Neural Reward Research Articles

Medial Prefrontal Cortex Activity to Reward Outcome Moderates the Association Between Victimization Due to Sexual Orientation and Depression in Youth

BackgroundSexual minority youth (SMY) are 3 times more likely to experience depression than heterosexual peers. Minority stress theory posits that this association is explained by sexual orientation victimization, which acts as a stressor to impact depression. For those vulnerable to the effects of stress, victimization may worsen depression by altering activity in neural reward systems. This study examines whether neural reward systems moderate the influence of sexual orientation victimization, a common and distressing experience in SMY, on depression. MethodsA total of 81 participants ages 15 to 22 years (41% SMY, 52% marginalized race) reported sexual orientation victimization, depression severity, and anhedonia severity, and underwent a monetary reward functional magnetic resonance imaging task. Significant activation to reward > neutral outcome (pfamilywise error < .05) was determined within a meta-analytically derived Neurosynth reward mask. A univariate linear model examined the impact of reward activation and identity on victimization–depression relationships. ResultsSMY reported higher depression (p < .001), anhedonia (p = .03), and orientation victimization (p < .001) than heterosexual youth. The bilateral ventral striatum, medial prefrontal cortex (mPFC), anterior cingulate cortex, and right orbitofrontal cortex were significantly active to reward. mPFC activation moderated associations between sexual orientation victimization and depression (p = .03), with higher depression severity observed in those with a combination of higher mPFC activation and greater orientation victimization. ConclusionsSexual orientation victimization was related to depression but only in the context of higher mPFC activation, a pattern observed in depressed youth. These novel results provide evidence for neural reward sensitivity as a vulnerability factor for depression in SMY, suggesting mechanisms for disparities, and are a first step toward a clinical neuroscience understanding of minority stress in SMY.

Development of Reward Circuitry During Adolescence: Depression, Social Context, and Considerations for Future Research on Disparities in Sexual and Gender Minority Youth

Depression is a common and debilitating psychiatric illness that typically emerges in adolescence and impacts mental, social, and academic well-being. Significant research has examined the biological factors implicated in adolescent depression, converging on the specific importance of altered dopamine neurotransmission and neural reward—including social reward—systems. Neural reward systems are themselves likely influenced by social factors and risk factors for depression, with adolescent depression potentially developing more readily in those who experience a combination of neural and social factors. Here we review the role of dopamine and neural reward systems, consider the social factors that impact these systems, and propose a model for the interaction of reward and dopamine systems with social influences as a pathway to depression. Using this model, we highlight possible mechanisms for the development of depression in sexual and gender minority youth, a population at exceedingly high risk for depression.

Anhedonia in Depression and Schizophrenia: Brain Reward and Aversion Circuits.

Anhedonia, which is defined as markedly diminished interest or pleasure, is a prominent symptom of psychiatric disorders, most notably major depressive disorder (MDD) and schizophrenia. Anhedonia is considered a transdiagnostic symptom that is associated with deficits in neural reward and aversion functions. Here, we review the characteristics of anhedonia in depression and schizophrenia as well as shared or disorder-specific anhedonia-related alterations in reward and aversion pathways of the brain. In particular, we highlight that anhedonia is characterized by impairments in anticipatory pleasure and integration of reward-related information in MDD, whereas anhedonia in schizophrenia is associated with neurocognitive deficits in representing the value of rewards. Dysregulation of the frontostriatal circuit and mesocortical and mesolimbic circuit systems may be the transdiagnostic neurobiological basis of reward and aversion impairments underlying anhedonia in these two disorders. Blunted aversion processing in depression and relatively strong aversion in schizophrenia are primarily attributed to the dysfunction of the habenula, insula, amygdala, and anterior cingulate cortex. Furthermore, patients with schizophrenia appear to exhibit greater abnormal activation and extended functional coupling than those with depression. From a transdiagnostic perspective, understanding the neural mechanisms underlying anhedonia in patients with psychiatric disorders may help in the development of more targeted and efficacious treatment and intervention strategies.

Multi-modal assessment of reward functioning in adolescent anhedonia.

Anhedonia is a core symptom of depression that predicts worse treatment outcomes. Dysfunction in neural reward circuits is thought to contribute to anhedonia. However, whether laboratory-based assessments of anhedonia and reward-related neural function translate to adolescents' subjective affective experiences in real-world contexts remains unclear. We recruited a sample of adolescents (n = 82; ages 12-18; mean = 15.83) who varied in anhedonia and measured the relationships among clinician-rated and self-reported anhedonia, behaviorally assessed reward learning ability, neural response to monetary reward and loss (as assessed with functional magnetic resonance imaging), and repeated ecological momentary assessment (EMA) of positive affect (PA) and negative affect (NA) in daily life. Anhedonia was associated with lower mean PA and higher mean NA across the 5-day EMA period. Anhedonia was not related to impaired behavioral reward learning, but low PA was associated with reduced nucleus accumbens response during reward anticipation and reduced medial prefrontal cortex (mPFC) response during reward outcome. Greater mean NA was associated with increased mPFC response to loss outcome. Traditional laboratory-based measures of anhedonia were associated with lower subjective PA and higher subjective NA in youths' daily lives. Lower subjective PA and higher subjective NA were associated with decreased reward-related striatal functioning. Higher NA was also related to increased mPFC activity to loss. Collectively, these findings demonstrate that laboratory-based measures of anhedonia translate to real-world contexts and that subjective ratings of PA and NA may be associated with neural response to reward and loss.

Neural and peripheral markers of reward during positive social evaluation are associated with less clinician-rated depression symptom severity in adolescence

Although blunted sensitivity to reward is thought to play a key role in promoting risk for depression, most research on this topic has utilized monetary reward paradigms and focused on currently depressed adults. To address this issue, we analyzed neural reward and β-endorphin data from the Psychobiology of Stress and Adolescent Depression (PSY SAD) Study, which recruited a well-characterized sample of adolescent girls at high vs. low risk for major depressive disorder (MDD) (N = 52, Mage = 14.90, SD = 1.35) based on their mothers’ lifetime history of MDD. As hypothesized, greater striatal activity while receiving positive (vs. neutral) social evaluation was associated with lower depression symptom severity as independently assessed by the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). This association was present for girls at high but not low risk for MDD, suggesting that this neural response may represent a pre-clinical marker of risk for depression. Consistent with these results, higher post-social evaluation levels of a peripheral marker of reward sensitivity, β-endorphin, were related to lower clinician-rated depression symptom severity. Together, these results indicate that neural and peripheral markers of responsivity to social reward are both related to depression severity, which may have implications for understanding the pathophysiology of depression.

Enhancement of Motor Cortical Gamma Oscillations and Sniffing Activity by Medial Forebrain Bundle Stimulation Precedes Locomotion.

The medial forebrain bundle (MFB) is a white matter pathway that traverses through mesolimbic structures and includes dopaminergic neural fibers ascending from the ventral tegmental area (VTA). Since dopaminergic signals represent hedonic responses, electrical stimulation of the MFB in animals has been used as a neural reward for operant and spatial tasks. MFB stimulation strongly motivates animals to rapidly learn to perform a variety of behavioral tasks to obtain a reward. Although the MFB is known to connect various brain regions and MFB stimulation dynamically modulates animal behavior, how central and peripheral functions are affected by MFB stimulation per se is poorly understood. To address this question, we simultaneously recorded electrocorticograms (ECoGs) in the primary motor cortex (M1), primary somatosensory cortex (S1), and olfactory bulb (OB) of behaving rats while electrically stimulating the MFB. We found that MFB stimulation increased the locomotor activity of rats. Spectral analysis confirmed that immediately after MFB stimulation, sniffing activity was facilitated and the power of gamma oscillations in the M1 was increased. After sniffing activity and motor cortical gamma oscillations were facilitated, animals started to move. These results provide insight into the importance of sniffing activity and cortical gamma oscillations for motor execution and learning facilitated by MFB stimulation.

Reward Processing in Alcohol-Dependent Patients and First-Degree Relatives: Functional Brain Activity During Anticipation of Monetary Gains and Losses

BackgroundAccording to the reward deficiency syndrome and allostatic hypotheses, hyposensitivity of mesocorticolimbic regions to non–alcohol-related stimuli predisposes to dependence or is long-lastingly enhanced by chronic substance use. To date, no study has directly compared mesocorticolimbic brain activity during non–drug reward anticipation between alcohol-dependent, at risk, and healthy subjects. MethodsSeventy-five abstinent alcohol-dependent human subjects (mean abstinence duration 957.66 days), 62 healthy first-degree relatives of alcohol-dependent individuals, and 76 healthy control subjects without family history of alcohol dependence performed a monetary incentive delay task. Functional magnetic resonance imaging data of the anticipation phase were analyzed, during which visual cues predicted that fast response to a target would result in monetary gain, avoidance of monetary loss, or a neutral outcome. ResultsDuring gain anticipation, there were no significant group differences. During loss anticipation, abstinent alcohol-dependent subjects showed lower activity in the left anterior insula compared with healthy control subjects without family history of alcohol dependence only (Montreal Neurological Institute [MNI] −25 19 –5; t206 = 4.17, familywise error corrected p = .009). However, this effect was no longer significant when age was included as a covariate. There were no group differences between abstinent alcohol-dependent subjects and healthy first-degree relatives or between healthy first-degree relatives and healthy control subjects during loss anticipation, respectively. ConclusionsNeither the neural reward deficiency syndrome nor the allostatic hypotheses are supported by the results. Future studies should investigate whether the incentive salience hypothesis allows for more accurate predictions regarding mesocorticolimbic brain activity of subjects with alcohol dependence and healthy individuals during reward and loss anticipation and further examine the neural substrates underlying a predisposition to dependence.

On the Animal Trail

On the Animal Trail

Associations between different facets of anhedonia and neural response to monetary, social, and food reward in emerging adults

Anhedonia is present in diverse psychiatric disorders and has been linked to reduced neural responses to reward. However, most studies of anhedonia have used monetary reward, making it unclear whether previously-observed deficits represent broad domain-general impairments, or whether associations with anhedonia might vary across incentive types. The present study (N = 120) investigated associations between multiple measures of self-reported anhedonia and reward responsiveness and the reward positivity (RewP), a neural index of reward processing, following monetary, social, and food reward. Greater social anhedonia was associated with a smaller RewP following positive social feedback, whereas reduced consummatory pleasure was associated with a smaller RewP following food reward. Associations among both self-report and neural measures of reward sensitivity were generally modest. Our findings suggest that neither anhedonia nor neural reward sensitivity are unidimensional constructs, and that category-specific reward deficits might better capture specific problems in hedonic functioning.

Motivating Machines: The Potential of Modeling Motivation as MoA for Behavior Change Systems

The pathway through which behavior change techniques have an effect on the behavior of an individual is referred to as the Mechanism of Action (MoA). Digitally enabled behavior change interventions could potentially benefit from explicitly modelling the MoA to achieve more effective, adaptive, and personalized interventions. For example, if ‘motivation’ is proposed as the targeted construct in any behavior change intervention, how can a model of this construct be used to act as a mechanism of action, mediating the intervention effect using various behavior change techniques? This article discusses a computational model for motivation based on the neural reward pathway with the aim to make it act as a mediator between behavior change techniques and target behavior. This model’s formal description and parametrization are described from a neurocomputational sciences prospect and elaborated with the help of a sub-question, i.e., what parameters/processes of the model are crucial for the generation and maintenance of motivation. An intervention scenario is simulated to show how an explicit model of ‘motivation’ and its parameters can be used to achieve personalization and adaptivity. A computational representation of motivation as a mechanism of action may also further advance the design, evaluation, and effectiveness of personalized and adaptive digital behavior change interventions.

P207. Associations Between Neural Reward Response and Anhedonia in High-Risk Adolescents

Adolescence exists as a major window of plasticity for higher order cognition, creating vulnerability for disease onset of depression, bipolar, schizophrenia, all which share a key feature in anhedonia. Neuroscience models propose that anhedonia in adults has a basis in neural reward circuitry, but data evaluating these models developmentally in the context of familial risk are fundamentally lacking. We address this gap by examining associations between risk, neural response to reward, and anhedonia.

P231. Medial Prefrontal Cortex Activation to Reward Outcome Moderates Influence of Sexual Orientation Victimization in Adolescents and Young Adults

Sexual minority youth (SMY) are at greater risk for depression than heterosexual counterparts. Minority stress theory posits that sexual orientation victimization acts as a chronic stressor to influence depression. For those responsive to stress, stress may worsen depression by altering activity in neural reward systems. This study examines whether orientation victimization impacts neural reward activity and depression, and whether these relationships differ by SMY status.

Executive functioning moderates neural mechanisms of irritability during reward processing in youth

Pediatric irritability is the most robust indicator of transdiagnostic psychopathology risk. It is associated with altered neural reward processing, including neural networks related to cognitive control, and better cognitive control has been hypothesized to mitigate irritability. We evaluated the relationship of executive functioning (EF) with irritability-related neural correlates of reward processing in youths with varying levels of irritability. Participants (N = 51, mean age=13.80 years, SD=1.94) completed a monetary incentive delay task during multiband fMRI acquisition. Irritability and EF were measured via the Affective Reactivity Index and the NIH Toolbox cognition battery, respectively. Whole-brain analyses, controlling for age, examined the moderating role of EF on irritability-related brain activation and connectivity (seeds: striatum, amygdala) during reward anticipation and performance feedback. Irritability-related neural patterns during reward processing depended on EF, in occipital areas during reward anticipation and limbic, frontal, and temporal networks during performance feedback. Higher irritability combined with higher EF was associated with neural patterns opposite to those observed for higher irritability with lower co-occurring EF. Although preliminary, findings suggest that EF may buffer irritability-related reward processing deficits. Additionally, individual differences in EF and their relation to irritability may be related to varied etiologic mechanisms of irritability with important implications for personalized prevention and intervention.

Neural function underlying reward expectancy and attainment in adolescents with diverse psychiatric symptoms

Reward dysfunction has been hypothesized to play a key role in the development of psychiatric conditions during adolescence. To help capture the complexity of reward function in youth, we used the Reward Flanker fMRI Task, which enabled us to examine neural activity during expectancy and attainment of both certain and uncertain rewards. Participants were 84 psychotropic-medication-free adolescents, including 67 with diverse psychiatric conditions and 17 healthy controls. Functional MRI used high-resolution acquisition and high-fidelity processing techniques modeled after the Human Connectome Project. Analyses examined neural activation during reward expectancy and attainment, and their associations with clinical measures of depression, anxiety, and anhedonia severity, with results controlled for family-wise errors using non-parametric permutation tests. As anticipated, reward expectancy activated regions within the fronto-striatal reward network, thalamus, occipital lobe, superior parietal lobule, temporoparietal junction, and cerebellum. Unexpectedly, however, reward attainment was marked by widespread deactivation in many of these same regions, which we further explored using cosine similarity analysis. Across all subjects, striatum and thalamus activation during reward expectancy negatively correlated with anxiety severity, while activation in numerous cortical and subcortical regions during reward attainment positively correlated with both anxiety and depression severity. These findings highlight the complexity and dynamic nature of neural reward processing in youth.

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.

Effects of OPRM1 and DRD2 on brain structure in drug-naïve adolescents: Genetic and neural vulnerabilities to substance use.

Genetic variants in the opioid receptor mu 1 (OPRM1) and dopamine receptor d2 (DRD2) genes are implicated in behavioral phenotypes related to substance use disorders (SUD). Despite associations among OPRM1 (rs179971) and DRD2 (rs6277) genes and structural alterations in neural reward pathways implicated in SUDs, little is known about the contribution of risk-related gene variants to structural neurodevelopment. In a 3-year longitudinal study of initially SU-naïve adolescents (N = 129; 70 females; 11-14years old), participants underwent an MRI structural scan at baseline and provided genetic assays for OPRM1 and DRD2 with SU behavior assessed during follow-up visits. Baseline differences in key reward-related brain regions (i.e., bilateral caudate and cingulate cortex) were detected in those with genetic liability for SU in OPRM1 who went onto engage in SU at subsequent waves of data collection. In addition, main effects of OPRM1, DRD2, and SU were related to variability in structure of the putamen, anterior cingulate, and nucleus accumbens, respectively. These data provide preliminary evidence that genetic risk factors interact with future SU to confer structural variability prior to SU in regions commonly implicated in risk for SU and the development of SUDs.

The interplay of childhood maltreatment and maternal depression in relation to the reward positivity in youth.

Guided by developmental psychopathology and dual-risk frameworks, the present study examined the interplay between childhood maltreatment and maternal major depression history in relation to neural reward responsiveness in youth. The sample consisted of 96 youth (ages 9-16; M = 12.29 years, SD = 2.20; 68.8% female) drawn from a large metropolitan city. Youth were recruited based on whether their mothers had a history of major depressive disorder (MDD) and were categorized into two groups: youth with mothers with a history of MDD (high risk; HR; n = 56) and youth with mothers with no history of psychiatric disorders (low risk; LR; n = 40). The reward positivity (RewP), an event-related potential component, was utilized to measure reward responsiveness and the Childhood Trauma Questionnaire measured childhood maltreatment. We found a significant two-way interaction between childhood maltreatment and risk group in relation to RewP. Simple slope analysis revealed that in the HR group, greater childhood maltreatment was significantly associated with reduced RewP. The relationship between childhood maltreatment and RewP was not significant among the LR youth. The present findings demonstrate that the association between childhood maltreatment and blunted reward responsiveness is dependent on whether offspring have mothers with histories of MDD.

Nonnutritive Sweeteners and Neural Reward Response in Women and Individuals With Obesity

Nonnutritive Sweeteners and Neural Reward Response in Women and Individuals With Obesity

Multiple pathways of risk taking in adolescence

In this review, we describe multiple pathways that may lead to risk-taking in adolescence. We review behavioral and neuroimaging studies showing heightened risk-taking tendencies and associated neural reward activity in mid to late adolescence, but evidence points to risk taking as highly context and sample dependent. Here, we suggest that individual differences, specifically reward drive, may be a differential susceptibility factor that shows heightened sensitivity in adolescents and that makes some adolescents more sensitive to their environment. Furthermore, we review evidence that an elevated reward drive in mid-adolescence in interaction with prosocial and cognitive development can lead to various trajectories of risk taking. In this review we propose to extend existing models with individual-difference factors, specifically reward drive, and accompanying developmental processes, including cognitive control and prosocial development, that drive the development of multiple pathways of risk taking.

Social relationship-dependent neural response to speech in dogs

In humans, social relationship with the speaker affects neural processing of speech, as exemplified by children’s auditory and reward responses to their mother's utterances. Family dogs show human analogue attachment behavior towards the owner, and neuroimaging revealed auditory cortex and reward center sensitivity to verbal praises in dog brains. Combining behavioral and non-invasive fMRI data, we investigated the effect of dogs’ social relationship with the speaker on speech processing. Dogs listened to praising and neutral speech from their owners and a control person. We found positive correlation between dogs’ behaviorally measured attachment scores towards their owners and neural activity increase for the owner’s voice in the caudate nucleus; and activity increase in the secondary auditory caudal ectosylvian gyrus and the caudate nucleus for the owner’s praise. Through identifying social relationship-dependent neural reward responses, our study reveals similarities in neural mechanisms modulated by infant-mother and dog-owner attachment.