Reward Processing Research Articles

Input-specific properties of excitatory synapses on oxytocin receptor-expressing neurons in the lateral septum

Oxytocin receptor (OXTR) is expressed in a distinct population of neurons in the lateral septum (LS), among other brain regions, and is responsible for regulating various social and non-social behaviors, including reward processing, feeding, social memory, anxiety, and fear. The LS serves as a key link between the cortical and subcortical regions, yet the synaptic inputs that drive the OXTR-expressing LS neurons have not been characterized. Here, we established retrograde and anterograde viral tracing in the mouse brain to map the input connections of the intermediate part of the LS where OXTR neurons are concentrated. Utilizing pathway-specific optogenetic activation, we identified that the strongest cortical inputs to LS OXTR neurons are from the posteromedial amygdala cortex (PMCo) and the ventral hippocampus (vHipp). We further determined that these excitatory inputs exhibit distinct presynaptic and postsynaptic properties, with PMCo synapses displaying a lower release probability and smaller AMPA receptor to NMDA receptor-mediated EPSC ratio compared to vHipp synapses. Our results also demonstrated that both vHipp and PMCo inputs establish a direct excitatory and a disynaptic inhibitory circuit on LS OXTR neurons. These findings deepen our understanding of the synaptic control of LS OXTR neurons by cortical regions, carrying significant implications for the affective behaviors in which these neurons are involved.

The Role of Videogame Micro-Transactions in the Relationship Between Motivations, Problem Gaming, and Problem Gambling

AbstractEmerging research has highlighted potential associations between micro-transaction use and problematic videogame and gambling behaviour. An increasingly prominent theory highlights that self-determined motivations and basic psychological needs may play crucial roles in the development of problematic videogame and gambling behaviour. However, literature discussing the role that micro-transaction use has in this relationship is scarce. The present study examined the role of micro-transactions in the relationship between self-determined motivations for gaming and gambling and problematic behaviour (internet gaming disorder and problem gambling severity). A sample of 370 participants (74.1% male, Mage = 28.24 years, SD = 7.88) answered questions related to their gaming and gambling motivations, basic psychological needs, micro-transaction use (i.e., type of micro-transaction, expenditure, and frequency of use), internet gaming disorder, and problem gambling. The present study used structural equation modelling methods to test relationships between these variables. The results indicated positive associations between extrinsic gaming and gambling motivations and frequency of micro-transaction use. Frequency of micro-transaction use (i) partially mediated the relationship between extrinsic gambling motivations and problem gambling severity, and (ii) fully mediated the relationship between externally regulated gaming motivations and problem gambling severity. Expenditure on micro-transactions and basic psychological needs were not found to be significant variables in the present study. Potential explanations for the findings, including a lack of self-esteem and a need to boost ego, social pressure, and rapid reward processes, are discussed. The implications and applications of the research are also discussed, focusing on limit setting and policy development focusing on frequency of micro-transaction use.

Neural Mechanism of Musical Pleasure Induced by Prediction Errors: An EEG Study

Background/Objectives: Musical pleasure is considered to be induced by prediction errors (surprise), as suggested in neuroimaging studies. However, the role of temporal changes in musical features in reward processing remains unclear. Utilizing the Information Dynamics of Music (IDyOM) model, a statistical model that calculates musical surprise based on prediction errors in melody and harmony, we investigated whether brain activities associated with musical pleasure, particularly in the θ, β, and γ bands, are induced by prediction errors, similar to those observed during monetary rewards. Methods: We used the IDyOM model to calculate the information content (IC) of surprise for melody and harmony in 70 musical pieces across six genres; eight pieces with varying IC values were selected. Electroencephalographic data were recorded during listening to the pieces, continuously evaluating the participants’ subjective pleasure on a 1–4 scale. Time–frequency analysis of electroencephalographic data was conducted, followed by general linear model analysis to fit the power-value time course in each frequency band to the time courses of subjective pleasure and IC for melody and harmony. Results: Significant positive fits were observed in the β and γ bands in the frontal region with both subjective pleasure and IC for melody and harmony. No significant fit was observed in the θ band. Both subjective pleasure and IC are associated with increased β and γ band power in the frontal regions. Conclusions: β and γ oscillatory activities in the frontal regions are strongly associated with musical rewards induced by prediction errors, similar to brain activity observed during monetary rewards.

Reward processing deficits arise early in familial frontotemporal dementia

Reward processing involves evaluation of stimuli to inform what an individual works to pursue or avoid. Patients with behavioral variant frontotemporal dementia (bvFTD) often display reward processing changes, including insensitivity to aversive stimuli. It is unknown how early in the disease course reward changes are detectable. We recruited mutation positive (symptomatic and asymptomatic) and negative members of families with known mutations in progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72). The sample included 4 groups: asymptomatic non-carriers (n = 34), asymptomatic carriers [Clinical Dementia Rating (CDR) 0, n = 16], mildly symptomatic carriers (CDR 0.5, n = 10) and bvFTD (sporadic and genetic, n = 45). A series of tasks utilized pleasant, unpleasant, and neutral olfactants to probe reward consumption and effort to obtain reward. A group by valence interaction showed unpleasant scent ratings were more positive in groups with greater disease severity [χ2(6) = 87.983, p < 0.001]. Mildly symptomatic carriers showed a small difference in ratings of pleasant and unpleasant stimuli, similar to bvFTD. In an effort task, where participants chose to avoid or receive scents, mildly symptomatic carriers and bvFTD chose to smell unpleasant scents more frequently than asymptomatic groups, with mildly symptomatic carriers exceeding bvFTD in their frequency of choosing to smell unpleasant scents. In this same task, motivated effort, determined by rate of button press, determined success at obtaining or avoiding scents. Success rate, calculated based on the number of responses where participants’ button presses exceeded an individual threshold set in a practice trial, differed across groups (p = 0.048), driven by mildly symptomatic carriers, who were consistently unsuccessful. There was a group difference in variability in button press rate across trials (p = 0.007), driven by mildly symptomatic carriers who showed less varied effort between scents. These findings suggest alterations to reward functioning can be detected early in bvFTD, even before meeting diagnostic criteria. These results may aid in identifying distinctive, initial reward changes in bvFTD that can facilitate early and accurate diagnosis and inspire efforts to identify anatomic underpinnings of early symptomatic changes.

Neurophysiological characteristics of reward processing in individuals at different levels of gaming.

Altered reward processing has been repeatedly reported in Internet gaming disorder (IGD). However, it remains unclear whether these changes are linked to the severity of addictive symptoms or the extent of gaming experience. This study examined the neurophysiological responses regarding reward anticipation and consummation in individuals at different levels of gaming (including 22 casual gamers, 31 regular gamers, and 27 individuals with IGD) through a monetary incentive delay task. Three event-related potential components during reward anticipation-cue-related P300 (Cue-P3), contingent negative variation, and stimulus-preceding negativity (SPN)-and two during reward consummation-feedback-related negativity and feedback-related P300 (FB-P3)-were measured. We found that IGD individuals exhibited greater Cue-P3 but lower SPN amplitude compared to casual gamers, while regular gamers fell between the two without significant differences. Regressions indicated that more extensive gaming experience, rather than the severity of the symptoms, primarily contributed to the increased Cue-P3 in IGD. No group differences were found during reward consummation. Our results highlight disrupted reward anticipation processing in IGD, characterized by increased attention bias toward reward cues (Cue-P3) but diminished cognitive resources for reward anticipation (SPN) and emphasize the role of gaming experience in increased attention bias in IGD.

Common and divergent neuroimaging features in major depression, posttraumatic stress disorder and their comorbidity

Abstract Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are common stress-related psychiatric disorders. Genetic and neurobiology research has supported the viewpoint that PTSD and MDD may possess common and disorder-specific underlying mechanisms. In this systematic review, we summarized evidence for the similarities and differences in brain functional and structural features of MDD, PTSD and their comorbidity, as well as the effects of extensively used therapies in patients with comorbid PTSD and MDD (PTSD + MDD). These functional magnetic resonance imaging (MRI) studies highlight the 1) shared hypoactivation in the prefrontal cortex during cognitive and emotional processing in MDD and PTSD, 2) higher activation in fear processing regions including amygdala, hippocampus and insula in PTSD compared to MDD, and 3) distinct functional deficits in brain regions involved in fear and reward processing in patients with PTSD + MDD relative to those with PTSD-alone. These structural MRI studies suggested that PTSD and MDD share features of reduced volume in focal frontal areas. The treatment effects in patients with PTSD + MDD may correlate with the normalization trend of structural alterations. Neuroimaging predictors of repetitive transcranial magnetic stimulation response in patients with PTSD + MDD may differ from the mono-diagnostic groups. In summary, neuroimaging studies to date have provided limited information about the shared and disorder-specific features in MDD and PTSD. Further research is essential to pave the way for developing improved diagnostic markers and eventually targeted treatment approaches for the shared and distinct brain alterations presented in patients with MDD and PTSD.

Cariprazine in Bipolar Disorder and Substance Use: A Dual Approach to Treatment?

Bipolar disorder (BD) is characterized by recurrent episodes of mania, hypomania, and depression and is often complicated by comorbid substance use disorders (SUDs). Up to 60% of individuals with BD experience SUDs, which exacerbate mood instability and increase the risk of rapid cycling, suicide, and poor clinical outcomes. Current treatment strategies, including lithium and valproate, show limited efficacy in treating both BD and SUD. Psychotherapeutic approaches such as cognitive behavioral therapy (CBT) offer benefits but lack a specific focus on substances such as cannabis and cocaine. Since there is still debate on how to treat this comorbidity, there is a need to find new therapeutic options; this mini-review examines the pharmacological properties of cariprazine and its emerging role in the treatment of comorbid BD and SUD. Cariprazine, an atypical antipsychotic with partial agonism at dopamine D2 and D3 receptors, has shown promise in treating both mood symptoms and cognitive dysfunction in BD. Its unique affinity for D3 receptors, which are involved in motivation and reward processing, may offer advantages in reducing drug craving. Clinical trials indicate that cariprazine effectively treats manic, depressive, and mixed episodes in BD with a favorable side effect profile, particularly at lower doses. Preliminary results suggest its potential to reduce craving and substance use in individuals with co-occurring BD and SUD. Therefore, cariprazine, with its unique pharmacodynamic mechanism, could be further studied for the treatment of BD in comorbidity with SUD. However, evidence on the role of cariprazine in the treatment of SUDs remains limited, based primarily on case reports and animal studies. Further research, including large-scale clinical trials, is needed to determine its full efficacy in this dual diagnosis.

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

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

Transformation of valence signaling in a mouse striatopallidal circuit

The ways in which sensory stimuli acquire motivational valence through association with other stimuli is one of the simplest forms of learning. Although we have identified many brain nuclei that play various roles in reward processing, a significant gap remains in understanding how valence encoding transforms through the layers of sensory processing. To address this gap, we carried out a comparative investigation of the mouse anteromedial olfactory tubercle (OT), and the ventral pallidum (VP) - 2 connected nuclei of the basal ganglia which have both been implicated in reward processing. First, using anterograde and retrograde tracing, we show that both D1 and D2 neurons of the anteromedial OT project primarily to the VP and minimally elsewhere. Using two-photon calcium imaging, we then investigated how the identity of the odor and reward contingency of the odor are differently encoded by neurons in either structure during a classical conditioning paradigm. We find that VP neurons robustly encode reward contingency, but not identity, in low-dimensional space. In contrast, the OT neurons primarily encode odor identity in high-dimensional space. Although D1 OT neurons showed larger responses to rewarded odors than other odors, consistent with prior findings, we interpret this as identity encoding with enhanced contrast. Finally, using a novel conditioning paradigm that decouples reward contingency and licking vigor, we show that both features are encoded by non-overlapping VP neurons. These results provide a novel framework for the striatopallidal circuit in which a high-dimensional encoding of stimulus identity is collapsed onto a low-dimensional encoding of motivational valence.

Transformation of valence signaling in a mouse striatopallidal circuit.

The ways in which sensory stimuli acquire motivational valence through association with other stimuli is one of the simplest forms of learning. Although we have identified many brain nuclei that play various roles in reward processing, a significant gap remains in understanding how valence encoding transforms through the layers of sensory processing. To address this gap, we carried out a comparative investigation of the mouse anteromedial olfactory tubercle (OT), and the ventral pallidum (VP) - 2 connected nuclei of the basal ganglia which have both been implicated in reward processing. First, using anterograde and retrograde tracing, we show that both D1 and D2 neurons of the anteromedial OT project primarily to the VP and minimally elsewhere. Using two-photon calcium imaging, we then investigated how the identity of the odor and reward contingency of the odor are differently encoded by neurons in either structure during a classical conditioning paradigm. We find that VP neurons robustly encode reward contingency, but not identity, in low-dimensional space. In contrast, the OT neurons primarily encode odor identity in high-dimensional space. Although D1 OT neurons showed larger responses to rewarded odors than other odors, consistent with prior findings, we interpret this as identity encoding with enhanced contrast. Finally, using a novel conditioning paradigm that decouples reward contingency and licking vigor, we show that both features are encoded by non-overlapping VP neurons. These results provide a novel framework for the striatopallidal circuit in which a high-dimensional encoding of stimulus identity is collapsed onto a low-dimensional encoding of motivational valence.

Increased functional connectivity between brain regions involved in social cognition, emotion and affective-value in psychedelic states induced by N,N-Dimethyltryptamine (DMT)

The modulation of social cognition is suggested as a possible mechanism contributing to the potential clinical efficacy of psychedelics in disorders involving socio-emotional and reward processing deficits. Resting-state functional Magnetic Resonance Imaging (rs-fMRI) can be used to detect changes in brain connectivity during psychedelic-induced states. Thus, this pharmacoimaging study investigates the effects of N,N-Dimethyltryptamine (DMT) on functional connectivity in brain areas relevant to social cognition, using a within-subject design in eleven healthy experienced users. The study included both an active and a control condition, conducted at different time points. The active condition involved DMT inhalation, while the control condition did not. Seed-based connectivity was measured for the two core regions involved in theory of mind and emotional processing, respectively, the posterior supramarginal gyrus and the amygdala. DMT increased supramarginal gyrus connectivity with the precuneus, posterior cingulate gyrus, amygdala, and orbitofrontal cortex. Additionally, increased connectivity emerged between the amygdala and orbitofrontal cortex. These results demonstrate that DMT modulates brain connectivity in socio-emotional and affective-value circuits, advancing our understanding of the neural mechanisms underlying the psychedelic experience and its potential therapeutic action.

Exploring distinct and joint contributions of the locus coeruleus and the substantia nigra/ventral tegmental area complex to reward and valence processing using high-resolution fMRI

Abstract Dopaminergic neurons in the substantia nigra and the ventral tegmental area (SN/VTA) are classically viewed as key mediators in reward processing, while noradrenergic cells in the locus coeruleus (LC) are thought to modulate (negative) saliency processing. However, this conventional distinction is being revised by more recent research in animals. To explore the respective contributions of both the LC and SN/VTA in reward and valence processing in humans, we assessed fMRI data during stimulus encoding and response phase of a rewarded emotion-discrimination task (n = 38). Participants responded significantly faster to reward predicting and negative valence stimuli compared with their non-salient counterparts. LC activity was overall higher during trials involving reward prospect, and in particular for reward trials featuring positive valence, demonstrating an additive effect of reward and positive valence in LC. Moreover, LC activity was differentially increased for negative compared with positive valence in the response phase, indexing its role in invigorating responses to negative events. The SN/VTA showed increased activity in the response phase of reward trials (neutral valence) and negative valence trials (no reward), which aligns with coding relative saliency of these events in their respective contexts. LC modulations were accompanied by covariations in occipital cortex, suggesting noradrenergic contributions to visual prioritization of salient events. The findings underscore the sensitivity of both LC and SN/VTA to reward prospects and negative valence, challenging the dominant view of SN/VTA’s involvement in merely positive events and emphasizing their essential role in action invigoration above and beyond mere stimulus encoding. The intricate roles of the DA and NA system in reward and emotional valence processing in humans warrant further exploration and validation, given the limitations inherent to neuroimaging of deep brain structures.

Differential temporal decline of cerebral oxytocin and μ-opioid receptor density during the aging process in mice.

Aging is often associated with changes in social, sexual, emotional and pain functioning, as well as with the increased prevalence of certain psychopathologies. However, the neurodevelopmental basis underpinning these age-related changes remains to be determined. Considering the key roles of oxytocin (OTR) and μ-opioid (MOPr) receptor systems in regulating social, sexual, pain, reward and emotional processing, it seems plausible that they are also implicated in age-related behavioural alterations. Although the ontogeny of both receptors has been well characterized in rodent brains from early development till adulthood, little is known concerning the neuroadaptations occurring from middle age to old age. Therefore, we mapped the neuroadaptations in OTR and MOPr in the brains of mice at those developmental endpoints. Quantitative OTR and MOPr autoradiographic binding was carried out in the brains of male mice at 2, 6, 9, 12 and 18 months of age. A significant whole brain decline in OTR density was detected between 2 and 6months of age, with no additional decline thereafter. Interestingly, for MOPrs, the decline in density was not detected until 9months of age. Region-specific age-related decline in OTR density was concentrated in the lateral anterior olfactory nuclei (AOL) and, for MOPr, in the AOL and the nucleus accumbens for MOPr. Identifying the tipping point of these age-related variations in both receptors may assist with our understanding of the neurobiology underlining age-related changes in social, pain and emotional functioning/processing. It may also help us target interventions to specific developmental windows to abrogate certain age-related psychopathologies.

A Short Glance at the Role of Olfactory Tubercle in Odour Processing

ABSTRACTThe mammalian olfactory system is one of the most precocious sensory systems during development and is innately endowed with versatile functions distinct from other sensory systems. Perception of time‐locked olfaction‐related stimuli quickly from the external environment and encoding them accurately via the olfactory system is paramount for the survival and reproduction in the animal kingdom. The olfactory system of mammals encompasses the main and accessory parts. As one key component of the ventral striatum, the olfactory tubercle (OT), is also an important as well as indispensable sub‐region of the main olfactory system and plays a crucial role in the central processing of odours. The OT also serves as a hub linking the olfactory system with the reward system in the brain. Although extensive research has underscored the involvement of the ventral striatum in the reward and punishment process as well as motivational behaviour, the encoding mechanism of neural circuits engaged in odour detection and recognition by the OT is still largely unknown. Herein, we make a brief overview of the olfactory system and underscore the crucial role of olfactory receptors in odour detection. We also emphasize the structural and functional characterisations of the OT and corresponding neural circuits involved in odour processing.

DNAJC13 influences responses of the extended reward system to conditioned stimuli: a genome-wide association study.

Reward system dysfunction is implicated in the pathogenesis of major psychiatric disorders. We conducted a genome-wide association study (GWAS) to identify genes that influence activation strength of brain regions within the extended reward system in humans. A homogeneous sample of 214 participants was genotyped and underwent functional magnetic resonance imaging (fMRI). All subjects performed the 'desire-reason dilemma' (DRD) paradigm allowing systematic investigation of systems-level mechanisms of reward processing in humans. As a main finding, we identified the single nucleotide variant rs113408797 in the DnaJ Heat Shock Protein Family Member C13 gene [DNAJC13], alias Receptor-Mediated Endocytosis 8 [RME-8], that was associated with the activation strength of the ventral tegmental area (VTA; p = 2.50E-07) and the nucleus accumbens (NAcc; p = 5.31E-05) in response to conditioned reward stimuli. Moreover, haplotype analysis assessing the information across the entire DNAJC13 locus demonstrated an impact of a five-marker haplotype on VTA activation (p = 3.21E-07), which further corroborates a link between this gene and reward processing. The present findings provide first direct empirical evidence that genetic variation of DNAJC13 influences neural responses within the extended reward system to conditioned stimuli. Further studies are required to investigate the role of this gene in the pathogenesis and pathophysiology of neuropsychiatric disorders.

Differential reconfiguration of brain networks in children in response to standard versus rewarded go/no-go task demands.

Response inhibition and sustained attention are critical for higher-order cognition and rely upon specific patterns of functional brain network organization. This study investigated how functional brain networks reconfigure to execute these cognitive processes during a go/no-go task with and without the presence of rewards in 26 children between the ages of 8 and 12 years. First, we compared task performance between standard and rewarded versions of a go/no-go task. We found that the presence of rewards reduced commission error rate, a measure considered to indicate improved response inhibition. Tau, thought to index sustained attention, did not change across task conditions. Next, changes in functional brain network organization were assessed between the resting state, the standard go/no-go task, and the rewarded go/no-go task. Relative to the resting state, integration decreased and segregation increased during the standard go/no-go task. A further decrease in integration and increase in segregation was observed when rewards were introduced. These patterns of reconfiguration were present globally and across several key brain networks of interest, as well as in individual regions implicated in the processes of response inhibition, attention, and reward processing. These findings align with patterns of brain network organization found to support the cognitive strategy of sustained attention, rather than response inhibition, during go/no-go task performance and suggest that rewards enhance this organization. Overall, this study used large-scale brain network organization and a within-subjects multi-task design to examine different cognitive strategies and the influence of rewards on response inhibition and sustained attention in late childhood.

Representation of Anticipated Rewards and Punishments in the Human Brain.

Subjective value is a core concept in neuroeconomics, serving as the basis for decision making. Despite the extensive literature on the neural encoding of subjective reward value in humans, the neural representation of punishment value remains relatively understudied. This review synthesizes current knowledge on the neural representation of reward value, including methodologies, involved brain regions, and the concept of common currency representation of diverse reward types in decision-making and learning processes. We then critically examine existing research on the neural representation of punishment value, highlighting conceptual and methodological challenges in human studies and insights gained from animal research. Finally, we explore how individual differences in reward and punishment processing may be linked to various mental illnesses, with a focus on stress-related psychopathologies. This review advocates for the integration of both rewards and punishments within value-based decision-making and learning frameworks, leveraging insights from cross-species studies and utilizing ecological gamified paradigms to reflect real-life scenarios.

Patterns of abnormal activations in severe mental disorders a transdiagnostic data-driven meta-analysis of task-based fMRI studies.

Studies suggest severe mental disorders (SMDs), such as schizophrenia, major depressive disorder and bipolar disorder, are associated with common alterations in brain activity, albeit with a graded level of impairment. However, discrepancies between study findings likely to results from both small sample sizes and the use of different functional magnetic resonance imaging (fMRI) tasks. To address these issues, data-driven meta-analytic approach designed to identify homogeneous brain co-activity patterns across tasks was conducted to better characterize the common and distinct alterations between these disorders. A hierarchical clustering analysis was conducted to identify groups of studies reporting similar neuroimaging results, independent of task type and psychiatric diagnosis. A traditional meta-analysis (activation likelihood estimation) was then performed within each of these groups of studies to extract their aberrant activation maps. A total of 762 fMRI study contrasts were targeted, comprising 13 991 patients with SMDs. Hierarchical clustering analysis identified 5 groups of studies (meta-analytic groupings; MAGs) being characterized by distinct aberrant activation patterns across SMDs: (1) emotion processing; (2) cognitive processing; (3) motor processes, (4) reward processing, and (5) visual processing. While MAG1 was mostly commonly impaired, MAG2 was more impaired in schizophrenia, while MAG3 and MAG5 revealed no differences between disorder. MAG4 showed the strongest between-diagnoses differences, particularly in the striatum, posterior cingulate cortex, and ventromedial prefrontal cortex. SMDs are characterized mostly by common deficits in brain networks, although differences between disorders are also present. This study highlights the importance of studying SMDs simultaneously rather than independently.

Ventral Striatum is Preferentially Correlated with the Salience Network Including Regions in Dorsolateral Prefrontal Cortex.

The ventral striatum (VS) receives input from the cerebral cortex and is modulated by midbrain dopaminergic projections in support of processing reward and motivation. Here we explored the organization of cortical regions linked to the human VS using within-individual functional connectivity MRI in intensively scanned participants. In two initial participants (scanned 31 sessions each), seed regions in the VS were preferentially correlated with distributed cortical regions that are part of the Salience (SAL) network. The VS seed region recapitulated SAL network topography in each individual including anterior and posterior midline regions, anterior insula, and dorsolateral prefrontal cortex (DLPFC) - a topography that was distinct from a nearby striatal seed region. The region of DLPFC linked to the VS is positioned adjacent to regions associated with domain-flexible cognitive control. The full pattern was replicated in independent data from the same two individuals and generalized to 15 novel participants (scanned 8 or more sessions each). These results suggest that the VS forms a cortico-basal ganglia loop as part of the SAL network. The DLPFC is a neuromodulatory target to treat major depressive disorder. The present results raise the possibility that the DLPFC may be an effective neuromodulatory target because of its preferential coupling to the VS and suggests a path toward further personalization.

The affective response to positive performance feedback is associated with motor learning.

Motor skill learning and performance are improved when successful actions are paired with extrinsic rewards, such as money. Positive feedback indicating successful task performance is thought to induce intrinsic reward associated with goal attainment, evidenced by increases in positive affect that correlate with neural reward signaling. However, it is not clear whether the subjective, internal reward processes elicited by positive feedback promote motor learning and performance.Here, we tested the hypothesis that intrinsic reward elicited by positive feedback promotes motor learning and performance. Participants practiced a visuomotor interception task using a joystick, and received feedback during practice indicating success or failure depending on their accuracy. During practice, the accuracy demands were adapted to control and vary the frequency of positive feedback across randomly ordered blocks of practice at either 50%, 70%, or 90%. Performance was measured for each condition as the average accuracy during practice. Learning was estimated by measuring the accuracy pre and post practice in the absence of feedback. We queried participants periodically on their enjoyment of the task to index affective responses to performance feedback.The intrinsic reward elicited by positive feedback, operationalized by the increase in enjoyment immediately following positive versus negative feedback, was positively correlated with learning from pre to post practice. However, increasing the overall amount of positive feedback by lower accuracy demands did not improve performance. These results suggest that experiencing intrinsic reward due to positive feedback benefits motor learning only when it is contingent on good performance.