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10.1016/j.neubiorev.2013.11.003

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

From conflict management to reward-based decision making: actors and critics in primate medial frontal cortex.

The role of the medial prefrontal cortex (mPFC) and especially the anterior cingulate cortex has been the subject of intense debate for the last decade. A number of theories have been proposed to account for its function. Broadly speaking, some emphasize cognitive control, whereas others emphasize value processing; specific theories concern reward processing, conflict detection, error monitoring, and volatility detection, among others. Here we survey and evaluate them relative to experimental results from neurophysiological, anatomical, and cognitive studies. We argue for a new conceptualization of mPFC, arising from recent computational modeling work. Based on reinforcement learning theory, these new models propose that mPFC is an Actor-Critic system. This system is aimed to predict future events including rewards, to evaluate errors in those predictions, and finally, to implement optimal skeletal-motor and visceromotor commands to obtain reward. This framework provides a comprehensive account of mPFC function, accounting for and predicting empirical results across different levels of analysis, including monkey neurophysiology, human ERP, human neuroimaging, and human behavior.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2013.10.003

Developmental cognitive neuroscience

Dev Cogn Neurosci

Gaining insight into adolescent vulnerability for social anxiety from developmental cognitive neuroscience.

Social anxiety disorder (SAD) markedly impairs daily functioning. For adolescents, SAD can constrain typical development precisely when social experiences broaden, peers' opinions are highly salient, and social approval is actively sought. Individuals with extreme, impairing social anxiety fear evaluation from others, avoid social interactions, and interpret ambiguous social cues as threatening. Yet some degree of social anxiety can be normative and non-impairing. Furthermore, a temperament of behavioral inhibition increases risk for SAD for some, but not all adolescents with this temperament. One fruitful approach taken to understand the mechanisms of social anxiety has been to use neuroimaging to link affect and cognition with neural networks implicated in the neurodevelopmental social reorientation of adolescence. Although initial neuroimaging studies of adolescent SAD and risk for SAD underscored the role of fear-processing circuits (e.g., the amygdala and ventral prefrontal cortex), recent work has expanded these circuits to include reward-processing structures in the basal ganglia. A growing focus on reward-related neural circuitry holds promise for innovative translational research needed to differentiate impairing from normative social anxiety and for novel ways to treat adolescent SAD that focus on both social avoidance and social approach.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0080766

PloS one

PLoS One

Dopamine and pain sensitivity: neither sulpiride nor acute phenylalanine and tyrosine depletion have effects on thermal pain sensations in healthy volunteers.

Based on animal studies and some indirect clinical evidence, dopamine has been suggested to have anti-nociceptive effects. Here, we investigated directly the effects of increased and decreased availability of extracellular dopamine on pain perception in healthy volunteers. In Study 1, participants ingested, in separate sessions, a placebo and a low dose of the centrally acting D2-receptor antagonist sulpiride, intended to increase synaptic dopamine via predominant pre-synaptic blockade. No effects were seen on thermal pain thresholds, tolerance, or temporal summation. Study 2 used the acute phenylalanine and tyrosine depletion (APTD) method to transiently decrease dopamine availability. In one session participants ingested a mixture that depletes the dopamine amino acid precursors, phenylalanine and tyrosine. In the other session they ingested a nutritionally balanced control mixture. APTD led to a small mood-lowering response following aversive thermal stimulation, but had no effects on the perception of cold, warm, or pain stimuli. In both studies the experimental manipulation of dopaminergic neurotransmission was successful as indicated by manipulation checks. The results contradict proposals that dopamine has direct anti-nociceptive effects in acute experimental pain. Based on dopamine's well-known role in reward processing, we hypothesize that also in the context of pain, dopamine acts on stimulus salience and might play a role in the initiation of avoidance behavior rather than having direct antinociceptive effects in acute experimental pain.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2013.00201

Frontiers in neuroscience

Front Neurosci

Dopaminergic control of cognitive flexibility in humans and animals.

Striatal dopamine (DA) is thought to code for learned associations between cues and reinforcers and to mediate approach behavior toward a reward. Less is known about the contribution of DA to cognitive flexibility-the ability to adapt behavior in response to changes in the environment. Altered reward processing and impairments in cognitive flexibility are observed in psychiatric disorders such as obsessive compulsive disorder (OCD). Patients with this disorder show a disruption of functioning in the frontostriatal circuit and alterations in DA signaling. In this review we summarize findings from animal and human studies that have investigated the involvement of striatal DA in cognitive flexibility. These findings may provide a better understanding of the role of dopaminergic dysfunction in cognitive inflexibility in psychiatric disorders, such as OCD.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2013.06.013

NeuroImage. Clinical

Neuroimage Clin

Abnormal corticostriatal-limbic functional connectivity in obsessive-compulsive disorder during reward processing and resting-state.

Compulsive behaviors in obsessive-compulsive disorder (OCD) may be related to deficits in reward processing mediated by corticostriatal circuitry, a brain network implicated in the pathophysiology of OCD. Performing compulsive actions can be perceived as a reward to OCD patients because it temporarily reduces the anxiety provoked by obsessions. Although most OCD literature provides evidence of altered regional activity in these corticostriatal circuits, very little is known about the connectivity between individual regions of the corticostriatal-limbic circuits, including the cognitive and affective neural circuitry associated with OCD. Thus, this study investigated the differences in functional connectivity (FC) patterns in this network during resting-state and incentive processing. Nineteen patients with OCD and 18 well-matched healthy controls were scanned during resting-state and a monetary incentive delay task (task state). FC was assessed using both voxel-wise and region-of-interest (ROI)-wise analyses. Voxel-wise FC analysis with the nucleus accumbens seed revealed that patients with OCD exhibited increased FC between the nucleus accumbens and the lateral orbitofrontal cortex during resting-state. Additionally, these patients showed decreased FC between the nucleus accumbens and limbic areas such as the amygdala during incentive processing. Exploratory ROI-wise FC analysis revealed that OCD patients demonstrated enhanced FC between the nucleus accumbens and the lateral orbitofrontal cortex and increased total connectivity of the lateral orbitofrontal cortex during resting-state. Additionally, patients showed alterations in FC between resting and task state. This study provides evidence that patients with OCD have altered FC in the corticostriatal-limbic network, particularly in striatal-amygdala and striatal-orbitofrontal circuitry, during incentive processing and resting-state. These findings also emphasize that functional connections in the network are modulated by affective/motivational states and further suggest that OCD patients may have abnormalities of such modulation in this network.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2013.03.004

NeuroImage. Clinical

Neuroimage Clin

Osmotic release oral system-methylphenidate improves neural activity during low reward processing in children and adolescents with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is neurobehavioral disorder characterized by inattention, hyperactivity/impulsivity and impaired reward system function, such as delay aversion and low reward sensitivity. The pharmacological treatment for ADHD includes methylphenidate (MPH), or osmotic release oral system-MPH (OROS-MPH), which increases extrasynaptic dopamine and noradrenaline levels by blocking their reuptake. Although previous functional magnetic resonance imaging (fMRI) studies revealed that acute treatment with MPH alters activation of the nucleus accumbens during delay aversion in children and adolescents with ADHD, the effects a relatively long period of OROS-MPH treatment on delay aversion as well as reward sensitivity remain unclear. Thus, we evaluated brain activation with fMRI during a reward sensitivity paradigm that consists of high monetary reward and low monetary reward conditions before and after a 3-month treatment with OROS-MPH in 17 children and adolescents with ADHD (mean age, 13.3 ± 2.2) and 17 age- and sex-matched healthy controls (mean age, 13.0 ± 1.9). We found that before treatment there was decreased activation of the nucleus accumbens and thalamus in patients with ADHD during only the low monetary reward condition, which was improved to same level as those of the healthy controls after the treatment. The observed change in brain activity was associated with improved ADHD symptom scores, which were derived from Japanese versions of the ADHD rating scale-IV. These results suggest that treatment with OROS-MPH for a relatively long period is effective in controlling reward sensitivity in children and adolescents with ADHD.

CognitiveConstruct

RewardProcessing

10.1017/S0033291713002584

Psychological medicine

Psychol Med

Temporal discounting in major depressive disorder.

Major depressive disorder (MDD) is associated with abnormalities in financial reward processing. Previous research suggests that patients with MDD show reduced sensitivity to frequency of financial rewards. However, there is a lack of conclusive evidence from studies investigating the evaluation of financial rewards over time, an important aspect of reward processing that influences the way people plan long-term investments. Beck's cognitive model posits that patients with MDD hold a negative view of the future that may influence the amount of resources patients are willing to invest into their future selves. We administered a delay discounting task to 82 participants: 29 healthy controls, 29 unmedicated participants with fully remitted MDD (rMDD) and 24 participants with current MDD (11 on medication). Patients with current MDD, relative to remitted patients and healthy subjects, discounted large-sized future rewards at a significantly higher rate and were insensitive to changes in reward size from medium to large. There was a main effect of clinical group on discounting rates for large-sized rewards, and discounting rates for large-sized rewards correlated with severity of depressive symptoms, particularly hopelessness. Higher discounting of delayed rewards in MDD seems to be state dependent and may be a reflection of depressive symptoms, specifically hopelessness. Discounting distant rewards at a higher rate means that patients are more likely to choose immediate financial options. Such impairments related to long-term investment planning may be important for understanding value-based decision making in MDD, and contribute to ongoing functional impairment.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2013.00772

Frontiers in psychology

Front Psychol

Witnessing hateful people in pain modulates brain activity in regions associated with physical pain and reward.

How does witnessing a hateful person in pain compare to witnessing a likable person in pain? The current study compared the brain bases for how we perceive likable people in pain with those of viewing hateful people in pain. While social bonds are built through sharing the plight and pain of others in the name of empathy, viewing a hateful person in pain also has many potential ramifications. In this functional Magnetic Resonance Imaging (fMRI) study, Caucasian Jewish male participants viewed videos of (1) disliked, hateful, anti-Semitic individuals, and (2) liked, non-hateful, tolerant individuals in pain. The results showed that, compared with viewing liked people, viewing hateful people in pain elicited increased responses in regions associated with observation of physical pain (the insular cortex, the anterior cingulate cortex (ACC), and the somatosensory cortex), reward processing (the striatum), and frontal regions associated with emotion regulation. Functional connectivity analyses revealed connections between seed regions in the left ACC and right insular cortex with reward regions, the amygdala, and frontal regions associated with emotion regulation. These data indicate that regions of the brain active while viewing someone in pain may be more active in response to the danger or threat posed by witnessing the pain of a hateful individual more so than the desire to empathize with a likable person's pain.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2013.00771

Frontiers in psychology

Front Psychol

Neural model for learning-to-learn of novel task sets in the motor domain.

During development, infants learn to differentiate their motor behaviors relative to various contexts by exploring and identifying the correct structures of causes and effects that they can perform; these structures of actions are called task sets or internal models. The ability to detect the structure of new actions, to learn them and to select on the fly the proper one given the current task set is one great leap in infants cognition. This behavior is an important component of the child's ability of learning-to-learn, a mechanism akin to the one of intrinsic motivation that is argued to drive cognitive development. Accordingly, we propose to model a dual system based on (1) the learning of new task sets and on (2) their evaluation relative to their uncertainty and prediction error. The architecture is designed as a two-level-based neural system for context-dependent behavior (the first system) and task exploration and exploitation (the second system). In our model, the task sets are learned separately by reinforcement learning in the first network after their evaluation and selection in the second one. We perform two different experimental setups to show the sensorimotor mapping and switching between tasks, a first one in a neural simulation for modeling cognitive tasks and a second one with an arm-robot for motor task learning and switching. We show that the interplay of several intrinsic mechanisms drive the rapid formation of the neural populations with respect to novel task sets.

CognitiveConstruct

RewardProcessing

10.1002/da.22202

Depression and anxiety

Depress Anxiety

Peril and pleasure: an rdoc-inspired examination of threat responses and reward processing in anxiety and depression.

As a step toward addressing limitations in the current psychiatric diagnostic system, the National Institute of Mental Health recently developed the Research Domain Criteria (RDoC) to stimulate integrative research-spanning self-report, behavior, neural circuitry, and molecular/genetic mechanisms-on core psychological processes implicated in mental illness. Here, we use the RDoC conceptualization to review research on threat responses, reward processing, and their interaction. The first section of the manuscript highlights the pivotal role of exaggerated threat responses-mediated by circuits connecting the frontal cortex, amygdala, and midbrain-in anxiety, and reviews data indicating that genotypic variation in the serotonin system is associated with hyperactivity in this circuitry, which elevates the risk for anxiety and mood disorders. In the second section, we describe mounting evidence linking anhedonic behavior to deficits in psychological functions that rely heavily on dopamine signaling, especially cost/benefit decision making and reward learning. The third section covers recent studies that document negative effects of acute threats and chronic stress on reward responses in humans. The mechanisms underlying such effects are unclear, but the fourth section reviews new optogenetic data in rodents indicating that GABAergic inhibition of midbrain dopamine neurons, driven by activation of the habenula, may play a fundamental role in stress-induced anhedonia. In addition to its basic scientific value, a better understanding of interactions between the neural systems that mediate threat and reward responses may offer relief from the burdensome condition of anxious depression.

CognitiveConstruct

RewardProcessing

10.1097/WNR.0000000000000024

Neuroreport

Neuroreport

It's all about money: oral contraception alters neural reward processing.

Mating preferences in phases of the natural menstrual cycle with a low probability to conceive have been associated with lower interest in characteristics promising genetic benefits but increased search for safety and future security. We hypothesized that this effect would also be evident under oral contraception and may therefore alter neural processing of monetary rewards as a proxy for potential safety. Our aim was to assess the activation of reward-related brain areas using a monetary incentive task in women with functional MRI (fMRI). We compared fMRI activation of 12 young women taking oral contraceptives with 12 women with a natural hormonal cycle in their follicular phase during the expectation of monetary rewards. Women under hormonal contraception who have already shown decreased anterior insula activation upon erotic stimulation in a previous study of the same sample now showed enhanced activation during monetary reward expectation in the anterior insula/inferior lateral prefrontal cortex (t=2.84; P<0.05) relative to young normal cycling women in the follicular phase. Our finding supports the notion that the switch in mating preferences related to different hormonal states in women is mirrored by a switch in the stimulus-dependent excitability of reward-related brain regions. Beyond highlighting hormonal effects on reward processing, our data underline the importance of monitoring hormonal states in fMRI research in women.

CognitiveConstruct

RewardProcessing

10.1111/ejn.12381

The European journal of neuroscience

Eur J Neurosci

Withdrawal from extended-access cocaine self-administration results in dysregulated functional activity and altered locomotor activity in rats.

Much work has focused on determining the consequences of cocaine self-administration on specific neurotransmitter systems, thus neglecting the global changes that occur. Previous imaging studies have focused on the effects of cocaine self-administration in the presence of high blood levels of cocaine, but have not determined the functional effects of cocaine self-administration after cocaine has cleared. Extended-access cocaine self-administration, where animals administer cocaine for 6 h each day, results in escalation in the rate of cocaine intake and is believed to model the transition from recreational use to addiction in humans. We aimed to determine the functional changes following acute (48 h) withdrawal from an extended-access, defined-intake self-administration paradigm (5 days, 40 injections/day, 6 h/day), a time point when behavioral changes are present. Using the 2-[(14) C]deoxyglucose method to measure rates of local cerebral glucose metabolism, an indicator of functional activity, we found reductions in circuits related to learning and memory, attention, sleep, and reward processing, which have important clinical implications for cocaine addiction. Additionally, lower levels of functional activity were found in the dorsal raphe and locus coeruleus, suggesting that cocaine self-administration may have broader effects on brain function than previously noted. These widespread neurochemical reductions were concomitant with substantial behavioral differences in these animals, highlighted by increased vertical activity and decreased stereotypy. These data demonstrate that behavioral and neurochemical impairments following cocaine self-administration are present in the absence of drug and persist after cocaine has been cleared.

CognitiveConstruct

RewardProcessing

10.1016/B978-0-444-53497-2.00022-X

Handbook of clinical neurology

Handb Clin Neurol

Evaluating the potential of deep brain stimulation for treatment-resistant anorexia nervosa.

Anorexia nervosa is a chronic and debilitating psychiatric disorder associated with one of the highest mortality rates of any psychiatric condition. Despite advances in neuroimaging, genetics, pharmacology, and psychosocial interventions in the last half-century, little progress has been made in altering the natural history of the condition or its outcomes. Evidence is now emerging that the condition is, at least in part, maintained by dysfunctional activity in key neuroanatomic circuits subserving illness-maintaining symptoms. Abnormal reward processing, compulsive hyperactivity, chronic anxiety, and depression, all suggest that anorexia nervosa shares much in common with other conditions, such as major depression and obsessive-compulsive disorder, for which surgical therapy with deep brain stimulation (DBS) has been tried, with promising results. As a result, the use of DBS in treatment-resistant anorexia nervosa should be evaluated in carefully designed, early-phase feasibility trials.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2013.00625

Frontiers in human neuroscience

Front Hum Neurosci

Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach.

Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.0143-13.2013

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

J Neurosci

Imaging social motivation: distinct brain mechanisms drive effort production during collaboration versus competition.

Collaborative and competitive interactions have been investigated extensively so as to understand how the brain makes choices in the context of strategic games, yet such interactions are known to influence a more basic dimension of behavior: the energy invested in the task. The cognitive mechanisms that motivate effort production in social situations remain poorly understood, and their neural counterparts have not been explored so far. A dominant idea is that the motivation provided by the social context is reducible to the personal utility of effort production, which decreases in collaboration and increases in competition. Using functional magnetic resonance imaging, we scanned human participants while they produced a physical effort in a collaborative or competitive context. We found that motivation was indeed primarily driven by personal utility, which was reflected in brain regions devoted to reward processing (the ventral basal ganglia). However, subjects who departed from utility maximization, working more in collaborative situations, showed greater functional activation and anatomical volume in a brain region implicated previously in social cognition (the temporoparietal junction). Therefore, this region might mediate a purely pro-social motivation to produce greater effort in the context of collaboration. More generally, our findings suggest that the individual propensity to invest energy in collaborative work might have an identifiable counterpart in the brain functional architecture.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.1686-13.2013

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

J Neurosci

Cannabinoid transmission in the prelimbic cortex bidirectionally controls opiate reward and aversion signaling through dissociable kappa versus μ-opiate receptor dependent mechanisms.

Cannabinoid, dopamine (DA), and opiate receptor pathways play integrative roles in emotional learning, associative memory, and sensory perception. Modulation of cannabinoid CB1 receptor transmission within the medial prefrontal cortex (mPFC) regulates the emotional valence of both rewarding and aversive experiences. Furthermore, CB1 receptor substrates functionally interact with opiate-related motivational processing circuits, particularly in the context of reward-related learning and memory. Considerable evidence demonstrates functional interactions between CB1 and DA signaling pathways during the processing of motivationally salient information. However, the role of mPFC CB1 receptor transmission in the modulation of behavioral opiate-reward processing is not currently known. Using an unbiased conditioned place preference paradigm with rats, we examined the role of intra-mPFC CB1 transmission during opiate reward learning. We report that activation or inhibition of CB1 transmission within the prelimbic cortical (PLC) division of the mPFC bidirectionally regulates the motivational valence of opiates; whereas CB1 activation switched morphine reward signaling into an aversive stimulus, blockade of CB1 transmission potentiated the rewarding properties of normally sub-reward threshold conditioning doses of morphine. Both of these effects were dependent upon DA transmission as systemic blockade of DAergic transmission prevented CB1-dependent modulation of morphine reward and aversion behaviors. We further report that CB1-mediated intra-PLC opiate motivational signaling is mediated through a μ-opiate receptor-dependent reward pathway, or a κ-opiate receptor-dependent aversion pathway, directly within the ventral tegmental area. Our results provide evidence for a novel CB1-mediated motivational valence switching mechanism within the PLC, controlling dissociable subcortical reward and aversion pathways.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2013.00609

Frontiers in psychology

Front Psychol

What would my avatar do? Gaming, pathology, and risky decision making.

Recent work has revealed a relationship between pathological video game use and increased impulsivity among children and adolescents. A few studies have also demonstrated increased risk-taking outside of the video game environment following game play, but this work has largely focused on one genre of video games (i.e., racing). Motivated by these findings, the aim of the current study was to examine the relationship between pathological and non-pathological video game use, impulsivity, and risky decision making. The current study also investigated the relationship between experience with two of the most popular genres of video games [i.e., first-person shooter (FPS) and strategy] and risky decision making. Consistent with previous work, ~7% of the current sample of college-aged adults met criteria for pathological video game use. The number of hours spent gaming per week was associated with increased impulsivity on a self-report measure and on the temporal discounting (TD) task. This relationship was sensitive to the genre of video game; specifically, experience with FPS games was positively correlated with impulsivity, while experience with strategy games was negatively correlated with impulsivity. Hours per week and pathological symptoms predicted greater risk-taking in the risk task and the Iowa Gambling task, accompanied by worse overall performance, indicating that even when risky choices did not pay off, individuals who spent more time gaming and endorsed more symptoms of pathological gaming continued to make these choices. Based on these data, we suggest that the presence of pathological symptoms and the genre of video game (e.g., FPS, strategy) may be important factors in determining how the amount of game experience relates to impulsivity and risky-decision making.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2013.08.004

Developmental cognitive neuroscience

Dev Cogn Neurosci

Different developmental trajectories for anticipation and receipt of reward during adolescence.

Typical adolescent behaviour such as increased risk-taking and novelty-seeking is probably related to developmental changes in the brain reward system. This functional MRI study investigated how brain activation related to two components of reward processing (Reward Anticipation and Reward Outcome) changes with age in a sample of 39 children, adolescents and young adults aged 10-25. Our data revealed age-related changes in brain activity during both components of reward processing. Activation related to Reward Anticipation increased with age, while activation related to Reward Outcome decreased in various regions of the reward network. This shift from outcome to anticipation was confirmed by subsequent analyses showing positive correlations between age and the difference in activation between Reward Anticipation and Reward Outcome. The shift was predominantly present in striatal regions and was accompanied by a significant effect of age on behaviour, with older participants showing more response speeding on potentially rewarding trials than younger participants. This study provides evidence for functional changes in the reward system which may underlie typical adolescent behaviour.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2013.09.016

Neuropsychologia

Neuropsychologia

Single pulse TMS differentially modulates reward behavior.

Greater knowledge of cortical brain regions in reward processing may set the stage for using transcranial magnetic stimulation (TMS) as a treatment in patients with avolition, apathy or other drive-related symptoms. This study examined the effects of single pulse (sp) TMS to two reward circuit targets on drive in healthy subjects. Fifteen healthy subjects performed the monetary incentive delay task (MID) while receiving fMRI-guided spTMS to either inferior parietal lobe (IPL) or supplemental motor area (SMA). The study demonstrated decreasing reaction times (RT) for increasing reward. It also showed significant differences in RT modulation for TMS pulses to the IPL versus the SMA. TMS pulses during the delay period produced significantly more RT slowing when targeting the IPL than those to the SMA. This RT slowing carried over into subsequent trials without TMS stimulation, with significantly slower RTs in sessions that had targeted the IPL compared to those targeting SMA. The results of this study suggest that both SMA and IPL are involved in reward processing, with opposite effects on RT in response to TMS stimulation. TMS to these target cortical regions may be useful in modulating reward circuit deficits in psychiatric populations.

CognitiveConstruct

RewardProcessing

10.1093/scan/nst149

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Reward sensitivity to faces versus objects in children: an ERP study.

How children respond to social and nonsocial rewards has important implications for understanding social cognitive development. Adults find faces intrinsically rewarding. However, little is known about how children respond to face vs nonface rewards. We utilized event-related potentials (the stimulus-preceding negativity, SPN) to measure differences in reward anticipation during a guessing game in 6- to 8-year-olds. Children were presented with reward indicators accompanied by incidental face or nonface stimuli. Nonface stimuli were comprised of scrambled faces in the shape of arrows, controlling for low-level properties of the two conditions. Children showed an increased SPN when the reward stimuli were accompanied by faces, relative to nonface stimuli. This suggests that children find a face stimulus more rewarding than a nonface stimulus. The results have important implications for processing social vs nonsocial rewards in typically developing children, and allow testing of populations with deficits in social reward processing, such as autism spectrum disorder.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropharm.2013.08.028

Neuropharmacology

Neuropharmacology

15 years of genetic approaches in vivo for addiction research: Opioid receptor and peptide gene knockout in mouse models of drug abuse.

The endogenous opioid system is expressed throughout the brain reinforcement circuitry, and plays a major role in reward processing, mood control and the development of addiction. This neuromodulator system is composed of three receptors, mu, delta and kappa, interacting with a family of opioid peptides derived from POMC (β-endorphin), preproenkephalin (pEnk) and preprodynorphin (pDyn) precursors. Knockout mice targeting each gene of the opioid system have been created almost two decades ago. Extending classical pharmacology, these mutant mice represent unique tools to tease apart the specific role of each opioid receptor and peptide in vivo, and a powerful approach to understand how the opioid system modulates behavioral effects of drugs of abuse. The present review summarizes these studies, with a focus on major drugs of abuse including morphine/heroin, cannabinoids, psychostimulants, nicotine or alcohol. Genetic data, altogether, set the mu receptor as the primary target for morphine and heroin. In addition, this receptor is essential to mediate rewarding properties of non-opioid drugs of abuse, with a demonstrated implication of β-endorphin for cocaine and nicotine. Delta receptor activity reduces levels of anxiety and depressive-like behaviors, and facilitates morphine-context association. pEnk is involved in these processes and delta/pEnk signaling likely regulates alcohol intake. The kappa receptor mainly interacts with pDyn peptides to limit drug reward, and mediate dysphoric effects of cannabinoids and nicotine. Kappa/dynorphin activity also increases sensitivity to cocaine reward under stressful conditions. The opioid system remains a prime candidate to develop successful therapies in addicted individuals, and understanding opioid-mediated processes at systems level, through emerging genetic and imaging technologies, represents the next challenging goal and a promising avenue in addiction research. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

CognitiveConstruct

RewardProcessing

10.1080/13546805.2013.823860

Cognitive neuropsychiatry

Cogn Neuropsychiatry

Active and observational reward learning in adults with autism spectrum disorder: relationship with empathy in an atypical sample.

Autism spectrum disorders (ASDs) are characterised by disturbances in social behaviour. A prevailing hypothesis suggests that these problems are related to deficits in assigning rewarding value to social stimuli. The present study aimed to examine monetary reward processing in adults with ASDs by means of event-related potentials (ERPs). Ten individuals with mild ASDs (Asperger's syndrome and high-functioning autism) and 12 healthy control subjects performed an active and an observational probabilistic reward-learning task. Both groups showed similar overall learning performance. With respect to reward processing, subjects with ASDs exhibited a general reduction in feedback-related negativity (FRN) amplitude, irrespective of feedback valence and type of learning (active or observational). Individuals with ASDs showed lower scores for cognitive empathy, while affective empathy did not differ between groups. Correlation analyses revealed that higher empathy (both cognitive and affective) negatively affected performance in observational learning in controls and in active learning in ASDs (only cognitive empathy). No relationships were seen between empathy and ERPs. Reduced FRN amplitudes are discussed in terms of a deficit in fast reward processing in ASDs, which may indicate altered reward system functioning.

CognitiveConstruct

RewardProcessing

10.1016/j.yhbeh.2013.02.008

Hormones and behavior

Horm Behav

Adolescent cognitive control and reward processing: implications for risk taking and substance use.

Adolescence is a unique, transitional period of human development. Once hallmark of this period is progressive improvements (relative to children) in cognitive control, core mental abilities enabling the 'top-down', endogenous control over behavior. However, as adolescents transition to more mature (adult) levels of functioning, limitations still exist in the ability to consistently and flexibly exert cognitive control across various contexts into the early twenties. Adolescence is also marked by peaks in sensation, novelty, and reward seeking behaviors thought to stem from normative increases in responsiveness in limbic and paralimbic brain structures, beginning around the onset of puberty. Asynchronous maturation in these systems during the adolescent period likely contributes to immature decision-making, strongly influenced by 'bottom-up' reward processes, and may help explain noted increases in risk taking behavior during adolescence. In this paper, structural and functional maturation in brain systems supporting reward and cognitive control processing are reviewed as a means to better understand risk taking. Particular emphasis is placed on adolescents' experimentation with drugs as a specific example of a risky behavior.

CognitiveConstruct

RewardProcessing

10.1016/j.yhbeh.2013.03.006

Hormones and behavior

Horm Behav

Impact of socio-emotional context, brain development, and pubertal maturation on adolescent risk-taking.

While there is little doubt that risk-taking is generally more prevalent during adolescence than before or after, the underlying causes of this pattern of age differences have long been investigated and debated. One longstanding popular notion is the belief that risky and reckless behavior in adolescence is tied to the hormonal changes of puberty. However, the interactions between pubertal maturation and adolescent decision making remain largely understudied. In the current review, we discuss changes in decision making during adolescence, focusing on the asynchronous development of the affective, reward-focused processing system and the deliberative, reasoned processing system. As discussed, differential maturation in the structure and function of brain systems associated with these systems leaves adolescents particularly vulnerable to socio-emotional influences and risk-taking behaviors. We argue that this asynchrony may be partially linked to pubertal influences on development and specifically on the maturation of the affective, reward-focused processing system.

CognitiveConstruct

RewardProcessing

10.5665/sleep.2958

Sleep

Sleep

Effect of psychostimulants on impulsivity and risk taking in narcolepsy with cataplexy.

To investigate the effect of psychostimulants on impulsivity, depressive symptoms, addiction, pathological gambling, and risk-taking using objective sensitivity tests in narcolepsy with cataplexy (NC). Drug-free patients with NC present alterations in reward processing, but changes with psychostimulants remain unknown. Prospective case-control study. Academic sleep disorders center. There were 120 participants: 41 drug-free patients with NC, 37 patients with NC taking psychostimulants, and 42 matched healthy controls. All participants underwent a semistructured clinical interview for impulse control and addictive behaviors and completed questionnaires for depression and impulsivity. Risk taking was analyzed through performance on a decision-making task under ambiguity (Iowa Gambling Task [IGT]) and under risk (Game of Dice Task [GDT]). All patients with NC underwent 1 night of polysomnography followed by a multiple sleep latency test for drug-free patients and a maintenance wakefulness test for treated patients. Depressive symptoms were higher in drug-free patients than in treated patients and controls, with no difference between controls and treated patients. No between-group differences were found for impulsivity, substance addiction, or pathological gambling. Drug-free and treated patients showed selective reduced performance on the IGT and normal performance on the GDT compared with controls, with no differences between patients taking medication and those who did not. No clinical or polysomnographic characteristics or medication type was associated with IGT scores. Our results demonstrated that, whether taking psychostimulants or not, patients with narcolepsy with cataplexy preferred risky choices on a decision-making task under ambiguity. However, the lack of association with impulsivity, pathological gambling, or substance addiction remains of major clinical interest in narcolepsy with cataplexy.

CognitiveConstruct

RewardProcessing

10.1007/s00406-013-0437-9

European archives of psychiatry and clinical neuroscience

Eur Arch Psychiatry Clin Neurosci

An fMRI study of reward circuitry in patients with minimal or extensive history of major depression.

Functional abnormalities in regions associated with reward processing are apparent in people with depression, but the extent to which disease burden impacts on the processing of reward is unknown. This research examined the neural correlates of reward processing in patients with major depressive disorder and varying degrees of past illness burden. Twenty-nine depressed patients and twenty-five healthy subjects with no lifetime history of psychiatric illness completed the study. Subsets of fourteen patients were presenting for first lifetime treatment of a depressive episode, and fifteen patients had at least three treated episodes of depression. We used functional magnetic resonance imaging to study blood oxygen level-dependent signals during the performance of a contingency reversal reward paradigm. The results identified group differences in the response to punishers bilaterally in the orbitofrontal and medial prefrontal regions. In addition, areas such as the nucleus accumbens, anterior cingulate and ventral prefrontal cortices were activated greatest by controls during reward processing, less by patients early in the course of illness and least by patients with highly recurrent illness-suggesting that these areas are sensitive to the impact of disease burden and repeated episodes of depression. Reward processing in people with depression may be associated with diminished signaling of incentive salience, a reduction in the formation of reward-related associations and heightened sensitivities for negatively valenced stimuli, all of which could contribute to symptoms of depression.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropharm.2013.07.033

Neuropharmacology

Neuropharmacology

Exogenous BDNF facilitates strategy set-shifting by modulating glutamate dynamics in the dorsal striatum.

Brain-derived neurotrophic factor (BDNF) signaling via tropomyosin-related kinase B (trkB) receptors exerts modulatory effects on glutamatergic transmission, learning, memory and reward processing. Although the role of BDNF in the regulation of mnemonic and affective/motivational processes is well studied, whether this neurotrophin could also regulate executive functions is not known. In the present study, we assessed the effects of intrastriatal infusions on BDNF (1-100 ng/hemisphere) in mice performing an operant strategy set-shifting task that required the animals to eliminate a visual cue-based strategy and adopt a new egocentric spatial response strategy to achieve rewards. Exogenous BDNF administration facilitated the acquisition of strategy shifting by minimizing response perseveration to the previously acquired strategy and this effect resemble an inverted-U shaped dose-response pattern. Faster acquisition of strategy switching in BDNF-infused animals was dependent upon the activation of striatal trkB receptors. Moreover, activation of mGluR2/3 receptors by the selective group II metabotropic receptor agonist LY379268 abolished BDNF-induced cognitive enhancement suggesting the involvement of presynaptic glutamatergic activity. Assessment of striatal glutamate dynamics using electrochemical recordings indicated that local application of BDNF directly induces glutamate release by activating presynaptic trkB receptors on glutamatergic terminals, and this effect followed a bell-shaped dose-response pattern similar to strategy shifting performance. These data suggest that activation of BDNF-trkB signaling in the dorsal striatum improves strategy switching by effectively minimizing response conflicts, and this effect primarily involves facilitation of glutamatergic transmission.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0071928

PloS one

PLoS One

The effect of the physical presence of co-players on perceived ostracism and event-related brain potentials in the cyberball paradigm.

The affective and cognitive mechanisms elicited by the experience of social exclusion-or ostracism-have recently been explored using behavioral and neurocognitive methods. Most of the studies took advantage of the Cyberball paradigm, a virtual ball tossing game with presumed co-players connected via the internet. Consistent behavioral findings indicate that exclusion obviously threatens fundamental social needs (belonging, self-esteem, meaningful existence, and control) and lowers mood. In this study, we followed the question whether the credibility of the setting affects the processing of social exclusion. In contrast to a control group (standard Cyberball setup), co-players were physically present in an experimental group. Although the credibility of the virtual ball tossing game was significantly enhanced in the experimental group, self-reported negative mood and need threat were not enhanced compared to the control group. Event-related brain potentials (ERPs), however, indicated a differential processing of social exclusion. The N2 amplitude triggered by occasional ball receptions was significantly reduced in the experimental group. This effect was restricted for an early time range (130-210 ms), and did not extend to the following P3 components. The ERP effect in the N2 time range can be related to a differential social reward processing in ostracism if co-players are physically present. The lack of a corresponding correlate in the behavioral data indicates that some facets of ostracism processing are not covered by questionnaire data.

CognitiveConstruct

RewardProcessing

10.1111/ejn.12319

The European journal of neuroscience

Eur J Neurosci

The dopamine patchwork of the rat nucleus accumbens core.

The dopamine (DA) terminal field in the rat dorsal striatum is organized as a patchwork of domains that show distinct DA kinetics. The rate and short-term plasticity of evoked DA release, the rate of DA clearance and the actions of several dopaminergic drugs are all domain-dependent. The patchwork arises in part from local variations in the basal extracellular concentration of DA, which establishes an autoinhibitory tone in slow but not fast domains. The present study addressed the hypothesis that a domain patchwork might also exist in the nucleus accumbens core (NAcc), a DA terminal field that is deeply involved in reward processing and the mechanisms underlying substance abuse. DA recordings in the NAcc by fast-scan voltammetry during electrical stimulation of the medial forebrain bundle confirmed that the NAcc contains a patchwork of fast and slow domains showing significantly different rates of evoked DA release and DA clearance. Moreover, the NAcc domains are substantially different from those in the dorsal striatum. There were no signs in the NAcc of short-term plasticity of DA release during multiple consecutive stimuli, and no signs of a domain-dependent autoinhibitory tone. Thus, the NAcc domains are distinct from each other and from the domains of the dorsal striatum.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2013.07.012

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

Ventral-striatal responsiveness during reward anticipation in ADHD and its relation to trait impulsivity in the healthy population: a meta-analytic review of the fMRI literature.

A review of the existing functional magnetic resonance imaging (fMRI) studies on reward anticipation in patients with attention-deficit/hyperactivity disorder (ADHD) is provided. Meta-analysis showed a significant medium effect size (Cohen's d=0.48-0.58) in terms of ventral-striatal (VS)-hyporesponsiveness in ADHD. Studies on VS-responsiveness and trait impulsivity in the healthy population demonstrate the opposite relationship, i.e. impulsivity-scores positively correlated with VS activation during reward processing. Against the background that ADHD may represent an extreme on a continuum of normal variability, the question arises as to how these contrasting findings can be integrated. We discuss three theoretical approaches, each of which integrates the opposing findings: (1) an inverted-u-shape model; (2) a (genetic) moderator model; and (3) the "unrelated model". We conclude that at the present stage the number of existing studies in the healthy population as well as in ADHD groups is too small for a final answer. Therefore, our presented integrative approaches should be understood as an attempt to frame future research directions by generating testable hypotheses and giving practical suggestions for future studies.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2013.07.001

Psychiatry research

Psychiatry Res

Exposure to traumatic experiences is associated with abnormal neural mechanism during charitable donation.

Previous studies suggested that posttraumatic stress disorder (PTSD) might be associated with dysfunctional reward processing. At present, little is known about the neural mechanisms of reward-related processing during a charitable donation task in trauma survivors who do not go on to develop PTSD. We used functional magnetic resonance imaging (fMRI) to investigate the neural basis of charitable donation in non-PTSD survivors of the Sichuan earthquake. Results showed that activations in the striatum of trauma survivors were reduced in both the low donation (donated a small amount to the Red Cross) and the high donation conditions (donated a large amount to the Red Cross) compared with the healthy controls. Furthermore, the trauma survivors also exhibited less activity in the insula than the healthy controls in the high donation condition. These findings suggest that abnormal reward-related activations might be associated with dysfunctions in the reward pathway of trauma survivors. Also, we discuss the possibility that traumatic experiences attenuate the reactivity of reward-related brain areas to positive emotions (as induced by advantageous donations).

CognitiveConstruct

RewardProcessing

10.1080/02791072.2013.785837

Journal of psychoactive drugs

J Psychoactive Drugs

Tentative evidence for striatal hyperactivity in adolescent cannabis-using boys: a cross-sectional multicenter fMRI study.

Adolescents' risk-taking behavior has been linked to a maturational imbalance between reward ("go") and inhibitory-control ("stop")-related brain circuitry. This may drive adolescent drug-taking, such as cannabis use. In this study, we assessed the non-acute effects of adolescent cannabis use on reward-related brain function. We performed a two-site (United States and Netherlands; pooled data) functional magnetic resonance imaging (fMRI) study with a cross-sectional design. Twenty-one abstinent but frequent cannabis-using boys were compared with 24 non-using peers on reward-related brain function, using a monetary incentive delay task with fMRI. Focus was on anticipatory and response stages of reward and brain areas critically involved in reward processing like the striatum. Performance in users was normal. Region-of-interest analysis indicated striatal hyperactivity during anticipatory stages of reward in users. Intriguingly, this effect was most pronounced during non-rewarding events. Striatal hyperactivity in adolescent cannabis users may signify an overly sensitive motivational brain circuitry. Frequent cannabis use during adolescence may induce diminished ability to disengage the motivational circuit when no reward can be obtained. This could strengthen the search for reinforcements like drugs of abuse, even when facing the negative (non-rewarding) consequences.

CognitiveConstruct

RewardProcessing

10.1017/S1092852913000345

CNS spectrums

CNS Spectr

Incentive salience: novel treatment strategies for major depression.

This article proposes that a recent shift in our understanding of dopamine function may support translational research to target deficits in positive emotions and reward processing in individuals with major depressive disorder (MDD). We review how dopamine functions to modulate approach behaviors in response to positive incentives, and we describe the incentive salience hypothesis, which posits that dopamine primarily modulates "wanting," or anticipatory reward, rather than "liking," or subjective pleasure. Although the incentive salience hypothesis was first proposed to help explain how drugs of abuse may reinforce harmful behaviors in the absence of continued pleasure or "liking," it may also provide a basis for understanding and developing new treatment approaches for MDD. Specifically, it provides a rationale for combining behaviorally activating psychotherapies and pro-dopaminergic agents to target impaired reward processing in MDD.

CognitiveConstruct

RewardProcessing

10.1037/a0033551

Behavioral neuroscience

Behav Neurosci

How bad do you want it? Reward modulation in the avian nidopallium caudolaterale.

The prefrontal cortex plays an important role in reward processing in humans and nonhuman primates. In the current study we examined reward modulation in the single cell activity of the avian analog of the prefrontal cortex, the nidopallium caudolaterale (NCL). Pigeons had to peck at stimuli that represented either no reward, a small reward, or a large reward in a no-choice condition (only one stimulus presented) or a choice condition (two stimuli presented simultaneously). Of the 92 recorded cells, 34 cells showed some form of reward modulation, either during the stimulus presentation or the delay activity preceding the delivery of reward in the no-choice or choice condition. Latencies to peck at the stimulus revealed that the differences in reward amount were behaviorally significant to the pigeons. Moreover, a majority of cells (approximately 70%) showed activity during the actual reward phase. Our results show that cells in the NCL modulate their response as a function of the amount of reward.

CognitiveConstruct

RewardProcessing

10.1016/j.neuron.2013.07.007

Neuron

Neuron

The expected value of control: an integrative theory of anterior cingulate cortex function.

The dorsal anterior cingulate cortex (dACC) has a near-ubiquitous presence in the neuroscience of cognitive control. It has been implicated in a diversity of functions, from reward processing and performance monitoring to the execution of control and action selection. Here, we propose that this diversity can be understood in terms of a single underlying function: allocation of control based on an evaluation of the expected value of control (EVC). We present a normative model of EVC that integrates three critical factors: the expected payoff from a controlled process, the amount of control that must be invested to achieve that payoff, and the cost in terms of cognitive effort. We propose that dACC integrates this information, using it to determine whether, where and how much control to allocate. We then consider how the EVC model can explain the diverse array of findings concerning dACC function.

CognitiveConstruct

RewardProcessing

10.1093/scan/nst110

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

The suggestible brain: posthypnotic effects on value-based decision-making.

Hypnosis can affect perception, motor function and memory. However, so far no study using neuroimaging has investigated whether hypnosis can influence reward processing and decision-making. Here, we assessed whether posthypnotic suggestions can diminish the attractiveness of unhealthy food and whether this is more effective than diminishing attractiveness by one's own effort via autosuggestion. In total, 16 participants were hypnotized and 16 others were instructed to associate a color cue (blue or green) with disgust regarding specific snacks (sweet or salty). Afterwards, participants bid for snack items shown on an either blue or green background during functional magnetic resonance imaging measurement. Both hypnosis and autosuggestion successfully devalued snacks. This was indicated by participants' decision-making, their self-report and by decreased blood oxygen level-dependent signal in the ventromedial prefrontal cortex (vmPFC), a region known to represent value. Different vmPFC subregions coded for cue and snack type. The cue had significantly stronger effects on vmPFC after hypnosis than after autosuggestion, indicating that hypnosis was more effective in genuinely reducing value. Supporting previous findings, the precuneus was involved in the hypnotic effects by encoding whether a snack was sweet or salty during hypnotic cue presentation. Our results demonstrate that posthypnotic suggestions can influence valuation and decision-making.

CognitiveConstruct

RewardProcessing

10.1080/15374416.2013.814544

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

J Clin Child Adolesc Psychol

Differentiating anxiety and depression in children and adolescents: evidence from event-related brain potentials.

The current study, which was a reanalysis of previous data, focused on the error-related negativity (ERN)-an event-related potential (ERP) associated with error monitoring-and the feedback negativity (FN)-an ERP associated with reward processing. Two objectives motivated this study: first, to illustrate the relationship between the ERN and anxious symptoms, and the relationship between the FN and depressive symptoms; second, to explore whether the ERN and the FN relate uniquely to anxiety and depression, respectively, in children. EEG was collected from twenty-five 11- to 13-year-old participants (12 female; 23 Caucasian, 1 Asian, 1 of Caucasian and Hispanic ethnicity) during tasks designed to elicit an ERN and an FN. Participants and a parent completed questionnaires assessing the participant's anxious and depressive symptomatology. Increasing anxiety was related to a larger ERN, and increasing depression was related to a smaller FN. Further analysis demonstrated that these relationships remained significant when controlling for the contribution of other variables; that is, the ERN continued to predict anxiety when controlling for the FN and depression, and the FN continued to predict depression when controlling for the ERN and anxiety. Thus, in late childhood and early adolescence, the ERN and the FN appear to relate uniquely to anxious and depressive symptoms, respectively. Although this research is still in early stages, the ERN and the FN have the potential to inform trajectories of risk for anxiety and depression, and could be utilized in clinical settings as cost- and labor-efficient neural biomarkers.

CognitiveConstruct

RewardProcessing

10.1002/erv.2246

European eating disorders review : the journal of the Eating Disorders Association

Eur Eat Disord Rev

Neurosurgical treatment of anorexia nervosa: review of the literature from leucotomy to deep brain stimulation.

This paper reviews the literature on the surgical treatment of refractory anorexia nervosa (AN) and examines how this literature can inform current circuit models of the disease. The literature contains reports of 35 patients undergoing a neurosurgical procedure for the specific treatment of refractory AN, with the first reported operation, a lobotomy, in 1950. All patients were deemed treatment resistant according to contemporary standards, with the nature of the procedure changing with evolving surgical techniques and methods. All procedures targeted the limbic system and, in a majority of cases, were associated with reported symptomatic improvement. Neurosurgery in AN has been, and continues to be, reserved for patients with chronic and life-threatening illness, for whom conventional treatment has failed. Early procedures, which were viewed as life-saving measures, were crude by today's standards but targeted anatomic structures and pathways implicated in modern models of AN. The last decade has seen a concerted effort in elucidating the neurocircuitry underlying prominent etiologic and maintaining factors in AN, including mood, anxiety and dysfunctional reward processing. This has translated into the development of novel, focused therapeutic options for patients with treatment-refractory AN.

CognitiveConstruct

RewardProcessing

10.1172/JCI44403

The Journal of clinical investigation

J Clin Invest

A link between FTO, ghrelin, and impaired brain food-cue responsivity.

Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight humans, we showed that subjects homozygous for the FTO "obesity-risk" rs9939609 A allele have dysregulated circulating levels of the orexigenic hormone acyl-ghrelin and attenuated postprandial appetite reduction. Using functional MRI (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype modulates the neural responses to food images in homeostatic and brain reward regions. Furthermore, AA and TT subjects exhibited divergent neural responsiveness to circulating acyl-ghrelin within brain regions that regulate appetite, reward processing, and incentive motivation. In cell models, FTO overexpression reduced ghrelin mRNA N6-methyladenosine methylation, concomitantly increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N6-methyladenosine methylation, and increased ghrelin mRNA abundance compared with TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of ingestive behavior, and offer insight into how FTO obesity-risk alleles predispose to increased energy intake and obesity in humans.

CognitiveConstruct

RewardProcessing

10.1017/S0033291713001815

Psychological medicine

Psychol Med

Altered reward processing in the orbitofrontal cortex and hippocampus in healthy first-degree relatives of patients with depression.

Healthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing. In a two-step functional magnetic resonance imaging (fMRI) investigation, we first evaluated whether positive and negative monetary outcomes were differentially processed by rMD+ individuals compared to healthy first-degree relatives of control probands (rMD-). Second, in a double-blinded placebo-controlled randomized trial we investigated whether a 4-week intervention with the selective serotonergic reuptake inhibitor (SSRI) escitalopram had a normalizing effect on behavior and brain responses of the rMD+ individuals. Negative outcomes increased the probability of risk-averse choices in the subsequent trial in rMD+ but not in rMD- individuals. The orbitofrontal cortex (OFC) displayed a stronger neural response when subjects missed a large reward after a low-risk choice in the rMD+ group compared to the rMD- group. The enhanced orbitofrontal response to negative outcomes was reversed following escitalopram intervention compared to placebo. Conversely, for positive outcomes, the left hippocampus showed attenuated response to high wins in the rMD+ compared to the rMD- group. The SSRI intervention reinforced the hippocampal response to large wins. A subsequent structural analysis revealed that the abnormal neural responses were not accounted for by changes in gray matter density in rMD+ individuals. Our study in first-degree relatives of depressive patients showed abnormal brain responses to aversive and rewarding outcomes in regions known to be dysfunctional in depression. We further confirmed the reversal of these aberrant activations with SSRI intervention.

CognitiveConstruct

RewardProcessing

10.1162/jocn_a_00447

Journal of cognitive neuroscience

J Cogn Neurosci

Neural and psychological maturation of decision-making in adolescence and young adulthood.

We examined the maturation of decision-making from early adolescence to mid-adulthood using fMRI of a variant of the Iowa gambling task. We have previously shown that performance in this task relies on sensitivity to accumulating negative outcomes in ventromedial PFC and dorsolateral PFC. Here, we further formalize outcome evaluation (as driven by prediction errors [PE], using a reinforcement learning model) and examine its development. Task performance improved significantly during adolescence, stabilizing in adulthood. Performance relied on greater impact of negative compared with positive PEs, the relative impact of which matured from adolescence into adulthood. Adolescents also showed increased exploratory behavior, expressed as a propensity to shift responding between options independently of outcome quality, whereas adults showed no systematic shifting patterns. The correlation between PE representation and improved performance strengthened with age for activation in ventral and dorsal PFC, ventral striatum, and temporal and parietal cortices. There was a medial-lateral distinction in the prefrontal substrates of effective PE utilization between adults and adolescents: Increased utilization of negative PEs, a hallmark of successful performance in the task, was associated with increased activation in ventromedial PFC in adults, but decreased activation in ventrolateral PFC and striatum in adolescents. These results suggest that adults and adolescents engage qualitatively distinct neural and psychological processes during decision-making, the development of which is not exclusively dependent on reward-processing maturation.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2013.06.039

Journal of affective disorders

J Affect Disord

The neural correlates of reward-related processing in major depressive disorder: a meta-analysis of functional magnetic resonance imaging studies.

A growing number of functional magnetic resonance imaging (fMRI) studies have been conducted in major depressive disorder (MDD) to elucidate reward-related brain functions. The aim of this meta-analysis was to examine the common reward network in the MDD brain and to further distinguish the brain activation patterns between positive stimuli and monetary rewards as well as reward anticipation and outcome. A series of activation likelihood estimation (ALE) meta-analyses were performed across 22 fMRI studies that examined reward-related processing, with a total of 341 MDD patients and 367 healthy controls. We observed several frontostriatal regions that participated in reward processing in MDD. The common reward network in MDD was characterized by decreased subcortical and limbic areas activity and an increased cortical response. In addition, the cerebellum, lingual gyrus, parahippocampal gyrus and fusiform gyrus preferentially responded to positive stimuli in MDD, while the insula, precuneus, cuneus, PFC and inferior parietal lobule selectively responded to monetary rewards. Our results indicated a reduced caudate response during both monetary anticipation and outcome stages as well as increased activation in the middle frontal gyrus and dorsal anterior cingulate during reward anticipation in MDD. The reward-related tasks and mood states of patients included in our analysis were heterogeneous. Our current findings suggest that there exist emotional or motivational pathway dysfunctions in MDD during reward-related processing. Future studies may be strengthened by paying careful attention to the types of reward used as well as the different components of reward processing examined.

CognitiveConstruct

RewardProcessing

10.1002/oby.20563

Obesity (Silver Spring, Md.)

Obesity (Silver Spring)

Neural responsivity during soft drink intake, anticipation, and advertisement exposure in habitually consuming youth.

Although soft drinks are heavily advertised, widely consumed, and have been associated with obesity, little is understood regarding neural responsivity to soft drink intake, anticipated intake, and advertisements. Functional MRI was used to assess examine neural response to carbonated soft drink intake, anticipated intake and advertisement exposure as well as milkshake intake in 27 adolescents that varied on soft drink consumer status. Intake and anticipated intake of carbonated Coke® activated regions implicated in gustatory, oral somatosensory, and reward processing, yet high-fat/sugar milkshake intake elicited greater activation in these regions vs. Coke intake. Advertisements highlighting the Coke product vs. nonfood control advertisements, but not the Coke logo, activated gustatory and visual brain regions. Habitual Coke consumers vs. nonconsumers showed greater posterior cingulate responsivity to Coke logo ads, suggesting that the logo is a conditioned cue. Coke consumers exhibited less ventrolateral prefrontal cortex responsivity during anticipated Coke intake relative to nonconsumers. Results indicate that soft drinks activate reward and gustatory regions, but are less potent in activating these regions than high-fat/sugar beverages, and imply that habitual soft drink intake promotes hyper-responsivity of regions encoding salience/attention toward brand specific cues and hypo-responsivity of inhibitory regions while anticipating intake.

CognitiveConstruct

RewardProcessing

10.2174/13816128113199990427

Current pharmaceutical design

Curr Pharm Des

Cannabinoids and schizophrenia: therapeutic prospects.

Approximately one third of patients diagnosed with schizophrenia do not achieve adequate symptom control with standard antipsychotic drugs (APs). Some of these may prove responsive to clozapine, but non-response to APs remains an important clinical problem and cause of increased health care costs. In a significant proportion of patients, schizophrenia is associated with natural and iatrogenic metabolic abnormalities (obesity, dyslipidaemia, impaired glucose tolerance or type 2 diabetes mellitus), hyperadrenalism and an exaggerated HPA response to stress, and chronic systemic inflammation. The endocannabinoid system (ECS) in the brain plays an important role in maintaining normal mental health. ECS modulates emotion, reward processing, sleep regulation, aversive memory extinction and HPA axis regulation. ECS overactivity contributes to visceral fat accumulation, insulin resistance and impaired energy expenditure. The cannabis plant synthesises a large number of pharmacologically active compounds unique to it known as phytocannabinoids. In contrast to the euphoric and pro-psychotic effects of delta-9-tetrahydrocannabinol (THC), certain non-intoxicating phytocannabinoids have emerged in pre-clinical and clinical models as potential APs. Since the likely mechanism of action does not rely upon dopamine D2 receptor antagonism, synergistic combinations with existing APs are plausible. The anti-inflammatory and immunomodulatory effects of the non-intoxicating phytocannabinoid cannabidiol (CBD) are well established and are summarised below. Preliminary data reviewed in this paper suggest that CBD in combination with a CB1 receptor neutral antagonist could not only augment the effects of standard APs but also target the metabolic, inflammatory and stress-related components of the schizophrenia phenotype.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.4317-12.2013

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

J Neurosci

Ventromedial prefrontal cortex encodes emotional value.

The ventromedial prefrontal cortex (vmPFC) plays a critical role in processing appetitive stimuli. Recent investigations have shown that reward value signals in the vmPFC can be altered by emotion regulation processes; however, to what extent the processing of positive emotion relies on neural regions implicated in reward processing is unclear. Here, we investigated the effects of emotion regulation on the valuation of emotionally evocative images. Two independent experimental samples of human participants performed a cognitive reappraisal task while undergoing fMRI. The experience of positive emotions activated the vmPFC, whereas the regulation of positive emotions led to relative decreases in vmPFC activation. During the experience of positive emotions, vmPFC activation tracked participants' own subjective ratings of the valence of stimuli. Furthermore, vmPFC activation also tracked normative valence ratings of the stimuli when participants were asked to experience their emotions, but not when asked to regulate them. A separate analysis of the predictive power of vmPFC on behavior indicated that even after accounting for normative stimulus ratings and condition, increased signal in the vmPFC was associated with more positive valence ratings. These results suggest that the vmPFC encodes a domain-general value signal that tracks the value of not only external rewards, but also emotional stimuli.

CognitiveConstruct

RewardProcessing

10.1111/ejn.12296

The European journal of neuroscience

Eur J Neurosci

Cocaine exposure enhances excitatory synaptic drive to cholinergic neurons in the laterodorsal tegmental nucleus.

Accumulating evidence indicates that the laterodorsal tegmental nucleus (LDT) is associated with reward processing and addiction. The cholinergic projection from the LDT to the ventral tegmental area is essential for a large dopamine release in the nucleus accumbens, which is critically involved in the reinforcing effects of addictive drugs, including cocaine. In contrast to the large number of studies on plasticity induced after cocaine exposure in the mesocorticolimbic dopaminergic system, it remains unknown whether LDT cholinergic neurons exhibit plastic changes following cocaine administration. To address this issue, we performed ex vivo whole-cell recordings in LDT cholinergic neurons obtained from rats following cocaine administration. Neurons obtained from 1 day after 5-day cocaine-treated rats showed significantly smaller paired-pulse ratios of evoked EPSCs and higher miniature EPSC frequencies than those from saline-treated rats, indicating an induction of presynaptic plasticity of increased glutamate release. This plasticity seemed to recover after a 5-day withdrawal from repeated cocaine exposure, and required NMDA receptor stimulation and nitric oxide production. Additionally, pharmacological suppression of activity of the medial prefrontal cortex inhibited the presynaptic plasticity in the LDT. On the other hand, AMPA/NMDA ratios were not different between saline- and cocaine-treated groups, revealing an absence of postsynaptic plasticity. These findings provide the first direct evidence of cocaine-induced synaptic plasticity in LDT cholinergic neurons and suggest that the presynaptic plasticity enhances the activity of LDT cholinergic neurons, contributing to the expression of cocaine-induced addictive behaviors through the dysregulation of the mesocorticolimbic system.

CognitiveConstruct

RewardProcessing

10.1037/a0030275

Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors

Psychol Addict Behav

Neuroimaging in clinical studies of craving: importance of reward and control networks.

Research on neurobiological mechanisms, especially the function of networks that underlie reward and cognitive control, may offer an opportunity to explore how existing treatments work and provide means for developing new treatments for substance use disorders. In this respect, the special issue of Psychology of Addictive Behaviors highlights efforts to integrate translational neuroimaging with clinical research by actively linking neuroimaging measures with psychosocial treatment mechanisms. Based on several of the articles in this special issue, mindfulness-based approaches appear poised to make rapid progress in terms of integrating neuroimaging with research on mechanisms that mediate treatment success. This commentary briefly discusses research on incentive salience and cognitive control networks in the context of addiction, followed by a discussion of specific studies within this special issue that address the integration of neuroimaging assessments in the context of mindfulness approaches. Future work may be able to leverage measures of changes in networks and regions that underlie reward processing and cognitive control to better understand how treatments work, especially for mindfulness-based approaches.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2013.05.029

Drug and alcohol dependence

Drug Alcohol Depend

Methamphetamine dependent individuals show attenuated brain response to pleasant interoceptive stimuli.

Mechano-receptive C-fiber (MR-CF) stimulation via slow stroking of C-fiber rich skin areas can be used to probe the relationship between reward and interoception. Individuals with substance use disorders show impaired reward processing, and dysfunctional interoceptive processing of MR-CF may contribute to this dysfunction. This study predicted that methamphetamine dependent (MD) individuals would exhibit altered responses to MR-CF stimulation in brain regions important for interoception. Recently abstinent MD (n=25) and comparison (CTL, n=17) subjects received a pleasant interoceptive stimulus ("Soft Touch" consisting of a slow brush stroke) to the palm or forearm during functional magnetic resonance imaging. Subjects were provided with cues signaling stimulation to examine anticipatory and stimulus-related processing. Subjective responses were measured using visual analog scales (VAS). Groups were similar on behavioral performance and ratings of the interoceptive stimuli, yet MD exhibited lower anterior insula, dorsal striatum, and thalamus activation than CTL, across anticipation and soft touch conditions. The lower the anterior insula activation, the faster the reaction time across conditions in MD, whereas the opposite pattern was evident in CTL. Striatal activation in MD was greater than CTL during anticipation, but lower during soft touch. Greater striatal attenuation was associated with higher VAS pleasantness ratings of soft touch. MD expend fewer brain processing resources during soft touch, a form of positively-valenced interoceptive stimuli, in brain areas that are important for both interoception and reward. Future studies will ascertain if sustained abstinence from methamphetamine use can normalize aberrant neural interoceptive processing.

CognitiveConstruct

RewardProcessing

10.1007/s10608-011-9413-8

Cognitive therapy and research

Cognit Ther Res

Perceived Stress, Anhedonia and Illusion of Control: Evidence for Two Mediational Models.

Illusion of control (IOC) refers to the perception that one has control over an outcome, that is, in actuality, uncontrollable; low IOC has been linked to depression. Prior studies in depression have mostly assessed IOC using paradigms involving positive outcomes, suggesting that IOC might be influenced by anhedonia. Recent evidence indicates that anhedonia, in turn, is linked to stress. To clarify such links, we examined putative relationships among perceived stress, anhedonia, and IOC (as assessed by a non-contingency task) in 63 participants. Perceived stress and anhedonia, but not general depressive symptoms, were associated with reduced IOC. Moreover, anhedonia fully mediated the relationship between stress perception and IOC, and perceived stress partially mediated the relationship between IOC and anhedonia. Findings suggest that (1) IOC is integrally related to hedonic capacity, (2) reward processing deficits may promote reduced IOC, and/or (3) a low IOC may promote depression via anhedonia-related mechanisms.

CognitiveConstruct

RewardProcessing

10.1016/j.jpsychires.2013.05.015

Journal of psychiatric research

J Psychiatr Res

Trait anhedonia is associated with reduced reactivity and connectivity of mesolimbic and paralimbic reward pathways.

Anhedonia is the inability to experience pleasure from normally pleasant stimuli. Although anhedonia is a prominent feature of many psychiatric disorders, trait anhedonia is also observed dimensionally in healthy individuals. Currently, the neurobiological basis of anhedonia is poorly understood because it has been mainly investigated in patients with psychiatric disorders. Thus, previous studies have not been able to adequately disentangle the neural correlates of anhedonia from other clinical symptoms. In this study, trait anhedonia was assessed in well-characterized healthy participants with no history of Axis I psychiatric illness. Functional magnetic resonance imaging with musical stimuli was used to examine brain responses and effective connectivity in relation to individual differences in anhedonia. We found that trait anhedonia was negatively correlated with pleasantness ratings of music stimuli and with activation of key brain structures involved in reward processing, including nucleus accumbens (NAc), basal forebrain and hypothalamus which are linked by the medial forebrain bundle to the ventral tegmental area (VTA). Brain regions important for processing salient emotional stimuli, including anterior insula and orbitofrontal cortex were also negatively correlated with trait anhedonia. Furthermore, effective connectivity between NAc, VTA and paralimbic areas, that regulate emotional reactivity to hedonic stimuli, was negatively correlated with trait anhedonia. Our results indicate that trait anhedonia is associated with reduced reactivity and connectivity of mesolimbic and related limbic and paralimbic systems involved in reward processing. Critically, this association can be detected even in individuals without psychiatric illness. Our findings have important implications both for understanding the neurobiological basis of anhedonia and for the treatment of anhedonia in psychiatric disorders.

CognitiveConstruct

RewardProcessing

10.1001/jamapsychiatry.2013.44

JAMA psychiatry

JAMA Psychiatry

Altered reward processing in adolescents with prenatal exposure to maternal cigarette smoking.

Higher rates of substance use and dependence have been observed in the offspring of mothers who smoked during pregnancy. Animal studies indicate that prenatal exposure to nicotine alters the development of brain areas related to reward processing, which might be a risk factor for substance use and addiction later in life. However, no study has examined the effect of maternal smoking on the offspring's brain response during reward processing. To determine whether adolescents with prenatal exposure to maternal cigarette smoking differ from their nonexposed peers in the response of the ventral striatum to the anticipation or the receipt of a reward. An observational case-control study. Data were obtained from the IMAGEN Study, a European multicenter study of impulsivity, reinforcement sensitivity, and emotional reactivity in adolescents. The IMAGEN sample consists of 2078 healthy adolescents (age range, 13-15 years) recruited from March 1, 2008, through December 31, 2011, in local schools. We assessed an IMAGEN subsample of 177 adolescents with prenatal exposure to maternal cigarette smoking and 177 nonexposed peers (age range, 13-15 years) matched by sex, maternal educational level, and imaging site. Response to reward in the ventral striatum measured with functional magnetic resonance imaging. In prenatally exposed adolescents, we observed a weaker response in the ventral striatum during reward anticipation (left side, F = 14.98 [P < .001]; right side, F = 15.95 [P < .001]) compared with their nonexposed peers. No differences were found regarding the responsivity of the ventral striatum to the receipt of a reward (left side, F = 0.21 [P = .65]; right side, F = 0.47 [P = .49]). The weaker responsivity of the ventral striatum to reward anticipation in prenatally exposed adolescents may represent a risk factor for substance use and development of addiction later in life. This result highlights the need for education and preventive measures to reduce smoking during pregnancy. Future analyses should assess whether prenatally exposed adolescents develop an increased risk for substance use and addiction and which role the reported neuronal differences during reward anticipation plays in this development.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2013.00266

Frontiers in human neuroscience

Front Hum Neurosci

Affective and motivational influences in person perception.

Interpersonal impression formation is highly consequential for social interactions in private and public domains. These perceptions of others rely on different sources of information and processing mechanisms, all of which have been investigated in independent research fields. In social psychology, inferences about states and traits of others as well as activations of semantic categories and corresponding stereotypes have attracted great interest. On the other hand, research on emotion and reward demonstrated affective and motivational influences of social cues on the observer, which in turn modulate attention, categorization, evaluation, and decision processes. While inferential and categorical social processes have been shown to recruit a network of cortical brain regions associated with mentalizing and evaluation, the affective influence of social cues has been linked to subcortical areas that play a central role in detection of salient sensory input and reward processing. In order to extend existing integrative approaches to person perception, both the inferential-categorical processing of information about others, and affective and motivational influences of this information on the beholder should be taken into account.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2013.04.029

Biological psychiatry

Biol Psychiatry

Robust changes in reward circuitry during reward loss in current and former cocaine users during performance of a monetary incentive delay task.

Abnormal function in reward circuitry in cocaine addiction could predate drug use as a risk factor, follow drug use as a consequence of substance-induced alterations, or both. We used a functional magnetic resonance imaging monetary incentive delay task (MIDT) to investigate reward-loss neural response differences among 42 current cocaine users, 35 former cocaine users, and 47 healthy subjects who also completed psychological measures and tasks related to impulsivity and reward. We found various reward processing-related group differences in several MIDT phases. Across task phases we found a control > current user > former user activation pattern, except for loss outcome, where former compared with current cocaine users activated ventral tegmental area more robustly. We also found regional prefrontal activation differences during loss anticipation between cocaine-using groups. Both groups of cocaine users scored higher than control subjects on impulsivity, compulsivity and reward-punishment sensitivity factors. In addition, impulsivity-related factors correlated positively with activation in amygdala and negatively with anterior cingulate activation during loss anticipation. Compared with healthy subjects, both former and current users displayed abnormal brain activation patterns during MIDT performance. Both cocaine groups differed similarly from healthy subjects, but differences between former and current users were localized to the ventral tegmental area during loss outcome and to prefrontal regions during loss anticipation, suggesting that long-term cocaine abstinence does not normalize most reward circuit abnormalities. Elevated impulsivity-related factors that relate to loss processing in current and former users suggest that these tendencies and relationships may pre-exist cocaine addiction.

CognitiveConstruct

RewardProcessing

10.1016/j.jpsychires.2013.05.014

Journal of psychiatric research

J Psychiatr Res

Disordered reward processing and functional connectivity in trichotillomania: a pilot study.

The neurobiology of Trichotillomania is poorly understood, although there is increasing evidence to suggest that TTM may involve alterations of reward processing. The current study represents the first exploration of reward processing in TTM and the first resting state fMRI study in TTM. We incorporate both event-related fMRI using a monetary incentive delay (MID) task, and resting state fMRI, using two complementary resting state analysis methodologies (functional connectivity to the nucleus accumbens and dual regression within a reward network) in a pilot study to investigate differences in reward processing between TTM and healthy controls (HC). 21 unmedicated subjects with TTM and 14 HC subjects underwent resting state fMRI scans. A subset (13 TTM and 12 HC) also performed the MID task. For the MID task, TTM subjects showed relatively decreased nucleus accumbens (NAcc) activation to reward anticipation, but relative over-activity of the NAcc to both gain and loss outcomes. Resting state functional connectivity analysis showed decreased connectivity of the dorsal anterior cingulate (dACC) to the NAcc in TTM. Dual regression analysis of a reward network identified through independent component analysis (ICA) also showed decreased dACC connectivity and more prominently decreased basolateral amygdala connectivity within the reward network in TTM. Disordered reward processing at the level of NAcc, also involving decreased modulatory input from the dACC and the basolateral amygdala may play a role in the pathophysiology of TTM.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2013.05.020

Drug and alcohol dependence

Drug Alcohol Depend

Neural mechanisms of risky decision-making and reward response in adolescent onset cannabis use disorder.

Neural mechanisms of decision-making and reward response in adolescent cannabis use disorder (CUD) are underexplored. Three groups of male adolescents were studied: CUD in full remission (n=15); controls with psychopathology without substance use disorder history (n=23); and healthy controls (n=18). We investigated neural processing of decision-making and reward under conditions of varying risk and uncertainty with the Decision-Reward Uncertainty Task while participants were scanned using functional magnetic resonance imaging. Abstinent adolescents with CUD compared to controls with psychopathology showed hyperactivation in one cluster that spanned left superior parietal lobule/left lateral occipital cortex/precuneus while making risky decisions that involved uncertainty, and hypoactivation in left orbitofrontal cortex to rewarded outcomes compared to no-reward after making risky decisions. Post hoc region of interest analyses revealed that both control groups significantly differed from the CUD group (but not from each other) during both the decision-making and reward outcome phase of the Decision-Reward Uncertainty Task. In the CUD group, orbitofrontal activations to reward significantly and negatively correlated with total number of individual drug classes the CUD patients experimented with prior to treatment. CUD duration significantly and negatively correlated with orbitofrontal activations to no-reward. The adolescent CUD group demonstrated distinctly different activation patterns during risky decision-making and reward processing (after risky decision-making) compared to both the controls with psychopathology and healthy control groups. These findings suggest that neural differences in risky decision-making and reward processes are present in adolescent addiction, persist after remission from first CUD treatment, and may contribute to vulnerability for adolescent addiction.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsycho.2013.05.021

Biological psychology

Biol Psychol

Up-regulation of emotional responses to reward-predicting stimuli: an ERP study.

Altered reward processing is a hallmark symptom of many psychiatric disorders. It has recently been shown that people are capable of down-regulating reward processing. Here, we examined whether people are capable of up-regulating emotional responses to reward-predicting stimuli. Participants passively viewed colored squares that predicted a reward or no reward, and up- or down-regulated their emotional responses to these reward-predicting stimuli by focusing on the reward meaning or the color of the squares respectively. The amplitude of the late positive potential (LPP) was taken as an objective index of regulation success. The LPP in response to reward-predicting squares was enhanced by up-regulation, suggesting that up-regulation of emotional responses to reward-predicting stimuli using a cognitive strategy is feasible. These results are highly relevant for the treatment of disorders characterized by diminished motivation, and for reward-based decision making in daily life.

CognitiveConstruct

RewardProcessing

10.1002/dev.21127

Developmental psychobiology

Dev Psychobiol

Age and sex differences in reward behavior in adolescent and adult rats.

Compared to adults, adolescents are at heightened risk for drug abuse and dependence. One of the factors contributing to this vulnerability may be age-dependent differences in reward processing, with adolescents approaching reward through stimulus-directed, rather than goal-directed, processes. However, the empirical evidence for this in rodent models of adolescence, particularly those that investigate both sexes, is limited. To address this, male and female rats that were adolescents (P30) or adults (P98) at the start of the experiment were trained in a Pavlovian approach (PA) task and were subsequently tested for the effects of reward devaluation, extinction, and re-acquisition. We found significant interactions between age and sex: females had enhanced acquisition of PA and poorer extinction, relative to males, while adolescents and females were less sensitive to reward devaluation than male adults. These results suggest that females and adolescents exhibit reward behavior that is more stimulus-directed, rather than goal-directed.

CognitiveConstruct

RewardProcessing

10.2741/e678

Frontiers in bioscience (Elite edition)

Front Biosci (Elite Ed)

Advances in studying phasic dopamine signaling in brain reward mechanisms.

The last sixty years of research has provided extraordinary advances of our knowledge of the reward system. Since its discovery as a neurotransmitter by Carlsson and colleagues (1), dopamine (DA) has emerged as an important mediator of reward processing. As a result, a number of electrochemical techniques have been developed to measure DA in the brain. Together, these techniques have begun to elucidate the complex roles of tonic and phasic DA signaling in reward processing and addiction. In this review, we will first provide a guide for the most commonly used electrochemical methods for DA detection and describe their utility in furthering our knowledge about DA's role in reward and addiction. Second, we will review the value of common in vitro and in vivo preparations and describe their ability to address different types of questions. Last, we will review recent data that has provided new mechanistic insight of in vivo phasic DA signaling and its role in reward processing and reward-mediated behavior.

CognitiveConstruct

RewardProcessing

10.1152/jn.00164.2012

Journal of neurophysiology

J Neurophysiol

Many hats: intratrial and reward level-dependent BOLD activity in the striatum and premotor cortex.

Human functional magnetic resonance imaging (fMRI) studies, as well as lesion, drug, and single-cell recording studies in animals, suggest that the striatum plays a key role in associating sensory events with rewarding actions, both by facilitating reward processing and prediction (i.e., reinforcement learning) and by biasing and later updating action selection. Previous human neuroimaging research has failed to dissociate striatal activity associated with reward, stimulus, and response processing, and previous electrophysiological research in nonhuman animals has typically only examined single striatal subregions. Overcoming both these limitations, we isolated blood oxygen level-dependent (BOLD) signal associated with four intratrial processes (stimulus, preparation of response, response, and feedback) in a visuomotor learning task and examined activity associated with each within four striatal subregions (ventral striatum, putamen, head of the caudate nucleus, and body of the caudate) and the lateral premotor cortex. Overall, the striatum and lateral premotor cortex were recruited during all trial components, confirming their importance in all aspects of visuomotor learning. However, the caudate was most active at stimulus and feedback, whereas the putamen peaked in activity at response. Activation in the lateral premotor cortex was, surprisingly, strongest during stimulus and following response as feedback approached. Activity was additionally examined at three reward magnitudes. Reward magnitude affected neural activity only during stimulus in the caudate, putamen, and premotor cortex, whereas the ventral striatum showed reward sensitivity during both stimulus and feedback. Collectively, these results indicate that each striatal region makes a unique contribution to visuomotor learning through functions performed at different points within single trials.

CognitiveConstruct

RewardProcessing

10.1177/0004867413491153

The Australian and New Zealand journal of psychiatry

Aust N Z J Psychiatry

Clinical correlates of nucleus accumbens volume in drug-naive, adult patients with obsessive-compulsive disorder.

Reward-processing deficits have been demonstrated in obsessive-compulsive disorder (OCD) and this has been linked to ventral striatal abnormalities. However, volumetric abnormalities of the nucleus accumbens (NAcc), a key structure in the reward pathway, have not been examined in OCD. We report on the volumetric abnormalities of NAcc and its correlation with illness severity in drug-naïve, adult patients with OCD. In this cross-sectional study of case-control design, the magnetic resonance imaging (MRI) 1.5-T (1-mm) volume of NAcc was measured using 3D Slicer software in drug-naïve OCD patients (n = 44) and age, sex and handedness-matched healthy controls (HCs) (n = 36) using a valid and reliable method. OCD symptoms were assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Symptom checklist and severity and the Clinical Global Impression-Severity (CGI-S) scale. There was no significant difference in NAcc volumes on either side between OCD patients and HCs (F = 3.45, p = 0.07). However, there was significant negative correlation between the right NAcc volume and Y-BOCS compulsion score (r = -0.48, p = 0.001). Study observations suggest involvement of the NAcc in the pathogenesis of OCD, indicating potential reward-processing deficits. Correlation between the right NAcc volume deficit and severity of compulsions offers further support for this region as a candidate for deep brain stimulation treatment in OCD.

CognitiveConstruct

RewardProcessing

10.1176/appi.ajp.2013.12070917

The American journal of psychiatry

Am J Psychiatry

Neural mechanisms of frustration in chronically irritable children.

Irritability is common in children and adolescents and is the cardinal symptom of disruptive mood dysregulation disorder, a new DSM-5 disorder, yet its neural correlates remain largely unexplored. The authors conducted a functional MRI study to examine neural responses to frustration in children with severe mood dysregulation. The authors compared emotional responses, behavior, and neural activity between 19 severely irritable children (operationalized using criteria for severe mood dysregulation) and 23 healthy comparison children during a cued-attention task completed under nonfrustrating and frustrating conditions. Children in both the severe mood dysregulation and the healthy comparison groups reported increased frustration and exhibited decreased ability to shift spatial attention during the frustration condition relative to the nonfrustration condition. However, these effects of frustration were more marked in the severe mood dysregulation group than in the comparison group. During the frustration condition, participants in the severe mood dysregulation group exhibited deactivation of the left amygdala, the left and right striatum, the parietal cortex, and the posterior cingulate on negative feedback trials, relative to the comparison group (i.e., between-group effect) and to the severe mood dysregulation group's responses on positive feedback trials (i.e., within-group effect). In contrast, neural response to positive feedback during the frustration condition did not differ between groups. In response to negative feedback received in the context of frustration, children with severe, chronic irritability showed abnormally reduced activation in regions implicated in emotion, attention, and reward processing. Frustration appears to reduce attention flexibility, particularly in severely irritable children, which may contribute to emotion regulation deficits in this population. Further research is needed to relate these findings to irritability specifically, rather than to other clinical features of severe mood dysregulation.

CognitiveConstruct

RewardProcessing

10.1038/npp.2013.141

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Dopamine controls the neural dynamics of memory signals and retrieval accuracy.

The human brain is capable of differentiating between new and already stored information rapidly to allow optimal behavior and decision-making. Although the neural mechanisms of novelty discrimination were often described as temporally constant (ie, with specific latencies), recent electrophysiological studies have demonstrated that the onset of neural novelty signals (ie, differences in event-related responses to new and old items) can be accelerated by reward motivation. While the precise physiological mechanisms underlying this acceleration remain unclear, the involvement of the neurotransmitter dopamine in both novelty and reward processing suggests that enhanced dopamine levels in the context of reward prospect may have a role. To investigate this hypothesis, we used magnetoencephalography (MEG) in combination with an old/new recognition memory task in which correct discrimination between old and new items was rewarded. Importantly, before the task, human subjects received either 150 mg of the dopamine precursor levodopa or placebo. For the placebo group, old/new signals peaked at ∼100 ms after stimulus onset over left temporal/occipital sensors. In contrast, after levodopa administration earliest old/new effects only emerged after ∼400 ms and retrieval accuracy was reduced as expressed in lower d' values. As such, our results point towards a previously unreported role of dopamine in controlling the chronometry of neural processes underlying the distinction between old and new information. They also suggest that this relationship follows a nonlinear function whereby slightly enhanced dopamine levels accelerate neural/cognitive processes and excessive dopamine levels impair them.

CognitiveConstruct

RewardProcessing

10.1002/oby.20375

Obesity (Silver Spring, Md.)

Obesity (Silver Spring)

Decreased insular and increased midbrain activations during decision-making under risk in adolescents with excess weight.

Functional magnetic resonance imaging (fMRI) was used to explore the brain substrates of decisions under risk in excess weight adolescents. Decreased activations of the brain regions signaling risk (orbitofrontal cortex [OFC], insula) were expected during anticipation of higher rewards and increased activations of the brain regions involved in reward processing (OFC, striatum) were expected after reward receipt in excess weight adolescents compared to normal weight controls. Fifty-two adolescents (age range 12-17), classified in three groups as a function of BMI: obese (n = 21), overweight (n = 15), or normal weight (n = 16) performed the Risky-Gains task as described by Paulus et al. in the fMRI scanner. Excess weight adolescents, compared to normal weight controls, showed decreased left insular and increased midbrain activations during anticipation of risky choices. In addition, excess weight adolescents showed increased activations of the inferior frontal gyrus, parahippocampus, thalamus, and posterior brain regions after reward receipt. Adolescents with excess weight showed reduced activations in brain regions signaling risk and increased activations in regions signaling reward during anticipation of decisions involving risk and reward. In addition, post-decision reward outcomes produced increased activations of regions involved in emotional salience in excess weight adolescents versus controls.

CognitiveConstruct

RewardProcessing

10.1093/scan/nst077

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Reward-related neural responses are dependent on the beneficiary.

Prior studies have suggested that positive social interactions are experienced as rewarding. Yet, it is not well understood how social relationships influence neural responses to other persons' gains. In this study, we investigated neural responses during a gambling task in which healthy participants (N = 31; 18 females) could win or lose money for themselves, their best friend or a disliked other (antagonist). At the moment of receiving outcome, person-related activity was observed in the dorsal medial prefrontal cortex (dmPFC), precuneus and temporal parietal junction (TPJ), showing higher activity for friends and antagonists than for self, and this activity was independent of outcome. The only region showing an interaction between the person-participants played for and outcome was the ventral striatum. Specifically, the striatum was more active following gains than losses for self and friends, whereas for the antagonist this pattern was reversed. Together, these results show that, in a context with social and reward information, social aspects are processed in brain regions associated with social cognition (mPFC, TPJ), and reward aspects are processed in primary reward areas (striatum). Furthermore, there is an interaction of social and reward information in the striatum, such that reward-related activity was dependent on social relationship.

CognitiveConstruct

RewardProcessing

10.1016/j.pbb.2013.05.011

Pharmacology, biochemistry, and behavior

Pharmacol Biochem Behav

Time of day influences the voluntary intake and behavioral response to methamphetamine and food reward.

The circadian timing system influences a vast array of behavioral responses. Substantial evidence indicates a role for the circadian system in regulating reward processing. Here we explore time of day effects on drug anticipation, locomotor activity, and voluntary methamphetamine (MA) and food intake in animals with ad libitum food access. We compared responses to drug versus a palatable treat during their normal sleep times in early day (zeitgeber time (ZT) 0400) or late day (ZT 1000). In the first study, using a between-subjects design, mice were given daily 1-h access to either peanut butter (PB-Alone) or to a low or high concentration of MA mixed in PB (MA+PB). In study 2, we repeated the experiment using a within-subjects design in which mice could choose between PB-Alone and MA+PB at either ZT 0400 or 1000. In study 3, the effects of MA-alone were investigated by evaluating anticipatory activity preceding exposure to nebulized MA at ZT 0400 vs. ZT 1000. Time of day effects were observed for both drug and palatable treat, such that in the between groups design, animals showed greater intake, anticipatory activity, and post-ingestional activity in the early day. Furthermore, there were differences among mice in the amount of MA ingested but individuals were self-consistent in their daily intake. The results for the within-subjects experiment also revealed robust individual differences in preference for MA+PB or PB-Alone. Interestingly, time of day effects on intake were observed only for the preferred substance. Anticipatory activity preceding administration of MA by nebulization was also greater at ZT 0400 than ZT 1000. Finally, pharmacokinetic response to MA administered intraperitoneally did not vary as a function of time of administration. The results indicate that time of day is an important variable mediating the voluntary intake and behavioral effects of reinforcers.

CognitiveConstruct

RewardProcessing

10.1016/j.jaac.2013.04.003

Journal of the American Academy of Child and Adolescent Psychiatry

J Am Acad Child Adolesc Psychiatry

Striatum-based circuitry of adolescent depression and anhedonia.

Striatum-based circuits have been implicated in both major depressive disorder (MDD) and anhedonia, a symptom that reflects deficits of reward processing. Yet adolescents with MDD often exhibit a wide range of anhedonia severity. Addressing this clinical phenomenon, we aimed to use intrinsic functional connectivity (iFC) to study striatum-based circuitry in relation to categorical diagnosis of MDD and anhedonia severity. A total of 21 psychotropic medication-free adolescents with MDD and 21 healthy controls (HC), group-matched for age and sex, underwent resting-state functional magnetic resonance imagining (fMRI) scans. Voxelwise maps indicating correlation strengths of spontaneous blood-oxygenation-level-dependent (BOLD) signals among 6 bilateral striatal seeds (dorsal caudate, ventral caudate, nucleus accumbens, dorsal-rostral putamen, dorsal-caudal putamen, ventral-rostral putamen) and the remaining brain regions were compared between groups. Relationships between striatal iFC and severity of MDD and anhedonia were examined in the MDD group. Analyses were corrected for multiple comparisons. Adolescents with MDD manifested increased iFC between all striatal regions bilaterally and the dorsomedial prefrontal cortex (dmPFC), as well as between the right ventral caudate and the anterior cingulate cortex (ACC). MDD severity was associated with iFC between the striatum and midline structures including the precuneus, posterior cingulate cortex, and dmPFC. However, distinct striatal iFC patterns involving the pregenual ACC, subgenual ACC, supplementary motor area, and supramarginal gyrus were associated with anhedonia severity. Although MDD diagnosis and severity were related to striatal networks involving midline cortical structures, distinct circuits within the reward system were associated with anhedonia. Findings support the incorporation of both categorical and dimensional approaches in neuropsychiatric research.

CognitiveConstruct

RewardProcessing

10.1177/0956797612469537

Psychological science

Psychol Sci

Compassion training alters altruism and neural responses to suffering.

Compassion is a key motivator of altruistic behavior, but little is known about individuals' capacity to cultivate compassion through training. We examined whether compassion may be systematically trained by testing whether (a) short-term compassion training increases altruistic behavior and (b) individual differences in altruism are associated with training-induced changes in neural responses to suffering. In healthy adults, we found that compassion training increased altruistic redistribution of funds to a victim encountered outside of the training context. Furthermore, increased altruistic behavior after compassion training was associated with altered activation in brain regions implicated in social cognition and emotion regulation, including the inferior parietal cortex and dorsolateral prefrontal cortex (DLPFC), and in DLPFC connectivity with the nucleus accumbens. These results suggest that compassion can be cultivated with training and that greater altruistic behavior may emerge from increased engagement of neural systems implicated in understanding the suffering of other people, executive and emotional control, and reward processing.

CognitiveConstruct

RewardProcessing

10.1007/s12035-013-8472-0

Molecular neurobiology

Mol Neurobiol

Regulating prefrontal cortex activation: an emerging role for the 5-HT₂A serotonin receptor in the modulation of emotion-based actions?

The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings of a regulatory effect of the PFC on the emotional control of our actions.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2013.05.043

NeuroImage

Neuroimage

Parcellation of the human substantia nigra based on anatomical connectivity to the striatum.

Substantia nigra/ventral tegmental area (SN/VTA) subregions, defined by dopaminergic projections to the striatum, are differentially affected by health (e.g. normal aging) and disease (e.g. Parkinson's disease). This may have an impact on reward processing which relies on dopaminergic regions and circuits. We acquired diffusion tensor imaging (DTI) with probabilistic tractography in 30 healthy older adults to determine whether subregions of the SN/VTA could be delineated based on anatomical connectivity to the striatum. We found that a dorsomedial region of the SN/VTA preferentially connected to the ventral striatum whereas a more ventrolateral region connected to the dorsal striatum. These SN/VTA subregions could be characterised by differences in quantitative structural imaging parameters, suggesting different underlying tissue properties. We also observed that these connectivity patterns differentially mapped onto reward dependence personality trait. We show that tractography can be used to parcellate the SN/VTA into anatomically plausible and behaviourally meaningful compartments, an approach that may help future studies to provide a more fine-grained synopsis of pathological changes in the dopaminergic midbrain and their functional impact.

CognitiveConstruct

RewardProcessing

10.1111/psyp.12053

Psychophysiology

Psychophysiology

Self-report and behavioral measures of reward sensitivity predict the feedback negativity.

Rewards are integral to learning associations that aid in survival. The feedback negativity (FN), an event-related potential that differentiates outcomes indicating monetary losses versus gains, has recently emerged as a possible neural measure of reward processing. If this view is correct, then the FN should correlate with measures of reward sensitivity in other domains, although few studies have investigated this question. In the current study, 46 participants completed a self-report measure of reward responsiveness, a signal detection task that generated a behavioral measure of reward sensitivity, and a gambling task that elicited an FN. Consistent with the view that the FN reflects reward-related neural activity, a larger FN correlated with increased behavioral and self-report measures of sensitivity to reward.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0061355

PloS one

PLoS One

Repeated cocaine exposure facilitates the expression of incentive motivation and induces habitual control in rats.

There is growing evidence that mere exposure to drugs can induce long-term alterations in the neural systems that mediate reward processing, motivation, and behavioral control, potentially causing the pathological pursuit of drugs that characterizes the addicted state. The incentive sensitization theory proposes that drug exposure potentiates the influence of reward-paired cues on behavior. It has also been suggested that drug exposure biases action selection towards the automatic execution of habits and away from more deliberate goal-directed control. The current study investigated whether rats given repeated exposure to peripherally administered cocaine would show alterations in incentive motivation (assayed using the Pavlovian-to-instrumental transfer (PIT) paradigm) or habit formation (assayed using sensitivity to reward devaluation). After instrumental and Pavlovian training for food pellet rewards, rats were given 6 daily injections of cocaine (15 mg/kg, IP) or saline, followed by a 10-d period of rest. Consistent with the incentive sensitization theory, cocaine-treated rats showed stronger cue-evoked lever pressing than saline-treated rats during the PIT test. The same rats were then trained on a new instrumental action with a new food pellet reward before undergoing a reward devaluation testing. Although saline-treated rats exhibited sensitivity to reward devaluation, indicative of goal-directed performance, cocaine-treated rats were insensitive to this treatment, suggesting a reliance on habitual processes. These findings, when taken together, indicate that repeated exposure to cocaine can cause broad alterations in behavioral control, spanning both motivational and action selection processes, and could therefore help explain aberrations of decision-making that underlie drug addiction.

CognitiveConstruct

RewardProcessing

10.1016/j.cortex.2013.02.014

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

Cortex

Hemispheric dissociation of reward processing in humans: insights from deep brain stimulation.

Rewards have various effects on human behavior and multiple representations in the human brain. Behaviorally, rewards notably enhance response vigor in incentive motivation paradigms and bias subsequent choices in instrumental learning paradigms. Neurally, rewards affect activity in different fronto-striatal regions attached to different motor effectors, for instance in left and right hemispheres for the two hands. Here we address the question of whether manipulating reward-related brain activity has local or general effects, with respect to behavioral paradigms and motor effectors. Neuronal activity was manipulated in a single hemisphere using unilateral deep brain stimulation (DBS) in patients with Parkinson's disease. Results suggest that DBS amplifies the representation of reward magnitude within the targeted hemisphere, so as to affect the behavior of the contralateral hand specifically. These unilateral DBS effects on behavior include both boosting incentive motivation and biasing instrumental choices. Furthermore, using computational modeling we show that DBS effects on incentive motivation can predict DBS effects on instrumental learning (or vice versa). Thus, we demonstrate the feasibility of causally manipulating reward-related neuronal activity in humans, in a manner that is specific to a class of motor effectors but that generalizes to different computational processes. As these findings proved independent from therapeutic effects on parkinsonian motor symptoms, they might provide insight into DBS impact on non-motor disorders, such as apathy or hypomania.

CognitiveConstruct

RewardProcessing

10.1038/npp.2013.102

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Midbrain-driven emotion and reward processing in alcoholism.

Alcohol dependence is associated with impaired control over emotionally motivated actions, possibly associated with abnormalities in the frontoparietal executive control network and midbrain nodes of the reward network associated with automatic attention. To identify differences in the neural response to alcohol-related word stimuli, 26 chronic alcoholics (ALC) and 26 healthy controls (CTL) performed an alcohol-emotion Stroop Match-to-Sample task during functional MR imaging. Stroop contrasts were modeled for color-word incongruency (eg, word RED printed in green) and for alcohol (eg, BEER), positive (eg, HAPPY) and negative (eg, MAD) emotional word content relative to congruent word conditions (eg, word RED printed in red). During color-Stroop processing, ALC and CTL showed similar left dorsolateral prefrontal activation, and CTL, but not ALC, deactivated posterior cingulate cortex/cuneus. An interaction revealed a dissociation between alcohol-word and color-word Stroop processing: ALC activated midbrain and parahippocampal regions more than CTL when processing alcohol-word relative to color-word conditions. In ALC, the midbrain region was also invoked by negative emotional Stroop words thereby showing significant overlap of this midbrain activation for alcohol-related and negative emotional processing. Enhanced midbrain activation to alcohol-related words suggests neuroadaptation of dopaminergic midbrain systems. We speculate that such tuning is normally associated with behavioral conditioning to optimize responses but here contributed to automatic bias to alcohol-related stimuli.

CognitiveConstruct

RewardProcessing

10.1111/bdi.12068

Bipolar disorders

Bipolar Disord

The risk variant in ODZ4 for bipolar disorder impacts on amygdala activation during reward processing.

Bipolar disorder is a severe mood disorder, which normally begins during adolescence or early adulthood and has a heritability of up to 80%. The largest genome-wide association analysis of bipolar disorder recently identified a new genome-wide associated variant in OZD4 (rs12576775). The aim of the present study was to further elucidate the role of this risk variant in the disease process using an imaging genetics approach. As increased amygdala and striatal responses during the processing of reward and emotion are characteristic for bipolar disorder patients, it was tested whether the risk variant has an influence on this endophenotype in healthy adolescents. We examined the impact of the risk variant rs12576775 on functional magnetic resonance imaging data in an adolescent sample (N = 485). Differential activation between carriers of the risk allele (G-allele) and homozygous A-allele carriers in the amygdala and the striatum during a modification of the monetary incentive delay task (examining reward) and a face task (examining emotion) was analyzed. Carriers of the risk allele showed an increased blood oxygen level-dependent response in the amygdala during reward sensitivity (p = 0.05) and reward expectation (p < 0.05) but not during the face task. No significant group differences were found in the striatum during both reward and emotion processing. Our results indicate that the ODZ4 risk variant influences reward processing in the amygdala. Alterations in the processing of emotion may have different underlying mechanisms and need to be further examined.

CognitiveConstruct

RewardProcessing

10.1080/10640266.2013.779190

Eating disorders

Eat Disord

What contributes to excessive diet soda intake in eating disorders: appetitive drive, weight concerns, or both?

Excessive diet soda intake is common in eating disorders. The present study examined factors contributing to excessive intake in a sample of individuals with lifetime eating disorders based on proposed DSM-5 criteria (n = 240) and non-eating disorder controls (n = 157). Individuals with eating disorders, particularly bulimia nervosa, consumed more diet soda than controls. Eating disorder symptoms that reflect increased appetitive drive or increased weight concerns were associated with increased diet soda intake. Increased weight concerns were associated with increased diet soda intake when levels of appetitive drive were high, but not when they were low. Results highlight the importance of monitoring diet soda intake in individuals with eating disorders and may have implications for the maintenance of dysregulated taste reward processing in bulimia nervosa.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2013.00133

Frontiers in human neuroscience

Front Hum Neurosci

Acute stress selectively reduces reward sensitivity.

Stress may promote the onset of psychopathology by disrupting reward processing. However, the extent to which stress impairs reward processing, rather than incentive processing more generally, is unclear. To evaluate the specificity of stress-induced reward processing disruption, 100 psychiatrically healthy females were administered a probabilistic stimulus selection task (PSST) that enabled comparison of sensitivity to reward-driven (Go) and punishment-driven (NoGo) learning under either "no stress" or "stress" (threat-of-shock) conditions. Cortisol samples and self-report measures were collected. Contrary to hypotheses, the groups did not differ significantly in task performance or cortisol reactivity. However, further analyses focusing only on individuals under "stress" who were high responders with regard to both cortisol reactivity and self-reported negative affect revealed reduced reward sensitivity relative to individuals tested in the "no stress" condition; importantly, these deficits were reward-specific. Overall, findings provide preliminary evidence that stress-reactive individuals show diminished sensitivity to reward, but not punishment, under stress. While such results highlight the possibility that stress-induced anhedonia might be an important mechanism linking stress to affective disorders, future studies are necessary to confirm this conjecture.

CognitiveConstruct

RewardProcessing

10.1016/j.tins.2013.03.003

Trends in neurosciences

Trends Neurosci

Dissecting the diversity of midbrain dopamine neurons.

Midbrain dopamine (DA) neurons are essential for controlling key functions of the brain, such as voluntary movement, reward processing, and working memory. The largest populations of midbrain DA neurons are localized in two neighboring nuclei, the substantia nigra (SN) and the ventral tegmental area (VTA). Regardless of their different axonal projections to subcortical and cortical targets, midbrain DA neurons have traditionally been regarded as a relatively homogeneous group of neurons, with a stereotypical set of intrinsic electrophysiological properties and in vivo pattern of activity. In this review, I highlight recent data supporting an unexpected degree of diversity among these midbrain DA neurons in the mammalian brain, ranging from their developmental lineages and different synaptic connectivity to their electrophysiological properties and behavioral functions.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropharm.2013.03.019

Neuropharmacology

Neuropharmacology

Reward and aversion in a heterogeneous midbrain dopamine system.

The ventral tegmental area (VTA) is a heterogeneous brain structure that serves a central role in motivation and reward processing. Abnormalities in the function of VTA dopamine (DA) neurons and the targets they influence are implicated in several prominent neuropsychiatric disorders including addiction and depression. Recent studies suggest that the midbrain DA system is composed of anatomically and functionally heterogeneous DA subpopulations with different axonal projections. These findings may explain a number of previously confusing observations that suggested a role for DA in processing both rewarding as well as aversive events. Here we will focus on recent advances in understanding the neural circuits mediating reward and aversion in the VTA and how stress as well as drugs of abuse, in particular cocaine, alter circuit function within a heterogeneous midbrain DA system. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

CognitiveConstruct

RewardProcessing

10.1007/s00441-013-1607-9

Cell and tissue research

Cell Tissue Res

Affective communication in rodents: ultrasonic vocalizations as a tool for research on emotion and motivation.

Mice and rats emit and perceive calls in the ultrasonic range, i.e., above the human hearing threshold of about 20 kHz: so-called ultrasonic vocalizations (USV). Juvenile and adult rats emit 22-kHz USV in aversive situations, such as predator exposure and fighting or during drug withdrawal, whereas 50-kHz USV occur in appetitive situations, such as rough-and-tumble play and mating or in response to drugs of abuse, e.g., amphetamine. Aversive 22-kHz USV and appetitive 50-kHz USV serve distinct communicative functions. Whereas 22-kHz USV induce freezing behavior in the receiver, 50-kHz USV lead to social approach behavior. These opposite behavioral responses are paralleled by distinct patterns of brain activation. Freezing behavior in response to 22-kHz USV is paralleled by increased neuronal activity in brain areas regulating fear and anxiety, such as the amygdala and periaqueductal gray, whereas social approach behavior elicited by 50-kHz USV is accompanied by reduced activity levels in the amygdala but enhanced activity in the nucleus accumbens, a brain area implicated in reward processing. These opposing behavioral responses, together with distinct patterns of brain activation, particularly the bidirectional tonic activation or deactivation of the amygdala elicited by 22-kHz and 50-kHz USV, respectively, concur with a wealth of behavioral and neuroimaging studies in humans involving emotionally salient stimuli, such as fearful and happy facial expressions. Affective ultrasonic communication therefore offers a translational tool for studying the neurobiology underlying socio-affective communication. This is particularly relevant for rodent models of neurodevelopmental disorders characterized by social and communication deficits, such as autism and schizophrenia.

CognitiveConstruct

RewardProcessing

10.1162/jocn_a_00399

Journal of cognitive neuroscience

J Cogn Neurosci

Effects of pulvinar inactivation on spatial decision-making between equal and asymmetric reward options.

The ability to selectively process visual inputs and to decide between multiple movement options in an adaptive manner is critical for survival. Such decisions are known to be influenced by factors such as reward expectation and visual saliency. The dorsal pulvinar connects to a multitude of cortical areas that are involved in visuospatial memory and integrate information about upcoming eye movements with expected reward values. However, it is unclear whether the dorsal pulvinar is critically involved in spatial memory and reward-based oculomotor decision behavior. To examine this, we reversibly inactivated the dorsal portion of the pulvinar while monkeys performed a delayed memory saccade task that included choices between equally or unequally rewarded options. Pulvinar inactivation resulted in a delay of saccade initiation toward memorized contralesional targets but did not affect spatial memory. Furthermore, pulvinar inactivation caused a pronounced choice bias toward the ipsilesional hemifield when the reward value in the two hemifields was equal. However, this choice bias could be alleviated by placing a high reward target into the contralesional hemifield. The bias was less affected by the manipulation of relative visual saliency between the two competing targets. These results suggest that the dorsal pulvinar is involved in determining the behavioral desirability of movement goals while being less critical for spatial memory and reward processing.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0058708

PloS one

PLoS One

Neural sensitivity to absolute and relative anticipated reward in adolescents.

Adolescence is associated with a dramatic increase in risky and impulsive behaviors that have been attributed to developmental differences in neural processing of rewards. In the present study, we sought to identify age differences in anticipation of absolute and relative rewards. To do so, we modified a commonly used monetary incentive delay (MID) task in order to examine brain activity to relative anticipated reward value (neural sensitivity to the value of a reward as a function of other available rewards). This design also made it possible to examine developmental differences in brain activation to absolute anticipated reward magnitude (the degree to which neural activity increases with increasing reward magnitude). While undergoing fMRI, 18 adolescents and 18 adult participants were presented with cues associated with different reward magnitudes. After the cue, participants responded to a target to win money on that trial. Presentation of cues was blocked such that two reward cues associated with $.20, $1.00, or $5.00 were in play on a given block. Thus, the relative value of the $1.00 reward varied depending on whether it was paired with a smaller or larger reward. Reflecting age differences in neural responses to relative anticipated reward (i.e., reference dependent processing), adults, but not adolescents, demonstrated greater activity to a $1 reward when it was the larger of the two available rewards. Adults also demonstrated a more linear increase in ventral striatal activity as a function of increasing absolute reward magnitude compared to adolescents. Additionally, reduced ventral striatal sensitivity to absolute anticipated reward (i.e., the difference in activity to medium versus small rewards) correlated with higher levels of trait Impulsivity. Thus, ventral striatal activity in anticipation of absolute and relative rewards develops with age. Absolute reward processing is also linked to individual differences in Impulsivity.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0058493

PloS one

PLoS One

Increased brain white matter axial diffusivity associated with fatigue, pain and hyperalgesia in Gulf War illness.

Gulf War exposures in 1990 and 1991 have caused 25% to 30% of deployed personnel to develop a syndrome of chronic fatigue, pain, hyperalgesia, cognitive and affective dysfunction. Gulf War veterans (n = 31) and sedentary veteran and civilian controls (n = 20) completed fMRI scans for diffusion tensor imaging. A combination of dolorimetry, subjective reports of pain and fatigue were correlated to white matter diffusivity properties to identify tracts associated with symptom constructs. Gulf War Illness subjects had significantly correlated fatigue, pain, hyperalgesia, and increased axial diffusivity in the right inferior fronto-occipital fasciculus. ROC generated thresholds and subsequent binary regression analysis predicted CMI classification based upon axial diffusivity in the right inferior fronto-occipital fasciculus. These correlates were absent for controls in dichotomous regression analysis. The right inferior fronto-occipital fasciculus may be a potential biomarker for Gulf War Illness. This tract links cortical regions involved in fatigue, pain, emotional and reward processing, and the right ventral attention network in cognition. The axonal neuropathological mechanism(s) explaining increased axial diffusivity may account for the most prominent symptoms of Gulf War Illness.

CognitiveConstruct

RewardProcessing

10.1038/nn.3364

Nature neuroscience

Nat Neurosci

Dopamine restores reward prediction errors in old age.

Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum, measured by diffusion tensor imaging, was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults. This drug effect was linked to restoration of a canonical neural RPE. Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2013.03.004

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

A systematic review of fMRI reward paradigms used in studies of adolescents vs. adults: the impact of task design and implications for understanding neurodevelopment.

The neural systems underlying reward-related behaviors across development have recently generated a great amount of interest. Yet, the neurodevelopmental literature on reward processing is marked by inconsistencies due to the heterogeneity of the reward paradigms used, the complexity of the behaviors being studied, and the developing brain itself as a moving target. The present review will examine task design as one source of variability across findings by compiling this literature along three dimensions: (1) task structures, (2) cognitive processes, and (3) neural systems. We start with the presentation of a heuristic neural systems model, the Triadic Model, as a way to provide a theoretical framework for the neuroscience research on motivated behaviors. We then discuss the principles guiding reward task development. Finally, we review the extant developmental neuroimaging literature on reward-related processing, organized by reward task type. We hope that this approach will help to clarify the literature on the functional neurodevelopment of reward-related neural systems, and to identify the role of the experimental parameters that significantly influence these findings.

CognitiveConstruct

RewardProcessing

10.1038/nature12041

Nature

Nature

Distinct extended amygdala circuits for divergent motivational states.

The co-morbidity of anxiety and dysfunctional reward processing in illnesses such as addiction and depression suggests that common neural circuitry contributes to these disparate neuropsychiatric symptoms. The extended amygdala, including the bed nucleus of the stria terminalis (BNST), modulates fear and anxiety, but also projects to the ventral tegmental area (VTA), a region implicated in reward and aversion, thus providing a candidate neural substrate for integrating diverse emotional states. However, the precise functional connectivity between distinct BNST projection neurons and their postsynaptic targets in the VTA, as well as the role of this circuit in controlling motivational states, have not been described. Here we record and manipulate the activity of genetically and neurochemically identified VTA-projecting BNST neurons in freely behaving mice. Collectively, aversive stimuli exposure produced heterogeneous firing patterns in VTA-projecting BNST neurons. By contrast, in vivo optically identified glutamatergic projection neurons displayed a net enhancement of activity to aversive stimuli, whereas the firing rate of identified GABAergic (γ-aminobutyric acid-containing) projection neurons was suppressed. Channelrhodopsin-2-assisted circuit mapping revealed that both BNST glutamatergic and GABAergic projections preferentially innervate postsynaptic non-dopaminergic VTA neurons, thus providing a mechanistic framework for in vivo circuit perturbations. In vivo photostimulation of BNST glutamatergic projections resulted in aversive and anxiogenic behavioural phenotypes. Conversely, activation of BNST GABAergic projections produced rewarding and anxiolytic phenotypes, which were also recapitulated by direct inhibition of VTA GABAergic neurons. These data demonstrate that functionally opposing BNST to VTA circuits regulate rewarding and aversive motivational states, and may serve as a crucial circuit node for bidirectionally normalizing maladaptive behaviours.

CognitiveConstruct

RewardProcessing

10.1002/oby.20386

Obesity (Silver Spring, Md.)

Obesity (Silver Spring)

Obesity is associated with white matter atrophy: a combined diffusion tensor imaging and voxel-based morphometric study.

Little is known about the mechanisms by which obesity influences brain structure. In this study, the obesity-related changes in brain white and gray matter integrity were examined. 23 morbidly obese subjects and 22 nonobese volunteers were studied using voxel-based analysis of diffusion tensor imaging and of T1-weighted MRI images. Full-volume statistical parametric mapping analysis was used to compare fractional anisotropy (FA) and mean diffusivity (MD) values as well as gray (GM) and white matter (WM) density between these groups. Obese subjects had lower FA and MD values and lower focal and global GM and WM volumes than control subjects did. The focal structural changes were observed in brain regions governing reward seeking, inhibitory control, and appetite. Regression analysis showed that FA and MD values as well as GM and WM density were negatively associated with body fat percentage. Moreover, the volume of abdominal subcutaneous fat was negatively associated with GM density in most regions. These findings imply that changes in GM and WM in obesity may be due to metabolic factors. Atrophy in regions involved in reward processing and appetite control may further promote abnormal reward seeking and eating behavior.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2013.02.017

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

Principles of motivation revealed by the diverse functions of neuropharmacological and neuroanatomical substrates underlying feeding behavior.

Circuits that participate in specific subcomponents of feeding (e.g., gustatory perception, peripheral feedback relevant to satiety and energy balance, reward coding, etc.) are found at all levels of the neural axis. Further complexity is conferred by the wide variety of feeding-modulatory neurotransmitters and neuropeptides that act within these circuits. An ongoing challenge has been to refine the understanding of the functional specificity of these neurotransmitters and circuits, and there have been exciting advances in recent years. We focus here on foundational work of Dr. Ann Kelley that identified distinguishable actions of striatal opioid peptide modulation and dopamine transmission in subcomponents of reward processing. We also discuss her work in overlaying these neuropharmacological effects upon anatomical pathways that link the telencephalon (cortex and basal ganglia) with feeding-control circuits in the hypothalamus. Using these seminal contributions as a starting point, we will discuss new findings that expand our understanding of (1) the specific, differentiable motivational processes that are governed by central dopamine and opioid transmission, (2) the manner in which other striatal neuromodulators, specifically acetylcholine, endocannabinoids and adenosine, modulate these motivational processes (including via interactions with opioid systems), and (3) the organization of the cortical-subcortical network that subserves opioid-driven feeding. The findings discussed here strengthen the view that incentive-motivational properties of food are coded by substrates and neural circuits that are distinguishable from those that mediate the acute hedonic experience of food reward. Striatal opioid transmission modulates reward processing by engaging frontotemporal circuits, possibly via a hypothalamic-thalamic axis, that ultimately impinges upon hypothalamic modules dedicated to autonomic function and motor pattern control. We will conclude by discussing implications for understanding disorders of "non-homeostatic" feeding.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2013.01.014

Biological psychiatry

Biol Psychiatry

Monetary reward processing in obese individuals with and without binge eating disorder.

An important step in obesity research involves identifying neurobiological underpinnings of nonfood reward processing unique to specific subgroups of obese individuals. Nineteen obese individuals seeking treatment for binge eating disorder (BED) were compared with 19 non-BED obese individuals (OB) and 19 lean control subjects (LC) while performing a monetary reward/loss task that parses anticipatory and outcome components during functional magnetic resonance imaging. Differences in regional activation were investigated in BED, OB, and LC groups during reward/loss prospect, anticipation, and notification. Relative to the LC group, the OB group demonstrated increased ventral striatal and ventromedial prefrontal cortex activity during anticipatory phases. In contrast, the BED group relative to the OB group demonstrated diminished bilateral ventral striatal activity during anticipatory reward/loss processing. No differences were observed between the BED and LC groups in the ventral striatum. Heterogeneity exists among obese individuals with respect to the neural correlates of reward/loss processing. Neural differences in separable groups with obesity suggest that multiple, varying interventions might be important in optimizing prevention and treatment strategies for obesity.

CognitiveConstruct

RewardProcessing

10.1016/j.conb.2013.02.005

Current opinion in neurobiology

Curr Opin Neurobiol

The multiple facets of opioid receptor function: implications for addiction.

Addiction is characterized by altered reward processing, disrupted emotional responses and poor decision-making. Beyond a central role in drug reward, increasing evidence indicate that opioid receptors are broadly involved in all these processes. Recent studies establish the mu opioid receptor as a main player in social reward, which attracts increasing attention in psychiatric research. There is growing interest in blocking the kappa opioid receptor to prevent relapse, and alleviate the negative affect of withdrawal. The delta opioid receptor emerges as a potent mood enhancer, whose involvement in addiction is less clear. All three opioid receptors are likely implicated in addiction-depression comorbidity, and understanding of their roles in cognitive deficits associated to drug abuse is only beginning.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.4942-12.2013

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

J Neurosci

Basolateral amygdala lesions facilitate reward choices after negative feedback in rats.

The orbitofrontal cortex (OFC) and basolateral amygdala (BLA) constitute part of a neural circuit important for adaptive, goal-directed learning. One task measuring flexibility of response to changes in reward is discrimination reversal learning. Damage to OFC produces well documented impairments on various forms of reversal learning in rodents, monkeys, and humans. Recent reports show that BLA, though highly interconnected with OFC, may be differentially involved in reversal learning. In the present experiment, we compared the effects of bilateral, ibotenic acid lesions of OFC or BLA (or SHAM) on visual discrimination and reversal learning. Specifically, we used pairwise visual discrimination methods, as is commonly administered in non-human primate studies, and analyzed how animals use positive and negative trial-by-trial feedback, domains not previously explored in a rat study. As expected, OFC lesions displayed significantly slower reversal learning than SHAM and BLA rats across sessions. Rats with BLA lesions, conversely, showed facilitated reversal learning relative to SHAM and OFC groups. Furthermore, a trial-by-trial analysis of the errors committed showed the BLA group benefited more from incorrectly performed trials (or negative feedback) on future choices than either SHAM or OFC rats. This provides evidence that BLA and OFC are involved in updating responses to changes in reward contingency and that the roles are distinct. Our results are discussed in relation to a competitive framework model for OFC and BLA in reward processing.

CognitiveConstruct

RewardProcessing

10.1111/adb.12041

Addiction biology

Addict Biol

Abstinence duration modulates striatal functioning during monetary reward processing in cocaine patients.

Pre-clinical and clinical studies in cocaine addiction highlight alterations in the striatal dopaminergic reward system that subserve maintenance of cocaine use. Using an instrumental conditioning paradigm with monetary reinforcement, we studied striatal functional alterations in long-term abstinent cocaine-dependent patients and striatal functioning as a function of abstinence and treatment duration. Eighteen patients and 20 controls underwent functional magnetic resonance imaging during a Monetary Incentive Delay task. Region of interest analyses based on masks of the dorsal and ventral striatum were conducted to test between-group differences and the functional effects in the cocaine group of time (in months) with no more than two lapses from the first time patients visited the clinical service to seek treatment at the scanning time (duration of treatment), and the functional effects of the number of months with no lapses or relapses at the scanning session time (length of abstinence). We applied a voxel-wise and a cluster-wise FWE-corrected level (pFWE) at a threshold of P < 0.05. The patient group showed lower activation in the right caudate during reward anticipation than the control group. The regression analyses in the patients group revealed a positive correlation between duration of treatment and brain activity in the left caudate during reward anticipation. Likewise, length of abstinence negatively correlated with brain activity in the bilateral nucleus accumbens during monetary outcome processing. In conclusion, caudate and nucleus accumbens show a different brain response pattern to non-drug rewards during cocaine addiction, which can be modulated by treatment success.

CognitiveConstruct

RewardProcessing

10.1038/tp.2013.6

Translational psychiatry

Transl Psychiatry

THC reduces the anticipatory nucleus accumbens response to reward in subjects with a nicotine addiction.

Recent evidence has implicated the endocannabinoid (eCB) system in nicotine addiction. The eCB system also has an important role in reward mechanisms, and nicotine addiction has been associated with aberrant reward processing. Motivated by this evidence, we tested the hypothesis that eCB modulation of reward processing is altered in subjects with a nicotine addiction (NAD). For this purpose, we compared reward-related activity in NAD with healthy controls (HC) in a pharmacological magnetic resonance imaging (MRI) study using Δ(9)-tetrahydrocannabinol (THC) administration to challenge the eCB system. Eleven HC and 10 NAD participated in a 3-T functional MRI (fMRI) study with a double-blind, cross-over, placebo-controlled design, using a Monetary Incentive Delay (MID) paradigm with three reward levels. Reward activity in the nucleus accumbens (NAcc) and caudate putamen during anticipation and feedback of reward was compared after THC and placebo. fMRI results indicated a significant reduction of reward anticipation activity in the NAcc in NAD after THC administration, which was not present in HC. This is indicated by a significant group by drug by reward interaction. Our data show that THC significantly reduces the NAcc response to monetary reward anticipation in NAD. These results suggest that nicotine addiction is associated with altered eCB modulation of reward processing in the NAcc. This study adds important human data to existing evidence implicating the eCB system in nicotine addiction.

CognitiveConstruct

RewardProcessing

10.1093/brain/awt027

Brain : a journal of neurology

Brain

Attenuated neural response to gamble outcomes in drug-naive patients with Parkinson's disease.

Parkinson's disease results from the degeneration of dopaminergic neurons in the substantia nigra, manifesting as a spectrum of motor, cognitive and affective deficits. Parkinson's disease also affects reward processing, but disease-related deficits in reinforcement learning are thought to emerge at a slower pace than motor symptoms as the degeneration progresses from dorsal to ventral striatum. Dysfunctions in reward processing are difficult to study in Parkinson's disease as most patients have been treated with dopaminergic drugs, which sensitize reward responses in the ventral striatum, commonly resulting in impulse control disorders. To circumvent this treatment confound, we assayed the neural basis of reward processing in a group of newly diagnosed patients with Parkinson's disease that had never been treated with dopaminergic drugs. Thirteen drug-naive patients with Parkinson's disease and 12 healthy age-matched control subjects underwent whole-brain functional magnetic resonance imaging while they performed a simple two-choice gambling task resulting in stochastic and parametrically variable monetary gains and losses. In patients with Parkinson's disease, the neural response to reward outcome (as reflected by the blood oxygen level-dependent signal) was attenuated in a large group of mesolimbic and mesocortical regions, comprising the ventral putamen, ventral tegmental area, thalamus and hippocampus. Although these regions showed a linear response to reward outcome in healthy individuals, this response was either markedly reduced or undetectable in drug-naive patients with Parkinson's disease. The results show that the core regions of the meso-cortico-limbic dopaminergic system, including the ventral tegmental area, ventral striatum, and medial orbitofrontal cortex, are already significantly compromised in the early stages of the disease and that these deficits cannot be attributed to the contaminating effect of dopaminergic treatment.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.4388-12.2013

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

J Neurosci

Neurons in monkey dorsal raphe nucleus code beginning and progress of step-by-step schedule, reward expectation, and amount of reward outcome in the reward schedule task.

The dorsal raphe nucleus is the major source of serotonin in the brain. It is connected to brain regions related to reward processing, and the neurons show activity related to predicted reward outcome. Clinical observations also suggest that it is important in maintaining alertness and its apparent role in addiction seems to be related to reward processing. Here, we examined whether the neurons in dorsal raphe carry signals about reward outcome and task progress during multitrial schedules. We recorded from 98 single neurons in dorsal raphe of two monkeys. The monkeys perform one, two, or three visual discrimination trials (schedule), obtaining one, two, or three drops of liquid. In the valid cue condition, the length and brightness of a visual cue indicated schedule progress and reward amount, respectively. In the random cue condition, the visual cue was randomly presented with respect to schedule length and reward amount. We found information encoded about (1) schedule onset, (2) reward expectation, (3) reward outcome, and (4) reward amount in the mean firing rates. Information theoretic analysis showed that the temporal variation of the neuronal responses contained additional information related to the progress of the schedule toward the reward rather than only discriminating schedule onset or reward/no reward. When considered in light of all that is known about the raphe in anatomy, physiology, and behavior, the rich encoding about both task progress and predicted reward outcome makes the raphe a strong candidate for providing signals throughout the brain to coordinate persistent goal-seeking behavior.

CognitiveConstruct

RewardProcessing

10.1111/acer.12037

Alcoholism, clinical and experimental research

Alcohol Clin Exp Res

Resting-state synchrony in short-term versus long-term abstinent alcoholics.

We previously reported that when compared with controls, long-term abstinent alcoholics (LTAA) have increased resting-state synchrony (RSS) of the inhibitory control network and reduced synchrony of the appetitive drive network, and hypothesized that these levels of synchrony are adaptive and support the behavioral changes required to maintain abstinence. In this study, we investigate whether these RSS patterns can be identified in short-term abstinent alcoholics (STAA). Resting-state functional magnetic resonance imaging data were collected from 27 STAA, 23 LTAA, and 23 nonsubstance abusing controls (NSAC). We examined baseline RSS using seed-based measures. We found ordered RSS effects from NSAC to STAA and then to LTAA within both the appetitive drive and executive control networks: increasing RSS of the executive control network and decreasing RSS of the reward processing network. Finally, we found significant correlations between strength of RSS in these networks and (i) cognitive flexibility, and (ii) current antisocial behavior. Findings are consistent with an adaptive progression of RSS from short- to long-term abstinence, so that, compared with normal controls, the synchrony (i) within the reward network progressively decreases, and (ii) within the executive control network progressively increases.

CognitiveConstruct

RewardProcessing

10.1017/S1461145712001678

The international journal of neuropsychopharmacology

Int J Neuropsychopharmacol

Acute NK₁ receptor antagonist administration affects reward incentive anticipation processing in healthy volunteers.

The primary brain structures of reward processing are mainly situated in the mid-brain dopamine system. The nucleus accumbens (NAc) receives dopaminergic projections from the ventral tegmental area and works as a key brain region for the positive incentive value of rewards. Because neurokinin-1 (NK₁) receptor, the cognate receptor for substance P (SP), is highly expressed in the NAc, we hypothesized that the SP/NK₁ receptor system might play a role in positive reward processing in the NAc in humans. Therefore, we conducted a functional MRI (fMRI) study to assess the effects of an NK₁ receptor antagonist on human reward processing through a monetary incentive delay task that is known to elicit robust activation in the NAc especially during gain anticipation. Eighteen healthy adults participated in two series of an fMRI study, taking either a placebo or the NK₁ receptor antagonist aprepitant. Behavioural measurements revealed that there was no significant difference in reaction time, hit rate, or self-reported effort for incentive cues between the placebo and aprepitant treatments. fMRI showed significant decrease in blood oxygenation-level-dependent signals in the NAc during gain anticipation with the aprepitant treatment compared to the placebo treatment. These results suggest that SP/NK₁ receptor system is involved in processing of positive incentive anticipation and plays a role in accentuating positive valence in association with the primary dopaminergic pathways in the reward circuit.

CognitiveConstruct

RewardProcessing

10.1177/1087054712473179

Journal of attention disorders

J Atten Disord

No Evidence for Inhibitory Deficits or Altered Reward Processing in ADHD: Data From a New Integrated Monetary Incentive Delay Go/No-Go Task.

Cognitive and motivational factors differentially affect individuals with mental health problems such as ADHD. Here we introduce a new task to disentangle the relative contribution of inhibitory control and reward anticipation on task performance in children with ADHD and/or autism spectrum disorders (ASD). Typically developing children, children with ADHD,  ASD, or both disorders worked during separate sessions for monetary or social rewards in go/no-go tasks with varying inhibitory load levels. Participants also completed a monetary temporal discounting (TD) task. As predicted, task performance was sensitive to both the effects of anticipated reward amount and inhibitory load. Reward amount had different effects depending on inhibitory load level. TD correlated with inhibitory control in the ADHD group. The integration of the monetary incentive delay and go/no-go paradigms was successful. Surprisingly, there was no evidence of inhibitory control deficits or altered reward anticipation in the clinical groups.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2013.01.025

NeuroImage

Neuroimage

The effects of poor quality sleep on brain function and risk taking in adolescence.

Insufficient sleep and poor quality sleep are pervasive during adolescence and relate to impairments in cognitive control and increased risk taking. However, the neurobiology underlying the association between sleep and adolescent behavior remains elusive. In the current study, we examine how poor sleep quality relates to cognitive control and reward related brain function during risk taking. Forty-six adolescents participated in a functional magnetic imaging (fMRI) scan during which they completed a cognitive control and risk taking task. Behaviorally, adolescents who reported poorer sleep also exhibited greater risk-taking. This association was paralleled by less recruitment of the dorsolateral prefrontal cortex (DLPFC) during cognitive control, greater insula activation during reward processing, and reduced functional coupling between the DLPFC and affective regions including the insula and ventral striatum during reward processing. Collectively, these results suggest that poor sleep may exaggerate the normative imbalance between affective and cognitive control systems, leading to greater risk-taking in adolescents.

CognitiveConstruct

RewardProcessing

10.1016/j.conb.2013.01.004

Current opinion in neurobiology

Curr Opin Neurobiol

Disordered gambling: a behavioral addiction.

Developments in psychiatry have ratified the existence of behavioral addictions, that certain activities such as gambling or video-game play may be considered addictive in the absence of exogenous (i.e. drug-induced) stimulation of brain reinforcement circuitry. This article describes recent advances in understanding the neurobiological basis of behavioral addiction, with a focus on pathological gambling as the prototypical disorder. We describe positron emission tomography (PET) studies characterizing dopaminergic transmission, and functional imaging studies of reward processing and gambling-related cognitive distortions. The current evidence not only indicates changes in pathological gamblers in core circuitry implicated in drug addiction, but also highlights some subtle differences. Behavioral addictions can also provide experimental traction on distinguishing vulnerability markers for addictions from the active detrimental effects of chronic drug use.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2012.12.005

Biological psychiatry

Biol Psychiatry

Phasic mesolimbic dopamine release tracks reward seeking during expression of Pavlovian-to-instrumental transfer.

Recent theories addressing mesolimbic dopamine's role in reward processing emphasize two apparently distinct functions, one in reinforcement learning (i.e., prediction error) and another in incentive motivation (i.e., the invigoration of reward seeking elicited by reward-paired cues). Here, we evaluate the latter. Using fast-scan cyclic voltammetry, we monitored, in real time, dopamine release in the nucleus accumbens core of rats (n = 9) during a Pavlovian-to-instrumental transfer task in which the effects of a reward-predictive cue on an independently trained instrumental action were assessed. Voltammetric data were parsed into slow and phasic components to determine whether these forms of dopamine signaling were differentially related to task performance. We found that a reward-paired cue, which increased reward-seeking actions, induced an increase in phasic mesolimbic dopamine release and produced slower elevations in extracellular dopamine. Interestingly, phasic dopamine release was temporally related to and positively correlated with lever-press activity generally, while slow dopamine changes were not significantly related to such activity. Importantly, the propensity of the reward-paired cue to increase lever pressing was predicted by the amplitude of phasic dopamine release events, indicating a possible mechanism through which cues initiate reward-seeking actions. These data suggest that those phasic mesolimbic dopamine release events thought to signal reward prediction error may also be related to the incentive motivational impact of reward-paired cues on reward-seeking actions.

CognitiveConstruct

RewardProcessing