Independent effects of emotional arousal and reward anticipation on episodic memory formation.

Events that elicit emotional arousal or are associated with reward are more likely remembered. Emotional arousal activates the amygdala and the central noradrenergic system, whereas reward anticipation results in an activity in the mesocorticolimbic dopaminergic system. The activation of both pathways enhances memory formation in the hippocampus where their effects are based on similar neural substrates, e.g. tagging of active hippocampal synapses. Moreover, emotional arousal and reward anticipation both enhance attention, which can also affect memory formation. In addition, both neuromodulators interact on the cellular level. Therefore, we tested in the current functional magnetic resonance imaging study whether simultaneously occurring emotional arousal and reward anticipation might have interacting effects on memory formation. We did not find evidence for such an interaction, neither on the behavioral nor on the neural level. Our results further suggest that reward anticipation enhances memory formation rather by an increase in anticipation-related arousal-reflected in activity in the dorsal anterior cingulate cortex-and not dopaminergic midbrain activity. Accompanying behavioral experiments indicated that the effect of reward anticipation on memory is (i) caused at least to some extent by anticipating the speeded response to obtain the reward and not by the valance of the outcome and (ii) can be observed already immediately after encoding, i.e. before consolidation.

A Meta-Analysis of Neural Correlates of Reward Anticipation in Individuals at Clinical Risk for Schizophrenia.

BACKGROUND: Aberrant striatal responses to reward anticipation have been observed in schizophrenia. However, it is unclear whether these dysfunctions predate the onset of psychosis and whether reward anticipation is impaired in individuals at clinical high risk for schizophrenia (CHR). METHODS: To examine the neural correlates of monetary anticipation in the prodromal phase of schizophrenia, we performed a whole-brain meta-analysis of 13 functional neuroimaging studies that compared reward anticipation signals between CHR individuals and healthy controls (HC). Three databases (PubMed, Web of Science, and ScienceDirect) were systematically searched from January 1, 2000, to May 1, 2022. RESULTS: Thirteen whole-brain functional magnetic resonance imaging studies including 318 CHR individuals and 426 HC were identified through comprehensive literature searches. Relative to HC, CHR individuals showed increased brain responses in the medial prefrontal cortex and anterior cingulate cortex and decreased activation in the mesolimbic circuit, including the putamen, parahippocampal gyrus, insula, cerebellum, and supramarginal gyrus, during reward anticipation. CONCLUSIONS: Our findings in the CHR group confirmed the existence of abnormal motivational-related activation during reward anticipation, thus demonstrating the pathophysiological characteristics of the risk populations. These results have the potential to lead to the early identification and more accurate prediction of subsequent psychosis as well as a deeper understanding of the neurobiology of high-risk state of psychotic disorder.

Electrophysiological Correlates of Reward Anticipation in Subjects with Schizophrenia: An ERP Microstate Study.

The current study aimed to investigate alterations of event-related potentials (ERPs) microstate during reward anticipation in subjects with schizophrenia (SCZ), and their association with hedonic experience and negative symptoms. EEG data were recorded in thirty SCZ and twenty-three healthy controls (HC) during the monetary incentive delay task in which reward, loss and neutral cues were presented. Microstate analysis and standardized low-resolution electromagnetic tomography (sLORETA) were applied to EEG data. Furthermore, analyses correlating a topographic index (the ERPs score), calculated to quantify brain activation in relationship to the microstate maps, and scales assessing hedonic experience and negative symptoms were performed. Alterations in the first (125.0-187.5 ms) and second (261.7-414.1 ms) anticipatory cue-related microstate classes were observed. In SCZ, reward cues were associated to shorter duration and earlier offset of the first microstate class as compared to the neutral condition. In the second microstate class, the area under the curve was smaller for both reward and loss anticipation cues in SCZ as compared to HC. Furthermore, significant correlations between ERPs scores and the anticipation of pleasure scores were detected, while no significant association was found with negative symptoms. sLORETA analysis showed that hypo-activation of the cingulate cortex, insula, orbitofrontal and parietal cortex was detected in SCZ as compared to HC. Abnormalities in ERPs could be traced already during the early stages of reward processing and were associated with the anticipation of pleasure, suggesting that these dysfunctions might impair effective evaluation of incoming pleasant experiences. Negative symptoms and anhedonia are partially independent results.

Altered neural mechanism of social reward anticipation in individuals with schizophrenia and social anhedonia.

Altered social reward anticipation could be found in schizophrenia (SCZ) patients and individuals with high levels of social anhedonia (SA). However, few research investigated the putative neural processing for altered social reward anticipation in these populations on the SCZ spectrum. This study aimed to examine the underlying neural mechanisms of social reward anticipation in these populations. Twenty-three SCZ patients and 17 healthy controls (HC), 37 SA individuals and 50 respective HCs completed the Social Incentive Delay (SID) imaging task while they were undertaking MRI brain scans. We used the group contrast to examine the alterations of BOLD activation and functional connectivity (FC, psychophysiological interactions analysis). We then characterized the beta-series social brain network (SBN) based on the meta-analysis results from NeuroSynth and examined their prediction effects on real-life social network (SN) characteristics using the partial least squared regression analysis. The results showed that SCZ patients exhibited hypo-activation of the left medial frontal gyrus and the negative FCs with the left parietal regions, while individuals with SA showed the hyper-activation of the left middle frontal gyrus when anticipating social reward. For the beta-series SBNs, SCZ patients had strengthened cerebellum-temporal FCs, while SA individuals had strengthened left frontal regions FCs. However, such FCs of the SBN failed to predict the real-life SN characteristics. These preliminary findings suggested that SCZ patients and SA individuals appear to exhibit altered neural processing for social reward anticipation, and such neural activities showed a weakened association with real-life SN characteristics.

Women with more severe premenstrual syndrome have an enhanced anticipatory reward processing: a magnetoencephalography study.

Laboratory studies reveal that young women with premenstrual syndrome (PMS) often exhibit decreased reward processing during the late luteal phase. However, studies based on the self-reports find opposite results (e.g., higher craving for high-sweet-fat food). These differences may lie in the difference between the stimulus used and measuring the different aspects of the reward. The present study was designed to expand previous work by using a classic monetary reward paradigm, simultaneously examining the motivational (i.e., reward anticipation, "wanting") and emotional (i.e., reward outcome, "liking") components of reward processing in women with high premenstrual symptoms (High PMS). College female students in their early twenties with High PMS (n = 20) and low premenstrual symptoms (Low PMS, n = 20) completed a monetary incentive delay task during their late luteal phase when the premenstrual symptoms typically peak. Brain activities in the reward anticipation phase and outcome phase were recorded using the magnetoencephalographic (MEG) imaging technique. No group differences were found in various behavioral measurements. For the MEG results, in the anticipation phase, when High PMS participants were presented with cues that predicted the upcoming monetary gains, they showed higher event-related magnetic fields (ERFs) than when they were presented with neutral non-reward cues. This pattern was reversed in Low PMS participants, as they showed lower reward cue-elicited ERFs than non-reward cue-elicited ones (cluster mass = 2560, cluster size = 891, p = .03, corrected for multiple comparisons), mainly in the right medial orbitofrontal and lateral orbitofrontal cortex (cluster mass = 375, cluster size = 140, p = .03, corrected for multiple comparisons). More importantly, women with High PMS had an overall significantly higher level of ERFs than women with Low PMS (cluster mass = 8039, cluster size = 2937, p = .0009, corrected for multiple comparisons) in the bilateral precentral gyrus, right postcentral gyrus, and left superior temporal gyrus (right: cluster mass = 410, cluster size = 128, p = .03; left: cluster mass = 352, cluster size = 98, p = .05; corrected for multiple comparisons). In the outcome phase, women with High PMS showed significantly lower theta power than the Low PMS ones for the expected non-reward feedback in the bilateral temporal-parietal regions (cluster mass = 47620, cluster size = 18308, p = .01, corrected for multiple comparisons). These findings reveal that the severity of PMS might alter reward anticipation. Specifically, women with High PMS displayed increased brain activities to reward-predicting cues and increased action preparation after the cues appear.

Cognitive control increases honesty in cheaters but cheating in those who are honest.

Every day, we are faced with the conflict between the temptation to cheat for financial gains and maintaining a positive image of ourselves as being a "good person." While it has been proposed that cognitive control is needed to mediate this conflict between reward and our moral self-image, the exact role of cognitive control in (dis)honesty remains elusive. Here we identify this role, by investigating the neural mechanism underlying cheating. We developed a task which allows for inconspicuously measuring spontaneous cheating on a trial-by-trial basis in the MRI scanner. We found that activity in the nucleus accumbens promotes cheating, particularly for individuals who cheat a lot, while a network consisting of posterior cingulate cortex, temporoparietal junction, and medial prefrontal cortex promotes honesty, particularly in individuals who are generally honest. Finally, activity in areas associated with cognitive control (anterior cingulate cortex and inferior frontal gyrus) helped dishonest participants to be honest, whereas it enabled cheating for honest participants. Thus, our results suggest that cognitive control is not needed to be honest or dishonest per se but that it depends on an individual's moral default.

Goal-striving tendencies moderate the relationship between reward-related brain function and peripheral inflammation.

Inflammation is associated with both lower and higher activity in brain regions that process rewarding stimuli. How can both low and high sensitivity to rewards be associated with higher inflammation? We propose that one potential mechanism underlying these apparently conflicting findings pertains to how people pursue goals in their environment. This prediction is based on evidence that both an inability to disengage from unattainable goals and low interest in and pursuit of important life goals are associated with poor health outcomes, including inflammation. Accordingly, this study examined the relationship between reward-related brain function and peripheral inflammation among individuals with different levels of ambitious goal-striving tendencies. Eighty-three participants completed an ambitious goal-striving tendency measure, an fMRI Monetary Incentive Delay task assessing orbitofrontal cortex (OFC) and nucleus accumbens (NAc) activation during reward anticipation and outcome, and a venous blood draw to assess the inflammatory biomarkers interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, and C-reactive protein, from which we computed an inflammation composite score. We observed a reward anticipation by goal-striving interaction on inflammation, such that high OFC and NAc activation to reward anticipation (but not outcome) were associated with more inflammation, among high goal-striving individuals. By contrast, low NAc activation during reward anticipation (but not outcome) was associated with more inflammation, among low goal-striving individuals. The current study provides further evidence that both blunted and elevated reward function can be associated with inflammation. It also highlights the role that goal-striving tendencies may play in moderating the relationship between neural reward anticipation and inflammation.

Reward anticipation buffers neuroendocrine and cardiovascular responses to acute psychosocial stress in healthy young adults.

Research over the last 10 years suggests that the brain's reward system plays a crucial role in stress resilience. Notably, reward processing includes both an anticipatory (cue-triggered "wanting") phase and a consummatory ("liking") phase. However, previous studies manipulated rewards via direct reward administration, which makes it difficult to isolate the buffering effect of anticipating the reward stimulus. In the current study, we designed a paradigm to manipulate participants into generating reward anticipation or not and investigated whether reward anticipation can buffer psychological, neuroendocrine, and cardiovascular responses to psychosocial stress. A sample of 78 healthy young adults underwent the Trier Social Stress Test or placebo-Trier Social Stress Test after a reward anticipation task. Results showed that reward anticipation relieved subjective stress feelings, as well as the overall cortisol secretion and the increased heart rate induced by psychosocial stress. Taken together, these findings expanded our understanding of the role the reward system plays in stress resilience, and the possible psychological mechanism of the buffering effect for future stress study was also discussed.HIGHLIGHTSReward processing includes both an anticipatory and consummatory phasesThe buffering effect of anticipating the reward stimulus requires elucidationWe examined if said anticipation buffers varied responses to psychosocial stressReward anticipation relieved subjective stress, cortisol secretion, and heart rateWe clarified the role of the reward system in stress resilience.

Examining the value of body gestures in social reward contexts.

Brain regions associated with the processing of tangible rewards (such as money, food, or sex) are also involved in anticipating social rewards and avoiding social punishment. To date, studies investigating the neural underpinnings of social reward have presented feedback via static or dynamic displays of faces to participants. However, research demonstrates that participants find another type of social stimulus, namely, biological motion, rewarding as well, and exert effort to engage with this type of stimulus. Here we examine whether feedback presented via body gestures in the absence of facial cues also acts as a rewarding stimulus and recruits reward-related brain regions. To achieve this, we investigated the neural underpinnings of anticipating social reward and avoiding social disapproval presented via gestures alone, using a social incentive delay task. As predicted, the anticipation of social reward and avoidance of social disapproval engaged reward-related brain regions, including the nucleus accumbens, in a manner similar to previous studies' reports of feedback presented via faces and money. This study provides the first evidence that human body motion alone engages brain regions associated with reward processing in a similar manner to other social (i.e. faces) and non-social (i.e. money) rewards. The findings advance our understanding of social motivation in human perception and behavior.

Role of TRPV1/TRPV3 channels in olanzapine-induced metabolic alteration: Possible involvement in hypothalamic energy-sensing, appetite regulation, inflammation and mesolimbic pathway.

Atypical antipsychotics (AAPs) have the tendency of inducing severe metabolic alterations like obesity, diabetes mellitus, insulin resistance, dyslipidemia and cardiovascular complications. These alterations have been attributed to altered hypothalamic appetite regulation, energy sensing, insulin/leptin signaling, inflammatory reactions and active reward anticipation. Line of evidence suggests that transient receptor potential vanilloid type 1 and 3 (TRPV1 and TRPV3) channels are emerging targets in treatment of obesity, diabetes mellitus and could modulate feed intake. The present study was aimed to investigate the putative role TRPV1/TRPV3 in olanzapine-induced metabolic alterations in mice. Female BALB/c mice were treated with olanzapine for six weeks to induce metabolic alterations. Non-selective TRPV1/TRPV3 antagonist (ruthenium red) and selective TRPV1 (capsazepine) and TRPV3 antagonists (2,2-diphenyltetrahydrofuran or DPTHF) were used to investigate the involvement of TRPV1/TRPV3 in chronic olanzapine-induced metabolic alterations. These metabolic alterations were differentially reversed by ruthenium red and capsazepine, while DPTHF didn't show any significant effect. Olanzapine treatment also altered the mRNA expression of hypothalamic appetite-regulating and nutrient-sensing factors, inflammatory genes and TRPV1/TRPV3, which were reversed with ruthenium red and capsazepine treatment. Furthermore, olanzapine treatment also increased expression of TRPV1/TRPV3 in nucleus accumbens (NAc), TRPV3 expression in ventral tegmental area (VTA), which were reversed by the respective antagonists. However, DPTHF treatment showed reduced feed intake in olanzapine treated mice, which might be due to TRPV3 specific antagonism and reduced hedonic feed intake. In conclusion, our results suggested the putative role TRPV1 in hypothalamic dysregulations and TRPV3 in the mesolimbic pathway; both regulate feeding in olanzapine treated mice.

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia.

BACKGROUND: Bipolar disorder I (BD-I) is defined by episodes of mania, depression and euthymic states. These episodes are among other symptoms characterized by altered reward processing and negative symptoms (NS), in particular apathy. However, the neural correlates of these deficits are not well understood. METHODS: We first assessed the severity of NS in 25 euthymic BD-I patients compared with 25 healthy controls (HC) and 27 patients with schizophrenia (SZ). Then, we investigated ventral (VS) and dorsal striatal (DS) activation during reward anticipation in a Monetary Incentive Delayed Task and its association with NS. RESULTS: In BD-I patients NS were clearly present and the severity of apathy was comparable to SZ patients. Apathy scores in the BD-I group but not in the SZ group correlated with sub-syndromal depression scores. At the neural level, we found significant VS and DS activation in BD-I patients and no group differences with HC or SZ patients. In contrast to patients with SZ, apathy did not correlate with striatal activation during reward anticipation. Explorative whole-brain analyses revealed reduced extra-striatal activation in BD-I patients compared with HC and an association between reduced activation of the inferior frontal gyrus and apathy. CONCLUSION: This study found that in BD-I patients apathy is present to an extent comparable to SZ, but is more strongly related to sub-syndromal depressive symptoms. The findings support the view of different pathophysiological mechanisms underlying apathy in the two disorders and suggest that extra-striatal dysfunction may contribute to impaired reward processing and apathy in BD-I.

Relationships between neural activation during a reward task and peripheral cytokine levels in youth with diverse psychiatric symptoms.

BACKGROUND: Inflammation has been hypothesized to contribute to reward dysfunction across psychiatric conditions, but little is known about this relationship in youth. Therefore, the present study investigated the associations between general and specific markers of inflammation and neural activation during reward processing, including anticipation and attainment, in youth with diverse psychiatric symptoms. METHODS: Forty-six psychotropic medication-free youth with diverse psychiatric symptoms underwent a blood draw to measure 41 cytokines, as well as structural and functional magnetic resonance imaging. The Reward Flanker Task examined neural activation during reward anticipation and attainment. Relationships between inflammation and neural activation were assessed using data reduction techniques across the whole-brain, as well as in specific reward regions of interest (basal ganglia, anterior and mid-cingulate cortex [ACC/MCC]). RESULTS: Whole-brain principal component analyses showed that factor 3 (12 cytokines: FGF-2, Flt3-L, fractalkine, GM-CSF, IFN-α2, IFN-γ, IL-3, IL-4, IL-7, IL-17A, MDC, and VEGF) was negatively correlated with precuneus/posterior cingulate cortex activity during anticipation. Factor 2 (11 cytokines: eotaxin, IL-1α, IL-1Rα, IL-2, IL-5, IL-9, IL-12p40, IL-13, IL-15, MCP-3, and TNF-ß) was negatively correlated with angular gyrus activity during attainment. ROI analyses additionally showed that multiple cytokines were related to activity in the basal ganglia (EGF, FGF-2, Flt-3L, IL-2, IL-13, IL-15, IL-1Rα, MCP-3) and ACC/MCC (Flt-3L) during attainment. C-reactive protein (CRP) was not associated with neural activation. CONCLUSIONS: Investigation of specific markers of immune function showed associations between inflammatory processes and activation of posterior default mode network, prefrontal cortex, and basal ganglia regions during multiple phases of reward processing.

Reward anticipation modulates the effect of stress-related increases in cortisol on episodic memory.

When acute stress is experienced shortly after an event is encoded into memory, this can slow the forgetting of the study event, which is thought to reflect the effect of cortisol on consolidation. In addition, when events are encoded under conditions of high reward they tend to be remembered better than those encoded under non-rewarding conditions, and these effects are thought to reflect the operation of the dopaminergic reward system. Although both modulatory systems are believed to impact the medial temporal lobe regions critical for episodic memory, the manner, and even the extent, to which these two systems interact is currently unknown. To address this question in the current study, participants encoded words under reward or non-reward conditions, then one half of the participants were stressed using the social evaluation cold pressor task and the other half completed a non-stress control task. After a two-hour delay, all participants received a free recall and recognition memory test. There were no significant effects of stress or reward on overall memory performance. However, for the non-reward items, increases in stress-related cortisol in stressed participants were related to increases in recall and increases in recollection-based recognition responses. In contrast, for the reward items, increases in stress-related cortisol were not related to increases in memory performance. The results indicate that the stress and the reward systems interact in the way they impact episodic memory. The results are consistent with tag and capture models in the sense that cortisol reactivity can only affect non-reward items because plasticity-related products are already provided by reward anticipation.

Cue-Evoked Dopamine Release Rapidly Modulates D2 Neurons in the Nucleus Accumbens During Motivated Behavior.

UNLABELLED: Dopaminergic neurons that project from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) fire in response to unpredicted rewards or to cues that predict reward delivery. Although it is well established that reward-related events elicit dopamine release in the NAc, the role of rapid dopamine signaling in modulating NAc neurons that respond to these events remains unclear. Here, we examined dopamine's actions in the NAc in the rat brain during an intracranial self-stimulation task in which a cue predicted lever availability for electrical stimulation of the VTA. To distinguish actions of dopamine at select receptors on NAc neurons during the task, we used a multimodal sensor that probes three aspects of neuronal communication simultaneously: neurotransmitter release, cell firing, and identification of dopamine receptor type. Consistent with prior studies, we first show dopamine release events in the NAc both at cue presentation and after lever press (LP). Distinct populations of NAc neurons encode these behavioral events at these same locations selectively. Using our multimodal sensor, we found that dopamine-mediated responses after the cue involve exclusively a subset of D2-like receptors (D2Rs), whereas dopamine-mediated responses proximal to the LP are mediated by both D1-like receptors (D1R) and D2Rs. These results demonstrate for the first time that dopamine-mediated responses after cues that predict reward availability are specifically linked to its actions at a subset of neurons in the NAc containing D2Rs. SIGNIFICANCE STATEMENT: Successful reward procurement typically involves the completion of a goal-directed behavior in response to appropriate environmental cues. Although numerous studies link the mesolimbic dopamine system with these processes, how dopamine's effects are mediated on the receptor level within a key neural substrate, the nucleus accumbens, remains elusive. Here, we used a unique multimodal sensor that reveals three aspects of neuronal interactions: neurotransmitter release, cell firing, and dopamine-receptor type. We identified a key role of D2-like receptor (D2R)-expressing neurons in response to a reward-predicting cue, whereas both the D2R and D1R types modulate responses of neurons proximal to the goal-directed action. This work provides novel insight into the unique role of D2R-mediated neuronal activity to reward-associated cues, a fundamental aspect of motivated behaviors.

Children with ADHD symptoms show decreased activity in ventral striatum during the anticipation of reward, irrespective of ADHD diagnosis.

BACKGROUND: Changes in reward processing are thought to be involved in the etiology of attention-deficit/hyperactivity disorder (ADHD), as well as other developmental disorders. In addition, different forms of therapy for ADHD rely on reinforcement principles. As such, improved understanding of reward processing in ADHD could eventually lead to more effective treatment options. However, differences in reward processing may not be specific to ADHD, but may be a trans-diagnostic feature of disorders that involve ADHD-like symptoms. METHODS: In this event-related fMRI study, we used a child-friendly version of the monetary incentive delay task to assess performance and brain activity during reward anticipation. Also, we collected questionnaire data to assess reward sensitivity in daily life. For final analyses, data were available for 27 typically developing children, 24 children with ADHD, and 25 children with an autism spectrum disorder (ASD) and ADHD symptoms. RESULTS: We found decreased activity in ventral striatum during anticipation of reward in children with ADHD symptoms, both for children with ADHD as their primary diagnosis and in children with autism spectrum disorder and ADHD symptoms. We found that higher parent-rated sensitivity to reward was associated with greater anticipatory activity in ventral striatum for children with ADHD symptoms. In contrast, there was no relationship between the degree of ADHD symptoms and activity in ventral striatum. CONCLUSIONS: We provide evidence of biological and behavioral differences in reward sensitivity in children with ADHD symptoms, regardless of their primary diagnosis. Ultimately, a dimensional brain-behavior model of reward sensitivity in children with symptoms of ADHD may be useful to refine treatment options dependent on reward processing.

Ventral striatum activity when watching preferred pornographic pictures is correlated with symptoms of Internet pornography addiction.

One type of Internet addiction is excessive pornography consumption, also referred to as cybersex or Internet pornography addiction. Neuroimaging studies found ventral striatum activity when participants watched explicit sexual stimuli compared to non-explicit sexual/erotic material. We now hypothesized that the ventral striatum should respond to preferred pornographic compared to non-preferred pornographic pictures and that the ventral striatum activity in this contrast should be correlated with subjective symptoms of Internet pornography addiction. We studied 19 heterosexual male participants with a picture paradigm including preferred and non-preferred pornographic materials. Subjects had to evaluate each picture with respect to arousal, unpleasantness, and closeness to ideal. Pictures from the preferred category were rated as more arousing, less unpleasant, and closer to ideal. Ventral striatum response was stronger for the preferred condition compared to non-preferred pictures. Ventral striatum activity in this contrast was correlated with the self-reported symptoms of Internet pornography addiction. The subjective symptom severity was also the only significant predictor in a regression analysis with ventral striatum response as dependent variable and subjective symptoms of Internet pornography addiction, general sexual excitability, hypersexual behavior, depression, interpersonal sensitivity, and sexual behavior in the last days as predictors. The results support the role for the ventral striatum in processing reward anticipation and gratification linked to subjectively preferred pornographic material. Mechanisms for reward anticipation in ventral striatum may contribute to a neural explanation of why individuals with certain preferences and sexual fantasies are at-risk for losing their control over Internet pornography consumption.

Cortisol alters reward processing in the human brain.

Dysfunctional reward processing is known to play a central role for the development of psychiatric disorders. Glucocorticoids that are secreted in response to stress have been shown to attenuate reward sensitivity and thereby might promote the onset of psychopathology. However, the underlying neurobiological mechanisms mediating stress hormone effects on reward processing as well as potential sex differences remain elusive. In this neuroimaging study, we administered 30mg cortisol or a placebo to 30 men and 30 women and subsequently tested them in the Monetary Incentive Delay Task. Cortisol attenuated anticipatory neural responses to a verbal and a monetary reward in the left pallidum and the right anterior parahippocampal gyrus. Furthermore, in men, activation in the amygdala, the precuneus, the anterior cingulate, and in hippocampal regions was reduced under cortisol, whereas in cortisol-treated women a signal increase was observed in these regions. Behavioral performance also indicated that reward learning in men is impaired under high cortisol concentrations, while it is augmented in women. These findings illustrate that the stress hormone cortisol substantially diminishes reward anticipation and provide first evidence that cortisol effects on the neural reward system are sensitive to sex differences, which might translate into different vulnerabilities for psychiatric disorders.

Subjective illusion of control modulates striatal reward anticipation in adolescence.

The perception of control over the environment constitutes a fundamental biological adaptive mechanism, especially during development. Previous studies comparing an active choice condition with a passive no-choice condition showed that the neural basis of this mechanism is associated with increased activity within the striatum and the prefrontal cortex. In the current study, we aimed to investigate whether subjective belief of control in an uncertain gambling situation induces elevated activation in a cortico-striatal network. We investigated 79 adolescents (age range: 13-16years) during reward anticipation with a slot machine task using functional magnetic resonance imaging. We assessed post-experimentally whether the participants experienced a subjective illusion of control on winning or losing in this task that was objectively not given. Nineteen adolescents experienced an illusion of control during slot machine gambling. This illusion of control group showed an increased neural activity during reward anticipation within a cortico-striatal network including ventral striatum (VS) as well as right inferior frontal gyrus (rIFG) relative to the group reporting no illusion of control. The rIFG activity was inversely associated with impulsivity in the no illusion of control group. The subjective belief about control led to an elevated ventral striatal activity, which is known to be involved in the processing of reward. This finding strengthens the notion that subjectively perceived control, not necessarily the objective presence of control, affects striatal reward-related processing.

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

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

Causal discovery in an adult ADHD data set suggests indirect link between DAT1 genetic variants and striatal brain activation during reward processing.

Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder affecting both children and adults. One of the candidate genes for ADHD is DAT1, encoding the dopamine transporter. In an attempt to clarify its mode of action, we assessed brain activity during the reward anticipation phase of the Monetary Incentive Delay (MID) task in a functional MRI paradigm in 87 adult participants with ADHD and 77 controls (average age 36.5 years). The MID task activates the ventral striatum, where DAT1 is most highly expressed. A previous analysis based on standard statistical techniques did not show any significant dependencies between a variant in the DAT1 gene and brain activation [Hoogman et al. (2013); Neuropsychopharm 23:469-478]. Here, we used an alternative method for analyzing the data, that is, causal modeling. The Bayesian Constraint-based Causal Discovery (BCCD) algorithm [Claassen and Heskes (2012); Proceedings of the 28th Conference on Uncertainty in Artificial Intelligence] is able to find direct and indirect dependencies between variables, determines the strength of the dependencies, and provides a graphical visualization to interpret the results. Through BCCD one gets an opportunity to consider several variables together and to infer causal relations between them. Application of the BCCD algorithm confirmed that there is no evidence of a direct link between DAT1 genetic variability and brain activation, but suggested an indirect link mediated through inattention symptoms and diagnostic status of ADHD. Our finding of an indirect link of DAT1 with striatal activity during reward anticipation might explain existing discrepancies in the current literature. Further experiments should confirm this hypothesis. © 2015 Wiley Periodicals, Inc.