Reward-related Brain Activity Research Articles

Research advances in reward positivity and internalizing and externalizing problems in children and adolescents

Adolescence is a critical period for the development of the reward circuit, and reward positivity (RewP) is one of the electrophysiological indicators reflecting reward processing. Many studies have shown that abnormalities in RewP is closely associated with internalizing and externalizing problems in children and adolescents. In addition, factors such as stressful life events and sleep disorders can affect reward-related brain activity and increase the risk of various psychopathological problems in this population. The article reviews the characteristics of changes in RewP among children and adolescents with various internalizing and externalizing problems in recent years, aiming to provide a reference for the basic research on the pathogenesis of these issues and to identify new targets for clinical diagnosis and treatment.

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.

Reward-Related Brain Activity Mediates the Relationship Between Decision-Making Deficits and Pediatric Depression Symptom Severity

BackgroundThe mechanisms that link neural and behavioral indices of reduced reward sensitivity in depression, particularly in children, remain unclear. Reward positivity (RewP), a neural index of reward processing, has been consistently associated with depression. Separately, recent studies using the drift-diffusion model on behavioral data have delineated computational indices of reward sensitivity. Therefore, in the current study, we examined whether RewP is a neural mediator of drift-diffusion model–based indices of reward processing in predicting pediatric depression across varying levels of symptom severity. MethodsA community sample of 166 girls, ages 8 to 14 years, completed 2 tasks. The first was a reward guessing task from which RewP was computed using electroencephalography; the second was a probabilistic reward-based decision-making task. On this second task, drift-diffusion model analysis was applied to behavioral data to quantify the efficiency of accumulating reward-related evidence (drift rate) and potential baseline bias (starting point) toward the differently rewarded choices. Depression severity was measured using the self-report Children’s Depression Inventory. ResultsRewP was correlated with drift rate, but not starting point bias, toward the more rewarded choice. Furthermore, RewP completely mediated the association between a slower drift rate toward the more rewarded option and higher depression symptom severity. ConclusionsOur findings suggest that reduced neural sensitivity to reward feedback may be a neural mechanism that underlies behavioral insensitivity to reward in children and adolescents with higher depression symptom severity, offering novel insights into the relationship between neural and computational indices of reward processing in this context.

Childhood anhedonia symptoms and stressful life events predict the development of reward-related brain activity across adolescence.

The reward positivity (RewP) is an event-related potential that indexes reinforcement learning and reward system activation. The RewP has been shown to increase across adolescence; however, most studies have examined the RewP across two assessments, and no studies have examined within-person changes across adolescence into young adulthood. Moreover, the RewP has been identified as a neurobiological risk factor for adolescent-onset depression, but it is unclear whether childhood psychosocial risk factors might predict RewP development across adolescence. In a sample of 317 8- to 14-year-old girls (Mage = 12.4, SD = 1.8), the present study examined self-report measures of depression symptoms and stressful life events at baseline and the ΔRewP during the doors guessing task across three timepoints. Growth modeling indicated that, across all participants, the ΔRewP did not demonstrate linear change across adolescence. However, baseline anhedonia symptoms predicted within-person changes in the ΔRewP, such that individuals with low anhedonia symptoms demonstrated a linear increase in the ΔRewP, but individuals with high anhedonia symptoms had no change in the ΔRewP across adolescence. Similar patterns were observed for stressful life events. The present study suggests that childhood risk factors impact the development of reward-related brain activity, which might subsequently increase risk for psychopathology.

Exposure to community violence as a mechanism linking neighborhood socioeconomic disadvantage and neural responses to reward.

A growing literature links socioeconomic disadvantage and adversity to brain function, including disruptions in reward processing. Less research has examined exposure to community violence (ECV) as a specific adversity related to differences in reward-related brain activation, despite the prevalence of community violence exposure for those living in disadvantaged contexts. The current study tested whether ECV was associated with reward-related ventral striatum (VS) activation after accounting for familial factors associated with differences in reward-related activation (e.g. parenting and family income). Moreover, we tested whether ECV is a mechanism linking socioeconomic disadvantage to reward-related activation in the VS. We utilized data from 444 adolescent twins sampled from birth records and residing in neighborhoods with above-average levels of poverty. ECV was associated with greater reward-related VS activation, and the association remained after accounting for family-level markers of disadvantage. We identified an indirect pathway in which socioeconomic disadvantage predicted greater reward-related activation via greater ECV, over and above family-level adversity. These findings highlight the unique impact of community violence exposure on reward processing and provide a mechanism through which socioeconomic disadvantage may shape brain function.

Light Cannabis Use and the Adolescent Brain: An 8-years Longitudinal Assessment of Mental Health, Cognition, and Reward Processing

RationaleFor decades, cannabis has been the most widely used illicit substance in the world, particularly among youth. Research suggests that mental health problems associated with cannabis use may result from its effect on reward brain circuit, emotional processes, and cognition. However, findings are mostly derived from correlational studies and inconsistent, particularly in adolescents.Objectives and MethodsUsing data from the IMAGEN study, participants (non-users, persistent users, abstinent users) were classified according to their cannabis use at 19 and 22 years-old. All participants were cannabis-naïve at baseline (14 years-old). Psychopathological symptoms, cognitive performance, and brain activity while performing a Monetary Incentive Delay task were used as predictors of substance use and to analyze group differences over time.ResultsHigher scores on conduct problems and lower on peer problems at 14 years-old (n = 318) predicted a greater likelihood of transitioning to cannabis use within 5 years. At 19 years of age, individuals who consistently engaged in low-frequency (i.e., light) cannabis use (n = 57) exhibited greater conduct problems and hyperactivity/inattention symptoms compared to non-users (n = 52) but did not differ in emotional symptoms, cognitive functioning, or brain activity during the MID task. At 22 years, those who used cannabis at both 19 and 22 years-old n = 17), but not individuals that had been abstinent for ≥ 1 month (n = 19), reported higher conduct problems than non-users (n = 17).ConclusionsImpairments in reward-related brain activity and cognitive functioning do not appear to precede or succeed cannabis use (i.e., weekly, or monthly use). Cannabis-naïve adolescents with conduct problems and more socially engaged with their peers may be at a greater risk for lighter yet persistent cannabis use in the future.

Neural response to monetary and social rewards and familial risk for psychopathology in adolescent females.

Adolescence is a key developmental period for the emergence of psychopathology. Reward-related brain activity increases across adolescence and has been identified as a potential neurobiological mechanism of risk for different forms of psychopathology. The reward positivity (RewP) is an event-related potential component that indexes reward system activation and has been associated with both concurrent and family history of psychopathology. However, it is unclear whether the RewP is also associated with higher-order psychopathology subfactors and whether this relationship is present across different types of reward. In a sample of 193 adolescent females and a biological parent, the present study examined the association between adolescent and parental psychopathology subfactors and adolescent RewP to monetary and social reward. Results indicated that the adolescent and parental distress subfactors were negatively associated with the adolescent domain-general RewP. The adolescent and parental positive mood subfactors were negatively associated with the adolescent domain-general and domain-specific monetary RewP, respectively. Conversely, the adolescent and parental fear/obsessions subfactors were positively associated with the adolescent domain-general RewP. The associations between parental and adolescent psychopathology subfactors and the adolescent RewP were independent of each other. The RewP in adolescent females is associated with both concurrent and parental psychopathology symptoms, suggesting that it indexes both severity and risk for higher-order subfactors.

Prebiotic diet changes neural correlates of food decision-making in overweight adults: a randomised controlled within-subject cross-over trial

ObjectiveAnimal studies suggest that prebiotic, plant-derived nutrients could improve homoeostatic and hedonic brain functions through improvements in microbiome–gut–brain communication. However, little is known if these results are applicable to humans....

Relationship between reward-related brain activity and opportunities to sit

The present study tested whether energy-minimizing behaviors evoke reward-related brain activity that promotes the repetition of these behaviors via reinforcement learning processes. Fifty-eight healthy young adults in a standing position performed a task where they could earn a reward either by sitting down or squatting while undergoing electroencephalographic (EEG) recording. Reward-prediction errors were quantified as the amplitude of the EEG-derived reward positivity. Results showed that reward positivity was larger on reward versus no reward trials, confirming the validity of our paradigm to measure evoked reward-related brain activity. However, results showed no evidence that sitting (versus standing and squatting) trials led to larger reward positivity. Moreover, we found no evidence suggesting that this effect was moderated by typical physical activity, physical activity on the day of the study, or energy expenditure during the experiment. However, at the behavioral level, results showed that the probability of choosing the stimulus more likely to lead to sitting than standing increased as the number of trials increased. In addition, results revealed that the probability of changing the selected stimulus was higher when the previous trial was a stand trial relative to a sit trial. In sum, neural results showed no evidence supporting the theory that opportunities to minimize energy expenditure are rewarding. However, behavioral findings suggested participants tend to choose the less effortful behavioral alternative and were therefore consistent with the theory of effort minimization (TEMPA).

The propensity to sign-track is associated with externalizing behavior and distinct patterns of reward-related brain activation in youth

Externalizing behaviors in childhood often predict impulse control disorders in adulthood; however, the underlying bio-behavioral risk factors are incompletely understood. In animals, the propensity to sign-track, or the degree to which incentive motivational value is attributed to reward cues, is associated with externalizing-type behaviors and deficits in executive control. Using a Pavlovian conditioned approach paradigm, we quantified sign-tracking in 40 healthy 9–12-year-olds. We also measured parent-reported externalizing behaviors and anticipatory neural activations to outcome-predicting cues using the monetary incentive delay fMRI task. Sign-tracking was associated with attentional and inhibitory control deficits and the degree of amygdala, but not cortical, activation during reward anticipation. These findings support the hypothesis that youth with a propensity to sign-track are prone to externalizing tendencies, with an over-reliance on subcortical cue-reactive brain systems. This research highlights sign-tracking as a promising experimental approach delineating the behavioral and neural circuitry of individuals at risk for externalizing disorders.

Food appearance affects reward-related brain activity in healthy adults: a functional magnetic resonance imaging study

A good appearance of food increases appetite. A new food product called iEat® resembles the appearance and softness of familiar foods. Previous studies have reported that iEat® foods increase appetite. However, the neuronal substrates underlying the increase in appetite following the observation of iEat® foods remain unknown. In the present study, the brain activity of 20 healthy adults during the visual presentation of iEat® and pureed foods and non-food objects was examined using functional magnetic resonance imaging. Compared with pureed foods and non-food objects, iEat® foods showed significantly greater activation in regions of the brain reward system, such as the amygdala, ventral striatum and orbital frontal cortex. In addition, individual differences in the activity of the left amygdala were positively correlated with subjective appetite ratings. These results suggest that the good appearance of foods, such as iEat® foods, may be useful for stimulating the appetite of patients with poor appetite.

Congenital Adrenal Hyperplasia and Brain Health: A Systematic Review of Structural, Functional, and Diffusion Magnetic Resonance Imaging (MRI) Investigations.

Congenital adrenal hyperplasia (CAH) is a group of genetic disorders that affects the adrenal glands and is the most common cause of primary adrenal insufficiency in children. In the past few decades, magnetic resonance imaging (MRI) has been implemented to investigate how the brain may be affected by CAH. A systematic review was conducted to evaluate and synthesize the reported evidence of brain findings related to CAH using structural, functional, and diffusion-weighted MRI. We searched bibliographical databases through July 2021 for brain MRI studies in individuals with CAH. Twenty-eight studies were identified, including 13 case reports or series, 10 studies that recruited and studied CAH patients vs unaffected controls, and 5 studies without a matched control group. Eleven studies used structural MRI to identify structural abnormalities or quantify brain volumes, whereas 3 studies implemented functional MRI to investigate brain activity, and 3 reported diffusion MRI findings to assess white matter microstructure. Some commonly reported findings across studies included cortical atrophy and differences in gray matter volumes, as well as white matter hyperintensities, altered white matter microstructure, and distinct patterns of emotion and reward-related brain activity. These findings suggest differences in brain structure and function in patients with CAH. Limitations of these studies highlight the need for CAH neuroimaging studies to incorporate larger sample sizes and follow best study design and MRI analytic practices, as well as clarify potential neurologic effects seen across the lifespan and in relation to clinical and behavioral CAH phenotypes.

Greater Cumulative Lifetime Stressor Exposure Predicts Blunted Reward Positivity in Adolescent Girls Followed for 2 Years

BackgroundAlthough research has found that life stress is associated with reward-related brain activity, few studies have examined how cumulative stressors occurring over the entire lifetime affect reward processing during adolescence. MethodsTo address this issue, we investigated how lifetime stressor exposure related to reward processing, indexed by the reward positivity, in 240 adolescent girls between ages 8 and 14 years (mean age = 12.4). Participants were followed for 2 years. They completed a reward task at baseline and follow-up and the Stress and Adversity Inventory at follow-up. ResultsAs hypothesized, greater lifetime stressor exposure was related to a blunted reward positivity at the follow-up session while controlling for baseline age, baseline reward positivity, and time between assessments. Furthermore, this association was evident for acute but not chronic lifetime stressors. ConclusionsThese data suggest that the development of adaptive reward processing may be adversely affected by experiencing major life stressors. The results may thus have implications for understanding how stressors increase risk for psychopathology, such as major depressive disorder.

Sexually divergent development of depression-related brain networks during healthy human adolescence.

Sexual differences in human brain development could be relevant to sex differences in the incidence of depression during adolescence. We tested for sex differences in parameters of normative brain network development using fMRI data on N = 298 healthy adolescents, aged 14 to 26 years, each scanned one to three times. Sexually divergent development of functional connectivity was located in the default mode network, limbic cortex, and subcortical nuclei. Females had a more “disruptive” pattern of development, where weak functional connectivity at age 14 became stronger during adolescence. This fMRI-derived map of sexually divergent brain network development was robustly colocated with i prior loci of reward-related brain activation ii a map of functional dysconnectivity in major depressive disorder (MDD), and iii an adult brain gene transcriptional pattern enriched for genes on the X chromosome, neurodevelopmental genes, and risk genes for MDD. We found normative sexual divergence in adolescent development of a cortico-subcortical brain functional network that is relevant to depression.

Δ9-THC reduces reward-related brain activity in healthy adults.

Greater availability of cannabis in the USA has raised concerns about adverse effects of the drug, including possible amotivational states. Lack of motivation may be assessed by examining acute effects of cannabinoids on reward processing. This study examined single doses of delta-9-tetrahydrocannabinol (∆9-THC; 7.5, 15mg oral) in healthy adults using a version of the monetary incentive delay (MID) task adapted for electroencephalography (EEG; e-MID) in a within-subjects, double blind design. Two phases of reward processing were examined: anticipation, which occurs with presentation of cues that indicate upcoming reward, punishment, or neutral conditions, and outcome, which occurs with feedback indicating hits or misses. During anticipation, we measured two event-related potential (ERP) components: the P300, which measures attention and motivation, and the LPP, which measures affective processing. During outcome processing, we measured P300 and LPP, as well as the RewP, which measures outcome evaluation. We found that ∆9-THC modulated outcome processing, but not reward anticipation. Specifically, both doses of ∆9-THC (7.5 and 15mg) reduced RewP amplitudes after outcome feedback (hits and misses) relative to placebo. ∆9-THC (15mg) also reduced P300 and LPP amplitudes following hits compared to misses, relative to both placebo and 7.5mg ∆9-THC. These findings suggest that ∆9-THC dampens responses to both reward and loss feedback, which may reflect an "amotivational" state. Future studies are needed to determine generalizability of this effect, such as its pharmacological specificity and its specificity to monetary vs other types of reward.

Neuronally-enriched exosomal microRNA-27b mediates acute effects of ibuprofen on reward-related brain activity in healthy adults: a randomized, placebo-controlled, double-blind trial

This double-blind, randomized, within-subjects design evaluated whether acute administration of an anti-inflammatory drug modulates neuron-specific, inflammation-modulating microRNAs linked to macroscopic changes in reward processing. Twenty healthy subjects (10 females, 10 males) underwent a functional magnetic resonance imaging scan while performing a monetary incentive delay (MID) task and provided blood samples after administration of placebo, 200 mg, or 600 mg of ibuprofen. Neuronally-enriched exosomal microRNAs were extracted from serum and sequenced. Results showed that: (1) 600 mg of ibuprofen exhibited higher miR-27b-3p, miR-320b, miR-23b and miR-203a-3p expression than placebo; (2) higher mir-27b-3p was associated with lower insula activation during MID loss anticipation; and (3) there was an inverse relationship between miR-27b-3p and MID gain anticipation in bilateral putamen during placebo, a pattern attenuated by both 200 mg and 600 mg of ibuprofen. These findings are consistent with the hypothesis that miR-27b could be an important messaging molecule that is associated with regulating the processing of positive or negative valenced information.

Multi‐band FMRI compromises detection of mesolimbic reward responses

Recent innovations in Functional Magnetic Resonance Imaging (FMRI) have sped data collection by enabling simultaneous scans of neural activity in multiple brain locations, but have these innovations come at a cost? In a meta-analysis and preregistered direct comparison of original data, we examined whether acquiring FMRI data with multi-band versus single-band scanning protocols might compromise detection of mesolimbic activity during reward processing. Meta-analytic results (n = 44 studies; cumulative n = 5005 subjects) indicated that relative to single-band scans, multi-band scans showed significantly decreased effect sizes for reward anticipation in the Nucleus Accumbens (NAcc) by more than half. Direct within-subject comparison of single-band versus multi-band scanning data (multi-band factors = 4 and 8; n = 12 subjects) acquired during repeated administration of the Monetary Incentive Delay task indicated that reductions in temporal signal-to-noise ratio could account for compromised detection of task-related responses in mesolimbic regions (i.e., the NAcc). Together, these findings imply that researchers should opt for single-band over multi-band scanning protocols when probing mesolimbic responses with FMRI. The findings also have implications for inferring mesolimbic activity during related tasks and rest, for summarizing historical results, and for using neuroimaging data to track individual differences in reward-related brain activity.

Investigating the association between smoking, environmental tobacco smoke exposure and reward-related brain activity in adolescent experimental smokers.

Reduced anticipatory reward‐related activity, especially in the ventral striatum (VS), may underly adolescent vulnerability to develop nicotine dependence. It remains unclear whether nicotine uptake caused by environmental tobacco smoke (ETS) exposure, known to be associated with future smoking, might prompt similar changes in the brain's reward system, rendering adolescents vulnerable for development of nicotine dependence. To address this question, we tested whether current ETS exposure and monthly smoking are associated with VS hypoactivity for non‐drug rewards in experimental smoking adolescents. One‐hundred adolescents performed a monetary incentive delay task while brain activity was measured using fMRI. To test the hypothesized relationship, we used a variety of approaches: (1) a whole‐brain voxel‐wise approach, (2) an region‐of‐interest approach in the VS using frequentist and Bayesian statistics and (3) a small volume voxel‐wise approach across the complete striatum. The results converged in revealing no significant relationships between monthly smoking, ETS exposure and reward‐related brain activation across the brain or in the (ventral) striatum specifically. However, Bayesian statistics showed only anecdotal evidence for the null hypothesis in the VS, providing limited insight into the (non‐)existence of the hypothesized relationship. Based on these results, we speculate that blunted VS reward‐related activity might only occur after relatively high levels of exposure or might be associated with more long term effects of smoking. Future studies would benefit from even larger sample sizes to reliably distinguish between the null and alternative models, as well as more objective measures of (environmental) smoking via using devices such as silicone wristbands.

Ventral striatal activation during reward differs between major depression with and without impaired mood reactivity

BackgroundRecent efforts to classify subtypes of major depressive disorder marked by different psychophysiological indicators have identified blunted reward-related brain activation in gambling tasks as a characteristic linked specifically to depressed participants with impaired mood reactivity. MethodsThe current study compared individuals diagnosed with current depressive disorder (n = 26) with healthy controls (n = 24) regarding brain responses to gain and loss trials in an fMRI version of the “Doors” choice-feedback task. Study aims were to examine reward-related brain activation in relation to depression, depressive subtypes, and course of depression. ResultsAcross the sample, participants showed a significant response to gain versus loss in left and right ventral striatum as well as medial and left lateral prefrontal cortex. Relative to controls, participants with current depression were characterized by blunted reactivity in left ventral striatum. Furthermore, activation in the left ventral striatum differentiated subgroups of depression with and without impaired mood reactivity. Finally, left striatal hypoactivation to reward predicted remission when controlling for current depressive symptomatology, albeit at a trend level. ConclusionsBlunted reward-related activation in the left ventral striatum might be useful as a marker for depression subtype and may have the potential to predict future course of depression.

Reward-Related Brain Activation, Resting-State Functional Connectivity, and White Matter Morphology Link Early Life Stress and Internalizing Symptoms in Adolescence

Adolescents exposed to early life stress (ELS) are at increased risk for internalizing disorders, including depression and anxiety. Although blunted striatal activation (Hanson et al., 2015) and weaker functional connectivity between the prefrontal cortex and ventral striatum (Marshall et al., 2018) has been shown to mediate the association between ELS and internalizing symptoms, less is known about relations between ELS and reward-related white matter morphology. Further, no study has used a multimodal approach to investigate ELS-related differences in task-based activation, resting-state functional connectivity, and diffusion-based white matter morphology of reward processing circuits and their relation to internalizing symptoms.