Datasets:

morteza

/

cogtext

like 0

10.1016/j.neuroimage.2015.10.021

NeuroImage

Neuroimage

A perspective on the future role of brain pet imaging in exercise science.

Positron Emission Tomography (PET) bears a unique potential for examining the effects of physical exercise (acute or chronic) within the central nervous system in vivo, including cerebral metabolism, neuroreceptor occupancy, and neurotransmission. However, application of Neuro-PET in human exercise science is as yet surprisingly sparse. To date the field has been dominated by non-invasive neuroelectrical techniques (EEG, MEG) and structural/functional magnetic resonance imaging (sMRI/fMRI). Despite PET having certain inherent disadvantages, in particular radiation exposure and high costs limiting applicability at large scale, certain research questions in human exercise science can exclusively be addressed with PET: The "metabolic trapping" properties of (18)F-FDG PET as the most commonly used PET-tracer allow examining the neuronal mechanisms underlying various forms of acute exercise in a rather unconstrained manner, i.e. under realistic training scenarios outside the scanner environment. Beyond acute effects, (18)F-FDG PET measurements under resting conditions have a strong prospective for unraveling the influence of regular physical activity on neuronal integrity and potentially neuroprotective mechanisms in vivo, which is of special interest for aging and dementia research. Quantification of cerebral glucose metabolism may allow determining the metabolic effects of exercise interventions in the entire human brain and relating the regional cerebral rate of glucose metabolism (rCMRglc) with behavioral, neuropsychological, and physiological measures. Apart from FDG-PET, particularly interesting applications comprise PET ligand studies that focus on dopaminergic and opioidergic neurotransmission, both key transmitter systems for exercise-related psychophysiological effects, including mood changes, reward processing, antinociception, and in its most extreme form 'exercise dependence'. PET ligand displacement approaches even allow quantifying specific endogenous neurotransmitter release under acute exercise interventions, to which modern PET/MR hybrid technology will be additionally fruitful. Experimental studies exploiting the unprecedented multimodal imaging capacities of PET/MR in human exercise sciences are as yet pending.

CognitiveConstruct

RewardProcessing

10.1007/s11920-015-0634-5

Current psychiatry reports

Curr Psychiatry Rep

Genetic Similarities between Compulsive Overeating and Addiction Phenotypes: A Case for "Food Addiction"?

There exists a continuous spectrum of overeating, where at the extremes there are casual overindulgences and at the other a 'pathological' drive to consume palatable foods. It has been proposed that pathological eating behaviors may be the result of addictive appetitive behavior and loss of ability to regulate the consumption of highly processed foods containing refined carbohydrates, fats, salt, and caffeine. In this review, we highlight the genetic similarities underlying substance addiction phenotypes and overeating compulsions seen in individuals with binge eating disorder. We relate these similarities to findings from neuroimaging studies on reward processing and clinical diagnostic criteria based on addiction phenotypes. The abundance of similarities between compulsive overeating and substance addictions puts forth a case for a 'food addiction' phenotype as a valid, diagnosable disorder.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.1937-15.2015

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

J Neurosci

Enhanced Functional Activity of the Cannabinoid Type-1 Receptor Mediates Adolescent Behavior.

Adolescence is characterized by drastic behavioral adaptations and comprises a particularly vulnerable period for the emergence of various psychiatric disorders. Growing evidence reveals that the pathophysiology of these disorders might derive from aberrations of normal neurodevelopmental changes in the adolescent brain. Understanding the molecular underpinnings of adolescent behavior is therefore critical for understanding the origin of psychopathology, but the molecular mechanisms that trigger adolescent behavior are unknown. Here, we hypothesize that the cannabinoid type-1 receptor (CB1R) may play a critical role in mediating adolescent behavior because enhanced endocannabinoid (eCB) signaling has been suggested to occur transiently during adolescence. To study enhanced CB1R signaling, we introduced a missense mutation (F238L) into the rat Cnr1 gene that encodes for the CB1R. According to our hypothesis, rats with the F238L mutation (Cnr1(F238L)) should sustain features of adolescent behavior into adulthood. Gain of function of the mutated receptor was demonstrated by in silico modeling and was verified functionally in a series of biochemical and electrophysiological experiments. Mutant rats exhibit an adolescent-like phenotype during adulthood compared with wild-type littermates, with typical high risk/novelty seeking, increased peer interaction, enhanced impulsivity, and augmented reward sensitivity for drug and nondrug reward. Partial inhibition of CB1R activity in Cnr1(F238L) mutant rats normalized behavior and led to a wild-type phenotype. We conclude that the activity state and functionality of the CB1R is critical for mediating adolescent behavior. These findings implicate the eCB system as an important research target for the neuropathology of adolescent-onset mental health disorders. We present the first rodent model with a gain-of-function mutation in the cannabinoid type-1 receptor (CB1R). Adult mutant rats exhibit an adolescent-like phenotype with typical high risk seeking, impulsivity, and augmented drug and nondrug reward sensitivity. Adolescence is a critical period for suboptimal behavioral choices and the emergence of neuropsychiatric disorders. Understanding the basis of these disorders therefore requires a comprehensive knowledge of how adolescent neurodevelopment triggers behavioral reactions. Our behavioral observations in adult mutant rats, together with reports on enhanced adolescent CB1R signaling, suggest a pivotal role for the CB1R in an adolescent brain as an important molecular mediator of adolescent behavior. These findings implicate the endocannabinoid system as a notable research target for adolescent-onset mental health disorders.

CognitiveConstruct

RewardProcessing

10.1038/mp.2015.153

Molecular psychiatry

Mol Psychiatry

Weight loss after bariatric surgery normalizes brain opioid receptors in morbid obesity.

Positron emission tomography (PET) studies suggest opioidergic system dysfunction in morbid obesity, while evidence for the role of the dopaminergic system is less consistent. Whether opioid dysfunction represents a state or trait in obesity remains unresolved, but could be assessed in obese subjects undergoing weight loss. Here we measured brain μ-opioid receptor (MOR) and dopamine D2 receptor (D2R) availability in 16 morbidly obese women twice-before and 6 months after bariatric surgery-using PET with [(11)C]carfentanil and [(11)C]raclopride. Data were compared with those from 14 lean control subjects. Receptor-binding potentials (BPND) were compared between the groups and between the pre- and postoperative scans among the obese subjects. Brain MOR availability was initially lower among obese subjects, but weight loss (mean=26.1 kg, s.d.=7.6 kg) reversed this and resulted in ~23% higher MOR availability in the postoperative versus preoperative scan. Changes were observed in areas implicated in reward processing, including ventral striatum, insula, amygdala and thalamus (P's<0.005). Weight loss did not influence D2R availability in any brain region. Taken together, the endogenous opioid system plays an important role in the pathophysiology of human obesity. Because bariatric surgery and concomitant weight loss recover downregulated MOR availability, lowered MOR availability is associated with an obese phenotype and may mediate excessive energy uptake. Our results highlight that understanding the opioidergic contribution to overeating is critical for developing new treatments for obesity.

CognitiveConstruct

RewardProcessing

10.3109/17518423.2015.1087436

Developmental neurorehabilitation

Dev Neurorehabil

Challenges of implementing a personalized mental task near-infrared spectroscopy brain-computer interface for a non-verbal young adult with motor impairments.

Near-infrared spectroscopy brain-computer interfaces (NIRS-BCIs) have been proposed as potential motor-free communication pathways. This paper documents the challenges of implementing an NIRS-BCI with a non-verbal, severely and congenitally impaired, but cognitively intact young adult. A 5-session personalized mental task NIRS-BCI training paradigm was invoked, whereby participant-specific mental tasks were selected either by the researcher or by the user, on the basis of prior performance or user preference. Although the personalized mental task selection and training framework had been previously demonstrated with able-bodied participants, the participant was not able to exceed chance-level accuracies. Challenges to the acquisition of BCI control may have included disinclination to BCI training, structural or functional brain atypicalities, heightened emotional arousal and confounding haemodynamic patterns associated with novelty and reward processing. Overall, we stress the necessity for further clinical NIRS-BCI research involving non-verbal individuals with severe motor impairments.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2015.09.021

Drug and alcohol dependence

Drug Alcohol Depend

The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study.

Chronic exposure to drugs of abuse disrupts frontostriatal glutamate transmission, which in turn meditates drug seeking. In animal models, N-Acetylcysteine normalizes dysregulated frontostriatal glutamatergic neurotransmission and prevents reinstated drug seeking; however, the effects of N-Acetylcysteine on human frontostriatal circuitry function and maintaining smoking abstinence is unknown. Thus, the current study tested the hypothesis that N-Acetylcysteine would be associated with stronger frontostriatal resting-state functional connectivity (rsFC), attenuated nicotine withdrawal and would help smokers to maintain abstinence over the study period. The present study examined the effects of N-Acetylcysteine on frontostriatal rsFC, nicotine-withdrawal symptoms and maintaining abstinence. Healthy adult, non-treatment seeking smokers (N=16; mean (SD) age 36.5±11.9; cigs/day 15.8±6.1; years/smoking 15.7±8.9) were randomized to a double-blind course of 2400mg N-Acetylcysteine (1200mg b.i.d.) or placebo over the course of 3½ days of monetary-incentivized smoking abstinence. On each abstinent day, measures of mood and craving were collected and participants attended a lab visit in order to assess smoking (i.e., expired-air carbon monoxide [CO]). On day 4, participants underwent fMRI scanning. As compared to placebo (n=8), smokers in the N-Acetylcysteine group (n=8) maintained abstinence, reported less craving and higher positive affect (all p's<.01), and concomitantly exhibited stronger rsFC between ventral striatal nodes, medial prefrontal cortex and precuneus-key default mode network nodes, and the cerebellum [p<.025; FWE]). Taken together, these findings suggest that N-Acetylcysteine may positively affect dysregulated corticostriatal connectivity, help to restructure reward processing, and help to maintain abstinence immediately following a quit attempt.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2015.09.036

Journal of affective disorders

J Affect Disord

Behavioral activation can normalize neural hypoactivation in subthreshold depression during a monetary incentive delay task.

Late adolescents are under increased risk of developing depressive symptoms. Behavioral activation is an effective treatment for subthreshold depression, which can prevent the development of subthreshold depression into a major depressive disorder. However, the neural mechanisms underlying the efficacy of behavioral activation have not been clearly understood. We investigated neural responses during reward processing by individuals with subthreshold depression to clarify the neural mechanisms of behavioral activation. Late adolescent university students with subthreshold depression (n=15, age 18-19 years) as indicated by a high score on the Beck's Depression Inventory-ll (BDI-ll) and 15 age-matched controls with a low BDI-ll score participated in functional magnetic resonance imaging scanning conducted during a monetary incentive delay task on two occasions. The Individuals in the subthreshold depression group received five, weekly behavioral activation sessions between the two scanning sessions. Moreover, they did not receive any medication until the study was completed. Behavioral activation significantly reduced depressive symptoms. Moreover, compared to the changes in brain functions in the control group, the behavioral activation group showed functional changes during loss anticipation in brain structures that mediates cognitive and emotional regulation, including the left ventrolateral prefrontal cortex and angular gyrus. Replication of the study with a larger sample size is required to increase the generalizability of these results. Behavioral activation results in improved functioning of the fronto-parietal region during loss anticipation. These results increase our understanding of the mechanisms underlying specific psychotherapies.

CognitiveConstruct

RewardProcessing

10.1038/npp.2015.313

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Dopamine Depletion Reduces Food-Related Reward Activity Independent of BMI.

Reward sensitivity and possible alterations in the dopaminergic-reward system are associated with obesity. We therefore aimed to investigate the influence of dopamine depletion on food-reward processing. We investigated 34 female subjects in a randomized placebo-controlled, within-subject design (body mass index (BMI)=27.0 kg/m(2) ±4.79 SD; age=28 years ±4.97 SD) using an acute phenylalanine/tyrosine depletion drink representing dopamine depletion and a balanced amino acid drink as the control condition. Brain activity was measured with functional magnetic resonance imaging during a 'wanting' and 'liking' rating of food items. Eating behavior-related traits and states were assessed on the basis of questionnaires. Dopamine depletion resulted in reduced activation in the striatum and higher activation in the superior frontal gyrus independent of BMI. Brain activity during the wanting task activated a more distributed network than during the liking task. This network included gustatory, memory, visual, reward, and frontal regions. An interaction effect of dopamine depletion and the wanting/liking task was observed in the hippocampus. The interaction with the covariate BMI was significant in motor and control regions but not in the striatum. Our results support the notion of altered brain activity in the reward and prefrontal network with blunted dopaminergic action during food-reward processing. This effect is, however, independent of BMI, which contradicts the reward-deficiency hypothesis. This hints to the hypothesis suggesting a different or more complex mechanism underlying the dopaminergic reward function in obesity.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.1703-15.2015

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

J Neurosci

Encoding of Vicarious Reward Prediction in Anterior Cingulate Cortex and Relationship with Trait Empathy.

Empathy--the capacity to understand and resonate with the experiences of others--can depend on the ability to predict when others are likely to receive rewards. However, although a plethora of research has examined the neural basis of predictions about the likelihood of receiving rewards ourselves, very little is known about the mechanisms that underpin variability in vicarious reward prediction. Human neuroimaging and nonhuman primate studies suggest that a subregion of the anterior cingulate cortex in the gyrus (ACCg) is engaged when others receive rewards. Does the ACCg show specialization for processing predictions about others' rewards and not one's own and does this specialization vary with empathic abilities? We examined hemodynamic responses in the human brain time-locked to cues that were predictive of a high or low probability of a reward either for the subject themselves or another person. We found that the ACCg robustly signaled the likelihood of a reward being delivered to another. In addition, ACCg response significantly covaried with trait emotion contagion, a necessary foundation for empathizing with other individuals. In individuals high in emotion contagion, the ACCg was specialized for processing others' rewards exclusively, but for those low in emotion contagion, this region also responded to information about the subject's own rewards. Our results are the first to show that the ACCg signals probabilistic predictions about rewards for other people and that the substantial individual variability in the degree to which the ACCg is specialized for processing others' rewards is related to trait empathy. Successfully cooperating, competing, or empathizing with others can depend on our ability to predict when others are going to get something rewarding. Although many studies have examined how the brain processes rewards we will get ourselves, very little is known about vicarious reward processing. Here, we show that a subregion of the anterior cingulate cortex in the gyrus (ACCg) shows a degree of specialization for processing others' versus one's own rewards. However, the degree to which the ACCg is specialized varies with people's ability to empathize with others. This new insight into how vicarious rewards are processed in the brain and vary with empathy may be key for understanding disorders of social behavior, including psychopathy and autism.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.2571-15.2015

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

J Neurosci

Reward Processing in the Adolescent Brain: Individual Differences and Relation to Risk Taking.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2015.01409

Frontiers in psychology

Front Psychol

Measuring anhedonia: impaired ability to pursue, experience, and learn about reward.

Ribot's (1896) long standing definition of anhedonia as "the inability to experience pleasure" has been challenged recently following progress in affective neuroscience. In particular, accumulating evidence suggests that reward consists of multiple subcomponents of wanting, liking and learning, as initially outlined by Berridge and Robinson (2003), and these processes have been proposed to relate to appetitive, consummatory and satiety phases of a pleasure cycle. Building on this work, we recently proposed to reconceptualize anhedonia as "impairments in the ability to pursue, experience, and/or learn about pleasure, which is often, but not always accessible to conscious awareness." (Rømer Thomsen et al., 2015). This framework is in line with Treadway and Zald's (2011) proposal to differentiate between motivational and consummatory types of anhedonia, and stresses the need to combine traditional self-report measures with behavioral measures or procedures. In time, this approach may lead to improved clinical assessment and treatment. In line with our reconceptualization, increasing evidence suggests that reward processing deficits are not restricted to impaired hedonic impact in major psychiatric disorders. Successful translations of animal models have led to strong evidence of impairments in the ability to pursue and learn about reward in psychiatric disorders such as major depressive disorder, schizophrenia, and addiction. It is of high importance that we continue to systematically target impairments in all phases of reward processing across disorders using behavioral testing in combination with neuroimaging techniques. This in turn has implications for diagnosis and treatment, and is essential for the purposes of identifying the underlying neurobiological mechanisms. Here I review recent progress in the development and application of behavioral procedures that measure subcomponents of anhedonia across relevant patient groups, and discuss methodological caveats as well as implications for assessment and treatment.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2015.00504

Frontiers in human neuroscience

Front Hum Neurosci

Neural correlates of reward processing in healthy siblings of patients with schizophrenia.

Deficits in motivational behavior and psychotic symptoms often observed in schizophrenia (SZ) may be driven by dysfunctional reward processing (RP). RP can be divided in two different stages; reward anticipation and reward consumption. Aberrant processing during reward anticipation seems to be related to SZ. Studies in patients with SZ have found less activation in the ventral striatum (VS) during anticipation of reward, but these findings do not provide information on effect of the genetic load on reward processing. Therefore, this study investigated RP in healthy first-degree relatives of SZ patients. The sample consisted of 94 healthy siblings of SZ patients and 57 healthy controls. Participants completed a classic RP task, the Monetary Incentive Delay task, during functional magnetic resonance imaging (fMRI). As expected, there were no behavioral differences between groups. In contrast to our expectations, we found no differences in any of the anticipatory reward related brain areas (region of interest analyses). Whole-brain analyses did reveal group differences during both reward anticipation and reward consumption; during reward anticipation siblings showed less deactivation in the insula, posterior cingulate cortex (PCC) and medial frontal gyrus (MFG) than controls. During reward consumption siblings showed less deactivation in the PCC and the right MFG compared to controls and activation in contrast to deactivation in controls in the precuneus and the left MFG. Exclusively in siblings, MFG activity correlated positively with subclinical negative symptoms. These regions are typically associated with the default mode network (DMN), which normally shows decreases in activation during task-related cognitive processes. Thus, in contrast to prior literature in patients with SZ, the results do not point to altered brain activity in classical RP brain areas, such as the VS. However, the weaker deactivation found outside the reward-related network in siblings could indicate reduced task-related suppression (i.e., hyperactivation) of the DMN. The presence of DMN hyperactivation during reward anticipation and reward consumption might indicate that siblings of patients with SZ have a higher baseline level of DMN activation and possible abnormal network functioning.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2015.00247

Frontiers in behavioral neuroscience

Front Behav Neurosci

Effects of social sustainability signaling on neural valuation signals and taste-experience of food products.

Value-based decision making occurs when individuals choose between different alternatives and place a value on each alternative and its attributes. Marketing actions frequently manipulate product attributes, by adding, e.g., health claims on the packaging. A previous imaging study found that an emblem for organic products increased willingness to pay (WTP) and activity in the ventral striatum (VS). The current study investigated neural and behavioral processes underlying the influence of Fair Trade (FT) labeling on food valuation and choice. Sustainability is an important product attribute for many consumers, with FT signals being one way to highlight ethically sustainable production. Forty participants valuated products in combination with an FT emblem or no emblem and stated their WTP in a bidding task while in an MRI scanner. After that, participants tasted-objectively identical-chocolates, presented either as "FT" or as "conventionally produced". In the fMRI task, WTP was significantly higher for FT products. FT labeling increased activity in regions important for reward-processing and salience, that is, in the VS, anterior and posterior cingulate, as well as superior frontal gyrus. Subjective value, that is, WTP was correlated with activity in the ventromedial prefrontal cortex (vmPFC). We find that the anterior cingulate, VS and superior frontal gyrus exhibit task-related increases in functional connectivity to the vmPFC when an FT product was evaluated. Effective connectivity analyses revealed a highly probable directed modulation of the vmPFC by those three regions, suggesting a network which alters valuation processes. We also found a significant taste-placebo effect, with higher experienced taste pleasantness and intensity for FT labeled chocolates. Our results reveal a possible neural mechanism underlying valuation processes of certified food products. The results are important in light of understanding current marketing trends as well as designing future interventions that aim at positively influencing food choice.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2015.08.014

Biological psychiatry

Biol Psychiatry

Reward Processing, Functional Connectivity, Psychopathy, and Research Domain Criteria.

CognitiveConstruct

RewardProcessing

10.1016/j.bandc.2015.09.002

Brain and cognition

Brain Cogn

Motivated to win: Relationship between anticipatory and outcome reward-related neural activity.

Reward-processing involves two temporal stages characterized by two distinct neural processes: reward-anticipation and reward-outcome. Intriguingly, very little research has examined the relationship between neural processes involved in reward-anticipation and reward-outcome. To investigate this, one needs to consider the heterogeneity of reward-processing within each stage. To identify different stages of reward processing, we adapted a reward time-estimation task. While EEG data were recorded, participants were instructed to button-press 3.5s after the onset of an Anticipation-Cue and received monetary reward for good time-estimation on the Reward trials, but not on No-Reward trials. We first separated reward-anticipation into event related potentials (ERPs) occurring at three sub-stages: reward/no-reward cue-evaluation, motor-preparation and feedback-anticipation. During reward/no-reward cue-evaluation, the Reward-Anticipation Cue led to a smaller N2 and larger P3. During motor-preparation, we report, for the first time, that the Reward-Anticipation Cue enhanced the Readiness Potential (RP), starting approximately 1s before movement. At the subsequent feedback-anticipation stage, the Reward-Anticipation Cue elevated the Stimulus-Preceding Negativity (SPN). We also separated reward-outcome ERPs into different components occurring at different time-windows: the Feedback-Related Negativity (FRN), Feedback-P3 (FB-P3) and Late-Positive Potentials (LPP). Lastly, we examined the relationship between reward-anticipation and reward-outcome ERPs. We report that individual-differences in specific reward-anticipation ERPs uniquely predicted specific reward-outcome ERPs. In particular, the reward-anticipation Early-RP (1-.8s before movement) predicted early reward-outcome ERPs (FRN and FB-P3), whereas, the reward-anticipation SPN most strongly predicted a later reward-outcome ERP (LPP). Results have important implications for understanding the nature of the relationship between reward-anticipation and reward-outcome neural-processes.

CognitiveConstruct

RewardProcessing

10.1016/j.brainres.2015.09.028

Brain research

Brain Res

The impact of cognitive load on reward evaluation.

The neural systems that afford our ability to evaluate rewards and punishments are impacted by a variety of external factors. Here, we demonstrate that increased cognitive load reduces the functional efficacy of a reward processing system within the human medial-frontal cortex. In our paradigm, two groups of participants used performance feedback to estimate the exact duration of one second while electroencephalographic (EEG) data was recorded. Prior to performing the time estimation task, both groups were instructed to keep their eyes still and avoid blinking in line with well established EEG protocol. However, during performance of the time-estimation task, one of the two groups was provided with trial-to-trial-feedback about their performance on the time-estimation task and their eye movements to induce a higher level of cognitive load relative to participants in the other group who were solely provided with feedback about the accuracy of their temporal estimates. In line with previous work, we found that the higher level of cognitive load reduced the amplitude of the feedback-related negativity, a component of the human event-related brain potential associated with reward evaluation within the medial-frontal cortex. Importantly, our results provide further support that increased cognitive load reduces the functional efficacy of a neural system associated with reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.appet.2015.09.035

Appetite

Appetite

Managing temptation in obesity treatment: A neurobehavioral model of intervention strategies.

Weight loss outcomes in lifestyle interventions for obesity are primarily a function of sustained adherence to a reduced-energy diet, and most lapses in diet adherence are precipitated by temptation from palatable food. The high nonresponse and relapse rates of lifestyle interventions suggest that current temptation management approaches may be insufficient for most participants. In this conceptual review, we discuss three neurobehavioral processes (attentional bias, temporal discounting, and the cold-hot empathy gap) that emerge during temptation and contribute to lapses in diet adherence. Characterizing the neurobehavioral profile of temptation highlights an important distinction between temptation resistance strategies aimed at overcoming temptation while it is experienced, and temptation prevention strategies that seek to avoid or minimize exposure to tempting stimuli. Many temptation resistance and temptation prevention strategies heavily rely on executive functions mediated by prefrontal systems that are prone to disruption by common occurrences such as stress, insufficient sleep, and even exposure to tempting stimuli. In contrast, commitment strategies are a set of devices that enable individuals to manage temptation by constraining their future choices, without placing heavy demands on executive functions. These concepts are synthesized in a conceptual model that categorizes temptation management approaches based on their intended effects on reward processing and degree of reliance on executive functions. We conclude by discussing the implications of our model for strengthening temptation management approaches in future lifestyle interventions, tailoring these approaches based on key individual difference variables, and suggesting high-priority topics for future research.

CognitiveConstruct

RewardProcessing

10.1503/jpn.140383

Journal of psychiatry & neuroscience : JPN

J Psychiatry Neurosci

Ventral striatal hypoactivation is associated with apathy but not diminished expression in patients with schizophrenia.

Negative symptoms of schizophrenia can be grouped in 2 dimensions: apathy and diminished expression. Increasing evidence suggests that negative symptoms are associated with altered neural activity of subcortical and cortical regions in the brain reward system. However, the neurobiological basis of the distinct symptom dimensions within negative symptoms is still poorly understood. The primary aim of our study was to examine the neural correlates of the negative symptom dimensions apathy and diminished expression during a reward processing task. Patients with schizophrenia and healthy controls underwent event-related fMRI while performing a variant of the Monetary Incentive Delay Task. We assessed negative symptom dimensions using the Brief Negative Symptom Scale. We included 27 patients and 25 controls in our study. Both groups showed neural activation indicated by blood oxygen-level dependent signal in the ventral striatum during reward anticipation. Ventral striatal activation during reward anticipation showed a strong negative correlation with apathy. Importantly, this effect was not driven by cognitive ability, medication, depressive or positive symptoms. In contrast, no significant correlation with the diminished expression dimension was observed. Although the results remain significant when controlling for chlorpromazine equivalents, we cannot fully exclude potential confounding effects of medication with atypical antipsychotics. The specific correlation of ventral striatal hypoactivation during reward anticipation with apathy demonstrates a differentiation of apathy and diminished expression on a neurobiological level and provides strong evidence for different pathophysiological mechanisms underlying these 2 negative symptom dimensions. Our findings contribute to a multilevel framework in which apathy and motivational impairment in patients with schizophrenia can be described on psychopathological, behavioural and neural levels.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsycho.2015.09.007

Biological psychology

Biol Psychol

Convergence of EEG and fMRI measures of reward anticipation.

Deficits in reward anticipation are putative mechanisms for multiple psychopathologies. Research indicates that these deficits are characterized by reduced left (relative to right) frontal electroencephalogram (EEG) activity and blood oxygenation level-dependent (BOLD) signal abnormalities in mesolimbic and prefrontal neural regions during reward anticipation. Although it is often assumed that these two measures capture similar mechanisms, no study to our knowledge has directly examined the convergence between frontal EEG alpha asymmetry and functional magnetic resonance imaging (fMRI) during reward anticipation in the same sample. Therefore, the aim of the current study was to investigate if and where in the brain frontal EEG alpha asymmetry and fMRI measures were correlated in a sample of 40 adults. All participants completed two analogous reward anticipation tasks--once during EEG data collection and the other during fMRI data collection. Results indicated that the two measures do converge and that during reward anticipation, increased relative left frontal activity is associated with increased left anterior cingulate cortex (ACC)/medial prefrontal cortex (mPFC) and left orbitofrontal cortex (OFC) activation. This suggests that the two measures may similarly capture PFC functioning, which is noteworthy given the role of these regions in reward processing and the pathophysiology of disorders such as depression and schizophrenia.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2015.01256

Frontiers in psychology

Front Psychol

Individual differences in the habitual use of cognitive reappraisal predict the reward-related processing.

Recent studies have shown that instructed cognitive reappraisal can regulate the neural processing of reward. However, it is still unclear whether the habitual use of cognitive reappraisal in everyday life is related to brain activity involved in reward processing. In the present study, participants' neural responses to reward were measured using electroencephalography (EEG) recorded during a gambling task and their tendency to use cognitive reappraisal was assessed using the Emotion Regulation Questionnaire (ERQ). Event-related potential (ERP) results indicated that losses on the gambling task elicited greater negative reward-related feedback negativity (FN) than gains. The differential FN between losses and gains was significantly correlated with cognitive reappraisal scores across participants such that individuals with a higher tendency to use cognitive reappraisal showed stronger reward processing (i.e., amplified FN difference between losses and gains). This correlation remained significant after controlling for expressive suppression scores. However, expressive suppression per se was not correlated with FN differences. Taken together, these results suggest that the habitual use of cognitive reappraisal is associated with increased neural processing of reward.

CognitiveConstruct

RewardProcessing

10.3389/fnins.2015.00314

Frontiers in neuroscience

Front Neurosci

Gambling on visual performance: neural correlates of metacognitive choice between visual lotteries.

A lottery is a list of mutually exclusive outcomes together with their associated probabilities of occurrence. Decision making is often modeled as choices between lotteries and-in typical research on decision under risk-the probabilities are given to the subject explicitly in numerical form. In this study, we examined lottery decision task where the probabilities of receiving various rewards are contingent on the subjects' own visual performance in a random-dot-motion (RDM) discrimination task, a metacognitive or second order judgment. While there is a large literature concerning the RDM task and there is also a large literature on decision under risk, little is known about metacognitive decisions when the source of uncertainty is visual. Using fMRI with humans, we found distinct fronto-striatal and fronto-parietal networks representing subjects' estimates of his or her performance, reward value, and the expected value (EV) of the lotteries. The fronto-striatal network includes the dorsomedial prefrontal cortex and the ventral striatum, involved in reward processing and value-based decision-making. The fronto-parietal network includes the intraparietal sulcus and the ventrolateral prefrontal cortex, which was shown to be involved in the accumulation of sensory evidence during visual decision making and in metacognitive judgments on visual performance. These results demonstrate that-while valuation of performance-based lotteries involves a common fronto-striatal valuation network-an additional network unique to the estimation of task-related performance is recruited for the integration of probability and reward information when probability is inferred from visual performance.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2015.09.005

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

Int J Psychophysiol

Reward processing deficits and impulsivity in high-risk offspring of alcoholics: A study of event-related potentials during a monetary gambling task.

Individuals at high risk to develop alcoholism often manifest neurocognitive deficits as well as increased impulsivity. The goal of the present study is to elucidate reward processing deficits, externalizing disorders, and impulsivity as elicited by electrophysiological, clinical and behavioral measures in subjects at high risk for alcoholism from families densely affected by alcoholism in the context of brain maturation across age groups and gender. Event-related potentials (ERPs) and current source density (CSD) during a monetary gambling task (MGT) were measured in 12-25 year old offspring (N=1864) of families in the Collaborative Study on the Genetics of Alcoholism (COGA) Prospective study; the high risk (HR, N=1569) subjects were from families densely affected with alcoholism and the low risk (LR, N=295) subjects were from community families. Externalizing disorders and impulsivity scores were also compared between LR and HR groups. HR offspring from older (16-25 years) male and younger (12-15 years) female subgroups showed lower P3 amplitude than LR subjects. The amplitude decrement was most prominent in HR males during the loss condition. Overall, P3 amplitude increase at anterior sites and decrease at posterior areas were seen in older compared to younger subjects, suggesting frontalization during brain maturation. The HR subgroups also exhibited hypofrontality manifested as weaker CSD activity during both loss and gain conditions at frontal regions. Further, the HR subjects had higher impulsivity scores and increased prevalence of externalizing disorders. P3 amplitudes during the gain condition were negatively correlated with impulsivity scores. Older male and younger female HR offspring, compared to their LR counterparts, manifested reward processing deficits as indexed by lower P3 amplitude and weaker CSD activity, along with higher prevalence of externalizing disorders and higher impulsivity scores. Reward related P3 is a valuable measure reflecting neurocognitive dysfunction in subjects at risk for alcoholism, as well as to characterize reward processing and brain maturation across gender and age group.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2015.00469

Frontiers in human neuroscience

Front Hum Neurosci

Adults with high social anhedonia have altered neural connectivity with ventral lateral prefrontal cortex when processing positive social signals.

Social anhedonia (SA) is a debilitating characteristic of schizophrenia, a common feature in individuals at psychosis-risk, and a vulnerability for developing schizophrenia-spectrum disorders. Prior work (Hooker et al., 2014) revealed neural deficits in the ventral lateral prefrontal cortex (VLPFC) when processing positive social cues in a community sample of people with high SA. Lower VLPFC neural activity was related to more severe self-reported schizophrenia-spectrum symptoms as well as the exacerbation of symptoms after social stress. In the current study, psycho-physiological interaction (PPI) analysis was applied to further investigate the neural mechanisms mediated by the VLPFC during emotion processing. PPI analysis revealed that, compared to low SA controls, participants with high SA exhibited reduced connectivity between the VLPFC and the motor cortex, the inferior parietal and the posterior temporal regions when viewing socially positive (relative to neutral) emotions. Across all participants, VLPFC connectivity correlated with behavioral and self-reported measures of attentional control, emotion management, and reward processing. Our results suggest that impairments to the VLPFC mediated neural circuitry underlie the cognitive and emotional deficits associated with social anhedonia, and may serve as neural targets for prevention and treatment of schizophrenia-spectrum disorders.

CognitiveConstruct

RewardProcessing

10.2174/1874473708666150916113131

Current drug abuse reviews

Curr Drug Abuse Rev

Can Decision Making Research Provide a Better Understanding of Chemical and Behavioral Addictions?

We reviewed the cognitive and neurobiological commonalities between chemical and behavioral addictions. Poor impulse control, limited executive function and abnormalities in reward processing are seen in both group of entities. Brain imaging shows consistent abnormalities in frontoparietal regions and the limbic system. In drug addiction, exaggerated risk taking behavior and temporal discounting may reflect an imbalance between a hyperactive mesolimbic and hypoactive executive systems. Several cognitive distortions are found in pathological gambling that seems to harness the brain reward system that has evolved to face situations related to skill, not random chance. Abnormalities in risk assessment and impulsivity are found in variety of eating disorders, in particularly related to eating behavior. Corresponding findings in eating disorder patients include abnormalities in the limbic system, i.e. orbitofrontal cortex (OFC), striatum and insula. Similarly, internet addiction disorder is associated with risky decision making and increased choice impulsivity with corresponding discrepant activation in the dorsolateral prefrontal cortex, OFC, anterior cingulate cortex, caudate and insula. Sexual addictions are in turn associated with exaggerated impulsive choice and suggestive evidence of abnormalities in reward processing. In sum, exploration of executive function and decision making abnormalities in chemical and behavioral addictions may increase understanding in their psychopathology and yield valuable targets for therapeutic interventions.

CognitiveConstruct

RewardProcessing

10.1038/tp.2015.129

Translational psychiatry

Transl Psychiatry

Abnormal context-reward associations in an immune-mediated neurodevelopmental mouse model with relevance to schizophrenia.

Impairments in central reward processing constitute an important aspect of the negative symptoms of schizophrenia. Despite its clinical relevance, the etiology of deficient reward processing in schizophrenia remains largely unknown. Here, we used an epidemiologically informed mouse model of schizophrenia to explore the effects of prenatal immune activation on reward-related functions. The model is based on maternal administration of the viral mimic PolyI:C and has been developed in relation to the epidemiological evidence demonstrating enhanced risk of schizophrenia and related disorders following prenatal maternal infection. We show that prenatal immune activation induces selective deficits in the expression (but not acquisition) of conditioned place preference for a natural reward (sucrose) without changing hedonic or neophobic responses to the reward. On the other hand, prenatal immune activation led to enhanced place preference for the psychostimulant drug cocaine, while it attenuated the locomotor reaction to the drug. The prenatal exposure did not alter negative reinforcement learning as assessed using a contextual fear conditioning paradigm. Our findings suggest that the nature of reward-related abnormalities following prenatal immune challenge depends on the specificity of the reward (natural reward vs drug of abuse) as well as on the valence domain (positive vs negative reinforcement learning). Moreover, our data indicate that reward abnormalities emerging in prenatally immune-challenged offspring may, at least in part, stem from an inability to retrieve previously established context-reward associations and to integrate such information for appropriate goal-directed behavior.

CognitiveConstruct

RewardProcessing

10.1038/npp.2015.288

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Consequences of Adolescent Ethanol Consumption on Risk Preference and Orbitofrontal Cortex Encoding of Reward.

Critical development of the prefrontal cortex occurs during adolescence, a period of increased independence marked by decision making that often includes engagement in risky behaviors, such as substance use. Consumption of alcohol during adolescence has been associated with increased impulsivity that persists across the lifespan, an effect which may be caused by long-term disruptions in cortical processing of rewards. To determine if alcohol consumption alters cortical encoding of rewards of different sizes and probabilities, we gave rats limited access to alcohol in gelatin during adolescence only. In adulthood, we recorded the electrophysiological activity of individual neurons of the orbitofrontal cortex while rats performed a risk task that varied the level of risk from day-to-day. Rats that had consumed higher levels of alcohol showed increased risk preference in the task compared with control and low alcohol-consuming rats. Patterns of neuronal responses were identified using principal component analysis. Of the multiple patterns observed, only one was modulated by adolescent alcohol consumption and showed strongest modulation after reward receipt. This subpopulation of neurons showed blunted firing rates following rewards in alcohol-consuming rats, suggesting a mechanism through which adolescent alcohol exposure may have lasting effects on reward processing in the context of decision making. The differences in OFC responses between high alcohol consumers and control animals not given access to alcohol support the idea that, regardless of potential variability in innate alcohol preferences, voluntary consumption of alcohol during adolescence biases choice patterns longitudinally through alterations in cortical function.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22989

Human brain mapping

Hum Brain Mapp

The accumbofrontal tract: Diffusion tensor imaging characterization and developmental change from childhood to adulthood.

The presence of an anatomical connection between the orbitofrontal cortex and ventral striatum, forming a so-called reward network, is well established across species. This connection has important implications for reward processing and is relevant to a number of neuropsychiatric disorders. Moreover, white matter (WM) is known to continue to mature across adolescence and into early adulthood, and developmental change in the reward network is an important component of models of decision making and risk taking. Despite the importance of this connection, the underlying WM has only recently been characterized in humans histologically, and not yet in-vivo using brain imaging. Here, we implemented diffusion tensor imaging (DTI) in a large cross-sectional sample of 295 healthy individuals ages 8-68 to further characterize the WM of this connection and its development from childhood into adulthood. We demonstrate that the accumbofrontal tract, connecting the orbitofrontal cortex and nucleus accumbens, can be identified using standard DTI sequences. Using Poisson modeling, we show that the accumbofrontal tract undergoes significant change across the lifespan, with males showing a higher and earlier peak compared to females. Moreover, the change occurs in a pattern consistent with developmental models of decision-making. These findings support the hypothesis that developmental differences in WM integrity may be a contributing factor to the observed risk taking that occurs in adolescence. The accumbofrontal tract is not yet included in standard WM atlases, but may be important for inclusion in studies investigating fronto-striatal networks, as well as in investigations of substance abuse and decision making.

CognitiveConstruct

RewardProcessing

10.1016/j.euroneuro.2015.07.023

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Eur Neuropsychopharmacol

Neurobiological underpinnings of sensation seeking trait in heroin abusers.

Neurobiological investigation of heroin revealed that abusers of this highly addictive substance show dysregulation in brain circuits for reward processing and cognitive control. Psychologically, personality traits related to reward processing and cognitive control differed between heroin abusers and non-abusers. Yet, there is no direct evidence on the relationship between these neurobiological and psychological findings on heroin abusers, and whether such relationship is altered in these abusers. The present study filled this research gap by integrating findings obtained via magnetic resonance imaging (structural volume and resting-state functional connectivity) and self-reported personality trait measures (Zuckerman׳s Sensation Seeking Scale and Barratt Impulsivity Scale) on 33 abstinent heroin users and 30 matched healthy controls. The key finding is a negative relationship between high sensation seeking tendency and midbrain structural volume in the heroin users. Importantly, there was stronger coupling between the midbrain and ventromedial prefrontal cortex and weaker coupling between the midbrain and dorsolateral prefrontal cortex in heroin users. Our findings offer significant insight into the neural underpinning of sensation seeking in heroin users. Importantly, the data shed light on a novel relationship between the mesolimbic-prefrontal pathway of the reward system and the high sensation seeking personality trait in heroin abusers.

CognitiveConstruct

RewardProcessing

10.1016/j.schres.2015.08.024

Schizophrenia research

Schizophr Res

Reward-dependent modulation of working memory is associated with negative symptoms in schizophrenia.

The negative symptoms of schizophrenia have been associated with altered neural activity during both reward processing and cognitive processing. Even though increasing evidence suggests a strong interaction between these two domains, it has not been studied in relation to negative symptoms. To elucidate neural mechanisms of the reward-cognition interaction, we applied a letter variant of the n-back working memory task and varied the financial incentives for performance. In the interaction contrast, we found a significantly activated cluster in the rostral anterior cingulate cortex (ACC), the middle frontal gyrus, and the bilateral superior frontal gyrus. The interaction did not differ significantly between the patient group and a healthy control group, suggesting that patients with schizophrenia are on average able to integrate reward information and utilize this information to maximize cognitive performance. However within the patient group, we found a significant inverse correlation of ACC activity with the factor diminished expression. This finding is consistent with the model that a lack of available cognitive resources leads to diminished expression. We therefore argue that patients with diminished expression have difficulties in recruiting additional cognitive resources (as implemented in the ACC) in response to an anticipated reward. Due to this lack of cognitive resources, less processing capacity is available for effective expression, resulting in diminished expressive behavior.

CognitiveConstruct

RewardProcessing

10.1002/brb3.357

Brain and behavior

Brain Behav

Blunted responses to reward in remitted post-traumatic stress disorder.

Recent evidence suggests blunted responses to rewarding stimuli in patients with post-traumatic stress disorder (PTSD). However, it is not clear whether these alterations in reward processing normalize in remitted PTSD patients. We tested behavioral and physiological responses to monetary reward in a spatial memory task in 13 accident survivors with remitted PTSD, 14 accident survivors who never had PTSD, and 16 nontrauma-exposed subjects. All accident survivors were recruited from two samples of severely physically injured patients, who had participated in previous prospective studies on the incidence of PTSD after accidental injury approximately 10 years ago. Reaction time, accuracy, skin conductance responses, and self-reported mood were assessed during the task. Accident survivors who never had PTSD and nontrauma exposed controls reported significantly higher positive mood in the reinforced versus nonreinforced condition (P < 0.045 and P < 0.001, respectively), while there was no effect of reinforcement in remitted PTSD subjects. Our findings suggest an alteration of the reward system in remitted PTSD. Further research is needed to investigate whether altered reward processing is a residual characteristic in PTSD after remission of symptoms or, alternatively, a preexisting risk factor for the development of PTSD after a traumatic event.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.1589-15.2015

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

J Neurosci

An Obesity-Predisposing Variant of the FTO Gene Regulates D2R-Dependent Reward Learning.

Variations in the fat mass and obesity-associated (FTO) gene are linked to obesity. However, the underlying neurobiological mechanisms by which these genetic variants influence obesity, behavior, and brain are unknown. Given that Fto regulates D2/3R signaling in mice, we tested in humans whether variants in FTO would interact with a variant in the ANKK1 gene, which alters D2R signaling and is also associated with obesity. In a behavioral and fMRI study, we demonstrate that gene variants of FTO affect dopamine (D2)-dependent midbrain brain responses to reward learning and behavioral responses associated with learning from negative outcome in humans. Furthermore, dynamic causal modeling confirmed that FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic predisposition alters reward processing not only in obesity, but also in other disorders with altered D2R-dependent impulse control, such as addiction. Significance statement: Variations in the fat mass and obesity-associated (FTO) gene are associated with obesity. Here we demonstrate that variants of FTO affect dopamine-dependent midbrain brain responses and learning from negative outcomes in humans during a reward learning task. Furthermore, FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic vulnerability in reward processing can increase predisposition to obesity.

CognitiveConstruct

RewardProcessing

10.5665/sleep.5460

Sleep

Sleep

Neural Reward Processing Mediates the Relationship between Insomnia Symptoms and Depression in Adolescence.

Emerging evidence suggests that insomnia may disrupt reward-related brain function-a potentially important factor in the development of depressive disorder. Adolescence may be a period during which such disruption is especially problematic given the rise in the incidence of insomnia and ongoing development of neural systems that support reward processing. The present study uses longitudinal data to test the hypothesis that disruption of neural reward processing is a mechanism by which insomnia symptoms-including nocturnal insomnia symptoms (NIS) and nonrestorative sleep (NRS)-contribute to depressive symptoms in adolescent girls. Participants were 123 adolescent girls and their caregivers from an ongoing longitudinal study of precursors to depression across adolescent development. NIS and NRS were assessed annually from ages 9 to 13 years. Girls completed a monetary reward task during a functional MRI scan at age 16 years. Depressive symptoms were assessed at ages 16 and 17 years. Multivariable regression tested the prospective associations between NIS and NRS, neural response during reward anticipation, and the mean number of depressive symptoms (omitting sleep problems). NRS, but not NIS, during early adolescence was positively associated with late adolescent dorsal medial prefrontal cortex (dmPFC) response to reward anticipation and depressive symptoms. DMPFC response mediated the relationship between early adolescent NRS and late adolescent depressive symptoms. These results suggest that NRS may contribute to depression by disrupting reward processing via altered activity in a region of prefrontal cortex involved in affective control. The results also support the mechanistic differentiation of NIS and NRS.

CognitiveConstruct

RewardProcessing

10.1177/0269881115602486

Journal of psychopharmacology (Oxford, England)

J Psychopharmacol

Impact of the glucocorticoid receptor BclI polymorphism on reward expectancy and prediction error related ventral striatal reactivity in depressed and healthy individuals.

There is evidence that reward-related neural reactivity is altered in depressive disorders. Glucocorticoids influence dopaminergic transmission, which is widely implicated in reward processing. However, no studies have examined the effect of glucocorticoid receptor gene polymorphisms on reward-related neural reactivity in depressed or healthy individuals. Fifty-nine depressed individuals with major depressive disorder (n=33) or bipolar disorder (n=26), and 32 healthy individuals were genotyped for the glucocorticoid receptor BclI G/C polymorphism, and underwent functional magnetic resonance imaging during a monetary reward task. We examined the effect of the glucocorticoid receptor BclI G/C polymorphism on reward expectancy (RE; expected outcome value) and prediction error (PE; discrepancy between expected and actual outcome) related ventral striatal reactivity. There was a significant interaction between reward condition and BclI genotype (p=0.007). C-allele carriers showed higher PE than RE-related right ventral striatal reactivity (p<0.001), whereas no such difference was observed in G/G homozygotes. Accordingly, C-allele carriers showed a greater difference between PE and RE-related right ventral striatal reactivity than G/G homozygotes (p<0.005), and also showed lower RE-related right ventral striatal reactivity than G/G homozygotes (p=0.011). These findings suggest a slowed transfer from PE to RE-related ventral striatal responses during reinforcement learning in C-allele carriers, regardless of diagnosis, possibly due to altered dopamine release associated with increased sensitivity to glucocorticoids.

CognitiveConstruct

RewardProcessing

10.1007/s00429-015-1098-4

Brain structure & function

Brain Struct Funct

Large-scale intrinsic functional network organization along the long axis of the human medial temporal lobe.

The medial temporal lobe (MTL), encompassing the hippocampus and parahippocampal gyrus (PHG), is a heterogeneous structure which plays a critical role in memory and cognition. Here, we investigate functional architecture of the human MTL along the long axis of the hippocampus and PHG. The hippocampus showed stronger connectivity with striatum, ventral tegmental area and amygdala-regions important for integrating reward and affective signals, whereas the PHG showed stronger connectivity with unimodal and polymodal association cortices. In the hippocampus, the anterior node showed stronger connectivity with the anterior medial temporal lobe and the posterior node showed stronger connectivity with widely distributed cortical and subcortical regions including those involved in sensory and reward processing. In the PHG, differences were characterized by a gradient of increasing anterior-to-posterior connectivity with core nodes of the default mode network. Left and right MTL connectivity patterns were remarkably similar, except for stronger left than right MTL connectivity with regions in the left MTL, the ventral striatum and default mode network. Graph theoretical analysis of MTL-based networks revealed higher node centrality of the posterior, compared to anterior and middle hippocampus. The PHG showed prominent gradients in both node degree and centrality along its anterior-to-posterior axis. Our findings highlight several novel aspects of functional heterogeneity in connectivity along the long axis of the human MTL and provide new insights into how its network organization supports integration and segregation of signals from distributed brain areas. The implications of our findings for a principledunderstanding of distributed pathways that support memory and cognition are discussed.

CognitiveConstruct

RewardProcessing

10.1152/jn.00711.2015

Journal of neurophysiology

J Neurophysiol

Ramping ensemble activity in dorsal anterior cingulate neurons during persistent commitment to a decision.

We frequently need to commit to a choice to achieve our goals; however, the neural processes that keep us motivated in pursuit of delayed goals remain obscure. We examined ensemble responses of neurons in macaque dorsal anterior cingulate cortex (dACC), an area previously implicated in self-control and persistence, in a task that requires commitment to a choice to obtain a reward. After reward receipt, dACC neurons signaled reward amount with characteristic ensemble firing rate patterns; during the delay in anticipation of the reward, ensemble activity smoothly and gradually came to resemble the postreward pattern. On the subset of risky trials, in which a reward was anticipated with 50% certainty, ramping ensemble activity evolved to the pattern associated with the anticipated reward (and not with the anticipated loss) and then, on loss trials, took on an inverted form anticorrelated with the form associated with a win. These findings enrich our knowledge of reward processing in dACC and may have broader implications for our understanding of persistence and self-control.

CognitiveConstruct

RewardProcessing

10.1001/jamapsychiatry.2015.1376

JAMA psychiatry

JAMA Psychiatry

Meta-analysis of Functional Neuroimaging of Major Depressive Disorder in Youth.

Despite its high prevalence and morbidity, the underlying neural basis of major depressive disorder (MDD) in youth is not well understood. To identify in youth diagnosed as having MDD the most reliable neural abnormalities reported in existing functional neuroimaging studies and characterize their relations with specific psychological dysfunctions. Searches were conducted in PubMed and Web of Science to identify relevant studies published from November 2006 through February 2015. The current analysis took place from August 21, 2014, to March 28, 2015. We retained articles that conducted a comparison of youth aged 4 to 24 years diagnosed as having MDD and age-matched healthy controls using task-based functional magnetic resonance imaging and a voxelwise whole-brain approach. We extracted coordinates of brain regions exhibiting differential activity in youth with MDD compared with healthy control participants. Multilevel kernel density analysis was used to examine voxelwise between-group differences throughout the whole brain. Correction for multiple comparisons was performed by computing null hypothesis distributions from 10 000 Monte Carlo simulations and calculating the cluster size necessary to obtain the familywise error rate control at P < .05. Abnormal levels of activation in youth diagnosed as having MDD compared with control participants during a variety of affective processing and executive functioning tasks. Compared with age-matched healthy control participants (n = 274), youth with MDD (n = 246) showed reliable patterns of abnormal activation, including the following task-general and task-specific effects: hyperactivation in subgenual anterior cingulate cortex (P < .05) and ventrolateral prefrontal cortex (P < .05) and hypoactivation in caudate (P < .01) across aggregated tasks; hyperactivation in thalamus (P < .03) and parahippocampal gyrus (P < .003) during affective processing tasks; hypoactivation in cuneus (P < .001), dorsal cingulate cortex (P < .05), and dorsal anterior insula (P < .05) during executive functioning tasks; hypoactivity in posterior insula (P < .005) during positive valence tasks; and hyperactivity in dorsolateral prefrontal cortex (P < .001) and superior temporal cortex (P < .003) during negative valence tasks. Altered activations in several distributed brain networks may help explain the following seemingly disparate symptoms of MDD in youth: hypervigilance toward emotional stimuli from the overactivation of central hubs in the subgenual anterior cingulate cortex and thalamus that lead to a cascade of other symptoms; ineffective emotion regulation despite increased activation of the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex during affective processing, which may reverse across development or the clinical course; maladaptive rumination and poor executive control from difficulties shifting from default mode network activity to task-positive network activity during cognitively demanding tasks; and anhedonia from hypoactivation of the cuneus and posterior insula during reward processing.

CognitiveConstruct

RewardProcessing

10.1002/oby.21200

Obesity (Silver Spring, Md.)

Obesity (Silver Spring)

Emotional eating is associated with increased brain responses to food-cues and reduced sensitivity to GLP-1 receptor activation.

The neural correlates and pathophysiology of emotional eating are insufficiently known. Glucagon-like peptide-1 (GLP-1), a postprandial hormone, plays a role in feeding behavior by signaling satiety to the brain. GLP-1 receptor agonists, used for treatment of type 2 diabetes (T2DM), promote weight loss. This study investigated the association between emotional eating and responses to food-cues in brain areas involved in satiety and reward processing, as well as GLP-1 receptor agonist-induced effects on these brain responses. T2DM patients with obesity, normoglycemic individuals with obesity, and lean individuals (n = 48) were studied in a randomized placebo-controlled crossover study. Using functional MRI, we determined the relation between emotional eating and regional brain responses to visual food stimuli and acute effects of intravenous administration of the GLP-1 receptor agonist exenatide on these responses. Emotional eating scores positively correlated with responses to food-cues in lean subjects in the insula, in normoglycemic subjects with obesity in the insula, and in T2DM patients in the amygdala, orbitofrontal cortex, and insula. Emotional eating scores negatively correlated with exenatide-induced reductions in responses to food-cues in normoglycemic subjects with obesity in the amygdala and in T2DM patients in the insula. Our findings indicate that emotional eaters have altered brain responses to food-cues and are less sensitive to the central effects of GLP-1 receptor activation.

CognitiveConstruct

RewardProcessing

10.3791/52468

Journal of visualized experiments : JoVE

J Vis Exp

Examination of Rapid Dopamine Dynamics with Fast Scan Cyclic Voltammetry During Intra-oral Tastant Administration in Awake Rats.

Rapid, phasic dopamine (DA) release in the mammalian brain plays a critical role in reward processing, reinforcement learning, and motivational control. Fast scan cyclic voltammetry (FSCV) is an electrochemical technique with high spatial and temporal (sub-second) resolution that has been utilized to examine phasic DA release in several types of preparations. In vitro experiments in single-cells and brain slices and in vivo experiments in anesthetized rodents have been used to identify mechanisms that mediate dopamine release and uptake under normal conditions and in disease models. Over the last 20 years, in vivo FSCV experiments in awake, freely moving rodents have also provided insight of dopaminergic mechanisms in reward processing and reward learning. One major advantage of the awake, freely moving preparation is the ability to examine rapid DA fluctuations that are time-locked to specific behavioral events or to reward or cue presentation. However, one limitation of combined behavior and voltammetry experiments is the difficulty of dissociating DA effects that are specific to primary rewarding or aversive stimuli from co-occurring DA fluctuations that mediate reward-directed or other motor behaviors. Here, we describe a combined method using in vivo FSCV and intra-oral infusion in an awake rat to directly investigate DA responses to oral tastants. In these experiments, oral tastants are infused directly to the palate of the rat--bypassing reward-directed behavior and voluntary drinking behavior--allowing for direct examination of DA responses to tastant stimuli.

CognitiveConstruct

RewardProcessing

10.1186/s13229-015-0043-y

Molecular autism

Mol Autism

Distinct effects of ASD and ADHD symptoms on reward anticipation in participants with ADHD, their unaffected siblings and healthy controls: a cross-sectional study.

Autism spectrum disorder (ASD) traits are continuously distributed throughout the population, and ASD symptoms are also frequently observed in patients with attention-deficit/hyperactivity disorder (ADHD). Both ASD and ADHD have been linked to alterations in reward-related neural processing. However, whether both symptom domains interact and/or have distinct effects on reward processing in healthy and ADHD populations is currently unknown. We examined how variance in ASD and ADHD symptoms in individuals with ADHD and healthy participants was related to the behavioural and neural response to reward during a monetary incentive delay (MID) task. Participants (mean age: 17.7 years, range: 10-28 years) from the NeuroIMAGE study with a confirmed diagnosis of ADHD (n = 136), their unaffected siblings (n = 83), as well as healthy controls (n = 105) performed an MID task in a magnetic resonance imaging (MRI) scanner. ASD and ADHD symptom scores were used as predictors of the neural response to reward anticipation and reward receipt. Behavioural responses were modeled using linear mixed models; neural responses were analysed using FMRIB's Software Library (FSL) proprietary mixed effects analysis (FLAMEO). ASD and ADHD symptoms were associated with alterations in BOLD activity during reward anticipation, but not reward receipt. Specifically, ASD scores were related to increased insular activity during reward anticipation across the sample. No interaction was found between this effect and the presence of ADHD, suggesting that ASD symptoms had no differential effect in ADHD and healthy populations. ADHD symptom scores were associated with reduced dorsolateral prefrontal activity during reward anticipation. No interactions were found between the effects of ASD and ADHD symptoms on reward processing. Variance in ASD and ADHD symptoms separately influence neural processing during reward anticipation in both individuals with (an increased risk of) ADHD and healthy participants. Our findings therefore suggest that both symptom domains affect reward processing through distinct mechanisms, underscoring the importance of multidimensional and multimodal assessment in psychiatry.

CognitiveConstruct

RewardProcessing

10.1016/j.psychres.2015.08.011

Psychiatry research

Psychiatry Res

Affective personality predictors of disrupted reward learning and pursuit in major depressive disorder.

Anhedonia, the diminished anticipation and pursuit of reward, is a core symptom of major depressive disorder (MDD). Trait behavioral activation (BA), as a proxy for anhedonia, and behavioral inhibition (BI) may moderate the relationship between MDD and reward-seeking. The present studies probed for reward learning deficits, potentially due to aberrant BA and/or BI, in active or remitted MDD individuals compared to healthy controls (HC). Active MDD (Study 1) and remitted MDD (Study 2) participants completed the modified monetary incentive delay task (mMIDT), a behavioral reward-seeking task whose response window parameters were individually titrated to theoretically elicit equivalent accuracy between groups. Participants completed the BI Scale and BA Reward-Responsiveness and Drive Scales. Despite individual titration, active MDD participants won significantly less money than HCs. Higher Reward-Responsiveness scores predicted more won; Drive and BI were not predictive. Remitted MDD participants' performance did not differ from controls', and trait BA and BI measures did not predict r-MDD performance. These results suggest that diminished reward-responsiveness may contribute to decreased motivation and reward pursuit during active MDD, but that reward learning is intact in remission. Understanding individual reward processing deficits in MDD may inform personalized intervention addressing anhedonia and motivation deficits in select MDD patients.

CognitiveConstruct

RewardProcessing

10.1007/s40473-015-0036-3

Current behavioral neuroscience reports

Curr Behav Neurosci Rep

Clinical Outcome and Mechanisms of Deep Brain Stimulation for Obsessive-Compulsive Disorder.

Clinical outcome of deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) shows robust effects in terms of a mean Yale-Brown Obsessive-Compulsive Scale (YBOCS) reduction of 47.7 % and a mean response percentage (minimum 35 % YBOCS reduction) of 58.2 %. It appears that most patients regain a normal quality of life (QoL) after DBS. Reviewing the literature of the last 4 years, we argue that the mechanisms of action of DBS are a combination of excitatory and inhibitory as well as local and distal effects. Evidence from DBS animal models converges with human DBS EEG and imaging findings, in that DBS may be effective for OCD by reduction of hyperconnectivity between frontal and striatal areas. This is achieved through reduction of top-down-directed synchrony and reduction of frontal low-frequency oscillations. DBS appears to counteract striatal dysfunction through an increase in striatal dopamine and through improvement of reward processing. DBS affects anxiety levels through reduction of stress hormones and improvement of fear extinction.

CognitiveConstruct

RewardProcessing

10.1017/S0033291715001452

Psychological medicine

Psychol Med

Neural reward processing in individuals remitted from major depression.

Dysfunctional behavioural and neural processing of reward has been found in currently depressed individuals. However, little is known about altered reward processing in remitted depressed individuals. A total of 23 medication-free individuals with remitted major depressive disorder (rMDD) and 23 matched healthy controls (HCs) performed a reward task during functional magnetic resonance imaging. We also investigated reward dependence, novelty seeking and harm avoidance using the Tridimensional Personality Questionnaire and their association with neural responses of reward processing. Compared to HCs, individuals with rMDD exhibited enhanced responses to reward-predicting cues in the hippocampus, amygdala and superior frontal gyrus. When reward was delivered, rMDD subjects did not significantly differ from HCs. In both groups neural activity during reward anticipation was negatively correlated with harm avoidance. Our results show that rMDD is characterized by hyperactivation in fronto-limbic regions during reward anticipation. Alterations in neural activation during reward processing might reflect an increased effort in remitted depressed individuals to allocate neural activity for executive and evaluative processes during anticipatory reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.ajp.2015.08.002

Asian journal of psychiatry

Asian J Psychiatr

Impaired neural reward processing in children and adolescents with reactive attachment disorder: A pilot study.

Reactive attachment disorder (RAD) is characterized by markedly disturbed and developmentally inappropriate social relatedness due to parental maltreatment. RAD patients often display a high number of comorbid attention deficit/hyperactivity disorder (ADHD) symptoms, and certain RAD symptoms are difficult to discriminate from ADHD. One of the core characteristics of ADHD is a decrease in neural reward processing due to dopamine dysfunction. The aim of the present study was to determine whether the brain activity involved in reward processing in RAD patients is impaired in comparison with ADHD patients and typically developed controls. Five RAD patients, 17 typically developed (TD) controls and 17 ADHD patients aged 10-16 years performed tasks with high and low monetary reward while undergoing functional magnetic resonance imaging. ADHD patients were tested before and after 3 months treatment with osmotic release oral system-methylphenidate. Before treatment, ADHD patients showed that striatal and thalamus activities only in the tasks with low monetary reward were lower than TD controls. RAD patients showed decrease in activity of the caudate, putamen and thalamus during both the high and low monetary reward conditions in comparison with all the other groups. In RAD patients, the activity of the putamen was associated with the severity of posttraumatic stress and overt dissociation. Reward sensitivity was markedly decreased in children and adolescents with RAD, as evidenced by a diminished neural response during reward perception. This suggests that dopaminergic dysfunction exists in these patients, and may inform future dopaminergic treatment strategies for RAD.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0136168

PloS one

PLoS One

Women's Preference for a Male Acquaintance Enhances Social Reward Processing of Material Goods in the Anterior Cingulate Cortex.

Men, like the male of many animal species, use gifts to build satisfactory relationships with a desired woman. From the woman's perspective, all gifts are not always equally rewarding; the reward value of a gift depends on two factors: (1) the giver and (2) the type of the gift (the gift's social meaning). In this study, we investigated how these two factors interactively determine the reward value of a gift. Specifically, we examined how the neural processing for understanding a gift's social meaning is modulated by preferences for the giver. We performed a functional magnetic resonance imaging (fMRI) study in which a female participant was asked to judge a gift from a male she was acquainted with in real life. We examined the interactive effects between (1) the female participant's attitude toward the male acquaintance (liked vs. uninteresting) and (2) the type of the gift (romantic [e.g., bouquet, earrings, and perfumes] vs. non-romantic [e.g., pencils, memo pad, and moneybox]). We found that preference for an acquaintance selectively modulated activity in the anterior cingulate cortex (ACC) in response to romantic gifts, compared to non-romantic gifts. In contrast, if the woman was indifferent toward an acquaintance, no activity modulation was observed in this area for the same gifts. In addition, the ACC showed functional connectivity with the supplementary motor area/dorsal ACC (SMA/dACC), an area within the dorsal mediofrontal cortex, suggesting that it integrates action monitoring and emotional and cognitive processing in decision-making. These results suggest that attitude toward an opposite sex member has a modulatory role in recognizing the social meaning of material goods--preference for the member is a powerful modulator of social reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.psyneuen.2015.08.004

Psychoneuroendocrinology

Psychoneuroendocrinology

Diet-induced obesity causes ghrelin resistance in reward processing tasks.

Diet-induced obesity (DIO) causes ghrelin resistance in hypothalamic Agouti-related peptide (AgRP) neurons. However, ghrelin promotes feeding through actions at both the hypothalamus and mesolimbic dopamine reward pathways. Therefore, we hypothesized that DIO would also establish ghrelin resistance in the ventral tegmental area (VTA), a major site of dopaminergic cell bodies important in reward processing. We observed reduced sucrose and saccharin consumption in Ghrelin KO vs Ghrelin WT mice. Moreover, DIO reduced saccharin consumption relative to chow-fed controls. These data suggest that the deletion of ghrelin and high fat diet both cause anhedonia. To assess if these are causally related, we tested whether DIO caused ghrelin resistance in a classic model of drug reward, conditioned place preference (CPP). Chow or high fat diet (HFD) mice were conditioned with ghrelin (1mg/kg in 10ml/kg ip) in the presence or absence of food in the conditioning chamber. We observed a CPP to ghrelin in chow-fed mice but not in HFD-fed mice. HFD-fed mice still showed a CPP for cocaine (20mg/kg), indicating that they maintained the ability to develop conditioned behaviour. The absence of food availability during ghrelin conditioning sessions induced a conditioned place aversion, an effect that was still present in both chow and HFD mice. Bilateral intra-VTA ghrelin injection (0.33μg/μl in 0.5μl) robustly increased feeding in both chow-fed and high fat diet (HFD)-fed mice; however, this was correlated with body weight only in the chow-fed mice. Our results suggest that DIO causes ghrelin resistance albeit not directly in the VTA. We suggest there is impaired ghrelin sensitivity in upstream pathways regulating reward pathways, highlighting a functional role for ghrelin linking appropriate metabolic sensing with reward processing.

CognitiveConstruct

RewardProcessing

10.1002/hbm.22944

Human brain mapping

Hum Brain Mapp

Impaired reward processing in the human prefrontal cortex distinguishes between persistent and remittent attention deficit hyperactivity disorder.

Symptoms of attention deficit hyperactivity disorder (ADHD) in children often persist into adulthood and can lead to severe antisocial behavior. However, to-date it remains unclear whether neuro-functional abnormalities cause ADHD, which in turn can then provide a marker of persistent ADHD. Using event-related functional magnetic resonance imaging (fMRI), we measured blood oxygenation level dependent (BOLD) signal changes in subjects during a reversal learning task in which choice of the correct stimulus led to a probabilistically determined 'monetary' reward or punishment. Participants were diagnosed with ADHD during their childhood (N=32) and were paired with age, gender, and education matched healthy controls (N=32). Reassessment of the ADHD group as adults resulted in a split between either persistent (persisters, N=17) or remitted ADHDs (remitters, N=15). All three groups showed significantly decreased activation in the medial prefrontal cortex (PFC) and the left striatum during punished correct responses, however only remitters and controls presented significant psycho-physiological interaction between these fronto-striatal reward and outcome valence networks. Comparing persisters to remitters and controls showed significantly inverted responses to punishment (P<0.05, family-wise error corrected) in left PFC region. Interestingly, the decreased activation shown after punishment was located in different areas of the PFC for remitters compared with controls, suggesting that remitters might have learned compensation strategies to overcome their ADHD symptoms. Thus, fMRI helps understanding the neuro-functional basis of ADHD related behavior differences and differentiates between persistent and remittent ADHD.

CognitiveConstruct

RewardProcessing

10.1101/lm.037317.114

Learning & memory (Cold Spring Harbor, N.Y.)

Learn Mem

Reward processing by the dorsal raphe nucleus: 5-HT and beyond.

The dorsal raphe nucleus (DRN) represents one of the most sensitive reward sites in the brain. However, the exact relationship between DRN neuronal activity and reward signaling has been elusive. In this review, we will summarize anatomical, pharmacological, optogenetics, and electrophysiological studies on the functions and circuit mechanisms of DRN neurons in reward processing. The DRN is commonly associated with serotonin (5-hydroxytryptamine; 5-HT), but this nucleus also contains neurons of the neurotransmitter phenotypes of glutamate, GABA and dopamine. Pharmacological studies indicate that 5-HT might be involved in modulating reward- or punishment-related behaviors. Recent optogenetic stimulations demonstrate that transient activation of DRN neurons produces strong reinforcement signals that are carried out primarily by glutamate. Moreover, activation of DRN 5-HT neurons enhances reward waiting. Electrophysiological recordings reveal that the activity of DRN neurons exhibits diverse behavioral correlates in reward-related tasks. Studies so far thus demonstrate the strong power of DRN neurons in reward signaling and at the same time invite additional efforts to dissect the roles and mechanisms of different DRN neuron types in various processes of reward-related behaviors.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2015.07.019

Journal of affective disorders

J Affect Disord

Examining reward-seeking, negative self-beliefs and over-general autobiographical memory as mechanisms of change in classroom prevention programs for adolescent depression.

Effective methods to prevent adolescent depressive symptoms could reduce suffering and burden across the lifespan. However, psychological interventions delivered to adolescents show efficacy only in symptomatic or high-risk youth. Targeting causal risk factors and assessing mechanistic change can help devise efficacious universal or classroom based prevention programs. A non-randomized longitudinal design was used to compare three classroom-based prevention programs for adolescent depression (Behavioral Activation with Reward Processing, "Thinking about Reward in Young People" (TRY); Cognitive Behavioral Therapy (CBT) and Mindfulness Based Cognitive Therapy (MBCT)), and determine cognitive mechanisms of change in these programs. Cognitive mechanisms examined were reward-seeking, negative self-beliefs (assessed with behavioral tasks) and over-general autobiographical memory. 256 healthy adolescents aged 13-14 participated with 236 (92%) and 227 (89%) completing the pre- and post-assessments. TRY was the only intervention associated with a reduction in depressive symptoms at follow-up. Reward-seeking increased following TRY. In the other programs there were non-significant changes in cognitive mechanisms, with more reflective negative self-beliefs in CBT and fewer over-general autobiographical memories in MBCT In the TRY program, which focused on increasing sensitivity to rewarding activities, reward seeking increased and this was associated with decreased depressive symptoms. Due to the infeasibility of a cluster randomized controlled trial, a non-randomized design was used. Increased reward-seeking was associated with decreased depressive symptoms and may be a mechanism of depressive symptom change in the intervention with a focus on enhancing sensitivity and awareness of reward. This study provides preliminary evidence to suggest that incorporating activities to enhance reward sensitivity may be fruitful in randomized controlled trials of universal prevention programs for depression.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2015.06.013

Psychiatry research

Psychiatry Res

Striatal dopamine type 2 receptor availability in anorexia nervosa.

The neurobiology of anorexia nervosa remains incompletely understood. Here we utilized PET imaging with the radiotracer [(11)C]raclopride to measure striatal dopamine type 2 (D2) receptor availability in patients with anorexia nervosa. 25 women with anorexia nervosa who were receiving treatment in an inpatient program participated, as well as 25 control subjects. Patients were scanned up to two times with the PET tracer [(11)C]raclopride: once while underweight, and once upon weight restoration. Control subjects underwent one PET scan. In the primary analyses, there were no significant differences between underweight patients (n=21) and control subjects (n=25) in striatal D2 receptor binding potential. Analysis of subregions (sensorimotor striatum, associative striatum, limbic striatum) did not reveal differences between groups. In patients completing both scans (n=15), there were no detectable changes in striatal D2 receptor binding potential after weight restoration. In this sample, there were no differences in striatal D2 receptor binding potential between patients with anorexia nervosa and control subjects. Weight restoration was not associated with a change in striatal D2 receptor binding. These findings suggest that disturbances in reward processing in this disorder are not attributable to abnormal D2 receptor characteristics, and that other reward-related neural targets may be of greater relevance.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.0560-15.2015

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

J Neurosci

Temporally Dissociable Contributions of Human Medial Prefrontal Subregions to Reward-Guided Learning.

In decision making, dorsal and ventral medial prefrontal cortex show a sensitivity to key decision variables, such as reward prediction errors. It is unclear whether these signals reflect parallel processing of a common synchronous input to both regions, for example from mesocortical dopamine, or separate and consecutive stages in reward processing. These two perspectives make distinct predictions about the relative timing of feedback-related activity in each of these regions, a question we address here. To reconstruct the unique temporal contribution of dorsomedial (dmPFC) and ventromedial prefrontal cortex (vmPFC) to simultaneously measured EEG activity in human subjects, we developed a novel trialwise fMRI-informed EEG analysis that allows dissociating correlated and overlapping sources. We show that vmPFC uniquely contributes a sustained activation profile shortly after outcome presentation, whereas dmPFC contributes a later and more peaked activation pattern. This temporal dissociation is expressed mainly in the alpha band for a vmPFC signal, which contrasts with a theta based dmPFC signal. Thus, our data show reward-related vmPFC and dmPFC responses have distinct time courses and unique spectral profiles, findings that support distinct functional roles in a reward-processing network. Multiple subregions of the medial prefrontal cortex are known to be involved in decision making and learning, and expose similar response patterns in fMRI. Here, we used a novel approach to analyzing simultaneous EEG-fMRI that allows to dissociate the individual time courses of brain regions. We find that vmPFC and dmPFC have distinguishable time courses and time-frequency patterns.

CognitiveConstruct

RewardProcessing

10.1007/s40263-015-0264-9

CNS drugs

CNS Drugs

Emotional Lability in Patients with Attention-Deficit/Hyperactivity Disorder: Impact of Pharmacotherapy.

Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder defined by persistent inattention and/or hyperactivity and impulsivity. These symptoms occur more frequently and are more severe in individuals with ADHD compared with those at a similar developmental level without ADHD, and can be conceptualized as deficits in executive functioning (EF). EF includes domains of metacognition and inhibition, which influence the ability to regulate responses elicited by emotional stimuli. EF deficits can lead to emotional lability (EL), which is characterized by sudden changes in emotion and behaviors of inappropriately high intensity that may include sudden bouts of anger, dysphoria, sadness, or euphoria. EL is common and estimated to occur in about 3.3-10% of the population. Recent estimates of EL prevalence in children and adolescents with ADHD range from 38 to 75%. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition does not include EL in diagnostic criteria for ADHD, but does include ADHD-associated features of low frustration tolerance, irritability, or mood lability. The neurobiological basis of EL is not well understood, but brain imaging studies support dividing EF into "cool" cognitive networks encompassing attention and planning activities, and "hot" motivational networks involved in temporal discounting, reward processing, and reward anticipation. Dysfunction in "hot" networks is thought to be related to EL. EL symptoms are associated with more severe ADHD and co-morbidities, have significant impact on functioning, and may respond to treatment with medications frequently used to treat ADHD. Treatment outcomes and areas for future research are discussed.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2015.08.001

NeuroImage

Neuroimage

Aberrant mesolimbic dopamine-opiate interaction in obesity.

Dopamine and opioid neurotransmitter systems share many functions such as regulation of reward and pleasure. μ-Opioid receptors (MOR) modulate the mesolimbic dopamine system in ventral tegmental area and striatum, key areas implicated in reward. We hypothesized that dopamine and opioid receptor availabilities correlate in vivo and that this correlation is altered in obesity, a disease with altered reward processing. Twenty lean females (mean BMI 22) and 25 non-binge eating morbidly obese females (mean BMI 41) underwent two positron emission tomography scans with [(11)C]carfentanil and [(11)C]raclopride to measure the MOR and dopamine D2 receptor (DRD2) availability, respectively. In lean subjects, the MOR and DRD2 availabilities were positively associated in the ventral striatum (r=0.62, p=0.003) and dorsal caudate nucleus (r=0.62, p=0.004). Moreover, DRD2 availability in the ventral striatum was associated with MOR availability in other regions of the reward circuitry, particularly in the ventral tegmental area. In morbidly obese subjects, this receptor interaction was significantly weaker in ventral striatum but unaltered in the caudate nucleus. Finally, the association between DRD2 availability in the ventral striatum and MOR availability in the ventral tegmental area was abolished in the morbidly obese. The study demonstrates a link between DRD2 and MOR availabilities in living human brain. This interaction is selectively disrupted in mesolimbic dopamine system in morbid obesity. We propose that interaction between the dopamine and opioid systems is a prerequisite for normal reward processing and that disrupted cross-talk may underlie altered reward processing in obesity.

CognitiveConstruct

RewardProcessing

10.1016/j.copsyc.2014.12.011

Current opinion in psychology

Curr Opin Psychol

Dysfunctional Reward Processing in Depression.

Anhedonia - diminished pleasure and/or decreased reactivity to pleasurable stimuli - is a core feature of depression that frequently persists after treatment. As a result, extensive effort has been directed towards characterizing the psychological and biological processes that mediate dysfunctional reward processing in depression. Reward processing can be parsed into sub-components that include motivation, reinforcement learning, and hedonic capacity, which, according to preclinical and neuroimaging evidence, involve partially dissociable brain systems. In line with this, recent findings indicate that behavioral impairments and neural abnormalities in depression vary across distinct reward-related constructs. Ultimately, improved understanding of precise reward-related dysfunctions in depression promises to improve diagnostic and therapeutic efforts in depression.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2015.01044

Frontiers in psychology

Front Psychol

Sex-dependent effects on tasks assessing reinforcement learning and interference inhibition.

Increasing evidence suggests that the prefrontal cortex (PFC) is influenced by sex steroids and that some cognitive functions dependent on the PFC may be sexually differentiated in humans. Past work has identified a male advantage on certain complex reinforcement learning tasks, but it is unclear which latent task components are important to elicit the sex difference. The objective of the current study was to investigate whether there are sex differences on measures of response inhibition and valenced feedback processing, elements that are shared by previously studied reinforcement learning tasks. Healthy young adults (90 males, 86 females) matched in general intelligence completed the Probabilistic Selection Task (PST), a Simon task, and the Stop-Signal task. On the PST, females were more accurate than males in learning from positive (but not negative) feedback. On the Simon task, males were faster than females, especially in the face of incongruent stimuli. No sex difference was observed in Stop-Signal reaction time. The current findings provide preliminary support for a sex difference in the processing of valenced feedback and in interference inhibition.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2015.08.001

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

Int J Psychophysiol

Self-reflection modulates the outcome evaluation process: Evidence from an ERP study.

Recent research demonstrated structural overlap between reward and self processing, but the functional relationship that explains how self processing influences reward processing remains unclear. The present study used an experimentally constrained reflection task to investigate whether individuals' outcome evaluations in a gambling task are modulated by task-unrelated self- and other-reflection processes. The self- and other-reflection task contained descriptions of the self or others, and brain event-related potentials (ERPs) were recorded while 16 normal adults performed a gambling task. The ERP analysis focused on the feedback-related negativity (FRN) component. We found that the difference wave of FRN increased in the self-reflection condition compared with the other-reflection condition. The present findings provide direct evidence that self processing can influence reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2015.07.083

NeuroImage

Neuroimage

Neural networks involved in adolescent reward processing: An activation likelihood estimation meta-analysis of functional neuroimaging studies.

Behavioral responses to, and the neural processing of, rewards change dramatically during adolescence and may contribute to observed increases in risk-taking during this developmental period. Functional MRI (fMRI) studies suggest differences between adolescents and adults in neural activation during reward processing, but findings are contradictory, and effects have been found in non-predicted directions. The current study uses an activation likelihood estimation (ALE) approach for quantitative meta-analysis of functional neuroimaging studies to: (1) confirm the network of brain regions involved in adolescents' reward processing, (2) identify regions involved in specific stages (anticipation, outcome) and valence (positive, negative) of reward processing, and (3) identify differences in activation likelihood between adolescent and adult reward-related brain activation. Results reveal a subcortical network of brain regions involved in adolescent reward processing similar to that found in adults with major hubs including the ventral and dorsal striatum, insula, and posterior cingulate cortex (PCC). Contrast analyses find that adolescents exhibit greater likelihood of activation in the insula while processing anticipation relative to outcome and greater likelihood of activation in the putamen and amygdala during outcome relative to anticipation. While processing positive compared to negative valence, adolescents show increased likelihood for activation in the posterior cingulate cortex (PCC) and ventral striatum. Contrasting adolescent reward processing with the existing ALE of adult reward processing reveals increased likelihood for activation in limbic, frontolimbic, and striatal regions in adolescents compared with adults. Unlike adolescents, adults also activate executive control regions of the frontal and parietal lobes. These findings support hypothesized elevations in motivated activity during adolescence.

CognitiveConstruct

RewardProcessing

10.1111/jnc.13273

Journal of neurochemistry

J Neurochem

Neuronal connectivity between habenular glutamate-kisspeptin1 co-expressing neurons and the raphe 5-HT system.

The habenula, located on the dorsal thalamic surface, is an emotional and reward processing center. As in the mammalian brain, the zebrafish habenula is divided into dorsal (dHb) and ventral (vHb) subdivisions that project to the interpeduncular nucleus and median raphe (MR) respectively. Previously, we have shown that kisspeptin 1 (Kiss1) expressing in the vHb, regulates the serotonin (5-HT) system in the MR. However, the connectivity between the Kiss1 neurons and the 5-HT system remains unknown. To resolve this issue, we generated a specific antibody against zebrafish Kiss1 receptor (Kiss-R1); using this primary antibody we found intense immunohistochemical labeling in the ventro-anterior corner of the MR (vaMR) but not in 5-HT neurons, suggesting the potential involvement of interneurons in 5-HT modulation by Kiss1. Double-fluorescence labeling showed that the majority of habenular Kiss1 neurons are glutamatergic. In the MR region, Kiss1 fibers were mainly seen in close association with glutamatergic neurons and only scarcely within GABAergic and 5-HT neurons. Our findings indicate that the habenular Kiss1 neurons potentially modulate the 5-HT system primarily through glutamatergic neurotransmission via as yet uncharacterized interneurons. The neuropeptide kisspeptin (Kiss1) play a key role in vertebrate reproduction. We have previously shown modulatory role of habenular Kiss1 in the raphe serotonin (5-HT) systems. This study proposed that the habenular Kiss1 neurons modulate the 5-HT system primarily through glutamatergic neurotransmission, which provides an important insight for understanding of the modulation of 5-HT system by the habenula-raphe pathway.

CognitiveConstruct

RewardProcessing

10.1038/npp.2015.236

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Sex-Steroid Hormone Manipulation Reduces Brain Response to Reward.

Mood disorders are twice as frequent in women than in men. Risk mechanisms for major depression include adverse responses to acute changes in sex-steroid hormone levels, eg, postpartum in women. Such adverse responses may involve an altered processing of rewards. Here, we examine how women's vulnerability for mood disorders is linked to sex-steroid dynamics by investigating the effects of a pharmacologically induced fluctuation in ovarian sex steroids on the brain response to monetary rewards. In a double-blinded placebo controlled study, healthy women were randomized to receive either placebo or the gonadotropin-releasing hormone agonist (GnRHa) goserelin, which causes a net decrease in sex-steroid levels. Fifty-eight women performed a gambling task while undergoing functional MRI at baseline, during the mid-follicular phase, and again following the intervention. The gambling task enabled us to map regional brain activity related to the magnitude of risk during choice and to monetary reward. The GnRHa intervention caused a net reduction in ovarian sex steroids (estradiol and testosterone) and increased depression symptoms. Compared with placebo, GnRHa reduced amygdala's reactivity to high monetary rewards. There was a positive association between the individual changes in testosterone and changes in bilateral insula response to monetary rewards. Our data provide evidence for the involvement of sex-steroid hormones in reward processing. A blunted amygdala response to rewarding stimuli following a rapid decline in sex-steroid hormones may reflect a reduced engagement in positive experiences. Abnormal reward processing may constitute a neurobiological mechanism by which sex-steroid fluctuations provoke mood disorders in susceptible women.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2015.07.079

NeuroImage

Neuroimage

Effects of aging on value-directed modulation of semantic network activity during verbal learning.

While impairments in memory recall are apparent in aging, older adults show a remarkably preserved ability to selectively remember information deemed valuable. Here, we use fMRI to compare brain activation in healthy older and younger adults during encoding of high and low value words to determine whether there are differences in how older adults achieve value-directed memory selectivity. We find that memory selectivity in older adults is associated with value-related changes in activation during word presentation in left hemisphere regions that are involved in semantic processing, similar to young adults. However, highly selective young adults show a relatively greater increase in semantic network activity during encoding of high-value items, whereas highly selective older adults show relatively diminished activity during encoding of low-value items. Additionally, only younger adults showed value-related increases in activity in semantic and reward processing regions during presentation of the value cue preceding each to-be-remembered word. Young adults therefore respond to cue value more proactively than do older adults, yet the magnitude of value-related differences in cue period brain activity did not predict individual differences in memory selectivity. Thus, our data also show that age-related reductions in prestimulus activity do not always lead to inefficient performance.

CognitiveConstruct

RewardProcessing

10.1101/pdb.top086330

Cold Spring Harbor protocols

Cold Spring Harb Protoc

Optogenetics in Freely Moving Mammals: Dopamine and Reward.

Brain reward systems play a central role in the cognitive and hedonic behaviors of mammals. Multiple neuron types and brain regions are involved in reward processing, posing fascinating scientific questions, and major experimental challenges. Using diverse approaches including genetics, electrophysiology, imaging, and behavioral analysis, a large body of research has focused on both normal functioning of the reward circuitry and on its potential significance in neuropsychiatric diseases. In this introduction, we illustrate a real-world application of optogenetics to mammalian behavior and physiology, delineating procedures and technologies for optogenetic control of individual components of the reward circuitry. We describe the experimental setup and protocol for integrating optogenetic modulation of dopamine neurons with fast-scan cyclic voltammetry, conditioned place preference, and operant conditioning to assess the causal role of well-defined electrical and biochemical signals in reward-related behavior.

CognitiveConstruct

RewardProcessing

10.1007/s40429-015-0048-9

Current addiction reports

Curr Addict Rep

Neuroimaging Risk Markers for Substance Abuse: Recent Findings on Inhibitory Control and Reward System Functioning.

Rates of alcohol and other drug use rise sharply throughout adolescence and peak in the early 20s. Likewise, prevalence of first-time substance use disorder (SUD) and past-year SUD both peak between ages 18-23. SUD is associated with a host of negative outcomes and is a serious health concern. Understanding the mechanisms that precede the onset and escalation of substance use is crucial in order to develop more effective prevention and intervention strategies for children and adolescents at risk for SUD. In this review, we discuss recent findings from functional neuroimaging studies in children, adolescents, and emerging adults that focus on uncovering the neural underpinnings of SUD risk. The focus is on inhibitory control and reward circuitry due to their involvement in risk-taking behaviors, which are heightened in adolescence and may facilitate substance use. We discuss convergences in the literature and highlight findings suggesting that the association between SUD risk and neurofunctioning may be moderated by age, gender, and history of substance use. Recommendations for future directions are also discussed.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2015.07.015

Drug and alcohol dependence

Drug Alcohol Depend

Cigarette craving is associated with blunted reward processing in nicotine-dependent smokers.

Dysfunctional reward processing leading to the undervaluation of non-drug rewards is hypothesized to play a crucial role in nicotine dependence. However, it is unclear if blunted reward responsivity and the desire to use nicotine are directly linked after a brief period of abstinence. Such an association would suggest that individuals with reduced reward responsivity may be at increased risk to experience nicotine craving. Reward function was evaluated with a probabilistic reward task (PRT), which measures reward responsivity to monetary incentives. To identify whether smoking status influenced reward function, PRT performance was compared between non-depressed, nicotine-dependent smokers and non-smokers. Within smokers, correlations were conducted to determine if blunted reward responsivity on the PRT was associated with increased nicotine craving. Time since last nicotine exposure was standardized to 4h for all smokers. Smokers and non-smokers did not differ in reward responsivity on the PRT. However, within smokers, a significant negative correlation was found between reward responsivity and intensity of nicotine craving. The current findings show that, among smokers, the intensity of nicotine craving is linked to lower sensitivity to non-drug rewards. This finding is in line with prior theories that suggest reward dysfunction in some clinical populations (e.g., depressive disorders, schizophrenia) may facilitate nicotine use. The current study expands on such theories by indicating that sub-clinical variations in reward function are related to motivation for nicotine use. Identifying smokers who show blunted sensitivity to non-drug rewards may help guide treatments aimed at mitigating the motivation to smoke.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2015.06.031

Journal of affective disorders

J Affect Disord

Identifying differences between depressed adolescent suicide ideators and attempters.

Adolescent depression and suicide are pressing public health concerns, and identifying key differences among suicide ideators and attempters is critical. The goal of the current study is to test whether depressed adolescent suicide attempters report greater anhedonia severity and exhibit aberrant effort-cost computations in the face of uncertainty. Depressed adolescents (n=101) ages 13-19 years were administered structured clinical interviews to assess current mental health disorders and a history of suicidality (suicide ideators=55, suicide attempters=46). Then, participants completed self-report instruments assessing symptoms of suicidal ideation, depression, anhedonia, and anxiety as well as a computerized effort-cost computation task. Compared with depressed adolescent suicide ideators, attempters report greater anhedonia severity, even after concurrently controlling for symptoms of suicidal ideation, depression, and anxiety. Additionally, when completing the effort-cost computation task, suicide attempters are less likely to pursue the difficult, high value option when outcomes are uncertain. Follow-up, trial-level analyses of effort-cost computations suggest that receipt of reward does not influence future decision-making among suicide attempters, however, suicide ideators exhibit a win-stay approach when receiving rewards on previous trials. Findings should be considered in light of limitations including a modest sample size, which limits generalizability, and the cross-sectional design. Depressed adolescent suicide attempters are characterized by greater anhedonia severity, which may impair the ability to integrate previous rewarding experiences to inform future decisions. Taken together, this may generate a feeling of powerlessness that contributes to increased suicidality and a needless loss of life.

CognitiveConstruct

RewardProcessing

10.1016/j.schres.2015.06.030

Schizophrenia research

Schizophr Res

Testosterone and reward prediction-errors in healthy men and men with schizophrenia.

Sex hormones impact reward processing, which is dysfunctional in schizophrenia; however, the degree to which testosterone levels relate to reward-related brain activity in healthy men and the extent to which this relationship may be altered in men with schizophrenia has not been determined. We used functional magnetic resonance imaging (fMRI) to measure neural responses in the striatum during reward prediction-errors and hormone assays to measure testosterone and prolactin in serum. To determine if testosterone can have a direct effect on dopamine neurons, we also localized and measured androgen receptors in human midbrain with immunohistochemistry and quantitative PCR. We found correlations between testosterone and prediction-error related activity in the ventral striatum of healthy men, but not in men with schizophrenia, such that testosterone increased the size of positive and negative prediction-error related activity in a valence-specific manner. We also identified midbrain dopamine neurons that were androgen receptor immunoreactive, and found that androgen receptor (AR) mRNA was positively correlated with tyrosine hydroxylase (TH) mRNA in human male substantia nigra. The results suggest that sex steroid receptors can potentially influence midbrain dopamine biosynthesis, and higher levels of serum testosterone are linked to better discrimination of motivationally-relevant signals in the ventral striatum, putatively by modulation of the dopamine biosynthesis pathway via AR ligand binding. However, the normal relationship between serum testosterone and ventral striatum activity during reward learning appears to be disrupted in schizophrenia.

CognitiveConstruct

RewardProcessing

10.1016/j.psyneuen.2015.07.609

Psychoneuroendocrinology

Psychoneuroendocrinology

Activation of the kynurenine pathway is associated with striatal volume in major depressive disorder.

Inflammation, which may be present in a subgroup of individuals with major depressive disorder (MDD), activates the kynurenine metabolic pathway to produce kynurenine metabolites kynurenic acid (KynA) and quinolinic acid (QA). We have previously reported an association between the ratio of KynA to QA and hippocampal volume in MDD. In animals, inflammation leads to deficits in incentive motivation. Given the central role of the nucleus accumbens (NAcc) and other regions of the striatum in motivated behavior, reward processing, and anhedonia, we hypothesized that abnormalities in the concentrations of kynurenine pathway metabolites would be associated with striatal volumes. As previously reported, after controlling for relevant confounds, the KynA/QA ratio was reduced in the serum of unmedicated patients with MDD (n=53) versus healthy controls (HC, n=47) and there was a non-significant trend in the correlation between KynA/QA and severity of anhedonia (r=-0.27, p<0.1). There was no significant difference between the MDD and HC groups in any of the individual kynurenine metabolites or volume of the striatum defined as the sum of the volumes of the NAcc, caudate, and putamen. After regressing out the effects of sex, analysis batch, and supratentorial volume, the kynurenine concentration and the ratio of kynurenine to tryptophan were inversely associated with striatal volumes in the MDD sample (p<0.05, uncorrected). Further, striatal volume was correlated with the items, "concentration difficulties", "lassitude", and "pessimism" from the Montgomery-Asberg Depression Rating Scale. Our results raise the possibility that activation of the kynurenine pathway is a marker of an inflammatory process that leads to reductions in striatal volume. However, unlike the hippocampus, the association does not appear to be mediated by the relative balance between KynA and QA.

CognitiveConstruct

RewardProcessing

10.1111/psyp.12504

Psychophysiology

Psychophysiology

Teasing apart the anticipatory and consummatory processing of monetary incentives: An event-related potential study of reward dynamics.

The monetary incentive delay (MID) task has been widely used in fMRI studies to investigate the neural networks involved in anticipatory and consummatory reward processing. Previous efforts to adapt the MID task for use with ERPs, however, have had limited success. Here, we sought to further decompose reward dynamics using a comprehensive set of anticipatory (cue-N2, cue-P3, contingent negative variation [CNV]) and consummatory ERPs (feedback negativity [FN], feedback P3 [fb-P3]). ERP data was recorded during adapted versions of the MID task across two experiments. Unlike previous studies, monetary incentive cues modulated the cue-N2, cue-P3, and CNV; however, cue-related ERPs and the CNV were uncorrelated with one another, indicating distinct anticipatory subprocesses. With regard to consummatory processing, FN amplitude primarily tracked outcome valence (reward vs. nonreward), whereas fb-P3 amplitude primarily tracked outcome salience (uncertain vs. certain). Independent modulation of the cue-P3 and fb-P3 was observed, indicating that these two P3 responses may uniquely capture the allocation of attention during anticipatory and consummatory reward processing, respectively. Overall, across two samples, consistent evidence of both anticipatory and consummatory ERP activity was observed on an adapted version of the MID paradigm, demonstrating for the first time how these ERP components may be integrated with one another to more fully characterize the time course of reward processing. This ERP-MID paradigm is well suited to parsing reward dynamics, and can be applied to both healthy and clinical populations.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2015.07.003

Developmental cognitive neuroscience

Dev Cogn Neurosci

Neural substrates of child irritability in typically developing and psychiatric populations.

Irritability is an aspect of the negative affectivity domain of temperament, but in severe and dysregulated forms is a symptom of a range of psychopathologies. Better understanding of the neural underpinnings of irritability, outside the context of specific disorders, can help to understand normative variation but also characterize its clinical salience in psychopathology diagnosis. This study assessed brain activation during reward and frustration, domains of behavioral deficits in childhood irritability. Children (age 6-9) presenting in mental health clinics for extreme and impairing irritability (n = 26) were compared to healthy children (n = 28). Using developmentally sensitive methods, neural activation was measured via a negative mood induction paradigm during fMRI scanning. The clinical group displayed more activation of the anterior cingulate and middle frontal gyrus during reward, but less activation during frustration, than healthy comparison children. The opposite pattern was found in the posterior cingulate. Further, in clinical subjects, parent report of irritability was dimensionally related to decreased activation of the anterior cingulate and striatum during frustration. The results of this study indicate neural dysfunction within brain regions related to reward processing, error monitoring, and emotion regulation underlying clinically impairing irritability. Results are discussed in the context of a growing field of neuroimaging research investigating irritable children.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2015.07.002

Developmental cognitive neuroscience

Dev Cogn Neurosci

Earlier adolescent substance use onset predicts stronger connectivity between reward and cognitive control brain networks.

Early adolescent onset of substance use is a robust predictor of future substance use disorders. We examined the relation between age of substance use initiation and resting state functional connectivity (RSFC) of the core reward processing (nucleus accumbens; NAcc) to cognitive control (prefrontal cortex; PFC) brain networks. Adolescents in a longitudinal study of Mexican-origin youth reported their substance use annually from ages 10 to 16 years. At age 16, 69 adolescents participated in a resting state functional magnetic resonance imaging scan. Seed-based correlational analyses were conducted using regions of interest in bilateral NAcc. The earlier that adolescents initiated substance use, the stronger the connectivity between bilateral NAcc and right dorsolateral PFC, right dorsomedial PFC, right pre-supplementary motor area, right inferior parietal lobule, and left medial temporal gyrus. The regions that demonstrated significant positive linear relationships between the number of adolescent years using substances and connectivity with NAcc are nodes in the right frontoparietal network, which is central to cognitive control. The coupling of reward and cognitive control networks may be a mechanism through which earlier onset of substance use is related to brain function over time, a trajectory that may be implicated in subsequent substance use disorders.

CognitiveConstruct

RewardProcessing

10.1037/abn0000081

Journal of abnormal psychology

J Abnorm Psychol

Blunted neural response to rewards as a vulnerability factor for depression: Results from a family study.

Depressive disorders are associated with significant economic and public health burdens as well as increased morbidity. Yet, perhaps due to the heterogeneous nature of the disease, prevention and intervention efforts are only moderately efficacious. A better understanding of core mechanisms of depressive disorders might aid in the development of more targeted intervention, and perhaps help identify individuals at risk. One mechanism that may be particularly important to depressive phenotypes is reward insensitivity. Examination of neurobiological correlates of reward-processing, which should relate more directly to the neuropathology of depression, may be helpful in identifying liability for the disorder. To that end, we used a family study design to examine whether a neural response to rewards is a familial risk factor for depression in a sample of probands with a wide range of internalizing psychopathology, as well as their biological siblings. Event-related potentials were recorded during a simple forced-choice gambling paradigm, in which participants could either win or lose small amounts of money. Lower levels of positive affect in probands predicted a reduced neural response to rewards in siblings, even over and above the sibling's own level of positive and negative affect. Additionally, the neural response to rewards was familial (i.e., correlated among siblings). Combined, these analyses suggest that a blunted neural response to rewards may be useful in identifying individuals vulnerable to depressive illnesses.

CognitiveConstruct

RewardProcessing

10.3109/15622975.2015.1054880

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

World J Biol Psychiatry

Oscillatory responses to reward processing in borderline personality disorder.

Previous electrophysiological studies have confirmed impaired reward processing in patients with BPD. However, it is not clear which aspects of reward processing are affected and which brain regions are involved. The present study investigated both evoked and induced event-related oscillations (EROs) to feedback events (thought to represent different aspects of feedback processing), and used source localization (sLORETA) to assess activity in two areas known to contribute to reward processing, the dorsomedial prefrontal/anterior cingulate cortex (dmPFC/ACC) and the orbitofrontal cortex (OFC). Eighteen patients with BPD and 22 healthy controls performed a gambling task, while 64-channel electroencephalographic activity was recorded. Evoked and induced theta and high-beta band EROs as well as activity in the two regions of interest were investigated depending on the valence and magnitude of feedback events. Theta-band responses to negative feedback were reduced in BPD, an effect that involved only evoked responses and the dmPFC/ ACC region, and was associated with trait impulsivity in patients. sLORETA analyses revealed disturbed evoked responses depending on feedback magnitude in the theta (OFC) and high-beta (dmPFC/ACC and OFC) frequency range. The results indicate multiple dysfunctions of feedback processing in patients with BPD, implicating several distinct subsets of reward-processing mechanisms.

CognitiveConstruct

RewardProcessing

10.1093/ijnp/pyv068

The international journal of neuropsychopharmacology

Int J Neuropsychopharmacol

Effects of Varenicline on Neural Correlates of Alcohol Salience in Heavy Drinkers.

Preclinical and emerging clinical evidence indicates that varenicline, a nicotinic partial agonist approved for smoking cessation, attenuates alcohol seeking and consumption. Reductions of alcohol craving have been observed under varenicline treatment and suggest effects of the medication on alcohol reward processing, but this hypothesis remains untested. In this double-blind, placebo-controlled randomized experimental medicine study, 29 heavy drinkers underwent a functional magnetic resonance imaging scan after 2 weeks of varenicline (2mg/d) or placebo administration. During functional magnetic resonance imaging, participants performed the Alcohol-Food Incentive Delay task, where they could earn points for snacks or alcohol. At baseline and after 3 weeks of medication, participants underwent intravenous alcohol self-administration sessions in the laboratory. During the functional magnetic resonance imaging scan, participants in the varenicline group (N=17) reported lower feelings of happiness and excitement on subjective mood scales when anticipating alcohol reward compared with the placebo group (N=12). Linear mixed effects analysis revealed that anticipation of alcohol reward was associated with significant blood oxygen level dependent activation of the ventral striatum, amygdala, and posterior insula in the placebo group; this activation was attenuated in the varenicline group. The varenicline group showed no difference in intravenous alcohol self-administration relative to the placebo group for either session. Participants with higher insula activation when anticipating alcohol reward showed higher alcohol self-administration behavior across groups. Our findings suggest that varenicline decreases blood oxygen level dependent activation in striato-cortico-limbic regions associated with motivation and incentive salience of alcohol in heavy drinkers. This mechanism may underlie the clinical effectiveness of varenicline in reducing alcohol intake and indicates its potential utility as a pharmacotherapy for alcohol use disorders.

CognitiveConstruct

RewardProcessing

10.1016/j.bcp.2015.07.014

Biochemical pharmacology

Biochem Pharmacol

Cholinergic modulation of dopamine pathways through nicotinic acetylcholine receptors.

Nicotine addiction is highly prevalent in current society and is often comorbid with other diseases. In the central nervous system, nicotine acts as an agonist for nicotinic acetylcholine receptors (nAChRs) and its effects depend on location and receptor composition. Although nicotinic receptors are found in most brain regions, many studies on addiction have focused on the mesolimbic system and its reported behavioral correlates such as reward processing and reinforcement learning. Profound modulatory cholinergic input from the pedunculopontine and laterodorsal tegmentum to dopaminergic midbrain nuclei as well as local cholinergic interneuron projections to dopamine neuron axons in the striatum may play a major role in the effects of nicotine. Moreover, an indirect mesocorticolimbic feedback loop involving the medial prefrontal cortex may be involved in behavioral characteristics of nicotine addiction. Therefore, this review will highlight current understanding of the effects of nicotine on the function of mesolimbic and mesocortical dopamine projections in the mesocorticolimbic circuit.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.1734-15.2015

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

J Neurosci

A Role for the Locus Ceruleus in Reward Processing: Encoding Behavioral Energy Required for Goal-Directed Actions.

CognitiveConstruct

RewardProcessing

10.1093/schbul/sbv093

Schizophrenia bulletin

Schizophr Bull

Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia.

Amotivation and reward-processing deficits have long been described in patients with schizophrenia and considered large contributors to patients' inability to integrate well in society. No effective treatments exist for these symptoms, partly because the neuromechanisms mediating such symptoms are poorly understood. Here, we propose a translational neuroscientific approach that can be used to assess reward/motivational deficits related to the negative symptoms of schizophrenia using behavioral paradigms that can also be conducted in experimental animals. By designing and using objective laboratory behavioral tools that are parallel in their parameters in rodents and humans, the neuromechanisms underlying behaviors with relevance to these symptoms of schizophrenia can be investigated. We describe tasks that measure the motivation of rodents to expend physical and cognitive effort to gain rewards, as well as probabilistic learning tasks that assess both reward learning and feedback-based decision making. The latter tasks are relevant because of demonstrated links of performance deficits correlating with negative symptoms in patients with schizophrenia. These tasks utilize operant techniques in order to investigate neural circuits targeting a specific domain across species. These tasks therefore enable the development of insights into altered mechanisms leading to negative symptom-relevant behaviors in patients with schizophrenia. Such findings will then enable the development of targeted treatments for these altered neuromechanisms and behaviors seen in schizophrenia.

CognitiveConstruct

RewardProcessing

10.1016/j.pnpbp.2015.07.006

Progress in neuro-psychopharmacology & biological psychiatry

Prog Neuropsychopharmacol Biol Psychiatry

Diminished caudate and superior temporal gyrus responses to effort-based decision making in patients with first-episode major depressive disorder.

Anhedonia, the loss of interest or pleasure in reward processing, is a hallmark feature of major depressive disorder (MDD), but its underlying neurobiological mechanism is largely unknown. The present study aimed to examine the underlying neural mechanism of reward-related decision-making in patients with MDD. We examined behavioral and neural responses to rewards in patients with first-episode MDD (N=25) and healthy controls (N=25) using the Effort-Expenditure for Rewards Task (EEfRT). The task involved choices about possible rewards of varying magnitude and probability. We tested the hypothesis that individuals with MDD would exhibit a reduced neural response in reward-related brain structures involved in cost-benefit decision-making. Compared with healthy controls, patients with MDD showed significantly weaker responses in the left caudate nucleus when contrasting the 'high reward'-'low reward' condition, and blunted responses in the left superior temporal gyrus and the right caudate nucleus when contrasting high and low probabilities. In addition, hard tasks chosen during high probability trials were negatively correlated with superior temporal gyrus activity in MDD patients, while the same choices were negatively correlated with caudate nucleus activity in healthy controls. These results indicate that reduced caudate nucleus and superior temporal gyrus activation may underpin abnormal cost-benefit decision-making in MDD.

CognitiveConstruct

RewardProcessing

10.3389/fpsyt.2015.00093

Frontiers in psychiatry

Front Psychiatry

A Positive Affective Neuroendocrinology Approach to Reward and Behavioral Dysregulation.

Emerging lines of research suggest that both testosterone and maladaptive reward processing can modulate behavioral dysregulation. Yet, to date, no integrative account has been provided that systematically explains neuroendocrine function, dysregulation of reward, and behavioral dysregulation in a unified perspective. This is particularly important given specific neuroendocrine systems are potential mechanisms underlying and giving rise to reward-relevant behaviors. In this review, we propose a forward-thinking approach to study the mechanisms of reward and behavioral dysregulation from a positive affective neuroendocrinology (PANE) perspective. This approach holds that testosterone increases reward processing and motivation, which increase the likelihood of behavioral dysregulation. Additionally, the PANE framework holds that reward processing mediates the effects of testosterone on behavioral dysregulation. We also explore sources of potential sex differences and the roles of age, cortisol, and individual differences within the PANE framework. Finally, we discuss future prospects for research questions and methodology in the emerging field of affective neuroendocrinology.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2015.06.004

Developmental cognitive neuroscience

Dev Cogn Neurosci

Reduced cerebellar brain activity during reward processing in adolescent binge drinkers.

Due to ongoing development, adolescence may be a period of heightened vulnerability to the neurotoxic effects of alcohol. Binge drinking may alter reward-driven behavior and neurocircuitry, thereby increasing risk for escalating alcohol use. Therefore, we compared reward processing in adolescents with and without a history of recent binge drinking. At their baseline study visit, all participants (age=14.86 ± 0.88) were free of heavy alcohol use and completed a modified version of the Wheel of Fortune (WOF) functional magnetic resonance imaging task. Following this visit, 17 youth reported binge drinking on ≥3 occasions within a 90 day period and were matched to 17 youth who remained alcohol and substance-naïve. All participants repeated the WOF task during a second visit (age=16.83 ± 1.22). No significant effects were found in a region of interest analysis of the ventral striatum, but whole-brain analyses showed significant group differences in reward response at the second study visit in the left cerebellum, controlling for baseline visit brain activity (p/α<0.05), which was negatively correlated with mean number of drinks consumed/drinking day in the last 90 days. These findings suggest that binge drinking during adolescence may alter brain activity during reward processing in a dose-dependent manner.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsycho.2015.07.001

Biological psychology

Biol Psychol

Brain activity elicited by reward and reward omission in individuals with psychopathic traits: An ERP study.

Psychopathy has been associated with behavioral adaptation deficits, which might be associated with problems in feedback and reward processing. In the present study, we examined the relation between psychopathic traits and reward processing in a passive gambling task. A total of 39 male participants who scored high (HP) and 39 male participants who scored low (LP) on the Triarchic Psychopathy Measure (TriPM), total score were tested. Feedback-related Event-Related Potentials (ERPs; i.e., P2, FRN, and P3) on predicted and unpredicted rewards and reward omissions were compared between both groups. It was found that in HP individuals, the P2 was enhanced for predicted rewards and reward omissions, but not for unpredicted stimuli. Moreover, HP individuals as compared to the LP individuals demonstrated a generally reduced P3 amplitude. The FRN amplitude, however, did not differ between the two groups. In addition, HP individuals showed enhanced reward sensitivity on the self-report level. Taken together, these findings suggest that HP individuals show enhanced sensitivity to early and reduced sensitivity to later markers of processing reinforcement learning signals, which points in the direction of compromised behavioral adaptation.

CognitiveConstruct

RewardProcessing

10.1176/appi.ajp.2015.14050594

The American journal of psychiatry

Am J Psychiatry

Moderation of the Relationship Between Reward Expectancy and Prediction Error-Related Ventral Striatal Reactivity by Anhedonia in Unmedicated Major Depressive Disorder: Findings From the EMBARC Study.

Anhedonia, disrupted reward processing, is a core symptom of major depressive disorder. Recent findings demonstrate altered reward-related ventral striatal reactivity in depressed individuals, but the extent to which this is specific to anhedonia remains poorly understood. The authors examined the effect of anhedonia on reward expectancy (expected outcome value) and prediction error- (discrepancy between expected and actual outcome) related ventral striatal reactivity, as well as the relationship between these measures. A total of 148 unmedicated individuals with major depressive disorder and 31 healthy comparison individuals recruited for the multisite EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study underwent functional MRI during a well-validated reward task. Region of interest and whole-brain data were examined in the first- (N=78) and second- (N=70) recruited cohorts, as well as the total sample, of depressed individuals, and in healthy individuals. Healthy, but not depressed, individuals showed a significant inverse relationship between reward expectancy and prediction error-related right ventral striatal reactivity. Across all participants, and in depressed individuals only, greater anhedonia severity was associated with a reduced reward expectancy-prediction error inverse relationship, even after controlling for other symptoms. The normal reward expectancy and prediction error-related ventral striatal reactivity inverse relationship concords with conditioning models, predicting a shift in ventral striatal responding from reward outcomes to reward cues. This study shows, for the first time, an absence of this relationship in two cohorts of unmedicated depressed individuals and a moderation of this relationship by anhedonia, suggesting reduced reward-contingency learning with greater anhedonia. These findings help elucidate neural mechanisms of anhedonia, as a step toward identifying potential biosignatures of treatment response.

CognitiveConstruct

RewardProcessing

10.1177/1073858415595005

The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry

Neuroscientist

How Has the Internet Reshaped Human Cognition?

Throughout our evolutionary history, our cognitive systems have been altered by the advent of technological inventions such as primitive tools, spoken language, writing, and arithmetic systems. Thirty years ago, the Internet surfaced as the latest technological invention poised to deeply reshape human cognition. With its multifaceted affordances, the Internet environment has profoundly transformed our thoughts and behaviors. Growing up with Internet technologies, "Digital Natives" gravitate toward "shallow" information processing behaviors characterized by rapid attention shifting and reduced deliberations. They engage in increased multitasking behaviors that are linked to increased distractibility and poor executive control abilities. Digital natives also exhibit higher prevalence of Internet-related addictive behaviors that reflect altered reward-processing and self-control mechanisms. Recent neuroimaging investigations have suggested associations between these Internet-related cognitive impacts and structural changes in the brain. Against mounting apprehension over the Internet's consequences on our cognitive systems, several researchers have lamented that these concerns were often exaggerated beyond existing scientific evidence. In the present review, we aim to provide an objective overview of the Internet's impacts on our cognitive systems. We critically discuss current empirical evidence about how the Internet environment has altered the cognitive behaviors and structures involved in information processing, executive control, and reward-processing.

CognitiveConstruct

RewardProcessing

10.1017/S0033291715001075

Psychological medicine

Psychol Med

Cognitive control, reward-related decision making and outcomes of late-life depression treated with an antidepressant.

Executive processes consist of at least two sets of functions: one concerned with cognitive control and the other with reward-related decision making. Abnormal performance in both sets occurs in late-life depression. This study tested the hypothesis that only abnormal performance in cognitive control tasks predicts poor outcomes of late-life depression treated with escitalopram. We studied older subjects with major depression (N = 53) and non-depressed subjects (N = 30). Executive functions were tested with the Iowa Gambling Test (IGT), Stroop Color-Word Test, Tower of London (ToL), and Dementia Rating Scale - Initiation/Perseveration domain (DRS-IP). After a 2-week placebo washout, depressed subjects received escitalopram (target daily dose: 20 mg) for 12 weeks. There were no significant differences between depressed and non-depressed subjects on executive function tests. Hierarchical cluster analysis of depressed subjects identified a Cognitive Control cluster (abnormal Stroop, ToL, DRS-IP), a Reward-Related cluster (IGT), and an Executively Unimpaired cluster. Decline in depression was greater in the Executively Unimpaired (t = -2.09, df = 331, p = 0.0375) and the Reward-Related (t = -2.33, df = 331, p = 0.0202) clusters than the Cognitive Control cluster. The Executively Unimpaired cluster (t = 2.17, df = 331, p = 0.03) and the Reward-Related cluster (t = 2.03, df = 331, p = 0.0433) had a higher probability of remission than the Cognitive Control cluster. Dysfunction of cognitive control functions, but not reward-related decision making, may influence the decline of symptoms and the probability of remission of late-life depression treated with escitalopram. If replicated, simple to administer cognitive control tests may be used to select depressed older patients at risk for poor outcomes to selective serotonin reuptake inhibitors who may require structured psychotherapy.

CognitiveConstruct

RewardProcessing

10.1017/S1355617715000491

Journal of the International Neuropsychological Society : JINS

J Int Neuropsychol Soc

Striatal and Pallidal Activation during Reward Modulated Movement Using a Translational Paradigm.

Human neuroimaging studies of reward processing typically involve tasks that engage decision-making processes in the dorsal striatum or focus upon the ventral striatum's response to feedback expectancy. These studies are often compared to the animal literature; however, some animal studies include both feedback and nonfeedback events that activate the dorsal striatum during feedback expectancy. Differences in task parameters, movement complexity, and motoric effort to attain rewards may partly explain ventral and dorsal striatal response differences across species. We, therefore, used a target capture task during functional neuroimaging that was inspired by a study of single cell modulation in the internal globus pallidus during reward-cued, rotational arm movements in nonhuman primates. In this functional magnetic resonance imaging study, participants used a fiberoptic joystick to make a rotational response to an instruction stimulus that indicated both a target location for a capture movement and whether or not the trial would end with feedback indicating either a small financial gain or a neutral outcome. Portions of the dorsal striatum and pallidum demonstrated greater neural activation to visual cues predicting potential gains relative to cues with no associated outcome. Furthermore, both striatal and pallidal regions displayed a greater response to financial gains relative to neutral outcomes. This reward-dependent modulation of dorsal striatal and pallidal activation in a target-capture task is consistent with findings from reward studies in animals, supporting the use of motorically complex tasks as translational paradigms to investigate the neural substrates of reward expectancy and outcome in humans.

CognitiveConstruct

RewardProcessing

10.1016/j.neulet.2015.06.054

Neuroscience letters

Neurosci Lett

Sensitivity of frontal beta oscillations to reward valence but not probability.

Reward feedback elicits a brief increase in power in the high-beta frequency range of the human electroencephalogram (EEG) over frontal areas of the scalp, but the functional role of this oscillatory activity remains unclear. An observed sensitivity to reward expectation (HajiHosseini, Rodríguez-Fornells, and Marco-Pallarés, 2012; [2]) suggests that reward-related beta may index a reward prediction error (RPE) signal for reinforcement learning. To investigate this possibility we reanalyzed EEG data from two prior experiments that revealed RPEs in the human event-related brain potential (Holroyd and Krigolson, 2007 [12]; Holroydet al., 2008 [13]). We found that feedback stimuli that indicated reward, when compared to feedback stimuli that indicated no-reward, elicited relatively more beta power (20-30 Hz) over a frontal area of the scalp. However, beta power was not sensitive to feedback probability. These results indicate that reward-related beta does not index an RPE but rather relates to a different reward processing function.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2015.06.002

Developmental cognitive neuroscience

Dev Cogn Neurosci

Feedback associated with expectation for larger-reward improves visuospatial working memory performances in children with ADHD.

We tested the interactive effect of feedback and reward on visuospatial working memory in children with ADHD. Seventeen boys with ADHD and 17 Normal Control (NC) boys underwent functional magnetic resonance imaging (fMRI) while performing four visuospatial 2-back tasks that required monitoring the spatial location of letters presented on a display. Tasks varied in reward size (large; small) and feedback availability (no-feedback; feedback). While the performance of NC boys was high in all conditions, boys with ADHD exhibited higher performance (similar to those of NC boys) only when they received feedback associated with large-reward. Performance pattern in both groups was mirrored by neural activity in an executive function neural network comprised of few distinct frontal brain regions. Specifically, neural activity in the left and right middle frontal gyri of boys with ADHD became normal-like only when feedback was available, mainly when feedback was associated with large-reward. When feedback was associated with small-reward, or when large-reward was expected but feedback was not available, boys with ADHD exhibited altered neural activity in the medial orbitofrontal cortex and anterior insula. This suggests that contextual support normalizes activity in executive brain regions in children with ADHD, which results in improved working memory.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2015.06.059

NeuroImage

Neuroimage

Psychosocial versus physiological stress - Meta-analyses on deactivations and activations of the neural correlates of stress reactions.

Stress is present in everyday life in various forms and situations. Two stressors frequently investigated are physiological and psychosocial stress. Besides similar subjective and hormonal responses, it has been suggested that they also share common neural substrates. The current study used activation-likelihood-estimation meta-analysis to test this assumption by integrating results of previous neuroimaging studies on stress processing. Reported results are cluster-level FWE corrected. The inferior frontal gyrus (IFG) and the anterior insula (AI) were the only regions that demonstrated overlapping activation for both stressors. Analysis of physiological stress showed consistent activation of cognitive and affective components of pain processing such as the insula, striatum, or the middle cingulate cortex. Contrarily, analysis across psychosocial stress revealed consistent activation of the right superior temporal gyrus and deactivation of the striatum. Notably, parts of the striatum appeared to be functionally specified: the dorsal striatum was activated in physiological stress, whereas the ventral striatum was deactivated in psychosocial stress. Additional functional connectivity and decoding analyses further characterized this functional heterogeneity and revealed higher associations of the dorsal striatum with motor regions and of the ventral striatum with reward processing. Based on our meta-analytic approach, activation of the IFG and the AI seems to indicate a global neural stress reaction. While physiological stress activates a motoric fight-or-flight reaction, during psychosocial stress attention is shifted towards emotion regulation and goal-directed behavior, and reward processing is reduced. Our results show the significance of differentiating physiological and psychosocial stress in neural engagement. Furthermore, the assessment of deactivations in addition to activations in stress research is highly recommended.

CognitiveConstruct

RewardProcessing

10.1016/j.cortex.2015.05.027

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

Cortex

Neural correlates of observing joint actions with shared intentions.

Studies on the neural bases of action perception have largely focused on the perception of individual actions. Little is known about perception of joint actions where two or more individuals coordinate their actions based on a shared intention. In this fMRI study we asked whether observing situations where two individuals act on a shared intention elicits a different neural response than observing situations where individuals act on their independent parallel intentions. We compared the neural response to perceptually identical yet intentionally ambiguous actions observed in varying contexts. A dialog between two individuals conveyed either a shared intention or two independent parallel intentions. The dialogs were followed by an identical video clip where the two individuals performed certain actions. In one task condition participants tracked the intentions of the actors, in the other, they monitored moving colored dots placed on the same videos. We found that in the intention task versus the color task, observing joint actions based on shared intentions activated the temporal poles, precuneus, and the ventral striatum compared to observing interactions based on parallel intentions. Precuneus and the temporal poles are thought to support mental state reasoning, the latter with a more specific role in retrieving memories associated with social scripts. Activation in the ventral striatum, an area involved in reward processing, likely indicates a hedonistic response to observed shared intentional relations similarly to those experienced when personally sharing mental states with others.

CognitiveConstruct

RewardProcessing

10.1503/jpn.140249

Journal of psychiatry & neuroscience : JPN

J Psychiatry Neurosci

Elevated cognitive control over reward processing in recovered female patients with anorexia nervosa.

Individuals with anorexia nervosa are thought to exert excessive self-control to inhibit primary drives. This study used functional MRI (fMRI) to interrogate interactions between the neural correlates of cognitive control and motivational processes in the brain reward system during the anticipation of monetary reward and reward-related feedback. In order to avoid confounding effects of undernutrition, we studied female participants recovered from anorexia nervosa and closely matched healthy female controls. The fMRI analysis (including node-to-node functional connectivity) followed a region of interest approach based on models of the brain reward system and cognitive control regions implicated in anorexia nervosa: the ventral striatum, medial orbitofrontal cortex (mOFC) and dorsolateral prefrontal cortex (DLPFC). We included 30 recovered patients and 30 controls in our study. There were no behavioural differences and no differences in hemodynamic responses of the ventral striatum and the mOFC in the 2 phases of the task. However, relative to controls, recovered patients showed elevated DLPFC activity during the anticipation phase, failed to deactivate this region during the feedback phase and displayed greater functional coupling between the DLPFC and mOFC. Recovered patients also had stronger associations than controls between anticipation-related DLPFC responses and instrumental responding. The results we obtained using monetary stimuli might not generalize to other forms of reward. Unaltered neural responses in ventral limbic reward networks but increased recruitment of and connectivity with lateral-frontal brain circuitry in recovered patients suggests an elevated degree of selfregulatory processes in response to rewarding stimuli. An imbalance between brain systems subserving bottom-up and top-down processes may be a trait marker of the disorder.

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2015.04.018

NeuroImage. Clinical

Neuroimage Clin

Cortical thickness, surface area, and folding alterations in male youths with conduct disorder and varying levels of callous-unemotional traits.

Previous studies have reported changes in gray matter volume in youths with conduct disorder (CD), although these differences are difficult to interpret as they may have been driven by alterations in cortical thickness, surface area (SA), or folding. The objective of this study was to use surface-based morphometry (SBM) methods to compare male youths with CD and age and sex-matched healthy controls (HCs) in cortical thickness, SA, and folding. We also tested for structural differences between the childhood-onset and adolescence-onset subtypes of CD and performed regression analyses to assess for relationships between CD symptoms and callous-unemotional (CU) traits and SBM-derived measures. We acquired structural neuroimaging data from 20 HCs and 36 CD participants (18 with childhood-onset CD and 18 with adolescence-onset CD) and analyzed the data using FreeSurfer. Relative to HCs, youths with CD showed reduced cortical thickness in the superior temporal gyrus, reduced SA in the orbitofrontal cortex (OFC), and increased cortical folding in the insula. There were no significant differences between the childhood-onset and adolescence-onset CD subgroups in cortical thickness or SA, but several frontal and temporal regions showed increased cortical folding in childhood-onset relative to adolescence-onset CD participants. Both CD subgroups also showed increased cortical folding relative to HCs. CD symptoms were negatively correlated with OFC SA whereas CU traits were positively correlated with insula folding. Cortical thinning in the superior temporal gyrus may contribute to the social cognitive impairments displayed by youths with CD, whereas reduced OFC SA may lead to impairments in emotion regulation and reward processing in youths with CD. The increased cortical folding observed in the insula may reflect a maturational delay in this region and could mediate the link between CU traits and empathy deficits. Altered cortical folding was observed in childhood-onset and adolescence-onset forms of CD.

CognitiveConstruct

RewardProcessing

10.1017/S1092852915000383

CNS spectrums

CNS Spectr

Overlapping neurobehavioral circuits in ADHD, obesity, and binge eating: evidence from neuroimaging research.

Attention-deficit/hyperactivity disorder (ADHD) and conditions involving excessive eating (eg, obesity, binge/loss of control eating) are increasingly prevalent within pediatric populations, and correlational and some longitudinal studies have suggested inter-relationships between these disorders. In addition, a number of common neural correlates are emerging across conditions, eg, functional abnormalities within circuits subserving reward processing and executive functioning. To explore this potential cross-condition overlap in neurobehavioral underpinnings, we selectively review relevant functional neuroimaging literature, specifically focusing on studies probing (i) reward processing, (ii) response inhibition, and (iii) emotional processing and regulation, and we outline 3 specific shared neurobehavioral circuits. Based on our review, we also identify gaps within the literature that would benefit from further research.

CognitiveConstruct

RewardProcessing

10.1111/gbb.12228

Genes, brain, and behavior

Genes Brain Behav

Replication study implicates COMT val158met polymorphism as a modulator of probabilistic reward learning.

Previous studies suggest that a single nucleotide polymorphism in the catechol-O-methyltransferase (COMT) gene (val158met) may modulate reward-guided decision making in healthy individuals. The polymorphism affects dopamine catabolism and thus modulates prefrontal dopamine levels, which may lead to variation in individual responses to risk and reward. We previously showed, using tasks that index reward responsiveness (measured by responses bias towards reinforced stimuli) and risk taking (measured by the Balloon Analogue Risk Task), that COMT met homozygotes had increased reward responsiveness and, thus, an increased propensity to seek reward. In this study, we sought to replicate these effects in a larger, independent cohort of Caucasian UK university students and staff with similar demographic characteristics (n = 101; 54 females, mean age: 22.2 years). Similarly to our previous study, we observed a significant trial × COMT genotype interaction (P = 0.047; η(2) = 0.052), which was driven by a significant effect of COMT on the incremental acquisition of response bias [response bias at block 3 - block 1 (met/met > val/val: P = 0.028) and block 3 - block 2 (met/met > val/val: P = 0.007)], suggesting that COMT met homozygotes demonstrated higher levels of reward responsiveness by the end of the task. However, we failed to see main effects of COMT genotype on overall response bias or risk-seeking behaviour. These results provide additional evidence that prefrontal dopaminergic variation may have a role in reward responsiveness, but not risk-seeking behaviour. Our findings may have implications for neuropsychiatric disorders characterized by clinical deficits in reward processing such as anhedonia.

CognitiveConstruct

RewardProcessing

10.1097/QAD.0000000000000680

AIDS (London, England)

AIDS

HIV infection results in ventral-striatal reward system hypo-activation during cue processing.

Functional MRI has thus far demonstrated that HIV has an impact on frontal-striatal systems involved in executive functioning. The potential impact of HIV on frontal-striatal systems involved in reward processing has yet to be examined by functional MRI. This study therefore aims to investigate the effects of HIV infection on reward processing by examining the function of the ventral-striatal reward system during a monetary incentive delay task. This is a cross-sectional case-control study. Eighteen combined antiretroviral therapy-naive HIV-positive (HIV+) participants, as well as 16 matched healthy controls, performed a monetary incentive delay task. This paradigm assesses behaviour as well as functional brain activity-associated reward anticipation and reward outcome. HIV+ participants showed a general decrease in activation associated with both neutral as well as potentially rewarding cues in their ventral striatum. We found normal activity related to reward outcome in the orbito-frontal cortex. Despite HIV+ participants' reaction times being significantly slower when independently measured from the reward paradigm, this performance deficit normalized during the performance of the reward task. HIV caused a decrease in activity during cue processing in the ventral striatum, with normal cortical functioning during reward outcome processing. Our results therefore suggest that HIV not only has an impact on fronto-striatal systems involved in executive functioning, but also has a direct impact on the function of the ventral-striatal reward system.

CognitiveConstruct

RewardProcessing

10.1038/npp.2015.172

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Greater Insula White Matter Fiber Connectivity in Women Recovered from Anorexia Nervosa.

Anorexia nervosa is a severe psychiatric disorder associated with reduced drive to eat. Altered taste-reward circuit white matter fiber organization in anorexia nervosa after recovery could indicate a biological marker that alters the normal motivation to eat. Women recovered from restricting-type anorexia (Recovered AN, n = 24, age = 30.3 ± 8.1 years) and healthy controls (n = 24, age = 27.4 ± 6.3 years) underwent diffusion weighted imaging of the brain. Probabilistic tractography analyses calculated brain white matter connectivity (streamlines) as an estimate of fiber connections in taste-reward-related white matter tracts, and microstructural integrity (fractional anisotropy, FA) was assessed using tract-based spatial statistics. Recovered AN showed significantly (range P<0.05-0.001, Bonferroni corrected) greater white matter connectivity between bilateral insula regions and ventral striatum, left insula and middle orbitofrontal cortex (OFC), and right insula projecting to gyrus rectus and medial OFC. Duration of illness predicted connectivity of tracts projecting from the insula to ventral striatum and OFC. Microstructural integrity was lower in Recovered AN in most insula white matter tracts, as was whole-brain FA in parts of the anterior corona radiata, external capsule, and cerebellum (P<0.05, family-wise error-corrected). This study indicates higher structural white matter connectivity, an estimate of fibers connections, in anorexia after recovery in tracts that connect taste-reward processing regions. Greater connectivity together with less-fiber integrity could indicate altered neural activity between those regions, which could interfere with normal food-reward circuit function. Correlations between connectivity and illness duration suggest that connectivity could be a marker for illness severity. Whether greater connectivity can predict prognosis of the disorder requires further study.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0127010

PloS one

PLoS One

Attenuated Neural Processing of Risk in Young Adults at Risk for Stimulant Dependence.

Approximately 10% of young adults report non-medical use of stimulants (cocaine, amphetamine, methylphenidate), which puts them at risk for the development of dependence. This fMRI study investigates whether subjects at early stages of stimulant use show altered decision making processing. 158 occasional stimulants users (OSU) and 50 comparison subjects (CS) performed a "risky gains" decision making task during which they could select safe options (cash in 20 cents) or gamble them for double or nothing in two consecutive gambles (win or lose 40 or 80 cents, "risky decisions"). The primary analysis focused on risky versus safe decisions. Three secondary analyses were conducted: First, a robust regression examined the effect of lifetime exposure to stimulants and marijuana; second, subgroups of OSU with >1000 (n = 42), or <50 lifetime marijuana uses (n = 32), were compared to CS with <50 lifetime uses (n = 46) to examine potential marijuana effects; third, brain activation associated with behavioral adjustment following monetary losses was probed. There were no behavioral differences between groups. OSU showed attenuated activation across risky and safe decisions in prefrontal cortex, insula, and dorsal striatum, exhibited lower anterior cingulate cortex (ACC) and dorsal striatum activation for risky decisions and greater inferior frontal gyrus activation for safe decisions. Those OSU with relatively more stimulant use showed greater dorsal ACC and posterior insula attenuation. In comparison, greater lifetime marijuana use was associated with less neural differentiation between risky and safe decisions. OSU who chose more safe responses after losses exhibited similarities with CS relative to those preferring risky options. Individuals at risk for the development of stimulant use disorders presented less differentiated neural processing of risky and safe options. Specifically, OSU show attenuated brain response in regions critical for performance monitoring, reward processing and interoceptive awareness. Marijuana had additive effects by diminishing neural risk differentiation.

CognitiveConstruct

RewardProcessing

10.1016/j.dcn.2015.05.005

Developmental cognitive neuroscience

Dev Cogn Neurosci

Does incentive-elicited nucleus accumbens activation differ by substance of abuse? An examination with adolescents.

Numerous questions surround the nature of reward processing in the developing adolescent brain, particularly in regard to polysubstance use. We therefore sought to examine incentive-elicited brain activation in the context of three common substances of abuse (cannabis, tobacco, and alcohol). Due to the role of the nucleus accumbens (NAcc) in incentive processing, we compared activation in this region during anticipation of reward and loss using a monetary incentive delay (MID) task. Adolescents (ages 14-18; 66% male) were matched on age, gender, and frequency of use of any common substances within six distinct groups: cannabis-only (n=14), tobacco-only (n=34), alcohol-only (n=12), cannabis+tobacco (n=17), cannabis+tobacco+alcohol (n=17), and non-using controls (n=38). All groups showed comparable behavioral performance on the MID task. The tobacco-only group showed decreased bilateral nucleus accumbens (NAcc) activation during reward anticipation as compared to the alcohol-only group, the control group, and both polysubstance groups. Interestingly, no differences emerged between the cannabis-only group and any of the other groups. Results from this study suggest that youth who tend toward single-substance tobacco use may possess behavioral and/or neurobiological characteristics that differentiate them from both their substance-using and non-substance-using peers.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2015.05.095

NeuroImage

Neuroimage

Beta oscillations and reward processing: Coupling oscillatory activity and hemodynamic responses.

Diverse cortical and subcortical regions are synergically engaged during reward processing. Previous studies using time-frequency decomposition of Electroencephalography (EEG) data have revealed an increase of mid-frontal beta oscillatory activity (BOA) after reward delivery, which could be a potential mechanism in the coordination of the different areas engaged during reward processing. In order to evaluate this hypothesis, twenty subjects performed a monetary gambling paradigm in two separate sessions (EEG and fMRI). Time-frequency oscillatory EEG data and fMRI activity were fused using Joint Independent Component Analysis (ICA). The present results showed that mid-frontal BOA elicited by monetary gains is associated with the engagement of a fronto-striatal-hippocampal network previously involved in reward-related memory enhancement, supporting the role of this activity during reward processing.

CognitiveConstruct

RewardProcessing

10.1016/j.drugalcdep.2015.04.019

Drug and alcohol dependence

Drug Alcohol Depend

Acute opioid withdrawal is associated with increased neural activity in reward-processing centers in healthy men: A functional magnetic resonance imaging study.

Opioid analgesics are frequently prescribed for chronic pain. One expected consequence of long-term opioid use is the development of physical dependence. Although previous resting state functional magnetic resonance imaging (fMRI) studies have demonstrated signal changes in reward-associated areas following morphine administration, the effects of acute withdrawal on the human brain have been less well-investigated. In an earlier study by our laboratory, ondansetron was shown to be effective in preventing symptoms associated with opioid withdrawal. The purpose of this current study was to characterize neural activity associated with acute opioid withdrawal and examine whether these changes are modified by ondansetron. Ten participants were enrolled in this placebo-controlled, randomized, double-blind, crossover study and attended three acute opioid withdrawal sessions. Participants received either placebo or ondansetron (8Ymg IV) before morphine administration (10Ymg/70Ykg IV). Participants then underwent acute naloxone-precipitated withdrawal during a resting state fMRI scan. Objective and subjective opioid withdrawal symptoms were assessed. Imaging results showed that naloxone-precipitated opioid withdrawal was associated with increased neural activity in several reward processing regions, including the right pregenual cingulate, putamen, and bilateral caudate, and decreased neural activity in networks involved in sensorimotor integration. Ondansetron pretreatment did not have a significant effect on the imaging correlates of opioid withdrawal. This study presents a preliminary investigation of the regional changes in neural activity during acute opioid withdrawal. The fMRI acute opioid withdrawal model may serve as a tool for studying opioid dependence and withdrawal in human participants.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsycho.2015.06.002

Biological psychology

Biol Psychol

Performance monitoring and empathy during active and observational learning in patients with major depression.

Previous literature established a link between major depressive disorder (MDD) and altered reward processing as well as between empathy and (observational) reward learning. The aim of the present study was to assess the effects of MDD on the electrophysiological correlates - the feedback-related negativity (FRN) and the P300 - of active and observational reward processing and to relate them to trait cognitive and affective empathy. Eighteen patients with MDD and 16 healthy controls performed an active and an observational probabilistic reward-learning task while event- related potentials were recorded. Also, participants were assessed with regard to self-reported cognitive and affective trait empathy. Relative to healthy controls, patients with MDD showed overall impaired learning and attenuated FRN amplitudes, irrespective of feedback valence and learning type (active vs. observational), but comparable P300 amplitudes. In the patient group, but not in controls, higher trait perspective taking scores were significantly correlated with reduced FRN amplitudes. The pattern of results suggests impaired prediction error processing and a negative effect of higher trait empathy on feedback-based learning in patients with MDD.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0129516

PloS one

PLoS One

Risk-Taking Behavior in a Computerized Driving Task: Brain Activation Correlates of Decision-Making, Outcome, and Peer Influence in Male Adolescents.

Increased propensity for risky behavior in adolescents, particularly in peer groups, is thought to reflect maturational imbalance between reward processing and cognitive control systems that affect decision-making. We used functional magnetic resonance imaging (fMRI) to investigate brain functional correlates of risk-taking behavior and effects of peer influence in 18-19-year-old male adolescents. The subjects were divided into low and high risk-taking groups using either personality tests or risk-taking rates in a simulated driving task. The fMRI data were analyzed for decision-making (whether to take a risk at intersections) and outcome (pass or crash) phases, and for the influence of peer competition. Personality test-based groups showed no difference in the amount of risk-taking (similarly increased during peer competition) and brain activation. When groups were defined by actual task performance, risk-taking activated two areas in the left medial prefrontal cortex (PFC) significantly more in low than in high risk-takers. In the entire sample, risky decision-specific activation was found in the anterior and dorsal cingulate, superior parietal cortex, basal ganglia (including the nucleus accumbens), midbrain, thalamus, and hypothalamus. Peer competition increased outcome-related activation in the right caudate head and cerebellar vermis in the entire sample. Our results suggest that the activation of the medial (rather than lateral) PFC and striatum is most specific to risk-taking behavior of male adolescents in a simulated driving situation, and reflect a stronger conflict and thus increased cognitive effort to take risks in low risk-takers, and reward anticipation for risky decisions, respectively. The activation of the caudate nucleus, particularly for the positive outcome (pass) during peer competition, further suggests enhanced reward processing of risk-taking under peer influence.

CognitiveConstruct

RewardProcessing

10.1007/s11682-015-9414-4

Brain imaging and behavior

Brain Imaging Behav

Anhedonia in combat veterans with penetrating head injury.

Anhedonia is a common symptom following traumatic brain injury. The neural basis of anhedonia is poorly understood, but believed to involve disturbed reward processing, rather than the loss of sense of pleasure. This analysis was undertaken to determine if injury to specific regions of prefrontal cortex (PFC) result in anhedonia. A CT-based lesion analysis was undertaken in 192 participants of the Vietnam Head Injury Study, most with penetrating head injury. Participants were divided into left and right ventrolateral prefrontal, bilateral ventromedial prefrontal, and other injury locations. Anhedonia was measured by self-report in each group using the four-item anhedonia subscale score of the Beck Depression Inventory-II. Individuals with right ventrolateral injury reported greater severity of anhedonia compared to those with injury in the left ventrolateral region. These findings support an association between injury in the right ventrolateral PFC and anhedonia.

CognitiveConstruct

RewardProcessing

10.1093/schbul/sbv075

Schizophrenia bulletin

Schizophr Bull

Impaired Activation in Cognitive Control Regions Predicts Reversal Learning in Schizophrenia.

Reinforcement learning deficits have been associated with schizophrenia (SZ). However, the pathophysiology that gives rise to these abnormalities remains unclear. To address this question, SZ patients (N = 58) and controls (CN; N = 36) completed a probabilistic reversal-learning paradigm during functional magnetic resonance imaging scanning. During the task, participants choose between 2 stimuli. Initially, 1 stimulus was frequently rewarded (80%); the other was infrequently rewarded (20%). The reward contingencies reversed periodically because the participant learned the more rewarded stimulus. The results indicated that SZ patients achieved fewer reversals than CN, and demonstrated decreased winstay-loseshift decision-making behavior. On loseshift compared to winstay trials, SZ patients showed reduced Blood Oxygen Level Dependent activation compared to CN in a network of brain regions widely associated with cognitive control, and striatal regions. Importantly, relationships between group membership and behavior were mediated by alterations in the activity of cognitive control regions, but not striatum. These findings indicate an important role for the cognitive control network in mediating the use and updating of value representations in SZ. Such results provide biological targets for further inquiry because researchers attempt to better characterize decision-making neural circuitry in SZ as a means to discover new pathways for interventions.

CognitiveConstruct

RewardProcessing