Changed ventral striatum structural covariance and grey matter volume in depression during a one-year follow-up.

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.

Ventral striatal-cingulate resting-state functional connectivity in healthy adolescents relates to later depression symptoms in adulthood.

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.

The acute effect of mindfulness-based regulation on neural indices of cue-induced craving in smokers.

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.

Cortico-striatal beta oscillations as a reward-related signal.

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.

Down-modulation of functional ventral striatum activation for emotional face stimuli in patients with insula damage.

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.

Intersubject correlations in reward and mentalizing brain circuits separately predict persuasiveness of two types of ISIS video propaganda.

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.

Task-induced deactivation dysfunction during reward processing is associated with low self-esteem in a possible subtype of major depression.

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.

Altered neural anticipation of reward and loss but not receipt in adolescents with obsessive-compulsive disorder.

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).

White matter integrity of right frontostriatal circuit predicts internet addiction severity among internet gamers.

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.

Common neural dysfunction of economic decision-making across psychiatric conditions.

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.

Corticostriatal responses to social reward are linked to trait reward sensitivity and subclinical substance use in young adults.

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.

In vivo structural connectivity of the reward system along the hippocampal long axis.

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.

Striatal Functional Alterations Link to Distinct Symptomatology Across Mood States in Bipolar Disorder.

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.

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

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

Neurobehavioral Mechanisms Influencing the Association Between Generativity, the Desire to Promote Well-Being of Younger Generations, and Purpose in Life in Older Adults at Risk for Alzheimer's Disease.

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.

Striatal Response to Reward Anticipation as a Biomarker for Schizophrenia and Negative Symptoms: Effects, Test-Retest Reliability, and Stability Across Sites.

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.

Impaired flexible reward learning in ADHD patients is associated with blunted reinforcement sensitivity and neural signals in ventral striatum and parietal cortex.

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.

Dopamine release in human associative striatum during reversal learning.

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.

Gender Dysphoria and Sexual Euphoria: A Bayesian Perspective on the Influence of Gender-Affirming Hormone Therapy on Sexual Arousal.

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.

Amphetamine use disorder is associated with striatum hypoactivation during anticipation of loss and reward.

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.