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Background: Depression is a significant public health concern. Identifying biopsychosocial risk factors for depression is important for developing targeted prevention. Studies have demonstrated that blunted striatal activation during reward processing is a risk factor for depression; however, few have prospectively examined whether adolescent reward-related resting-state functional connectivity (rsFC) predicts depression symptoms in adulthood and how this relates to known risk factors (e.g., childhood trauma)., Methods: At baseline, 66 adolescents (mean age = 14.7, SD = 1.4, 68 % female) underwent rsFC magnetic resonance imaging and completed the Children's Depression Inventory (CDI). At follow-up (mean time between adolescent scan and adult follow-up = 10.1 years, SD = 1.6, mean adult age = 24.8 years, SD = 1.7), participants completed the Childhood Trauma Questionnaire (CTQ) and Beck Depression Inventory- Second Edition (BDI-2). Average rsFC was calculated between nodes in mesocorticolimbic reward circuitry: ventral striatum (VS), rostral anterior cingulate cortex (rACC), medial orbitofrontal cortex, and ventral tegmental area. Linear regressions assessed associations between rsFC, BDI-2, and CTQ, controlling for adolescent CDI, sex assigned at birth, and scan age (Bonferroni corrected)., Results: Greater childhood trauma was associated with higher adulthood depression symptoms. Stronger VS-rACC rsFC during adolescence was associated with greater depression symptoms in adulthood and greater childhood trauma., Limitations: The small sample size, limited depression severity, and seed-based approach are limitations., Conclusions: The associations between adolescent striatal-cingulate rsFC and childhood trauma and adult depression symptoms suggest this connectivity may be an early neurobiological risk factor for depression and that early life experience plays an important role. Increased VS-rACC connectivity may represent an over-regulatory response on the striatum, commonly reported in depression, and warrants further investigation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Published by Elsevier B.V.)

Anhedonia emerges during adolescence and is characteristic of severe mental illness (SMI). To understand how anhedonia emerges, changes with time, and relates with other symptoms, there is a need to understand patterns of this symptom's course reflecting change or stability-and associations with clinical symptoms and neural reward circuitry in adolescents at risk of SMI. In total, 113 adolescents at low or high familial risk of developing SMI completed clinical measures at up to five time points across 2 years and functional magnetic resonance imaging scanning during a guessing reward task at baseline. Growth curve analysis was used to determine the trajectory of anhedonia across 2 years, including different phases (consummatory and anticipatory) and their association with clinical features (risk status, average suicidal ideation, and average depression across time) and neural activation in response to rewards (ventral striatum and dorsal medial prefrontal cortex). The findings revealed anhedonia decreased across 2 years. Furthermore, lower depression severity was associated with decreases in anhedonia across 2 years. There were no interactions between neural reward activation and anhedonia slopes in predicting clinical features. Exploratory analyses examining latent classes revealed three trajectory classes of anhedonia across phases. While preliminary, in the low and decreasing consummatory anhedonia trajectory class, there was a positive association between neural activation of the right ventral striatum in response to rewards and depression. Certain patterns of anhedonia development could confer risk or resilience for specific types of psychopathologies. The results are preliminary but do highlight the complexity and heterogeneity in anhedonia development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Empirical findings suggest reduced cortico-striatal structural connectivity in patients with major depressive disorder (MDD). However, the relationship between the abnormal structural covariance and one-year outcome of first-episode drug-naive patients has not been evaluated. This longitudinal study aimed to identify specific changes of ventral striatum-related brain structural covariance and grey matter volume in forty-two first-episode patients with major depression disorder compared with thirty-seven healthy controls at the baseline and the one-year follow-up conditions. At the baseline, patients showed decreased structural covariance between the left ventral striatum and the bilateral superior frontal gyrus (SFG), bilateral middle frontal gyrus (MFG), right supplementary motor area (SMA) and left precentral gyrus and increased grey matter volume at the left fusiform and left parahippocampus. At the one-year follow-up, patients showed decreased structural covariance between the left ventral striatum and the right SFG, right MFG, left precentral gyrus and left postcentral gyrus, and increased structural covariance between the right ventral striatum and the right amygdala, right hippocampus, right parahippocampus, right superior temporal pole, right insula and right olfactory bulb and decreased volume at the left SMA compared with controls. These findings suggest that specific ventral striatum connectivity changes contribute to the early brain development of the MDD., Competing Interests: Declaration of competing interest All authors have nothing to disclose relevant conflict of interest to the present work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The value associated with reward is sensitive to external factors, such as the time between the choice and reward delivery as classically manipulated in temporal discounting tasks. Subjective preference for two reward options is dependent on objective variables of reward magnitude and reward delay. Single neuron correlates of reward value have been observed in regions, including ventral striatum, orbital, and medial prefrontal cortex. Brain imaging studies show cortico-striatal-limbic network activity related to subjective preferences. To explore how oscillatory dynamics represent reward processing across brain regions, we measured local field potentials of rats performing a temporal discounting task. Our goal was to use a data-driven approach to identify an electrophysiological marker that correlates with reward preference. We found that reward-locked oscillations at beta frequencies signaled the magnitude of reward and decayed with longer temporal delays. Electrodes in orbitofrontal/medial prefrontal cortex, anterior insula, ventral striatum, and amygdala individually increased power and were functionally connected at beta frequencies during reward outcome. Beta power during reward outcome correlated with subjective value as defined by a computational model fit to the discounting behavior. These data suggest that cortico-striatal beta oscillations are a reward signal correlated, which may represent subjective value and hold potential to serve as a biomarker and potential therapeutic target., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Cigarette smoking is associated with elevated risk of disease and mortality and contributes to heavy healthcare-related economic burdens. The nucleus accumbens is implicated in numerous reward-related behaviors, including reinforcement learning and incentive salience. The established functional connectivity of the accumbens includes regions associated with motivation, valuation, and affective processing. Although the high comorbidity of cigarette smoking with drinking behaviors may collectively affect brain activity, there could be independent effects of smoking in alcohol use disorder that impact brain function and behavior. We hypothesized that smoking status, independent of alcohol use, would be associated with aberrations of nucleus accumbens functional connectivity to brain regions that facilitate reward processing, salience attribution, and inhibitory control. Resting state functional magnetic resonance imaging data from thirty-one nonsmokers and nineteen smoking individuals were analyzed using seed-based correlations of the bilateral accumbens with all other brain voxels. Statistical models accounted for drinks consumed per week. The smoking group demonstrated significantly higher functional connectivity between the left accumbens and the bilateral insula and anterior cingulate cortex, as well as hyperconnectivity between the right accumbens and the insula. Confirmatory analyses using the insula and cingulate clusters generated from the original analysis as seed regions reproduced the hyperconnectivity in smokers between the bilateral insular regions and the accumbens. In conclusion, smoking status had distinct effects on neural activity; hyperconnectivity between the accumbens and insula in smokers may reflect enhanced encoding of the reinforcing effects of smoking and greater orientation toward smoking-associated stimuli., Competing Interests: Declarations. Ethics approval: This study was approved by the Indiana University Institutional Review Board. Consent to participate: All participants provided written informed consent. Consent for publication: All authors consented to submit this work for publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Elevated pediatric irritability is a transdiagnostic symptom that predicts multiple mental health problems in adolescence and adulthood. Altered top-down regulatory networks, such as inhibitory control networks that suppress an impulse in favor of goal-directed behavior, are thought to contribute to high levels of youth irritability. Nevertheless, little work has examined links between youth irritability and neural processes supporting inhibitory control in large diverse samples, nor have they focused on the key period ramping up to adolescence (i.e., preadolescence)., Method: Functional MRI data from 5380 preadolescents (age M=9.97 years, SD=0.62) in the baseline Adolescent Brain and Cognitive Development (ABCD) Study were analyzed. Parents reported on their preadolescent's irritability. The stop signal task (SST) was leveraged to probe successful and failed inhibitory control. Activation and functional connectivity with amygdala, ventral striatum, and prefrontal seed regions were calculated during the SST and used in whole brain and region of interest (ROI) group-level analyses evaluating irritability effects., Results: Preadolescents with higher levels of irritability displayed decreases in functional connectivity among amygdala, ventral striatum, and prefrontal cortex regions during both successful and failed inhibitory control conditions. These results remained after adjusting for co-occurring anxiety, depression, and attention-deficit/hyperactivity symptoms., Conclusions: Findings suggest neural aberrations in inhibitory control play a role in the pathophysiology of preadolescent irritability and associations are not merely due to co-occurring symptoms. Neural mechanisms of inhibitory control associated with irritability may provide novel intervention targets., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to report., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mindfulness has garnered attention for its potential in alleviating cigarette cravings; however, the neural mechanisms underlying its efficacy remain inadequately understood. This study (N=46, all men) aims to examine the impact of a mindfulness strategy on regulating cue-induced craving and associated brain activity. Twenty-three smokers, consuming over 10 cigarettes daily for at least 2 years， were compared to twenty-three non-smokers. During a regulation of craving task, participants were asked to practice mindfulness during smoking cue-exposure or passively view smoking cues while fMRI scans were completed. A 2 (condition: mindfulness-cigarette and look-cigarette) × 2 (phase: early, late of whole smoking cue-exposure period) repeated measures ANOVA showed a significant interaction of the craving scores between condition and phase, indicating that the mindfulness strategy dampened late-phase craving. Additionally, within the smoker group, the fMRI analyses revealed a significant main effect of mindfulness condition and its interaction with time in several brain networks involving reward, emotion, and interoception. Specifically, the bilateral insula, ventral striatum, and amygdala showed lower activation in the mindfulness condition, whereas the activation of right orbitofrontal cortex mirrored the strategy-time interaction effect of the craving change. This study illuminates the dynamic interplay between mindfulness, smoking cue-induced craving, and neural activity, offering insights into how mindfulness may effectively regulate cigarette cravings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: As a central hub in cognitive and emotional brain circuits, the striatum is considered likely to be integrally involved in the psychopathology of bipolar disorder (BD). However, it remains unclear how alterations in striatal function contribute to distinct symptomatology of BD during different mood states., Methods: Behavioral assessment (i.e., emotional symptoms and cognitive performance) and neuroimaging data were collected from 125 participants comprising 31 (hypo)manic, 31 depressive, and 31 euthymic patients with BD, and 32 healthy control participants. We compared the functional connectivity (FC) of striatal subregions across BD mood states with healthy control participants and then used a multivariate data-driven approach to explore dimensional associations between striatal connectivity and behavioral performance. Finally, we compared the FC and behavioral composite scores, which reflect the individual weighted representation of the associations, among different mood states., Results: Patients in all mood states exhibited increased FC between the bilateral ventral rostral putamen and ventrolateral thalamus. Bipolar (hypo)mania uniquely exhibited increased ventral rostral putamen connectivity and superior ventral striatum connectivity. One latent component was identified, whereby increased FCs of striatal subregions were associated with distinct psychopathological symptomatology (more manic symptoms, elevated positive mood, less depressive symptoms, and worse cognitive performance). Patients with bipolar (hypo)mania had the highest FC and behavioral composite scores while bipolar patients with depression had the lowest scores., Conclusions: Our data demonstrated both trait features of BD and state features specific to bipolar (hypo)mania. The findings underscored the fundamental role of the striatum in the pathophysiological processes underlying specific symptomatology across all mood states., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Ventral striatal hypoactivation during reward anticipation has consistently been observed in patients with schizophrenia. In addition, that hypoactivation has been shown to correlate negatively with negative symptoms, and in particular with apathy. However, little is known about the stability of these results over time and their reliability across different centers., Methods: In total, 67 patients with schizophrenia (15 females) and 55 healthy controls (13 females) were recruited in 2 centers in Switzerland and Germany. To assess the neural bases of reward anticipation, all participants performed a variant of the Monetary Incentive Delay task while undergoing event-related functional magnetic resonance imaging at baseline and after 3 months. Stability over time was measured using intra-class correlation (ICC(A,1)) and stability between centers was measured with mixed models., Results: Results showed the expected ventral striatal hypoactivation in patients compared to controls during reward anticipation. We showed that these results were stable across centers. The primary analysis did not reveal an effect of time. Test-retest reliability was moderate for controls, and poor for patients. We did not find an association between ventral striatal hypoactivation and negative symptoms in patients., Conclusions: Our results align with the hypothesis that ventral striatal activation is related to modulation of motivational saliency during reward anticipation. They also confirm that patients with schizophrenia show impaired reward anticipation. However, the poor test-retest reliability and the absence of an association with symptoms suggests that further research is needed before ventral striatal activity can be used as a biomarker on the individual patient level., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Insula damage results in substantial impairments in facial emotion recognition. In particular, left hemispheric damage appears to be associated with poorer recognition of aversively rated facial expressions. Functional imaging can provide information on differences in the processing of these stimuli in patients with insula lesions when compared to healthy matched controls (HCs). We therefore investigated 17 patients with insula lesions in the chronic stage following stroke and 13 HCs using a passive-viewing task with pictures of facial expressions testing the blood oxygenation dependent (BOLD) effect in predefined regions of interest (ROIs). We expected a decrease in functional activation in an area modulating emotional response (left ventral striatum) but not in the facial recognition areas in the left inferior fusiform gyrus. Quantification of BOLD-response in ROIs but also voxel-based statistics confirmed this hypothesis. The voxel-based analysis demonstrated that the decrease in BOLD in the left ventral striatum was driven by left hemispheric damaged patients (n = 10). In our patient group, insula activation was strongly associated with the intensity rating of facial expressions. In conclusion, the combination of performance testing and functional imaging in patients following circumscribed brain damage is a challenging method for understanding emotion processing in the human brain., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 K. et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Deep brain stimulation (DBS) is a promising treatment option for treatment-refractory obsessive-compulsive disorder (OCD). Several stimulation targets have been used, mostly in and around the anterior limb of the internal capsule and ventral striatum. However, the precise target within this region remains a matter of debate., Methods: Here, we retrospectively studied a multicenter cohort of 82 patients with OCD who underwent DBS of the ventral capsule/ventral striatum and mapped optimal stimulation sites in this region., Results: DBS sweet-spot mapping performed on a discovery set of 58 patients revealed 2 optimal stimulation sites associated with improvements on the Yale-Brown Obsessive Compulsive Scale, one in the anterior limb of the internal capsule that overlapped with a previously identified OCD-DBS response tract and one in the region of the inferior thalamic peduncle and bed nucleus of the stria terminalis. Critically, the nucleus accumbens proper and anterior commissure were associated with beneficial but suboptimal clinical improvements. Moreover, overlap with the resulting sweet- and sour-spots significantly estimated variance in outcomes in an independent cohort of 22 patients from 2 additional DBS centers. Finally, beyond obsessive-compulsive symptoms, stimulation of the anterior site was associated with optimal outcomes for both depression and anxiety, while the posterior site was only associated with improvements in depression., Conclusions: Our results suggest how to refine targeting of DBS in OCD and may be helpful in guiding DBS programming in existing patients., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Adaptive decision-making, which is often impaired in various psychiatric conditions, is essential for well-being. Recent evidence has indicated that decision-making capacity in multiple tasks could be accounted for by latent dimensions, enlightening the question of whether there is a common disruption of brain networks in economic decision-making across psychiatric conditions. Here, we addressed the issue by combining activation/lesion network mapping analyses with a transdiagnostic brain imaging meta-analysis. Our findings indicate that there were transdiagnostic alterations in the thalamus and ventral striatum during the decision or outcome stage of decision-making. The identified regions represent key nodes in a large-scale network, which is composed of multiple heterogeneous brain regions and plays a causal role in motivational functioning. The findings suggest that disturbances in the network associated with emotion- and reward-related processing play a key role in dysfunctions of decision-making observed in various psychiatric conditions. This study provides the first meta-analytic evidence of common neural alterations linked to deficits in economic decision-making., Competing Interests: Declaration of competing interest The authors are unaware of any conflicts of interest, financial or otherwise., (Copyright © 2024. Published by Elsevier Inc.)

Recent work has identified a critical role for the hippocampus in reward-sensitive behaviors, including motivated memory, reinforcement learning, and decision-making. Animal histology and human functional neuroimaging have shown that brain regions involved in reward processing and motivation are more interconnected with the ventral/anterior hippocampus. However, direct evidence examining gradients of structural connectivity between reward regions and the hippocampus in humans is lacking. The present study used diffusion MRI (dMRI) and probabilistic tractography to quantify the structural connectivity of the hippocampus with key reward processing regions in vivo. Using a large sample of subjects (N = 628) from the human connectome dMRI data release, we found that connectivity profiles with the hippocampus varied widely between different regions of the reward circuit. While the dopaminergic midbrain (ventral tegmental area) showed stronger connectivity with the anterior versus posterior hippocampus, the ventromedial prefrontal cortex showed stronger connectivity with the posterior hippocampus. The limbic (ventral) striatum demonstrated a more homogeneous connectivity profile along the hippocampal long axis. This is the first study to generate a probabilistic atlas of the hippocampal structural connectivity with reward-related networks, which is essential to investigating how these circuits contribute to normative adaptive behavior and maladaptive behaviors in psychiatric illness. These findings describe nuanced structural connectivity that sets the foundation to better understand how the hippocampus influences reward-guided behavior in humans., (© 2024 Wiley Periodicals LLC.)

Aberrant levels of reward sensitivity have been linked to substance use disorder and are characterized by alterations in reward processing in the ventral striatum (VS). Less is known about how reward sensitivity and subclinical substance use relate to striatal function during social rewards (e.g. positive peer feedback). Testing this relation is critical for predicting risk for development of substance use disorder. In this pre-registered study, participants (N = 44) underwent fMRI while completing well-matched tasks that assess neural response to reward in social and monetary domains. Contrary to our hypotheses, aberrant reward sensitivity blunted the relationship between substance use and striatal activation during receipt of rewards, regardless of domain. Moreover, exploratory whole-brain analyses showed unique relations between substance use and social rewards in temporoparietal junction. Psychophysiological interactions demonstrated that aberrant reward sensitivity is associated with increased connectivity between the VS and ventromedial prefrontal cortex during social rewards. Finally, we found that substance use was associated with decreased connectivity between the VS and dorsomedial prefrontal cortex for social rewards, independent of reward sensitivity. These findings demonstrate nuanced relations between reward sensitivity and substance use, even among those without substance use disorder, and suggest altered reward-related engagement of cortico-VS responses as potential predictors of developing disordered behavior., (© The Author(s) 2024. Published by Oxford University Press.)

The Islamist group ISIS has been particularly successful at recruiting Westerners as terrorists. A hypothesized explanation is their simultaneous use of two types of propaganda: Heroic narratives, emphasizing individual glory, alongside Social narratives, which emphasize oppression against Islamic communities. In the current study, functional MRI was used to measure brain responses to short ISIS propaganda videos distributed online. Participants were shown 4 Heroic and 4 Social videos categorized as such by another independent group of subjects. Persuasiveness was measured using post-scan predictions of recruitment effectiveness. Inter-subject correlation (ISC) was used to measure commonality of brain activity time courses across individuals. ISCs in ventral striatum predicted rated persuasiveness for Heroic videos, while ISCs in mentalizing and default networks, especially in dmPFC, predicted rated persuasiveness for Social videos. This work builds on past findings that engagement of the reward circuit and of mentalizing brain regions predicts preferences and persuasion. The observed dissociation as a function of stimulus type is novel, as is the finding that intersubject synchrony in ventral striatum predicts rated persuasiveness. These exploratory results identify possible neural mechanisms by which political extremists successfully recruit prospective members and specifically support the hypothesized distinction between Heroic and Social narratives for ISIS propaganda., (© 2024. The Author(s).)

Introduction: Low self-esteem is a frequent symptom in major depressive disorder (MDD). This functional magnetic resonance imaging study investigated whether MDD patients with low self-esteem show a distinct neural pathophysiology. Previous studies linked low self-esteem to reduced task-induced deactivation of the pregenual anterior cingulate cortex (pgACC) as a part of the default mode network, and to reduced connectivity between pgACC and reward system. Goya-Maldonado et al. identified an MDD subtype with pgACC and ventral striatal overactivations during reward processing. We hypothesized that this subtype might be characterized by low self-esteem., Methods: Eighty-three MDD patients performed the desire-reason dilemma task and completed the Rosenberg Self-Esteem Scale (RSES). Brain activity during bottom-up reward processing was regressed upon the RSES scores, controlling for depression severity measured by the Montgomery-Åsberg Depression Rating Scale. To corroborate the findings, we compared self-esteem scores between patient subgroups with impaired task-induced deactivation (n = 31) and with preserved task-induced deactivation (n = 31) of the pgACC., Results: Consistent with our a priori hypothesis, activity in a bilateral fronto-striatal network including pgACC and ventral striatum correlated negatively with RSES scores, also when controlling for depression severity. In the additional analysis, patients with impaired task-induced pgACC deactivation showed lower self-esteem (t (52.82) = -2.27; p = .027, d = 0.58) compared to those with preserved task-induced pgACC deactivation., Conclusions: We conclude that low self-esteem in MDD patients is linked to a task-induced deactivation dysfunction of the pgACC. Our findings suggest that a previously described possible subtype of MDD with pgACC and ventral striatal overactivations during reward processing is clinically characterized by low self-esteem., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Background: Affiliating with delinquent peers may stimulate the development of antisocial behavior, especially for adolescents who are sensitive to social rewards. The current study examines whether the association between delinquent peer affiliation (DPA) and disruptive behavior interacts with functional brain correlates of reward sensitivity in early onset male adolescents delinquents., Methods: Childhood arrestees ( n = 126, mean age = 17.7 [s.d. 1.6]) completed a DPA questionnaire, and participated in an fMRI study in which reward sensitivity was operationalized through responsiveness of the ventral striatum ( VS ), amygdala, and medial prefrontal cortex (mPFC) during the monetary incentive delay paradigm (reward anticipation and outcome). Symptoms of disruptive behavior disorders (DBD) were assessed through structured psychiatric interviews (Diagnostic Interview Schedule for Children) with adolescents., Results: DPA had a main effect on DBD symptoms. Adolescents with high VS reward responses showed a stronger significant positive association between DPA and DBD symptoms compared to low VS responders. No evidence for an interaction effect was found for the amygdala and mPFC. Post-hoc analyses revealed the positive association between DPA and DBD was only present in males, with a diminishing effect as age increased., Conclusions: We found evidence for a biosocial interaction between DPA and reward sensitivity of the VS in relation to DBD symptom severity. This study provides the first evidence of an interaction effect between a brain mechanism and an environmental factor in relation to DBD symptoms, implying that susceptibility to influences of delinquent peers may intertwine with individual biological differences.

Objectives: Generativity, the desire and action to improve the well-being of younger generations, is associated with purpose in life among older adults. However, the neurobehavioral factors supporting the relationship between generativity and purpose in life remain unknown. This study aims to identify the functional neuroanatomy of generativity and mechanisms linking generativity with purpose in life in at-risk older adults., Methods: Fifty-eight older adults (mean age = 70.8, SD = 5.03, 45 females) with a family history of Alzheimer's disease (AD) were recruited from the PREVENT-AD cohort. Participants underwent brain imaging and completed questionnaires assessing generativity, social support, and purpose in life. Mediation models examined whether social support mediated the association between generativity and purpose in life. Seed-to-voxel analyses investigated the association between generativity and resting-state functional connectivity (rsFC) to the ventromedial prefrontal cortex (vmPFC) and ventral striatum (VS), and whether this rsFC moderated the relationship between generativity and purpose in life., Results: Affectionate social support mediated the association between generative desire and purpose in life. Generative desire was associated with rsFC between VS and precuneus, and, vmPFC and right dorsolateral prefrontal cortex (rdlPFC). The vmPFC-rdlPFC rsFC moderated the association between generative desire and purpose in life., Discussion: These findings provide insight into how the brain supports complex social behavior and, separately, purpose in life in at-risk aging. Affectionate social support may be a putative target process to enhance purpose in life in older adults. This knowledge contributes to future developments of personalized interventions that promote healthy aging., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Obsessive-compulsive disorder (OCD) is characterized by persistent, unwanted thoughts and repetitive actions. Such repetitive thoughts and/or behaviors may be reinforced either by reducing anxiety or by avoiding a potential threat or harm, and thus may be rewarding to the individual. The possible involvement of the reward system in the symptomatology of OCD is supported by studies showing altered reward processing in reward-related regions, such as the ventral striatum (VS) and the orbitofrontal cortex (OFC), in adults with OCD. However, it is not clear whether this also applies to adolescents with OCD., Methods: Using functional magnetic resonance imaging, two sessions were conducted focusing on the anticipation and receipt of monetary reward (1) or loss (2), each contrasted to a verbal (control) condition. In each session, adolescents with OCD (n1=31/n2=26) were compared with typically developing (TD) controls (n1=33/ n2=31), all aged 10-19 years, during the anticipation and feedback phase of an adapted Monetary Incentive Delay task., Results: Data revealed a hyperactivation of the VS, but not the OFC, when anticipating both monetary reward and loss in the OCD compared to the TD group., Conclusions: These findings suggest that aberrant neural reward and loss processing in OCD is associated with greater motivation to gain or maintain a reward but not with the actual receipt. The greater degree of reward 'wanting' may contribute to adolescents with OCD repeating certain actions more and more frequently, which then become habits (i.e., OCD symptomatology)., (© 2024. The Author(s).)

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., (© The Author(s) 2024. Published by Oxford University Press.)

Excessive use of the internet, which is a typical scenario of self-control failure, could lead to potential consequences such as anxiety, depression, and diminished academic performance. However, the underlying neuropsychological mechanisms remain poorly understood. This study aims to investigate the structural basis of self-control and internet addiction. In a cohort of 96 internet gamers, we examined the relationships among grey matter volume and white matter integrity within the frontostriatal circuits and internet addiction severity, as well as self-control measures. The results showed a significant and negative correlation between dACC grey matter volume and internet addiction severity (p < 0.001), but not with self-control. Subsequent tractography from the dACC to the bilateral ventral striatum (VS) was conducted. The fractional anisotropy (FA) and radial diffusivity of dACC-right VS pathway was negatively (p = 0.011) and positively (p = 0.020) correlated with internet addiction severity, respectively, and the FA was also positively correlated with self-control (p = 0.036). These associations were not observed for the dACC-left VS pathway. Further mediation analysis demonstrated a significant complete mediation effect of self-control on the relationship between FA of the dACC-right VS pathway and internet addiction severity. Our findings suggest that the dACC-right VS pathway is a critical neural substrate for both internet addiction and self-control. Deficits in this pathway may lead to impaired self-regulation over internet usage, exacerbating the severity of internet addiction., (© 2024 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Self-reported sexual orientation of transgender individuals occasionally changes over transition. Using functional magnetic resonance imaging, we tested the hypothesis that neural and behavioral patterns of sexual arousal in transgender individuals would shift from the assigned to the experienced gender (e.g., trans women's responses becoming more dissimilar to those of cis men and more similar to those of cis women). To this aim, trans women (N = 12) and trans men (N = 20) as well as cisgender women (N = 24) and cisgender men (N = 14) rated visual stimuli showing male-female, female-female or male-male intercourse for sexual arousal before and after four months of gender-affirming hormone therapy. A Bayesian framework allowed us to incorporate previous behavioral findings. The hypothesized changes could indeed be observed in the behavioral responses with the strongest results for trans men and female-female scenes. Activation of the ventral striatum supported our hypothesis only for female-female scenes in trans women. The respective application or depletion of androgens in trans men and trans women might partly explain this observation. The prominent role of female-female stimuli might be based on the differential responses they elicit in cis women and men or, in theory, the controversial concept of autogynephilia. We show that correlates of sexual arousal in transgender individuals might change in the direction of the experienced gender. Future investigations should elucidate the mechanistic role of sex hormones and the cause of the differential neural and behavioral findings.The study was registered at ClinicalTrials.gov (NCT02715232), March 22, 2016., (© 2024. The Author(s).)

Background: Dysregulated ventral striatum function has been proposed as one important process occurring in individuals with substance use disorder. This study investigates the role of altered reward and loss anticipation, which is an important component of impaired decision-making, impulsivity, and vulnerability to relapse in individuals with amphetamine use disorder (AMP)., Aims: To determine whether AMP is associated with blunted striatum, prefrontal cortex, and insula signals during win and loss anticipation., Methods: Participants with and without AMP (AMP+ n  = 46, AMP- n  = 90) from the Tulsa 1000 study completed a monetary incentive delay (MID) task during functional magnetic resonance imaging., Results: Group main effects indicated that: (1) AMP+ exhibited lower bilateral caudate/putamen and left nucleus accumbens signal than AMP- across anticipation of wins and losses; and (2) AMP+ showed slower reaction times than AMP- during loss anticipation. Group*condition interactions demonstrated that AMP+ exhibited greater right amygdala signal than AMP- while anticipating large wins, a pattern that reversed when anticipating small losses. Left caudate/putamen attenuations in AMP+ during small loss anticipation were also evident. Groups did not differ in prefrontal or insula signals., Conclusions: AMP+ individuals have altered neural processing and response patterns during reward and loss anticipation, potentially reflecting impairments in dopamine function, which may influence their decision-making and reactions to different win/loss scenarios. These findings help to explain why AMP+ have difficulty with decision-making and exhibit a heightened focus on immediate rewards or punishments., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The dopaminergic system is firmly implicated in reversal learning but human measurements of dopamine release as a correlate of reversal learning success are lacking. Dopamine release and hemodynamic brain activity in response to unexpected changes in action-outcome probabilities are here explored using simultaneous dynamic [11C]Raclopride PET-fMRI and computational modelling of behavior. When participants encounter reversed reward probabilities during a card guessing game, dopamine release is observed in associative striatum. Individual differences in absolute reward prediction error and sensitivity to errors are associated with peak dopamine receptor occupancy. The fMRI response to perseverance errors at the onset of a reversal spatially overlap with the site of dopamine release. Trial-by-trial fMRI correlates of absolute prediction errors show a response in striatum and association cortices, closely overlapping with the location of dopamine release, and separable from a valence signal in ventral striatum. The results converge to implicate striatal dopamine release in associative striatum as a central component of reversal learning, possibly signifying the need for increased cognitive control when new stimuli-responses should be learned., (© 2024. The Author(s).)

Reward-based learning and decision-making are prime candidates to understand symptoms of attention deficit hyperactivity disorder (ADHD). However, only limited evidence is available regarding the neurocomputational underpinnings of the alterations seen in ADHD. This concerns flexible behavioral adaption in dynamically changing environments, which is challenging for individuals with ADHD. One previous study points to elevated choice switching in adolescent ADHD, which was accompanied by disrupted learning signals in medial prefrontal cortex. Here, we investigated young adults with ADHD (n = 17) as compared to age- and sex-matched controls (n = 17) using a probabilistic reversal learning experiment during functional magnetic resonance imaging (fMRI). The task requires continuous learning to guide flexible behavioral adaptation to changing reward contingencies. To disentangle the neurocomputational underpinnings of the behavioral data, we used reinforcement learning (RL) models, which informed the analysis of fMRI data. ADHD patients performed worse than controls particularly in trials before reversals, i.e., when reward contingencies were stable. This pattern resulted from 'noisy' choice switching regardless of previous feedback. RL modelling showed decreased reinforcement sensitivity and enhanced learning rates for negative feedback in ADHD patients. At the neural level, this was reflected in a diminished representation of choice probability in the left posterior parietal cortex in ADHD. Moreover, modelling showed a marginal reduction of learning about the unchosen option, which was paralleled by a marginal reduction in learning signals incorporating the unchosen option in the left ventral striatum. Taken together, we show that impaired flexible behavior in ADHD is due to excessive choice switching ('hyper-flexibility'), which can be detrimental or beneficial depending on the learning environment. Computationally, this resulted from blunted sensitivity to reinforcement of which we detected neural correlates in the attention-control network, specifically in the parietal cortex. These neurocomputational findings remain preliminary due to the relatively small sample size., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Habenula (HB) function is implicated in substance use disorders and is involved in inhibiting dopamine release in the ventral striatum (VS). While blunted VS reward responsivity is implicated in risk for later substance use, links between HB reinforcement processing and progression of use have not, to our knowledge, been examined among adolescents. In the present study, we longitudinally assessed HB and VS responsivity to social rewards and punishments across adolescence and examined associations with substance use., Methods: Within a longitudinal design, 170 adolescents (53.5% female) completed 1 to 3 functional magnetic resonance imaging scans across 6th to 9th grade and reported yearly substance use across 6th to 11th grade. We examined VS and HB responsivity to social reinforcement during a social incentive delay task in which adolescents received social rewards (smiling faces) and punishments (scowling faces)., Results: We observed increased VS responsivity to social rewards (vs. reward omissions) and increased VS, but decreased HB, responsivity to social punishment avoidance versus receipt. However, contrary to hypotheses, the HB displayed increased responsivity to social rewards (vs. reward omissions). Further, adolescents reporting regular substance use displayed longitudinally declining HB responsivity to social rewards (vs. reward omissions), whereas adolescents reporting no substance use displayed longitudinally increasing HB responsivity. In contrast, whereas VS responsivity to punishment avoidance versus receipt increased longitudinally among regular substance users, it stayed relatively stable among nonusers., Conclusions: These results suggest that differential HB and VS social reinforcement processing trajectories across adolescence are associated with substance use., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Abnormal reward functioning is central to anhedonia and amotivation symptoms of schizophrenia (SCZ). Reward processing encompasses a series of psychological components. This systematic review and meta-analysis examined the brain dysfunction related to reward processing of individuals with SCZ spectrum disorders and risks, covering multiple reward components., Methods: After a systematic literature search, 37 neuroimaging studies were identified and divided into four groups based on their target psychology components (i.e. reward anticipation, reward consumption, reward learning, effort computation). Whole-brain Seed-based d Mapping (SDM) meta-analyses were conducted for all included studies and each component., Results: The meta-analysis for all reward-related studies revealed reduced functional activation across the SCZ spectrum in the striatum, orbital frontal cortex, cingulate cortex, and cerebellar areas. Meanwhile, distinct abnormal patterns were found for reward anticipation (decreased activation of the cingulate cortex and striatum), reward consumption (decreased activation of cerebellum IV/V areas, insula and inferior frontal gyri), and reward learning processing (decreased activation of the striatum, thalamus, cerebellar Crus I, cingulate cortex, orbitofrontal cortex, and parietal and occipital areas). Lastly, our qualitative review suggested that decreased activation of the ventral striatum and anterior cingulate cortex was also involved in effort computation., Conclusions: These results provide deep insights on the component-based neuro-psychopathological mechanisms for anhedonia and amotivation symptoms of the SCZ spectrum.

Background: Previous studies have focused on both ventral striatum (VS) and dorsal striatum (DS) in characterizing dopaminergic deficits in addiction. Animal studies suggest VS and DS dysfunction each in association with impulsive and compulsive cocaine use during early and later stages of addiction. However, few human studies have aimed to distinguish the roles of VS and DS dysfunction in cocaine misuse., Methods: We examined VS and DS resting-state functional connectivity (rsFC) of 122 recently abstinent cocaine-dependent individuals (CDs) and 122 healthy controls (HCs) in 2 separate cohorts. We followed published routines in imaging data analyses and evaluated the results at a corrected threshold with age, sex, years of drinking, and smoking accounted for., Results: CDs relative to HCs showed higher VS rsFC with the left inferior frontal cortex (IFC), lower VS rsFC with the hippocampus, and higher DS rsFC with the left orbitofrontal cortex. Region-of-interest analyses confirmed the findings in the 2 cohorts examined separately. In CDs, VS-left IFC and VS-hippocampus connectivity was positively and negatively correlated with average monthly cocaine use in the prior year, respectively. In the second cohort where participants were assessed with the Barratt Impulsivity Scale (BIS-11), VS-left IFC and VS-hippocampus connectivity was also positively and negatively correlated with BIS-11 scores in CDs. In contrast, DS-orbitofrontal cortex connectivity did not relate significantly to cocaine use metrics or BIS-11 scores., Conclusion: These findings associate VS rsFC with impulsivity and the severity of recent cocaine use. How DS connectivity partakes in cocaine misuse remains to be investigated., (© The Author(s) 2023. Published by Oxford University Press on behalf of CINP.)

A growing body of research has placed the ventral striatum at the center of a network of cerebral regions involved in anticipating rewards in healthy controls. However, little is known about the functional connectivity of the ventral striatum associated with reward anticipation in healthy controls. In addition, few studies have investigated reward anticipation in healthy humans with different levels of schizotypy. Here, we investigated reward anticipation in eighty-four healthy individuals (44 females) recruited based on their schizotypy scores. Participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI.Participants showed the expected decrease in response times for highly rewarded trials compared to non-rewarded trials. Whole-brain activation analyses replicated previous results, including activity in the ventral and dorsal striatum. Whole-brain psycho-physiological interaction analyses of the left and right ventral striatum revealed increased connectivity during reward anticipation with widespread regions in frontal, parietal and occipital cortex as well as the cerebellum and midbrain. Finally, we found no association between schizotypal personality severity and neural activity and cortico-striatal functional connectivity. In line with the motivational, attentional, and motor functions of rewards, our data reveal multifaceted cortico-striatal networks taking part in reward anticipation in healthy individuals. The ventral striatum is connected to regions of the salience, attentional, motor and visual networks during reward anticipation and thereby in a position to orchestrate optimal goal-directed behavior., (© 2023. The Author(s).)

The overconsumption of palatable energy-dense foods drives obesity, but few human studies have investigated dopamine (DA) release in response to the consumption of a palatable meal, a putative mediator of excess intake in obesity. We imaged [ 11 C]raclopride in the brain with positron emission tomography (PET) to assess striatal dopamine (DA) receptor binding pre- and post-consumption of a highly palatable milkshake (250 mL, 420 kcal) in 11 females, 6 of whom had severe obesity, and 5 of whom had healthy-weight. Those with severe obesity underwent assessments pre- and 3 months post-vertical sleeve gastrectomy (VSG). Our results demonstrated decreased post- vs. pre-meal DA receptor binding in the ventral striatum ( p = 0.032), posterior putamen ( p = 0.012), and anterior caudate ( p = 0.018), consistent with meal-stimulated DA release. Analysis of each group separately suggested that results in the caudate and putamen were disproportionately driven by meal-associated changes in the healthy-weight group. Baseline (pre-meal) DA receptor binding was lower in severe obesity than in the healthy-weight group. Baseline DA receptor binding and DA release did not change from pre- to post-surgery. The results of this small pilot study suggest that milkshake acutely stimulates DA release in the ventral and dorsal striatum. This phenomenon likely contributes to the overconsumption of highly palatable foods in the modern environment.

Ventral striatum (VS) processes rewarding and punishing stimuli. Women and men vary in externalizing and internalizing traits, which may influence neural responses to reward and punishment. To investigate sex differences in how individual traits influence VS responses to reward and punishment, we curated the data of the Human Connectome Project and identified 981 (473 men) subjects evaluated by the Achenbach Adult Self-Report Syndrome Scales. We processed the imaging data with published routines and extracted VS response (β) to win and to loss vs. baseline in a gambling task for correlation with externalizing and internalizing symptom severity. Men vs. women showed more severe externalizing symptoms and higher VS response to monetary losses (VS-loss β) but not to wins. Men but not women showed a significant, positive correlation between VS-loss β and externalizing traits, and the sex difference was confirmed by a slope test. The correlations of VS-loss vs. externalizing and of VS-win vs. externalizing and those of VS-loss vs. externalizing and of VS-loss vs. internalizing traits both differed significantly in slope, confirming its specificity, in men. Further, the sex-specific relationship between VS-loss β and externalizing trait did not extend to activities during exposure to negative emotion in the face matching task. To conclude, VS responses to loss but not to win and their correlation with externalizing rather than internalizing symptom severity showed sex differences in young adults. The findings highlight the relationship of externalizing traits and VS response to monetary loss and may have implications for psychological models of externalizing behaviors in men., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Economic and decision-making theories suppose that people would disengage from a task with near zero success probability, because this implicates little normative utility values. However, humans often are motivated for an extremely challenging task, even without any extrinsic incentives. The current study aimed to address the nature of this challenge-based motivation and its neural correlates. We found that, when participants played a skill-based task without extrinsic incentives, their task enjoyment increased as the chance of success decreased, even if the task was almost impossible to achieve. However, such challenge-based motivation was not observed when participants were rewarded for the task or the reward was determined in a probabilistic manner. The activation in the ventral striatum/pallidum tracked the pattern of task enjoyment. These results suggest that people are intrinsically motivated to challenge a nearly impossible task but only when the task requires certain skills and extrinsic rewards are unavailable., (© 2022. The Author(s).)

Regret is a common negative emotion in daily life, and long-term immersion in regret affects mental health. Therefore, to regulate and reduce regret is of wide concern. The current fMRI study aimed to investigate whether outcome anticipation before decision-making could reduce regret and its neural correlates. In the task, participants were asked to anticipate the possible poor outcomes of subsequent decisions, such as missing rewards and meeting punishment, and then made sequential risk-taking decisions. Behavioral results showed that outcome anticipation before decision-making could decrease the intensity of regret, that is, participants felt less regret when they anticipated the outcome before decision-making (anticipation condition, Ant), compared to making sequential risk-taking decisions without any anticipation of the outcome in advance (non-anticipation condition, NAnt). Consistently, at the neural level, stronger activities of ventral striatum (VS) and dorsal medial prefrontal cortex (dmPFC), and greater VS-dmPFC functional connectivity were observed in Ant relative to NAnt. Moreover, the activity of dmPFC was negatively correlated with the intensity of regret in Ant. The current study highlighted that outcome anticipation before decision-making could regulate regret effectively, and dmPFC played a vital role in this process., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Avoiding loss is a crucial, adaptive guide to human behavior. While previous developmental research has primarily focused on gaining rewards, less attention has been paid to loss processing and its avoidance. In daily life, it is often unknown how likely an action will result in a loss, making the role of uncertainty in loss processing particularly important. By using functional magnetic resonance imaging, we investigated the influence of varying outcome probabilities (12%, 34%, and 67%) on brain regions implicated in loss processing (ventral striatum (VS), anterior insula (AI)) by comparing 28 adolescents (10-18 years) and 24 adults (22-32 years) during the anticipation of potential monetary loss.Overall, results revealed slower RTs in adolescents compared to adults with both groups being faster in the experimental (monetary condition) vs. control trials (verbal condition). Fastest RTs were observed for the 67% outcome probability in both age groups. An age group × outcome probability interaction effect revealed the greatest differences between the groups for the 12% vs. the 67% outcome probability. Neurally, both age groups demonstrated a higher percent signal change in the VS and AI during the anticipation of potential monetary loss versus the verbal condition. However, adults demonstrated an even greater activation of VS and AI than adolescents during the anticipation of potential monetary loss, but not during the verbal condition. This may indicate that adolescents differ from adults regarding their experience of avoiding losing monetary rewards.

Background: Poor sleep and anxiety disorders are highly comorbid in youth, and each predicts altered ventral striatum (VS) response to rewards, which may impact mental health risk. Contrasting evidence suggests previously reported negative associations between sleep health and VS response may be stronger or weaker in youth with anxiety, indicating sensitivity to win/loss information or blunted reward processing, respectively. We cross-sectionally examined the role of sleep in VS response to rewards among youth with anxiety versus a no-psychiatric-diagnosis comparison (ND) group. We expected a group*sleep interaction on VS response to rewards but did not hypothesize directionality., Methods: As part of the pretreatment battery for a randomized clinical trial, 74 youth with anxiety and 31 ND youth (ages 9-14 years; n = 55 female) completed a monetary reward task during fMRI. During the same pretreatment window, actigraphy and diary-estimated sleep were collected over 5 days, and participants and their parents each reported participants' total sleep problems. We examined group*sleep interactions on VS response to monetary rewards versus losses via three mixed linear models corresponding to actigraphy, diary, and questionnaires, respectively., Results: Each model indicated group*sleep interactions on VS response to rewards. Actigraphy and diary-estimated time awake after sleep onset predicted reduced VS response in youth with anxiety but not ND youth. Parent-reported sleep problems similarly interacted with group, but simple slopes were nonsignificant., Conclusions: Wake after sleep onset was associated with blunted reward response in youth with anxiety. These data suggest a potential pathway through which sleep could contribute to perturbed reward function and reward-related psychopathology (e.g., depression) in youth with anxiety., (© 2022 Association for Child and Adolescent Mental Health.)

Major depressive disorder is associated with a reward deficit manifested by abnormal striatal function. However, differences between treatment-resistant depression (TRD) and non TRD (nTRD) in striatal whole-brain functional connectivity (FC) have not been elucidated. Thirty-eight patients with TRD, 42 patients with nTRD, and 39 healthy controls (HCs) were recruited for this study. A seed-based FC approach was used to analyze abnormalities in six predefined striatal subregion circuits in the three groups of subjects, and further explore the correlation between abnormal FC and clinical symptoms. Results revealed that compared with the nTRD group, the TRD group showed increased FC of the inferior ventral striatum with the bilateral orbital area of the middle frontal gyrus, right cerebellum posterior lobe, left parahippocampal gyrus, left middle occipital gyrus and left lingual gyrus. Compared with the HC group, the TRD group showed a wider range of altered striatal function than the nTRD group. In the TRD group, the HAMD-17 scores were positively correlated with the FC between the right VRP and the left caudate. This study provides new insights into understanding the specificity of TRD striatal circuits., Competing Interests: Declaration of Competing Interest No conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Altered reward sensitivity has been proposed to underlie symptoms of attention deficit hyperactivity disorder (ADHD). Functional magnetic resonance imaging (fMRI) studies have reported hypoactivation to reward-predicting cues in the ventral striatum among individuals with ADHD, using experimental designs with and without behavioral response requirements. These studies have typically used monetary incentives as rewards; however, it is unclear if these findings extend to other reward types. The current study examined striatal responses to anticipation and delivery of both affiliative and food reward images using a classical conditioning paradigm. Data from 20 typically developing young adults, and 20 individuals diagnosed with ADHD were included in a region-of-interest analysis for a priori striatal regions. Consistent with findings from studies using monetary rewards, individuals with ADHD showed decreased activation to cues predicting affiliative rewards in the bilateral ventral and dorsal striatum and increased activation to the delivery of affiliative rewards in the ventral striatum. No group differences were found in striatal responses to food reward cues or images. These results suggest hyposensitivity to reward-predicting cues in ADHD extends to affiliative rewards, with important implications for understanding and managing the learning and social functioning of those with ADHD., Competing Interests: Declaration of Competing Interest PM received research grant and speaker honoraria from Takeda in the last three years., (Copyright © 2022. Published by Elsevier B.V.)

Dysregulation of frontal cortical inputs to the striatum is foundational in the neural basis of substance use disorder (SUD). Neuroanatomical and electrophysiological data increasingly show that striatal nodes receive appreciable input from numerous cortical areas, and that the combinational properties of these multivariate "connectivity profiles" play a predominant role in shaping striatal activity and function. Yet, how abnormal configuration of striatal connectivity profiles might contribute to SUD is unknown. Here, we implemented a novel "connectivity profile analysis" (CPA) approach using resting-state functional connectivity data to facilitate detection of different types of connectivity profile "misconfiguration" that may reflect distinct forms of aberrant circuit plasticity in SUD. We examined 46 nicotine-dependent smokers and 33 non-smokers and showed that both dorsal striatum (DS) and ventral striatum (VS) connectivity profiles with frontal cortex were misconfigured in smokers-but in doubly distinct fashions. DS misconfigurations were stable across sated and acute abstinent states (indicative of a "trait" circuit adaptation) whereas VS misconfigurations emerged only during acute abstinence (indicative of a "state" circuit adaptation). Moreover, DS misconfigurations involved abnormal connection strength rank order arrangement, whereas VS misconfigurations involved abnormal aggregate strength. We found that caudal ventral putamen in smokers uniquely displayed multiple types of connectivity profile misconfiguration, whose interactive magnitude was linked to dependence severity, and that VS misconfiguration magnitude correlated positively with withdrawal severity during acute abstinence. Findings underscore the potential for approaches that more aptly model the neurobiological composition of corticostriatal circuits to yield deeper insights into the neural basis of SUD., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Impulsive-compulsive behaviours manifest in a substantial proportion of subjects with Parkinson's disease. Reduced ventral striatum dopamine receptor availability, and increased dopamine release is noted in patients with these symptoms. Prior studies of impulsivity suggest that midbrain D2 autoreceptors regulate striatal dopamine release in a feedback inhibitory manner, and in healthy populations, greater impulsivity is linked to poor proficiency of this inhibition. This has not been assessed in a Parkinson's disease population. Here, we applied 18F-fallypride PET studies to assess striatal and extrastriatal D2-like receptor uptake in a placebo-controlled oral dextroamphetamine sequence. We hypothesized that Parkinson's disease patients with impulsive-compulsive behaviours would have greater ventral striatal dopaminergic response to dextroamphetamine, and that an inability to attenuate ventral striatal dopamine release via midbrain D2 autoreceptors would underlie this response. Twenty patients with Parkinson's disease (mean age = 64.1 ± 5.8 years) both with (n = 10) and without (n = 10) impulsive-compulsive behaviours, participated in a single-blind dextroamphetamine challenge (oral; 0.43 mg/kg) in an OFF dopamine state. All completed PET imaging with 18F-fallypride, a high-affinity D2-like receptor ligand, in the placebo and dextroamphetamine state. Both voxelwise and region of interest analyses revealed dextroamphetamine-induced endogenous dopamine release localized to the ventral striatum, and the caudal-medial orbitofrontal cortex. The endogenous dopamine release observed in the ventral striatum correlated positively with patient-reported participation in reward-based behaviours, as quantified by the self-reported Questionnaire for Impulsivity in Parkinson's disease Rating Scale. In participants without impulsive-compulsive behaviours, baseline midbrain D2 receptor availability negatively correlated with ventral striatal dopamine release; however, this relationship was absent in those with impulsive-compulsive behaviours. These findings emphasize that reward-based behaviours in Parkinson's disease are regulated by ventral striatal dopamine release, and suggest that loss of inhibitory feedback from midbrain autoreceptors may underlie the manifestation of impulsive-compulsive behaviours., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Self-control is important for long-term success and could be a protective factor against maladaptive behaviours such as excessive gaming activity or Internet gaming disorder (IGD). However, the neurobiological basis of self-control and its relationship to IGD remain elusive. Using resting-state fMRI data from 89 participants aged from 18 to 26, we found that self-control and the number of IGD symptoms (IGD-S) were positively and negatively correlated with functional connectivity between right ventral striatum (rVS) and dorsal anterior cingulate cortex (dACC), respectively. A mediation analysis indicated that self-control influenced IGD-S partially through the rVS-dACC connectivity. In addition, step-wise regression analyses revealed that the rVS connectivity in a reward-anticipation limbic pathway contributed to IGD-S but not self-control, independent of the dACC pathway. These results suggest that the cingulate-ventral striatal functional connectivity may serve as an important neurobiological underpinning of self-control to regulate maladaptive behaviours such as these manifesting IGD through striatal circuitry balance., (© 2022 Society for the Study of Addiction.)

The default mode network (DMN) has been theorized to participate in a range of social, cognitive, and affective functions. Yet, previous accounts do not consider how the DMN contributes to other brain regions depending on psychological context, thus rendering our understanding of DMN function incomplete. We addressed this gap by applying a novel network-based psychophysiological interaction (nPPI) analysis to the reward task within the Human Connectome Project. We first focused on the task-evoked responses of the DMN and other networks involving the prefrontal cortex, including the executive control network (salience network) and the left and right frontoparietal networks. Consistent with a host of prior studies, the DMN exhibited a relative decrease in activation during the task, while the other networks exhibited a relative increase during the task. Next, we used nPPI analyses to assess whether these networks exhibit task-dependent changes in connectivity with other brain regions. Strikingly, we found that the experience of reward enhances task-dependent connectivity between the DMN and the ventral striatum, an effect that was specific to the DMN. Surprisingly, the strength of DMN-VS connectivity was correlated with personality characteristics relating to openness. Taken together, these results advance models of DMN by demonstrating how it contributes to other brain systems during task performance and how those contributions relate to individual differences., Competing Interests: Declaration of Competing Interest The authors have no conflicts to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Social relationships change across the lifespan as social networks narrow and motivational priorities shift to the present. Interestingly, aging is also associated with changes in executive function, including decision-making abilities, but it remains unclear how age-related changes in both domains interact to impact financial decisions involving other people. To study this problem, we recruited 50 human participants (N younger  = 26, ages 18-34; N older  = 24, ages 63-80) to play an economic trust game as the investor with three partners (friend, stranger, and computer) who played the role of investee. Investors underwent functional magnetic resonance imaging (fMRI) during the trust game while investees were seated outside of the scanner. Building on our previous work with younger adults showing both enhanced striatal responses and altered default-mode network (DMN) connectivity as a function of social closeness during reciprocated trust, we predicted that these relations would exhibit age-related differences. We found that striatal responses to reciprocated trust from friends relative to strangers and computers were blunted in older adults relative to younger adults, thus supporting our primary pre-registered hypothesis regarding social closeness. We also found that older adults exhibited enhanced DMN connectivity with the temporoparietal junction (TPJ) during reciprocated trust from friends compared to computers while younger adults exhibited the opposite pattern. Taken together, these results advance our understanding of age-related differences in sensitivity to social closeness in the context of trusting others., Competing Interests: Conflict of interest statement The authors have no conflicts to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Self-enhancement, the tendency to view oneself positively, is a pervasive social motive widely investigated in the psychological sciences. Relatively little is known about the neurocognitive mechanisms underlying this motive, specifically in social-evaluative situations. To investigate whether positive emotion regulation circuitry, circuitry involved in modulating positive affect, relates to the self-enhancement motive in social contexts, we conducted an functional magnetic resonance imaging (fMRI) study in a healthy young adult sample. We hypothesized that self-enhancement indices (state and trait self-esteem) would relate to greater functional connectivity between right ventrolateral prefrontal cortex (RVLPFC), a region implicated in emotion regulation, and the ventral striatum (VS), a region associated with reward-related affect, during a social feedback task. Following social evaluation, participants experienced stable or decreased state self-esteem. Results showed that stable state self-esteem from pre- to post-scan and higher trait self-esteem related to greater RVLPFC-VS connectivity during positive evaluation. Stable-state self-esteem also related to greater RVLPFC-VS connectivity during negative evaluation. Moreover, RVLPFC activation during all types of feedback processing and left VS activation during negative feedback processing was greater for participants with stable-state self-esteem. These findings implicate neurocognitive mechanisms underlying emotion regulation in the self-enhancement motive and highlight a pathway through which self-enhancement may restore feelings of self-worth during threatening situations., (© The Author(s) 2022. Published by Oxford University Press.)

Although altered reward sensitivity has been observed in individuals with bipolar disorder (BD), the brain function findings related to reward processing remain unexplored and inconsistent. This meta-analysis aimed to identify brain activation alterations underlying reward anticipation in BD. A systematic literature research was conducted to identify fMRI studies of reward-relevant tasks performed by BD individuals. Using Anisotropic Effect Size Signed Differential Mapping, whole-brain and ROI of the ventral striatum (VS) coordinate-based meta-analyses were performed to explore brain regions showing anomalous activation in individuals with BD compared to healthy controls (HC), respectively. A total of 21 studies were identified in the meta-analysis, 15 of which were included in the whole-brain meta-analysis and 17 in the ROI meta-analysis. The whole-brain meta-analysis revealed hypoactivation in the bilateral angular gyrus and right inferior frontal gyrus during reward anticipation in individuals with BD compared to HC. No significant activation differences were observed in bilateral VS between two groups by whole-brain or ROI-based meta-analysis. Individuals with BD type I and individuals with euthymic BD showed altered activation in prefrontal, angular, fusiform, middle occipital gyrus, and striatum. Hypoactivation in the right angular gyrus was positively correlated with the illness duration of BD. The present study reveals the potential neural mechanism underlying impairment in reward anticipation in BD. Some clinical features such as clinical subtype, mood state, and duration of illness confound the underlying neurobiological abnormality reward anticipation in BD. These findings may have implications for identifying clinically relevant biomarkers to guide intervention strategies for BD., (© 2022. The Author(s).)

The association between childhood trauma exposure and risk of developing psychopathology may in part be mediated by the effects of chronic stress on dopaminergic neurotransmission. However, little is known about the differential effects of distinct trauma types on reward processing, particularly in adults without concurrent medical or psychiatric disorders. We examined the association of childhood trauma exposure, including the differential effects of abuse and neglect, with reward processing in healthy adults (n = 114). Functional magnetic resonance imaging during a monetary incentive delay task was used to assess neural activity in the ventral striatum and orbitofrontal cortex in relation to reward anticipation and reward outcome, respectively. Exposure to childhood trauma, including abuse and neglect, was assessed using the Childhood Trauma Questionnaire-Short Form. We found a significant effect for abuse on ventral striatal activation during reward anticipation, adjusting for age, sex, scanner site, educational level, and household monthly income. There were no effects for abuse or neglect, independently or combined, on orbitofrontal cortex activation during reward outcome. Our findings suggest differential effects of childhood abuse on ventral striatum activation during reward anticipation in healthy adults., (© 2022 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Objective: Research in adolescent depression has found aberrant intrinsic functional connectivity (iFC) among the ventral striatum (VS) and several brain regions implicated in reward processing. The present study probes this question by taking advantage of the availability of data from a large youth cohort, the IMAGEN Consortium., Methods: iFC data from 303 adolescents (48% of them female) were used to examine associations of VS connectivity at baseline (at age 14) with depressive disorders at baseline and at 2-year (N=250) and 4-year (N=219) follow-ups. Eleven regions of interest, key nodes of the reward system, were used to probe the reward network and calculate the connectivity strength of the VS within this network (VS connectivity rw ). The main analyses assessed associations of VS connectivity rw with depressive disorders, anhedonia, and low mood using logistic regression. Autoregressive models accounting for carryover effects over time were conducted to further evaluate these brain-behavior associations., Results: Higher right VS connectivity rw was associated with higher probability of depressive disorders at baseline (odds ratio=2.65, 95% CI=1.40, 5.05). This finding was confirmed in the autoregressive model, adjusting for carryover effects of the depressive disorders across the three time points. VS connectivity rw was not predictive of depressive disorders at follow-up assessments. Longitudinal associations between VS connectivity rw and anhedonia emerged in the structural equation model: left VS connectivity rw was associated with anhedonia at 2 years (odds ratio=2.20, 95% CI=1.54, 3.14), and right VS connectivity rw was linked to anhedonia at 4 years (odds ratio=1.87, 95% CI=1.09, 3.21). VS connectivity rw did not predict low mood at any time point in the structural equation model., Conclusions: The connectivity strength of the VS within the reward network showed distinct patterns of association with depressive disorders and anhedonia from mid to late adolescence, suggesting that the role of this circuitry in depression changes with age. This study replicates, in an independent sample, the association between the VS and depression previously reported in younger adolescents. The findings suggest a role of VS connectivity rw in anhedonia but not in low mood.

Identifying the circuits responsible for cognition and understanding their embedded computations is a challenge for neuroscience. We establish here a hierarchical cross-scale approach, from behavioral modeling and fMRI in task-performing mice to cellular recordings, in order to disentangle local network contributions to olfactory reinforcement learning. At mesoscale, fMRI identifies a functional olfactory-striatal network interacting dynamically with higher-order cortices. While primary olfactory cortices respectively contribute only some value components, the downstream olfactory tubercle of the ventral striatum expresses comprehensively reward prediction, its dynamic updating, and prediction error components. In the tubercle, recordings reveal two underlying neuronal populations with non-redundant reward prediction coding schemes. One population collectively produces stabilized predictions as distributed activity across neurons; in the other, neurons encode value individually and dynamically integrate the recent history of uncertain outcomes. These findings validate a cross-scale approach to mechanistic investigations of higher cognitive functions in rodents., (© 2022. The Author(s).)

Flexible decision-making requires animals to forego immediate rewards (exploitation) and try novel choice options (exploration) to discover if they are preferable to familiar alternatives. Using the same task and a partially observable Markov decision process (POMDP) model to quantify the value of choices, we first determined that the computational basis for managing explore-exploit tradeoffs is conserved across monkeys and humans. We then used fMRI to identify where in the human brain the immediate value of exploitative choices and relative uncertainty about the value of exploratory choices were encoded. Consistent with prior neurophysiological evidence in monkeys, we observed divergent encoding of reward value and uncertainty in prefrontal and parietal regions, including frontopolar cortex, and parallel encoding of these computations in motivational regions including the amygdala, ventral striatum, and orbitofrontal cortex. These results clarify the interplay between prefrontal and motivational circuits that supports adaptive explore-exploit decisions in humans and nonhuman primates., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Although various studies have reported a high prevalence of depression among Parkinson's disease (PD) patients, the pathophysiological mechanism of depression in PD (DPD) is still unclear. The core region of the reward network, the ventral striatum (VS), is critical in the occurrence and development of DPD. This study aimed to explore the altered functional connectivity (FC) of VS subregions in DPD. We recruited 20 DPD patients, 37 non-depressed PD (NDPD) patients, and 41 healthy controls (HC) matched in age, gender, and years of education. The patients' diagnosis with PD was de-novo. We then used resting-state functional magnetic resonance imaging to detect the FC differences of VS subregions among these groups. The FC between the left ventral caudate (vCa&#95;L) and the left middle occipital gyrus (MOG.L) was significantly increased in DPD than in NDPD patients or HC. Compared with HC, NDPD patients exhibited significantly increased FCs between bilateral ventromedial putamen and the left paracentral lobule, the right ventromedial putamen (vmPu&#95;R), and the right precentral gyrus, the vmPu&#95;R, and the left precuneus. Besides, a significant negative correlation was found between the FC values of the vCa&#95;L with the MOG.L and the HAMD-17 scores in the DPD group. The hyperconnectivity between vCa&#95;L and the MOG.L might be viewed as a compensatory mechanism for depression in the early stage of PD. This study provides new insight into the neural mechanism of depression in the early stage of PD and contributes to explore the potential neuroimaging markers for DPD., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The ventral striatum (VS) is implicated in reward processing and motivation. Human and non-human primate studies demonstrate that the VS and prefrontal cortex (PFC), which comprise the frontostriatal circuit, interact to influence motivated behavior. However, there is a lack of research that precisely maps and quantifies VS-PFC white matter tracts. Moreover, no studies have linked frontostriatal white matter to VS activation. Using a multimodal neuroimaging approach with diffusion MRI (dMRI) and functional MRI (fMRI), the present study had two objectives: 1) to chart white matter tracts between the VS and specific PFC structures and 2) assess the association between the degree of VS-PFC white matter tract connectivity and VS activation in 187 adolescents. White matter connectivity was assessed with probabilistic tractography and functional activation was examined with two fMRI tasks (one task with social reward and another task using monetary reward). We found widespread but variable white matter connectivity between the VS and areas of the PFC, with the anterior insula and subgenual cingulate cortex demonstrating the greatest degree of connectivity with the VS. VS-PFC structural connectivity was related to functional activation in the VS though activation depended on the specific PFC region and reward task., (Copyright © 2022 Elsevier B.V. All rights reserved.)