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10.1177/1754073910380973

Emotion review : journal of the International Society for Research on Emotion

Emot Rev

From Basic Processes to Real-World Problems: How Research on Emotion and Emotion Regulation Can Inform Understanding of Psychopathology, and Vice Versa.

Research on emotion and emotion regulation is expected to improve our understanding of psychopathology. However, achieving this understanding requires overcoming several obstacles, including the paucity of objective markers of specific emotions or psychiatric diagnoses, and the fact that emotion regulation is a concept that can be difficult to operationalize. We review affective neuroscience research that has addressed these issues by focusing on psychological and neural mechanisms implicated in approach and avoidance behaviors, as revealed by studies of fear, anxiety, and reward processing. Dysfunction in these mechanisms may serve as risk markers for psychopathology, while emotion regulation research demonstrates that some of them are susceptible to volitional control. The conclusion acknowledges limitations of affective neuroscience and highlights goals for future work.

CognitiveConstruct

RewardProcessing

10.1016/j.physbeh.2011.04.052

Physiology & behavior

Physiol Behav

Cholinergic modulation of mesolimbic dopamine function and reward.

The substantial health risk posed by obesity and compulsive drug use has compelled a serious research effort to identify the neurobiological substrates that underlie the development these pathological conditions. Despite substantial progress, an understanding of the neurochemical systems that mediate the motivational aspects of drug-seeking and craving remains incomplete. Important work from the laboratory of Bart Hoebel has provided key information on neurochemical systems that interact with dopamine (DA) as potentially important components in both the development of addiction and the expression of compulsive behaviors such as binge eating. One such modulatory system appears to be cholinergic pathways that interact with DA systems at all levels of the reward circuit. Cholinergic cells in the pons project to DA-rich cell body regions in the ventral tegmental area (VTA) and substantial nigra (SN) where they modulate the activity of dopaminergic neurons and reward processing. The DA terminal region of the nucleus accumbens (NAc) contains a small but particularly important group of cholinergic interneurons, which have extensive dendritic arbors that make synapses with a vast majority of NAc neurons and afferents. Together with acetylcholine (ACh) input onto DA cell bodies, cholinergic systems could serve a vital role in gating information flow concerning the motivational value of stimuli through the mesolimbic system. In this report we highlight evidence that CNS cholinergic systems play a pivotal role in behaviors that are motivated by both natural and drug rewards. We argue that the search for underlying neurochemical substrates of compulsive behaviors, as well as attempts to identify potential pharmacotherapeutic targets to combat them, must include a consideration of central cholinergic systems.

CognitiveConstruct

RewardProcessing

10.1007/7854_2011_130

Current topics in behavioral neurosciences

Curr Top Behav Neurosci

The dopamine system in mediating alcohol effects in humans.

Recent brain-imaging studies revealed that the development and maintenance of alcohol dependence is determined by a complex interaction of different neurotransmitter systems and multiple psychological factors. In this context, the dopaminergic reinforcement system appears to be of fundamental importance. We focus on the excitatory and depressant effects of acute versus chronic alcohol intake and its impact on dopaminergic neurotransmission. Furthermore, we describe alterations in dopaminergic neurotransmission as associated with symptoms of alcohol dependence. We specifically focus on neuroadaptations to chronic alcohol consumption and their effect on central processing of alcohol-associated and reward-related stimuli. Dysfunctional reward processing, impaired reinforcement learning and increased salience attribution to alcohol-associated stimuli enable alcohol cues to drive alcohol seeking and consumption. Finally, we will discuss how the neurobiological and neurochemical mechanisms of alcohol-associated alterations in reward processing and learning can interact with personality traits, cognition and emotion processing.

CognitiveConstruct

RewardProcessing

10.1002/hbm.21288

Human brain mapping

Hum Brain Mapp

Contextual interaction between novelty and reward processing within the mesolimbic system.

Medial temporal lobe (MTL) dependent long-term memory for novel events is modulated by a circuitry that also responds to reward and includes the ventral striatum, dopaminergic midbrain, and medial orbitofrontal cortex (mOFC). This common neural network may reflect a functional link between novelty and reward whereby novelty motivates exploration in the search for rewards; a link also termed novelty "exploration bonus." We used fMRI in a scene encoding paradigm to investigate the interaction between novelty and reward with a focus on neural signals akin to an exploration bonus. As expected, reward related long-term memory for the scenes (after 24 hours) strongly correlated with activity of MTL, ventral striatum, and substantia nigra/ventral tegmental area (SN/VTA). Furthermore, the hippocampus showed a main effect of novelty, the striatum showed a main effect of reward, and the mOFC signalled both novelty and reward. An interaction between novelty and reward akin to an exploration bonus was found in the hippocampus. These data suggest that MTL novelty signals are interpreted in terms of their reward-predicting properties in the mOFC, which biases striatal reward responses. The striatum together with the SN/VTA then regulates MTL-dependent long-term memory formation and contextual exploration bonus signals in the hippocampus.

CognitiveConstruct

RewardProcessing

10.1002/hbm.21268

Human brain mapping

Hum Brain Mapp

The obese brain: association of body mass index and insulin sensitivity with resting state network functional connectivity.

Obesity is a key risk factor for the development of insulin resistance, Type 2 diabetes and associated diseases; thus, it has become a major public health concern. In this context, a detailed understanding of brain networks regulating food intake, including hormonal modulation, is crucial. At present, little is known about potential alterations of cerebral networks regulating ingestive behavior. We used "resting state" functional magnetic resonance imaging to investigate the functional connectivity integrity of resting state networks (RSNs) related to food intake in lean and obese subjects using independent component analysis. Our results showed altered functional connectivity strength in obese compared to lean subjects in the default mode network (DMN) and temporal lobe network. In the DMN, obese subjects showed in the precuneus bilaterally increased and in the right anterior cingulate decreased functional connectivity strength. Furthermore, in the temporal lobe network, obese subjects showed decreased functional connectivity strength in the left insular cortex. The functional connectivity magnitude significantly correlated with body mass index (BMI). Two further RSNs, including brain regions associated with food and reward processing, did not show BMI, but insulin associated functional connectivity strength. Here, the left orbitofrontal cortex and right putamen functional connectivity strength was positively correlated with fasting insulin levels and negatively correlated with insulin sensitivity index. Taken together, these results complement and expand previous functional neuroimaging findings by demonstrating that obesity and insulin levels influence brain function during rest in networks supporting reward and food regulation.

CognitiveConstruct

RewardProcessing

10.1002/hbm.21267

Human brain mapping

Hum Brain Mapp

Topography, power, and current source density of θ oscillations during reward processing as markers for alcohol dependence.

Recent studies have linked alcoholism with a dysfunctional neural reward system. Although several electrophysiological studies have explored reward processing in healthy individuals, such studies in alcohol-dependent individuals are quite rare. The present study examines theta oscillations during reward processing in abstinent alcoholics. The electroencephalogram (EEG) was recorded in 38 abstinent alcoholics and 38 healthy controls as they performed a single outcome gambling task, which involved outcomes of either loss or gain of an amount (10 or 50¢) that was bet. Event-related theta band (3.0-7.0 Hz) power following each outcome stimulus was computed using the S-transform method. Theta power at the time window of the outcome-related negativity (ORN) and positivity (ORP) (200-500 ms) was compared across groups and outcome conditions. Additionally, behavioral data of impulsivity and task performance were analyzed. The alcoholic group showed significantly decreased theta power during reward processing compared to controls. Current source density (CSD) maps of alcoholics revealed weaker and diffuse source activity for all conditions and weaker bilateral prefrontal sources during the Loss 50 condition when compared with controls who manifested stronger and focused midline sources. Furthermore, alcoholics exhibited increased impulsivity and risk-taking on the behavioral measures. A strong association between reduced anterior theta power and impulsive task-performance was observed. It is suggested that decreased power and weaker and diffuse CSD in alcoholics may be due to dysfunctional neural reward circuitry. The relationship among alcoholism, theta oscillations, reward processing, and impulsivity could offer clues to understand brain circuitries that mediate reward processing and inhibitory control.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.0577-11.2011

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

J Neurosci

Environmental enrichment confers stress resiliency to social defeat through an infralimbic cortex-dependent neuroanatomical pathway.

Enriched environmental (EE) housing dampens stress-induced alterations in neurobiological systems, promotes adaptability, and extinguishes submissive behavioral traits developed during social defeat stress (SD). In the present study, we hypothesized that enrichment before SD can confer stress resiliency and, furthermore, that neuronal activity in the prefrontal cortex (PFC) is requisite for this resiliency. To test these hypotheses, mice were housed in EE, standard (SE), or impoverished (IE) housing and then exposed to SD. EE conferred resilience to SD as measured in several behavioral tasks. EE-housed mice expressed elevated FosB/ΔFosB immunostaining in areas associated with emotional regulation and reward processing, i.e., infralimbic, prelimbic, and anterior cingulate cortices, amygdala, and nucleus accumbens, and this expression was mostly preserved in mice receiving EE followed by SD. In contrast, in SE- or IE-housed animals, SD increased maladaptive behaviors and greatly reduced FosB/ΔFosB staining in the forebrain. We tested the putative involvement of the PFC in mediating resilience by lesioning individual regions of the PFC either before or after EE housing and then exposing the mice to SD. We found that discrete lesions of the infralimbic but not prelimbic or cingulate cortex made before but not after EE abolished the behavioral resiliency to stress afforded by EE and attenuated FosB/ΔFosB expression in the accumbens and amygdala while increasing it in the paraventricular hypothalamic nucleus. These data suggest that pathological ventromedial PFC outputs to downstream limbic targets could predispose an individual to anxiety disorders in stressful situations, whereas enhanced ventromedial PFC outputs could convey stress resilience.

CognitiveConstruct

RewardProcessing

10.1038/mp.2011.29

Molecular psychiatry

Mol Psychiatry

Pharmacological differentiation of opioid receptor antagonists by molecular and functional imaging of target occupancy and food reward-related brain activation in humans.

Opioid neurotransmission has a key role in mediating reward-related behaviours. Opioid receptor (OR) antagonists, such as naltrexone (NTX), can attenuate the behaviour-reinforcing effects of primary (food) and secondary rewards. GSK1521498 is a novel OR ligand, which behaves as an inverse agonist at the μ-OR sub-type. In a sample of healthy volunteers, we used [(11)C]-carfentanil positron emission tomography to measure the OR occupancy and functional magnetic resonance imaging (fMRI) to measure activation of brain reward centres by palatable food stimuli before and after single oral doses of GSK1521498 (range, 0.4-100 mg) or NTX (range, 2-50 mg). GSK1521498 had high affinity for human brain ORs (GSK1521498 effective concentration 50 = 7.10 ng ml(-1)) and there was a direct relationship between receptor occupancy (RO) and plasma concentrations of GSK1521498. However, for both NTX and its principal active metabolite in humans, 6-β-NTX, this relationship was indirect. GSK1521498, but not NTX, significantly attenuated the fMRI activation of the amygdala by a palatable food stimulus. We thus have shown how the pharmacological properties of OR antagonists can be characterised directly in humans by a novel integration of molecular and functional neuroimaging techniques. GSK1521498 was differentiated from NTX in terms of its pharmacokinetics, target affinity, plasma concentration-RO relationships and pharmacodynamic effects on food reward processing in the brain. Pharmacological differentiation of these molecules suggests that they may have different therapeutic profiles for treatment of overeating and other disorders of compulsive consumption.

CognitiveConstruct

RewardProcessing

10.3109/15622975.2011.562244

The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry

World J Biol Psychiatry

A meta-analysis of circulating BDNF concentrations in anorexia nervosa.

Brain derived neurotrophic factor (BDNF) is involved in neuroplasticity, and in the homeostatic regulation of food intake and energy expenditure. It also has a role in stress responsivity and reward processing. On the basis of its involvement in these various processes, BDNF can be hypothesized to be an important factor in the development and maintenance of anorexia nervosa (AN). This study meta-analytically summarizes investigations of serum BDNF concentrations in people currently ill with AN, in comparison to healthy controls. Seven studies measuring BDNF in serum of individuals with AN (n=155) and healthy controls (n=174) were identified and included in the meta-analysis of the mean differences between case and control groups. This study confirms that AN is associated with decreased serum BDNF concentrations, in comparison to healthy controls. The combined effect size (standardized mean difference, SMD) was large (SMD=-0.96; 95% CI -1.33 to -0.59; P<0.001). Significant heterogeneity of effect sizes was identified (I(2)=58.3%; P<0.001), which emerged as being primarily attributable to the first published study on the investigated association. The present meta-analytical summary of studies measuring circulating BDNF concentrations in women with AN and healthy controls confirms that it is significantly reduced in this patient group. Difficulties associated with the measurement of BDNF have been identified and potential confounding factors have been discussed. Current data do not allow inferences to be made about causal links between levels of circulating BDNF and AN. However, possible explanations for the relationship between BDNF and AN have been presented.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2011.02.014

Biological psychiatry

Biol Psychiatry

Cocaine cues drive opposing context-dependent shifts in reward processing and emotional state.

Prominent neurobiological theories of addiction posit a central role for aberrant mesolimbic dopamine release but disagree as to whether repeated drug experience blunts or enhances this system. Although drug withdrawal diminishes dopamine release, drug sensitization augments mesolimbic function, and both processes have been linked to drug seeking. One possibility is that the dopamine system can rapidly switch from dampened to enhanced release depending on the specific drug-predictive environment. To test this, we examined dopamine release when cues signaled delayed cocaine delivery versus imminent cocaine self-administration. Fast-scan cyclic voltammetry was used to examine real-time dopamine release while simultaneously monitoring behavioral indexes of aversion as rats experienced a sweet taste cue that predicted delayed cocaine availability and during self-administration. Furthermore, the impact of cues signaling delayed drug availability on intracranial self-stimulation, a broad measure of reward function, was assessed. We observed decreased mesolimbic dopamine concentrations, decreased reward sensitivity, and negative affect in response to the cocaine-predictive taste cue that signaled delayed cocaine availability. Importantly, dopamine concentration rapidly switched to elevated levels to cues signaling imminent cocaine delivery in the subsequent self-administration session. These findings show rapid, bivalent contextual control over brain reward processing, affect, and motivated behavior and have implications for mechanisms mediating substance abuse.

CognitiveConstruct

RewardProcessing

10.1007/s10802-011-9503-9

Journal of abnormal child psychology

J Abnorm Child Psychol

Abnormal neural sensitivity to monetary gains versus losses among adolescents at risk for depression.

Major depressive disorder aggregates within families, although the mechanisms of transfer across generations are not well understood. In light of converging biological and behavioral evidence that depressive symptoms are associated with impaired reward processing, we examined whether adolescent girls with a parental history of depression would also exhibit abnormal reward sensitivity. We performed a negative mood induction and then recorded the feedback negativity, a neural index of reward processing, while individuals completed a gambling task. High-risk adolescents reported greater sadness following the mood induction compared to low-risk adolescents. Among the high-risk group, sadness was strongly associated with a blunted feedback negativity, even after controlling for baseline mood and trait neuroticism. This suggests that high-risk adolescents are more reactive to negative stimuli, which significantly alter neural sensitivity to monetary gains and losses. The feedback negativity might be used to identify information processing abnormalities in high-risk populations prior to the onset of a major depressive episode.

CognitiveConstruct

RewardProcessing

10.1037/a0022357

Neuropsychology

Neuropsychology

Executive functions, information sampling, and decision making in narcolepsy with cataplexy.

Narcolepsy with cataplexy (NC) affects neurotransmitter systems regulating emotions and cognitive functions. This study aimed to assess executive functions, information sampling, reward processing, and decision making in NC. Twenty-one NC patients and 58 healthy participants performed an extensive neuropsychological test battery. NC patients scored as controls in executive function tasks assessing set shifting, reversal learning, working memory, and planning. Group differences appeared in a task measuring information sampling and reward sensitivity. NC patients gathered less information, tolerated a higher level of uncertainty, and were less influenced by reward contingencies than controls. NC patients also showed reduced learning in decision making and had significantly lower scores than controls in the fifth block of the IOWA gambling task. No correlations were found with measures of sleepiness. NC patients may achieve high performance in several neuropsychological domains, including executive functions. Specific differences between NC patients and controls highlight the importance of the hypocretin system in reward processing and decision making and are in line with previous neuroimaging and neurophysiological studies.

CognitiveConstruct

RewardProcessing

10.1111/j.1530-0277.2011.01452.x

Alcoholism, clinical and experimental research

Alcohol Clin Exp Res

Cortical thickness, surface area, and volume of the brain reward system in alcohol dependence: relationships to relapse and extended abstinence.

At least 60% of those treated for an alcohol use disorder will relapse. Empirical study of the integrity of the brain reward system (BRS) is critical to understanding the mechanisms of relapse as this collection of circuits is implicated in the development and maintenance of all forms of addictive disorders. This study compared thickness, surface area, and volume in neocortical components of the BRS among nonsmoking light-drinking controls (controls), individuals who remained abstinent and those who relapsed after treatment. Seventy-five treatment-seeking alcohol-dependent individuals (abstinent for 7±3 days) and 43 controls completed 1.5T proton magnetic resonance imaging studies. Parcellated morphological data were obtained for following bilateral components of the BRS: rostral and caudal anterior cingulate cortex, insula, medial and lateral orbitofrontal cortex (OFC), rostral and caudal middle and superior frontal gyri, amygdala and hippocampus as well as for 26 other bilateral neocortical regions. Alcohol-dependent participants were followed over 12-months after baseline study and were classified as abstainers (no alcohol consumption; n=24) and relapsers (any alcohol consumption; n=51) at follow-up. Relapsers and abstainers demonstrated lower cortical thickness in the vast majority of BRS regions as well as lower global thickness compared to controls. Relapsers had lower total BRS surface area than both controls and abstainers, but abstainers were not significantly different from controls on any surface area measure. Relapsers demonstrated lower volumes than controls in the majority of regions, while abstainers showed lower volumes than controls in the superior frontal gyrus, insula, amygdala, and hippocampus, bilaterally. Relapsers exhibited smaller volumes than abstainers in the right rostral middle and caudal middle frontal gyri and the lateral OFC, bilaterally. In relapsers, lower baseline volumes and surface areas in multiple regions were associated with a greater magnitude of post-treatment alcohol consumption. Results suggest relapsers demonstrated morphological abnormalities in regions involved in the "top down" regulation/modulation of internal drive states, emotions, reward processing, and behavior, which may impart increased risk for the relapse/remit cycle that afflicts many with an alcohol use disorder. Results also highlight the importance of examining both cortical thickness and surface area to better understand the nature of regional volume loss frequently observed in alcohol use disorders. Results from this report are consistent with previous research implicating plastic neurobiological changes in the BRS in the maintenance of addictive disorders.

CognitiveConstruct

RewardProcessing

10.1073/pnas.1017732108

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

Proc Natl Acad Sci U S A

Risk preference following adolescent alcohol use is associated with corrupted encoding of costs but not rewards by mesolimbic dopamine.

Several emerging theories of addiction have described how abused substances exploit vulnerabilities in decision-making processes. These vulnerabilities have been proposed to result from pharmacologically corrupted neural mechanisms of normal brain valuation systems. High alcohol intake in rats during adolescence has been shown to increase risk preference, leading to suboptimal performance on a decision-making task when tested in adulthood. Understanding how alcohol use corrupts decision making in this way has significant clinical implications. However, the underlying mechanism by which alcohol use increases risk preference remains unclear. To address this central issue, we assessed dopamine neurotransmission with fast-scan cyclic voltammetry during reward valuation and risk-based decision making in rats with and without a history of adolescent alcohol intake. We specifically targeted the mesolimbic dopamine system, the site of action for virtually all abused substances. This system, which continuously develops during the adolescent period, is central to both reward processing and risk-based decision making. We report that a history of adolescent alcohol use alters dopamine signaling to risk but not to reward. Thus, a corruption of cost encoding suggests that adolescent alcohol use leads to long-term changes in decision making by altering the valuation of risk.

CognitiveConstruct

RewardProcessing

10.1111/j.1460-9568.2011.07649.x

The European journal of neuroscience

Eur J Neurosci

Independent neural coding of reward and movement by pedunculopontine tegmental nucleus neurons in freely navigating rats.

Phasic firing of dopamine (DA) neurons in the ventral tegmental area (VTA) and substantia nigra (SN) is likely to be crucial for reward processing that guides learning. One of the key structures implicated in the regulation of this DA burst firing is the pedunculopontine tegmental nucleus (PPTg), which projects to both the VTA and SN. Different literatures suggest that the PPTg serves as a sensory-gating area for DA cells or it regulates voluntary movement. This study recorded PPTg single-unit activity as rats perform a spatial navigation task to examine the potential for both reward and movement contributions. PPTg cells showed significant changes in firing relative to reward acquisition, the velocity of movement across the maze and turning behaviors of the rats. Reward, but not movement, correlates were impacted by changes in context, and neither correlate type was affected by reward manipulations (e.g. changing the expected location of a reward). This suggests that the PPTg conjunctively codes both reward and behavioral information, and that the reward information is processed in a context-dependent manner. The distinct anatomical distribution of reward and movement cells emphasizes different models of synaptic control by PPTg of DA burst firing in the VTA and SN. Relevant to both VTA and SN learning systems, however, PPTg appears to serve as a sensory gating mechanism to facilitate reinforcement learning, while at the same time provides reinforcement-based guidance of ongoing goal-directed behaviors.

CognitiveConstruct

RewardProcessing

10.1016/j.pnpbp.2011.02.018

Progress in neuro-psychopharmacology & biological psychiatry

Prog Neuropsychopharmacol Biol Psychiatry

Deficits in sustaining reward responses in subsyndromal and syndromal major depression.

Preliminary findings suggest a reduction in capacity to sustain reward responses in major depression. However, relatively little is known about the stability of reward learning over time and the effect of stress on reward responses in depressed individuals. This study aimed to evaluate sustained behaviour to maximize reward in the context of known reinforcement contingencies and to evaluate the extent to which stress influences such behaviour in clinically depressed patients (n=43), subsyndromally depressed individuals (n=43), and healthy controls (n=44). A probabilistic reward learning task with contingencies known to participants was used to evaluate the change of reward response over time in both 'stress' and 'non-stress' conditions. Stress was induced by salient negative feedback during the task performance. Questionnaires capturing subjective affect were also administered to all participants after completion of the task. Response bias to the stimulus signaling greater reward decreased significantly over time in both subsyndromally and clinically depressed participants, but not in healthy controls. Healthy controls demonstrated a trend of dysfunctional reward processing under the stress condition. Moreover, in the stress condition, the deficit in sustaining behaviour to maximize reward was associated with subjective rating of pleasure in participants with either subsyndromal depression or major depression. These findings suggest that individuals with depression have difficulty sustaining behaviour during a known reinforcement schedule. Participants with anhedonic symptoms are even less likely to sustain behaviour to maximize reward under stress.

CognitiveConstruct

RewardProcessing

10.1037/a0022038

Behavioral neuroscience

Behav Neurosci

A comparison of adult and adolescent rat behavior in operant learning, extinction, and behavioral inhibition paradigms.

Poor self-control, lack of inhibition, and impulsivity contribute to the propensity of adolescents to engage in risky or dangerous behaviors. Brain regions (e.g., prefrontal cortex) involved in impulse-control, reward-processing, and decision-making continue to develop during adolescence, raising the possibility that an immature brain contributes to dangerous behavior during adolescence. However, very few validated animal behavioral models are available for behavioral neuroscientists to explore the relationship between brain development and behavior. To that end, a valid model must be conducted in the relatively brief window of adolescence and not use manipulations that potentially compromise development. The present experiments used three operant arrangements to assess whether adolescent rats differ from adults in measures of learning, behavioral inhibition, and impulsivity, within the aforementioned time frame without substantial food restriction. In Experiment 1, separate squads of rats were trained to lever-press and then transitioned to two types of extinction. Relative to their baselines, adolescent rats responded more during extinction than adults, suggesting that they were less sensitive to the abolishment of the reinforcement contingency. Experiment 2 demonstrated similar age-related differences during exposure to a differential reinforcement of low rates schedule, a test of behavioral inhibition. Lastly, in Experiment 3, adolescent's responding decreased more slowly than adults during exposure to a resetting delay of reinforcement schedule, suggesting impaired self-control. Results from these experiments suggest that adolescents exhibit impaired learning, behavioral inhibition and self-control, and in concert with recent reports, provide researchers with three behavioral models to more fully explore neurobiology of risk-taking behavior in adolescence.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0016406

PloS one

PLoS One

Functional magnetic resonance imaging reveals different neural substrates for the effects of orexin-1 and orexin-2 receptor antagonists.

Orexins are neuro-modulatory peptides involved in the control of diverse physiological functions through interaction with two receptors, orexin-1 (OX1R) and orexin-2 (OX2R). Recent evidence in pre-clinical models points toward a putative dichotomic role of the two receptors, with OX2R predominantly involved in the regulation of the sleep/wake cycle and arousal, and the OX1R being more specifically involved in reward processing and motivated behaviour. However, the specific neural substrates underlying these distinct processes in the rat brain remain to be elucidated. Here we used functional magnetic resonance imaging (fMRI) in the rat to map the modulatory effect of selective OXR blockade on the functional response produced by D-amphetamine, a psychostimulant and arousing drug that stimulates orexigenic activity. OXR blockade was produced by GSK1059865 and JNJ1037049, two novel OX1R and OX2R antagonists with unprecedented selectivity at the counter receptor type. Both drugs inhibited the functional response to D-amphetamine albeit with distinct neuroanatomical patterns: GSK1059865 focally modulated functional responses in striatal terminals, whereas JNJ1037049 induced a widespread pattern of attenuation characterised by a prominent cortical involvement. At the same doses tested in the fMRI study, JNJ1037049 exhibited robust hypnotic properties, while GSK1059865 failed to display significant sleep-promoting effects, but significantly reduced drug-seeking behaviour in cocaine-induced conditioned place preference. Collectively, these findings highlight an essential contribution of the OX2R in modulating cortical activity and arousal, an effect that is consistent with the robust hypnotic effect exhibited by JNJ1037049. The subcortical and striatal pattern observed with GSK1059865 represent a possible neurofunctional correlate for the modulatory role of OX1R in controlling reward-processing and goal-oriented behaviours in the rat.

CognitiveConstruct

RewardProcessing

10.1002/hbm.21184

Human brain mapping

Hum Brain Mapp

Temporal dynamics of reward processing revealed by magnetoencephalography.

Monetary gains and losses in gambling situations are associated with a distinct electroencephalographic signature: in the event-related potentials (ERPs), a mediofrontal feedback-related negativity (FRN) is seen for losses, whereas oscillatory activity shows a burst of in the θ-range for losses and in the β-range for gains. We used whole-head magnetoencephalography to pinpoint the magnetic counterparts of these effects in young healthy adults and explore their evolution over time. On each trial, participants bet on one of two visually presented numbers (25 or 5) by button-press. Both numbers changed color: if the chosen number turned green (red), it indicated a gain (loss) of the corresponding sum in Euro cent. For losses, we found the magnetic correlate of the FRN extending between 230 and 465 ms. Source localization with low-resolution electromagnetic tomography indicated a first generator in posterior cingulate cortex with subsequent activity in the anterior cingulate cortex. Importantly, this effect was sensitive to the magnitude of the monetary loss (25 cent > 5 cent). Later activation was also found in the right insula. Time-frequency analysis revealed a number of oscillatory components in the theta, alpha, and high-beta/low-gamma bands associated to gains, and in the high-beta band, associated to the magnitude of the loss. All together, these effects provide a more fine-grained picture of the temporal dynamics of the processing of monetary rewards and losses in the brain.

CognitiveConstruct

RewardProcessing

10.1002/hbm.21182

Human brain mapping

Hum Brain Mapp

Event-related potential activity in the basal ganglia differentiates rewards from nonrewards: temporospatial principal components analysis and source localization of the feedback negativity.

Event-related potential studies of reward processing have consistently identified the feedback negativity (FN), an early neural response that differentiates feedback indicating unfavorable versus favorable outcomes. Several important questions remain, however, about the nature of this response. In this study, the FN was recorded in response to monetary gains and losses during a laboratory gambling task, and temporospatial principal components analysis was used to separate the FN from overlapping responses. The FN was identified as a positive deflection at frontocentral recording sites that was enhanced for rewards compared with nonrewards. Furthermore, source localization techniques identified the striatum as a likely neural generator. These data indicate that this apparent FN reflects increased striatal activation in response to favorable outcomes that is reduced or absent for unfavorable outcomes, thereby providing unique information about the timing and nature of basal ganglia activity related to reward processing.

CognitiveConstruct

RewardProcessing

10.1007/DCR.0b013e31820348ac

Diseases of the colon and rectum

Dis Colon Rectum

Relief of fecal incontinence by sacral nerve stimulation linked to focal brain activation.

This study aimed to test the hypothesis that sacral nerve stimulation affects afferent vagal projections to the central nervous system associated with frontal cortex activation in patients with fecal incontinence. Nine women and one man received temporary sacral nerve stimulation with permanent electrodes as a treatment for fecal incontinence. We used positron emission tomography to record indices of regional cerebral blood flow before and after 30 minutes of continuous stimulation. We repeated this procedure after 2 weeks of continued stimulation, before and 30 minutes after arrest of the stimulation. The initial stimulation activated a region of the contralateral frontal cortex that normally is active during focused attention. After 2 weeks of stimulation, this activation had been replaced by activity in parts of the ipsilateral caudate nucleus, a region of the brain thought to be specifically involved in learning and reward processing. Sacral nerve stimulation induces changes in cerebral activity consistent with an effect on afferent projections of the vagus. The initial activation of the frontal cortex may reflect focused attention, whereas the subsequent activation of the caudate nucleus may reflect recruitment of mechanisms involved in learning and reward processing. These changes may contribute to the improved continence, which is an acquired result of the stimulation.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2011.01.072

NeuroImage

Neuroimage

Developmental effects of reward on sustained attention networks.

Adolescence is typified by significant maturation in higher-level attention functions coupled with less developed control over motivation, and enhanced sensitivity to novelty and reward. This study used event-related functional magnetic resonance imaging (fMRI) in seventy male and female participants aged between 10 and 43 years to identify age-related linear changes in cognitive sustained attention systems and the impact of reward on these systems, using a sustained attention task with and without a rewarded condition. For the non-rewarded sustained attention contrast, increasing age was associated with activation increases in typical regions of sustained attention including right inferior frontal, superior temporo-parietal and cerebellar cortices. Age-related activation decreases were observed within more posterior regions including posterior cingulate, insula and posterior cerebellar cortices, presumably mediating visual-spatial saliency detection. The effect of reward on sustained attention networks was associated with increased activation with age in regions associated with both executive attention control and reward processing, including dorsolateral, inferior and ventromedial prefrontal cortices (PFC), striatum, and temporo-parietal regions, suggestive of greater integration and executive control of motivation and cognition with maturity. Activation in paralimbic posterior cingulate and inferior temporal brain regions of visual-spatial saliency processing was progressively reduced in activation with increasing development. Thus, with increasing development between adolescence and adulthood, reward appears to enhance maturing cognitive sustained attention and executive reward-processing networks, whilst reducing paralimbic regions of saliency detection. These findings may be the neural underpinnings for the progressive maturation of motivational control over risk taking behaviours between adolescence and adulthood.

CognitiveConstruct

RewardProcessing

10.1007/s00213-011-2166-y

Psychopharmacology

Psychopharmacology (Berl)

Reward processing in male adults with childhood ADHD--a comparison between drug-naïve and methylphenidate-treated subjects.

Dysfunctional reward processing has been proposed as a main deficit in attention-deficit/hyperactivity disorder (ADHD), which could be modulated by treatment with methylphenidate (MPH). We examined differences in reward processing in adulthood (independent of actual ADHD) depending on MPH treatment during childhood. Eleven males with childhood ADHD treated with MPH, 12 drug-naïve males with childhood ADHD, and 12 controls matched by age, handedness, and smoking behavior were studied drug-free using functional magnetic resonance imaging. BOLD-responses were compared during a monetary incentive delay task using an ANOVA design focusing on the ventral striatum during anticipation and the orbitofrontal cortex during outcome. Controls, drug-naïve, and treated subjects did not differ significantly in their activations in the ventral striatum and orbitofrontal cortex. Explorative analyses revealed decreased insula activation during outcome of loss avoidance in drug-naïve subjects in comparison to both groups, while treated subjects did not differ from controls. Insula activation correlated significantly positive with harm avoidance in the treated group. Furthermore, comparing subjects with actual ADHD symptoms, remitters and controls we observed decreased putamen activition in ADHD persisters. Basal ganglia reward processing seemed to be unrelated to MPH pretreatment, but was related to remission. On the other hand, the revealed differences between treated and drug-naïve subjects with childhood ADHD, i.e., in the insula, give evidence for more pronounced abnormal activation in reward-associated brain regions in untreated subjects with childhood ADHD and underpin the need of prospective studies on long-term effects of psychostimulant treatment.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2011.01.045

Behavioural brain research

Behav Brain Res

Changes in phosphorylation of CREB, ERK, and c-fos induction in rat ventral tegmental area, hippocampus and prefrontal cortex after conditioned place preference induced by chemical stimulation of lateral hypothalamus.

Experimental evidence indicates that chemical stimulation of lateral hypothalamus (LH) by carbachol can produce conditioned place preference (CPP) in rats. Several lines of evidence have shown that cAMP-response element binding protein (CREB), extracellular signal-regulated kinase (ERK), and c-fos have pivotal role in CPP induced by drugs of abuse, such as morphine, cocaine, nicotine, and alcohol. Therefore, in the present study, we investigated the changes in phosphorylated-CREB (p-CREB) and -ERK (p-ERK), and c-fos induction within ventral tegmental area (VTA), hippocampus and prefrontal cortex (PFC) after the acquisition of CPP induced by intra-LH administration of carbachol. Animals were unilaterally implanted by cannula into LH. For chemical stimulation of LH, carbachol (250 nmol/0.5 μl saline) was microinjected once each day, during 3-day conditioning phase (acquisition period) of CPP paradigm. After the acquisition period, the brains were removed, and p-CREB and p-ERK, and c-fos induction in the ipsilateral VTA, hippocampus and PFC were measured by Western blot analysis. The results indicated a significant increase in level of phosphorylated CREB (P<0.01) in VTA, and PFC (P<0.05), during LH stimulation-induced CPP, while its level decreased in hippocampus (P<0.05). Also, in aforementioned regions, an increase in c-fos level was observed, but this enhancement in PFC was not significant. Moreover, p-ERK changed in these areas, but not significantly. Our findings suggest that studying the intracellular signals and their changes, such as phosphorylated-CREB, can elucidate a functional relationship between LH and other brain structures involved in reward processing in rats.

CognitiveConstruct

RewardProcessing

10.1007/s10803-011-1177-1

Journal of autism and developmental disorders

J Autism Dev Disord

Atypical brain responses to reward cues in autism as revealed by event-related potentials.

Social motivation deficit theories suggest that children with autism do not properly anticipate and appreciate the pleasure of social stimuli. In this study, we investigated event-related brain potentials evoked by cues that triggered social versus monetary reward anticipation in children with autism. Children with autism showed attenuated P3 activity in response to cues associated with a timely reaction to obtain a reward, irrespective of reward type. We attribute this atypical P3 activity in response to reward cues as reflective of diminished motivated attention to reward signals, a possible contributor to reduced social motivation in autism. Thus, our findings suggest a general reward processing deficit rather than a specific social reward dysfunction in autism.

CognitiveConstruct

RewardProcessing

Revista de neurologia

Rev Neurol

[Cognitive remediation in addictions treatment].

More recent theories of addiction suggest that neurocognitive mechanisms, such as attentional processing, cognitive control, and reward processing play a key role in the development or maintenance of addiction. Ultimately, the addiction (with or without substances) is based on the alteration of brain decision-making processes. The neurosciences, particularly those responsible for behavior modification, must take into account the neurobiological processes underlying the observable behavior. Treatments of addiction usually do not take into account these findings, which may be at the base of the low retention rates and high dropout rates of addicted patients. Considered as an alteration of brain functioning, addiction could be addressed successfully through cognitive rehabilitation treatments used in other clinical pathologies such as brain damage or schizophrenia. Although there are few studies, it is suggest that intervention to improve patients' cognitive functioning can improve the efficiency of well-established cognitive-behavioral therapies, such as relapse prevention. This paper reviews the available evidence on cognitive rehabilitation in treating addiction as well as in other pathologies, in order to formulate interventions that may be included in comprehensive rehabilitation programs for people with addictive disorders.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2010.12.003

Biological psychiatry

Biol Psychiatry

Dysfunctional reward circuitry in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is primarily conceived as an anxiety disorder but has features resembling addictive behavior. Patients with OCD may develop dependency upon compulsive behaviors because of the rewarding effects following reduction of obsession-induced anxiety. Reward processing is critically dependent on ventral striatal-orbitofrontal circuitry and brain imaging studies in OCD have consistently shown abnormal activation within this circuitry. This is the first functional imaging study to investigate explicitly reward circuitry in OCD. Brain activity during reward anticipation and receipt was compared between 18 OCD patients and 19 healthy control subjects, using a monetary incentive delay task and functional magnetic resonance imaging. Reward processing was compared between OCD patients with predominantly contamination fear and patients with predominantly high-risk assessment. Obsessive-compulsive disorder patients showed attenuated reward anticipation activity in the nucleus accumbens compared with healthy control subjects. Reduced activity of the nucleus accumbens was more pronounced in OCD patients with contamination fear than in patients with high-risk assessment. Brain activity during reward receipt was similar between patients and control subjects. A hint toward more dysfunctional reward processing was found in treatment-resistant OCD patients who subsequently were successfully treated with deep brain stimulation of the nucleus accumbens. Obsessive-compulsive disorder patients may be less able to make beneficial choices because of altered nucleus accumbens activation when anticipating rewards. This finding supports the conceptualization of OCD as a disorder of reward processing and behavioral addiction.

CognitiveConstruct

RewardProcessing

10.1177/0956797610397667

Psychological science

Psychol Sci

Us versus them: social identity shapes neural responses to intergroup competition and harm.

Intergroup competition makes social identity salient, which in turn affects how people respond to competitors' hardships. The failures of an in-group member are painful, whereas those of a rival out-group member may give pleasure-a feeling that may motivate harming rivals. The present study examined whether valuation-related neural responses to rival groups' failures correlate with likelihood of harming individuals associated with those rivals. Avid fans of the Red Sox and Yankees teams viewed baseball plays while undergoing functional magnetic resonance imaging. Subjectively negative outcomes (failure of the favored team or success of the rival team) activated anterior cingulate cortex and insula, whereas positive outcomes (success of the favored team or failure of the rival team, even against a third team) activated ventral striatum. The ventral striatum effect, associated with subjective pleasure, also correlated with self-reported likelihood of aggressing against a fan of the rival team (controlling for general aggression). Outcomes of social group competition can directly affect primary reward-processing neural systems, which has implications for intergroup harm.

CognitiveConstruct

RewardProcessing

Rivista di psichiatria

Riv Psichiatr

[Reward processing and psychopathology].

Reward processing permits to establish if and how an environmental stimulus or a future goal is reinforcing or punishing for the subject. This process is at the basis of reinforcement learning and decision making; is principally based on the orbitofrontal cortex and its connections with the striatum and the limbic system. If a dysfunctional reward processing has been often reported in substance abusers or pathologic gamblers, recent studies reported a dysfunction of this process in patients with other psychiatric disorders, previously not assessed by this experimental perspective, for example attention deficit/hyperactivity disorder, mood disorders, eating behaviour disorders and cluster B personality disorders. Experimental findings on a dysfunctional reward processing in these disorders are reviewed and discussed, in order to trace directions for future studies, that need to clarify if different dysfunctions are associated to different psychiatric disorders.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2010.00239

Frontiers in human neuroscience

Front Hum Neurosci

Aberrant Effective Connectivity in Schizophrenia Patients during Appetitive Conditioning.

It has recently been suggested that schizophrenia involves dysfunction in brain connectivity at a neural level, and a dysfunction in reward processing at a behavioral level. The purpose of the present study was to link these two levels of analyses by examining effective connectivity patterns between brain regions mediating reward learning in patients with schizophrenia and healthy, age-matched controls. To this aim, we used functional magnetic resonance imaging and galvanic skin recordings (GSR) while patients and controls performed an appetitive conditioning experiment with visual cues as the conditioned (CS) stimuli, and monetary reward as the appetitive unconditioned stimulus (US). Based on explicit stimulus contingency ratings, conditioning occurred in both groups; however, based on implicit, physiological GSR measures, patients failed to show differences between CS+ and CS- conditions. Healthy controls exhibited increased blood-oxygen-level dependent (BOLD) activity across striatal, hippocampal, and prefrontal regions and increased effective connectivity from the ventral striatum to the orbitofrontal cortex (OFC BA 11) in the CS+ compared to the CS- condition. Compared to controls, patients showed increased BOLD activity across a similar network of brain regions, and increased effective connectivity from the striatum to hippocampus and prefrontal regions in the CS- compared to the CS+ condition. The findings of increased BOLD activity and effective connectivity in response to the CS- in patients with schizophrenia offer insight into the aberrant assignment of motivational salience to non-reinforced stimuli during conditioning that is thought to accompany schizophrenia.

CognitiveConstruct

RewardProcessing

10.1162/jocn.2011.21618

Journal of cognitive neuroscience

J Cogn Neurosci

The influence of emotion regulation on decision-making under risk.

Cognitive strategies typically involved in regulating negative emotions have recently been shown to also be effective with positive emotions associated with monetary rewards. However, it is less clear how these strategies influence behavior, such as preferences expressed during decision-making under risk, and the underlying neural circuitry. That is, can the effective use of emotion regulation strategies during presentation of a reward-conditioned stimulus influence decision-making under risk and neural structures involved in reward processing such as the striatum? To investigate this question, we asked participants to engage in imagery-focused regulation strategies during the presentation of a cue that preceded a financial decision-making phase. During the decision phase, participants then made a choice between a risky and a safe monetary lottery. Participants who successfully used cognitive regulation, as assessed by subjective ratings about perceived success and facility in implementation of strategies, made fewer risky choices in comparison with trials where decisions were made in the absence of cognitive regulation. Additionally, BOLD responses in the striatum were attenuated during decision-making as a function of successful emotion regulation. These findings suggest that exerting cognitive control over emotional responses can modulate neural responses associated with reward processing (e.g., striatum) and promote more goal-directed decision-making (e.g., less risky choices), illustrating the potential importance of cognitive strategies in curbing risk-seeking behaviors before they become maladaptive (e.g., substance abuse).

CognitiveConstruct

RewardProcessing

10.1007/7854_2010_82

Current topics in behavioral neurosciences

Curr Top Behav Neurosci

Cognitions and emotions in eating disorders.

The cognitive model of eating disorders (EDs) states that the processing of external and internal stimuli might be biased in mental disorders. These biases, or cognitive errors, systematically distort the individual's experiences and, in that way, maintains the eating disorder. This chapter presents an updated literature review of experimental studies investigating these cognitive biases. Results indicate that ED patients show biases in attention, interpretation, and memory when it comes to the processing of food-, weight-, and body shape-related cues. Some recent studies show that they also demonstrate errors in general cognitive abilities such as set shifting, central coherence, and decision making. A future challenge is whether cognitive biases and processes can be manipulated. Few preliminary studies suggest that an attention retraining and training in the cognitive modulation of food reward processing might be effective strategies to change body satisfaction, food cravings, and eating behavior.

CognitiveConstruct

RewardProcessing

10.1111/j.1469-7610.2010.02374.x

Journal of child psychology and psychiatry, and allied disciplines

J Child Psychol Psychiatry

Common alterations in sensitivity to type but not amount of reward in ADHD and autism spectrum disorders.

Children with attention deficit/hyperactivity disorder (ADHD) display abnormalities in reward processing. Most reward studies have focused on the effects of material or monetary rewards. Studies with autism spectrum disorder (ASD) have focused on social rewards. In this study we compared the effects of amount and type of reward in children with ADHD and those with ASD. Two adapted versions of the Monetary Incentive Delay Task were used to study the effects of monetary and social reward anticipation on performance in 40 typically developing (TD) children and adolescents (8-16y), 35 children and adolescents with ADHD and 31 children and adolescents with ASD. Monetary and social reward improved accuracy and response time (RT) in all groups. The higher the anticipated reward, the more accurate and faster were responses. Independent of these effects, there was a differential effect of reward type. Both clinical groups, but not TD, responded faster for monetary than social rewards. The results, while not supporting hyposensitivity to changes in reward amount in ADHD and ASD, do suggest that both groups are generally less motivated in settings where social as opposed to monetary rewards can be earned.

CognitiveConstruct

RewardProcessing

10.1093/sleep/34.1.99

Sleep

Sleep

Decision making in narcolepsy with cataplexy.

To investigate decision-making and addictive behaviors in narcolepsy-cataplexy (NC). NC is caused by the loss of hypothalamic neurons that produce hypocretins. The hypocretin system plays a crucial role in sleep, wakefulness, and energy homeostasis, and is also involved in emotion regulation, reward processing, and addiction. Academic sleep center. 23 subject with NC and 23 matched healthy controls. We used the Iowa Gambling Task (IGT) to assess decision making under ambiguity condition based on emotional feedback processing and the Game of Dice Task (GDT) to assess decision making under risk condition. All participants underwent a semi-structured psychiatric interview and completed the Beck Depression Inventory-II and the UPPS Impulsive Behavior Scale. Patients underwent one night of polysomnography followed by an MSLT, with neuropsychological evaluation performed between MSLT sessions. NC patients had higher depressive symptoms and showed a significant lack of perseverance. One NC patient had a past history of drug dependence. NC patients also exhibited selective reduced IGT performance and normal performance on the GDT. No clinical or polysomnographic characteristics were associated with increased sensitivity to reward and/or decreased sensitivity to punishment. However, lack of perseverance in NC patients was associated with disadvantageous decision making on the IGT. We demonstrated a lack of perseverance and a selective reduced performance on decision making under ambiguity in NC in contrast to normal decision making under explicit conditions. Patients with narcolepsy-cataplexy may opt for choices with higher immediate emotional valence, regardless of higher future punishment, to compensate for their reduced reactivity to emotional stimuli.

CognitiveConstruct

RewardProcessing

10.1038/tp.2011.53

Translational psychiatry

Transl Psychiatry

The neural basis of video gaming.

Video game playing is a frequent recreational activity. Previous studies have reported an involvement of dopamine-related ventral striatum. However, structural brain correlates of video game playing have not been investigated. On magnetic resonance imaging scans of 154 14-year-olds, we computed voxel-based morphometry to explore differences between frequent and infrequent video game players. Moreover, we assessed the Monetary Incentive Delay (MID) task during functional magnetic resonance imaging and the Cambridge Gambling Task (CGT). We found higher left striatal grey matter volume when comparing frequent against infrequent video game players that was negatively correlated with deliberation time in CGT. Within the same region, we found an activity difference in MID task: frequent compared with infrequent video game players showed enhanced activity during feedback of loss compared with no loss. This activity was likewise negatively correlated with deliberation time. The association of video game playing with higher left ventral striatum volume could reflect altered reward processing and represent adaptive neural plasticity.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2010.12.012

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

Common and distinct networks underlying reward valence and processing stages: a meta-analysis of functional neuroimaging studies.

To better understand the reward circuitry in human brain, we conducted activation likelihood estimation (ALE) and parametric voxel-based meta-analyses (PVM) on 142 neuroimaging studies that examined brain activation in reward-related tasks in healthy adults. We observed several core brain areas that participated in reward-related decision making, including the nucleus accumbens (NAcc), caudate, putamen, thalamus, orbitofrontal cortex (OFC), bilateral anterior insula, anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC), as well as cognitive control regions in the inferior parietal lobule and prefrontal cortex (PFC). The NAcc was commonly activated by both positive and negative rewards across various stages of reward processing (e.g., anticipation, outcome, and evaluation). In addition, the medial OFC and PCC preferentially responded to positive rewards, whereas the ACC, bilateral anterior insula, and lateral PFC selectively responded to negative rewards. Reward anticipation activated the ACC, bilateral anterior insula, and brain stem, whereas reward outcome more significantly activated the NAcc, medial OFC, and amygdala. Neurobiological theories of reward-related decision making should therefore take distributed and interrelated representations of reward valuation and valence assessment into account.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroscience.2010.12.016

Neuroscience

Neuroscience

Fast dopamine release events in the nucleus accumbens of early adolescent rats.

Subsecond fluctuations in dopamine (dopamine transients) in the nucleus accumbens are often time-locked to rewards and cues and provide an important learning signal during reward processing. As the mesolimbic dopamine system undergoes dynamic changes during adolescence in the rat, it is possible that dopamine transients encode reward and stimulus presentations differently in adolescents. However, to date no measurements of dopamine transients in awake adolescents have been made. Thus, we used fast scan cyclic voltammetry to measure dopamine transients in the nucleus accumbens core of male rats (29-30 days of age) at baseline and with the presentation of various stimuli that have been shown to trigger dopamine release in adult rats. We found that dopamine transients were detectable in adolescent rats and occurred at a baseline rate similar to adult rats (71-72 days of age). However, unlike adults, adolescent rats did not reliably exhibit dopamine transients at the unexpected presentation of visual, audible and odorous stimuli. In contrast, brief interaction with another rat increased dopamine transients in both adolescent and adult rats. While this effect habituated in adults at a second interaction, it persisted in the adolescents. These data are the first demonstration of dopamine transients in adolescent rats and reveal an important divergence from adults in the occurrence of these transients that may result in differential learning about rewards.

CognitiveConstruct

RewardProcessing

10.1111/j.1600-0447.2010.01659.x

Acta psychiatrica Scandinavica

Acta Psychiatr Scand

Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is characterized by the dysfunction of control and reward mechanisms. However, only few neuroimaging studies of OCD have examined the reward processing. We examined the neural responses during incentive processing in OCD. Twenty unmedicated patients with OCD and 20 age-, sex-, and IQ-matched healthy controls underwent functional magnetic resonance imaging while performing a modified monetary incentive delay task. Compared with controls, patients with OCD showed increased ventral striatal activation in the no-loss minus loss outcome contrast and a significant positive correlation between the ventral striatal activation and compulsion symptom severity. In addition, patients with OCD showed increased activations in the frontostriatal regions in the gain minus no-gain outcomes contrast. During loss anticipation, patients with OCD showed less activations in the lateral prefrontal and inferior parietal cortices. However, during gain anticipation, patients with OCD and healthy controls did not differ in the ventral striatal activation. These findings provide neural evidence for altered incentive processing in unmedicated patients with OCD, suggesting an elevated sensitivity to negatively affect stimuli as well as dysfunction of the ventral striatum.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2010.12.012

Neuropsychologia

Neuropsychologia

ADHD related behaviors are associated with brain activation in the reward system.

Neuroimaging studies on attention-deficit/hyperactivity disorder (ADHD) suggest dysfunctional reward processing, with hypo-responsiveness during reward anticipation in the reward system including the nucleus accumbens (NAcc). In this study, we investigated the association between ADHD related behaviors and the reward system using functional magnetic resonance imaging in a non-clinical sample. Participants were 31 healthy, female undergraduate students with varying levels of self-reported ADHD related behaviors measured by the adult ADHD self-report scale. The anticipation of different types of reward was investigated: monetary reward, punishment avoidance, and verbal feedback. All three reward anticipation conditions were found to be associated with increased brain activation in the reward system, with the highest activation in the monetary reward anticipation condition, followed by the punishment avoidance anticipation condition, and the lowest activation in the verbal feedback anticipation condition. Most interestingly, in all three conditions, NAcc activation was negatively correlated with ADHD related behaviors. In conclusion, our results from a non-clinical sample are in accordance with reported deficits in the reward system in ADHD patients: the higher the number and severity of ADHD related behaviors, the lower the neural responses in the dopaminergic driven reward anticipation task. Thus, our data support current aetiological models of ADHD which assume that deficits in the reward system might be responsible for many of the ADHD related behaviors.

CognitiveConstruct

RewardProcessing

10.1080/13803395.2010.524150

Journal of clinical and experimental neuropsychology

J Clin Exp Neuropsychol

Iowa gambling task in Parkinson's disease.

Cognitive impairments are common in patients with Parkinson's disease (PD) from the early stages. Recent studies reported that medicated PD patients have poor performances, with respect to age-matched healthy controls, in a decision-making task like the Iowa Gambling Task (IGT), which detects the ability to alter choice behavior in response to fluctuations in reward contingencies. The IGT principally activates functions related to the orbitofrontal cortex, which plays a crucial role in the generation of outcome expectancies and processing of rewards. The analysis of IGT performances of PD patients is of particular interest because PD represents a good clinical model to study reward processing when its neural bases are affected by a neuropathology or are overdosed by dopaminergic therapies. As a matter of fact, either PD-related neuropathology in advanced stages of the disease or the dopamine replacement therapy from earlier stages of PD may affect the functioning of the orbitofrontal cortex. Three causal hypotheses on a dysfunctional decision making in PD patients, as assessed by IGT, are discussed. Finally, the possible relation between the phenomenon of decision-making impairment and impulse control disorders, a psychiatric complication observed with increasing frequency in PD patients, is discussed.

CognitiveConstruct

RewardProcessing

10.1001/archgenpsychiatry.2010.178

Archives of general psychiatry

Arch Gen Psychiatry

Integrating neurobiological markers of depression.

Although psychiatric disorders are, to date, diagnosed on the basis of behavioral symptoms and course of illness, the interest in neurobiological markers of psychiatric disorders has grown substantially in recent years. However, current classification approaches are mainly based on data from a single biomarker, making it difficult to predict disorders characterized by complex patterns of symptoms. To integrate neuroimaging data associated with multiple symptom-related neural processes and demonstrate their utility in the context of depression by deriving a predictive model of brain activation. Two groups of participants underwent functional magnetic resonance imaging during 3 tasks probing neural processes relevant to depression. Participants were recruited from the local population by use of advertisements; participants with depression were inpatients from the Department of Psychiatry, Psychosomatics, and Psychotherapy at the University of Wuerzburg, Wuerzburg, Germany. We matched a sample of 30 medicated, unselected patients with depression by age, sex, smoking status, and handedness with 30 healthy volunteers. Accuracy of single-subject classification based on whole-brain patterns of neural responses from all 3 tasks. Integrating data associated with emotional and affective processing substantially increases classification accuracy compared with single classifiers. The predictive model identifies a combination of neural responses to neutral faces, large rewards, and safety cues as nonredundant predictors of depression. Regions of the brain associated with overall classification comprise a complex pattern of areas involved in emotional processing and the analysis of stimulus features. Our method of integrating neuroimaging data associated with multiple, symptom-related neural processes can provide a highly accurate algorithm for classification. The integrated biomarker model shows that data associated with both emotional and reward processing are essential for a highly accurate classification of depression. In the future, large-scale studies will need to be conducted to determine the practical applicability of our algorithm as a biomarker-based diagnostic aid.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2010.09.049

Biological psychiatry

Biol Psychiatry

Individuals family history positive for alcoholism show functional magnetic resonance imaging differences in reward sensitivity that are related to impulsivity factors.

Substance-abusing individuals tend to display abnormal reward processing and a vulnerability to being impulsive. Detoxified alcoholics show differences in regional brain activation during a monetary incentive delay task. However, there is limited information on whether this uncharacteristic behavior represents a biological predisposition toward alcohol abuse, a consequence of chronic alcohol use, or both. We investigated proposed neural correlates of substance disorder risk by examining reward system activity during a monetary incentive delay task with separate reward prospect, reward anticipation, and reward outcome phases in 30 individuals with and 19 without family histories of alcoholism. All subjects were healthy, lacked DSM-IV past or current alcohol or substance abuse histories, and were free of illegal substances as verified by a urine toxicology screening at the time of scanning. Additionally, we explored specific correlations between task-related nucleus accumbens (NAcc) activation and distinct factor analysis-derived domains of behavioral impulsivity. During reward anticipation, functional magnetic resonance imaging data confirmed blunted NAcc activation in family history positive subjects. In addition, we found atypical activation in additional reward-associated brain regions during additional task phases. We further found a significant negative correlation between NAcc activation during reward anticipation and an impulsivity construct. Overall, results demonstrate that sensitivity of the reward circuit, including NAcc, is functionally different in alcoholism family history positive individuals in multiple regards.

CognitiveConstruct

RewardProcessing

10.1016/j.psychres.2010.11.006

Psychiatry research

Psychiatry Res

Feedback and reward processing in high-functioning autism.

Individuals with high-functioning autism often display deficits in social interactions and high-level cognitive functions. Such deficits may be influenced by poor ability to process feedback and rewards. The feedback-related negativity (FRN) is an event-related potential (ERP) that is more negative following losses than gains. We examined FRN amplitude in 25 individuals with Autism Spectrum Disorder (ASD) and 25 age- and IQ-matched typically developing control participants who completed a guessing task with monetary loss/gain feedback. Both groups demonstrated a robust FRN that was more negative to loss trials than gain trials; however, groups did not differ in FRN amplitude as a function of gain or loss trials. N1 and P300 amplitudes did not differentiate groups. FRN amplitude was positively correlated with age in individuals with ASD, but not measures of intelligence, anxiety, behavioral inhibition, or autism severity. Given previous findings of reduced-amplitude error-related negativity (ERN) in ASD, we propose that individuals with ASD may process external, concrete, feedback similar to typically developing individuals, but have difficulty with internal, more abstract, regulation of performance.

CognitiveConstruct

RewardProcessing

10.1038/npp.2010.164

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

fMRI studies of reward processing in adolescent depression.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2010.11.004

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

Int J Psychophysiol

The effect of pre- vs. post-reward attainment on EEG asymmetry in melancholic depression.

Clinical investigators have long theorized about the role of reward processing and positive affect in depression. One theory posits that compared to nonmelancholic depressives, melancholic depressives experience less consummatory (i.e., post-reward), but comparably low anticipatory (prior to reward), positive affect. We tested whether frontal EEG asymmetry, a putative marker of the anticipatory reward system, is present only before an individual receives a reward or also after receiving a reward (i.e., during consummatory reward processing). We also examined whether melancholic depression, a condition characterized by a deficit in consummatory reward processing, is associated with abnormal EEG asymmetries in alpha band power. Effects in other frequency bands (delta, theta, or beta) were also explored. EEG was recorded in 34 controls, 48 nonmelancholic depressives, and 17 melancholic depressives during a slot machine task designed to elicit anticipatory and consummatory reward processing. Results indicated that, for alpha, the frontal EEG asymmetry of greater relative left activity was specific to anticipatory reward processing. During the consummatory phase, individuals with melancholic depression exhibited different posterior EEG asymmetries than individuals with nonmelancholic depression (and controls at a trend level). This second finding was largely due to melancholics exhibiting relatively lower right posterior activity and nonmelancholics exhibiting relatively lower left activity. These results suggest that a posterior asymmetry may be a marker for melancholic depression and aberrant consummatory reward processing.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2010.00176

Frontiers in neuroscience

Front Neurosci

From bad to worse: striatal coding of the relative value of painful decisions.

The majority of decision-related research has focused on how the brain computes decisions over outcomes that are positive in expectation. However, much less is known about how the brain integrates information when all possible outcomes in a decision are negative. To study decision-making over negative outcomes, we used fMRI along with a task in which participants had to accept or reject 50/50 lotteries that could result in more or fewer electric shocks compared to a reference amount. We hypothesized that behaviorally, participants would treat fewer shocks from the reference amount as a gain, and more shocks from the reference amount as a loss. Furthermore, we hypothesized that this would be reflected by a greater BOLD response to the prospect of fewer shocks in regions typically associated with gain, including the ventral striatum and orbitofrontal cortex. The behavioral data suggest that participants in our study viewed all outcomes as losses, despite our attempt to induce a status quo. We find that the ventral striatum showed an increase in BOLD response to better potential gambles (i.e., fewer expected shocks). This lends evidence to the idea that the ventral striatum is not solely responsible for reward processing but that it might also signal the relative value of an expected outcome or action, regardless of whether the outcome is entirely appetitive or aversive. We also find a greater response to worse gambles in regions previously associated with aversive valuation, suggesting an opposing but simultaneous valuation signal to that conveyed by the striatum.

CognitiveConstruct

RewardProcessing

10.1111/j.1469-8986.2010.01152.x

Psychophysiology

Psychophysiology

On the number of trials needed for a stable feedback-related negativity.

Feedback-related negativity is an event-related brain potential elicited by negative feedback. Its properties make it a valuable tool for the assessment of cognitive-affective processes that are involved in feedback and reward processing. The present study sought to determine the minimum number of trials that are required to obtain a reliable FRN component using a simple gambling paradigm. Three independent groups of young participants and one group of old participants were used. In the experimental conditions with healthy young controls, 20 trials were sufficient to measure the optimal FRN amplitude. In older participants, 50 trials were needed to obtain a reliable FRN. Whereas 20 trials would be enough to ensure a reliable FRN component in studies with nonclinical samples, the number of trials needed in clinical and cognitively impaired populations has to be determined based on the signal-to-noise ratios and the characteristics of the signals recorded.

CognitiveConstruct

RewardProcessing

10.1016/j.mehy.2010.10.038

Medical hypotheses

Med Hypotheses

Anorexia nervosa and the insula.

Anorexia nervosa is a serious illness with major physical and psychological morbidity. It has largely been understood in terms of cultural and environmental explanations. However these are insufficient to explain the diverse clinical features of the illness, nor its rarity given the universality of sociocultural factors. Over the last 20 years, there has been a steady accumulation of neurobiological evidence requiring a re-formulation of current causal models. We now offer a new empirically-derived hypothesis implicating underlying rate-limiting dysfunction of insula cortex as a crucial risk factor for the development of anorexia nervosa. Supporting evidence for this hypothesis is drawn from anatomical and clinical research of insula cortex damage in humans and neuroscientific studies of relevant clinical features including taste, pain perception and reward processing. This hypothesis, if sustainable, would be the first fully to explain the disorder and predicts promising novel treatment possibilities including Cognitive Remediation and Motivation Enhancement Therapies. The knowledge that the challenging behaviours, so characteristic of AN, are the result of underlying cerebral dysfunction, rather than being purely volitional, could help to reduce the stigma patients experience and improve the therapeutic alliance in this poorly understood and difficult to treat disorder.

CognitiveConstruct

RewardProcessing

10.1080/17470919.2010.527169

Social neuroscience

Soc Neurosci

A genetic contribution to cooperation: dopamine-relevant genes are associated with social facilitation.

Social loafing and social facilitation are stable behavioral effects that describe increased or decreased motivation, as well as effort and cooperation in teamwork as opposed to individual working situations. Recent twin studies demonstrate the heritability of cooperative behavior. Brain imaging studies have shown that reciprocity, cooperativeness, and social rewards activate reward processing areas with strong dopaminergic input, such as the ventral striatum. Thus, candidate genes for social behavior are hypothesized to affect dopaminergic neurotransmission. In the present study, we investigated the dopaminergic genetic contribution to social cooperation, especially to social loafing and social facilitation. N = 106 healthy, Caucasian subjects participated in the study and were genotyped for three polymorphisms relevant to the dopaminergic system (COMTval158met, DRD2 c957t, DRD2 rs#2283265). In addition to a main effect indicating an increased performance in teamwork situations, we found a significant interaction between a haplotype block covering both DRD2 single nucleotide polymorphisms (SNPs) (rs#6277 and rs#2283265), henceforth referred to as the DRD2-haplotype block, and the COMT val158met polymorphism (rs#4680) with social facilitation. Carriers of the DRD2 CT-haplotype block and at least one Val-allele showed a greater increase in performance in teamwork settings when compared with carriers of the CT-haplotype block and the Met/Met-genotype. Our results suggest that epistasis between COMTval158met and the two DRD2 SNPs contributes to individual differences in cooperativeness in teamwork settings.

CognitiveConstruct

RewardProcessing

10.3389/fnagi.2010.00144

Frontiers in aging neuroscience

Front Aging Neurosci

Remedial effects of motivational incentive on declining cognitive control in healthy aging and Parkinson's disease.

The prospect of reward may provide a motivational incentive for optimizing goal-directed behavior. Animal work demonstrates that reward-processing networks and oculomotor-control networks in the brain are connected through the dorsal striatum, and that reward anticipation can improve oculomotor control via this nexus. Due perhaps to deterioration in dopaminergic striatal circuitry, goal-directed oculomotor control is subject to decline in healthy seniors, and even more in individuals with Parkinson's disease (PD). Here we examine whether healthy seniors and PD patients are able to utilize reward prospects to improve their impaired antisaccade performance. Results confirmed that oculomotor control declined in PD patients compared to healthy seniors, and in healthy seniors compared to young adults. However, the motivational incentive of reward expectation resulted in benefits in antisaccade performance in all groups alike. These findings speak against structural and non-modifiable decline in cognitive control functions, and emphasize the remedial potential of motivational incentive mechanisms in healthy as well as pathological aging.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0013309

PloS one

PLoS One

Viewing pictures of a romantic partner reduces experimental pain: involvement of neural reward systems.

The early stages of a new romantic relationship are characterized by intense feelings of euphoria, well-being, and preoccupation with the romantic partner. Neuroimaging research has linked those feelings to activation of reward systems in the human brain. The results of those studies may be relevant to pain management in humans, as basic animal research has shown that pharmacologic activation of reward systems can substantially reduce pain. Indeed, viewing pictures of a romantic partner was recently demonstrated to reduce experimental thermal pain. We hypothesized that pain relief evoked by viewing pictures of a romantic partner would be associated with neural activations in reward-processing centers. In this functional magnetic resonance imaging (fMRI) study, we examined fifteen individuals in the first nine months of a new, romantic relationship. Participants completed three tasks under periods of moderate and high thermal pain: 1) viewing pictures of their romantic partner, 2) viewing pictures of an equally attractive and familiar acquaintance, and 3) a word-association distraction task previously demonstrated to reduce pain. The partner and distraction tasks both significantly reduced self-reported pain, although only the partner task was associated with activation of reward systems. Greater analgesia while viewing pictures of a romantic partner was associated with increased activity in several reward-processing regions, including the caudate head, nucleus accumbens, lateral orbitofrontal cortex, amygdala, and dorsolateral prefrontal cortex--regions not associated with distraction-induced analgesia. The results suggest that the activation of neural reward systems via non-pharmacologic means can reduce the experience of pain.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2010.07.037

Biological psychiatry

Biol Psychiatry

Differentiating frontostriatal and fronto-cerebellar circuits in attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) has long been conceptualized as a neurobiological disorder of the prefrontal cortex and its connections. Circuits with the prefrontal cortex relevant to ADHD include dorsal frontostriatal, orbitofronto-striatal, and fronto-cerebellar circuits. Dorsal frontostriatal circuitry has been linked to cognitive control, whereas orbitofronto-striatal loops have been related to reward processing. Fronto-cerebellar circuits have been implicated in timing. Neurobiological dysfunction in any of these circuits could lead to symptoms of ADHD, as behavioral control could be disturbed by: 1) deficits in the prefrontal cortex itself; or 2) problems in the circuits relaying information to the prefrontal cortex, leading to reduced signaling for control. This article suggests a model for differentiating between interlinked reciprocal circuits with the prefrontal cortex in ADHD. If such a differentiation can be achieved, it might permit a neurobiological subtyping of ADHD, perhaps by defining "dorsal fronto-striatal," "orbitofronto-striatal," or "fronto-cerebellar" subtypes of ADHD. This could be useful as a template for investigating the neurobiology of ADHD and, ultimately, clinically.

CognitiveConstruct

RewardProcessing

10.1016/j.eurpsy.2010.07.011

European psychiatry : the journal of the Association of European Psychiatrists

Eur Psychiatry

Functional neuroimaging in anorexia nervosa: a clinical approach.

To provide a review of the available literature about the functional neuroimaging of anorexia nervosa, and to summarize the possible role of neurobiological factors in its pathogenesis. A systematic review of the literature was performed using PubMed and Medline electronic database (1950-September 2009). Eligible studies were restricted to those involving the main parameters of cerebral activity and functional neuroimaging techniques. Findings of the reviewed studies have been grouped on a diagnostic subtype basis, and their comparison has been interpreted in terms of concordance. We found a high level of concordance among available studies with regard to the presence of frontal, parietal and cingulate functional disturbances in both anorexia nervosa restricting and binge/purging subtypes. Concordance among studies conducted regardless of the anorexia nervosa subtypes suggests an alteration in temporal and parietal functions and striatal metabolism. The most consistent alterations in anorexia nervosa cerebral activity seem to involve the dorsolateral prefrontal cortex, the inferior parietal lobule, the anterior cingulate cortex and the caudate nucleus. They may affect different neural systems such as the frontal visual system, the attention network, the arousal and emotional processing systems, the reward processing network, and the network for the body schema.

CognitiveConstruct

RewardProcessing

10.1016/j.cub.2010.08.048

Current biology : CB

Curr Biol

Differentiable neural substrates for learned and described value and risk.

Studies of human decision making emerge from two dominant traditions: learning theorists [1-3] study choices in which options are evaluated on the basis of experience, whereas behavioral economists and financial decision theorists study choices in which the key decision variables are explicitly stated. Growing behavioral evidence suggests that valuation based on these different classes of information involves separable mechanisms [4-8], but the relevant neuronal substrates are unknown. This is important for understanding the all-too-common situation in which choices must be made between alternatives that involve one or another kind of information. We studied behavior and brain activity while subjects made decisions between risky financial options, in which the associated utilities were either learned or explicitly described. We show a characteristic effect in subjects' behavior when comparing information acquired from experience with that acquired from description, suggesting that these kinds of information are treated differently. This behavioral effect was reflected neurally, and we show differential sensitivity to learned and described value and risk in brain regions commonly associated with reward processing. Our data indicate that, during decision making under risk, both behavior and the neural encoding of key decision variables are strongly influenced by the manner in which value information is presented.

CognitiveConstruct

RewardProcessing

10.1007/s00213-010-2009-2

Psychopharmacology

Psychopharmacology (Berl)

Effects of early life stress on cognitive and affective function: an integrated review of human literature.

The investigation of putative effects of early life stress (ELS) in humans on later behavior and neurobiology is a fast developing field. While epidemiological and neurobiological studies paint a somber picture of negative outcomes, relatively little attention has been devoted to integrating the breadth of findings concerning possible cognitive and emotional deficits associated with ELS. Emerging findings from longitudinal studies examining developmental trajectories of the brain in healthy samples may provide a new framework to understand mechanisms underlying ELS sequelae. The goal of this review was twofold. The first was to summarize findings from longitudinal data on normative brain development. The second was to utilize this framework of normative brain development to interpret changes in developmental trajectories associated with deficits in cognitive and affective function following ELS. Five principles of normative brain development were identified and used to discuss behavioral and neural sequelae of ELS. Early adversity was found to be associated with deficits in a range of cognitive (cognitive performance, memory, and executive functioning) and affective (reward processing, processing of social and affective stimuli, and emotion regulation) functions. Three general conclusions emerge: (1) higher-order, complex cognitive and affective functions associated with brain regions undergoing protracted postnatal development are particularly vulnerable to the deleterious effects of ELS; (2) the amygdala is particularly sensitive to early ELS; and (3) several deficits, particularly those in the affective domain, appear to persist years after ELS has ceased and may increase risk for later psychopathology.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsq078

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Individual differences in reward-prediction-error: extraversion and feedback-related negativity.

Medial frontal scalp-recorded negativity occurring ∼200-300 ms post-stimulus [known as feedback-related negativity (FRN)] is attenuated following unpredicted reward and potentiated following unpredicted non-reward. This encourages the view that FRN may partly reflect dopaminergic 'reward-prediction-error' signalling. We examined the influence of a putatively dopamine-based personality trait, extraversion (N = 30), and a dopamine-related gene polymorphism, DRD2/ANKK1 (N = 24), on FRN during an associative reward-learning paradigm. FRN was most negative following unpredicted non-reward and least-negative following unpredicted reward. A difference wave contrasting these conditions was significantly more pronounced for extraverted participants than for introverts, with a similar but non-significant trend for participants carrying at least one copy of the A1 allele of the DRD2/ANKK1 gene compared with those without the allele. Extraversion was also significantly higher in A1 allele carriers. Results have broad relevance to neuroscience and personality research concerning reward processing and dopamine function.

CognitiveConstruct

RewardProcessing

10.1016/j.yhbeh.2010.09.006

Hormones and behavior

Horm Behav

Lesions of orexin neurons block conditioned place preference for sexual behavior in male rats.

The hypothalamic neuropeptide orexin (hypocretin) mediates reward related to drugs of abuse and food intake. However, a role for orexin in sexual reward has yet to be investigated. Orexin neurons are activated by sexual behavior, but endogenous orexin does not appear to be essential for sexual performance and motivation in male rats. Therefore, the goal of the current study was to test the hypothesis that orexin is critically involved in processing of sexual reward in male rats. First, it was demonstrated following exposure to conditioned contextual cues associated with sexual behavior in a conditioned place preference paradigm that cFos expression is induced in orexin neurons, indicating activation of orexin neurons by cues predicting sexual reward. Next, orexin-cell specific lesions were utilized to determine the functional role of orexin in sexual reward processing. Hypothalami of adult male rats were infused with orexin-B-conjugated saporin, resulting in greater than 80% loss of orexin neurons in the perifornical-dorsomedial and lateral hypothalamus. Orexin lesions did not affect expression of sexual behavior, but prevented formation of conditioned place preference for a sexual behavior paired chamber. In contrast, intact sham-treated males or males with partial lesions developed a conditioned place preference for mating. Orexin lesioned males maintained the ability to form a conditioned place aversion to lithium chloride-induced visceral illness, indicating that orexin lesions did not disrupt associative contextual memory. Overall, these findings suggest that orexin is not essential for sexual performance or motivation, but is critical for reward processing and conditioned cue-induced seeking of sexual behavior.

CognitiveConstruct

RewardProcessing

10.1002/hbm.21127

Human brain mapping

Hum Brain Mapp

Association between reward-related activation in the ventral striatum and trait reward sensitivity is moderated by dopamine transporter genotype.

The impact of individual differences on human reward processing has been a focus of research in recent years, particularly, as they are associated with a variety of neuropsychiatric diseases including addiction and attention-deficit/hyperactivity disorder. Studies exploring the neural basis of individual differences in reward sensitivity have consistently implicated the ventral striatum (VS) as a core component of the human reward system. However, the mechanisms of dopaminergic neurotransmission underlying ventral striatal activation as well as trait reward sensitivity remain speculative. We addressed this issue by investigating the triadic interplay between VS reactivity during reward anticipation using functional magnetic resonance imaging, trait reward sensitivity, and dopamine (DA) transporter genotype (40-bp 3'VNTR of DAT, SLC6A3) affecting synaptic DA neurotransmission. Our results show that DAT variation moderates the association between VS-reactivity and trait reward sensitivity. Specifically, homozygote carriers of the DAT 10-repeat allele exhibit a strong positive correlation between reward sensitivity and reward-related VS activity whereas this relationship is absent in the DAT 9-repeat allele carriers. We discuss the possibility that this moderation of VS-trait relation might arise from DAT-dependent differences in DA availability affecting synaptic plasticity within the VS. Generally, studying the impact of dopaminergic gene variations on the relation between reward-related brain activity and trait reward sensitivity might facilitate the investigation of complex mechanisms underlying disorders linked to dysregulation of DA neurotransmission.

CognitiveConstruct

RewardProcessing

10.1016/j.brainresrev.2010.09.001

Brain research reviews

Brain Res Rev

Prefrontal cortex and drug abuse vulnerability: translation to prevention and treatment interventions.

Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and humans. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals.

CognitiveConstruct

RewardProcessing

10.1093/cercor/bhq160

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

Cereb Cortex

Parental education predicts corticostriatal functionality in adulthood.

Socioeconomic disadvantage experienced in early development predicts ill health in adulthood. However, the neurobiological pathways linking early disadvantage to adult health remain unclear. Lower parental education-a presumptive indicator of early socioeconomic disadvantage-predicts health-impairing adult behaviors, including tobacco and alcohol dependencies. These behaviors depend, in part, on the functionality of corticostriatal brain systems that 1) show developmental plasticity and early vulnerability, 2) process reward-related information, and 3) regulate impulsive decisions and actions. Hence, corticostriatal functionality in adulthood may covary directly with indicators of early socioeconomic disadvantage, particularly lower parental education. Here, we tested the covariation between parental education and corticostriatal activation and connectivity in 76 adults without confounding clinical syndromes. Corticostriatal activation and connectivity were assessed during the processing of stimuli signaling monetary gains (positive feedback [PF]) and losses (negative feedback). After accounting for participants' own education and other explanatory factors, lower parental education predicted reduced activation in anterior cingulate and dorsomedial prefrontal cortices during PF, along with reduced connectivity between these cortices and orbitofrontal and striatal areas implicated in reward processing and impulse regulation. In speculation, adult alterations in corticostriatal functionality may represent facets of a neurobiological endophenotype linked to socioeconomic conditions of early development.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.0111-10.2010

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

J Neurosci

Microstructural brain differences predict functional hemodynamic responses in a reward processing task.

Many aspects of human behavior are driven by rewards, yet different people are differentially sensitive to rewards and punishment. In this study, we show that white matter microstructure in the uncinate/inferior fronto-occipital fasciculus, defined by fractional anisotropy values derived from diffusion tensor magnetic resonance images, correlates with both short-term (indexed by the fMRI blood oxygenation level-dependent response to reward in the nucleus accumbens) and long-term (indexed by the trait measure sensitivity to punishment) reactivity to rewards. Moreover, trait measures of reward processing were also correlated with reward-related functional activation in the nucleus accumbens. The white matter tract revealed by the correlational analysis connects the anterior temporal lobe with the medial and lateral orbitofrontal cortex and also supplies the ventral striatum. The pattern of strong correlations suggests an intimate relationship between white matter structure and reward-related behavior that may also play a role in a number of pathological conditions, such as addiction and pathological gambling.

CognitiveConstruct

RewardProcessing

10.1016/j.schres.2010.07.023

Schizophrenia research

Schizophr Res

Reduced intra-amygdala activity to positively valenced faces in adolescent schizophrenia offspring.

Studies suggest that the affective response is impaired in both schizophrenia and adolescent offspring of schizophrenia patients. Adolescent offspring of patients are developmentally vulnerable to impairments in several domains, including affective responding, yet the bases of these impairments and their relation to neuronal responses within the limbic system are poorly understood. The amygdala is the central region devoted to the processing of emotional valence and its sub-nuclei including the baso-lateral and centro-medial are organized in a relative hierarchy of affective processing. Outputs from the centro-medial nucleus converge on regions involved in the autonomous regulation of behavior, and outputs from the baso-lateral nucleus modulate the response of reward processing regions. Here using fMRI we assessed the intra-amygdala response to positive, negative, and neutral valenced faces in a group of controls (with no family history of psychosis) and offspring of schizophrenia parents (n=44 subjects in total). Subjects performed an affective continuous performance task during which they continually appraised whether the affect signaled by a face on a given trial was the same or different from the previous trial (regardless of facial identity). Relative to controls, offspring showed reduced activity in the left centro-medial nucleus to positively (but not negatively or neutral) valenced faces. These results were independent of behavioral/cognitive performance (equal across groups) suggesting that an impaired affective substrate in the intra-amygdala response may lie at the core of deficits of social behavior that have been documented in this population.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2010.00039

Frontiers in behavioral neuroscience

Front Behav Neurosci

Reward sensitivity for a palatable food reward peaks during pubertal developmental in rats.

Puberty is a critical period for the initiation of drug use and abuse. Because early drug use onset often accounts for a more severe progression of addiction, it is of importance to understand the underlying mechanisms and neurodevelopmental changes during puberty that are contributing to enhanced reward processing in teenagers. The present study investigated the progression of reward sensitivity toward a natural food reward over the whole course of adolescence in male rats (postnatal days 30-90) by monitoring consummatory, motivational behavior and neurobiological correlates of reward. Using a limited-free intake paradigm, consumption of sweetened condensed milk (SCM) was measured repeatedly in adolescent and adult rats. Additionally, early- and mid-pubertal animals were tested in Progressive Ratio responding for SCM and c-fos protein expression in reward-associated brain structures was examined after odor conditioning for SCM. We found a transient increase in SCM consumption and motivational incentive for SCM during puberty. This increased reward sensitivity was most pronounced around mid-puberty. The behavioral findings are paralleled by enhanced c-fos staining in reward-related structures revealing an intensified neuronal response after reward-cue presentation, distinctive for pubertal animals. Taken together, these data indicate an increase in reward sensitivity during adolescence accompanied by enhanced responsiveness of reward-associated brain structures to incentive stimuli, and it seems that both is strongly pronounced around mid-puberty. Therefore, higher reward sensitivity during pubertal maturation might contribute to the enhanced vulnerability of teenagers for the initiation of experimental drug use.

CognitiveConstruct

RewardProcessing

10.1038/ijo.2010.155

International journal of obesity (2005)

Int J Obes (Lond)

Taste, olfactory and food texture reward processing in the brain and obesity.

Complementary neuronal recordings and functional neuroimaging in humans, 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. Further, there are individual differences in the representation of the reward value of food in the OFC. It is argued that overeating 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, which overrides 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/mds.23326

Movement disorders : official journal of the Movement Disorder Society

Mov Disord

Decision making in restless legs syndrome.

The dopamine system is implicated in reward-based decision making with explicit information (decision making under risk) and implicit probabilities (decision making under ambiguity). Although the pathophysiology of restless legs syndrome (RLS) is not yet fully understood, the genetic factors, iron status, and dopaminergic system are thought to play a role. RLS provides an opportunity to test the dopaminergic hypothesis in a drug-free population and to characterize reward processing using decision-making paradigms. We investigated impulsivity, impulse control disorders, and decision making in 50 untreated patients with primary RLS compared with 60 sex- and age-matched normal controls using one night of polysomnography recording, a structured psychiatric interview, and questionnaires (RLS Severity Scale, Beck Depression Inventory, and Urgency Premeditation Perseverance Impulsive Behavior Scale). Subjects performed the Iowa Gambling Task to assess decision making under ambiguity and the Game of Dice Task to assess decision making under risk. Patients with RLS showed selective changes in decision making on the Iowa Gambling Task and normal decision making on the Game of Dice Task compared with controls. Patients with RLS had greater depressive symptoms than controls, but no difference was found in impulsivity, impulse control disorders, or addictive behaviors. Clinical and polysomnographic variables were unrelated to decision-making performance. Results indicate reduced decision-making performance under ambiguity in drug-free patients with RLS. From a clinical perspective, when using dopaminergic medication to treat RLS, patients with abnormal baseline behaviors should be closely monitored.

CognitiveConstruct

RewardProcessing

10.1007/s11031-010-9160-2

Motivation and emotion

Motiv Emot

Cueing task goals and earning money: Relatively high monetary rewards reduce failures to act on goals in a Stroop task.

We examined the role of monetary rewards in failures to act on goals in a Stroop task. Based on recent developments in theorizing on the interplay between rewards and cognitive control, we hypothesized that relatively high monetary rewards enhance the focus and stability of a cued task goal compared to low monetary rewards, and hence cause a reduction in failures to act on current task goals under circumstances that warrant top-down goal implementation. To test this, participants received a modified version of the Stroop task, in which they were either briefly cued with the goal of naming the color or meaning of targets on a trial-by-trial basis. After goal cuing, but before presenting the target, either a low or high reward cue was presented. Results showed that higher rewards produced a general speed-up. More importantly, Stroop interference on error rates was lower in the high reward condition compared to the low reward condition, revealing that the rewards enhanced focus and stability of the cued goal. These results provide support for theorizing that reward processing modulates utility assessment of current goals by affecting attention to facilitate goal-directed behavior.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2010.00048

Frontiers in human neuroscience

Front Hum Neurosci

Striatal BOLD Response Reflects the Impact of Herd Information on Financial Decisions.

Like other species, humans are sensitive to the decisions and actions of conspecifics, which can lead to herd behavior and undesirable outcomes such as stock market bubbles and bank runs. However, how the brain processes this socially derived influence is only poorly understood. Using functional magnetic resonance imaging (fMRI), we scanned participants as they made decisions on whether to buy stocks after observing others' buying decisions. We demonstrate that activity in the ventral striatum, an area heavily implicated in reward processing, tracked the degree of influence on participants' decisions arising from the observation of other peoples' decisions. The signal did not track non-human, non-social control decisions. These findings lend weight to the notion that the ventral striatum is involved in the processing of complex social aspects of decision making and identify a possible neural basis for herd behavior.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2010.05.033

Neuropsychologia

Neuropsychologia

A virtual reality-based FMRI study of reward-based spatial learning.

Although temporo-parietal cortices mediate spatial navigation in animals and humans, the neural correlates of reward-based spatial learning are less well known. Twenty-five healthy adults performed a virtual reality fMRI task that required learning to use extra-maze cues to navigate an 8-arm radial maze and find hidden rewards. Searching the maze in the spatial learning condition compared to the control conditions was associated with activation of temporo-parietal regions, albeit not including the hippocampus. The receipt of rewards was associated with activation of the hippocampus in a control condition when using the extra-maze cues for navigation was rendered impossible by randomizing the spatial location of cues. Our novel experimental design allowed us to assess the differential contributions of the hippocampus and other temporo-parietal areas to searching and reward processing during reward-based spatial learning. This translational research will permit parallel studies in animals and humans to establish the functional similarity of learning systems across species; cellular and molecular studies in animals may then inform the effects of manipulations on these systems in humans, and fMRI studies in humans may inform the interpretation and relevance of findings in animals.

CognitiveConstruct

RewardProcessing

10.1016/j.cpr.2010.05.007

Clinical psychology review

Clin Psychol Rev

Neurobiological correlates of social functioning in autism.

Although autism is defined by deficits in three areas of functioning (social, communicative, and behavioral), impairments in social interest and restricted behavioral repertoires are central to the disorder. As a result, a detailed understanding of the neurobiological systems subserving social behavior may have implications for prevention, early identification, and intervention for affected families. In this paper, we review a number of potential neurobiological mechanisms--across several levels of analysis--that subserve normative social functioning. These include neural networks, neurotransmitters, and hormone systems. After describing the typical functioning of each system, we review available empirical findings specific to autism. Among the most promising potential mechanisms of social behavioral deficits in autism are those involving neural networks including the amygdala, the mesocorticolimbic dopamine system, and the oxytocin system. Particularly compelling are explanatory models that integrate mechanisms across biological systems, such as those linking dopamine and oxytocin with brain regions critical to reward processing.

CognitiveConstruct

RewardProcessing

10.1177/0269881110367731

Journal of psychopharmacology (Oxford, England)

J Psychopharmacol

Dopaminergic modulation of the human reward system: a placebo-controlled dopamine depletion fMRI study.

Reward related behaviour is linked to dopaminergic neurotransmission. Our aim was to gain insight into dopaminergic involvement in the human reward system. Combining functional magnetic resonance imaging with dopaminergic depletion by α-methylparatyrosine we measured dopamine-related brain activity in 10 healthy volunteers. In addition to blood-oxygen-level-dependent (BOLD) contrast we assessed the effect of dopaminergic depletion on prolactin response, peripheral markers for dopamine and norepinephrine. In the placebo condition we found increased activation in the left caudate and left cingulate gyrus during anticipation of reward. In the α-methylparatyrosine condition there was no significant brain activation during anticipation of reward or loss. In α-methylparatyrosine, anticipation of reward vs. loss increased activation in the right insula, left frontal, right parietal cortices and right cingulate gyrus. Comparing placebo versus α-methylparatyrosine showed increased activation in the left cingulate gyrus during anticipation of reward and the left medial frontal gyrus during anticipation of loss. α-methylparatyrosine reduced levels of dopamine in urine and homovanillic acid in plasma and increased prolactin. No significant effect of α-methylparatyrosine was found on norepinephrine markers. Our findings implicate distinct patterns of BOLD underlying reward processing following dopamine depletion, suggesting a role of dopaminergic neurotransmission for anticipation of monetary reward.

CognitiveConstruct

RewardProcessing

10.1177/155005941004100208

Clinical EEG and neuroscience

Clin EEG Neurosci

Dopamine, reward, and frontostriatal circuitry in impulse control disorders in Parkinson's disease: insights from functional imaging.

Dopamine agonists have been implicated in the development of impulse control disorders (ICDs). This may be due to the ability of agonists to tonically stimulate dopamine receptors. Recent neuroimaging data provided evidence that dopamine agonists induce significant changes in those frontostriatal circuits that process reward and mediate our ability to control impulses. Tonic stimulation of dopamine receptors via agonists may impair reward processing and inhibitory control mechanisms in ways that promote pathological repetition of behaviors. We will provide an overview of the current understanding of the neurobiology underlying ICDs in Parkinson's disease (PD).

CognitiveConstruct

RewardProcessing

10.1016/j.concog.2010.05.001

Consciousness and cognition

Conscious Cogn

Boosting or choking--how conscious and unconscious reward processing modulate the active maintenance of goal-relevant information.

Two experiments examined similarities and differences in the effects of consciously and unconsciously perceived rewards on the active maintenance of goal-relevant information. Participants could gain high and low monetary rewards for performance on a word span task. The reward value was presented supraliminally (consciously visible) or subliminally at different stages during the task. In Experiment 1, rewards were presented before participants processed the target words. Enhanced performance was found in response to higher rewards, regardless whether they were presented supraliminally or subliminally. In Experiment 2, rewards were presented after participants processed the target words, i.e., during maintenance. Performance increased in response to relatively high rewards when they were presented subliminally, but decreased when they were presented supraliminally. We conclude that both consciously and unconsciously perceived rewards boost resources supporting the maintenance of task-relevant information. Conscious processing of rewards can, however, heavily interfere with an ongoing maintenance process and impair performance.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsq044

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Neural correlates of emotional synchrony.

Facial expressions can trigger emotions: when we smile we feel happy, when we frown we feel sad. However, the mimicry literature also shows that we feel happy when our interaction partner behaves the way we do. Thus what happens if we express our sadness and we perceive somebody who is imitating us? In the current study, participants were presented with either happy or sad faces, while expressing one of these emotions themselves. Functional magnetic resonance imaging was used to measure neural responses on trials where the observed emotion was either congruent or incongruent with the expressed emotion. Our results indicate that being in a congruent emotional state, irrespective of the emotion, activates the medial orbitofrontal cortex and ventromedial prefrontal cortex, brain areas that have been associated with positive feelings and reward processing. However, incongruent emotional states activated the dorsolateral prefrontal cortex as well as posterior superior temporal gyrus/sulcus, both playing a role in conflict processing.

CognitiveConstruct

RewardProcessing

10.1007/s00213-010-1880-1

Psychopharmacology

Psychopharmacology (Berl)

Dopamine precursor depletion improves punishment prediction during reversal learning in healthy females but not males.

The neurotransmitter dopamine has frequently been implicated in reward processing but is also, increasingly, implicated in punishment processing. We have previously shown that both patients with Parkinson's disease and healthy individuals with low dopamine (DA) synthesis are better at reversal learning based on punishment than reward. Here, we extend these prior findings by examining the effects of artificially reducing DA synthesis in healthy individuals performing this previously employed task. In a double-blind, placebo-controlled crossover design, we applied the acute tyrosine and phenylalanine depletion (ATPD) procedure to reduce global DA synthesis in 15 female and 14 male subjects. Each subject performed the reward- and punishment-based reversal-learning paradigm. There was a significant three-way interaction between ATPD, the valence of the outcome signalling reversal and the gender of the participants. Examination of punishment and reward-based reversals separately revealed that this was driven by a significant improvement in punishment processing in female but not male subjects following DA depletion. Reducing DA synthesis in healthy individuals shifted sensitivity of performance from reward to punishment processing. Gender differences in DA synthesis might underlie the selectivity of this effect to female subjects. Such gender biases may go some way towards explaining the gender biases in certain psychiatric disorders such as depression and Parkinson's disease.

CognitiveConstruct

RewardProcessing

10.1038/nn.2558

Nature neuroscience

Nat Neurosci

A unique adolescent response to reward prediction errors.

Previous work has shown that human adolescents may be hypersensitive to rewards, but it is not known which aspect of reward processing is responsible for this. We separated decision value and prediction error signals and found that neural prediction error signals in the striatum peaked in adolescence, whereas neural decision value signals varied depending on how value was modeled. This suggests that heightened dopaminergic prediction error responsivity contributes to adolescent reward seeking.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2010.05.012

NeuroImage

Neuroimage

Age-related functional changes in gustatory and reward processing regions: An fMRI study.

Changes in appetite in older adults may result in unhealthy weight change and negatively affect overall nutrition. Research examining gustatory processing in young adults has linked changes in patterns of the hemodynamic response of gustatory and motivation related brain regions to the physiological states of hunger and satiety. Whether the same brain regions are involved in taste processing in older adults is unknown. The current study used functional magnetic resonance imaging (fMRI) to examine age-related changes in gustatory processing during hedonic assessment. Caffeine, citric acid, sucrose, and NaCl were administered orally during two event-related fMRI sessions, one during hunger and one after a pre-load. Participants assessed the pleasantness of the solutions in each session. Increased activity of the insula was seen in both age groups during hunger. Activity of secondary and higher order taste processing and reward regions such as the orbitofrontal cortex, amygdala, hippocampus, thalamus, and caudate nucleus was also observed. Hunger and satiety differentially affected the hemodynamic response, resulting in positive global activation during hunger and negative during satiety in both age groups. While in a state of hunger, the frequency and consistency of positive activation in gustatory and reward processing regions was greater in older adults. Additional regions not commonly associated with taste processing were also activated in older adults. Investigating the neurological response of older adults to taste stimuli under conditions of hunger and satiety may aid in understanding appetite, health, and functional changes in this population.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2010.04.251

NeuroImage

Neuroimage

Nicotine replacement in abstinent smokers improves cognitive withdrawal symptoms with modulation of resting brain network dynamics.

Symptoms of cognitive impairment during smoking withdrawal can be ameliorated by nicotine replacement. To define brain mechanisms contributing to this therapeutic effect, we conducted a functional connectivity analysis of resting-state fMRI in 17 abstinent smokers following nicotine replacement in a double-blind, placebo-controlled, crossover design. We found that individual differences in cognitive withdrawal symptom improvements after nicotine replacement were associated with increased inverse coupling between executive control and default mode brain networks. Furthermore, improvements in withdrawal symptoms were negatively correlated with altered functional connectivity within the default mode network, and with connectivity between the executive control network and regions implicated in reward processing. These findings demonstrate that nicotine administration in abstinent smokers modulates dynamic interactions between large-scale cognitive brain networks in the resting state. We specifically highlight the role of midline and prefrontal network regions in the neurocognitive response to nicotine pharmacotherapy and suggest that altered functional connectivity patterns of these networks reflect their engagement in reward and salience processing during smoking withdrawal. Individual differences in resting brain functional connectivity may predict therapeutic outcomes in nicotine addiction and other conditions associated with cognitive impairments.

CognitiveConstruct

RewardProcessing

10.1038/ijo.2010.84

International journal of obesity (2005)

Int J Obes (Lond)

Obese children show hyperactivation to food pictures in brain networks linked to motivation, reward and cognitive control.

To investigate the neural mechanisms of food motivation in children and adolescents, and examine brain activation differences between healthy weight (HW) and obese participants. Ten HW children (ages 11-16; BMI < 85%ile) and 10 obese children (ages 10-17; BMI >95%ile) matched for age, gender and years of education. Functional magnetic resonance imaging (fMRI) scans were conducted twice: when participants were hungry (pre-meal) and immediately after a standardized meal (post-meal). During the fMRI scans, the participants passively viewed blocked images of food, non-food (animals) and blurred baseline control. Both groups of children showed brain activation to food images in the limbic and paralimbic regions (PFC/OFC). The obese group showed significantly greater activation to food pictures in the PFC (pre-meal) and OFC (post-meal) than the HW group. In addition, the obese group showed less post-meal reduction of activation (vs pre-meal) in the PFC, limbic and the reward-processing regions, including the nucleus accumbens. Limbic and paralimbic activation in high food motivation states was noted in both groups of participants. However, obese children were hyper-responsive to food stimuli as compared with HW children. In addition, unlike HW children, brain activations in response to food stimuli in obese children failed to diminish significantly after eating. This study provides initial evidence that obesity, even among children, is associated with abnormalities in neural networks involved in food motivation, and that the origins of neural circuitry dysfunction associated with obesity may begin early in life.

CognitiveConstruct

RewardProcessing

10.1002/aur.122

Autism research : official journal of the International Society for Autism Research

Autism Res

Reward processing in autism.

The social motivation hypothesis of autism posits that infants with autism do not experience social stimuli as rewarding, thereby leading to a cascade of potentially negative consequences for later development. While possible downstream effects of this hypothesis such as altered face and voice processing have been examined, there has not been a direct investigation of social reward processing in autism. Here we use functional magnetic resonance imaging to examine social and monetary rewarded implicit learning in children with and without autism spectrum disorders (ASD). Sixteen males with ASD and sixteen age- and IQ-matched typically developing (TD) males were scanned while performing two versions of a rewarded implicit learning task. In addition to examining responses to reward, we investigated the neural circuitry supporting rewarded learning and the relationship between these factors and social development. We found diminished neural responses to both social and monetary rewards in ASD, with a pronounced reduction in response to social rewards (SR). Children with ASD also demonstrated a further deficit in frontostriatal response during social, but not monetary, rewarded learning. Moreover, we show a relationship between ventral striatum activity and social reciprocity in TD children. Together, these data support the hypothesis that children with ASD have diminished neural responses to SR, and that this deficit relates to social learning impairments.

CognitiveConstruct

RewardProcessing

10.1017/S1461145710000453

The international journal of neuropsychopharmacology

Int J Neuropsychopharmacol

Reduced neural response to reward following 7 days treatment with the cannabinoid CB1 antagonist rimonabant in healthy volunteers.

Reduced subjective experience of reward (anhedonia) is a key symptom of major depression. The anti-obesity drug and cannabinoid type 1 receptor (CB(1)) antagonist, rimonabant, is associated with significant rates of depression and anxiety in clinical use and was recently withdrawn from the market because of these adverse effects. Using a functional magnetic resonance imaging (fMRI) model of reward we hypothesized that rimonabant would impair reward processing. Twenty-two healthy participants were randomly allocated to receive rimonabant (20 mg), or placebo, for 7 d in a double-blind, parallel group design. We used fMRI to measure the neural response to rewarding (sight and/or flavour of chocolate) and aversive (sight of mouldy strawberries and/or an unpleasant strawberry taste) stimuli on the final day of drug treatment. Rimonabant reduced the neural response to chocolate stimuli in key reward areas such as the ventral striatum and the orbitofrontal cortex. Rimonabant also decreased neural responses to the aversive stimulus condition in the caudate nucleus and ventral striatum, but increased lateral orbitofrontal activations to the aversive sight and taste of strawberry condition. Our findings are the first to show that the anti-obesity drug rimonabant inhibits the neural processing of rewarding food stimuli in humans. This plausibly underlies its ability to promote weight loss, but may also indicate a mechanism for inducing anhedonia which could lead to the increased risk of depressive symptomatology seen in clinical use. fMRI may be a useful method of screening novel agents for unwanted effects on reward and associated clinical adverse reactions.

CognitiveConstruct

RewardProcessing

10.1016/j.brainres.2010.04.030

Brain research

Brain Res

Processing of food pictures: influence of hunger, gender and calorie content.

In most cases obesity, a major risk factor for diabetes mellitus type 2 and other associated chronic diseases, is generated by excessive eating. For a better understanding of eating behavior, it is necessary to determine how it is modulated by factors such as the calorie content of food, satiety and gender. Twelve healthy normal weighted participants (six female) were investigated in a functional magnetic resonance imaging (fMRI) study. In order to prevent the influence of social acceptability, an implicit one-back task was chosen for stimulus presentation. We presented food (high- and low-caloric) and non-food pictures in a block design and subjects had to indicate by button press whether two consecutive pictures were the same or not. Each subject performed the task in a hungry and satiated state on two different days. High-caloric pictures compared to low-caloric pictures led to increased activity in food processing and reward related areas, like the orbitofrontal and the insular cortex. In addition, we found activation differences in visual areas (occipital lobe), despite the fact that the stimuli were matched for their physical features. Detailed investigation also revealed gender specific effects in the fusiform gyrus. Women showed higher activation in the fusiform gyrus while viewing high-caloric pictures in the hungry state. This study shows that the calorie content of food pictures modulates the activation of brain areas related to reward processing and even early visual areas. In addition, satiation seems to influence the processing of food pictures differently in men and women. Even though an implicit task was used, activation differences could also be observed in the orbitofrontal cortex, known to be activated during explicit stimulation with food related stimuli.

CognitiveConstruct

RewardProcessing

10.1017/s1092852900027437

CNS spectrums

CNS Spectr

Altered regional cerebral glucose metabolism in internet game overusers: a 18F-fluorodeoxyglucose positron emission tomography study.

Internet game overuse is an emerging disorder and features diminished impulse control and poor reward-processing. In an attempt to understand the neurobiological bases of Internet game overuse, we investigated the differences in regional cerebral glucose metabolism at resting state between young individuals with Internet game overuse and those with normal use using 18F-fluorodeoxyglucose positron emission tomography study. Twenty right-handed male participants (9 normal users: 24.7+/-2.4 years of age, 11 overusers: 23.5+/-2.9 years of age) participated. A trait measure of impulsivity was also completed after scanning. Internet game overusers showed greater impulsiveness than the normal users and there was a positive correlation between the severity of Internet game overuse and impulsiveness. Imaging data showed that the overusers had increased glucose metabolism in the right middle orbitofrontal gyrus, left caudate nucleus, and right insula, and decreased metabolism in the bilateral postcentral gyrus, left precentral gyrus, and bilateral occipital regions compared to normal users. Internet game overuse may be associated with abnormal neurobiological mechanisms in the orbitofrontal cortex, striatum, and sensory regions, which are implicated in impulse control, reward processing, and somatic representation of previous experiences. Our results support the idea that Internet game overuse shares psychological and neural mechanisms with other types of impulse control disorders and substance/non-substance-related addiction.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroscience.2010.04.010

Neuroscience

Neuroscience

Early life protein restriction alters dopamine circuitry.

Adverse prenatal environment, such as intrauterine growth retardation (IUGR), increases the risk for negative neurobehavioral outcomes. IUGR, affecting approximately 10% of all US infants, is a known risk factor for attention deficit hyperactivity disorder (ADHD), schizophrenia spectrum disorders and addiction. Mouse dams were fed a protein deficient (8.5% protein) or isocaloric control (18% protein) diet through pregnancy and lactation (a well validated rodent model of IUGR). Dopamine-related gene expression, dopamine content and behavior were examined in adult offspring. IUGR offspring have six to eightfold over-expression of dopamine (DA)-related genes (tyrosine hydroxylase (TH) and dopamine transporter) in brain regions related to reward processing (ventral tegmental area (VTA), nucleus accumbens, prefrontal cortex (PFC)) and homeostatic control (hypothalamus), as well as increased number of TH-ir neurons in the VTA and increased dopamine in the PFC. Cyclin-dependent kinase inhibitor 1C (Cdkn1c) is critical for dopaminergic neuron development. Methylation of the promoter region of Cdkn1c was decreased by half and there was a resultant two to sevenfold increase in Cdkn1c mRNA expression across brain regions. IUGR animals demonstrated alterations in dopamine-dependent behaviors, including altered reward-processing, hyperactivity and exaggerated locomotor response to cocaine. These data describe significant dopamine-related molecular and behavioral abnormalities in a mouse model of IUGR. This animal model, with both face validity (behavior) and construct validity (link to IUGR and dopamine dysfunction) may prove useful in identifying underlying mechanisms linking IUGR and adverse neurobehavioral outcomes such as ADHD.

CognitiveConstruct

RewardProcessing

10.1007/s00213-010-1836-5

Psychopharmacology

Psychopharmacology (Berl)

Depressive-like effects of the kappa opioid receptor agonist salvinorin A are associated with decreased phasic dopamine release in the nucleus accumbens.

Kappa opioid receptors (KORs) have been implicated in depressive-like states associated with chronic administration of drugs of abuse and stress. Although KOR agonists decrease dopamine in the nucleus accumbens (NAc), KOR modulation of phasic dopamine release in the core and shell subregions of the NAc-which have distinct roles in reward processing-remains poorly understood. Studies were designed to examine whether the time course of effects of KOR activation on phasic dopamine release in the NAc core or shell are similar to effects on motivated behavior. The effect of systemic administration of the KOR agonist salvinorin A (salvA)-at a dose (2.0 mg/kg) previously determined to have depressive-like effects-was measured on electrically evoked phasic dopamine release in the NAc core or shell of awake and behaving rats using fast scan cyclic voltammetry. In parallel, the effects of salvA on intracranial self-stimulation (ICSS) and sucrose-reinforced responding were assessed. For comparison, a threshold dose of salvA (0.25 mg/kg) was also tested. The active, but not threshold, dose of salvA significantly decreased phasic dopamine release without affecting dopamine reuptake in the NAc core and shell. SalvA increased ICSS thresholds and significantly lowered breakpoint on the progressive ratio schedule, indicating a decrease in motivation. The time course of the KOR-mediated decrease in dopamine in the core was qualitatively similar to the effects on motivated behavior. These data suggest that the effects of KOR activation on motivation are due, in part, to inhibition of phasic dopamine signaling in the NAc core.

CognitiveConstruct

RewardProcessing

10.1016/j.ejphar.2010.01.030

European journal of pharmacology

Eur J Pharmacol

Group II metabotropic glutamate receptors (mGlu2/3) in drug addiction.

Drug addiction is characterized by maladaptive decision-making and dysfunctional brain circuitry regulating motivated behaviors, resulting in loss of the behavioral flexibility needed to abstain from drug seeking. Hence, addicts face high risk of relapse even after prolonged periods of abstinence from drug use. This is thought to result from long-lasting drug-induced neuroadaptations of glutamate and dopaminergic transmission in the mesocorticolimbic and cortico-striatal circuits where group II metabotropic glutamate receptors (mGlu(2/3) receptors) are densely expressed. mGlu(2/3) receptors presynaptically control glutamate as well as dopamine release throughout the mesocorticolimbic structures involved in reward processing and drug seeking, and their function is reduced after prolonged exposure to drugs of abuse. In pre-clinical models, mGlu(2/3) receptors have been shown to regulate both reward processing and drug seeking, in part through the capacity to control release of dopamine and glutamate respectively. Specifically, mGlu(2/3) receptor agonists administered systemically or locally into certain brain structures reduce the rewarding value of commonly abused drugs and inhibit the reinstatement of drug seeking. Given the ability of mGlu(2/3) receptor agonists to compensate for and possibly reverse drug-induced neuroadaptations in mesocorticolimbic circuitry, this class of receptors emerges as a new therapeutic target for reducing relapse in drug addiction.

CognitiveConstruct

RewardProcessing

10.1001/archgenpsychiatry.2010.13

Archives of general psychiatry

Arch Gen Psychiatry

Neural processing of reward and loss in girls at risk for major depression.

Deficits in reward processing and their neural correlates have been associated with major depression. However, it is unclear if these deficits precede the onset of depression or are a consequence of this disorder. To determine whether anomalous neural processing of reward characterizes children at familial risk for depression in the absence of a personal history of diagnosable disorder. Comparison of neural activity among children at low and high risk for depression as they process reward and loss. University functional magnetic resonance imaging facility. Thirteen 10- to 14-year-old never-disordered daughters of mothers with recurrent depression ("high risk") and 13 age-matched never-disordered daughters with no family history of depression ("low risk"). Main Outcome Measure Neural activity, as measured using functional magnetic resonance imaging, in key reward and attention neural circuitry during anticipation and receipt of reward and loss. While anticipating gains, high-risk participants showed less activation than did their low-risk counterparts in the putamen and left insula but showed greater activation in the right insula. When receiving punishment, high-risk participants showed greater activation in the dorsal anterior cingulate gyrus than did low-risk participants, who showed greater activation in the caudate and putamen. Familial risk for depression affects neural mechanisms underlying the processing of reward and loss; young girls at risk for depression exhibit anomalies in the processing of reward and loss before the onset of depressive symptoms. Longitudinal studies are needed to examine whether these characteristics predict the subsequent onset of depression.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.4936-09.2010

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

J Neurosci

Essential role of dopamine D2 receptor in the maintenance of wakefulness, but not in homeostatic regulation of sleep, in mice.

Dopamine (DA) and its D(2) receptor (R) are involved in cognition, reward processing, and drug addiction. However, their roles in sleep-wake regulation remain unclear. Herein we investigated the role of D(2)R in sleep-wake regulation by using D(2)R knock-out (KO) mice and pharmacological manipulation. Compared with WT mice, D(2)R KO mice exhibited a significant decrease in wakefulness, with a concomitant increase in non-rapid eye movement (non-REM, NREM) and REM sleep and a drastic decrease in the low-frequency (0.75-2 Hz) electroencephalogram delta power of NREM sleep, especially during the first 4 h after lights off. The KO mice had decreased mean episode duration and increased episode numbers of wake and NREM sleep, many stage transitions between wakefulness and NREM sleep during the dark period, suggesting the instability of the wake stage in these D(2)R KO mice. When the KO mice were subjected to a cage change or an intraperitoneal saline injection, the latency to sleep in the KO mice decreased to half of the level for WT mice. The D(2)R antagonist raclopride mimicked these effects in WT mice. When GBR12909, a dopamine transport inhibitor, was administered intraperitoneally, it induced wakefulness in WT mice in a dose-dependent manner, but its arousal effect was attenuated to one-third in the D(2)R KO mice. However, these 2 genotypes showed an identical response in terms of sleep rebound after 2, 4, and 6 h of sleep deprivation. These results indicate that D(2)R plays an essential role in the maintenance of wakefulness, but not in homeostatic regulation of NREM sleep.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2010.03.036

NeuroImage

Neuroimage

Dissociable responses to punishment in distinct striatal regions during reversal learning.

Adaptive behavior depends on the ability to flexibly alter our choices in response to changes in reward and punishment contingencies. One brain region frequently implicated in such behavior is the striatum. However, this region is functionally diverse and there are a number of apparent inconsistencies across previous studies. For instance, how can significant BOLD responses in the ventral striatum during punishment-based reversal learning be reconciled with the frequently demonstrated role of the ventral striatum in reward processing? Here we attempt to address this question by separately examining BOLD responses during reversal learning driven by reward and during reversal learning driven by punishment. We demonstrate simultaneous valence-specific and valence-nonspecific signals in the striatum, with the posterior dorsal striatum responding only to unexpected reward, and the anterior ventral striatum responding to both unexpected punishment as well as unexpected reward. These data help to reconcile conflicting findings from previous studies by showing that distinct regions of the striatum exhibit dissociable responses to punishment during reversal learning.

CognitiveConstruct

RewardProcessing

10.1037/a0018647

Health psychology : official journal of the Division of Health Psychology, American Psychological Association

Health Psychol

Genetic influences on the dynamics of pain and affect in fibromyalgia.

The purpose of the present investigation was to determine if variation in the catechol-O-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genes is associated with pain-related positive affective regulation in fibromyalgia (FM). Forty-six female patients with FM completed an electronic diary that included daily assessments of positive affect and pain. Between- and within-person analyses were conducted with multilevel modeling. Daily positive affect was the primary outcome measure. Analyses revealed a significant gene x experience interaction for COMT, such that individuals with met/met genotype experienced a greater decline in positive affect on days when pain was elevated than did either val/met or val/val individuals. This finding supports a role for catecholamines in positive affective reactivity to FM pain. A gene x experience interaction for OPRM1 also emerged, indicating that individuals with at least one asp allele maintained greater positive affect despite elevations in daily pain than those homozygous for the asn allele. This finding may be explained by the asp allele's role in reward processing. Together, the findings offer researchers ample reason to further investigate the contribution of the catecholamine and opioid systems, and their associated genomic variants, to the still poorly understood experience of FM.

CognitiveConstruct

RewardProcessing

10.1080/17470911003633750

Social neuroscience

Soc Neurosci

Why do I like you when you behave like me? Neural mechanisms mediating positive consequences of observing someone being imitated.

Social psychological and developmental research revealed that imitation serves a fundamental social function. It has been shown that human beings have the tendency to automatically mirror the behavior of others-the so-called chameleon effect. Furthermore, it has been demonstrated that being imitated leads to positive feelings toward the imitator. But why do we feel more positive about someone who imitates us? In the current fMRI study we aimed at exploring the neural correlates of the positive consequences of being imitated by means of an observation paradigm. Our results indicate that being imitated compared to not being imitated activates brain areas that have been associated with emotion and reward processing, namely medial orbitofrontal cortex/ventromedial prefrontal cortex (mOFC/vmPFC, GLM whole-brain contrast). Moreover mOFC/vmPFC shows higher effective connectivity with striatum and mid-posterior insula during being imitated compared to not being imitated.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2010.01.013

Biological psychiatry

Biol Psychiatry

Increased echogenicity of the substantia nigra in children and adolescents with attention-deficit/hyperactivity disorder.

Recent neurobiological models on attention-deficit/hyperactivity disorder (ADHD) as well as findings from imaging studies suggest a crucial involvement of dopaminergic midbrain nuclei, especially the substantia nigra (SN), in the pathogenesis of ADHD symptoms. The current study aimed to investigate whether alterations in the sonographic features of the SN could serve as a biological marker in ADHD patients. The current study employed transcranial sonography in 29 children and adolescents with ADHD and 27 healthy control participants to assess midbrain abnormalities in ADHD. The ADHD patients showed an increase in echogenic size of the SN that was correlated with symptoms of inattention, hyperactivity, and impulsivity but not oppositional or dissocial symptoms. Hyperechogenicity, defined as echogenic size above the 90th percentile in the control group, was present in 48% of ADHD patients. Our findings indicate an increased vulnerability of the nigrostriatal system in ADHD. Transcranial sonography could be successfully used in the future to explore whether ADHD patients with distinct SN hyperechogenicity constitute a specific subgroup or whether hyperechogenicity relates functionally to differences in reward processing, learning, and motor function.

CognitiveConstruct

RewardProcessing

10.1002/ana.21825

Annals of neurology

Ann Neurol

Abnormal activity in reward brain circuits in human narcolepsy with cataplexy.

Hypothalamic hypocretins (or orexins) regulate energy metabolism and arousal maintenance. Recent animal research suggests that hypocretins may also influence reward-related behaviors. In humans, the loss of hypocretin-containing neurons results in a major sleep-wake disorder called narcolepsy-cataplexy, which is associated with emotional disturbances. Here, we aim to test whether narcoleptic patients show an abnormal pattern of brain activity during reward processing. We used functional magnetic resonance imaging in 12 unmedicated patients with narcolepsy-cataplexy to measure the neural responses to expectancy and experience of monetary gains and losses. We statistically compared the patients' data with those obtained in a group of 12 healthy matched controls. Our results reveal that activity in the dopaminergic ventral midbrain (ventral tegmental area) was not modulated in narcolepsy-cataplexy patients during high reward expectancy (unlike controls), and that ventral striatum activity was reduced during winning. By contrast, the patients showed abnormal activity increases in the amygdala and in dorsal striatum for positive outcomes. In addition, we found that activity in the nucleus accumbens and the ventral-medial prefrontal cortex correlated with disease duration, suggesting that an alternate neural circuit could be privileged over the years to control affective responses to emotional challenges and compensate for the lack of influence from ventral midbrain regions. Our study offers a detailed picture of the distributed brain network involved during distinct stages of reward processing and shows for the first time, to our knowledge, how this network is affected in hypocretin-deficient narcoleptic patients.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.4874-09.2010

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

J Neurosci

Neurons in anterior cingulate cortex multiplex information about reward and action.

The dorsal anterior cingulate cortex (dACC) is thought to play a critical role in forming associations between rewards and actions. Currently available physiological data, however, remain inconclusive regarding the question of whether dACC neurons carry information linking particular actions to reward or, instead, encode abstract reward information independent of specific actions. Here we show that firing rates of a majority of dACC neurons in a population studied in an eight-option variably rewarded choice task were sensitive to both saccade direction and reward value. Furthermore, the influences of reward and saccade direction on neuronal activity were approximately equal in magnitude over the range of rewards tested and were statistically independent. Our results indicate that dACC neurons multiplex information about both reward and action, endorsing the idea that this area links motivational outcomes to behavior and undermining the notion that its neurons solely contribute to reward processing in the abstract.

CognitiveConstruct

RewardProcessing

10.1111/j.1530-0277.2010.01149.x

Alcoholism, clinical and experimental research

Alcohol Clin Exp Res

Increased activation of the ACC during a spatial working memory task in alcohol-dependence versus heavy social drinking.

Activation of the anterior cingulate cortex (ACC) in a spatial working memory task has been associated with risk factors for alcohol use disorders such as low alcohol effects and positive alcohol expectations in adolescents. To transfer these results into adults, we used the same task in adults. During functional magnetic resonance imaging, 12 light social, 7 heavy social, and 11 non-abstinent-dependent alcohol drinkers performed a spatial working memory task and completed measures of automatic alcohol-related thoughts and behavior (Obsessive-Compulsive Drinking Scale-OCDS), alcohol use of the last 90 days, and general intelligence. Behavioral performance in the spatial working memory task was not significantly different in all 3 groups. Controlling for differences in general intelligence alcohol-dependent participants showed a higher task-related activation of the dorsal ACC (dACC) in comparison with light and heavy social drinkers. Measures of the OCDS were positively correlated with the activation in the left hippocampus and right thalamus in all participants. Our results support the findings of increased dACC activation during a spatial working memory task as a risk factor for alcohol dependence. Increased task-related activation in the dACC was only observed in alcohol-dependent participants and not in heavy social drinkers with comparable alcohol consumption. Furthermore, the absence of behavioral performance differences between groups as well as an association between dACC activation and working memory performance indicates subtle working memory deficits. Low capacity of working memory has been linked to more automatic and less self-regulated behavior in studies on natural reward processing. Therefore, additional neural activation during performance of the non-alcohol-related working memory task in participants with higher OCDS values in the left hippocampus and the right thalamus may be a consequence of decreased neural capacity because of distracting alcohol-related thoughts.

CognitiveConstruct

RewardProcessing

10.3389/neuro.09.006.2010

Frontiers in human neuroscience

Front Hum Neurosci

Adolescent development of the reward system.

Adolescence is a developmental period characterized by increased reward-seeking behavior. Investigators have used functional magnetic resonance imaging (fMRI) in conjunction with reward paradigms to test two opposing hypotheses about adolescent developmental changes in the striatum, a region implicated in reward processing. One hypothesis posits that the striatum is relatively hypo-responsive to rewards during adolescence, such that heightened reward-seeking behavior is necessary to achieve the same activation as adults. Another view suggests that during adolescence the striatal reward system is hyper-responsive, which subsequently results in greater reward-seeking. While evidence for both hypotheses has been reported, the field has generally converged on this latter hypothesis based on compelling evidence. In this review, I describe the evidence to support this notion, speculate on the disparate fMRI findings and conclude with future areas of inquiry to this fascinating question.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0009296

PloS one

PLoS One

Sugar overconsumption during adolescence selectively alters motivation and reward function in adult rats.

There has been a dramatic escalation in sugar intake in the last few decades, most strikingly observed in the adolescent population. Sugar overconsumption has been associated with several adverse health consequences, including obesity and diabetes. Very little is known, however, about the impact of sugar overconsumption on mental health in general, and on reward-related behavioral disorders in particular. This study examined in rats the effects of unlimited access to sucrose during adolescence on the motivation for natural and pharmacological rewards in adulthood. Adolescent rats had free access to 5% sucrose or water from postnatal day 30 to 46. The control group had access to water only. In adulthood, rats were tested for self-administration of saccharin (sweet), maltodextrin (non-sweet), and cocaine (a potent drug of abuse) using fixed- and progressive-ratio schedules, and a concentration-response curve for each substance. Adult rats, exposed or not exposed to sucrose, were tested for saccharin self-administration later in life to verify the specificity of adolescence for the sugar effects. Sugar overconsumption during adolescence, but not during adulthood, reduced the subsequent motivation for saccharin and maltodextrin, but not cocaine. This selective decrease in motivation is more likely due to changes in brain reward processing than changes in gustatory perception. Sugar overconsumption induces a developmental stage-specific chronic depression in reward processing that may contribute to an increase in the vulnerability to reward-related psychiatric disorders.

CognitiveConstruct

RewardProcessing

10.1037/a0018464

Behavioral neuroscience

Behav Neurosci

The role of the nucleus accumbens core in impulsive choice, timing, and reward processing.

The present series of experiments aimed to pinpoint the source of nucleus accumbens core (AcbC) effects on delay discounting. Rats were trained with an impulsive choice procedure between an adjusting smaller sooner reward and a fixed larger later reward. The AcbC-lesioned rats produced appropriate choice behavior when the reward magnitude was equal. An increase in reward magnitude resulted in a failure to increase preference for the larger later reward in the AcbC-lesioned rats, whereas a decrease in the larger later reward duration resulted in normal alterations in choice behavior in AcbC-lesioned rats. Subsequent experiments with a peak timing (Experiments 2 and 3) and a behavioral contrast (Experiment 4) indicated that the AcbC-lesioned rats suffered from decreased incentive motivation during changes in reward magnitude (Experiments 2 and 4) and when expected rewards were omitted (Experiments 2 and 3), but displayed intact anticipatory timing of reward delays (Experiments 2 and 3). The results indicate that the nucleus accumbens core is critical for determining the incentive value of rewards, but does not participate in the timing of reward delays.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0009042

PloS one

PLoS One

Optimal waist-to-hip ratios in women activate neural reward centers in men.

Secondary sexual characteristics convey information about reproductive potential. In the same way that facial symmetry and masculinity, and shoulder-to-hip ratio convey information about reproductive/genetic quality in males, waist-to-hip-ratio (WHR) is a phenotypic cue to fertility, fecundity, neurodevelopmental resources in offspring, and overall health, and is indicative of "good genes" in women. Here, using fMRI, we found that males show activation in brain reward centers in response to naked female bodies when surgically altered to express an optimal (approximately 0.7) WHR with redistributed body fat, but relatively unaffected body mass index (BMI). Relative to presurgical bodies, brain activation to postsurgical bodies was observed in bilateral orbital frontal cortex. While changes in BMI only revealed activation in visual brain substrates, changes in WHR revealed activation in the anterior cingulate cortex, an area associated with reward processing and decision-making. When regressing ratings of attractiveness on brain activation, we observed activation in forebrain substrates, notably the nucleus accumbens, a forebrain nucleus highly involved in reward processes. These findings suggest that an hourglass figure (i.e., an optimal WHR) activates brain centers that drive appetitive sociality/attention toward females that represent the highest-quality reproductive partners. This is the first description of a neural correlate implicating WHR as a putative honest biological signal of female reproductive viability and its effects on men's neurological processing.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2009.11.008

Psychiatry research

Psychiatry Res

Neurobiological correlates of problem gambling in a quasi-realistic blackjack scenario as revealed by fMRI.

In the present study we obtained functional magnetic resonance imaging (fMRI) data in occasional gamblers (OG) and problem gamblers (PG) during a quasi-realistic blackjack game. We focused on neuronal correlates of risk assessment and reward processing. Participants had to decide whether to draw or not to draw a card in a high-risk or low-risk blackjack situation. We assumed PG would show differences in prefrontal and ventral striatal brain regions in comparison to OG during risk assessment and due to the winning or losing of money. Although both groups did not differ in behavioral data, blood oxygen level dependent (BOLD) signals in PG and OG significantly differed in thalamic, inferior frontal, and superior temporal regions. Whereas PG demonstrated a consistent signal increase during high-risk situations and a decrease in low-risk situations, OG presented the opposite pattern. During reward processing as derived from contrasting winning vs. losing situations, both PG and OG groups showed an enhancement of ventral striatal and posterior cingulate activity. Furthermore, PG demonstrated a distinct fronto-parietal activation pattern which has been discussed to reflect a cue-induced addiction memory network which was triggered by gambling-related cues.

CognitiveConstruct

RewardProcessing

10.1111/j.1530-0277.2009.01139.x

Alcoholism, clinical and experimental research

Alcohol Clin Exp Res

Individual differences in alcohol drinking frequency are associated with electrophysiological responses to unexpected nonrewards.

It has been suggested that alcohol use is related to sensitivity of the reward system. Although there are several studies using self-reported measures supportive of this notion, objective biological data in humans on this issue are lacking. This study is designed to test whether alcohol drinking frequency is associated with electrophysiological indices of reward processing. In a passive gambling task, stimuli predicted the presence (reward) and absence (nonreward) of rewards resulting in P2 and medial frontal negativity (MFN) indices of reward processing. Forty-seven undergraduate students were asked about their habitual drinking frequency and the P2 and MFN to stimuli predicting reward were measured. Most importantly, the MFN to unpredicted nonrewards at the frontal midline (Fz) location correlated significantly with drinking frequency, with frequent drinkers showing larger MFN amplitudes. The results did not show a significant association between frequency and alcohol drinking and P2. Although several studies showing increased reward-sensitivity in addictive behaviors, the present results indicate that, in frequent alcohol drinkers, electrophysiological responsiveness is particularly activated by unpredicted nonrewards. In general, this may point to the involvement of the reward system in alcohol drinking frequency. More specifically, the results demonstrate an increased vulnerability of high frequency drinkers to signals of (frustrative) nonrewards.

CognitiveConstruct

RewardProcessing