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10.1111/psyp.12855

Psychophysiology

Psychophysiology

Reward processing in gain versus loss context: An ERP study.

Previous research has shown that consummatory ERP components are sensitive to contextual valence. The present study investigated the contextual valence effect across anticipatory and consummatory phases by requiring participants to play a simple gambling task during a gain context and a loss context. During the anticipatory phase, the cue-P3 was more positive in the gain context compared to the loss context, whereas the stimulus-preceding negativity (SPN) was comparable across the two contexts. With respect to the consummatory phase, the feedback-related negativity (FRN) in response to the zero-value outcome was more negative in the gain versus loss context, whereas the feedback P3 (fb-P3) in response to the zero-value outcome was insensitive to contextual valence. These findings suggest that contextual valence effect occurs at a relative early stage of both the reward anticipation and consumption. Moreover, across the gain and loss contexts, the SPN was selectively correlated with the FRN, whereas the cue-P3 was selectively associated with the fb-P3, pointing to a close association between the anticipatory and consummatory phases in reward dynamics.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0173872

PloS one

PLoS One

Bupropion for the treatment of apathy in Huntington's disease: A multicenter, randomised, double-blind, placebo-controlled, prospective crossover trial.

To evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington's disease (HD). In this phase 2b multicentre, double-blind, placebo-controlled crossover trial, individuals with HD and clinical signs of apathy according to the Structured Clinical Interview for Apathy-Dementia (SCIA-D), but not depression (n = 40) were randomized to receive either bupropion 150/300mg or placebo daily for 10 weeks. The primary outcome parameter was a significant change of the Apathy Evaluation Scale (AES) score after ten weeks of treatment as judged by an informant (AES-I) living in close proximity with the study participant. The secondary outcome parameters included changes of 1. AES scores determined by the patient (AES-S) or the clinical investigator (AES-C), 2. psychiatric symptoms (NPI, HADS-SIS, UHDRS-Behavior), 3. cognitive performance (SDMT, Stroop, VFT, MMSE), 4. motor symptoms (UHDRS-Motor), 5. activities of daily function (TFC, UHDRS-Function), and 6. caregiver distress (NPI-D). In addition, we investigated the effect of bupropion on brain structure as well as brain responses and functional connectivity during reward processing in a gambling task using magnetic resonance imaging (MRI). At baseline, there were no significant treatment group differences in the clinical primary and secondary outcome parameters. At endpoint, there was no statistically significant difference between treatment groups for all clinical primary and secondary outcome variables. Study participation, irrespective of the intervention, lessened symptoms of apathy according to the informant and the clinical investigator. Bupropion does not alleviate apathy in HD. However, study participation/placebo effects were observed, which document the need for carefully controlled trials when investigating therapeutic interventions for the neuropsychiatric symptoms of HD. ClinicalTrials.gov 01914965.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2017.03.032

NeuroImage

Neuroimage

Functional changes in the reward circuit in response to gaming-related cues after training with a commercial video game.

In the present longitudinal study, we aimed to investigate video game training associated neuronal changes in reward processing using functional magnetic resonance imaging (fMRI). We recruited 48 healthy young participants which were assigned to one of 2 groups: A group in which participants were instructed to play a commercial video game ("Super Mario 64 DS") on a portable Nintendo DS handheld console at least 30minutes a day over a period of two months (video gaming group; VG) or to a matched passive control group (CG). Before and after the training phase, in both groups, fMRI imaging was conducted during passively viewing reward and punishment-related videos sequences recorded from the trained video game. The results show that video game training may lead to reward related decrease in neuronal activation in the dorsolateral prefrontal cortex (DLPFC) and increase in the hippocampus. Additionally, the decrease in DLPFC activation was associated with gaming related parameters experienced during playing. Specifically, we found that in the VG, gaming related parameters like performance, experienced fun and frustration (assessed during the training period) were correlated to decrease in reward related DLPFC activity. Thus, neuronal changes in terms of video game training seem to be highly related to the appetitive character and reinforcement schedule of the game. Those neuronal changes may also be related to the often reported video game associated improvements in cognitive functions.

CognitiveConstruct

RewardProcessing

10.1007/s10578-017-0720-5

Child psychiatry and human development

Child Psychiatry Hum Dev

The Development of Severe and Chronic Violence Among Youth: The Role of Psychopathic Traits and Reward Processing.

Psychopathic traits are a manifestation of a personality pathology that comprises a core affective-interpersonal dysfunction (callous-unemotional traits) and an impulsive-antisocial behavioral component. Of particular importance, psychopathic traits are associated with the perpetration of some of the most severe acts of violence, and they appear to indicate a subset of youth at risk for earlier onset, greater frequency, and persistence of violent offending. Although these youth represent a minority of the population, they commit a significant proportion of the violence in the general community. In our review, we highlight evidence of a unique neurobiological predisposition that underlies the core affective deficits and describe contemporary accounts for the developmental processes leading to the antisocial behavior associated with psychopathy. Current evidence suggests that, for this subset of youth, the structure and function of neural circuitry supporting emotion processing, reward learning, decision making, and the development of emotion related to empathy may be crucial to understanding why they are at risk for violence. In particular, a reward dominant pattern of neurobehavioral conditioning may explain how these youth progress to some of the most severe and persistent forms of violence. However, this pattern of conditioning may also be essential to the primary prevention of such deleterious behavior. We suspect that effective strategies to prevent such violence may ultimately be informed by understanding these affective and motivational mechanisms.

CognitiveConstruct

RewardProcessing

10.1146/annurev-clinpsy-032816-044957

Annual review of clinical psychology

Annu Rev Clin Psychol

Reward Processing, Neuroeconomics, and Psychopathology.

Abnormal reward processing is a prominent transdiagnostic feature of psychopathology. The present review provides a framework for considering the different aspects of reward processing and their assessment, and highlights recent insights from the field of neuroeconomics that may aid in understanding these processes. Although altered reward processing in psychopathology has often been treated as a general hypo- or hyperresponsivity to reward, increasing data indicate that a comprehensive understanding of reward dysfunction requires characterization within more specific reward-processing domains, including subjective valuation, discounting, hedonics, reward anticipation and facilitation, and reinforcement learning. As such, more nuanced models of the nature of these abnormalities are needed. We describe several processing abnormalities capable of producing the types of selective alterations in reward-related behavior observed in different forms of psychopathology, including (mal)adaptive scaling and anchoring, dysfunctional weighting of reward and cost variables, competition between valuation systems, and reward prediction error signaling.

CognitiveConstruct

RewardProcessing

10.1002/jclp.22447

Journal of clinical psychology

J Clin Psychol

Depressive Symptoms and the Anticipation and Experience of Uplifting Events in Everyday Life.

Despite proliferation of laboratory-based studies examining reward functioning in depression, few studies have examined these processes in everyday life. We addressed this shortcoming by exploring experience and anticipation of uplifting experiences under ecologically valid conditions METHOD: One hundred fifty-seven young adults, oversampled for depressive symptoms, completed a 14-day diary tracking mood in relation to recent and anticipated positive events RESULTS: Consistent with studies supporting "mood-brightening" effects in depression, participants with greater baseline dysphoria showed stronger associations between elevated daily uplifts and lower daily depressive symptoms, particularly when events were interpersonal in nature. Baseline dysphoria was associated with lower daily anticipation of positive next-day experiences; however, when dysphoric individuals did anticipate positive experiences, they experienced greater reductions in depressed mood CONCLUSION: Results suggest that despite reward processing deficits found in laboratory studies, dysphoric individuals show improvements in mood in conjunction with anticipation and consumption of uplifting events in daily life.

CognitiveConstruct

RewardProcessing

10.1111/jcpp.12713

Journal of child psychology and psychiatry, and allied disciplines

J Child Psychol Psychiatry

Annual Research Review: Childhood maltreatment, latent vulnerability and the shift to preventative psychiatry - the contribution of functional brain imaging.

Childhood maltreatment is a potent predictor of poor mental health across the life span. We argue that there is a need to improve the understanding of the mechanisms that confer psychiatric vulnerability following maltreatment, if we are to progress from simply treating those with a manifest disorder, to developing effective preventative approaches that can help offset the likelihood that such disorders will emerge in the first place. We review extant functional neuroimaging studies of children and adolescents exposed to early neglect and/or maltreatment, including physical, sexual and emotional abuse across four neurocognitive domains: threat processing, reward processing, emotion regulation and executive control. Findings are discussed in the context of 'latent vulnerability', where alterations in neurocognitive function are considered to carry adaptive value in early adverse caregiving environments but confer long-term risk. Studies on threat processing indicate heightened as well as depressed neural responsiveness in maltreated samples, particularly in the amygdala, thought to reflect threat hypervigilance and avoidance respectively. Studies on reward processing generally report blunted neural response to anticipation and receipt of rewards, particularly in the striatum, patterns associated with depressive symptomatology. Studies on emotion regulation report increased activation of the anterior cingulate cortex (ACC) during active emotion regulation, possibly reflecting greater effortful processing. Finally, studies of executive control report increased dorsal ACC activity during error monitoring and inhibition. An emerging body of work indicates that altered neurocognitive functioning following maltreatment: (a) is evident even in the absence of overt psychopathology; (b) is consistent with perturbations seen in individuals presenting with psychiatric disorder; (c) can predict future psychiatric symptomatology. These findings suggest that maltreatment leads to neurocognitive alterations that embed latent vulnerability to psychiatric disorder, establishing a compelling case for identifying those children at most risk and developing mechanistically informed models of preventative intervention. Such interventions should aim to offset the likelihood of any future psychiatric disorder.

CognitiveConstruct

RewardProcessing

10.3389/fnsys.2017.00006

Frontiers in systems neuroscience

Front Syst Neurosci

Brief Mental Training Reorganizes Large-Scale Brain Networks.

Emerging evidences have shown that one form of mental training-mindfulness meditation, can improve attention, emotion regulation and cognitive performance through changing brain activity and structural connectivity. However, whether and how the short-term mindfulness meditation alters large-scale brain networks are not well understood. Here, we applied a novel data-driven technique, the multivariate pattern analysis (MVPA) to resting-state fMRI (rsfMRI) data to identify changes in brain activity patterns and assess the neural mechanisms induced by a brief mindfulness training-integrative body-mind training (IBMT), which was previously reported in our series of randomized studies. Whole brain rsfMRI was performed on an undergraduate group who received 2 weeks of IBMT with 30 min per session (5 h training in total). Classifiers were trained on measures of functional connectivity in this fMRI data, and they were able to reliably differentiate (with 72% accuracy) patterns of connectivity from before vs. after the IBMT training. After training, an increase in positive functional connections (60 connections) were detected, primarily involving bilateral superior/middle occipital gyrus, bilateral frontale operculum, bilateral superior temporal gyrus, right superior temporal pole, bilateral insula, caudate and cerebellum. These results suggest that brief mental training alters the functional connectivity of large-scale brain networks at rest that may involve a portion of the neural circuitry supporting attention, cognitive and affective processing, awareness and sensory integration and reward processing.

CognitiveConstruct

RewardProcessing

10.1038/mp.2017.16

Molecular psychiatry

Mol Psychiatry

The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment.

Bipolar affective disorder is a common neuropsychiatric disorder. Although its neurobiological underpinnings are incompletely understood, the dopamine hypothesis has been a key theory of the pathophysiology of both manic and depressive phases of the illness for over four decades. The increased use of antidopaminergics in the treatment of this disorder and new in vivo neuroimaging and post-mortem studies makes it timely to review this theory. To do this, we conducted a systematic search for post-mortem, pharmacological, functional magnetic resonance and molecular imaging studies of dopamine function in bipolar disorder. Converging findings from pharmacological and imaging studies support the hypothesis that a state of hyperdopaminergia, specifically elevations in D2/3 receptor availability and a hyperactive reward processing network, underlies mania. In bipolar depression imaging studies show increased dopamine transporter levels, but changes in other aspects of dopaminergic function are inconsistent. Puzzlingly, pharmacological evidence shows that both dopamine agonists and antidopaminergics can improve bipolar depressive symptoms and perhaps actions at other receptors may reconcile these findings. Tentatively, this evidence suggests a model where an elevation in striatal D2/3 receptor availability would lead to increased dopaminergic neurotransmission and mania, whilst increased striatal dopamine transporter (DAT) levels would lead to reduced dopaminergic function and depression. Thus, it can be speculated that a failure of dopamine receptor and transporter homoeostasis might underlie the pathophysiology of this disorder. The limitations of this model include its reliance on pharmacological evidence, as these studies could potentially affect other monoamines, and the scarcity of imaging evidence on dopaminergic function. This model, if confirmed, has implications for developing new treatment strategies such as reducing the dopamine synthesis and/or release in mania and DAT blockade in bipolar depression.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2017.03.020

Journal of affective disorders

J Affect Disord

Neural reactivity to reward in school-age offspring of depressed mothers.

Identifying neural profiles predictive of future psychopathology in at-risk individuals is important to efficiently direct preventive care. Alterations in reward processing may be a risk factor for depression. The current study characterized neural substrates of reward processing in children at low- and high-risk for psychopathology due to maternal depression status. Children with (n=27) and without (n=19) maternal depression (ages 5.9-9.6 years) performed a monetary incentive delay task in which they received rewards, if they successfully hit a target, or no reward regardless of performance, during fMRI acquisition. Multiple dorsal prefrontal, temporal, and striatal regions showed significant Group (high- vs. low-risk)×Performance (hit vs. miss)×Condition (no reward vs. reward) interactions in a whole-brain analysis. All regions exhibited similar patterns, whereby the high-risk group showed blunted activation differences between trials with vs. without rewards when participants hit the target. Moreover, high-risk children showed activation differences between trials with vs. without rewards in the opposite direction, compared to the low-risk group, when they missed the target. This study had a modest sample size, though larger than existing studies. Children with maternal depression are at elevated risk for future psychopathology, yet not all experience clinically significant symptoms; longitudinal research is necessary to fully track the pathway from risk to disorder. Children of depressed mothers exhibited attenuated neural activation differences and activation patterns opposite to children without depressed mothers. Our findings may provide targets for hypothesis-driven preventive interventions and lead to earlier identification of individuals at risk.

CognitiveConstruct

RewardProcessing

10.1038/srep44374

Scientific reports

Sci Rep

Valuation in major depression is intact and stable in a non-learning environment.

The clinical diagnosis and symptoms of major depressive disorder (MDD) have been closely associated with impairments in reward processing. In particular, various studies have shown blunted neural and behavioral responses to the experience of reward in depression. However, little is known about whether depression affects individuals' valuation of potential rewards during decision-making, independent from reward experience. To address this question, we used a gambling task and a model-based analytic approach to measure two types of individual sensitivity to reward values in participants with MDD: 'risk preference,' indicating how objective values are subjectively perceived, and 'inverse temperature,' determining the degree to which subjective value differences between options influence participants' choices. On both of these measures of value sensitivity, participants with MDD were comparable to non-psychiatric controls. In addition, both risk preference and inverse temperature were stable over four laboratory visits and comparable between the groups at each visit. Neither valuation measure varied with severity of clinical symptoms in MDD. These data suggest intact and stable value processing in MDD during risky decision-making.

CognitiveConstruct

RewardProcessing

10.1007/s00213-017-4584-y

Psychopharmacology

Psychopharmacology (Berl)

Social defeat disrupts reward learning and potentiates striatal nociceptin/orphanin FQ mRNA in rats.

Mood disorders can be triggered by stress and are characterized by deficits in reward processing, including disrupted reward learning (the ability to modulate behavior according to past rewards). Reward learning is regulated by the anterior cingulate cortex (ACC) and striatal circuits, both of which are implicated in the pathophysiology of mood disorders. Here, we assessed in rats the effects of a potent stressor (social defeat) on reward learning and gene expression in the ACC, ventral tegmental area (VTA), and striatum. Adult male Wistar rats were trained on an operant probabilistic reward task (PRT) and then exposed to 3 days of social defeat before assessment of reward learning. After testing, the ACC, VTA, and striatum were dissected, and expression of genes previously implicated in stress was assessed. Social defeat blunted reward learning (manifested as reduced response bias toward a more frequently rewarded stimulus) and was associated with increased nociceptin/orphanin FQ (N/OFQ) peptide mRNA levels in the striatum and decreased Fos mRNA levels in the VTA. Moreover, N/OFQ peptide and nociceptin receptor mRNA levels in the ACC, VTA and striatum were inversely related to reward learning. The behavioral findings parallel previous data in humans, suggesting that stress similarly disrupts reward learning in both species. Increased striatal N/OFQ mRNA in stressed rats characterized by impaired reward learning is consistent with accumulating evidence that antagonism of nociceptin receptors, which bind N/OFQ, has antidepressant-like effects. These results raise the possibility that nociceptin systems represent a molecular substrate through which stress produces reward learning deficits in mood disorders.

CognitiveConstruct

RewardProcessing

10.1109/EMBC.2016.7592052

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

Annu Int Conf IEEE Eng Med Biol Soc

Development of semi-chronic microdrive system for large-scale circuit mapping in macaque mesolimbic and basal ganglia systems.

The development of novel neurotechnologies for treating refractory neuropsychiatry disorders depends on understanding and manipulating the dynamics of neural circuits across large-scale brain networks. The mesolimbic pathway plays an essential role in reward processing and mood regulation and disorders of this pathway underlie many neuropsychiatric disorders. Here, we present the design of a customized semi-chronic microdrive array that precisely targets the anatomical structures of non-human primate (NHP) mesolimbic and basal ganglia systems. We present an integrated experimental paradigm that uses this device to map and manipulate large-scale neural circuits. The system combines electrophysiology, spatiotemporal multisite patterned intracortical microstimulation (ICMS), and diffusion tractography. We propose that this system provides a flexible platform for exploring and identifying neural signatures which can serve as novel targets for closed-loop stimulation in the clinical treatment of neuropsychiatric disorders.

CognitiveConstruct

RewardProcessing

10.1109/EMBC.2016.7591342

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

Annu Int Conf IEEE Eng Med Biol Soc

Sound preference test in animal models of addicts and phobias.

Biased or too strong preference for a particular object is often problematic, resulting in addiction and phobia. In animal models, alternative forced-choice tasks have been routinely used, but such preference test is far from daily situations that addicts or phobic are facing. In the present study, we developed a behavioral assay to evaluate the preference of sounds in rodents. In the assay, several sounds were presented according to the position of free-moving rats, and quantified the sound preference based on the behavior. A particular tone was paired with microstimulation to the ventral tegmental area (VTA), which plays central roles in reward processing, to increase sound preference. The behaviors of rats were logged during the classical conditioning for six days. Consequently, some behavioral indices suggest that rats search for the conditioned sound. Thus, our data demonstrated that quantitative evaluation of preference in the behavioral assay is feasible.

CognitiveConstruct

RewardProcessing

10.1016/j.soard.2016.12.031

Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery

Surg Obes Relat Dis

Impulsivity predicts weight loss after obesity surgery.

There is evidence that executive function, and specifically inhibitory control, is related to obesity and eating behavior. The goal of this study was to determine whether personality traits and inhibitory control predict weight loss after bariatric procedures. Although the impressive weight reduction after bariatric surgery has been shown in short- and medium-term studies, the effect of personality traits on this reduction is uncertain. Specifically, the effect of impulsivity is still largely unknown. Patients attending either a multidisciplinary information session or outpatient clinic at the Imperial Weight Management Centre were recruited with informed consent into the trial over a 4-month period from January to April 2013. Participants were invited to attend behavioral testing on an outpatient basis in a silent room invigilated by a single researcher. Forty-five bariatric patients participated in the study (25 patients had a gastric bypass, with a mean BMI of 41.8 and age of 39.0 years; 20 had a sleeve gastrectomy, with a mean BMI of 47.2 and age of 49.0 years). All patients completed personality measures of impulsivity-Barratt's Impulsivity Scale, as well as behavioral measures of impulsivity-the stop-signal reaction-time (SSRT) task measuring inhibitory control and the temporal discounting task measuring reward processing. Those measures were examined in relation to weight loss 6 months after surgery. The surgical procedure and changes in the behavioral measure of inhibitory control (SSRT) were found to be significant predictors of reduction in body mass index (BMI) in patients undergoing bariatric surgery. The sleeve gastrectomy group found a reduction in BMI of 14.1%, which was significantly less than the 25% reduction in BMI in the gastric bypass group. The direction (parameter estimate) of the significant effect was positive for SSRT change, which indicates that pre- and postreduction in impulsivity predicts reduction in BMI. Impulsivity measures predict weight reduction in patients undergoing bariatric surgery. This result has implications for predicting outcomes from surgical treatments of obesity.

CognitiveConstruct

RewardProcessing

10.1016/j.pbb.2017.02.006

Pharmacology, biochemistry, and behavior

Pharmacol Biochem Behav

Viral vector strategies for investigating midbrain dopamine circuits underlying motivated behaviors.

Midbrain dopamine (DA) neurons have received significant attention in brain research because of their central role in reward processing and their dysfunction in neuropsychiatric disorders such as Parkinson's disease, drug addiction, depression and schizophrenia. Until recently, it has been thought that DA neurons form a homogeneous population whose primary function is the computation of reward prediction errors. However, through the implementation of viral vector strategies, an unexpected complexity and diversity has been revealed at the anatomical, molecular and functional level. In this review, we discuss recent viral vector approaches that have been leveraged to dissect how different circuits involving distinct DA neuron subpopulations may contribute to the role of DA in reward- and aversion-related behaviors. We focus on studies that have used cell type- and projection-specific optogenetic manipulations, discuss the strengths and limitations of each approach, and critically examine emergent organizational principles that have led to a reclassification of midbrain DA neurons.

CognitiveConstruct

RewardProcessing

10.1016/j.brs.2017.01.004

Brain stimulation

Brain Stimul

The human globus pallidus internus is sensitive to rewards - Evidence from intracerebral recordings.

The globus pallidus internus (GPi) is the final output relay of the basal ganglia for the control of movements but has also been shown to belong to a second pathway projecting to the lateral habenula. This latter pathway is related to reward processing. This prompted us to record, in eight patients receiving deep brain stimulation of the GPi for the alleviation of various movement disorders, local field potentials (LFP) while these patients performed a lottery task. The task entailed choosing between a higher and a lower number, which changed their color after the patient's choice with red (green) signaling a loss (win, in Euro cents) corresponding to the chosen number. Surface recordings showed a feedback related negativity from a frontal midline site, while time domain averages in the GPi showed differential modulation depending on the valence of the stimulus with polarity inversion indicating that this reward-modulated activity was indeed generated locally. Furthermore, wavelet decomposition of the LFP showed a reward-related response in the high beta/low gamma range. We conclude that human GPi is involved in reward processing, possibly in relation to the lateral habenula.

CognitiveConstruct

RewardProcessing

10.1007/s11682-017-9687-x

Brain imaging and behavior

Brain Imaging Behav

Orbitofrontal overactivation in reward processing in borderline personality disorder: the role of non-suicidal self-injury.

Borderline Personality Disorder (BPD) is a disabling and difficult-to-treat mental disease. One of its core features is a significant difficulty in affect regulation, which is often accompanied by Non-Suicidal Self-Injury (NSSI). It is suggested that this type of behavior elicits positive emotions and mitigates emotional distress, and therefore can ultimately be reinforced and promoted. In spite of the high prevalence of NSSI behaviors (also in non-BPD samples), their role in modulating reward-related processes has not yet been investigated in BPD patients. In the present study, this lack of research was addressed. A large sample of BPD patients (N = 40), divided into two groups depending on the presence of NSSI, and a group of matched healthy controls underwent functional Magnetic Resonance Imaging (fMRI) while performing a gambling task. Patients who committed NSSI acts exhibited enhanced activation of the orbitofrontal cortex following an unexpected reward, when compared with controls and BPD patients with no NSSI behavior. In addition, the NSSI group showed diminished functional connectivity between the left orbitofrontal cortex and the right parahippocampal gyrus. These findings might suggest impaired ability to update reward associations of potential choices when both BPD and NSSI are present. We propose that the presence of NSSI involves alterations in the reward system independently of BPD, and thus can be considered as a possible phenotype for reward-related alterations.

CognitiveConstruct

RewardProcessing

10.1016/j.bpsc.2016.07.007

Biological psychiatry. Cognitive neuroscience and neuroimaging

Biol Psychiatry Cogn Neurosci Neuroimaging

Intact Ventral Striatal Prediction Error Signaling in Medicated Schizophrenia Patients.

Midbrain dopaminergic neurons code a computational quantity, reward prediction error (RPE), which has been causally related to learning. Recently, this insight has been leveraged to link phenomenological and biological levels of understanding in psychiatric disorders, such as schizophrenia. However, results have been mixed, possibly due to small sample sizes. Here we present results from two studies with relatively large Ns to assess VS RPE in schizophrenia. In the current study we analyzed data from two independent studies, involving a total of 87 chronic medicated schizophrenia patients and 61 controls. Subjects completed a probabilistic reinforcement-learning task in conjunction with fMRI scanning. We fit each participant's choice behavior to a Q-learning model and derived trial-wise RPEs. We then modeled BOLD signal data with parametric regressor functions using these values to determine whether patient and control groups differed in prediction-error-related BOLD signal modulations. Both groups demonstrated robust VS RPE BOLD activations. Interestingly, these BOLD activation patterns did not differ between groups in either study. This was true when we included all participants in the analysis, as well as when we excluded participants whose data was not sufficiently fit by the models. These data demonstrate the utility of computational methods in isolating/testing underlying mechanisms of interest in psychiatric disorders. Importantly, similar VS RPE signal encoding across groups suggests that this mechanism does not drive task deficits in these patients. Deficits may instead stem from aberrant prefrontal/parietal circuits associated with maintenance and selection of goal-relevant information.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2017.02.001

Journal of affective disorders

J Affect Disord

Reward processing and mood-related symptoms: An RDoC and translational neuroscience perspective.

Two objectives of the NIMH Research Domain Criteria (RDoC) initiative are to identify (a) mechanisms that are common to multiple psychiatric disorders, and (b) mechanisms that are unique to specific psychiatric symptoms, and that reflect markers of differential risk for these symptoms. With respect to these objectives, a brain-behavior dimension that has received considerable attention and that is directly relevant to the Positive Valence Systems domain of the RDoC initiative involves reward processing. The present review paper first examines the relationship between reward processing and mood-related symptoms from an RDoC perspective. We then place this work in a larger context by examining the relationship between reward processing abnormalities and psychiatric symptoms defined broadly, including mood-related symptoms, schizophrenia, and addiction. Our review suggests that reward hyposensitivity relates to a subtype of anhedonia characterized by motivational deficits in unipolar depression, and reward hypersensitivity relates to a cluster of hypo/manic symptoms characterized by excessive approach motivation in the context of bipolar disorder. Integrating this perspective with research on reward processing abnormalities in schizophrenia and addiction, we further argue that the principles of equifinality and multifinality may be preferable to a transdiagnostic perspective for conceptualizing the relationship between reward processing and psychiatric symptoms defined broadly. We propose that vulnerability to either motivational anhedonia or approach-related hypo/manic symptoms involve extreme and opposite profiles of reward processing. We further propose that an equifinality and multifinality perspective may serve as a useful framework for future research on reward processing abnormalities and psychiatric symptoms.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2017.02.019

Behavioural brain research

Behav Brain Res

Acute and long-term effects of adolescent methylphenidate on decision-making and dopamine receptor mRNA expression in the orbitofrontal cortex.

Though commonly used as a treatment for ADHD, the psychostimulant methylphenidate (MPH) is also misused and abused in adolescence in both clinical and general populations. Although MPH acts via pathways activated by other drugs of abuse, the short- and long-term effects of MPH on reward processing in learning and decision-making are not clearly understood. We examined the effect of adolescent MPH treatment on a battery of reward-directed behaviors both in adolescence during its administration and in adulthood after its discontinuation. We further measured whether MPH had lasting effects on dopamine receptor mRNA expression in orbitofrontal cortex (OFC) that may correspond with behavior. Long-Evans rats were injected with MPH (0, 1, 2.5, or 5mg/kg IP) twice daily from middle to late adolescence (PD38-57). During adolescence, the high dose of MPH reduced preference for large rewards in a Reward Magnitude Discrimination task, but did not affect preference for smaller-sooner rewards in a Delay Discounting task. In adulthood, after discontinuation of MPH, animals previously treated with the moderate dose of MPH showed improved acquisition, but not reversal, in a Reversal Learning task. MPH exposure did not increase preference for large-risky rewards in a Risk task in adulthood. We then quantified mRNA expression of D1, D2, and D3 receptors in the OFC using qPCR. MPH increased mRNA expression of dopamine D3 receptor subtype, but not D1 or D2. Overall, these results indicate that MPH has both immediate and lasting effects on reward-dependent learning and decisions, as well as dopaminergic function in rodents.

CognitiveConstruct

RewardProcessing

10.1038/srep42631

Scientific reports

Sci Rep

Undervaluing delayed rewards explains adolescents' impulsivity in inter-temporal choice: an ERP study.

Adolescence has frequently been characterized as a period of choice impulsivity relative to adulthood. According to the control-integrated valuation model of inter-temporal choice, this choice impulsivity may be driven partly by an age-related difference in reward processing. We hypothesized that, compared to adults, adolescents would undervalue delayed rewards during reward processing and would thus be more impulsive in inter-temporal choice. To test this hypothesis at the behavioural and neural levels, we first measured the choice impulsivity of 18 adolescents and 19 adults using a delay discounting task (DDT). Then, we recorded event-related potentials (ERPs) from the participants while they were performing the valuation task, in which monetary gains and losses were either immediate or delayed. The behavioural results showed that adolescents were more impulsive than adults in the DDT. The ERP results showed that, whilst both groups valued immediate rewards, implied by a similarly strong feedback-related negativity (FRN) effect associated with immediate outcomes, adolescents devalued delayed rewards more than adults did, as they produced a significantly smaller FRN effect associated with delayed outcomes. As predicted, the mediation analysis revealed that the adolescents' lower FRN effect of delayed outcomes underpinned their stronger impulsive decision making in the DDT.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.3499-16.2017

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

J Neurosci

Unresponsive Choline Transporter as a Trait Neuromarker and a Causal Mediator of Bottom-Up Attentional Biases.

Some rats [sign-trackers (STs)] are prone to attribute incentive salience to reward cues, which can manifest as a propensity to approach and contact pavlovian cues, and for addiction-like behavior. STs also exhibit poor attentional performance, relative to goal-trackers (GTs), which is associated with attenuated acetylcholine (ACh) levels in prefrontal cortex (Paolone et al., 2013). Here, we demonstrate a cellular mechanism, linked to ACh synthesis, that accounts for attenuated cholinergic capacity in STs. First, we found that electrical stimulation of the basal forebrain increased cortical choline transporter (CHT)-mediated choline transport in GTs, paralleled by a redistribution of CHTs to the synaptic plasma membrane. Neither increases in choline uptake nor translocation of CHTs occurred in STs. Second, and consistent with uptake/translocation alterations, STs demonstrated a reduced ability to support cortical ACh release compared with GTs after reverse-dialysis to elevate extracellular potassium levels. Third, rats were significantly more likely to develop sign-tracking behavior if treated systemically before pavlovian conditioned approach training with the CHT inhibitor VU6001221. Consistent with its proposed mechanisms, administration of VU6001221 attenuated potassium-evoked ACh levels in prefrontal cortex measured with microdialysis. We propose that loss of CHT-dependent activation of cortical cholinergic activity in STs degrades top-down executive control over behavior, producing a bias for bottom-up or stimulus-driven attention. Such an attentional bias contributes to nonadaptive reward processing and thus identifies a novel mechanism that can support psychopathology, including addiction. The vulnerability for addiction-like behavior has been associated with psychological traits, such as the propensity to attribute incentive salience to reward cues that is modeled in rats by sign-tracking behavior. Sign-trackers tend to approach and contact cues associated with reward, whereas their counterparts, the goal-trackers, have a preference for approaching the location of the reward. Here, we show that the capacity of presynaptic cholinergic synapses to respond to stimulation by elevating presynaptic choline uptake and releasing acetylcholine is attenuated in sign-trackers. Furthermore, pharmacological inhibition of choline transport induced sign-tracking behavior. Our findings suggest that reduced levels of cholinergic neuromodulation can mediate an attentional bias toward reward-related cues, thereby allowing such cues to exert relatively greater control over behavior.

CognitiveConstruct

RewardProcessing

10.1111/jopy.12306

Journal of personality

J Pers

Amplitude of Low-Frequency Fluctuations During Resting State Differentially Predicts Authentic and Hubristic Pride.

Pride is an important, self-conscious emotion composed of two distinct conceptual facets: arrogant, egotistic "hubristic pride," and pro-social, achievement-oriented "authentic pride." However, little is known about the neural basis of the two facets of pride. Here, we investigated the association between spontaneous brain activity and these two facets of pride in resting state. We measured 276 participants on authentic and hubristic pride. The fractional amplitude of low-frequency fluctuations (fALFF) was used to identify pride-related regions. The results revealed individual differences in authentic pride were associated with the fALFF in the bilateral superior temporal gyrus (STG), which has been implicated in social processing. In contrast, individual differences in hubristic pride were associated with the fALFF in the left orbitofrontal cortex (OFC) and posterior cingulate cortex (PCC), which have been implicated in self-referential and reward processing. Together, our results provide initial evidence for the distinct neural substrates for authentic and hubristic pride.

CognitiveConstruct

RewardProcessing

10.1016/j.biopsych.2016.12.022

Biological psychiatry

Biol Psychiatry

Mu Opioid Receptors in Gamma-Aminobutyric Acidergic Forebrain Neurons Moderate Motivation for Heroin and Palatable Food.

Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward. We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons. We characterized the genetic deletion by histology, electrophysiology, and microdialysis; probed neuronal activation by c-Fos immunohistochemistry and resting-state functional magnetic resonance imaging; and investigated main behavioral responses to opiates, including motivation to obtain heroin and palatable food. Mutant mice showed MOR transcript deletion mainly in the striatum. In the ventral tegmental area, local MOR activity was intact, and reduced activity was only observed at the level of striatonigral afferents. Heroin-induced neuronal activation was modified at both sites, and whole-brain functional networks were altered in live animals. Morphine analgesia was not altered, and neither was physical dependence to chronic morphine. In contrast, locomotor effects of heroin were abolished, and heroin-induced catalepsy was increased. Place preference to heroin was not modified, but remarkably, motivation to obtain heroin and palatable food was enhanced in operant self-administration procedures. Our study reveals dissociable MOR functions across mesocorticolimbic networks. Thus, beyond a well-established role in reward processing, operating at the level of local ventral tegmental area neurons, MORs also moderate motivation for appetitive stimuli within forebrain circuits that drive motivated behaviors.

CognitiveConstruct

RewardProcessing

10.1002/hbm.23522

Human brain mapping

Hum Brain Mapp

Network-level assessment of reward-related activation in patients with ADHD and healthy individuals.

Reward processing is a key aspect of cognitive control processes, putatively instantiated by mesolimbic and mesocortical brain circuits. Deficient signaling within these circuits has been associated with psychopathology. We applied a network discovery approach to assess specific functional networks associated with reward processing in participants with attention-deficit/hyperactivity disorder (ADHD). To describe task-related processes in terms of integrated functional networks, we applied independent component analysis (ICA) to task response maps of 60 healthy participants who performed a monetary incentive delay (MID) task. The resulting components were interpreted on the basis of their similarity with group-level task responses as well as their similarity with brain networks derived from resting state fMRI analyses. ADHD-related effects on network characteristics including functional connectivity and communication between networks were examined in an independent sample comprising 150 participants with ADHD and 48 healthy controls. We identified 23 components to be associated with 4 large-scale functional networks: the default-mode, visual, executive control, and salience networks. The salience network showed a specific association with reward processing as well as the highest degree of within-network integration. ADHD was associated with decreased functional connectivity between the salience and executive control networks as well as with peripheral brain regions. Reward processing as measured with the MID task involves one reward-specific and three general functional networks. Participants with ADHD exhibited alterations in connectivity of both the salience and executive control networks and associated brain regions during task performance. Hum Brain Mapp 38:2359-2369, 2017. © 2017 Wiley Periodicals, Inc.

CognitiveConstruct

RewardProcessing

10.1111/psyp.12822

Psychophysiology

Psychophysiology

Learning processes underlying avoidance of negative outcomes.

Successful avoidance of a threatening event may negatively reinforce the behavior due to activation of brain structures involved in reward processing. Here, we further investigated the learning-related properties of avoidance using feedback-related negativity (FRN). The FRN is modulated by violations of an intended outcome (prediction error, PE), that is, the bigger the difference between intended and actual outcome, the larger the FRN amplitude is. Twenty-eight participants underwent an operant conditioning paradigm, in which a behavior (button press) allowed them to avoid a painful electric shock. During two learning blocks, participants could avoid an electric shock in 80% of the trials by pressing one button (avoidance button), or by not pressing another button (punishment button). After learning, participants underwent two test blocks, which were identical to the learning ones except that no shocks were delivered. Participants pressed the avoidance button more often than the punishment button. Importantly, response frequency increased throughout the learning blocks but it did not decrease during the test blocks, indicating impaired extinction and/or habit formation. In line with a PE account, FRN amplitude to negative feedback after correct responses (i.e., unexpected punishment) was significantly larger than to positive feedback (i.e., expected omission of punishment), and it increased throughout the blocks. Highly anxious individuals showed equal FRN amplitudes to negative and positive feedback, suggesting impaired discrimination. These results confirm the role of negative reinforcement in motivating behavior and learning, and reveal important differences between high and low anxious individuals in the processing of prediction errors.

CognitiveConstruct

RewardProcessing

10.1038/npp.2017.28

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Neuroanatomical Prediction of Anhedonia in Adolescents.

Anhedonia is a transdiagnostic risk factor implicated in mental illness onset, treatment non-response, and suicidal behaviors. Prior cross-sectional research in adults has shown that anhedonia is associated with reduced dorsal striatal volume, but it is unknown whether this relationship extends to adolescents and whether reduced striatal volume prospectively predicts anhedonia. To address these gaps, the current study investigated whether striatal volume predicted anhedonia severity in adolescents. At baseline, healthy female adolescents aged 12-14 years (n=50) completed a clinical assessment, and structural MRI data were acquired on a 3 Tesla MR scanner. While in the scanner, participants also completed a peer feedback task where subjective ratings following peer 'acceptance' or 'rejection' were obtained. At the three-month follow-up, participants provided self-report assessments of anhedonia, depression, and anxiety symptoms. Three main findings emerged. First, in cross-sectional analyses, right nucleus accumbens volume was inversely related to anhedonia severity. Second, reduced bilateral putamen volume prospectively predicted anhedonia severity while controlling for baseline anhedonia, depression, and anxiety symptoms. Third, a blunted subjective response to peer acceptance (ie, neutral response to positive feedback), but not a more negative subjective response to peer rejection, contributed to anhedonia severity, but only among youth with smaller putamen volume. Collectively, these results suggest that smaller volume in striatal regions critically implicated in reward processing is associated with current and future anhedonic symptoms among healthy female youth. These anatomical features may confer vulnerability to anhedonia and thus, may inform early identification of individuals at high risk for mental illness.

CognitiveConstruct

RewardProcessing

10.1007/s00213-017-4544-6

Psychopharmacology

Psychopharmacology (Berl)

Dopamine-dependent visual attention preference to social stimuli in nonhuman primates.

Dopamine (DA) plays a central role in reward processing. Accumulating evidence suggests that social interaction and social stimuli have rewarding properties that activate the DA reward circuits. However, few studies have attempted to investigate how DA is involved in the processing of social stimuli. In this study, we investigated the effects of pharmacological manipulations of DA D1 and D2 receptors on social vs. nonsocial visual attention preference in macaques. Japanese macaques were subjected to behavioral tests in which visual attention toward social (monkey faces with and without affective expressions) and nonsocial stimuli was examined, with D1 and D2 antagonist administration. The macaques exhibited significantly longer durations of gazing toward the images with social cues than did those with nonsocial cues. Both D1 and D2 antagonist administration decreased duration of gazing toward the social images with and without affective valences. In addition, although D1 antagonist administration increased the duration of gazing toward the nonsocial images, D2 antagonism had no effect. These results suggest that both D1 and D2 receptors may have roles in the processing of social signals but through separate mechanisms.

CognitiveConstruct

RewardProcessing

10.1001/jamapsychiatry.2016.3084

JAMA psychiatry

JAMA Psychiatry

Disruption of Reward Processing in Addiction : An Image-Based Meta-analysis of Functional Magnetic Resonance Imaging Studies.

Disrupted reward processing, mainly driven by striatal dysfunction, is a key characteristic of addictive behaviors. However, functional magnetic resonance imaging (fMRI) studies have reported conflicting results, with both hypoactivations and hyperactivations during anticipation and outcome notification of monetary rewards in addiction. To determine the nature and direction of reward-processing disruptions during anticipation and outcome notification of monetary rewards in individuals with addiction using image-based meta-analyses of fMRI studies. Relevant publications were identified searching PubMed (inclusion until March 2015) using the following terms: reward, fMRI, substance use, cocaine, cannabis, opiates, alcohol, nicotine, smokers, gambling, gamblers, gaming, and gamers. Authors of included articles were contacted to obtain statistical fMRI maps. Inclusion criteria: reward task involving monetary reward anticipation and/or outcome; participants showing addictive behaviors; and healthy control group. Exclusion criteria: participants aged younger than 18 years; recreational substance use or gambling; participants at risk for addictive behaviors; and studies using the same patient data as other included studies. Study procedures were conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. Using Seed-based d Mapping software, meta-analyses were performed using random-effect nonparametric statistics with group whole brain T-maps from individual studies as input. Analyses were performed across all addictions and for substance and gambling addictions separately. Group differences (individuals with addiction vs control individuals) in reward-related brain activation during reward anticipation and outcome using fMRI (planned before data collection). Twenty-five studies were included in the meta-analysis, representing 643 individuals with addictive behaviors and 609 healthy control individuals. During reward anticipation, individuals with substance and gambling addictions showed decreased striatal activation compared with healthy control individuals. During reward outcome, individuals with substance addiction showed increased activation in the ventral striatum, whereas individuals with gambling addiction showed decreased activation in the dorsal striatum compared with healthy control individuals. Striatal hypoactivation in individuals with addiction during reward anticipation and in individuals with gambling addiction during reward outcome is in line with the reward-deficiency theory of addiction. However, the combination of hypoactivation during reward anticipation and hyperactivation during reward outcome in the striatum of individuals with substance addiction may be explained using learning-deficit theory.

CognitiveConstruct

RewardProcessing

10.1038/tp.2016.289

Translational psychiatry

Transl Psychiatry

Further support for association between GWAS variant for positive emotion and reward systems.

A recent genome-wide association study (GWAS) identified a significant single-nucleotide polymorphism (SNP) for trait-positive emotion at rs322931 on chromosome 1, which was also associated with brain activation in the reward system of healthy individuals when observing positive stimuli in a functional magnetic resonance imaging (fMRI) study. In the current study, we aimed to further validate the role of variation at rs322931 in reward processing. Using a similar fMRI approach, we use two paradigms that elicit a strong ventral striatum (VS) blood oxygen-level dependency (BOLD) response in a sample of young, healthy individuals (N=82). In the first study we use a similar picture-viewing task to the discovery sample (positive>neutral stimuli) to replicate an effect of the variant on emotion processing. In the second study we use a probabilistic reversal learning procedure to identify reward processing during decision-making under uncertainly (reward>punishment). In a region of interest (ROI) analysis of the bilateral VS, we show that the rs322931 genotype was associated with BOLD in the left VS during the positive>neutral contrast (P=0.045) and during the reward>punishment contrast (P=0.018), although the effect of passive picture viewing was in the opposite direction from that reported in the discovery sample. These findings suggest that the recently identified GWAS hit may influence positive emotion via individual differences in activity in the key hubs of the brain's reward system. Furthermore, these effects may not be limited to the passive viewing of positive emotional scenes, but may also be observed during dynamic decision-making. This study suggests that future studies of this GWAS locus may yield further insight into the biological mechanisms of psychopathologies characterised by deficits in reward processing and positive emotion.

CognitiveConstruct

RewardProcessing

10.1016/j.appet.2017.01.032

Appetite

Appetite

Volitional regulation of brain responses to food stimuli in overweight and obese subjects: A real-time fMRI feedback study.

Obese subjects who achieve weight loss show increased functional connectivity between dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC), key areas of executive control and reward processing. We investigated the potential of real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback training to achieve healthier food choices by enhancing self-control of the interplay between these brain areas. We trained eight male individuals with overweight or obesity (age: 31.8 ± 4.4 years, BMI: 29.4 ± 1.4 kg/m) to up-regulate functional connectivity between the dlPFC and the vmPFC by means of a four-day rt-fMRI neurofeedback protocol including, on each day, three training runs comprised of six up-regulation and six passive viewing trials. During the up-regulation runs of the four training days, participants successfully learned to increase functional connectivity between dlPFC and vmPFC. In addition, a trend towards less high-calorie food choices emerged from before to after training, which however was associated with a trend towards increased covertly assessed snack intake. Findings of this proof-of-concept study indicate that overweight and obese participants can increase functional connectivity between brain areas that orchestrate the top-down control of appetite for high-calorie foods. Neurofeedback training might therefore be a useful tool in achieving and maintaining weight loss.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0167606

PloS one

PLoS One

Single-Session Transcranial Direct Current Stimulation Temporarily Improves Symptoms, Mood, and Self-Regulatory Control in Bulimia Nervosa: A Randomised Controlled Trial.

Evidence suggests that pathological eating behaviours in bulimia nervosa (BN) are underpinned by alterations in reward processing and self-regulatory control, and by functional changes in neurocircuitry encompassing the dorsolateral prefrontal cortex (DLPFC). Manipulation of this region with transcranial direct current stimulation (tDCS) may therefore alleviate symptoms of the disorder. This double-blind sham-controlled proof-of-principle trial investigated the effects of bilateral tDCS over the DLPFC in adults with BN. Thirty-nine participants (two males) received three sessions of tDCS in a randomised and counterbalanced order: anode right/cathode left (AR/CL), anode left/cathode right (AL/CR), and sham. A battery of psychological/neurocognitive measures was completed before and after each session and the frequency of bulimic behaviours during the following 24-hours was recorded. AR/CL tDCS reduced eating disorder cognitions (indexed by the Mizes Eating Disorder Cognitions Questionnaire-Revised) when compared to AL/CR and sham tDCS. Both active conditions suppressed the self-reported urge to binge-eat and increased self-regulatory control during a temporal discounting task. Compared to sham stimulation, mood (assessed with the Profile of Mood States) improved after AR/CL but not AL/CR tDCS. Lastly, the three tDCS sessions had comparable effects on the wanting/liking of food and on bulimic behaviours during the 24 hours post-stimulation. These data suggest that single-session tDCS transiently improves symptoms of BN. They also help to elucidate possible mechanisms of action and highlight the importance of selecting the optimal electrode montage. Multi-session trials are needed to determine whether tDCS has potential for development as a treatment for adult BN.

CognitiveConstruct

RewardProcessing

10.1111/ajad.12500

The American journal on addictions

Am J Addict

Neuroimaging the neural correlates of increased risk for substance use disorders in attention-deficit/hyperactivity disorder-A systematic review.

Children with attention-deficit/hyperactivity disorder (ADHD) are nearly three times more likely to develop substance use disorders (SUD) than their typically developing peers. Our objective was to review the existing neuroimaging research on high-risk ADHD (ie, ADHD with disruptive behavior disorders, familial SUD and/or early substance use), focusing on impulsivity as one possible mechanism underlying SUD risk. A PubMed literature search was conducted using combinations of the keywords "ADHD," "substance use," "substance use disorder," "SUD," "addiction," "dependence," "abuse," "risk," "brain" "MRI," "imaging" and "neuroimaging." Studies had to include cohorts that met diagnostic criteria for ADHD; studies of individuals with ADHD who all met criteria for SUD were excluded. Eight studies met the search criteria. Individuals with high-risk ADHD have hyperactivation in the motivation-reward processing brain network during tasks of impulsive choice, emotion processing, and risky decision-making. During response inhibition tasks, they have hypoactivation in the inhibitory control brain network. However, studies focusing on this latter circuit found hypoactivation during inhibitory control tasks, decreased white matter microstructure coherence and reduced cortical thickness in ADHD independent of substance use history. An exaggerated imbalance between the inhibitory control network and the motivation-reward processing network is theorized to distinguish individuals with high-risk ADHD. Preliminary findings suggest that an exaggerated aberrant reward processing network may be the driving neural correlate of increased SUD risk in ADHD. Neural biomarkers of increased SUD risk in ADHD could help clinicians identify which patients may benefit most from SUD prevention. Thus, more neuroimaging research on this vulnerable population is needed. (Am J Addict 2017;26:99-111).

CognitiveConstruct

RewardProcessing

10.1111/adb.12493

Addiction biology

Addict Biol

Binge drinking differentially affects cortical and subcortical microstructure.

Young adult binge drinkers represent a model for endophenotypic risk factors for alcohol misuse and early exposure to repeated binge cycles. Chronic or harmful alcohol use leads to neurochemical, structural and morphological neuroplastic changes, particularly in regions associated with reward processing and motivation. We investigated neural microstructure in 28 binge drinkers compared with 38 matched healthy controls. We used a recently developed diffusion magnetic resonance imaging acquisition and analysis, which uses three-compartment modelling (of intracellular, extracellular and cerebrospinal fluid) to determine brain tissue microstructure features including neurite density and orientation dispersion index (ODI). Binge drinkers had reduced ODI, a proxy of neurite complexity, in frontal cortical grey matter and increased ODI in parietal grey matter. Neurite density was higher in cortical white matter in adjacent regions of lower ODI in binge drinkers. Furthermore, binge drinkers had higher ventral striatal grey matter ODI that was positively correlated with binge score. Healthy volunteers showed no such relationships. We demonstrate disturbed dendritic complexity of higher-order prefrontal and parietal regions, along with higher dendritic complexity of a subcortical region known to mediate reward-related motivation. The findings illustrate novel microstructural abnormalities that may reflect an infnce of alcohol bingeing on critical neurodevelopmental processes in an at-risk young adult group.

CognitiveConstruct

RewardProcessing

10.1111/cns.12671

CNS neuroscience & therapeutics

CNS Neurosci Ther

Behavioral and Electrophysiological Alterations for Reinforcement Learning in Manic and Euthymic Patients with Bipolar Disorder.

Bipolar disorder is characterized by behavioral changes such as risk-taking and increasing goal-directed activities, which may result from altered reward processing. Patients with bipolar disorder show impaired reward learning in situations that require the integration of reinforced feedback over time. In this study, we examined the behavioral and electrophysiological characteristics of reward learning in manic and euthymic patients with bipolar disorder using a probabilistic reward task. Twenty-four manic and 20 euthymic patients with bipolar I disorder and 24 healthy control subjects performed the probabilistic reward task. We assessed response bias (RB) as a preference for the stimulus paired with the more frequent reward and feedback-related negativity (FRN) to correct identification of the rich stimulus. Both manic and euthymic patients showed significantly lower RB scores in the early learning stage (block 1) in comparison with the late learning stage (block 2 or block 3) of the task, as well as significantly lower RB scores in the early stage compared to healthy subjects. Relatively more negative FRN amplitude is elicited by no presentation of an expected reward, compared to that elicited by presentation of expected feedback. The FRN became significantly more negative from the early (block 1) to the later stages (blocks 2 and 3) in both manic and euthymic patients, but not in healthy subjects. Changes in RB scores and FRN amplitudes between blocks 2 and 3 and block 1 correlated positively in healthy controls, but correlated negatively in manic and euthymic patients. The severity of manic symptoms correlated positively with reward learning scores and negatively with the FRN. These findings suggest that patients with bipolar disorder during euthymic or manic states have behavioral and electrophysiological alterations in reward learning compared to healthy subjects. This dysfunctional reward processing may be related to the abnormal decision-making or altered goal-directed activities frequently seen in patients with bipolar disorder.

CognitiveConstruct

RewardProcessing

10.1097/j.pain.0000000000000720

Pain

Pain

Brain substrates of reward processing and the μ-opioid receptor: a pathway into pain?

The processing of reward and reinforcement learning seems to be important determinants of pain chronicity. However, reward processing is already altered early in life and if this is related to the development of pain symptoms later on is not known. The aim of this study was first to examine whether behavioural and brain-related indicators of reward processing at the age of 14 to 15 years are significant predictors of pain complaints 2 years later, at 16 to 17 years. Second, we investigated the contribution of genetic variations in the opioidergic system, which is linked to the processing of both, reward and pain, to this prediction. We used the monetary incentive delay task to assess reward processing, the Children's Somatization Inventory as measure of pain complaints and tested the effects of 2 single nucleotide polymorphisms (rs1799971/rs563649) of the human μ-opioid receptor gene. We found a significant prediction of pain complaints by responses in the dorsal striatum during reward feedback, independent of genetic predisposition. The relationship of pain complaints and activation in the periaqueductal gray and ventral striatum depended on the T-allele of rs563649. Carriers of this allele also showed more pain complaints than CC-allele carriers. Therefore, brain responses to reward outcomes and higher sensitivity to pain might be related already early in life and may thus set the course for pain complaints later in life, partly depending on a specific opioidergic genetic predisposition.

CognitiveConstruct

RewardProcessing

10.1038/ncomms13877

Nature communications

Nat Commun

Dopaminergic dynamics underlying sex-specific cocaine reward.

Although both males and females become addicted to cocaine, females transition to addiction faster and experience greater difficulties remaining abstinent. We demonstrate an oestrous cycle-dependent mechanism controlling increased cocaine reward in females. During oestrus, ventral tegmental area (VTA) dopamine neuron activity is enhanced and drives post translational modifications at the dopamine transporter (DAT) to increase the ability of cocaine to inhibit its function, an effect mediated by estradiol. Female mice conditioned to associate cocaine with contextual cues during oestrus have enhanced mesolimbic responses to these cues in the absence of drug. Using chemogenetic approaches, we increase VTA activity to mechanistically link oestrous cycle-dependent enhancement of VTA firing to enhanced cocaine affinity at DAT and subsequent reward processing. These data have implications for sexual dimorphism in addiction vulnerability and define a mechanism by which cellular activity results in protein alterations that contribute to dysfunctional learning and reward processing.

CognitiveConstruct

RewardProcessing

10.1038/tp.2016.272

Translational psychiatry

Transl Psychiatry

Functional neuroimaging effects of recently discovered genetic risk loci for schizophrenia and polygenic risk profile in five RDoC subdomains.

Recently, 125 loci with genome-wide support for association with schizophrenia were identified. We investigated the impact of these variants and their accumulated genetic risk on brain activation in five neurocognitive domains of the Research Domain Criteria (working memory, reward processing, episodic memory, social cognition and emotion processing). In 578 healthy subjects we tested for association (i) of a polygenic risk profile score (RPS) including all single-nucleotide polymorphisms (SNPs) reaching genome-wide significance in the recent genome-wide association studies (GWAS) meta-analysis and (ii) of all independent genome-wide significant loci separately that showed sufficient distribution of all allelic groups in our sample (105 SNPs). The RPS was nominally associated with perigenual anterior cingulate and posterior cingulate/precuneus activation during episodic memory (P=0.047) and social cognition (P=0.025), respectively. Single SNP analyses revealed that rs9607782, located near EP300, was significantly associated with amygdala recruitment during emotion processing (P=1.63 × 10, surpassing Bonferroni correction for the number of SNPs). Importantly, this association was replicable in an independent sample (N=150; P<0.025). Other SNP effects previously associated with imaging phenotypes were nominally significant, but did not withstand correction for the number of SNPs tested. To assess whether there was true signal within our data, we repeated single SNP analyses with 105 randomly chosen non-schizophrenia-associated variants, observing fewer significant results and lower association probabilities. Applying stringent methodological procedures, we found preliminary evidence for the notion that genetic risk for schizophrenia conferred by rs9607782 may be mediated by amygdala function. We critically evaluate the potential caveats of the methodological approaches employed and offer suggestions for future studies.

CognitiveConstruct

RewardProcessing

10.1097/YCO.0000000000000314

Current opinion in psychiatry

Curr Opin Psychiatry

Psychological and physical pain as predictors of suicide risk: evidence from clinical and neuroimaging findings.

Suicide is a multidimensional clinical phenomenon with complex biological, social and psychological risk factors. Therefore, it is imperative for studies to focus on developing a unified understanding of suicide risk that integrates current clinical and neurobiological findings. A recent line of research has implicated different classifications of pain in understanding suicide risk, including the concepts of psychache and pain tolerance. Although psychache is defined as the experience of unbearable psychological pain, pain tolerance refers to the greatest duration or intensity of painful stimuli that one is able to bear. This review will focus on integrating current clinical and neurobiological findings by which psychache and pain tolerance confer suicide risk. Results indicate that psychache has been identified as a significant risk factor for suicide and that psychache may be associated with the neurocircuitry involved in the modulation of physical pain. Converging evidence has also been found linking pain tolerance to self-injurious behaviours and suicide risk. The experience of psychache and physical pain in relation to other predictors of suicide, including reward processing, hopelessness and depression, are further discussed. Future research examining the pain-suicide connection is required to understand the mechanism behind clinically relevant risk factors for suicide, which can ultimately inform the construction of empirically supported suicide risk assessment and intervention techniques.

CognitiveConstruct

RewardProcessing

10.1017/S1092852916000535

CNS spectrums

CNS Spectr

Investigating the role of anticipatory reward and habit strength in obsessive-compulsive disorder.

Aims To determine the rates and associated illness characteristics of obsessive-compulsive disorder (OCD) patients who describe their symptoms as either rewarding or habitual. Seventy-three treatment-seeking OCD patients had their dominant compulsive behavior assessed with a structured interview (the Temporal Impulsive-Compulsive Scale-Revised) to track the progression of rewarding (ie, gain in positive affect), aversive (ie, decrease in negative affect), and neutral (or non-affective) states and a self-report scale (the Self-Report Habit Index) to evaluate their habitual features. Additional measures included structured diagnostic interviews for axis I and II disorders, measures of OCD symptoms severity, and a battery of instruments to comprehensively assess relevant aspects of sensitivity to reward and fear. Almost half (49%) of our OCD patients (particularly washers) endorsed that they anticipated obtaining a reward (ie, positive affect) from the enactment of their dominant compulsive behavior. Washers stood out in that their positive affects during and after compulsive behaviors were highly (and positively) correlated with duration of illness. In contrast, habit strength did not differ between washers, checkers, and arrangers, although it also correlated with duration of illness among checkers. Furthermore, the severity of OCD and comorbidity with impulse control disorders predicted up to 35% of the variance in the habit strength of OCD behaviors. Compulsive washing may be more clearly characterized by problems in reward processing. In contrast, duration of checking, severity of OCD, and comorbidity with impulse control disorders shape compulsive behaviors by imparting them with habitual tendencies.

CognitiveConstruct

RewardProcessing

10.1016/j.cobeha.2016.11.015

Current opinion in behavioral sciences

Curr Opin Behav Sci

Stress and Decision Making: Effects on Valuation, Learning, and Risk-taking.

A wide range of stressful experiences can influence human decision making in complex ways beyond the simple predictions of a fight-or-flight model. Recent advances may provide insight into this complicated interaction, potentially in directions that could result in translational applications. Early research suggests that stress exposure influences basic neural circuits involved in reward processing and learning, while also biasing decisions towards habit and modulating our propensity to engage in risk-taking. That said, a substantial array of theoretical and methodological considerations in research on the topic challenge strong cross study comparisons necessary for the field to move forward. In this review we examine the multifaceted stress construct in the context of human decision making, emphasizing stress' effect on valuation, learning, and risk-taking.

CognitiveConstruct

RewardProcessing

10.1038/npp.2016.289

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During Monetary Reward Anticipation in Drug and Alcohol Dependence.

Evidence suggests that disturbances in neurobiological mechanisms of reward and inhibitory control maintain addiction and provoke relapse during abstinence. Abnormalities within the dopamine system may contribute to these disturbances and pharmacologically targeting the D3 dopamine receptor (DRD3) is therefore of significant clinical interest. We used functional magnetic resonance imaging to investigate the acute effects of the DRD3 antagonist GSK598809 on anticipatory reward processing, using the monetary incentive delay task (MIDT), and response inhibition using the Go/No-Go task (GNGT). A double-blind, placebo-controlled, crossover design approach was used in abstinent alcohol dependent, abstinent poly-drug dependent and healthy control volunteers. For the MIDT, there was evidence of blunted ventral striatal response to reward in the poly-drug-dependent group under placebo. GSK598809 normalized ventral striatal reward response and enhanced response in the DRD3-rich regions of the ventral pallidum and substantia nigra. Exploratory investigations suggested that the effects of GSK598809 were mainly driven by those with primary dependence on alcohol but not on opiates. Taken together, these findings suggest that GSK598809 may remediate reward deficits in substance dependence. For the GNGT, enhanced response in the inferior frontal cortex of the poly-drug group was found. However, there were no effects of GSK598809 on the neural network underlying response inhibition nor were there any behavioral drug effects on response inhibition. GSK598809 modulated the neural network underlying reward anticipation but not response inhibition, suggesting that DRD3 antagonists may restore reward deficits in addiction.

CognitiveConstruct

RewardProcessing

10.1017/S0954579416001280

Development and psychopathology

Dev Psychopathol

Adolescent cannabis use, change in neurocognitive function, and high-school graduation: A longitudinal study from early adolescence to young adulthood.

The main objective of this prospective longitudinal study was to investigate bidirectional associations between adolescent cannabis use (CU) and neurocognitive performance in a community sample of 294 young men from ages 13 to 20 years. The results showed that in early adolescence, and prior to initiation to CU, poor short-term and working memory, but high verbal IQ, were associated with earlier age of onset of CU. In turn, age of CU onset and CU frequency across adolescence were associated with (a) specific neurocognitive decline in verbal IQ and executive function tasks tapping trial and error learning and reward processing by early adulthood and (b) lower rates of high-school graduation. The association between CU onset and change in neurocognitive function, however, was found to be accounted for by CU frequency. Whereas the link between CU frequency across adolescence and change in verbal IQ was explained (mediated) by high school graduation, the link between CU frequency and tasks tapping trial and error learning were independent from high school graduation, concurrent cannabis and other substance use, adolescent alcohol use, and externalizing behaviors. Findings support prevention efforts aimed at delaying onset and reducing frequency of CU.

CognitiveConstruct

RewardProcessing

10.1002/da.22594

Depression and anxiety

Depress Anxiety

Altered resting state functional connectivity of fear and reward circuitry in comorbid PTSD and major depression.

Individuals with comorbid posttraumatic stress disorder and major depressive disorder (PTSD-MDD) often exhibit greater functional impairment and poorer treatment response than individuals with PTSD alone. Research has not determined whether PTSD-MDD is associated with different network connectivity abnormalities than PTSD alone. We used functional magnetic resonance imaging (fMRI) to measure resting state functional connectivity (rs-FC) patterns of brain regions involved in fear and reward processing in three groups: patients with PTSD-alone (n = 27), PTSD-MDD (n = 21), and trauma-exposed healthy controls (TEHCs, n = 34). Based on previous research, seeds included basolateral amygdala (BLA), centromedial amygdala (CMA), and nucleus accumbens (NAcc). Regardless of MDD comorbidity, PTSD was associated with decreased connectivity of BLA-orbitalfrontal cortex (OFC) and CMA-thalamus pathways, key to fear processing, and fear expression, respectively. PTSD-MDD, compared to PTSD-alone and TEHC, was associated with decreased connectivity across multiple amygdala and striatal-subcortical pathways: BLA-OFC, NAcc-thalamus, and NAcc-hippocampus. Further, while both the BLA-OFC and the NAcc-thalamus pathways were correlated with MDD symptoms, PTSD symptoms correlated with the amygdala pathways (BLA-OFC; CMA-thalamus) only. Comorbid PTSD-MDD may be associated with multifaceted functional connectivity alterations in both fear and reward systems. Clinical implications are discussed.

CognitiveConstruct

RewardProcessing

10.1016/j.ijpsycho.2016.12.007

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

Int J Psychophysiol

A KCNJ6 gene polymorphism modulates theta oscillations during reward processing.

Event related oscillations (EROs) are heritable measures of neurocognitive function that have served as useful phenotype in genetic research. A recent family genome-wide association study (GWAS) by the Collaborative Study on the Genetics of Alcoholism (COGA) found that theta EROs during visual target detection were associated at genome-wide levels with several single nucleotide polymorphisms (SNPs), including a synonymous SNP, rs702859, in the KCNJ6 gene that encodes GIRK2, a G-protein inward rectifying potassium channel that regulates excitability of neuronal networks. The present study examined the effect of the KCNJ6 SNP (rs702859), previously associated with theta ERO to targets in a visual oddball task, on theta EROs during reward processing in a monetary gambling task. The participants were 1601 adolescent and young adult offspring within the age-range of 17-25years (800 males and 801 females) from high-dense alcoholism families as well as control families of the COGA prospective study. Theta ERO power (3.5-7.5Hz, 200-500ms post-stimulus) was compared across genotype groups. ERO theta power at central and parietal regions increased as a function of the minor allele (A) dose in the genotype (AA>AG>GG) in both loss and gain conditions. These findings indicate that variations in the KCNJ6 SNP influence magnitude of theta oscillations at posterior loci during the evaluation of loss and gain, reflecting a genetic influence on neuronal circuits involved in reward-processing. Increased theta power as a function of minor allele dose suggests more efficient cognitive processing in those carrying the minor allele of the KCNJ6 SNPs. Future studies are needed to determine the implications of these genetic effects on posterior theta EROs as possible "protective" factors, or as indices of delays in brain maturation (i.e., lack of frontalization).

CognitiveConstruct

RewardProcessing

10.1111/ejn.13507

The European journal of neuroscience

Eur J Neurosci

Interhemispheric functional connectivity in anorexia and bulimia nervosa.

The functional interplay between hemispheres is fundamental for behavioral, cognitive, and emotional control. Anorexia nervosa (AN) and bulimia nervosa (BN) have been largely studied with brain magnetic resonance imaging (MRI) in relation to the functional mechanisms of high-level processing, but not in terms of possible inter-hemispheric functional connectivity anomalies. Using resting-state functional MRI (fMRI), voxel-mirrored homotopic connectivity (VMHC) and regional inter-hemispheric spectral coherence (IHSC) were studied in 15 AN and 13 BN patients and 16 healthy controls (HC). Using T1-weighted and diffusion tensor imaging MRI scans, regional VMHC values were correlated with the left-right asymmetry of corresponding homotopic gray matter volumes and with the white matter callosal fractional anisotropy (FA). Compared to HC, AN patients exhibited reduced VMHC in cerebellum, insula, and precuneus, while BN patients showed reduced VMHC in dorso-lateral prefrontal and orbito-frontal cortices. The regional IHSC analysis highlighted that the inter-hemispheric functional connectivity was higher in the 'Slow-5' band in all regions except the insula. No group differences in left-right structural asymmetries and in VMHC vs. callosal FA correlations were significant in the comparisons between cohorts. These anomalies, not explained by structural changes, indicate that AN and BN, at least in their acute phase, are associated with a loss of inter-hemispheric connectivity in regions implicated in self-referential, cognitive control and reward processing. These findings may thus gather novel functional markers to explore aberrant features of these eating disorders.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2016.12.011

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

The search for neuroimaging and cognitive endophenotypes: A critical systematic review of studies involving unaffected first-degree relatives of individuals with bipolar disorder.

The phenomenology and underlying pathophysiology of bipolar disorder (BD) are heterogeneous. The identification of putative endophenotypes for BD can aid in the investigation of unique patho-etiological pathways, which may lead to the development of personalised preventative and therapeutic approaches for this multi-faceted disorder. We included original studies involving unaffected first-degree relatives of BD patients (URs) and a healthy control (HC) comparison group with no first-degree family history of mental disorders, investigating: 'cold' and 'hot' cognition and functional and structural neuroimaging. Seventy-seven cross-sectional studies met the inclusion criteria. The present review revealed that URs in comparison with HCs showed: (i) widespread deficits in verbal memory, sustained attention, and executive function; (ii) abnormalities in the reactivity to and regulation of emotional information along with aberrant reward processing, and heightened attentional interference by emotional stimuli; and (iii) less consistency in the findings regarding structural and resting state neuroimaging, and electrophysiological measures.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0166860

PloS one

PLoS One

Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women.

Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p < 0.005 uncorrected. Furthermore, the level of the test subjects' Interest-In-Infants was positively associated with the intensity of right fusiform gyrus response to infant faces and uncomfortable infant faces compared to sad adult faces. In addition, the Perspective Taking subscale score on the Interpersonal Reactivity Index-Chinese was significantly correlated with precuneus activity during uncomfortable infant faces compared to sad adult faces. Our findings suggest that regional brain areas may bias cognitive and emotional responses to infant facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and perspective taking ability.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2016.12.004

Behavioural brain research

Behav Brain Res

Voluntary ethanol consumption changes anticipatory ultrasonic vocalizations but not novelty response.

Novelty and sensation seeking (NSS) and affective disorders are correlated with earlier ethanol (ETOH) consumption, and sustained drinking into adulthood. Understanding the NSS response and affective response before and after voluntary ETOH consumption could elucidate important individual differences promoting sustained ETOH consumption. This study determined that NSS and affective response to rewarding stimulation-measured by ultrasonic vocalizations (USVs)-change after adolescent ETOH voluntary drinking. Rats were tested for their NSS response using the inescapable novelty test. Then rats were tested for their affective response to a natural reward and USVs were measured. The natural reward was experimenter-induced play behavior. Rats were exposed to ETOH for 8 weeks using an intermittent two bottle paradigm. After 8 weeks of voluntary consumption, rats were retested for their response to NSS and affective response to natural reward. Results indicate that voluntary ETOH consumption did not change the response to novelty. Control and ETOH exposed rats decreased their novelty response equally after ETOH consumption, suggesting the decrease was due to age. Importantly, voluntary ETOH consumption changed affective USVs. Compared to water-drinking control rats, ETOH-consuming rats elicited greater anticipatory trill USVs to a natural reward-associated context during a post-drinking probe test. Tickle-induced trill USVs did not change differently between ETOH and control rats. These results provide evidence that voluntary intermittent ETOH exposure increases the anticipation of reward and may represent a form of incentive salience. We postulate these diverging effects could be due to differences in incentive salience or reward processing. Together, these results suggest that voluntary ETOH consumption changes the affective response to conditioned and unconditioned natural rewards and offers a behavioral mechanism for studying affective reward processing after ETOH consumption.

CognitiveConstruct

RewardProcessing

10.1186/s12888-016-1148-3

BMC psychiatry

BMC Psychiatry

Effects of delaying binge drinking on adolescent brain development: a longitudinal neuroimaging study.

Onset of alcohol use by 14 relative to 21 years of age strongly predicts elevated risk for severe alcohol use problems, with 27% versus 4% of individuals exhibiting alcohol dependence within 10 years of onset. What remains unclear is whether this early alcohol use (i) is a marker for later problems, reflected as a pre-existing developmental predisposition, (ii) causes global neural atrophy or (iii) specifically disturbs neuro-maturational processes implicated in addiction, such as executive functions or reward processing. Since our group has demonstrated that a novel intervention program targeting personality traits associated with adolescent alcohol use can prevent the uptake of drinking and binge drinking by 40 to 60%, a crucial question is whether prevention of early onset alcohol misuse will protect adolescent neurodevelopment and which domains of neurodevelopment can be protected. A subsample of 120 youth at high risk for substance misuse and 30 low-risk youth will be recruited from the Co-Venture trial (Montreal, Canada) to take part in this 5-year follow-up neuroimaging study. The Co-Venture trial is a community-based cluster-randomised trial evaluating the effectiveness of school-based personality-targeted interventions on substance use and cognitive outcomes involving approximately 3800 Grade 7 youths. Half of the 120 high-risk participants will have received the preventative intervention program. Cognitive tasks and structural and functional neuroimaging scans will be conducted at baseline, and at 24- and 48-month follow-up. Two functional paradigms will be used: the Stop-Signal Task to measure motor inhibitory control and a modified version of the Monetary Incentive Delay Task to evaluate reward processing. The expected results should help identify biological vulnerability factors, and quantify the consequences of early alcohol abuse as well as the benefits of early intervention using brain metrics.

CognitiveConstruct

RewardProcessing

10.1111/adb.12484

Addiction biology

Addict Biol

Smokers and ex-smokers have shared differences in the neural substrates for potential monetary gains and losses.

Despite an increased understanding of nicotine addiction, there is a scarcity of research comparing the neural correlates of non-drug reward between smokers and ex-smokers. Long-term changes in reward-related brain functioning for non-drug incentives may elucidate patterns of functioning that potentially contribute to ongoing smoking behaviour in current smokers. Similarly, examining the effects of previous chronic nicotine exposure during a period of extended abstinence may reveal whether there are neural correlates responsible for non-drug reward processing that are different from current smokers. The current study, therefore, sets out to examine the neural correlates of reward and loss anticipation, and their respective outcomes, in smokers, ex-smokers and matched controls using a monetary incentive delay task during functional magnetic resonance imaging. Here, we report that in the absence of any significant behavioural group differences, both smokers and ex-smokers showed a significantly greater activation change in the lateral orbitofrontal/anterior insular cortex compared with smokers when anticipating both potential monetary gains and losses. We further report that ex-smokers showed a significantly greater activation change in the ventral putamen compared with both controls and smokers and in the caudate compared with controls during the anticipation of potential monetary losses only. The results suggest that smoking may sensitize striato-orbitofrontal circuitry subserving motivational processes for loss avoidance and reward gain in nicotine addiction.

CognitiveConstruct

RewardProcessing

10.1007/s00213-016-4494-4

Psychopharmacology

Psychopharmacology (Berl)

Deficits in autonomic indices of emotion regulation and reward processing associated with prescription opioid use and misuse.

Prescription opioid misuse and high-dose opioid use may result in allostatic dysregulation of hedonic brain circuitry, leading to reduced emotion regulation capacity. In particular, opioid misuse may blunt the ability to experience and upregulate positive affect from natural rewards. The purpose of this study was to examine associations between opioid use/misuse and autonomic indices of emotion regulation capability in a sample of chronic pain patients receiving prescription opioid pharmacotherapy. Chronic pain patients taking long-term opioid analgesics (N = 40) completed an emotion regulation task while heart rate variability (HRV) was recorded, and also completed self-report measures of opioid misuse, craving, pain severity, and emotional distress. Based on a validated cut-point on the Current Opioid Misuse Measure, participants were grouped as opioid misusers or non-misusers. Opioid misuse status and morphine equivalent daily dose (MEDD) were examined as predictors of HRV and self-reports of emotion regulation. Opioid misusers exhibited significantly less HRV during positive and negative emotion regulation, and significantly less positive effect, than non-misusers, after controlling for confounders including pain severity and emotional distress. MEDD was inversely associated with positive emotion regulation efficacy. Findings implicate the presence of reward processing deficits among chronic pain patients with opioid-misusing behaviors, and opioid dosage was associated with deficient emotion regulation, suggesting the presence of compromised top-down cognitive control over bottom-up hedonic processes. Emotion regulation among opioid misusers may represent an important treatment target.

CognitiveConstruct

RewardProcessing

10.1016/j.jad.2016.11.042

Journal of affective disorders

J Affect Disord

Neural correlates of RDoC reward constructs in adolescents with diverse psychiatric symptoms: A Reward Flanker Task pilot study.

There has been growing interest under the Research Domain Criteria initiative to investigate behavioral constructs and their underlying neural circuitry. Abnormalities in reward processes are salient across psychiatric conditions and may precede future psychopathology in youth. However, the neural circuitry underlying such deficits has not been well defined. Therefore, in this pilot, we studied youth with diverse psychiatric symptoms and examined the neural underpinnings of reward anticipation, attainment, and positive prediction error (PPE, unexpected reward gain). Clinically, we focused on anhedonia, known to reflect deficits in reward function. Twenty-two psychotropic medication-free youth, 16 with psychiatric symptoms, exhibiting a full range of anhedonia, were scanned during the Reward Flanker Task. Anhedonia severity was quantified using the Snaith-Hamilton Pleasure Scale. Functional magnetic resonance imaging analyses were false discovery rate corrected for multiple comparisons. Anticipation activated a broad network, including the medial frontal cortex and ventral striatum, while attainment activated memory and emotion-related regions such as the hippocampus and parahippocampal gyrus, but not the ventral striatum. PPE activated a right-dominant fronto-temporo-parietal network. Anhedonia was only correlated with activation of the right angular gyrus during anticipation and the left precuneus during PPE at an uncorrected threshold. Findings are preliminary due to the small sample size. This pilot characterized the neural circuitry underlying different aspects of reward processing in youth with diverse psychiatric symptoms. These results highlight the complexity of the neural circuitry underlying reward anticipation, attainment, and PPE. Furthermore, this study underscores the importance of RDoC research in youth.

CognitiveConstruct

RewardProcessing

10.1101/lm.042598.116

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

Learn Mem

Conditioned object preference: an alternative approach to measuring reward learning in rats.

Pavlovian conditioned approach behavior can be directed as much toward discrete cues as it is toward the environmental contexts in which those cues are encountered. The current experiments characterized a tendency of rats to approach object cues whose prior exposure had been paired with reward (conditioned object preference, COP). To demonstrate the phenomenon, rats were conditioned to associate cocaine or saline with two different objects. Rats acquired a preference, assessed using investigation times directed toward each object, for the cocaine-paired object following conditioning. Furthermore, high levels of object investigation during cocaine conditioning predicted stronger preferences for the cocaine-paired object in the test phase. Conditioned approach diminished across extinction but was reinstated through a priming injection of cocaine. To determine whether preferences are affected by reward value, rats were conditioned using three objects paired with 0, 5, or 20 mg/kg of cocaine. This produced object preferences in the post-test that scaled with cocaine dose used for conditioning. Finally, we explored whether contextual cues modulate expression of COP by testing rats for renewal of cocaine seeking. When conditioning was conducted in one context and extinction training in a second context, COP was renewed when the rats were retested in the original context. Thus, conditioned object preferences are readily acquired, easily measured, and amenable to a number of standard Pavlovian conditioning manipulations. This task promises to become a valuable addition to the panoply of behavioral tools available to test mechanisms underlying adaptive and maladaptive reward processing.

CognitiveConstruct

RewardProcessing

10.1111/add.13629

Addiction (Abingdon, England)

Addiction

The potential of neuroimaging for identifying predictors of adolescent alcohol use initiation and misuse.

Dysfunction in brain regions underlying impulse control, reward processing and executive function have been associated previously with adolescent alcohol misuse. However, identifying pre-existing neurobiological risk factors, as distinct from changes arising from early alcohol-use, is difficult. Here, we outline how neuroimaging data can identify the neural predictors of adolescent alcohol-use initiation and misuse by using prospective longitudinal studies to follow initially alcohol-naive individuals over time and by neuroimaging adolescents with inherited risk factors for alcohol misuse. A comprehensive narrative of the literature regarding neuroimaging studies published between 2010 and 2016 focusing on predictors of adolescent alcohol use initiation and misuse. Prospective, longitudinal neuroimaging studies have identified pre-existing differences between adolescents who remained alcohol-naive and those who transitioned subsequently to alcohol use. Both functional and structural grey matter differences were observed in temporal and frontal regions, including reduced brain activity in the superior frontal gyrus and temporal lobe, and thinner temporal cortices of future alcohol users. Interactions between brain function and genetic predispositions have been identified, including significant association found between the Ras protein-specific guanine nucleotide releasing factor 2 (RASGRF2) gene and reward-related striatal functioning. Neuroimaging predictors of alcohol use have shown modest utility to date. Future research should use out-of-sample performance as a quantitative measure of a predictor's utility. Neuroimaging data should be combined across multiple modalities, including structural information such as volumetrics and cortical thickness, in conjunction with white-matter tractography. A number of relevant neurocognitive systems should be assayed; particularly, inhibitory control, reward processing and executive functioning. Combining a rich magnetic resonance imaging data set could permit the generation of neuroimaging risk scores, which could potentially yield targeted interventions.

CognitiveConstruct

RewardProcessing

10.1016/j.jtbi.2016.11.025

Journal of theoretical biology

J Theor Biol

A mathematical model of reward and executive circuitry in obsessive compulsive disorder.

The neuronal circuit that controls obsessive and compulsive behaviors involves a complex network of brain regions (some with known involvement in reward processing). Among these are cortical regions, the striatum and the thalamus (which compose the CSTC pathway), limbic areas such as the amygdala and the hippocampus, as well as dopamine pathways. Abnormal dynamic behavior in this brain network is a hallmark feature of patients with increased anxiety and motor activity, like the ones affected by OCD. There is currently no clear understanding of precisely what mechanisms generate these behaviors. We attempt to investigate a collection of connectivity hypotheses of OCD by means of a computational model of the brain circuitry that governs reward and motion execution. Mathematically, we use methods from ordinary differential equations and continuous time dynamical systems. We use classical analytical methods as well as computational approaches to study phenomena in the phase plane (e.g., behavior of the system's solutions when given certain initial conditions) and in the parameter space (e.g., sensitive dependence of initial conditions). We find that different obsessive-compulsive subtypes may correspond to different abnormalities in the network connectivity profiles. We suggest that it is a combination of parameters (connectivity strengths between regions), rather than the value of any one parameter taken independently, that provide the best basis for predicting behavior, and for understanding the heterogeneity of the illness.

CognitiveConstruct

RewardProcessing

10.1523/JNEUROSCI.2350-16.2016

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

J Neurosci

The Lateral Habenula Circuitry: Reward Processing and Cognitive Control.

There has been a growing interest in understanding the role of the lateral habenula (LHb) in reward processing, affect regulation, and goal-directed behaviors. The LHb gets major inputs from the habenula-projecting globus pallidus and the mPFC, sending its efferents to the dopaminergic VTA and SNc, serotonergic dorsal raphe nuclei, and the GABAergic rostromedial tegmental nucleus. Recent studies have made advances in our understanding of the LHb circuit organization, yet the precise mechanisms of its involvement in complex behaviors are largely unknown. To begin to address this unresolved question, we present here emerging cross-species perspectives with a goal to provide a more refined understanding of the role of the LHb circuits in reward and cognition. We begin by highlighting recent findings from rodent experiments using optogenetics, electrophysiology, molecular, pharmacology, and tracing techniques that reveal diverse neural phenotypes in the LHb circuits that may underlie previously undescribed behavioral functions. We then discuss results from electrophysiological studies in macaques that suggest that the LHb cooperates with the anterior cingulate cortex to monitor action outcomes and signal behavioral adjustment. Finally, we provide an integrated summary of cross-species findings and discuss how further research on the connectivity, neural signaling, and physiology of the LHb circuits can deepen our understanding of the role of the LHb in normal and maladaptive behaviors associated with mental illnesses and drug abuse.

CognitiveConstruct

RewardProcessing

10.1007/s40473-016-0098-x

Current behavioral neuroscience reports

Curr Behav Neurosci Rep

The Neural Mechanisms of Meditative Practices: Novel Approaches for Healthy Aging.

Meditation has been shown to have physical, cognitive, and psychological health benefits that can be used to promote healthy aging. However, the common and specific mechanisms of response remain elusive due to the diverse nature of mind-body practices. In this review, we aim to compare the neural circuits implicated in focused-attention meditative practices that focus on present-moment awareness to those involved in active-type meditative practices (e.g., yoga) that combine movement, including chanting, with breath practices and meditation. Recent meta-analyses and individual studies demonstrated common brain effects for attention-based meditative practices and active-based meditations in areas involved in reward processing and learning, attention and memory, awareness and sensory integration, and self-referential processing and emotional control, while deactivation was seen in the amygdala, an area implicated in emotion processing. Unique effects for were found in brain regions involved in body awareness, attention, and the integration of emotion and sensory processing. Effects specific to appeared in brain areas involved in self-control, social cognition, language, speech, tactile stimulation, sensorimotor integration, and motor function. This review suggests that mind-body practices can target different brain systems that are involved in the regulation of attention, emotional control, mood, and executive cognition that can be used to treat or prevent mood and cognitive disorders of aging, such as depression and caregiver stress, or serve as "brain fitness" exercise. Benefits may include improving brain functional connectivity in brain systems that generally degenerate with Alzheimer's disease, Parkinson's disease, and other aging-related diseases.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0165646

PloS one

PLoS One

EEG to Primary Rewards: Predictive Utility and Malleability by Brain Stimulation.

Theta burst stimulation (TBS) is thought to affect reward processing mechanisms, which may increase and decrease reward sensitivity. To test the ability of TBS to modulate response to strong primary rewards, participants hypersensitive to primary rewards were recruited. Twenty men and women with at least two opposite-sex, sexual partners in the last year received two forms of TBS. Stimulations were randomized to avoid order effects and separated by 2 hours to reduce carryover. The two TBS forms have been demonstrated to inhibit (continuous) or excite (intermittent) the left dorsolateral prefrontal cortex using different pulse patterns, which links to brain areas associated with reward conditioning. After each TBS, participants completed tasks assessing their reward responsiveness to monetary and sexual rewards. Electroencephalography (EEG) was recorded. They also reported their number of orgasms in the weekend following stimulation. This signal was malleable by TBS, where excitatory TBS resulted in lower EEG alpha relative to inhibitory TBS to primary rewards. EEG responses to sexual rewards in the lab (following both forms of TBS) predicted the number of orgasms experienced over the forthcoming weekend. TBS may be useful in modifying hypersensitivity or hyposensitivity to primary rewards that predict sexual behaviors. Since TBS altered the anticipation of a sexual reward, TBS may offer a novel treatment for sexual desire problems.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0167095

PloS one

PLoS One

Cerebellum Transcriptome of Mice Bred for High Voluntary Activity Offers Insights into Locomotor Control and Reward-Dependent Behaviors.

The role of the cerebellum in motivation and addictive behaviors is less understood than that in control and coordination of movements. High running can be a self-rewarding behavior exhibiting addictive properties. Changes in the cerebellum transcriptional networks of mice from a line selectively bred for High voluntary running (H) were profiled relative to an unselected Control (C) line. The environmental modulation of these changes was assessed both in activity environments corresponding to 7 days of Free (F) access to running wheel and to Blocked (B) access on day 7. Overall, 457 genes exhibited a significant (FDR-adjusted P-value < 0.05) genotype-by-environment interaction effect, indicating that activity genotype differences in gene expression depend on environmental access to running. Among these genes, network analysis highlighted 6 genes (Nrgn, Drd2, Rxrg, Gda, Adora2a, and Rab40b) connected by their products that displayed opposite expression patterns in the activity genotype contrast within the B and F environments. The comparison of network expression topologies suggests that selection for high voluntary running is linked to a predominant dysregulation of hub genes in the F environment that enables running whereas a dysregulation of ancillary genes is favored in the B environment that blocks running. Genes associated with locomotor regulation, signaling pathways, reward-processing, goal-focused, and reward-dependent behaviors exhibited significant genotype-by-environment interaction (e.g. Pak6, Adora2a, Drd2, and Arhgap8). Neuropeptide genes including Adcyap1, Cck, Sst, Vgf, Npy, Nts, Penk, and Tac2 and related receptor genes also exhibited significant genotype-by-environment interaction. The majority of the 183 differentially expressed genes between activity genotypes (e.g. Drd1) were under-expressed in C relative to H genotypes and were also under-expressed in B relative to F environments. Our findings indicate that the high voluntary running mouse line studied is a helpful model for understanding the molecular mechanisms in the cerebellum that influence locomotor control and reward-dependent behaviors.

CognitiveConstruct

RewardProcessing

10.1038/npp.2016.265

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Dopamine and Opioid Neurotransmission in Behavioral Addictions: A Comparative PET Study in Pathological Gambling and Binge Eating.

Although behavioral addictions share many clinical features with drug addictions, they show strikingly large variation in their behavioral phenotypes (such as in uncontrollable gambling or eating). Neurotransmitter function in behavioral addictions is poorly understood, but has important implications in understanding its relationship with substance use disorders and underlying mechanisms of therapeutic efficacy. Here, we compare opioid and dopamine function between two behavioral addiction phenotypes: pathological gambling (PG) and binge eating disorder (BED). Thirty-nine participants (15 PG, 7 BED, and 17 controls) were scanned with [C]carfentanil and [F]fluorodopa positron emission tomography using a high-resolution scanner. Binding potentials relative to non-displaceable binding (BP) for [C]carfentanil and influx rate constant (K) values for [F]fluorodopa were analyzed with region-of-interest and whole-brain voxel-by-voxel analyses. BED subjects showed widespread reductions in [C]carfentanil BP in multiple subcortical and cortical brain regions and in striatal [F]fluorodopa K compared with controls. In PG patients, [C]carfentanil BP was reduced in the anterior cingulate with no differences in [F]fluorodopa K compared with controls. In the nucleus accumbens, a key region involved in reward processing, [C]Carfentanil BP was 30-34% lower and [F]fluorodopa K was 20% lower in BED compared with PG and controls (p<0.002). BED and PG are thus dissociable as a function of dopaminergic and opioidergic neurotransmission. Compared with PG, BED patients show widespread losses of mu-opioid receptor availability together with presynaptic dopaminergic defects. These findings highlight the heterogeneity underlying the subtypes of addiction and indicate differential mechanisms in the expression of pathological behaviors and responses to treatment.

CognitiveConstruct

RewardProcessing

10.3945/ajcn.116.136903

The American journal of clinical nutrition

Am J Clin Nutr

Food portion size and energy density evoke different patterns of brain activation in children.

Large portions of food promote intake, but the mechanisms that drive this effect are unclear. Previous neuroimaging studies have identified the brain-reward and decision-making systems that are involved in the response to the energy density (ED) (kilocalories per gram) of foods, but few studies have examined the brain response to the food portion size (PS). We used functional MRI (fMRI) to determine the brain response to food images that differed in PSs (large and small) and ED (high and low). Block-design fMRI was used to assess the blood oxygen level-dependent (BOLD) response to images in 36 children (7-10 y old; girls: 50%), which was tested after a 2-h fast. Pre-fMRI fullness and liking were rated on visual analog scales. A whole-brain cluster-corrected analysis was used to compare BOLD activation for main effects of the PS, ED, and their interaction. Secondary analyses were used to associate BOLD contrast values with appetitive traits and laboratory intake from meals for which the portions of all foods were increased. Compared with small-PS cues, large-PS cues were associated with decreased activation in the inferior frontal gyrus (P < 0.01). Compared with low-ED cues, high-ED cues were associated with increased activation in multiple regions (e.g., in the caudate, cingulate, and precentral gyrus) and decreased activation in the insula and superior temporal gyrus (P < 0.01 for all). A PS × ED interaction was shown in the superior temporal gyrus (P < 0.01). BOLD contrast values for high-ED cues compared with low-ED cues in the insula, declive, and precentral gyrus were negatively related to appetitive traits (P < 0.05). There were no associations between the brain response to the PS and either appetitive traits or intake. Cues regarding food PS may be processed in the lateral prefrontal cortex, which is a region that is implicated in cognitive control, whereas ED activates multiple areas involved in sensory and reward processing. Possible implications include the development of interventions that target decision-making and reward systems differently to moderate overeating.

CognitiveConstruct

RewardProcessing

10.1016/j.jaac.2016.09.503

Journal of the American Academy of Child and Adolescent Psychiatry

J Am Acad Child Adolesc Psychiatry

Neural Correlates of Reward Processing in Depressed and Healthy Preschool-Age Children.

Adults and adolescents with major depressive disorder (MDD) show a blunted neural response to rewards. Depression has been validated in children as young as age 3; however, it remains unclear whether blunted response to reward is also a core feature of preschool-onset depression. If so, this would provide further validation for the continuity of the neural correlates of depression across the life span and would identify a potential target for treatment in young children. Fifty-three 4- to 7-year-old children with depression and 25 psychiatrically healthy 4- to 7-year-old children completed a simple guessing task in which points could be won or lost on each trial while event-related potentials (ERPs) were recorded. Psychiatric diagnosis was established using a preschool version of the Kiddie Schedule for Affective Disorders and Depression. Young children with depression showed a reduced differentiation between response to gains and losses, and this finding was driven by a blunted response to reward (i.e., the reward positivity [RewP]). These findings held even when controlling for co-occurring attention-deficit/hyperactivity disorder, oppositional defiant disorder, and generalized anxiety disorder. The RewP did not vary as a function of depression severity within the group with depression. Similar to adults and adolescents with depression, preschoolers with depression display reductions in responsivity to rewards as indexed by the RewP. These findings provide further evidence for continuity in the neural mechanisms associated with depression across the lifespan, and point to altered reward sensitivity as an early-emerging potential target for intervention in preschool-onset depression. Clinical trial registration information-A Randomized Controlled Trial of PCIT-ED for Preschool Depression; http://clinicaltrials.gov/; NCT02076425.

CognitiveConstruct

RewardProcessing

10.1111/bdi.12444

Bipolar disorders

Bipolar Disord

Stress and reward processing in bipolar disorder: a functional magnetic resonance imaging study.

A link between negative life stress and the onset of mood episodes in bipolar disorder (BD) has been established, but processes underlying such a link remain unclear. Growing evidence suggests that stress can negatively affect reward processing and related neurobiological substrates, indicating that a dysregulated reward system may provide a partial explanation. The aim of this study was to test the impact of stress on reward-related neural functioning in BD. Thirteen euthymic or mildly depressed individuals with BD and 15 controls performed a Monetary Incentive Delay (MID) task while undergoing functional magnetic resonance imaging during no-stress and stress (negative psychosocial stressor involving poor performance feedback and threat of monetary deductions) conditions. In hypothesis-driven region-of-interest analyses, a significant group-by-condition interaction emerged in the amygdala during reward anticipation. Relative to controls, while anticipating a potential reward, subjects with BD were characterized by amygdalar hyperactivation in the no-stress condition but hypoactivation during stress. Moreover, relative to controls, subjects with BD had significantly larger amygdala volumes. After controlling for structural differences, the effects of stress on amygdalar function remained, whereas groups no longer differed during the no-stress condition. During reward consumption, a group-by-condition interaction emerged in the putamen due to increased putamen activation in response to rewards in participants with BD during stress, but an opposite pattern in controls. Overall, findings highlight possible impairments in using reward-predicting cues to adaptively engage in goal-directed actions in BD, combined with stress-induced hypersensitivity to reward consumption. Potential clinical implications are discussed.

CognitiveConstruct

RewardProcessing

10.1002/jnr.23878

Journal of neuroscience research

J Neurosci Res

Sex-dependent effects of nicotine on the developing brain.

The use of tobacco products represents a major public health concern, especially among women. Epidemiological data have consistently demonstrated that women have less success quitting tobacco use and a higher risk for developing tobacco-related diseases. The deleterious effects of nicotine are not restricted to adulthood, as nicotinic acetylcholine receptors regulate critical aspects of neural development. However, the exact mechanisms underlying the particular sensitivity of women to develop tobacco dependence have not been well elucidated. In this mini-review, we show that gonadal hormone-mediated sexual differentiation of the brain may be an important determinant of sex differences in the effects of nicotine. We highlight direct interactions between sex steroid hormones and ligand-gated ion channels critical for brain maturation, and discuss the extended and profound sexual differentiation of the brain. We emphasize that nicotine exposure during the perinatal and adolescent periods interferes with normal sexual differentiation and can induce long-lasting, sex-dependent alterations in neuronal structure, cognitive and executive function, learning and memory, and reward processing. We stress important age and sex differences in nicotine's effects and emphasize the importance of including these factors in preclinical research that models tobacco dependence. © 2016 Wiley Periodicals, Inc.

CognitiveConstruct

RewardProcessing

10.1037/abn0000245

Journal of abnormal psychology

J Abnorm Psychol

"Neurobehavioral markers of resilience to depression amongst adolescents exposed to child abuse": Correction to Dennison et al. (2016).

Reports an error in "Neurobehavioral markers of resilience to depression amongst adolescents exposed to child abuse" by Meg J. Dennison, Margaret A. Sheridan, Daniel S. Busso, Jessica L. Jenness, Matthew Peverill, Maya L. Rosen and Katie A. McLaughlin (, 2016[Nov], Vol 125[8], 1201-1212). In the article there was an error in the title. The word "Adolescents" was singular. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2016-52992-014.) Childhood maltreatment is strongly associated with depression, which is characterized by reduced reactivity to reward. Identifying factors that mitigate risk for depression in maltreated children is important for understanding etiological links between maltreatment and depression as well as improving early intervention and prevention. We examine whether high reward reactivity at behavioral and neurobiological levels is a marker of resilience to depressive symptomology in adolescence following childhood maltreatment. A sample of 59 adolescents (21 with a history of maltreatment; Mean Age = 16.95 years, SD = 1.44) completed an fMRI task involving passive viewing of emotional stimuli. BOLD signal changes to positive relative to neutral images were extracted in basal ganglia regions of interest. Participants also completed a behavioral reward-processing task outside the scanner. Depression symptoms were assessed at the time of the MRI and again 2 years later. Greater reward reactivity across behavioral and neurobiological measures moderated the association of maltreatment with baseline depression. Specifically, faster reaction time (RT) to cues paired with monetary reward relative to those unpaired with reward and greater BOLD signal in the left pallidum was associated with lower depression symptoms in maltreated youth. Longitudinally, greater BOLD signal in the left putamen moderated change in depression scores over time, such that higher levels of reward response were associated with lower increases in depression over time among maltreated youths. Reactivity to monetary reward and positive social images, at both behavioral and neurobiological levels, is a potential marker of resilience to depression among adolescents exposed to maltreatment. These findings add to a growing body of work highlighting individual differences in reactivity to reward as a core neurodevelopmental mechanism in the etiology of depression. (PsycINFO Database Record

CognitiveConstruct

RewardProcessing

10.1007/s00429-016-1339-1

Brain structure & function

Brain Struct Funct

Effects of alexithymia and empathy on the neural processing of social and monetary rewards.

Empathy has been found to affect the neural processing of social and monetary rewards. Alexithymia, a subclinical condition showing a close inverse relationship with empathy is linked to dysfunctions of socio-emotional processing in the brain. Whether alexithymia alters the neural processing of rewards, which is currently unknown. Here, we investigated the influence of both alexithymia and empathy on reward processing using a social incentive delay (SID) task and a monetary incentive delay (MID) task in 45 healthy men undergoing functional magnetic resonance imaging. Controlling for temperament-character dimensions and rejection sensitivity, the relationship of alexithymia and empathy with neural activity in several a priori regions of interest (ROIs) was examined by means of partial correlations, while participants anticipated and received social and monetary rewards. Results were considered significant if they survived Holm-Bonferroni correction for multiple comparisons. Alexithymia modulated neural activity in several ROIs of the emotion and reward network, both during the anticipation of social and monetary rewards and in response to the receipt of monetary rewards. In contrast, empathy did not affect reward anticipation and modulated ROI activity only in response to the receipt of social rewards. These results indicate a significant influence of alexithymia on the processing of social and monetary rewards in the healthy brain.

CognitiveConstruct

RewardProcessing

10.1016/j.pscychresns.2016.10.004

Psychiatry research. Neuroimaging

Psychiatry Res Neuroimaging

Differential activation of the frontal pole to high vs low calorie foods: The neural basis of food preference in Anorexia Nervosa?

Neuroimaging studies in anorexia nervosa (AN) suggest that altered food reward processing may result from dysfunction in both limbic reward and cortical control centers of the brain. This fMRI study aimed to index the neural correlates of food reward in a subsample of individuals with restrictive AN: twelve currently ill, fourteen recovered individuals and sixteen healthy controls. Participants were shown pictures of high and low-calorie foods and asked to evaluate how much they wanted to eat each one following a four hour fast. Whole-brain task-activated analysis was followed by psychophysiological interaction analysis (PPI) of the amygdala and caudate. In the AN group, we observed a differential pattern of activation in the lateral frontal pole: increasing following presentation of high-calorie stimuli and decreasing in during presentation of low-calorie food pictures, the opposite of which was seen in the healthy control (HC) group. In addition, decreased activation to food pictures was observed in somatosensory regions in the AN group. PPI analyses suggested hypo-connectivity in reward pathways, and between the caudate and both somatosensory and visual processing regions in the AN group. No significant between-group differences were observed between the recovered group and the currently ill and healthy controls in the PPI analysis. Taken together, these findings further our understanding of the neural processes which may underpin the avoidance of high-calorie foods in those with AN and might exacerbate the development of compulsive weight-loss behavior, despite emaciation.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2016.11.011

NeuroImage

Neuroimage

Independent functional connectivity networks underpin food and monetary reward sensitivity in excess weight.

Overvaluation of palatable food is a primary driver of obesity, and is associated with brain regions of the reward system. However, it remains unclear if this network is specialized in food reward, or generally involved in reward processing. We used functional magnetic resonance imaging (fMRI) to characterize functional connectivity during processing of food and monetary rewards. Thirty-nine adults with excess weight and 37 adults with normal weight performed the Willingness to Pay for Food task and the Monetary Incentive Delay task in the fMRI scanner. A data-driven graph approach was applied to compare whole-brain, task-related functional connectivity between groups. Excess weight was associated with decreased functional connectivity during the processing of food rewards in a network involving primarily frontal and striatal areas, and increased functional connectivity during the processing of monetary rewards in a network involving principally frontal and parietal areas. These two networks were topologically and anatomically distinct, and were independently associated with BMI. The processing of food and monetary rewards involve segregated neural networks, and both are altered in individuals with excess weight.

CognitiveConstruct

RewardProcessing

10.3389/fpsyg.2016.01687

Frontiers in psychology

Front Psychol

No Apparent Influence of Reward upon Visual Statistical Learning.

Humans are capable of detecting and exploiting a variety of environmental regularities, including stimulus-stimulus contingencies (e.g., visual statistical learning) and stimulus-reward contingencies. However, the relationship between these two types of learning is poorly understood. In two experiments, we sought evidence that the occurrence of rewarding events enhances or impairs visual statistical learning. Across all of our attempts to find such evidence, we employed a training stage during which we grouped shapes into triplets and presented triplets one shape at a time in an undifferentiated stream. Participants subsequently performed a surprise recognition task in which they were tested on their knowledge of the underlying structure of the triplets. Unbeknownst to participants, triplets were also assigned no-, low-, or high-reward status. In Experiments 1A and 1B, participants viewed shape streams while low and high rewards were "randomly" given, presented as low- and high-pitched tones played through headphones. Rewards were always given on the third shape of a triplet (Experiment 1A) or the first shape of a triplet (Experiment 1B), and high- and low-reward sounds were always consistently paired with the same triplets. Experiment 2 was similar to Experiment 1, except that participants were required to learn value associations of a subset of shapes before viewing the shape stream. Across all experiments, we observed significant visual statistical learning effects, but the strength of learning did not differ amongst no-, low-, or high-reward conditions for any of the experiments. Thus, our experiments failed to find any influence of rewards on statistical learning, implying that visual statistical learning may be unaffected by the occurrence of reward. The system that detects basic stimulus-stimulus regularities may operate independently of the system that detects reward contingencies.

CognitiveConstruct

RewardProcessing

10.1371/journal.pone.0166704

PloS one

PLoS One

Neural Correlates of Contrast and Humor: Processing Common Features of Verbal Irony.

Irony is a kind of figurative language used by a speaker to say something that contrasts with the context and, to some extent, lends humor to a situation. However, little is known about the brain regions that specifically support the processing of these two common features of irony. The present study had two main aims: (i) investigate the neural basis of irony processing, by delivering short ironic spoken sentences (and their literal counterparts) to participants undergoing fMRI; and (ii) assess the neural effect of two irony parameters, obtained from normative studies: degree of contrast and humor appreciation. Results revealed activation of the bilateral inferior frontal gyrus (IFG), posterior part of the left superior temporal gyrus, medial frontal cortex, and left caudate during irony processing, suggesting the involvement of both semantic and theory-of-mind networks. Parametric models showed that contrast was specifically associated with the activation of bilateral frontal and subcortical areas, and that these regions were also sensitive to humor, as shown by a conjunction analysis. Activation of the bilateral IFG is consistent with the literature on humor processing, and reflects incongruity detection/resolution processes. Moreover, the activation of subcortical structures can be related to the reward processing of social events.

CognitiveConstruct

RewardProcessing

10.3389/fnhum.2016.00555

Frontiers in human neuroscience

Front Hum Neurosci

Reward Anticipation Dynamics during Cognitive Control and Episodic Encoding: Implications for Dopamine.

Dopamine (DA) modulatory activity critically supports motivated behavior. This modulation operates at multiple timescales, but the functional roles of these distinct dynamics on cognition are still being characterized. Reward processing has been robustly linked to DA activity; thus, examining behavioral effects of reward anticipation at different timing intervals, corresponding to different putative dopaminergic dynamics, may help in characterizing the functional role of these dynamics. Towards this end, we present two research studies investigating reward motivation effects on cognitive control and episodic memory, converging in their manipulation of rapid vs. multi-second reward anticipation (consistent with timing profiles of phasic vs. ramping DA, respectively) on performance. Under prolonged reward anticipation, both control and memory performances were enhanced, specifically when combined with other experimental factors: task-informative cues (control task) and reward uncertainty (memory task). Given observations of ramping DA under uncertainty (Fiorillo et al., 2003) and arguments that uncertainty may act as a control signal increasing environmental monitoring (Mushtaq et al., 2011), we suggest that task information and reward uncertainty can both serve as "need for control" signals that facilitate learning via enhanced monitoring, and that this activity may be supported by a ramping profile of dopaminergic activity. Observations of rapid (i.e., phasic) reward on control and memory performance can be interpreted in line with prior evidence, but review indicates that contributions of different dopaminergic timescales in these processes are not well-understood. Future experimental work to clarify these dynamics and characterize a cross-domain role for reward motivation and DA in goal-directed behavior is suggested.

CognitiveConstruct

RewardProcessing

10.1080/08039488.2016.1250948

Nordic journal of psychiatry

Nord J Psychiatry

Adolescents newly diagnosed with eating disorders have structural differences in brain regions linked with eating disorder symptoms.

Adults with eating disorders (ED) show brain volume reductions in the frontal, insular, cingulate, and parietal cortices, as well as differences in subcortical regions associated with reward processing. However, little is known about the structural differences in adolescents with behavioural indications of early stage ED. This is the first study to investigate structural brain changes in adolescents newly diagnosed with ED compared to healthy controls (HC), and to study whether ED cognitions correlate with structural changes in adolescents with ED of short duration. Fifteen adolescent females recently diagnosed with ED, and 28 age-matched HC individuals, were scanned with structural magnetic resonance imaging (MRI). Whole-brain and region-of-interest analyses were conducted using voxel-based morphometry (VBM). ED cognitions were measured with self-report questionnaires and working memory performance was measured with a neuropsychological computerized test. The left superior temporal gyrus had a smaller volume in adolescents with ED than in HC, which correlated with ED cognitions (concerns about eating, weight, and shape). Working memory reaction time correlated positively with insula volumes in ED participants, but not HC. In ED, measurements of restraint and obsession was negatively correlated with temporal gyrus volumes, and positively correlated with cerebellar and striatal volumes. Thus, adolescents with a recent diagnosis of ED had volumetric variations in brain areas linked to ED cognitions, obsessions, and working memory. The findings emphasize the importance of early identification of illness, before potential long-term effects on structure and behaviour occur.

CognitiveConstruct

RewardProcessing

Austin addiction sciences

Austin Addict Sci

Fifty Years in the Development of a Glutaminergic-Dopaminergic Optimization Complex (KB220) to Balance Brain Reward Circuitry in Reward Deficiency Syndrome: A Pictorial.

Dopamine along with other chemical messengers like serotonin, cannabinoids, endorphins and glutamine, play significant roles in brain reward processing. There is a devastating opiate/opioid epidemicin the United States. According to the Centers for Disease Control and Prevention (CDC), at least 127 people, young and old, are dying every day due to narcotic overdose and alarmingly heroin overdose is on the rise. The Food and Drug Administration (FDA) has approved some Medication-Assisted Treatments (MATs) for alcoholism, opiate and nicotine dependence, but nothing for psychostimulant and cannabis abuse. While these pharmaceuticals are essential for the short-term induction of "psychological extinction," in the long-term caution is necessary because their use favors blocking dopaminergic function indispensable for achieving normal satisfaction in life. The two institutions devoted to alcoholism and drug dependence (NIAAA & NIDA) realize that MATs are not optimal and continue to seek better treatment options. We review, herein, the history of the development of a glutaminergic-dopaminergic optimization complex called KB220 to provide for the possible eventual balancing of the brain reward system and the induction of "dopamine homeostasis." This complex may provide substantial clinical benefit to the victims of Reward Deficiency Syndrome (RDS) and assist in recovery from iatrogenically induced addiction to unwanted opiates/opioids and other addictive behaviors.

CognitiveConstruct

RewardProcessing

10.1016/j.gtc.2016.07.009

Gastroenterology clinics of North America

Gastroenterol Clin North Am

Physiologic and Neural Controls of Eating.

Multiple physiologic and neural systems contribute to the controls over what and how much we eat. These systems include signaling involved in the detection and signaling of nutrient availability, signals arising from consumed nutrients that provide feedback information during a meal to induce satiation, and signals related to the rewarding properties of eating. Each of these has a separate neural representation, but important interactions among these systems are critical to the overall controls of food intake.

CognitiveConstruct

RewardProcessing

10.1523/ENEURO.0022-16.2016

eNeuro

eNeuro

Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation.

The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats () were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.

CognitiveConstruct

RewardProcessing

10.1080/15374416.2016.1233502

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

J Clin Child Adolesc Psychol

Dampening Positive Affect and Neural Reward Responding in Healthy Children: Implications for Affective Inflexibility.

Blunted reward processing is evident in and may contribute to the onset of major depressive disorder. However, it is unclear what mechanisms contribute to the development of blunted reward-response prior to depression onset. The current study examined how individual differences in the tendency to dampen positive affect, an affect regulation strategy that decreases positive affect, are associated with reward responding and related brain activation in 39 healthy children (ages 7-10; 51% female; 79% White). To do this, we examined neural responses to winning a reward (candy) within the context of a previous loss, win, or neutral outcome. Whole-brain regression analyses revealed that self-reported tendencies to engage in dampening were associated with blunted striatum and thalamic activation during a winning outcome when following a previous loss outcome, as compared to when following a neutral outcome. This finding was above and beyond the influence of current depressive symptoms. However, tendencies to dampen positive affect were not associated with neural activity during the second of 2 consecutive win outcomes, and thus did not support the notion that dampening is associated with an inability to maintain reward responding. In youth, tendencies to dampen positive affect may be associated with less ability to flexibly upregulate neural reward responding following a loss, possibly leading to the development of affective inflexibility and increased vulnerability to depression. Dampening positive affect may be one mechanism that contributes to aberrant neural reward responding via affective inflexibility and may be a target for prevention in youth.

CognitiveConstruct

RewardProcessing

10.1037/abn0000215

Journal of abnormal psychology

J Abnorm Psychol

Neurobehavioral markers of resilience to depression amongst adolescents exposed to child abuse.

Childhood maltreatment is strongly associated with depression, which is characterized by reduced reactivity to reward. Identifying factors that mitigate risk for depression in maltreated children is important for understanding etiological links between maltreatment and depression as well as improving early intervention and prevention. We examine whether high reward reactivity at behavioral and neurobiological levels is a marker of resilience to depressive symptomology in adolescence following childhood maltreatment. A sample of 59 adolescents (21 with a history of maltreatment; Mean Age = 16.95 years, SD = 1.44) completed an fMRI task involving passive viewing of emotional stimuli. BOLD signal changes to positive relative to neutral images were extracted in basal ganglia regions of interest. Participants also completed a behavioral reward-processing task outside the scanner. Depression symptoms were assessed at the time of the MRI and again 2 years later. Greater reward reactivity across behavioral and neurobiological measures moderated the association of maltreatment with baseline depression. Specifically, faster reaction time (RT) to cues paired with monetary reward relative to those unpaired with reward and greater BOLD signal in the left pallidum was associated with lower depression symptoms in maltreated youth. Longitudinally, greater BOLD signal in the left putamen moderated change in depression scores over time, such that higher levels of reward response were associated with lower increases in depression over time among maltreated youths. Reactivity to monetary reward and positive social images, at both behavioral and neurobiological levels, is a potential marker of resilience to depression among adolescents exposed to maltreatment. These findings add to a growing body of work highlighting individual differences in reactivity to reward as a core neurodevelopmental mechanism in the etiology of depression. (PsycINFO Database Record

CognitiveConstruct

RewardProcessing

10.1016/j.nicl.2016.10.006

NeuroImage. Clinical

Neuroimage Clin

Functional connectivity in cortico-subcortical brain networks underlying reward processing in attention-deficit/hyperactivity disorder.

Many patients with attention-deficit/hyperactivity disorder (ADHD) display aberrant reward-related behavior. Task-based fMRI studies have related atypical reward processing in ADHD to altered BOLD activity in regions underlying reward processing such as ventral striatum and orbitofrontal cortex. However, it remains unclear whether the observed effects are region-specific or related to changes in functional connectivity of networks supporting reward processing. Here we use resting-state fMRI to comprehensively delineate the functional connectivity architecture underlying aberrant reward processing in ADHD. We assessed resting-state functional connectivity of four networks that support reward processing. These networks showed high spatial overlap with the default mode, fronto-parietal, lateral visual, and salience networks, yet only activity within the salience network was effectively sensitive to reward value. We parcelled these networks into their functional cortical and subcortical subregions and obtained functional connectivity matrices by computing Pearson correlations between the regional time series. We compared functional connectivity within each of the four networks between participants with ADHD and controls, and related functional connectivity to dimensional ADHD symptom scores across all participants ( = 444; age range: 8.5-30.5; mean age: 17.7). We did not observe significant ADHD-related alterations in functional connectivity of the salience network, which included key reward regions. Instead, levels of inattention symptoms modulated functional connectivity of the default-mode and fronto-parietal networks, which supported general task processing. The present study does not corroborate previous childhood evidence for functional connectivity alterations between key reward processing regions in adolescents and young adults with ADHD. Our findings could point to developmental normalization or indicate that reward-processing deficits result from functional connectivity alterations in general task-related networks.

CognitiveConstruct

RewardProcessing

10.1016/j.jaac.2016.08.005

Journal of the American Academy of Child and Adolescent Psychiatry

J Am Acad Child Adolesc Psychiatry

Altered Neural Efficiency of Decision Making During Temporal Reward Discounting in Anorexia Nervosa.

The ability of individuals with anorexia nervosa (AN) to resist hunger and restrict caloric intake is often believed to reflect an unusual amount of self-control. However, the underlying neural substrate is poorly understood, especially in adolescent patients. Functional magnetic resonance imaging was used during an intertemporal choice task to probe the hemodynamic correlates of a common measurement of self-control-delayed (monetary) reward discounting-in a sample of acutely ill, predominately adolescent female patients with AN (n = 31) and age-matched healthy controls (n = 31). Delayed discounting rates did not differ between the groups, but decision making was consistently faster in the AN group. Although no group differences in the neural correlates of reward valuation were evident, activation associated with decision making was decreased in the AN group, most notably in the lateral prefrontal and posterior parietal regions implicated in executive control. Follow-up analysis of difficult decisions showed decreased activation in the AN group in a region of the dorsal anterior cingulate cortex. Decreased activation in frontoparietal regions involved in decision making, but faster and more consistent choice behavior, suggests that the altered efficiency of neural resource allocation might underlie an increased level of self-control in AN. This pattern of neural activation and behavior might reflect an ingrained "habit" to sustain high-level proactive (anticipatory) cognitive control in AN, which in turn might compromise reactive control mechanisms needed to adapt to changing cognitive demands, such as when difficult decisions must be made.

CognitiveConstruct

RewardProcessing

10.1016/j.jaac.2016.07.778

Journal of the American Academy of Child and Adolescent Psychiatry

J Am Acad Child Adolesc Psychiatry

Reward-Based Spatial Learning in Teens With Bulimia Nervosa.

To assess the functioning of mesolimbic and fronto-striatal areas involved in reward-based spatial learning in teenaged girls with bulimia nervosa (BN) that might be involved in the development and maintenance of maladaptive behaviors characteristic of the disorder. We compared functional magnetic resonance imaging blood oxygen level-dependent response in 27 adolescent girls with BN to that of 27 healthy, age-matched control participants during a reward-based learning task that required learning to use extra-maze cues to navigate a virtual 8-arm radial maze to find hidden rewards. We compared groups in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudo-randomly to experimentally prevent learning. Both groups learned to navigate the maze to find hidden rewards, but group differences in brain activity associated with maze navigation and reward processing were detected in the fronto-striatal regions and right anterior hippocampus. Unlike healthy adolescents, those with BN did not engage the right inferior frontal gyrus during maze navigation, activated the right anterior hippocampus during the receipt of unexpected rewards (control condition), and deactivated the left superior frontal gyrus and right anterior hippocampus during expected reward receipt (learning condition). These patterns of hippocampal activation in the control condition were significantly associated with the frequency of binge-eating episodes. Adolescents with BN displayed abnormal functioning of the anterior hippocampus and fronto-striatal regions during reward-based spatial learning. These findings suggest that an imbalance in control and reward circuits may arise early in the course of BN. Clinical trial registration information-An fMRI Study of Self-Regulation in Adolescents With Bulimia Nervosa; https://clinicaltrials.gov/; NCT00345943.

CognitiveConstruct

RewardProcessing

10.1016/j.jaac.2016.07.779

Journal of the American Academy of Child and Adolescent Psychiatry

J Am Acad Child Adolesc Psychiatry

Brain Reward Processing in Eating Disorders: Opportunities to Build Upon?

CognitiveConstruct

RewardProcessing

10.1017/S0033291716001963

Psychological medicine

Psychol Med

Neural alterations of fronto-striatal circuitry during reward anticipation in euthymic bipolar disorder.

Bipolar disorder (BD), with the hallmark symptoms of elevated and depressed mood, is thought to be characterized by underlying alterations in reward-processing networks. However, to date the neural circuitry underlying abnormal responses during reward processing in BD remains largely unexplored. The aim of this study was to investigate whether euthymic BD is characterized by aberrant ventral striatal (VS) activation patterns and altered connectivity with the prefrontal cortex in response to monetary gains and losses. During functional magnetic resonance imaging 20 euthymic BD patients and 20 age-, gender- and intelligence quotient-matched healthy controls completed a monetary incentive delay paradigm, to examine neural processing of reward and loss anticipation. A priori defined regions of interest (ROIs) included the VS and the anterior prefrontal cortex (aPFC). Psychophysiological interactions (PPIs) between these ROIs were estimated and tested for group differences for reward and loss anticipation separately. BD participants, relative to healthy controls, displayed decreased activation selectively in the left and right VS during anticipation of reward, but not during loss anticipation. PPI analyses showed decreased functional connectivity between the left VS and aPFC in BD patients compared with healthy controls during reward anticipation. This is the first study showing decreased VS activity and aberrant connectivity in the reward-processing circuitry in euthymic, medicated BD patients during reward anticipation. Our findings contrast with research supporting a reward hypersensitivity model of BD, and add to the body of literature suggesting that blunted activation of reward processing circuits may be a vulnerability factor for mood disorders.

CognitiveConstruct

RewardProcessing

10.3233/JAD-160107

Journal of Alzheimer's disease : JAD

J Alzheimers Dis

Brain Regions Involved in Arousal and Reward Processing are Associated with Apathy in Alzheimer's Disease and Frontotemporal Dementia.

Apathy is a common and problematic symptom of several neurodegenerative illnesses, but its neuroanatomical bases are not understood. To determine the regions associated with apathy in subjects with mild Alzheimer's disease (AD) using a method that accounts for the significant co-linearity of regional atrophy and neuropsychiatric symptoms. We identified 57 subjects with mild AD (CDR = 1) and neuropsychiatric symptoms in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We performed a multivariate multiple regression with LASSO regularization on all symptom subscales of the Neuropsychiatric Inventory and the whole-brain ROI volumes calculated from their baseline MRIs with FreeSurfer. We compared our results to those from a previous study using the same method in patients with frontotemporal dementia (FTD) and corticobasal syndrome (CBS). Of neuropsychiatric symptoms, apathy showed the most robust neuroanatomical associations in the AD subjects. Atrophy of the following regions were independently associated with apathy: the ventromedial prefrontal cortex; ventrolateral prefrontal cortex; posterior cingulate cortex and adjacent lateral cortex; and the bank of the superior temporal sulcus. These results replicate previous studies using FTD and CBS patients, mostly agree with the previous literature on apathy in AD, and correspond to the Medial and Orbital Prefrontal Cortex networks identified in non-human primates. The current study, previous studies from our laboratory, and the previous literature suggest that impairment of the same brain networks involved in arousal, threat response, and reward processing are associated with apathy in AD and FTD.

CognitiveConstruct

RewardProcessing

10.1093/schbul/sbw142

Schizophrenia bulletin

Schizophr Bull

Ventral Striatal Dysfunction and Symptom Expression in Individuals With Schizotypal Personality Traits and Early Psychosis.

Striatal abnormalities play a crucial role in the pathophysiology of schizophrenia. Growing evidence suggests an association between aberrant striatal activity during reward anticipation and symptom dimensions in schizophrenia. However, it is not clear whether this holds across the psychosis continuum. The aim of the present study was to investigate alterations of ventral striatal activation during reward anticipation and its relationship to symptom expression in persons with schizotypal personality traits (SPT) and first-episode psychosis. Twenty-six individuals with high SPT, 26 patients with non-affective first-episode psychosis (including 13 with brief psychotic disorder (FEP-BPD) and 13 with first-episode schizophrenia [FEP-SZ]) and 25 healthy controls underwent event-related functional magnetic resonance imaging while performing a variant of the Monetary Incentive Delay task. Ventral striatal activation was positively correlated with total symptom severity, in particular with levels of positive symptoms. This association was observed across the psychosis continuum and within each subgroup. Patients with FEP-SZ showed the strongest elevation of striatal activation during reward anticipation, although symptom levels did not differ between groups in the psychosis continuum. While our results provide evidence that variance in striatal activation is mainly explained by dimensional symptom expression, patients with schizophrenia show an additional dysregulation of striatal activation. Trans-diagnostic approaches are promising in order to disentangle dimensional and categorical neural mechanisms in the psychosis continuum.

CognitiveConstruct

RewardProcessing

10.1038/nm.4218

Nature medicine

Nat Med

Re-evaluating the link between neuropsychiatric disorders and dysregulated adult neurogenesis.

People diagnosed with neuropsychiatric disorders such as depression, anxiety, addiction or schizophrenia often have dysregulated memory, mood, pattern separation and/or reward processing. These symptoms are indicative of a disrupted function of the dentate gyrus (DG) subregion of the brain, and they improve with treatment and remission. The dysfunction of the DG is accompanied by structural maladaptations, including dysregulation of adult-generated neurons. An increasing number of studies using modern inducible approaches to manipulate new neurons show that the behavioral symptoms in animal models of neuropsychiatric disorders can be produced or exacerbated by the inhibition of DG neurogenesis. Thus, here we posit that the connection between neuropsychiatric disorders and dysregulated DG neurogenesis is beyond correlation or epiphenomenon, and that the regulation of adult-generated DG neurogenesis merits continued and focused attention in the ongoing effort to develop novel treatments for neuropsychiatric disorders.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsw141

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Reward processing in the value-driven attention network: reward signals tracking cue identity and location.

Through associative reward learning, arbitrary cues acquire the ability to automatically capture visual attention. Previous studies have examined the neural correlates of value-driven attentional orienting, revealing elevated activity within a network of brain regions encompassing the visual corticostriatal loop [caudate tail, lateral occipital complex (LOC) and early visual cortex] and intraparietal sulcus (IPS). Such attentional priority signals raise a broader question concerning how visual signals are combined with reward signals during learning to create a representation that is sensitive to the confluence of the two. This study examines reward signals during the cued reward training phase commonly used to generate value-driven attentional biases. High, compared with low, reward feedback preferentially activated the value-driven attention network, in addition to regions typically implicated in reward processing. Further examination of these reward signals within the visual system revealed information about the identity of the preceding cue in the caudate tail and LOC, and information about the location of the preceding cue in IPS, while early visual cortex represented both location and identity. The results reveal teaching signals within the value-driven attention network during associative reward learning, and further suggest functional specialization within different regions of this network during the acquisition of an integrated representation of stimulus value.

CognitiveConstruct

RewardProcessing

10.1093/scan/nsw122

Social cognitive and affective neuroscience

Soc Cogn Affect Neurosci

Neural responses to reward in childhood: relations to early behavioral inhibition and social anxiety.

Behavioral inhibition (BI) is an early temperamental profile characterized by negative reactivity to novelty, withdrawal from social situations, and increased risk for social anxiety. Previous research associated BI assessed in early childhood to striatal hypersensitivity in mid-to-late adolescence. The present study examined this association among 10 year-olds, characterized with BI at ages 24 and 36 months on measures of temperamental reactivity. Participants (n = 40) were studied at age 10 using a reward processing task during functional magnetic resonance imaging (fMRI). Child- and maternal-report of social anxiety symptoms was collected at ages 10 and 13. Findings indicate greater caudate activation and stronger striatal connectivity in high, compared to low, behaviorally inhibited children. Caudate activation related to social anxiety symptoms at both ages. These findings suggest that enhanced striatal responsivity reliably manifests among high behaviorally inhibited children as early as age 10. This may reflect hyper-sensitivity to reward or excessive motivation to avoid errors.

CognitiveConstruct

RewardProcessing

10.1073/pnas.1614340113

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

Proc Natl Acad Sci U S A

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia.

Dopamine (DA) promotes wakefulness, and DA transporter inhibitors such as dextroamphetamine and methylphenidate are effective for increasing arousal and inducing reanimation, or active emergence from general anesthesia. DA neurons in the ventral tegmental area (VTA) are involved in reward processing, motivation, emotion, reinforcement, and cognition, but their role in regulating wakefulness is less clear. The current study was performed to test the hypothesis that selective optogenetic activation of VTA DA neurons is sufficient to induce arousal from an unconscious, anesthetized state. Floxed-inverse (FLEX)-Channelrhodopsin2 (ChR2) expression was targeted to VTA DA neurons in DA transporter (DAT)-cre mice (ChR2+ group; = 6). Optical VTA stimulation in ChR2+ mice during continuous, steady-state general anesthesia (CSSGA) with isoflurane produced behavioral and EEG evidence of arousal and restored the righting reflex in 6/6 mice. Pretreatment with the D1 receptor antagonist SCH-23390 before optical VTA stimulation inhibited the arousal responses and restoration of righting in 6/6 ChR2+ mice. In control DAT-cre mice, the VTA was targeted with a viral vector lacking the ChR2 gene (ChR2- group; = 5). VTA optical stimulation in ChR2- mice did not restore righting or produce EEG changes during isoflurane CSSGA in 5/5 mice. These results provide compelling evidence that selective stimulation of VTA DA neurons is sufficient to induce the transition from an anesthetized, unconscious state to an awake state, suggesting critical involvement in behavioral arousal.

CognitiveConstruct

RewardProcessing

10.3389/fnbeh.2016.00189

Frontiers in behavioral neuroscience

Front Behav Neurosci

Adolescent Maturational Transitions in the Prefrontal Cortex and Dopamine Signaling as a Risk Factor for the Development of Obesity and High Fat/High Sugar Diet Induced Cognitive Deficits.

Adolescence poses as both a transitional period in neurodevelopment and lifestyle practices. In particular, the developmental trajectory of the prefrontal cortex (PFC), a critical region for behavioral control and self-regulation, is enduring, not reaching functional maturity until the early 20 s in humans. Furthermore, the neurotransmitter dopamine is particularly abundant during adolescence, tuning the brain to rapidly learn about rewards and regulating aspects of neuroplasticity. Thus, adolescence is proposed to represent a period of vulnerability towards reward-driven behaviors such as the consumption of palatable high fat and high sugar diets. This is reflected in the increasing prevalence of obesity in children and adolescents as they are the greatest consumers of "junk foods". Excessive consumption of diets laden in saturated fat and refined sugars not only leads to weight gain and the development of obesity, but experimental studies with rodents indicate they evoke cognitive deficits in learning and memory process by disrupting neuroplasticity and altering reward processing neurocircuitry. Consumption of these high fat and high sugar diets have been reported to have a particularly pronounced impact on cognition when consumed during adolescence, demonstrating a susceptibility of the adolescent brain to enduring cognitive deficits. The adolescent brain, with heightened reward sensitivity and diminished behavioral control compared to the mature adult brain, appears to be a risk for aberrant eating behaviors that may underpin the development of obesity. This review explores the neurodevelopmental changes in the PFC and mesocortical dopamine signaling that occur during adolescence, and how these potentially underpin the overconsumption of palatable food and development of obesogenic diet-induced cognitive deficits.

CognitiveConstruct

RewardProcessing

10.1016/j.neubiorev.2016.09.021

Neuroscience and biobehavioral reviews

Neurosci Biobehav Rev

The research domain criteria framework: The case for anterior cingulate cortex.

The United States National Institute of Mental Health has recently promoted the Research Domain Criteria framework, which emphasizes the study of neurocognitive constructs that cut across different disorders. These constructs are said to express dimensionally across the population, giving rise to psychopathologies only in the extreme cases where that expression is maladaptive. Inspired by the RDoC framework, we propose that recent insights into the function of anterior cingulate cortex (ACC), a brain area said to be responsible for selecting and motivating extended behaviors, may elucidate the etiology of a diverse array of mental disorders. We argue that ACC function contributes to individual differences in personality traits related to reward sensitivity and persistence, and propose that the maladaptive expression of these traits contributes to multiple mental and neurological disorders. Our discussion is organized around a computational framework that relates the reward processing and control functions of ACC, as revealed by two electrophysiological phenomena called the reward positivity and frontal midline theta oscillations, to a distributed neural system underlying cognitive control.

CognitiveConstruct

RewardProcessing

10.1038/ncomms13154

Nature communications

Nat Commun

Phasic dopamine release in the rat nucleus accumbens predicts approach and avoidance performance.

Dopamine (DA) is critical for reward processing, but significantly less is known about its role in punishment avoidance. Using a combined approach-avoidance task, we measured phasic DA release in the nucleus accumbens (NAc) of rats during presentation of cues that predicted reward, punishment or neutral outcomes and investigated individual differences based on avoidance performance. Here we show that DA release within a single microenvironment is higher for reward and avoidance cues compared with neutral cues and positively correlated with poor avoidance behaviour. We found that DA release delineates trial-type during sessions with good avoidance but is non-selective during poor avoidance, with high release correlating with poor performance. These data demonstrate that phasic DA is released during cued approach and avoidance within the same microenvironment and abnormal processing of value signals is correlated with poor performance.

CognitiveConstruct

RewardProcessing

10.1016/j.bbr.2016.10.012

Behavioural brain research

Behav Brain Res

Decreasing GABA function within the medial prefrontal cortex or basolateral amygdala decreases sociability.

Decreased sociability is a symptom of psychiatric conditions including autism-spectrum disorder and schizophrenia. Both of these conditions are associated with decreases in GABA function, particularly in the medial prefrontal cortex (PFC) and the basolateral amygdala (BLA); structures that are components of the social brain. Here, we determined if decreasing GABA transmission within either the PFC or the BLA decreases social behavior. Rats were implanted with cannulae aimed at either the medial PFC or the BLA and then were tested on up to 4 behavioral tests following bilateral infusions of 0.5μl bicuculline methiodide (BMI, a GABA receptor antagonist) at doses of 0, 25, or 50ng/μl. Rats were tested in the social interaction test, the social preference test, the sucrose preference test and for locomotor activity (BLA infusions only). Intra-BLA or PFC BMI infusions decreased the amount of time and the number of social interactions in the social interaction test. Further, in the social preference test, rats infused with 50ng BMI no longer exhibited a preference to explore a social over a non-social stimulus. The change in sociability was not due to a change in reward processing or locomotor behavior. Decreasing GABA transmission in either the medial PFC or BLA decreased sociability. Thus, changes in GABA signaling observed in conditions such as autism or schizophrenia may mediate the social withdrawal characteristic of these conditions. Moreover, they suggest that social withdrawal may be treated by drugs that potentiate GABA transmission.

CognitiveConstruct

RewardProcessing

10.1002/da.22576

Depression and anxiety

Depress Anxiety

Spared internal but impaired external reward prediction error signals in major depressive disorder during reinforcement learning.

Major depressive disorder (MDD) creates debilitating effects on a wide range of cognitive functions, including reinforcement learning (RL). In this study, we sought to assess whether reward processing as such, or alternatively the complex interplay between motivation and reward might potentially account for the abnormal reward-based learning in MDD. A total of 35 treatment resistant MDD patients and 44 age matched healthy controls (HCs) performed a standard probabilistic learning task. RL was titrated using behavioral, computational modeling and event-related brain potentials (ERPs) data. MDD patients showed comparable learning rate compared to HCs. However, they showed decreased lose-shift responses as well as blunted subjective evaluations of the reinforcers used during the task, relative to HCs. Moreover, MDD patients showed normal internal (at the level of error-related negativity, ERN) but abnormal external (at the level of feedback-related negativity, FRN) reward prediction error (RPE) signals during RL, selectively when additional efforts had to be made to establish learning. Collectively, these results lend support to the assumption that MDD does not impair reward processing per se during RL. Instead, it seems to alter the processing of the emotional value of (external) reinforcers during RL, when additional intrinsic motivational processes have to be engaged.

CognitiveConstruct

RewardProcessing

10.1038/npp.2016.189

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Neuropsychopharmacology

Prior Cocaine Experience Impairs Normal Phasic Dopamine Signals of Reward Value in Accumbens Shell.

Dopamine signals have repeatedly been linked to associative learning and motivational processes. However, there is considerably less agreement on a role for dopamine in reward processing, and therefore whether neuroplastic changes in dopamine function following chronic exposure to drugs of abuse such as cocaine may impair appropriate valuation of rewarding stimuli. To quantify this, we voltammetrically measured real-time dopamine release in the nucleus accumbens (NAc) core or shell while rats received unsignaled deliveries of either a small (1 pellet) or large (2 pellets) reward. In drug-naive controls, core dopamine signals did not discriminate between reward size at any point, while in the shell dopamine encoded magnitude differences only in a slower postpeak period. Despite this lack of discrimination between rewards by the peak DA response, controls easily discriminated between reward options in a subsequent choice task. In contrast, phasic dopamine reward signals were strongly altered by cocaine experience; core dopamine decreased peak response but increased discrimination between reward magnitudes while shell lost phasic responses to reward receipt altogether. Notably, animals with cocaine-associated alterations in dopamine signals for reward magnitude failed to subsequently discriminate between reward options. These findings suggest that cocaine self-administration alters the ability for dopamine signals to appropriately assign value to rewards and thus may in part contribute to later deficits in behaviors that depend on appropriate outcome valuation.

CognitiveConstruct

RewardProcessing

10.1016/j.neuroimage.2016.08.067

NeuroImage

Neuroimage

Acute stress increases risky decisions and dampens prefrontal activation among adolescent boys.

Adolescence is characterized by increased risky decision-making, enhanced mesolimbic response to risk and reward, increased perceived stress, and heightened physiological response to stress relative to other age groups. In adults, evidence suggests that acute stress increases risky decision-making by stress-induced increases of dopamine in regions implicated in reward processing and decision-making. Acute stress also increases risky decision-making in adolescents, but the underlying neurobiological mechanisms remained unexplored. In this study, daily self-reports of stress were documented in adolescents and adults. Participants completed two fMRI visits during which they performed a risky decision-making task: once each when they endorsed a high and low level of stress. Results revealed that adolescent males took more advantageous risks under high stress relative to low stress whereas adult males took fewer non-advantageous risks under high stress relative to low stress. Adolescent males also showed a stress-related decrease in prefrontal activation when making risky decisions from high stress to low stress while adult males maintained prefrontal activation when making risky decisions across stress conditions. Adolescent and adult females did not exhibit stress-related changes in risky decisions. Moreover, greater prefrontal activation under stress was associated with fewer non-advantageous risks taken under stress. Implications for risk-taking under stress are discussed in light of these findings.

CognitiveConstruct

RewardProcessing

10.1176/appi.ajp.2016.16010111

The American journal of psychiatry

Am J Psychiatry

Dopaminergic Enhancement of Striatal Response to Reward in Major Depression.

Major depressive disorder is characterized by reduced reward-related striatal activation and dysfunctional reward learning, putatively reflecting decreased dopaminergic signaling. The goal of this study was to test whether a pharmacological challenge designed to facilitate dopaminergic transmission can enhance striatal responses to reward and improve reward learning in depressed individuals. In a double-blind placebo-controlled design, 46 unmedicated depressed participants and 43 healthy control participants were randomly assigned to receive either placebo or a single low dose (50 mg) of the D/D receptor antagonist amisulpride, which is believed to increase dopamine signaling through presynaptic autoreceptor blockade. To investigate the effects of increased dopaminergic transmission on reward-related striatal function and behavior, a monetary incentive delay task (in conjunction with functional MRI) and a probabilistic reward learning task were administered at absorption peaks of amisulpride. Depressed participants selected previously rewarded stimuli less frequently than did control participants, indicating reduced reward learning, but this effect was not modulated by amisulpride. Relative to depressed participants receiving placebo (and control participants receiving amisulpride), depressed participants receiving amisulpride exhibited increased striatal activation and potentiated corticostriatal functional connectivity between the nucleus accumbens and the midcingulate cortex in response to monetary rewards. Stronger corticostriatal connectivity in response to rewards predicted better reward learning among depressed individuals receiving amisulpride as well as among control participants receiving placebo. Acute enhancement of dopaminergic transmission potentiated reward-related striatal activation and corticostriatal functional connectivity in depressed individuals but had no behavioral effects. Taken together, the results suggest that targeted pharmacological treatments may normalize neural correlates of reward processing in depression; despite such acute effects on neural function, behavioral modification may require more chronic exposure. This is consistent with previous reports that antidepressant effects of amisulpride in depression emerged after sustained administration.

CognitiveConstruct

RewardProcessing

10.1016/j.physbeh.2016.10.004

Physiology & behavior

Physiol Behav

Age differences in appetitive Pavlovian conditioning and extinction in rats.

Mounting evidence indicates that adolescents exhibit heightened sensitivity to rewards and reward-related cues compared to adults, and that adolescents are often unable to exert behavioral control in the face of such cues. Moreover, differences in reward processing during adolescence have been linked to heightened risk taking and impulsivity. However, little is known about the processes by which adolescents learn about the appetitive properties of environmental stimuli that signal reward. To address this, Pavlovian conditioning procedures were used to test for differences in excitatory conditioning between adult and adolescent rats using various schedules of reinforcement. Specifically, separate cohorts of adult and adolescent rats were trained under conditions of consistent (continuous) or intermittent (partial) reinforcement. We found that the acquisition of anticipatory responding to a continuously-reinforced cue proceeded similarly in adolescents and adults. In contrast, responding increased at a greater rate in adolescents compared to adults during presentations of a partially-reinforced cue. We subsequently compared the ability of adolescent and adult rats to dynamically adjust the representation of a reward-predictive cue during extinction trials, in which a secondary inhibitory representation is acquired for the previously-reinforced stimulus. We observed significant age differences in the ability to flexibly update cue representations during extinction, in that the appetitive properties of cues with a history of either continuous or partial reinforcement persisted to a greater extent in adolescents relative to adults.

CognitiveConstruct

RewardProcessing

10.1016/j.neuropsychologia.2016.09.015

Neuropsychologia

Neuropsychologia

Influence of subthalamic deep-brain stimulation on cognitive action control in incentive context.

Subthalamic nucleus deep-brain stimulation (STN-DBS) is an effective treatment in Parkinson's disease (PD), but can have cognitive side effects, such as increasing the difficulty of producing appropriate responses when a habitual but inappropriate responses represent strong alternatives. STN-DBS also appears to modulate representations of incentives such as monetary rewards. Furthermore, conflict resolution can be modulated by incentive context. We therefore used a rewarded Simon Task to assess the influence of promised rewards on cognitive action control in 50 patients with PD, half of whom were being treated with STN-DBS. Results were analyzed according to the activation-suppression model. We showed that STN-DBS (i) favored the expression of motor impulsivity, as measured with the Barratt Impulsiveness Scale, (ii) facilitated the expression of incentive actions as observed with a greater increase in speed according to promised reward in patients with versus without DBS and (iii) may increase impulsive action selection in an incentive context. In addition, analysis of subgroups of implanted patients suggested that those who exhibited the most impulsive action selection had the least severe disease. This may indicate that patients with less marked disease are more at risk of developing impulsivity postoperatively. Finally, in these patients, incentive context increased the difficulty of resolving conflict situations. As a whole, the current study revealed that in patients with PD, STN-DBS affects the cognitive processes involved in conflict resolution, reward processing and the influence of promised rewards on conflict resolution.

CognitiveConstruct

RewardProcessing