Parsing patterns of reward responsiveness: Initial evidence from latent profile analysis.

Variation in reward responsiveness has been linked to psychopathology. Reward responsiveness is a complex phenomenon that encompasses different temporal dimensions (i.e., reward anticipation or consumption) that can be measured using multiple appetitive stimuli. Furthermore, distinct measures, such as neural and self-report measures, reflect related but distinct aspects of reward responsiveness. To understand reward responsiveness more comprehensively and better identify deficits in reward responsiveness implicated in psychopathology, we examined ways multiple measures of reward responsiveness jointly contribute to distinct psychological problems by using latent profile analysis. Specifically, we identified three profiles of reward responsiveness among 139 female participants based on their neural responses to money, food, social acceptance, and erotic images and self-reported responsiveness to reward anticipation and consumption. Profile 1 (n = 30) exhibited blunted neural responses to social rewards and erotic images, low self-reported reward responsiveness, but average neural responses to monetary and food rewards. Profile 2 (n = 71) showed elevated neural response to monetary rewards, average neural responses to other stimuli, and average self-reported reward responsiveness. Profile 3 (n = 38) showed more variable neural responses to reward (e.g., hypersensitivity to erotic images, hyposensitivity to monetary rewards), and high self-reported reward responsiveness. These profiles were differentially associated with variables generally linked to aberrations in reward responsiveness. For example, Profile 1 was most strongly associated with anhedonic depression and social dysfunction, whereas Profile 3 was associated with risk-taking behaviors. These preliminary findings may help to elucidate ways different measures of reward responsiveness manifest within and across individuals and identify specific vulnerabilities for distinct psychological problems.

Circadian, Reward, and Emotion Systems in Teens prospective longitudinal study: protocol overview of an integrative reward-circadian rhythm model of first onset of bipolar spectrum disorder in adolescence.

BACKGROUND: Bipolar spectrum disorders (BSDs) are associated with a heightened sensitivity to rewards and elevated reward-related brain function in cortico-striatal circuitry. A separate literature documents social and circadian rhythm disruption in BSDs. Recently, integrated reward-circadian models of BSDs have been proposed. These models draw on work indicating that the two systems influence each other and interact to affect mood functioning. When dysregulated, reward and circadian system signaling may combine to form a positive feedback loop, whereby dysregulation in one system exacerbates dysregulation in the other. Project CREST (Circadian, Reward, and Emotion Systems in Teens) provides a first systematic test of reward-circadian dysregulation as a synergistic and dynamic vulnerability for first onset of BSD and increases in bipolar symptoms during adolescence. METHODS: This NIMH-funded R01 study is a 3-year prospective, longitudinal investigation of approximately 320 community adolescents from the broader Philadelphia area, United States of America. Eligible participants must be 13-16 years old, fluent in English, and without a prior BSD or hypomanic episode. They are being selected along the entire dimension of self-reported reward responsiveness, with oversampling at the high tail of the dimension in order to increase the likelihood of BSD onsets. At Times 1-6, every 6 months, participants will complete assessments of reward-relevant and social rhythm disruption life events and self-report and diagnostic assessments of bipolar symptoms and episodes. Yearly, at Times 1, 3, and 5, participants also will complete self-report measures of circadian chronotype (morningness-eveningness) and social rhythm regularity, a salivary dim light melatonin onset (DLMO) procedure to assess circadian phase, self-report, behavioral, and neural (fMRI) assessments of monetary and social reward responsiveness, and a 7-day ecological momentary assessment (EMA) period. During each EMA period, participants will complete continuous measures of sleep/wake and activity (actigraphy), a daily sleep diary, and three within-day (morning, afternoon, evening) measures of life events coded for reward-relevance and social rhythm disruption, monetary and social reward responsiveness, positive and negative affect, and hypo/manic and depressive symptoms. The fMRI scan will occur on the day before and the DLMO procedure will occur on the first evening of the 7-day EMA period. DISCUSSION: This study is an innovative integration of research on multi-organ systems involved in reward and circadian signaling in understanding first onset of BSD in adolescence. It has the potential to facilitate novel pharmacological, neural, and behavioral interventions to treat, and ideally prevent, bipolar conditions.

Effects of stress-induced inflammation on reward processing in healthy young women.

BACKGROUND: Anhedonia, or loss of interest or pleasure, is a feature of depression and transdiagnostic construct in psychopathology. Theory and compelling evidence from preclinical models implicates stress-induced inflammation as a psychobiological pathway to anhedonic behavior; however, this pathway has not been tested in human models. Further, although anhedonia may reflect dysregulation in multiple dimensions of reward, the extent to which stress-induced inflammation alters these dimensions is unclear. Thus, the current experimental study used a standardized laboratory stressor task to elicit an inflammatory response and evaluate effects of stress-induced inflammation on multiple behavioral indices of reward processing. METHODS: Healthy young women (age 18-25) completed behavioral reward tasks assessing reward learning, motivation, and sensitivity and were randomized to undergo an acute psychosocial stressor (n = 37) or a no-stress active control (n = 17). Tasks were re-administered 90-120 min post-stress to coincide with the peak of the stress-induced inflammatory response. Blood samples were collected for assessment of the pro-inflammatory cytokine interleukin-6 (IL-6) at baseline and 90 and 120 min post stressor. RESULTS: Stress-induced IL-6 was associated with increased response bias during reward learning and increased motivation when probability of receiving a reward was low. Sensitivity to reward in the context of a motivation task was not altered in association with stress-induced IL-6. CONCLUSIONS: Contrary to hypotheses, mild increases in IL-6 following acute stress were associated with increased reward responsiveness during reward learning and selective increases in motivation. Results contribute to an emerging and nuanced literature linking inflammation to reward processing, and demonstrate that behavioral effects of stress-induced inflammation may be detected in the laboratory setting. CLINICAL TRIAL REGISTRATION: NCT03828604.

Cue-Reactive Imagery Mediates the Relationships of Reward Responsiveness with Both Cue-Reactive Urge to Gamble and Positive Affect in Poker-Machine Gamblers.

Previous research has demonstrated that gambling cues (e.g., flashing lights on poker-machines) can trigger an urge to gamble in poker-machine gamblers. However, the psychological mechanisms that promote the urge to gamble remain poorly understood. The present study explored whether reward responsiveness predicted urge to gamble and positive affect, and whether cue-reactive rationality, volitional control and imagery mediated these relationships. Ninety-three (45% male and 55% female) Australian regular poker-machine gamblers aged between 18 and 77 participated in an online cue-reactivity experiment. Participants initially completed the Problem Gambling Severity Index and Reward Responsiveness scale. Subsequently, at three time points (i.e., baseline, directly after a neutral cue and directly after a gambling cue) participants completed the rationality, volitional control and imagery subscales of the Phenomenology of Consciousness Inventory and two visual analogue scales that measured urge to gamble and positive affect. Analyses indicated that gambling cues triggered statistically significant increases in both urge to gamble and positive affect and these variables were statistically significantly positively correlated with reward responsiveness. Furthermore, only cue-reactive imagery mediated the relationships between reward responsiveness and the two outcome variables (i.e., cue-reactive urge to gamble and positive affect). These findings highlight the potential importance of targeting reward responsiveness and cue-reactive mental imagery in the context of exposure therapies for poker-machine problem gamblers.

Co-Occurring Depressive and Substance Use Disorders in Adolescents: An Examination of Reward Responsiveness During Treatment.

The goals of the present study were to examine: (a) putative dysfunctions in reward responsiveness in a sample of adolescents (n = 40) with co-occurring depressive and substance use disorders; (b) possible links between reward responsiveness and symptoms of depression, anhedonia, anxiety, and motivation for change in relation to alcohol and drug use; and (c) potential gender differences in findings. Before and after a 2-week residential treatment, adolescents completed self-report assessments of depression, anhedonia, anxiety symptoms, and motivation for change in relation to substance use. In addition, participants completed a computer-based Probabilistic Reward Task (PRT) to examine reward responsiveness (i.e., participants' ability to modulate behavior as a function of reinforcement history). Results indicated that depression and anhedonia symptoms decreased, and motivation for change in relation to drug use increased. Improved reward responsiveness over the course of residential treatment emerged in female, but not male, participants.

Effects of acute stress on reward processing: A comprehensive meta-analysis of rodent and human studies.

Stressors can initiate a cascade of central and peripheral changes that modulate mesocorticolimbic dopaminergic circuits and, ultimately, behavioral response to rewards. Driven by the absence of conclusive evidence on this topic and the Research Domain Criteria framework, random-effects meta-analyses were adopted to quantify the effects of acute stressors on reward responsiveness, valuation, and learning in rodent and human subjects. In rodents, acute stress reduced reward responsiveness (g = -1.43) and valuation (g = -0.32), while amplifying reward learning (g = 1.17). In humans, acute stress had marginal effects on valuation (g = 0.25), without affecting responsiveness and learning. Moderation analyses suggest that acute stress neither has unitary effects on reward processing in rodents nor in humans and that the duration of the stressor and specificity of reward experience (i.e., food vs drugs) may produce qualitatively and quantitatively different behavioral endpoints. Subgroup analyses failed to reduce heterogeneity, which, together with the presence of publication bias, pose caution on the conclusions that can be drawn and point to the need of guidelines for the conduction of future studies in the field.

Reward and Immune Systems in Emotion (RISE) prospective longitudinal study: Protocol overview of an integrative reward-inflammation model of first onset of major depression in adolescence.

Background: Depression is associated with a reduced sensitivity to rewards and low reward-related brain function in cortico-striatal circuitry. A separate literature documents elevated peripheral inflammation in depression. Recently, integrated reward-inflammation models of depression have been proposed. These models draw on work indicating that peripheral inflammatory proteins access the brain, where they lower reward responsiveness. This blunted reward responsiveness is proposed to initiate unhealthy behaviors (substance use, poor diet), as well as sleep disruption and stress generation, which further heighten inflammation. Over time, dysregulation in reward responsiveness and immune signaling may synergize in a positive feedback loop, whereby dysregulation in each system exacerbates dysregulation in the other. Project RISE (Reward and Immune Systems in Emotion) provides a first systematic test of reward-immune dysregulation as a synergistic and dynamic vulnerability for first onset of major depressive disorder and increases in depressive symptoms during adolescence. Methods: This NIMH-funded R01 study is a 3-year prospective, longitudinal investigation of approximately 300 community adolescents from the broader Philadelphia area, United States of America. Eligible participants must be 13-16 years old, fluent in English, and without a prior major depressive disorder. They are being selected along the entire dimension of self-reported reward responsiveness, with oversampling at the low tail of the dimension in order to increase the likelihood of major depression onsets. At Time 1 (T1), T3, and T5, each a year apart, participants complete blood draws to quantify biomarkers of low-grade inflammation, self-report and behavioral measures of reward responsiveness, and fMRI scans of reward neural activity and functional connectivity. At T1-T5 (with T2 and T4 six months between the yearly sessions), participants also complete diagnostic interviews and measures of depressive symptoms, reward-relevant life events, and behaviors that increase inflammation. Adversity history is assessed at T1 only. Discussion: This study is an innovative integration of research on multi-organ systems involved in reward and inflammatory signaling in understanding first onset of major depression in adolescence. It has the potential to facilitate novel neuroimmune and behavioral interventions to treat, and ideally prevent, depression.

Pre-frontal stimulation does not reliably increase reward responsiveness.

Depression is the leading cause of disability worldwide and its effects can be fatal, with over 800,000 people dying by suicide each year. Neuromodulatory treatments such as transcranial magnetic stimulation (TMS) are being used to treat depression. Despite its endorsement by two regulatory bodies: NICE (2016) and the FDA (2008), there are major questions about the treatment efficacy and biological mechanisms of TMS. Ahn et al.'s (2013) justified the use of TMS in a clinical context in an important study indicating that excitatory TMS increases reward responsiveness. A pseudo-replication of this study by Duprat et al., (2016) also found a similar effect of active TMS, but only with the addition of an exploratory covariate to the analyses-trait reward responsiveness. Here we replicate Ahn et al.'s (2013) key study, and to test the reliability of the effects, and their dependency on trait reward responsiveness as described by Duprat et al., (2016). Using excitatory and sham TMS, we tested volunteers using the probabilistic learning task to measure their reward responsiveness both before and after stimulation. We also examined affect (positive, negative) following stimulation. Irrespective of TMS, the task was shown to be sensitive to reward responsiveness. However, we did not show TMS to be effective in increasing reward responsiveness and we did not replicate Ahn et al., (2013) or Duprat et al., (2016)'s key findings for TMS efficacy, where we provide evidence favouring the null. Moreover, exploratory analyses suggested following active stimulation, positive affect was reduced. Given our findings, we question the basic effects, which support the use of TMS for depression, particularly considering potential deleterious effects of reduced positive affect in patients with depression.

Longitudinal Associations Between Reward Responsiveness and Depression Across Adolescence.

OBJECTIVE: Lower neural response to reward predicts subsequent depression during adolescence. Both pubertal development and biological sex have important effects on reward system development and depression during this period. However, relations among these variables across the transition from childhood to adolescence are not well characterized. METHOD: Depressive symptoms, pubertal status, and the reward positivity (RewP) event-related potential component, a neural indicator of reward responsivity, were assessed in 609 community-recruited youth at 9, 12, and 15 years of age. Structural equation modeling was used to examine concurrent and prospective relations within and between depression and reward responsiveness as well as the influence of pubertal status and biological sex on these variables across assessments. RESULTS: Stability paths for depression, the RewP, and pubertal status were significant across assessments. Compared with male participants, female participants reported more advanced pubertal status at all assessments, a smaller RewP at age 9, and higher levels of depression at age 15. More advanced pubertal status was associated with a larger RewP at age 15. Most importantly, there were bidirectional prospective effects between the RewP and depression from ages 12 to 15; a lower RewP at age 12 predicted increases in depression at age 15, whereas increased depression at age 12 predicted a lower RewP at age 15. CONCLUSION: These findings indicate that there are bidirectional prospective effects between reward responsiveness and depression that emerge between ages 12 and 15. This may be a crucial time for studying bidirectional reward responsiveness-depression associations across time.

Influence of game features on attention in adults.

Introduction: The incorporation of game features into cognitive tasks can inform us about the influence of reward and motivation on attention. Continuous performance tasks (CPTs), designed to assess attention abilities, are examples of cognitive tasks that have been targeted for the addition of game features. However, previous results have been mixed regarding how game elements affect attention abilities and task performance. Methods: Here, we studied if there were factors that predict which individuals exhibit changes in attention from game features added to a CPT. Participants (N = 94, aged 21-71) played a traditional CPT and a game CPT with identical mechanics, but featured engaging game elements (aesthetics, storyline, competition, feedback, and reward). Results: We first found corroborating evidence that game features have mixed effects on attention performance: most attention metrics of interest exhibited no overall difference between the traditional and game CPT, while game elements reduced performance for a few metrics. Importantly, we also found that specific behavioral and demographic profiles predicted individual differences in performance on the game CPT compared to the traditional CPT. Those with more attention difficulties (ADHD symptoms), more reward responsiveness, and younger adults performed better on the game CPT while, conversely, those with fewer ADHD symptoms, less reward responsiveness, and older adults performed better on the traditional CPT. Discussion: These findings provide insights into how game features can influence attention in different individuals and have important implications for the use of game elements in cognitive tasks and training interventions.