderated medication/A118G effects. There was a three-way interaction between medication and A118G and DAT1 genotypes on VS activation, such that, among G-allele carriers who received NTX, DAT1 10-repeat-allele (10R) homozygotes had less activation than 9-repeat-allele (9R) carriers. Further, 10R homozygotes who received NTX had less mPFC activation than 9R carriers. Polymorphic variation in OPRM1 and DAT1 should be considered in future studies of NTX, particularly regarding its effects on reward processing.

CognitiveConstruct

RewardProcessing

10.1007/s00406-012-0370-3

European archives of psychiatry and clinical neuroscience

Eur Arch Psychiatry Clin Neurosci

Cigarette smoking modulates medication-associated deficits in a monetary reward task in patients with schizophrenia.

Imaging studies of reward processing have demonstrated a mesolimbic-mesocortical dopaminergic dysfunction in schizophrenia. Such studies on reward processing in patients and also in healthy controls showed that differential activations of dopaminergic brain areas are associated with adaptive changes in response speed related to different reward values. Given this relationship, we investigated reward processing on the behavioural level in a larger sample of 49 medicated patients with a diagnosis of schizophrenia (ICD-10 F20) and 49 healthy controls. Subjects were instructed to react by button press upon two different stimuli in order to retain a 60 % chance winning a previously announced high (1$) or low (20¢) amount of money paid to participants after the experiment. Concordant with previous reports on deficits in reward processing, acceleration of reaction times in patients upon low rewards differed significantly (p < 0.05) from healthy controls in our present behavioural study. This effect was pronounced in the non-smoking subgroup of patients (n = 24). In this subgroup, we also observed a significant (p < 0.05) positive correlation with medication type (relatively high vs. low D2 receptor affinity) and with the PANSS score, the latter with a trend to significance (p = 0.08). Our study demonstrates that reaction time measures in a monetary reward task might constitute a feasible behavioural proxy for dopaminergic dysfunction and its different dimensions regarding psychopathology but also medication in patients with schizophrenia. In line with clinical observations, our findings support the notion that smoking modulates medication-associated side effects on reward processing in patients with schizophrenia.

CognitiveConstruct

RewardProcessing

10.1186/1471-244X-12-152

BMC psychiatry

BMC Psychiatry

Neural mechanisms of subclinical depressive symptoms in women: a pilot functional brain imaging study.

Studies of individuals who do not meet criteria for major depressive disorder (MDD) but with subclinical levels of depressive symptoms may aid in the identification of neurofunctional abnormalities that possibly precede and predict the development of MDD. The purpose of this study was to evaluate relations between subclinical levels of depressive symptoms and neural activation patterns during tasks previously shown to differentiate individuals with and without MDD. Functional magnetic resonance imaging (fMRI) was used to assess neural activations during active emotion regulation, a resting state scan, and reward processing. Participants were twelve females with a range of depressive symptoms who did not meet criteria for MDD. Increased depressive symptom severity predicted (1) decreased left midfrontal gyrus activation during reappraisal of sad stimuli; (2) increased right midfrontal gyrus activation during distraction from sad stimuli; (3) increased functional connectivity between a precuneus seed region and left orbitofrontal cortex during a resting state scan; and (4) increased paracingulate activation during non-win outcomes during a reward-processing task. These pilot data shed light on relations between subclinical levels of depressive symptoms in the absence of a formal MDD diagnosis and neural activation patterns. Future studies will be needed to test the utility of these activation patterns for predicting MDD onset in at-risk samples.

CognitiveConstruct

RewardProcessing

10.1111/j.1369-1600.2012.00498.x

Addiction biology

Addict Biol

Individual differences in decision making and reward processing predict changes in cannabis use: a prospective functional magnetic resonance imaging study.

Decision-making deficits are thought to play an important role in the development and persistence of substance use disorders. Individual differences in decision-making abilities and their underlying neurocircuitry may, therefore, constitute an important predictor for the course of substance use and the development of substance use disorders. Here, we investigate the predictive value of decision making and neural mechanisms underlying decision making for future cannabis use and problem severity in a sample of heavy cannabis users. Brain activity during a monetary decision-making task (Iowa gambling task) was compared between 32 heavy cannabis users and 41 matched non-using controls using functional magnetic resonance imaging. In addition, within the group of heavy cannabis users, associations were examined between task-related brain activations, cannabis use and cannabis use-related problems at baseline, and change in cannabis use and problem severity after a 6-month follow-up. Despite normal task performance, heavy cannabis users compared with controls showed higher activation during wins in core areas associated with decision making. Moreover, within the group of heavy cannabis users, win-related activity and activity anticipating loss outcomes in areas generally involved in executive functions predicted change in cannabis use after 6 months. These findings are consistent with previous studies and point to abnormal processing of motivational information in heavy cannabis users. A new finding is that individuals who are biased toward immediate rewards have a higher probability of increasing drug use, highlighting the importance of the relative balance between motivational processes and regulatory executive processes in the development of substance use disorders.

CognitiveConstruct

RewardProcessing

10.1017/S0029665112000821

The Proceedings of the Nutrition Society

Proc Nutr Soc

Taste, olfactory and food texture reward processing in the brain and the control of appetite.

Complementary neuronal recordings and functional neuroimaging in human subjects show that the primary taste cortex in the anterior insula provides separate and combined representations of the taste, temperature and texture (including fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex (OFC), these sensory inputs are for some neurons combined by learning with olfactory and visual inputs, and these neurons encode food reward in that they only respond to food when hungry, and in that activations correlate with subjective pleasantness. Cognitive factors, including word-level descriptions, and attention modulate the representation of the reward value of food in the OFC and a region to which it projects, the anterior cingulate cortex. Further, there are individual differences in the representation of the reward value of food in the OFC. It is argued that over-eating and obesity are related in many cases to an increased reward value of the sensory inputs produced by foods, and their modulation by cognition and attention that over-ride existing satiety signals. It is proposed that control of all rather than one or several of these factors that influence food reward and eating may be important in the prevention and treatment of overeating and obesity.

CognitiveConstruct

RewardProcessing

10.1002/syn.21609

Synapse (New York, N.Y.)

Synapse

Temporal changes in N-acylethanolamine content and metabolism throughout the peri-adolescent period.

Fatty acid amide hydrolase (FAAH) regulates tissue concentrations of N-acylethanolamines (NAEs), including the endocannabinoid, N-arachidonylethanolamide (anandamide, AEA). FAAH activity and NAEs are widely distributed throughout the brain and FAAH activity regulates an array of processes including emotion, cognition, inflammation, and feeding. However, there is relatively little research describing how this system develops throughout adolescence, particularly within limbic circuits regulating stress and reward processing. Thus, this study characterized temporal changes in NAE content (AEA, oleoylethanolamine [OEA], and palmitoylethanolamide [PEA]) and FAAH activity across the peri-adolescent period, in four corticolimbic structures (amygdala, hippocampus, prefrontal cortex, and hypothalamus). Brain tissue of male Sprague-Dawley rats was collected on postnatal days (PND) 25, 35, 45, and 70, representing pre-adolescence, early- to mid-adolescence, late adolescence, and adulthood, respectively. Tissue was analyzed for AEA, OEA, and PEA content as well as FAAH activity at each time point. AEA, OEA, and PEA exhibited a similar temporal pattern in all four brain regions. NAE concentrations were lowest at PND 25 and highest at PND 35. NAE concentrations decreased between PNDs 35 and 45 and increased between PNDs 45 and 70. FAAH activity mirrored the pattern of NAE content in which it decreased between PNDs 25 and 35, increased between PNDs 35 and 45, and decreased between PNDs 45 and 70. These age-dependent patterns of NAE content and FAAH activity demonstrate temporal specificity to the development of this system and could contribute to alterations in stress sensitivity, emotionality, and executive function which also fluctuate during this developmental period.

CognitiveConstruct

RewardProcessing

10.3758/s13415-012-0122-x

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

High temporal discounters overvalue immediate rewards rather than undervalue future rewards: an event-related brain potential study.

Impulsivity is characterized in part by heightened sensitivity to immediate relative to future rewards. Although previous research has suggested that "high discounters" in intertemporal choice tasks tend to prefer immediate over future rewards because they devalue the latter, it remains possible that they instead overvalue immediate rewards. To investigate this question, we recorded the reward positivity, a component of the event-related brain potential (ERP) associated with reward processing, with participants engaged in a task in which they received both immediate and future rewards and nonrewards. The participants also completed a temporal discounting task without ERP recording. We found that immediate but not future rewards elicited the reward positivity. High discounters also produced larger reward positivities to immediate rewards than did low discounters, indicating that high discounters relatively overvalued immediate rewards. These findings suggest that high discounters may be more motivated than low discounters to work for monetary rewards, irrespective of the time of arrival of the incentives.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2012.08.078

NeuroImage

Neuroimage

Counterfactual thinking and reward processing: an fMRI study of responses to gamble outcomes.

The process of comparing obtained outcomes to alternative possible outcomes, known as counterfactual thinking, is inescapable in daily life; however, the neurocognitive mechanisms underlying counterfactual thinking and how they influence emotional responses to better and worse outcomes is not well understood. We conducted an event-related functional magnetic resonance imaging (fMRI) gambling study in which participants were informed of two equally possible outcomes of a card gamble before they selected a card. Participants reported experiencing mixed emotions (i.e., both positive and negative affect) for disappointing wins (winning the lesser of two amounts) and relieving losses (losing the lesser of two amounts). Neuroimaging results supported the hypothesis that these mixed emotions were associated with activation of a fronto-parietal network, which subsequently influenced processing in reward and punishment regions (dorsal and ventral striatum, right anterior insula). The fronto-parietal network was sensitive to outcomes that resulted in mixed emotions, whereas reward and punishment regions were sensitive to comparisons between obtained and unobtained outcomes. These findings provide insight into the neurocognitive mechanisms underlying the mixed emotional experiences that result from counterfactual comparisons, and inform our understanding of how the brain is optimized to use the wealth of environmental information to inform current and future behavior.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.3157-12.2012

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

J Neurosci

Interpersonal closeness and social reward processing.

CognitiveConstruct

RewardProcessing

10.1007/s00213-012-2852-4

Psychopharmacology

Psychopharmacology (Berl)

The effects of AMPA receptor blockade in the prelimbic cortex on systemic and ventral tegmental area opiate reward sensitivity.

The medial prefrontal cortex (mPFC) is a key neural region involved in opiate-related reward memory processing. AMPA receptor transmission in the mPFC modulates opiate-related reward memory processing, and chronic opiate exposure is associated with alterations in intra-mPFC AMPA receptor function. The objectives of this study were to examine how pharmacological blockade of AMPA receptor transmission in the prelimbic (PLC) division of the mPFC may modulate opiate reward memory acquisition and whether opiate exposure state may modulate the functional role of intra-PLC AMPA receptor transmission during opiate reward learning. Using an unbiased conditioned place preference (CPP) procedure in rats, we performed discrete, bilateral intra-PLC microinfusions of the AMPA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, prior to behavioral morphine CPP conditioning, using sub-reward threshold conditioning doses of either systemic (0.05 mg/kg; i.p.) or intra-ventral tegmental area (VTA) morphine (250 ng/0.5 μl). We show that, in both opiate-naïve and opiate-dependent states, intra-PLC blockade of AMPA receptor transmission, but not the infralimbic cortex, increases the behavioral reward magnitude of systemic or intra-VTA morphine. This effect is dependent on dopamine (DA)ergic signaling because pre-administration of cis-(Z)-flupenthixol-dihydrochloride (α-flu), a broad-spectrum dopamine receptor antagonist, blocked the morphine-reward potentiating effects of AMPA receptor blockade. These findings suggest a critical role for intra-PLC AMPA receptor transmission in the processing of opiate reward signaling. Furthermore, blockade of AMPA transmission specifically within the PLC is capable of switching opiate reward processing to a DA-dependent reward system, independently of previous opiate exposure history.

CognitiveConstruct

RewardProcessing

10.3389/fphar.2012.00159

Frontiers in pharmacology

Front Pharmacol

mGluR-Dependent Synaptic Plasticity in Drug-Seeking.

A primary feature of drug addiction is the compulsive use despite negative consequences. A general consensus is emerging on the capacity of addictive substances to co-opt synaptic transmission and synaptic plasticity in brain circuits which are involved in reinforcement and reward processing. A current hypothesis is that drug-driven neuroadaptations during learning and memory processes divert the functions of these brain circuits, eventually leading to addictive behaviors. Metabotropic glutamate receptors (mGluRs) not only lead to long-term modulation of synaptic transmission but they have been implicated in drug-evoked synaptic plasticity and drug-seeking behaviors in two important ways. mGluR-dependent modulation of synaptic transmission is impaired by drug experience but interestingly their activation has been indicated as a strategy to restore baseline transmission after drug-evoked synaptic plasticity. Here we focus on the cellular mechanisms underlying mGluR-dependent long-term changes of excitatory synapses, and review results implicating these receptors in drug-evoked synaptic plasticity.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2012.00243

Frontiers in human neuroscience

Front Hum Neurosci

Human striatum is differentially activated by delayed, omitted, and immediate registering feedback.

The temporal contingency of feedback during conversations is an essential requirement of a successful dialog. In the current study, we investigated the effects of delayed and omitted registering feedback on fMRI activation and compared both unexpected conditions to immediate feedback. In the majority of trials of an auditory task, participants received an immediate visual feedback which merely indicated that a button press was registered but not whether the response was correct or not. In a minority of trials, and thus unexpectedly, the feedback was omitted, or delayed by 500 ms. The results reveal a response hierarchy of activation strength in the dorsal striatum and the substantia nigra: the response to the delayed feedback was larger compared to immediate feedback and immediate feedback showed a larger activation compared to the omission of feedback. This suggests that brain regions typically involved in reward processing are also activated by non-rewarding, registering feedback. Furthermore, the comparison with immediate feedback revealed that both omitted and delayed feedback significantly modulated activity in a network of brain regions that reflects attentional demand and adjustments in cognitive and action control, i.e., the posterior medial frontal cortex (pMFC), right dorsolateral prefrontal cortex (dlPFC), bilateral anterior insula (aI), inferior frontal gyrus (Gfi), and inferior parietal lobe (Lpi). This finding emphasizes the importance of immediate feedback in human-computer interaction, as the effects of delayed feedback on brain activity in the described network seem to be similar to that of omitted feedback.

CognitiveConstruct

RewardProcessing

10.3758/s13415-012-0119-5

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Neurophysiological differences in reward processing in anhedonics.

Anhedonia is characterized by a reduced capacity to experience pleasure in response to rewarding stimuli and has been considered a possible candidate endophenotype in depression and schizophrenia. However, it is still not well understood whether these reward deficits are confined to anticipatory and/or to consummatory experiences of pleasure. In the present study, we recorded electrophysiological responses (event-related brain potentials [ERPs] and oscillatory activity) to monetary gains and losses in extreme groups of anhedonic and nonanhedonic participants. The anhedonic participants showed reduced motivation to incur risky decisions, especially after monetary rewards. These sequential behavioral effects were correlated with an increased sensitivity to punishment, which psychometrically characterized the anhedonic group. In contrast, both electrophysiological measures associated with the impacts of monetary losses and gains--the feedback-related negativity (FRN) and the beta-gamma oscillatory component--clearly revealed preserved consummatory responses in anhedonic participants. However, anhedonics showed a drastic increase in frontal medial theta power after receiving the maximum monetary gain. This increase in theta oscillatory activity could be associated with an increase in conflict and cognitive control for unexpected large positive rewards, thus indexing the violation of default negative expectations built up across the task in anhedonic participants. Thus, the present results showed that participants with elevated scores on Chapman's Physical Anhedonia Scale were more sensitive to possible punishments, showed deficits in the correct integration of response outcomes in their actions, and evidenced deficits in sustaining positive expectations of future rewards. This overall pattern suggests an effect of anhedonia in the motivational aspects of approach behavior rather than in consummatory processes.

CognitiveConstruct

RewardProcessing

10.1016/j.pbb.2012.08.021

Pharmacology, biochemistry, and behavior

Pharmacol Biochem Behav

Neuroanatomical substrates of the disruptive effect of olanzapine on rat maternal behavior as revealed by c-Fos immunoreactivity.

Olanzapine is one of the most widely prescribed atypical antipsychotic drugs in the treatment of schizophrenia. Besides its well-known side effect on weight gain, it may also impair human parental behavior. In this study, we took a preclinical approach to examine the behavioral effects of olanzapine on rat maternal behavior and investigated the associated neural basis using the c-Fos immunohistochemistry. On postpartum days 6-8, Sprague-Dawley mother rats were given a single injection of sterile water or olanzapine (1.0, 3.0 or 5.0mg/kg, sc). Maternal behavior was tested 2h later, after which rats were sacrificed and brain tissues were collected. Ten brain regions that were either implicated in the action of antipsychotic drugs and/or in the regulation of maternal behavior were examined for c-Fos immunoreactivity. Acute olanzapine treatment dose-dependently disrupted various components of maternal behavior (e.g., pup retrieval, pup licking, nest building, crouching) and increased c-Fos immunoreactivity in the medial prefrontal cortex (mPFC), nucleus accumbens shell and core (NAs and NAc), dorsolateral striatum (DLSt), ventral lateral septum (LSv), central amygdala (CeA) and ventral tegmental area (VTA), important brain areas generally implicated in the incentive motivation and reward processing. In contrast, olanzapine treatment did not alter c-Fos in the medial preoptic nucleus (MPN), ventral bed nucleus of the stria terminalis (vBST) and medial amygdala (MeA), the core brain areas directly involved in the mediation of rat maternal behavior. These findings suggest that olanzapine disrupts rat maternal behavior primarily by suppressing incentive motivation and reward processing via its action on the mesocorticolimbic dopamine systems, other limbic and striatal areas, but not by disrupting the core processes involved in the mediation of maternal behavior in particular.

CognitiveConstruct

RewardProcessing

10.1016/j.cub.2012.07.062

Current biology : CB

Curr Biol

Sensitivity to temporal reward structure in amygdala neurons.

The time of reward and the temporal structure of reward occurrence fundamentally influence behavioral reinforcement and decision processes [1-11]. However, despite knowledge about timing in sensory and motor systems [12-17], we know little about temporal mechanisms of neuronal reward processing. In this experiment, visual stimuli predicted different instantaneous probabilities of reward occurrence that resulted in specific temporal reward structures. Licking behavior demonstrated that the animals had developed expectations for the time of reward that reflected the instantaneous reward probabilities. Neurons in the amygdala, a major component of the brain's reward system [18-29], showed two types of reward signal, both of which were sensitive to the expected time of reward. First, the time courses of anticipatory activity preceding reward delivery followed the specific instantaneous reward probabilities and thus paralleled the temporal reward structures. Second, the magnitudes of responses following reward delivery covaried with the instantaneous reward probabilities, reflecting the influence of temporal reward structures at the moment of reward delivery. In being sensitive to temporal reward structure, the reward signals of amygdala neurons reflected the temporally specific expectations of reward. The data demonstrate an active involvement of amygdala neurons in timing processes that are crucial for reward function.

CognitiveConstruct

RewardProcessing

10.1186/1866-1955-4-17

Journal of neurodevelopmental disorders

J Neurodev Disord

Abnormal social reward processing in autism as indexed by pupillary responses to happy faces.

Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding. We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects. Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group. We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli.

CognitiveConstruct

RewardProcessing

10.1186/1866-1955-4-20

Journal of neurodevelopmental disorders

J Neurodev Disord

Reward processing in autism: a thematic series.

This thematic series presents theoretical and empirical papers focused on understanding autism from the perspective of reward processing deficits. Although the core symptoms of autism have not traditionally been conceptualized with respect to altered reward-based processes, it is clear that brain reward circuitry plays a critical role in guiding social and nonsocial learning and behavior throughout development. Additionally, brain reward circuitry may respond to social sources of information in ways that are similar to responses to primary rewards, and recent clinical data consistently suggest abnormal behavioral and neurobiologic responses to rewards in autism. This thematic series presents empirical data and review papers that highlight the utility of considering autism from the perspective of reward processing deficits. Our hope is that this novel framework may further elucidate autism pathophysiology, with the ultimate goal of yielding novel insights with potential therapeutic implications.

CognitiveConstruct

RewardProcessing

10.1037/a0029823

Psychology and aging

Psychol Aging

Stress modulates reinforcement learning in younger and older adults.

Animal research and human neuroimaging studies indicate that stress increases dopamine levels in brain regions involved in reward processing, and stress also appears to increase the attractiveness of addictive drugs. The current study tested the hypothesis that stress increases reward salience, leading to more effective learning about positive than negative outcomes in a probabilistic selection task. Changes to dopamine pathways with age raise the question of whether stress effects on incentive-based learning differ by age. Thus, the present study also examined whether effects of stress on reinforcement learning differed for younger (age 18-34) and older participants (age 65-85). Cold pressor stress was administered to half of the participants in each age group, and salivary cortisol levels were used to confirm biophysiological response to cold stress. After the manipulation, participants completed a probabilistic learning task involving positive and negative feedback. In both younger and older adults, stress enhanced learning about cues that predicted positive outcomes. In addition, during the initial learning phase, stress diminished sensitivity to recent feedback across age groups. These results indicate that stress affects reinforcement learning in both younger and older adults and suggests that stress exerts different effects on specific components of reinforcement learning depending on their neural underpinnings.

CognitiveConstruct

RewardProcessing

10.1001/archgenpsychiatry.2012.1101

JAMA psychiatry

JAMA Psychiatry

Prenatal exposure to maternal cigarette smoking, amygdala volume, and fat intake in adolescence.

Prenatal exposure to maternal cigarette smoking is a well-established risk factor for obesity, but the underlying mechanisms are not known. Preference for fatty foods, regulated in part by the brain reward system, may contribute to the development of obesity. To examine whether prenatal exposure to maternal cigarette smoking is associated with enhanced fat intake and risk for obesity, and whether these associations may be related to subtle structural variations in brain regions involved in reward processing. Cross-sectional study of a population-based cohort. The Saguenay Youth Study, Quebec, Canada. A total of 378 adolescents (aged 13 to 19 years; Tanner stage 4 and 5 of sexual maturation), half of whom were exposed prenatally to maternal cigarette smoking (mean [SD], 11.1 [6.8] cigarettes/d). Fat intake was assessed with a 24-hour food recall (percentage of energy intake consumed as fat). Body adiposity was measured with anthropometry and multifrequency bioimpedance. Volumes of key brain structures involved in reward processing, namely the amygdala, nucleus accumbens, and orbitofrontal cortex, were measured with magnetic resonance imaging. Exposed vs nonexposed subjects exhibited a higher total body fat (by approximately 1.7 kg; P = .009) and fat intake (by 2.7%; P = .001). They also exhibited a lower volume of the amygdala (by 95 mm3; P < .001) but not of the other 2 brain structures. Consistent with its possible role in limiting fat intake, amygdala volume correlated inversely with fat intake (r = -0.15; P = .006). Prenatal exposure to maternal cigarette smoking may promote obesity by enhancing dietary preference for fat, and this effect may be mediated in part through subtle structural variations in the amygdala.

CognitiveConstruct

RewardProcessing

10.1016/j.brainres.2012.08.034

Brain research

Brain Res

Reward processing and intertemporal decision making in adults and adolescents: the role of impulsivity and decision consistency.

Several studies report differences between adults and adolescents in reward processing and impulsivity. Consistently, adolescents are more impulsive in their decision making, as measured by intertemporal choice tasks. Since impulsivity affects an individual's perception and neural processing of rewards, it is unclear whether previously reported differences in brain activation between adults and adolescents are primarily due to maturation of the brain reward system or differences in impulsivity (i.e. discounting behaviour). To disentangle this, we analysed data from 235 adolescents and 29 adults who performed an intertemporal choice task in which monetary rewards were adapted to individual impulsivity. Using functional magnetic resonance imaging (fMRI), we measured brain activity and assessed impulsivity and consistency of choices at the behavioural level. Although adolescents discounted delayed rewards more steeply than adults, when controlling for impulsivity, neural processing of reward value did not differ between groups. However, more impulsive subjects showed a lower brain response to delayed rewards, independent of age. Concerning decision making, adolescents exhibited a lower consistency of choices and less brain activity in the parietal network than adults. We conclude that processing of the value of prospective delayed rewards is more sensitive to discounting behaviour than to chronological age. Lower consistency of intertemporal choices might indicate ongoing maturation of parietal brain areas in adolescents.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2012.06.034

Biological psychiatry

Biol Psychiatry

Acute nicotine differentially impacts anticipatory valence- and magnitude-related striatal activity.

Dopaminergic activity plays a role in mediating the rewarding aspects of abused drugs, including nicotine. Nicotine modulates the reinforcing properties of other motivational stimuli, yet the mechanisms of this interaction are poorly understood. This study aimed to ascertain the impact of nicotine exposure on neuronal activity associated with reinforcing outcomes in dependent smokers. Smokers (n = 28) and control subjects (n = 28) underwent functional imaging during performance of a monetary incentive delay task. Using a randomized, counterbalanced design, smokers completed scanning after placement of a nicotine or placebo patch; nonsmokers were scanned twice without nicotine manipulation. In regions along dopaminergic pathway trajectories, we considered event-related activity for valence (reward/gain vs. punishment/loss), magnitude (small, medium, large), and outcome (successful vs. unsuccessful). Both nicotine and placebo patch conditions were associated with reduced activity in regions supporting anticipatory valence, including ventral striatum. In contrast, relative to controls, acute nicotine increased activity in dorsal striatum for anticipated magnitude. Across conditions, anticipatory valence-related activity in the striatum was negatively associated with plasma nicotine concentration, whereas the number of cigarettes daily correlated negatively with loss anticipation activity in the medial prefrontal cortex only during abstinence. These data suggest a partial dissociation in the state- and trait-specific effects of smoking and nicotine exposure on magnitude- and valence-dependent anticipatory activity within discrete reward processing brain regions. Such variability may help explain, in part, nicotine's impact on the reinforcing properties of nondrug stimuli and speak to the continued motivation to smoke and cessation difficulty.

CognitiveConstruct

RewardProcessing

10.1517/17530059.2012.673583

Expert opinion on medical diagnostics

Expert Opin Med Diagn

Advances in the diagnosis of anorexia nervosa and bulimia nervosa using brain imaging.

INTRODUCTION: Anorexia and bulimia nervosa are severe psychiatric disorders and the availability of brain imaging techniques hold promise that those techniques will be useful in clinical practice. AREAS COVERED: In this review I describe currently available brain imaging techniques and focus on the brain imaging methods functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Those techniques have helped describe alterations in brain circuitry in AN and BN that related to anxiety and reward processing. Novel computational models help further define brain function in relation to particular neurotransmitters. EXPERT OPINION: Brain imaging techniques are exciting methods to learn about brain function and progress has been made to identify in healthy populations brain circuits that code behaviors. These techniques have been used in AN and BN over the past decade and have improved our understanding of brain function in those disorders. Still, human brain imaging is not at a point yet where it could be used diagnostically. However, with the refinement of imaging hardware as well as improved models that describe brain function we will get closer to our aims to not only better understand the neurobiology of those disorders, but predict illness development, treatment response and long term prognosis.

CognitiveConstruct

RewardProcessing

10.1016/j.psyneuen.2012.08.001

Psychoneuroendocrinology

Psychoneuroendocrinology

Incentive processing in Congenital Adrenal Hyperplasia (CAH): a reward-based antisaccade study.

Little is known about how steroid hormones contribute to the beneficial effect of incentives on cognitive control during adolescent development. In this study, 27 adolescents with Congenital Adrenal Hyperplasia (CAH, mean age 15.6 years, 12 female), a disorder of cortisol deficiency and androgen excess, and 36 healthy participants (mean age 16.3 years, 18 female) completed a reward-based antisaccade task. In this mixed-saccade task, participants performed eye movements towards (prosaccades) or away (antisaccades) from a peripherally occuring stimulus. On incentive trials, monetary reward was provided for correct performance, while no such reward was provided on no-incentive trials. Consistent with the hypothesis, the results showed that healthy, but not CAH adolescents, significantly improved their inhibitory control (antisaccade accuracy) during incentive trials relative to no-incentive trials. These findings were not driven by severity of CAH (salt wasters vs. simple virilizers), individual hormone levels, sex, age-at-diagnosis, or medication type (dexamethasone vs. hydrocortisone). In addition, no significant differences between groups were found on orienting responses (prosaccades). Additional analyses revealed an impact of glucocorticoid (GC) dosage, such that higher GC dose predicted better antisaccade performance. However, this effect did not impact incentive processing. The data are discussed within the context of steroid hormone mediated effects on cognitive control and reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2012.08.002

Neuropsychologia

Neuropsychologia

Epistasis effects of dopamine genes on interval timing and reward magnitude in humans.

We tested human participants on a modified peak procedure in order to investigate the relation between interval timing and reward processing, and examine the interaction of this relation with three different dopamine-related gene polymorphisms. These gene polymorphisms affected the expression of catechol-o-methyltransferase, which catabolizes synaptic dopamine primarily in the prefrontal cortex (COMT Val158Met polymorphism), D2 dopamine receptors primarily in the striatum (DRD2/ANKK1-Taq1a polymorphism), and dopamine transporters, which clear synaptic dopamine in the striatum (DAT 3' VNTR variant). The inclusion of these polymorphisms allowed us to investigate dissociable aspects of the dopamine system and their interaction with reward magnitude manipulations in shaping timed behavior. These genes were chosen for their roles in reward processing and cortico-striatal information processing that have been implicated for interval timing. Consistent with recent animal studies, human participants initiated their timed anticipatory responding earlier when expecting a larger reward in the absence of any changes in the timing of response termination or perceived time. This effect however was specific to two out of four evaluated COMT and DRD2 polymorphism combinations that lead to high prefrontal dopamine coupled with high D2 density and low prefrontal dopamine coupled with low D2 density. Larger rewards also decreased timing precision indices, some of which interacted with the COMT polymorphism. Furthermore, the COMT polymorphism that leads to higher prefrontal dopamine resulted in weaker manifestation of memory variability (relative to threshold variability) in timed behavior. There was no effect of DAT polymorphisms on any of the core behavioral measures. These results suggest that the reward modulates decision thresholds rather than clock speed, and that these effects are specific to COMT and DRD2 epistasis effects that presumably constitute a balanced prefrontal and striatal dopamine transmission.

CognitiveConstruct

RewardProcessing

10.1080/15374416.2012.710162

Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53

J Clin Child Adolesc Psychol

Appetitive motivation and negative emotion reactivity among remitted depressed youth.

Depression has been characterized as involving altered appetitive motivation and emotional reactivity. Yet no study has examined objective indices of emotional reactivity when the appetitive/approach system is suppressed in response to failure to attain a self-relevant goal and desired reward. Three groups of youth (N = 98, ages 9-15; remitted depressed, n = 34; externalizing disordered without depression, n = 30; and healthy controls, n = 34) participated in a novel reward striving task designed to activate the appetitive/approach motivation system. Objective facial expressions of emotion were videotaped and coded throughout both failure (i.e., nonreward) and control (success and reward) conditions. Observational coding of facial expressions as well as youths' subjective emotion reports showed that the remitted depressed youth specifically exhibited more negative emotional reactivity to failure in the reward striving task, but not the control condition. Neither externalizing disordered (i.e., attention deficit hyperactivity disorder, conduct disorder, and/or oppositional defiant disorder) nor control youth displayed greater negative emotional reactivity in either the failure or control condition. Findings suggest that depression among youth is related to dysregulated appetitive motivation and associated negative emotional reactivity after failing to achieve an important, self-relevant goal and not attaining reward. These deficits in reward processing appear to be specific to depression as externalizing disordered youth did not display negative emotional reactivity to failure after their appetitive motivation system was activated.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2012.00218

Frontiers in human neuroscience

Front Hum Neurosci

Prediction-error in the context of real social relationships modulates reward system activity.

The human reward system is sensitive to both social (e.g., validation) and non-social rewards (e.g., money) and is likely integral for relationship development and reputation building. However, data is sparse on the question of whether implicit social reward processing meaningfully contributes to explicit social representations such as trust and attachment security in pre-existing relationships. This event-related fMRI experiment examined reward system prediction-error activity in response to a potent social reward-social validation-and this activity's relation to both attachment security and trust in the context of real romantic relationships. During the experiment, participants' expectations for their romantic partners' positive regard of them were confirmed (validated) or violated, in either positive or negative directions. Primary analyses were conducted using predefined regions of interest, the locations of which were taken from previously published research. Results indicate that activity for mid-brain and striatal reward system regions of interest was modulated by social reward expectation violation in ways consistent with prior research on reward prediction-error. Additionally, activity in the striatum during viewing of disconfirmatory information was associated with both increases in post-scan reports of attachment anxiety and decreases in post-scan trust, a finding that follows directly from representational models of attachment and trust.

CognitiveConstruct

RewardProcessing

10.1037/a0029600

Behavioral neuroscience

Behav Neurosci

Role of amygdala central nucleus in feature negative discriminations.

Consistent with a popular theory of associative learning, the Pearce-Hall (1980) model, the surprising omission of expected events enhances cue associability (the ease with which a cue may enter into new associations), across a wide variety of behavioral training procedures. Furthermore, previous experiments from this laboratory showed that these enhancements are absent in rats with impaired function of the amygdala central nucleus (CeA). A notable exception to these assertions is found in feature negative (FN) discrimination learning, in which a "target" stimulus is reinforced when it is presented alone but nonreinforced when it is presented in compound with another, "feature" stimulus. According to the Pearce-Hall model, reinforcer omission on compound trials should enhance the associability of the feature relative to control training conditions. However, prior experiments have shown no evidence that CeA lesions affect FN discrimination learning. Here we explored this apparent contradiction by evaluating the hypothesis that the surprising omission of an event confers enhanced associability on a cue only if that cue itself generates the disconfirmed prediction. Thus, in a FN discrimination, the surprising omission of the reinforcer on compound trials would enhance the associability of the target stimulus but not that of the feature. Our data confirmed this hypothesis and showed this enhancement to depend on intact CeA function, as in other procedures. The results are consistent with modern reformulations of both cue and reward processing theories that assign roles for both individual and aggregate error terms in associative learning.

CognitiveConstruct

RewardProcessing

Brain and nerve = Shinkei kenkyu no shinpo

Brain Nerve

[Roles of altered striatal function in major depression].

Major depression, a psychiatric disorder characterized by depressive mood and loss of interest and pleasure, is a leading cause of disability and suicide in developed countries. However, the mechanisms that underlie major depression remain to be elucidated. Clinical studies on patients with major depression have shown abnormalities in multiple brain areas, each of which can account for a distinct symptom or endophenotype. Notably, the striatum in healthy control subjects responds to positive emotional stimuli and to positive feedback signals during cognitive tasks, but these striatal responses are greatly reduced in depressive patients. Given the role of the striatum in behavioral learning with positive reinforcers, abnormalities as such suggest that impairment in reward processing and/or reinforcement learning in major depression is the basis of anhedonia and reduced psychomotor activity. In animal studies, stress -a risk factor for major depression- is frequently used to induce behavioral depression. Repeated social defeat stress increases the excitability of dopamine neurons and subsequent CREB-mediated transcription in the nucleus accumbens shell, leading to behavioral depression. Surprisingly, this pathway seems not to be involved in behavioral depression caused by prolonged social isolation, suggesting distinct mechanisms underlying the two stressful contexts. In contrast, ΔFosB-mediated gene expression in the nucleus accumbens shell confers resilience to stress. Repeated social defeat stress induces accumbal ΔFosB expression in a stress-resilient subset of individuals, whereas prolonged social isolation decreases this expression, leading to stress susceptibility. In addition to emotional changes, chronic stress also alters the mode of instrumental behavior from goal-directed to habitual responding, with consistent morphological changes in striatal subregions responsible for the corresponding behavioral modes. Therefore, these clinical and preclinical findings suggest that striatal abnormalities play a role in emotional and cognitive changes associated with major depression.

CognitiveConstruct

RewardProcessing

10.1001/archgenpsychiatry.2012.847

Archives of general psychiatry

Arch Gen Psychiatry

Improvement of brain reward abnormalities by antipsychotic monotherapy in schizophrenia.

CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE To investigate changes in reward-related brain activations in schizophrenia before and after antipsychotic monotherapy with a dopamine D2/D3 antagonist. DESIGN Longitudinal cohort study. SETTING Psychiatric inpatients and outpatients in the Capital Region of Denmark. PARTICIPANTS Twenty-three antipsychotic-naive patients with first-episode schizophrenia and 24 healthy controls initially matched on age, sex, and parental socioeconomic status were examined with functional magnetic resonance imaging while playing a variant of the monetary incentive delay task. INTERVENTIONS Patients were treated for 6 weeks with the antipsychotic compound amisulpride. Controls were followed up without treatment. MAIN OUTCOME MEASURES Task-related blood oxygen level-dependent activations as measured by functional magnetic resonance imaging before and after antipsychotic treatment. RESULTS At baseline, patients, as compared with controls, demonstrated an attenuation of brain activation during reward anticipation in the ventral striatum, bilaterally. After 6 weeks of treatment, patients showed an increase in the anticipation-related functional magnetic resonance imaging signal and were no longer statistically distinguishable from healthy controls. Among the patients, there was a correlation between the improvement of positive symptoms and normalization of reward-related activation. Those who showed the greatest clinical improvement in positive symptoms also showed the greatest increase in reward-related activation after treatment. CONCLUSIONS To our knowledge, this is the first controlled, longitudinal study of reward disturbances in schizophrenic patients before and after their first antipsychotic treatment. Our results demonstrate that alterations in reward processing are fundamental to the illness and are seen prior to any treatment. Antipsychotic treatment tends to normalize the response of the reward system; this was especially seen in the patients with the most pronounced treatment effect on the positive symptoms. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01154829.

CognitiveConstruct

RewardProcessing

10.1016/j.jpsychires.2012.07.013

Journal of psychiatric research

J Psychiatr Res

Prefrontal cortical thickness in depressed patients with high-risk for suicidal behavior.

Major depressive disorder (MDD) is associated with an increased risk for suicide. There is considerable evidence that a predisposition to suicidal behavior may exist which is independent of the MDD itself. Recent studies suggest a familial transmission of the diathesis for suicidal behavior, reflected in the observation of suicide aggregation in families and higher rate of suicidal behavior in first-degree relatives of suicide attempters with MDD. One of these transmission factors may be neurobiological alterations. The main goal of the present study was therefore to study abnormalities in cortical thickness in the hypothesized fronto-cingulate network in depressed patients with high risk for suicide. 15 MDD patients with documented own suicidal behavior and/or with suicidal behavior in first-degree relatives (high risk group), 15 depressed patients with non-high risk for suicide and 30 matched healthy controls participated in the study. Using an automated surface based approach (FreeSurfer) structural T1-weighted volumes were analyzed for differences in cortical thickness on a node by node basis covering the entire cortex. Patients with high risk for suicide showed significantly thinner cortex in the left dorsolateral, ventrolateral prefrontal cortex and the anterior cingulate in contrast to non-high risk patients. Together with previous morphometric results of our group, this new finding provides strong evidence for structural brain alterations in depressed patients with high risk for suicide in the fronto-cingulo-striatal network, which is strongly involved in reward processing and behavioral/emotional control. This alteration may constitute the neurobiological basis for an increased predisposition to suicidal behavior.

CognitiveConstruct

RewardProcessing

10.1080/17470919.2012.713316

Social neuroscience

Soc Neurosci

Attitude toward money modulates outcome processing: an ERP study.

Love of money (LOM) is concerned with the attitude toward money, which can be measured by the LOM scale through affective, behavioral, and cognitive dimensions. Research has observed that monetary attitude was tightly related to reward processing and could affect economic behavior. This study examined how monetary attitude modulated risky behavior and the underlying neural mechanisms of reward processing using event-related potential (ERP) technique. We compared both the risk level and brain responses of a high-level LOM (HLOM) group to a low-level LOM (LLOM) group using a simple gambling task. The behavioral results showed that the HLOM group was more risky than the LLOM group, particularly after loss. The feedback-related negativity (FRN) was measured as the difference wave (gain-related ERP was subtracted from loss-related ERP). The FRN difference wave was larger in the HLOM group than that in the LLOM group. The P3 in the HLOM group was more positive than that in the LLOM group. These results suggest that monetary attitude can modulate both the underlying neural mechanisms and behavioral performance in a reward-related task. The HLOM participants are more sensitive to gain/loss than the LLOM participants.

CognitiveConstruct

RewardProcessing

10.1007/s12402-012-0086-2

Attention deficit and hyperactivity disorders

Atten Defic Hyperact Disord

ADHD and autism: differential diagnosis or overlapping traits? A selective review.

According to DSM-IV TR and ICD-10, a diagnosis of autism or Asperger Syndrome precludes a diagnosis of attention-deficit/hyperactivity disorder (ADHD). However, despite the different conceptualization, population-based twin studies reported symptom overlap, and a recent epidemiologically based study reported a high rate of ADHD in autism and autism spectrum disorders (ASD). In the planned revision of the DSM-IV TR, dsm5 (www.dsm5.org), the diagnoses of autistic disorder and ADHD will not be mutually exclusive any longer. This provides the basis of more differentiated studies on overlap and distinction between both disorders. This review presents data on comorbidity rates and symptom overlap and discusses common and disorder-specific risk factors, including recent proteomic studies. Neuropsychological findings in the areas of attention, reward processing, and social cognition are then compared between both disorders, as these cognitive abilities show overlapping as well as specific impairment for one of both disorders. In addition, selective brain imaging findings are reported. Therapeutic options are summarized, and new approaches are discussed. The review concludes with a prospectus on open questions for research and clinical practice.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2012.00219

Frontiers in human neuroscience

Front Hum Neurosci

When unconscious rewards boost cognitive task performance inefficiently: the role of consciousness in integrating value and attainability information.

Research has shown that high vs. low value rewards improve cognitive task performance independent of whether they are perceived consciously or unconsciously. However, efficient performance in response to high value rewards also depends on whether or not rewards are attainable. This raises the question of whether unconscious reward processing enables people to take into account such attainability information. Building on a theoretical framework according to which conscious reward processing is required to enable higher level cognitive processing, the present research tested the hypothesis that conscious but not unconscious reward processing enables integration of reward value with attainability information. In two behavioral experiments, participants were exposed to mask high and low value coins serving as rewards on a working memory (WM) task. The likelihood for conscious processing was manipulated by presenting the coins relatively briefly (17 ms) or long and clearly visible (300 ms). Crucially, rewards were expected to be attainable or unattainable. Requirements to integrate reward value with attainability information varied across experiments. Results showed that when integration of value and attainability was required (Experiment 1), long reward presentation led to efficient performance, i.e., selectively improved performance for high value attainable rewards. In contrast, in the short presentation condition, performance was increased for high value rewards even when these were unattainable. This difference between the effects of long and short presentation time disappeared when integration of value and attainability information was not required (Experiment 2). Together these findings suggest that unconsciously processed reward information is not integrated with attainability expectancies, causing inefficient effort investment. These findings are discussed in terms of a unique role of consciousness in efficient allocation of effort to cognitive control processes.

CognitiveConstruct

RewardProcessing

The Hastings law journal

Hastings Law J

The Relevance of Immaturities in the Juvenile Brain to Culpability and Rehabilitation.

The overreaching aim of this Article is to describe how developmental cognitive neuroscience can inform juvenile law. Fundamental to culpability and responsibility is the ability to effectively execute voluntary executive behavior. Executive function, including cognitive control and working memory, has a protracted development with key aspects continuing to mature through adolescence. These limitations in executive control are due in great part to still maturing brain processes. Gray and white matter changes are still becoming established in adolescence, enhancing efficiency and the speed of brain processing supporting executive control. Dopamine, a neurotransmitter that underlies reward processing and learning, peaks in adolescence-supporting known increases in sensation seeking but also in adaptable learning. Functional Magnetic Resonance Imaging ("fMRI") studies show that adolescent limitations in recruiting brain systems that support response planning, error processing, the ability to sustain an executive state, and top-down prefrontal executive control of behavior underlie limitations in executive control in adolescence. Moreover, adolescents show over-reactivity to reward incentives, thus engaging response systems that may contribute to impulsive responses in situations with high motivation. Neurobiological evidence indicating that adolescence is a transitional stage of limited executive control in the context of increased vulnerability to sensation seeking can inform culpability, long-term sentencing, and greater amenability for rehabilitation. Finally, it is important to note that executive control, while limited in its efficiency, is available in adolescence, and given time to deliberate with guidance from mature adults, adolescents can make responsible decisions.

CognitiveConstruct

RewardProcessing

10.1016/j.celrep.2012.05.011

Cell reports

Cell Rep

Selective activation of cholinergic interneurons enhances accumbal phasic dopamine release: setting the tone for reward processing.

Dopamine plays a critical role in motor control, addiction, and reward-seeking behaviors, and its release dynamics have traditionally been linked to changes in midbrain dopamine neuron activity. Here, we report that selective endogenous cholinergic activation achieved via in vitro optogenetic stimulation of nucleus accumbens, a terminal field of dopaminergic neurons, elicits real-time dopamine release. This mechanism occurs via direct actions on dopamine terminals, does not require changes in neuron firing within the midbrain, and is dependent on glutamatergic receptor activity. More importantly, we demonstrate that in vivo selective activation of cholinergic interneurons is sufficient to elicit dopamine release in the nucleus accumbens. Therefore, the control of accumbal extracellular dopamine levels by endogenous cholinergic activity results from a complex convergence of neurotransmitter/neuromodulator systems that may ultimately synergize to drive motivated behavior.

CognitiveConstruct

RewardProcessing

10.1152/jn.00070.2012

Journal of neurophysiology

J Neurophysiol

Reward processing: a global brain phenomenon?

Rewards and punishments (reinforcement) powerfully shape behavior. Accordingly, their neuronal representation is of significant interest, both for understanding normal brain-behavior relationships and the pathophysiology of disorders such as depression and addiction. A recent article by Vickery and colleagues (Neuron 72: 166-177, 2011) provides evidence that the neural response to rewards and punishments is surprisingly widespread, suggesting the need for examination of the specific roles of areas not commonly included in the canonical reward circuitry in processing reinforcement.

CognitiveConstruct

RewardProcessing

10.1038/nature11304

Nature

Nature

A subset of dopamine neurons signals reward for odour memory in Drosophila.

Animals approach stimuli that predict a pleasant outcome. After the paired presentation of an odour and a reward, Drosophila melanogaster can develop a conditioned approach towards that odour. Despite recent advances in understanding the neural circuits for associative memory and appetitive motivation, the cellular mechanisms for reward processing in the fly brain are unknown. Here we show that a group of dopamine neurons in the protocerebral anterior medial (PAM) cluster signals sugar reward by transient activation and inactivation of target neurons in intact behaving flies. These dopamine neurons are selectively required for the reinforcing property of, but not a reflexive response to, the sugar stimulus. In vivo calcium imaging revealed that these neurons are activated by sugar ingestion and the activation is increased on starvation. The output sites of the PAM neurons are mainly localized to the medial lobes of the mushroom bodies (MBs), where appetitive olfactory associative memory is formed. We therefore propose that the PAM cluster neurons endow a positive predictive value to the odour in the MBs. Dopamine in insects is known to mediate aversive reinforcement signals. Our results highlight the cellular specificity underlying the various roles of dopamine and the importance of spatially segregated local circuits within the MBs.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2011.10.002

Psychiatry research

Psychiatry Res

Early orbitofrontal hyperactivation in obsessive-compulsive disorder.

Dysfunctional activity in the orbitofrontal cortex (OFC) is one of the core features in the pathophysiology of obsessive-compulsive disorder (OCD). Neuroimaging studies indicate orbitofrontal hyperactivation during the resting state as well as during symptom provocation, whereas orbitofrontal hypoactivation has been reported during tasks designed to dissociate specific cognitive processes. Combined magnetoencephalic and functional magnetic resonance imaging studies show early involvement of the OFC in stimulus processing in healthy subjects. However, it is unclear whether OFC activation is dysfunctional at an early stage in patients with OCD. We investigated early electrical OFC activation evoked by reward and punishment feedback in a visual probabilistic object reversal task (pORT). Patients with OCD (n=23) and healthy controls (n=27), matched for gender, age and educational level, performed the pORT during a 29-channel electroencephalographic recording. Low resolution brain electromagnetic tomography was applied to localize orbitofrontal sources of neuronal activity at 80 to 200 ms post-stimulus. Group comparison showed significantly higher orbitofrontal activation in OCD patients at 100-120 ms after the reward stimulus. No group differences were found with respect to OFC activation in response to punishment stimuli and in task performance. Results substantiate dysfunctional OFC activity at a very early stage in the processing of reward stimuli in patients with OCD. Our results provide support for the assumption that the OFC plays a more active role in the processing of visual stimuli as previously supposed. As orbitofrontal hyperactivation following rewarding feedback occurred as early as 100 ms after receipt of the visual stimulus in patients with OCD, and as we did not find any OFC dysfunction following negative feedback, our findings may point towards a specific early disturbance of reward processing in OCD. This finding might have implications for cognitive behavioural therapy of this disorder.

CognitiveConstruct

RewardProcessing

10.1017/S0954579412000272

Development and psychopathology

Dev Psychopathol

The neurobiology of oppositional defiant disorder and conduct disorder: altered functioning in three mental domains.

This review discusses neurobiological studies of oppositional defiant disorder and conduct disorder within the conceptual framework of three interrelated mental domains: punishment processing, reward processing, and cognitive control. First, impaired fear conditioning, reduced cortisol reactivity to stress, amygdala hyporeactivity to negative stimuli, and altered serotonin and noradrenaline neurotransmission suggest low punishment sensitivity, which may compromise the ability of children and adolescents to make associations between inappropriate behaviors and forthcoming punishments. Second, sympathetic nervous system hyporeactivity to incentives, low basal heart rate associated with sensation seeking, orbitofrontal cortex hyporeactiviy to reward, and altered dopamine functioning suggest a hyposensitivity to reward. The associated unpleasant emotional state may make children and adolescents prone to sensation-seeking behavior such as rule breaking, delinquency, and substance abuse. Third, impairments in executive functions, especially when motivational factors are involved, as well as structural deficits and impaired functioning of the paralimbic system encompassing the orbitofrontal and cingulate cortex, suggest impaired cognitive control over emotional behavior. In the discussion we argue that more insight into the neurobiology of oppositional defiance disorder and conduct disorder may be obtained by studying these disorders separately and by paying attention to the heterogeneity of symptoms within each disorder.

CognitiveConstruct

RewardProcessing

10.1159/000337130

Neuropsychobiology

Neuropsychobiology

Ventral striatal activation during reward processing in subjects with ultra-high risk for schizophrenia.

Early dysfunction of the brain reward system in schizophrenia might be already recognized in the prodromal phase of this illness. We used functional magnetic resonance imaging to assess the blood oxygen level-dependent response in the ventral striatum (VS) of subjects with ultra-high risk for psychosis during the presentation of reward-indicating and loss-indicating stimuli. Thirteen prodromal patients (mean age: 25.5 ± 4.6 years) and 13 age-matched healthy volunteers participated in an incentive monetary delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus will gain money, avoid losing money or have no consequence. Compared with the neutral condition, anticipation of reward loss-avoidance elicited significant activation of the VS in both healthy subjects and subjects with ultra-high risk for psychosis, but there was only a statistical tendency for less activation during loss-avoidance anticipation in prodromal compared to healthy subjects. This study provides a first weak hint, as revealed by functional magnetic resonance imaging, for impaired activation of a central area of the mesolimbic dopaminergic brain reward system, the VS, already in subjects with ultra-high risk for psychosis, which is in line with results of patients with full-blown schizophrenic psychosis. This pilot study has, however, strong limitations, and its results need to be replicated first before they can be used e.g. for early recognition of patients in the schizophrenic prodrome.

CognitiveConstruct

RewardProcessing

10.1007/s10567-012-0118-7

Clinical child and family psychology review

Clin Child Fam Psychol Rev

Impaired neurocognitive functions affect social learning processes in oppositional defiant disorder and conduct disorder: implications for interventions.

In this review, a conceptualization of oppositional defiant (ODD) and conduct disorder (CD) is presented according to which social learning processes in these disorders are affected by neurocognitive dysfunctions. Neurobiological studies in ODD and CD suggest that the ability to make associations between behaviors and negative and positive consequences is compromised in children and adolescents with these disorders due to reduced sensitivity to punishment and to reward. As a result, both learning of appropriate behavior and learning to refrain from inappropriate behavior may be affected. Likewise, problem solving is impaired due to deficiencies in inhibition, attention, cognitive flexibility, and decision making. Consequently, children and adolescents with ODD and CD may have difficulty learning to optimize their behavior in changeable environments. This conceptualization of ODD and CD is relevant for the improvement of the effect of psychological treatments. Behavioral and cognitive-behavioral interventions that have been shown to be modestly effective in ODD and CD are based on social learning. Limited effectiveness of these interventions may be caused by difficulties in social learning in children and adolescents with ODD and CD. However, although these impairments have been observed at a group level, the deficits in reward processing, punishment processing, and cognitive control mentioned above may not be present to the same extent in each individual with ODD and CD. Therefore, the neurocognitive characteristics in children and adolescents with ODD and CD should be assessed individually. Thus, instead of delivering interventions in a standardized way, these programs may benefit from an individualized approach that depends on the weaknesses and strengths of the neurocognitive characteristics of the child and the adolescent.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2012.00204

Frontiers in human neuroscience

Front Hum Neurosci

Neural correlates of feedback processing in decision-making under risk.

Event-related brain potentials (ERPs) provide important information about the sensitivity of the brain to process varying risks. The aim of the present study was to determine how different risk levels are reflected in decision-related ERPs, namely the feedback-related negativity (FRN) and the P300. Twenty participants conducted a probabilistic two-choice gambling task while an electroencephalogram (EEG) was recorded. Choices were provided between a low-risk option yielding low rewards and low losses and a high-risk option yielding high rewards and high losses. While options differed in expected risks, they were equal in expected values and in feedback probabilities. At the behavioral level, participants were generally risk-averse but modulated their risk-taking behavior according to reward history. An early positivity (P200) was enhanced on negative feedbacks in high-risk compared to low-risk choices. With regard to the FRN, there were significant amplitude differences between positive and negative feedbacks on high-risk choices, but not on low-risk choices. While the FRN on negative feedbacks did not vary with decision riskiness, reduced amplitudes were found for positive feedbacks in high-risk relative to low-risk choices. P300 amplitudes were larger in high-risk decisions, and in an additive way, after negative compared to positive feedback. The present study revealed significant influences of risk and valence processing on ERPs. FRN findings suggest that the reward prediction error signal is increased after high-risk decisions. The increased P200 on negative feedback in risky decisions suggests that large negative prediction errors are already processed in the P200 time range. The later P300 amplitude is sensitive to feedback valence as well as to the risk associated with a decision. Thus, the P300 carries additional information for reward processing, mainly the enhanced motivational significance of risky decisions.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2012.00036

Frontiers in behavioral neuroscience

Front Behav Neurosci

Monitoring extracellular pH, oxygen, and dopamine during reward delivery in the striatum of primates.

Dopamine projections that extend from the ventral tegmental area to the striatum have been implicated in the biological basis for behaviors associated with reward and addiction. Until recently, it has been difficult to evaluate the complex balance of energy utilization and neural activity in the striatum. Many techniques such as electrophysiology, functional magnetic resonance imaging (fMRI), and fast-scan cyclic voltammetry have been employed to monitor these neurochemical and neurophysiological changes. In this brain region, physiological responses to cues and rewards cause local, transient pH changes. Oxygen and pH are coupled in the brain through a complex system of blood flow and metabolism as a result of transient neural activity. Indeed, this balance is at the heart of imaging studies such as fMRI. To this end, we measured pH and O(2) changes with fast-scan cyclic voltammetry in the striatum as indices of changes in metabolism and blood flow in vivo in three Macaca mulatta monkeys during reward-based behaviors. Specifically, the animals were presented with Pavlovian conditioned cues that predicted different probabilities of liquid reward. They also received free reward without predictive cues. The primary detected change consisted of pH shifts in the striatal extracellular environment following the reward predicting cues or the free reward. We observed three types of cue responses that consisted of purely basic pH shifts, basic pH shifts followed by acidic pH shifts, and purely acidic pH shifts. These responses increased with reward probability, but were not significantly different from each other. The pH changes were accompanied by increases in extracellular O(2). The changes in pH and extracellular O(2) are consistent with current theories of metabolism and blood flow. However, they were of sufficient magnitude that they masked dopamine changes in the majority of cases. The findings suggest a role of these chemical responses in neuronal reward processing.

CognitiveConstruct

RewardProcessing

10.3758/s13415-012-0104-z

Cognitive, affective & behavioral neuroscience

Cogn Affect Behav Neurosci

Better late than never? The effect of feedback delay on ERP indices of reward processing.

The feedback negativity (FN), an early neural response that differentiates rewards from losses, appears to be generated in part by reward circuits in the brain. A prominent model of the FN suggests that it reflects learning processes by which environmental feedback shapes behavior. Although there is evidence that human behavior is more strongly influenced by rewards that quickly follow actions, in nonlaboratory settings, optimal behaviors are not always followed by immediate rewards. However, it is not clear how the introduction of a delay between response selection and feedback impacts the FN. Thus, the present study used a simple forced choice gambling task to elicit the FN, in which feedback about rewards and losses was presented after either 1 or 6 s. Results suggest that, at short delays (1 s), participants clearly differentiated losses from rewards, as evidenced in the magnitude of the FN. At long delays (6 s), on the other hand, the difference between losses and rewards was negligible. Results are discussed in terms of eligibility traces and the reinforcement learning model of the FN.

CognitiveConstruct

RewardProcessing

10.1016/j.euroneuro.2012.05.011

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Eur Neuropsychopharmacol

The dopamine transporter haplotype and reward-related striatal responses in adult ADHD.

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable disorder and several genes increasing disease risk have been identified. The dopamine transporter gene, SLC6A3/DAT1, has been studied most extensively in ADHD research. Interestingly, a different haplotype of this gene (formed by genetic variants in the 3' untranslated region and intron 8) is associated with childhood ADHD (haplotype 10-6) and adult ADHD (haplotype 9-6). The expression of DAT1 is highest in striatal regions in the brain. This part of the brain is of interest to ADHD because of its role in reward processing is altered in ADHD patients; ADHD patients display decreased striatal activation during reward processing. To better understand how the DAT1 gene exerts effects on ADHD, we studied the effect of this gene on reward-related brain functioning in the area of its highest expression in the brain, the striatum, using functional magnetic resonance imaging. In doing so, we tried to resolve inconsistencies observed in previous studies of healthy individuals and ADHD-affected children. In a sample of 87 adult ADHD patients and 77 healthy comparison subjects, we confirmed the association of the 9-6 haplotype with adult ADHD. Striatal hypoactivation during the reward anticipation phase of a monetary incentive delay task in ADHD patients was again shown, but no significant effects of DAT1 on striatal activity were found. Although the importance of the DAT1 haplotype as a risk factor for adult ADHD was again demonstrated in this study, the mechanism by which this gene increases disease risk remains largely unknown.

CognitiveConstruct

RewardProcessing

10.1016/j.alcohol.2011.11.008

Alcohol (Fayetteville, N.Y.)

Alcohol

Effects of exposure to moderate levels of ethanol during prenatal brain development on dendritic length, branching, and spine density in the nucleus accumbens and dorsal striatum of adult rats.

Reductions in measures of dendritic morphology in the agranular insular cortex have been identified as consequences of prenatal exposure to moderate levels of ethanol in the rat. Motivated by the strong connectivity between this region of frontal cortex and the striatum and a growing body of data linking specific components of the mesocortical/limbic system to effects of ethanol and ethanol self-administration, the current study investigated the effects of moderate fetal ethanol exposure on the dendritic morphology of medium spiny neurons (MSNs) in several regions of the striatum. Throughout gestation, pregnant rat dams either consumed a saccharin solution (control) or achieved average daily blood ethanol concentrations of 84 mg% via voluntary consumption of a 5% ethanol solution. The brains of adult male offspring were extracted and processed for Golgi-Cox staining. MSNs from the dorsomedial striatum, dorsolateral striatum and the nucleus accumbens core and shell were sampled for analysis. Relative to saccharin controls, robust reductions in dendritic length and branching, but not spine density, were observed in the shell of the nucleus accumbens in fetal-ethanol-exposed rats. No significant prenatal ethanol effects were found in the other regions of the striatum. These findings suggest that exposure to moderate levels of ethanol in utero can have profound effects on brain regions related to reward processing and provide possible clues relevant to understanding increased self-administration of drugs of abuse in animals exposed to ethanol during brain development.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2012.02.029

Biological psychiatry

Biol Psychiatry

Neuroeconomics: a bridge for translational research.

Neuroeconomic methods combine behavioral economic experiments to parameterize aspects of reward-related decision-making with neuroimaging techniques to record corresponding brain activity. In this introductory article to the current special issue, we propose that neuroeconomics is a potential bridge for translational research in psychiatry for several reasons. First, neuroeconomics-derived theoretical predictions about optimal adaptation in a changing environment provide an objective metric to examine psychopathology. Second, neuroeconomics provides a "multilevel" research approach that combines performance (behavioral) measures with intermediate measures between behavior and neurobiology (e.g., neuroimaging) and uses a common metaphor to describe decision-making across multiple levels of explanation. As such, ecologically valid behavioral paradigms closely mirror the physical mechanisms of reward processing. Third, neuroeconomics provides a platform for investigators from neuroscience, economics, psychiatry, and social and clinical psychology to develop a common language for studying reward-related decision making in psychiatric disorders. Therefore, neuroeconomics can provide promising candidate endophenotypes that might help clarify the basis of high heritability associated with psychiatric disorders and that might, in turn, inform treatment.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0039135

PloS one

PLoS One

DAT1 polymorphism is associated with risk taking in the Balloon Analogue Risk Task (BART).

Twin-studies suggest that a significant portion of individual differences in the propensity to take risks resides in people's genetic make-up and there is evidence that variability in dopaminergic systems relates to individual differences in risky choice. We examined the link between risk taking in a risk taking task (the Balloon Analogue Risk Task, BART) and a variable number tandem repeat (VNTR) polymorphism in the 3'UTR of the dopamine transporter gene (SLC6A3/DAT1). Behavior in BART is known to be associated with activity in striatal reward-processing regions, and DAT1 is assumed to modulate striatal dopamine levels. We find that carriers of DAT1 alleles, which presumably result in lower striatal dopamine availability, showed more risk taking, relative to carriers of the alleles associated with higher striatal dopamine availability. Our analyses suggest that the mechanism underlying this association is diminished sensitivity to rewards among those who take more risks. Overall, our results support the notion that a behavioral genetic approach can be helpful in uncovering the basis of individual differences in risk taking.

CognitiveConstruct

RewardProcessing

10.1016/j.jaac.2012.05.006

Journal of the American Academy of Child and Adolescent Psychiatry

J Am Acad Child Adolesc Psychiatry

Striatal sensitivity during reward processing in attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) has been linked to deficits in the dopaminergic reward-processing circuitry; yet, existing evidence is limited, and the influence of genetic variation affecting dopamine signaling remains unknown. We investigated striatal responsivity to rewards in ADHD combined type (ADHD-CT) using functional magnetic resonance imaging (fMRI), and whether it is modulated by variation in the dopamine transporter gene (DAT1). We tested 29 male adolescents with ADHD-CT and 30 age-, handedness-, and gender-matched healthy controls who were selected for DAT1(10/6) haplotype dosage. Based on previous research, we focused our analysis on the ventral striatum and the caudate nucleus. Three main findings emerged. First, male adolescents with ADHD-CT did not differ from controls in terms of blood oxygen-level dependent (BOLD) fMRI response to reward-predicting cues (gain or loss-avoidance) in the ventral striatum. Second, male adolescents with ADHD-CT showed a relative increase, compared with controls, in the striatal BOLD response to successful outcomes. Third, DAT1(10/6) dosage differentially modulated neural activation to reward-predicting cues in the caudate nucleus in the ADHD-CT and control groups. The findings challenge the idea of a deficit in anticipation-related activation in the ventral striatum in male adolescents with ADHD-CT, while suggesting that the processing of reward outcomes is dysfunctional, consistent with a recent neurobiological model of the disorder. Preliminary evidence suggests that polymorphic variations in genes affecting dopamine signaling need to be taken into consideration when investigating reward-related deficits in ADHD-CT.

CognitiveConstruct

RewardProcessing

10.1016/j.cortex.2012.05.008

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

Cortex

Value and prediction error estimation account for volatility effects in ACC: a model-based fMRI study.

In order to choose the best action for maximizing fitness, mammals can estimate the reward expectations (value) linked to available actions based on past environmental outcomes. Value updates are performed by comparing the current value with the actual environmental outcomes (prediction error). The anterior cingulate cortex (ACC) has been shown to be critically involved in the computation of value and its variability across time (volatility). Previously, we proposed a new neural model of the ACC based on single-unit ACC neurophysiology, the Reward Value and Prediction Model (RVPM). Here, using the RVPM in computer simulations and in a model-based fMRI study, we found that highly uncertain but non-volatile environments activate ACC more than volatile environments, demonstrating that value estimation by means of prediction error computation can account for the effect of volatility in ACC. These findings suggest that ACC response to volatility can be parsimoniously explained by basic ACC reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2012.06.004

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

Int J Psychophysiol

Brain potentials in outcome evaluation: when social comparison takes effect.

Social comparison, in which people evaluate their opinions and abilities by comparing them with the opinions and abilities of others, is a central feature of human social life. Previous work has highlighted the importance of social comparison in reward processing. However, the time-course of the social comparison effect in outcome evaluation remains largely unknown. The purpose of this study was to explore to what extent brain activity is modulated by social comparison between an individual and their anonymous partner. Event-related potentials (ERPs) were measured while the participants viewed their own and their partner's gain and loss outcomes based on their performance in a dot estimation task. Analysis of ERPs revealed that the feedback-related negativity (FRN) amplitude differences between gains and losses were not modulated by social comparison. In contrast, the P300 was larger for gains and showed an effect of social comparison independent of feedback valence. A late component, the late positive potential (LPP), was also modulated by social comparison, but it was insensitive to feedback valence. The data suggest that social comparison modulates outcome evaluation at several points in the information processing stream. Social comparison has no effect on the early coarse evaluation stage, but modulates the late cognitive/affective appraisal and re-appraisal processes. These findings provide neurophysiological evidence for the importance of social comparisons in outcome evaluations by the human brain.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.6237-11.2012

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

J Neurosci

Neural correlates of specific and general Pavlovian-to-Instrumental Transfer within human amygdalar subregions: a high-resolution fMRI study.

It is widely held that the interaction between instrumental and Pavlovian conditioning induces powerful motivational biases. Pavlovian-Instrumental Transfer (PIT) is one of the key paradigms demonstrating this effect, which can further be decomposed into a general and specific component. Although these two forms of PIT have been studied at the level of amygdalar subregions in rodents, it is still unknown whether they involve different areas of the human amygdala. Using a high-resolution fMRI (hr-fMRI) protocol optimized for the amygdala in combination with a novel free operant task designed to elicit effects of both general and specific PIT, we demonstrate that a region of ventral amygdala within the boundaries of the basolateral complex and the ventrolateral putamen are involved in specific PIT, while a region of dorsal amygdala within the boundaries of the centromedial complex is involved in general PIT. These results add to a burgeoning literature indicating different functional contributions for these different amygdalar subregions in reward-processing and motivation.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2012.05.008

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

Learning from experience: event-related potential correlates of reward processing, neural adaptation, and behavioral choice.

To behave adaptively, we must learn from the consequences of our actions. Studies using event-related potentials (ERPs) have been informative with respect to the question of how such learning occurs. These studies have revealed a frontocentral negativity termed the feedback-related negativity (FRN) that appears after negative feedback. According to one prominent theory, the FRN tracks the difference between the values of actual and expected outcomes, or reward prediction errors. As such, the FRN provides a tool for studying reward valuation and decision making. We begin this review by examining the neural significance of the FRN. We then examine its functional significance. To understand the cognitive processes that occur when the FRN is generated, we explore variables that influence its appearance and amplitude. Specifically, we evaluate four hypotheses: (1) the FRN encodes a quantitative reward prediction error; (2) the FRN is evoked by outcomes and by stimuli that predict outcomes; (3) the FRN and behavior change with experience; and (4) the system that produces the FRN is maximally engaged by volitional actions.

CognitiveConstruct

RewardProcessing

10.1016/j.nbd.2012.05.007

Neurobiology of disease

Neurobiol Dis

Neurogenetics of depression: a focus on reward processing and stress sensitivity.

Major depressive disorder (MDD) is etiologically complex and has a heterogeneous presentation. This heterogeneity hinders the ability of molecular genetic research to reliably detect the small effects conferred by common genetic variation. As a result, significant research efforts have been directed at investigating more homogenous intermediate phenotypes believed to be more proximal to gene function and lie between genes and/or environmental effects and disease processes. In the current review we survey and integrate research on two promising intermediate phenotypes linked to depression: reward processing and stress sensitivity. A synthesis of this burgeoning literature indicates that a molecular genetic approach focused on intermediate phenotypes holds significant promise to fundamentally improve our understanding of the pathophysiology and etiology of depression, which will be required for improved diagnostic definitions and the development of novel and more efficacious treatment and prevention strategies. We conclude by highlighting challenges facing intermediate phenotype research and future development that will be required to propel this pivotal research into new directions.

CognitiveConstruct

RewardProcessing

10.1093/cercor/bhs136

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

Cereb Cortex

Dopamine-dependent architecture of cortico-subcortical network connectivity.

Maladaptive dopaminergic mediation of reward processing in humans is thought to underlie multiple neuropsychiatric disorders, including addiction, Parkinson's disease, and schizophrenia. Mechanisms responsible for the development of such disorders may depend on individual differences in neural signaling within large-scale cortico-subcortical circuitry. Using a combination of functional neuroimaging and pharmacological challenges in healthy volunteers, we identified opposing dopamine agonistic and antagonistic neuromodulatory effects on distributed functional interactions between specific subcortical regions and corresponding neocortical "resting-state" networks, known to be involved in distinct aspects of cognition and reward processing. We found that, relative to a placebo, levodopa and haloperidol challenges, respectively, increased or decreased the functional connectivity between (1) the midbrain and a "default mode" network, (2) the right caudate and a right-lateralized frontoparietal network, and (3) the ventral striatum and a fronto-insular network. Further, we found drug-specific associations between brain circuitry reactivity to dopamine modulation and individual differences in trait impulsivity, revealing dissociable drug-personality interaction effects across distinct dopamine-dependent cortico-subcortical networks. Our findings identify possible systems underlying pathogenesis and treatment efficacy in disorders of dopamine deficiency.

CognitiveConstruct

RewardProcessing

10.1080/02791072.2012.662859

Journal of psychoactive drugs

J Psychoactive Drugs

Behavioral addictions: an overview.

The legitimacy of nonsubstance addictions has received increased attention from clinicians, researchers and the general population as more and more individuals report symptoms consistent with impairment of impulse control. The clinical presentation of these disorders is varied, as compulsive activities may include: gambling, eating, sex, shopping, use of the Internet or videogames or even exercising, working or falling in love. As such, there is great controversy in diagnosing, treating or even naming these conditions, as many of these behaviors are daily rituals instrumental to our ultimate survival. Historically, the phrase "impulse control disorders" described these conditions but many researchers and clinicians also use the term "behavioral addictions," "process addictions" or "impulsive-compulsive behaviors" to report behavioral pathology. This review summarizes the data of each of these behavioral addictions from epidemiology to neurobiology to treatment options. Research suggests similarities between natural and drug reward processing but clinical evidence supports the utilization of treatment modalities for these behavioral conditions that can sometimes differ from traditional drug treatment.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0036572

PloS one

PLoS One

Deep brain stimulation of nucleus accumbens region in alcoholism affects reward processing.

The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H(2)[(15)O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction. Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated. These findings suggest that DBS of the NAcc may act partially by improving behavioral control.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0037306

PloS one

PLoS One

The neural basis of decision-making and reward processing in adults with euthymic bipolar disorder or attention-deficit/hyperactivity disorder (ADHD).

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) share DSM-IV criteria in adults and cause problems in decision-making. Nevertheless, no previous report has assessed a decision-making task that includes the examination of the neural correlates of reward and gambling in adults with ADHD and those with BD. We used the Iowa gambling task (IGT), a task of rational decision-making under risk (RDMUR) and a rapid-decision gambling task (RDGT) which elicits behavioral measures as well as event-related potentials (ERPs: fERN and P3) in connection to the motivational impact of events. We did not observe between-group differences for decision-making under risk or ambiguity (RDMUR and IGT); however, there were significant differences for the ERP-assessed RDGT. Compared to controls, the ADHD group showed a pattern of impaired learning by feedback (fERN) and insensitivity to reward magnitude (P3). This ERP pattern (fERN and P3) was associated with impulsivity, hyperactivity, executive function and working memory. Compared to controls, the BD group showed fERN- and P3-enhanced responses to reward magnitude regardless of valence. This ERP pattern (fERN and P3) was associated with mood and inhibitory control. Consistent with the ERP findings, an analysis of source location revealed reduced responses of the cingulate cortex to the valence and magnitude of rewards in patients with ADHD and BD. Our data suggest that neurophysiological (ERPs) paradigms such as the RDGT are well suited to assess subclinical decision-making processes in patients with ADHD and BD as well as for linking the cingulate cortex with action monitoring systems.

CognitiveConstruct

RewardProcessing

10.1017/S0033291712001158

Psychological medicine

Psychol Med

'The risks of playing it safe': a prospective longitudinal study of response to reward in the adolescent offspring of depressed parents.

Alterations in reward processing may represent an early vulnerability factor for the development of depressive disorder. Depression in adults is associated with reward hyposensitivity and diminished reward seeking may also be a feature of depression in children and adolescents. We examined the role of reward responding in predicting depressive symptoms, functional impairment and new-onset depressive disorder over time in the adolescent offspring of depressed parents. In addition, we examined group differences in reward responding between currently depressed adolescents, psychiatric and healthy controls, and also cross-sectional associations between reward responding and measures of positive social/environmental functioning. Method We conducted a 1-year longitudinal study of adolescents at familial risk for depression (n = 197; age range 10-18 years). Reward responding and self-reported social/environmental functioning were assessed at baseline. Clinical interviews determined diagnostic status at baseline and at follow-up. Reports of depressive symptoms and functional impairment were also obtained. Low reward seeking predicted depressive symptoms and new-onset depressive disorder at the 1-year follow-up in individuals free from depressive disorder at baseline, independently of baseline depressive symptoms. Reduced reward seeking also predicted functional impairment. Adolescents with current depressive disorder were less reward seeking (i.e. bet less at favourable odds) than adolescents free from psychopathology and those with externalizing disorders. Reward seeking showed positive associations with social and environmental functioning (extra-curricular activities, humour, friendships) and was negatively associated with anhedonia. There were no group differences in impulsivity, decision making or psychomotor slowing. Reward seeking predicts depression severity and onset in adolescents at elevated risk of depression. Adaptive reward responses may be amenable to change through modification of existing preventive psychological interventions.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0034917

PloS one

PLoS One

Reward-related dorsal striatal activity differences between former and current cocaine dependent individuals during an interactive competitive game.

Cocaine addiction is characterized by impulsivity, impaired social relationships, and abnormal mesocorticolimbic reward processing, but their interrelationships relative to stages of cocaine addiction are unclear. We assessed blood-oxygenation-level dependent (BOLD) signal in ventral and dorsal striatum during functional magnetic resonance imaging (fMRI) in current (CCD; n = 30) and former (FCD; n = 28) cocaine dependent subjects as well as healthy control (HC; n = 31) subjects while playing an interactive competitive Domino game involving risk-taking and reward/punishment processing. Out-of-scanner impulsivity-related measures were also collected. Although both FCD and CCD subjects scored significantly higher on impulsivity-related measures than did HC subjects, only FCD subjects had differences in striatal activation, specifically showing hypoactivation during their response to gains versus losses in right dorsal caudate, a brain region linked to habituation, cocaine craving and addiction maintenance. Right caudate activity in FCD subjects also correlated negatively with impulsivity-related measures of self-reported compulsivity and sensitivity to reward. These findings suggest that remitted cocaine dependence is associated with striatal dysfunction during social reward processing in a manner linked to compulsivity and reward sensitivity measures. Future research should investigate the extent to which such differences might reflect underlying vulnerabilities linked to cocaine-using propensities (e.g., relapses).

CognitiveConstruct

RewardProcessing

10.1111/j.1460-9568.2012.08125.x

The European journal of neuroscience

Eur J Neurosci

Dissociation of BOLD responses to reward prediction errors and reward receipt by a model comparison.

The representation of reward anticipation and reward prediction errors is the basis for reward-associated learning. The representation of whether or not a reward occurred (reward receipt) is important for decision making. Recent studies suggest that, while reward anticipation and reward prediction errors are encoded in the midbrain and the ventral striatum, reward receipts are encoded in the medial orbitofrontal cortex. In order to substantiate this functional specialization we analyzed data from an fMRI study in which 59 subjects completed two simple monetary reward paradigms. Because reward receipts and reward prediction errors were correlated, a statistical model comparison was applied separating the effects of the two. Reward prediction error fitted BOLD responses significantly better than reward receipt in the midbrain and the ventral striatum. Conversely, reward receipt fitted BOLD responses better in the orbitofrontal cortex. Activation related to reward anticipation was found in the orbitofrontal cortex. The results confirm a functional specialization of behaviorally important aspects of reward processing within the mesolimbic dopaminergic system.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2012.04.002

Developmental cognitive neuroscience

Dev Cogn Neurosci

Developmental effects of decision-making on sensitivity to reward: an fMRI study.

Studies comparing neural correlates of reward processing across development yield inconsistent findings. This challenges theories characterizing adolescents as globally hypo- or hypersensitive to rewards. Developmental differences in reward sensitivity may fluctuate based on reward magnitude, and on whether rewards require decision-making. We examined whether these factors modulate developmental differences in neural response during reward anticipation and/or receipt in 26 adolescents (14.05±2.37 yrs) and 26 adults (31.25±8.23 yrs). Brain activity was assessed with fMRI during reward anticipation, when subjects made responses with-vs.-without decision-making, to obtain large-vs.-small rewards, and during reward receipt. When reward-receipt required decision-making, neural activity did not differ by age. However, when reward receipt did not require decision-making, neural activity varied by development, reward magnitude, and stage of the reward task. During anticipation, adolescents, but not adults, exhibited greater activity in the insula, extending into putamen, and cingulate gyrus for large-vs.-small incentives. During feedback, adults, but not adolescents, exhibited greater activity in the precuneus for large-vs.-small incentives. These data indicate that age-related differences in reward sensitivity cannot be characterized by global hypo- or hyper-responsivity. Instead, neural responding in striatum, prefrontal cortex and precuneus is influenced by both situational demands and developmental factors. This suggests nuanced maturational effects in adolescent reward sensitivity.

CognitiveConstruct

RewardProcessing