Reward-related Brain Function Research Articles

Neural mechanisms of reward processing in preadolescent irritability: Insights from the ABCD study

Elevated youth irritability is characterized by increased proneness to frustration relative to peers when rewards are blocked, and is a transdiagnostic symptom that predicts multiple forms of psychopathology and poorer socioeconomic outcomes in adulthood. Although mechanistic models propose that irritability is the result of aberrant reward-related brain function, youth irritability as it relates to multiple components of reward processes, including reward anticipation, gain, and loss, has yet to be examined in large, population-based samples. Data from the Adolescent Brain and Cognitive Development (ABCD) baseline sample (N = 5923) was used to examine associations between youth irritability (measured by parent-report) and reward-related brain activation and connectivity in a large, preadolescent sample. Preadolescents (M age = 9.96 years, SD = 0.63) performed the Monetary Incentive Delay task during functional MRI acquisition. In the task, during the anticipation period, participants were informed of the upcoming trial type (win money, lose money, no money at stake) and waited to hit a target; during the feedback period, participants were informed of their success. Whole brain and region of interest (ROI) analyses evaluated task conditions in relation to irritability level. Preadolescents with higher compared to lower levels of irritability demonstrated blunted prefrontal cortex activation in the anticipation period and exaggerated striatum-prefrontal connectivity differences among reward conditions during the feedback period. These effects persisted after adjusting for co-occurring anxiety, depression, and attention-deficit/hyperactivity disorder symptoms. These findings provide evidence for the role of reward salience in pathophysiological models of youth irritability, suggesting a mechanism that may contribute to exaggerated behavioral responses.

Early life stress moderates the relation between systemic inflammation and neural activation to reward in adolescents both cross-sectionally and longitudinally.

Elevated levels of systemic inflammation are associated with altered reward-related brain function in ventral striatal areas of the brain like the nucleus accumbens (NAcc). In adolescents, cross-sectional research indicates that exposure to early life stress (ELS) can moderate the relation between inflammation and neural activation, which may contribute to atypical reward function; however, no studies have tested whether this moderation by ELS of neuroimmune associations persists over time. Here, we conducted a cross-sectional analysis and the first exploratory longitudinal analysis testing whether cumulative severity of ELS moderates the association of systemic inflammation with reward-related processing in the NAcc in adolescents (n = 104; 58F/46M; M[SD] age = 16.00[1.45] years; range = 13.07-19.86 years). For the cross-sectional analysis, we modeled a statistical interaction between ELS and levels of C-reactive protein (CRP) predicting NAcc activation during the anticipation and outcome phases of a monetary reward task. We found that higher CRP was associated with blunted NAcc activation during the outcome of reward in youth who experienced higher levels of ELS (β = -0.31; p = 0.006). For the longitudinal analysis, we modeled an interaction between ELS and change in CRP predicting change in NAcc activation across 2 years. This analysis similarly showed that increasing CRP over time was associated with decreasing NAcc during reward outcomes in youth who experienced higher levels of ELS (β = -0.47; p = 0.022). Both findings support contemporary theoretical frameworks involving associations among inflammation, reward-related brain function, and ELS exposure, and suggest that experiencing ELS can have significant and enduring effects on neuroimmune function and adolescent neurodevelopment.

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

BackgroundBipolar 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.MethodsThis 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.DiscussionThis 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.

Sex differences in addiction-relevant behavioral outcomes in rodents following early life stress

In humans, exposure to early life stress (ELS) is an established risk factor for the development of substance use disorders (SUDs) during later life. Similarly, rodents exposed to ELS involving disrupted mother-infant interactions, such as maternal separation (MS) or adverse caregiving due to scarcity-adversity induced by limited bedding and nesting (LBN) conditions, also exhibit long-term alterations in alcohol and drug consumption. In both humans and rodents, there is a range of addiction-related behaviors that are associated with drug use and even predictive of subsequent SUDs. In rodents, these include increased anxiety-like behavior, impulsivity, and novelty-seeking, altered alcohol and drug intake patterns, as well as disrupted reward-related processes involving consummatory and social behaviors. Importantly, the expression of these behaviors often varies throughout the lifespan. Moreover, preclinical studies suggest that sex differences play a role in how exposure to ELS impacts reward and addiction-related phenotypes as well as underlying brain reward circuitry. Here, addiction-relevant behavioral outcomes and mesolimbic dopamine (DA) dysfunction resulting from ELS in the form of MS and LBN are discussed with a focus on age- and sex-dependent effects. Overall, these findings suggest that ELS may increase susceptibility for later life drug use and SUDs by interfering with the normal maturation of reward-related brain and behavioral function.

Effects of gonadal steroids on reward circuitry function and anhedonia in women with a history of postpartum depression

BackgroundReward system dysfunction is evident across neuropsychiatric conditions. Here we present data from a double-blinded pharmaco-fMRI study investigating the triggering of anhedonia and reward circuit activity in women. MethodsThe hormonal states of pregnancy and parturition were simulated in euthymic women with a history of postpartum depression (PPD+; n = 15) and those without such a history (PPD−; n = 15) by inducing hypogonadism, adding back estradiol and progesterone for 8 weeks (“addback”), and then withdrawing both steroids (“withdrawal”). Anhedonia was assessed using the Inventory of Depression and Anxiety Symptoms (IDAS) during each hormone phase. Those who reported a 30 % or greater increase in IDAS anhedonia, dysphoria, or ill temper during addback or withdrawal, compared with pre-treatment, were identified as hormone sensitive (HS+) and all others were identified as non-hormone sensitive (HS−). The monetary incentive delay (MID) task was administered during fMRI sessions at pre-treatment and during hormone withdrawal to assess brain activation during reward anticipation and feedback. ResultsOn average, anhedonia increased during addback and withdrawal in PPD+ but not PPD−. During reward feedback, both HS+ (n = 10) and HS− (n = 18) showed decreased activation in clusters in the right putamen (p < .031, FWE-corrected) and left postcentral and supramarginal gyri (p < .014, FWE-corrected) at the withdrawal scans, relative to pre-treatment scans. LimitationsA modest sample size, stringent exclusion criteria, and relative lack of diversity in study participants limit the generalizability of results. ConclusionAlthough results do not explain differential hormone sensitivity in depression, they demonstrate significant effects of reproductive hormones on reward-related brain function in women.

Reward-Related Neural Activity Associated With General Psychopathology in 9- And 10-Year-Olds From the ABCD Study

The general psychopathology factor (P) accounts for variance common to all mental disorders through a dimensional, multi-domain approach. Relatedly, reward-processing abnormalities have been identified as a transdiagnostic feature across multiple psychopathologies. The present study examined reward-related brain function as a predictor of P over and above relevant demographic and self-report measures. Investigating multi-domain predictors of P may help identify early risk indicators in preadolescence when psychopathology begins to emerge.

The Interplay between Reward-Relevant Life Events and Trait Reward Sensitivity in Neural Responses to Reward Cues.

The reward hypersensitivity model posits that trait reward hypersensitivity should elicit hyper/hypo approach motivation following exposure to recent life events that activate (goal-striving and goal-attainment) or deactivate (goal-failure) the reward system, respectively. To test these hypotheses, eighty-seven young adults with high (HRew) versus moderate (MRew) trait reward sensitivity reported frequency of life events via the Life Event Interview. Brain activation was assessed during the fMRI Monetary Incentive Delay task. Greater exposure to goal-striving events was associated with higher nucleus accumbens (NAc) reward anticipation among HRew participants and lower orbitofrontal cortex (OFC) reward anticipation among MRew participants. Greater exposure to goal-failure events was associated with higher NAc and OFC reward anticipation only among HRew participants. This study demonstrated different neural reward anticipation (but not outcome) following reward-relevant events for HRew versus MRew individuals. Trait reward sensitivity and reward-relevant life events may jointly modulate reward-related brain function, with implications for understanding psychopathology.

Decreased reward-related brain function prospectively predicts increased substance use.

Substance use and addiction are prominent global health concerns and are associated with abnormalities in reward sensitivity. Reward sensitivity and approach motivation are supported by a fronto-striatal neural circuit including the orbitofrontal cortex (OFC), ventral striatum (VS), and dorsal striatum (DS). Although research highlights abnormalities in reward neural circuitry among individuals with problematic substance use, questions remain about whether such use arises from excessively high, or excessively low, reward sensitivity. This study examined whether reward-related brain function predicted subsequent substance use course. Participants were 79 right-handed individuals (Mage = 21.52, SD = 2.19 years), who completed a monetary incentive delay (MID) fMRI task, and follow-up measures assessing substance use frequency and impairment. The average duration of the follow-up period was 9.1 months. Regions-of-interest analyses focused on the reward anticipation phase of the MID. Decreased activation in the VS during reward anticipation predicted increased substance use frequency at follow-up. Decreased DS activation during reward anticipation predicted increased substance use frequency at follow-up, but this finding did not pass correction for multiple comparisons. Analyses adjusted for relevant covariates, including baseline substance use and the presence or absence of a lifetime substance use disorder prior to MRI scanning. Results support the reward hyposensitivity theory, suggesting that decreased reward-related brain function is a risk factor for increased substance use. Results have implications for understanding the pathophysiology of problematic substance use and highlight the importance of the fronto-striatal reward circuit in the development and maintenance of addiction. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

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

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

Assessment of Reward-Related Brain Function After a Single Dose of Oxytocin in Autism: A Randomized Controlled Trial

BackgroundAutism spectrum disorder (ASD) is characterized by difficulties in social communication and interaction, which have been related to atypical neural processing of rewards, especially in the social domain. As intranasal oxytocin has been shown to modulate activation of the brain’s reward circuit, oxytocin might ameliorate the processing of social rewards in ASD and thus improve social difficulties. MethodsIn this randomized, double-blind, placebo-controlled, crossover functional magnetic resonance imaging study, we examined effects of a 24-IU dose of intranasal oxytocin on reward-related brain function in 37 men with ASD without intellectual impairment and 37 age- and IQ-matched control participants. Participants performed an incentive delay task that allows the investigation of neural activity associated with the anticipation and receipt of monetary and social rewards. ResultsNonsignificant tests suggested that oxytocin did not influence neural processes related to the anticipation of social or monetary rewards in either group. Complementary Bayesian analyses indicated moderate evidence for a null model, relative to an alternative model. Our results were inconclusive regarding possible oxytocin effects on amygdala responsiveness to social rewards during reward consumption. There were no significant differences in reward-related brain function between the two groups under placebo. ConclusionsOur results do not support the hypothesis that intranasal oxytocin generally enhances activation of reward-related neural circuits in men with and without ASD.

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.

Neural mechanisms of reward processing in adolescent irritability.

Irritability is impairing and prevalent across pediatric psychiatric disorders and typical development, yet its neural mechanisms are largely unknown. This study evaluated the relation between adolescent irritability and reward-related brain function as a candidate neural mechanism. Adolescents from intervention-seeking families in the community (N=52; mean age=13.80, SD=1.94) completed a monetary incentive delay task to assess reward anticipation and feedback (reward receipt and omission) during fMRI acquisition. Whole-brain analyses, controlling for age, examined brain activation and striatal and amygdala connectivity in relation to irritability. Irritability was measured using the parent- and youth-reported Affective Reactivity Index. Irritability was associated with altered reward processing-related activation and connectivity in multiple networks during reward anticipation and feedback, including increased striatal activation and altered ventral striatum connectivity with prefrontal areas. Our findings suggest that irritability is associated with altered neural patterns during reward processing and that aberrant prefrontal cortex-mediated top-down control may be related to irritability. These findings inform our understanding of the etiology of youth irritability and the development of mechanism-based interventions.

Reward-Related Brain Function in Lifetime Depression, Anxiety, and Comorbid Depression and Anxiety

Reward-Related Brain Function in Lifetime Depression, Anxiety, and Comorbid Depression and Anxiety

95. Identifying Sensitive Periods for the Impact of Insufficient Sleep on Reward-Related Brain Function and Future Depression Among At-Risk Youth

95. Identifying Sensitive Periods for the Impact of Insufficient Sleep on Reward-Related Brain Function and Future Depression Among At-Risk Youth

F200. Too Tired to Care: A Combination of Sleepiness and Poor Sleep Continuity Attenuate Reward-Related Brain Activation

Insomnia, characterized by sleep continuity complaints and daytime symptoms (e.g., sleepiness, fatigue), is a well-replicated risk factor for affective disorders. We examined the independent and combined effects of sleep continuity and sleepiness on reward-related brain function as a putative neural pathway linking insomnia and depression.

Negative affect amplifies the relation between appetitive-food-related neural responses and weight gain over three-year follow-up among adolescents.

Obesity is a major public health concern that is associated with disruption in food reward-related brain function. This study examined if negative affect and stressful events enhance the relation between the food reward-related neural response and future weight gain. Initially healthy weight adolescents (N = 135) completed fMRI paradigms in which they tasted milkshakes and viewed palatable food images, and reported on negative affect and stressful events at baseline; BMI was measured annually over 3-year follow-up. Whole-brain analyses revealed that among participants with higher negative affect, weight gain over 3-year follow-up was predicted by elevated response to appetitive versus unappetitive food images in the left hippocampus, and elevated response in the vermis and the bilateral precuneus to tastes of milkshake versus tasteless solution. Among participants who experienced more stressful events, elevated right middle occipital gyrus response to milkshakes predicted future weight gain. Profiling analyses suggested that participants with higher negative affect or more stressful events who later gained weight reported engaging in more restrained eating and eating disorder-related behaviors. Results suggest that negative affect or stressful events may amplify the relation of neural response to food and the risk for future weight gain.

Preschool- and School-Age Irritability Predict Reward-Related Brain Function

Although chronic irritability in childhood is prevalent, impairing, and predictive of later maladjustment, its pathophysiology is largely unknown. Deficits in reward processing are hypothesized to play a role in irritability. The current study aimed to identify how the developmental timing of irritability during preschool- and school-age relates to reward-related brain function during school-age. Children's irritability was assessed during the preschool period (wave 1; ages 3.0-5.9 years) and 3 years later (wave 2; ages 5.9-9.6 years) using a clinical interview. At wave 2, children (N= 46; 28 female and 18 male) performed a monetary incentive delay task in which they received rewards, if they successfully hit a target, or no reward regardless of performance, during functional magnetic resonance imaging. Children with more versus less severe preschool irritability, controlling for concurrent irritability, exhibited altered reward-related connectivity: right amygdala with insula and inferior parietal lobe as well as left ventral striatum with lingual gyrus, postcentral gyrus, superior parietal lobe, and culmen. Children with more versus less severe concurrent irritability, controlling for preschool irritability, exhibited a similar pattern of altered connectivity between left and right amygdalae and superior frontal gyrus and between left ventral striatum and precuneus and culmen. Neural differences associated with irritability were most evident between reward and no-reward conditions when participants missed the target. Preschool-age irritability and concurrent irritability were uniquely associated with aberrant patterns of reward-related connectivity, highlighting the importance of developmental timing of irritability for brain function.

241. Risk for Bipolar Spectrum Disorders and Associations Between Inflammation and Reward-Related Brain Function

Reward hypersensitivity increases risk for first onset and recurrences of bipolar spectrum disorders (BSDs), and individuals with BSDs exhibit elevated proinflammatory cytokines in manic, euthymic, and depressed states. Some recent studies find that inflammation is associated with elevated reward responsiveness when potential reward probability or magnitude is high.

The Effects of Nicotine and Tobacco Use on Brain Reward Function: Interaction With Nicotine Dependence Severity.

This study investigated the effects of nicotine/tobacco on neural activation during performance of a monetary incentive delay task. Prior to each scan, nonsmokers received nicotine or placebo nasal spray, and smokers were smoking satiated or 24-hour withdrawn. During the scan, participants made timed responses to reward-related cues and received feedback. Parameter estimates from cue- and feedback-related activation in medial prefrontal regions and the nucleus accumbens were extracted and underwent within- and between-group analyses. Smokers' nicotine dependence severity was included as a continuous predictor variable for neural activation. Among smokers (n = 21), withdrawal decreased cue-related activation in the supplementary motor area and ventromedial prefrontal cortex, and the difference in activation (satiety > withdrawal) in these regions negatively correlated with nicotine dependence severity (Fagerström Test for Nicotine Dependence). Among nonsmokers (n = 22), nicotine increased the difference in nucleus accumbens activation between rewarded and nonrewarded feedback phases. Tobacco withdrawal and acute nicotine also had widespread effects on activation throughout the brain during the feedback phase. Acute nicotine in nonsmokers may have increased the salience of feedback information, but produced few effects on reward-related activation overall, perhaps reflecting nicotine's modest, indirect effects on reward processing. Conversely, tobacco withdrawal decreased activation compared with satiety, and this difference between conditions correlated with nicotine dependence severity. This suggests that as smokers become more dependent on nicotine, tobacco withdrawal has a more pronounced effect on reward processing. Relative to the acute effects of nicotine in nonsmokers, withdrawal from daily tobacco use had more significant effects on reward-related brain activation. This study suggests that the effects of tobacco withdrawal on reward-related brain function interact with subjects' level of nicotine dependence severity. These are potentially important sources of variability that could contribute to smoking cessation outcomes.

A longitudinal examination of event-related potentials sensitive to monetary reward and loss feedback from late childhood to middle adolescence.

Brain regions involved in reward processing undergo developmental changes from childhood to adolescence, and alterations in reward-related brain function are thought to contribute to the development of psychopathology. Event-related potentials (ERPs), such as the reward positivity (RewP) component, are valid measures of reward responsiveness that are easily assessed across development and provide insight into temporal dynamics of reward processing. Little work has systematically examined developmental changes in ERPs sensitive to reward. In this longitudinal study of 75 youth assessed 3 times across 6years, we used principal components analyses (PCA) to differentiate ERPs sensitive to monetary reward and loss feedback in late childhood, early adolescence, and middle adolescence. We then tested reliability of, and developmental changes in, ERPs. A greater number of ERP components differentiated reward and loss feedback in late childhood compared to adolescence, but components in childhood accounted for only a small proportion of variance. A component consistent with RewP was the only one to consistently emerge at each of the 3 assessments. RewP demonstrated acceptable reliability, particularly from early to middle adolescence, though reliability estimates varied depending on scoring approach and developmental period. The magnitude of the RewP component did not significantly change across time. Results provide insight into developmental changes in the structure of ERPs sensitive to reward, and indicate that RewP is a consistently observed and relatively stable measure of reward responsiveness, particularly across adolescence.