Activity In Striatum Research Articles

The role of neural reward sensitivity in the longitudinal relations between parents’ familism values and Latinx American youth’s prosocial behaviors

Past research suggests that parents’ familism values play a positive role in Latinx American youth’s prosocial tendencies. However, little is known about how individual differences in youth’s neural development may contribute to this developmental process. Therefore, using two-wave longitudinal data of 1916 early adolescents (mean age = 9.90 years; 50% girls) and their parents (mean age = 38.43 years; 90% mothers) from the Adolescent Brain Cognitive Development study, this pre-registered study took a biopsychosocial approach to examine the moderating role of youth’s neural reward sensitivity in the link between parents’ familism values and youth’s prosocial behaviors. Results showed that parents’ familism values were associated with increased prosocial behaviors among youth two years later, controlling for baseline prosocial behaviors and demographic covariates. Notably, parents’ familism values played a larger role in promoting youth’s prosocial behaviors among youth who showed lower ventral striatum activation during reward anticipation. Moreover, such association between parents’ familism values and youth’s later prosocial behaviors was stronger among youth who showed lower levels of prosocial behaviors initially. Taken together, the findings highlight individual differences in neurobiological development and baseline prosocial behaviors as markers of sensitivity to cultural environments with regard to Latinx American youth’s prosocial development.

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.

Phosphodiesterase 7 inhibitor reduces stress-induced behavioral and cytoarchitectural changes in C57BL/6J mice by activating the BDNF/TrkB pathway.

Phosphodiesterase 7 (PDE7) plays a role in neurological function. Increased expression and activity of PDE7 has been detected in several central nervous system diseases. However, the role of PDE7 in regulating stress levels remains unclear. Thus, this study aimed to determine whether and how PDE7 involved in the stress-induced behavioral and neuron morphological changes. The single prolonged stress (SPS) was used to build a stress exposure model in C57BL/6J mice and detected PDE7 activity in hippocampus, amygdala, prefrontal cortex and striatum. Next, three doses (0.2, 1, and 5mg/kg) of the PDE7 inhibitor BRL-50481 were intraperitoneally administered for 10 days, then behavioral, biochemical, and morphological tests were conducted. PDE7 activity in hippocampus of mice significantly increased at all times after SPS. BRL-50481 significantly attenuated SPS induced anxiety-like behavior and fear response in both context and cue. In addition, BRL-50481 increased the levels of key molecules in the cAMP signaling pathway which were impaired by SPS. Immunofluorescent staining and Sholl analysis demonstrated that BRL-50481 also restored the nucleus/cytoplasm ratio of hippocampal neurons and improved neuronal plasticity. These effects of BRL-50481 were partially blocked by the TrkB inhibitor ANA-12. PDE7 inhibitors attenuate stress-induced behavioral changes by protecting the neuron cytoarchitecture and the neuronal plasticity in hippocampus, which is mediated at least partly through the activation of BDNF/TrkB signaling pathway. These results proved that PDE7 is a potential target for treating stress-induced behavioral and physiological abnormalities.

Transitioning from childhood into adolescence: A comprehensive longitudinal behavioral and neuroimaging study on prosocial behavior and social inclusion

Acting prosocially and feeling socially included are important factors for developing social relations. However, little is known about the development of neural trajectories of prosocial behavior and social inclusion in the transition from middle childhood to early adolescence. In this pre-registered study, we investigated the development of prosocial behavior, social inclusion, and their neural mechanisms in a three-wave longitudinal design (ages 7–13 years; NT1 = 512; NT2 = 456; NT3 = 336). We used the Prosocial Cyberball Game, a ball tossing game in which one player is excluded, to measure prosocial compensating behavior. Prosocial compensating behavior showed a linear developmental increase, similar to parent-reported prosocial behavior, whereas parent-reported empathy showed a quadratic trajectory with highest levels in late childhood. On a neural level we found a peak in ventral striatum activity during prosocial compensating behavior. Neural activity during social inclusion showed quadratic age effects in anterior cingulate cortex, insula, striatum, and precuneus, and a linear increase in temporo-parietal junction. Finally, changes in prosocial compensating behavior were negatively associated with changes in ventral striatum and mPFC activity during social inclusion, indicating an important co-occurrence between development in brain and social behavior. Together these findings shed a light on the mechanisms underlying social development from childhood into adolescence.

Add-on pramipexole for anhedonic depression: study protocol for a randomised controlled trial and open-label follow-up in Lund, Sweden

IntroductionMany depressed patients do not achieve remission with available treatments. Anhedonia is a common residual symptom associated with treatment resistance as well as low function and quality of life. There...

The remodeling of metabolic brain pattern in patients with extracranial diffuse large B-cell lymphoma

BackgroundOwing to the advances in diagnosis and therapy, survival or remission rates for lymphoma have improved prominently. Apart from the lymphoma- and chemotherapy-related somatic symptom burden, increasing attention has been drawn to the health-related quality of life. The application of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has been routinely recommended for the staging and response assessment of FDG-avid lymphoma. However, up till now, only a few researches have investigated the brain metabolic impairments in patients with pre-treatment lymphoma. The determination of the lymphoma-related metabolic brain pattern would facilitate exploring the tailored therapeutic regimen to alleviate not only the physiological, but also the psychological symptoms. In this retrospective study, we aimed to establish the diffuse large B-cell lymphoma-related pattern (DLBCLRP) of metabolic brain network and investigate the correlations between DLBCLRP and several indexes of the staging and response assessment.ResultsThe established DLBCLRP was characterized by the increased metabolic activity in bilateral cerebellum, brainstem, thalamus, striatum, hippocampus, amygdala, parahippocampal gyrus and right middle temporal gyrus and by the decreased metabolic activity in bilateral occipital lobe, parietal lobe, anterior cingulate gyrus, midcingulate cortex and medial frontal gyrus. Significant difference in the baseline expression of DLBCLRP was found among complete metabolic response (CMR), partial metabolic response (PMR) and progressive metabolic disease (PMD) groups (P < 0.01). DLBCLRP expressions were also significantly or tended to be positively correlated with international prognostic index (IPI) (rs = 0.306, P < 0.05), lg(total metabolic tumor volume, TMTV) (r = 0.298, P < 0.05) and lg(total lesion glycolysis, TLG) (r = 0.233, P = 0.064). Though no significant correlation of DLBCLRP expression was found with Ann Arbor staging or tumor SUVmax (P > 0.05), the post-treatment declines of DLBCLRP expression were significantly positively correlated with Ann Arbor staging (rs = 0.284, P < 0.05) and IPI (rs = 0.297, P < 0.05).ConclusionsThe proposed DLBCLRP would lay the foundation for further investigating the cerebral dysfunction related to DLBCL itself and/or treatments. Besides, the expression of DLBCLRP was associated with the tumor burden of lymphoma, implying a potential biomarker for prognosis.

Habits and Persistent Food Restriction in Patients with Anorexia Nervosa: A Scoping Review.

The aetiology of anorexia nervosa (AN) presents a puzzle for researchers. Recent research has sought to understand the behavioural and neural mechanisms of these patients' persistent choice of calorie restriction. This scoping review aims to map the literature on the contribution of habit-based learning to food restriction in AN. PRISMA-ScR guidelines were adopted. The search strategy was applied to seven databases and to grey literature. A total of 35 studies were included in this review. The results indicate that the habit-based learning model has gained substantial attention in current research, employing neuroimaging methods, scales, and behavioural techniques. Food choices were strongly associated with dorsal striatum activity, and habitual food restriction based on the self-report restriction index was associated with clinical impairment in people chronically ill with restricting AN. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and Regulating Emotions and Changing Habits (REaCH) have emerged as potential treatments. Future research should employ longitudinal studies to investigate the time required for habit-based learning and analyse how developmental status, such as adolescence, influences the role of habits in the progression and severity of diet-related illnesses. Ultimately, seeking effective strategies to modify persistent dietary restrictions controlled by habits remains essential.

The road not taken: Common and distinct neural correlates of regret and relief

Humans anticipate and evaluate both obtained and counterfactual outcomes – outcomes that could have been had an alternate decision been taken – and experience associated emotions of regret and relief. Although many functional magnetic resonance imaging (fMRI) studies have examined the neural correlates of these emotions, there is substantial heterogeneity in their results. We conducted coordinate-based ALE and network-based ANM meta-analysis of fMRI studies of experienced regret and relief to examine commonalities and differences in their neural correlates. Regionally, we observed that the experience of both regret and relief was associated with greater activation in the right ventral striatum (VS), which is implicated in tracking reward prediction error. At the network level, regret and relief shared the reward-sensitive mesocorticolimbic network with preferential activation of the medial orbitofrontal cortex (mOFC) for regret processing and medial cingulate cortex (MCC) for relief processing. Our research identified shared and separable brain systems subserving regret and relief experience, which may inform the treatment of regret-related mood disorders.

Remembering unexpected beauty: Contributions of the ventral striatum to the processing of reward prediction errors regarding the facial attractiveness in face memory

The COVID-19 pandemic has led people to predict facial attractiveness from partially covered faces. Differences in the predicted and observed facial attractiveness (i.e., masked and unmasked faces, respectively) are defined as reward prediction error (RPE) in a social context. Cognitive neuroscience studies have elucidated the neural mechanisms underlying RPE-induced memory improvements in terms of monetary rewards. However, little is known about the mechanisms underlying RPE-induced memory modulation in terms of social rewards. To elucidate this, the present functional magnetic resonance imaging (fMRI) study investigated activity and functional connectivity during face encoding. In encoding trials, participants rated the predicted attractiveness of faces covered except for around the eyes (prediction phase) and then rated the observed attractiveness of these faces without any cover (outcome phase). The difference in ratings between these phases was defined as RPE in facial attractiveness, and RPE was categorized into positive RPE (increased RPE from the prediction to outcome phases), negative RPE (decreased RPE from the prediction to outcome phases), and non-RPE (no difference in RPE between the prediction and outcome phases). During retrieval, participants were presented with individual faces that had been seen and unseen in the encoding trials, and were required to judge whether or not each face had been seen in the encoding trials. Univariate activity in the ventral striatum (VS) exhibited a linear increase with increased RPE in facial attractiveness. In the multivariate pattern analysis (MVPA), activity patterns in the VS and surrounding areas (extended VS) significantly discriminated between positive/negative RPE and non-RPE. In the functional connectivity analysis, significant functional connectivity between the extended VS and the hippocampus was observed most frequently in positive RPE. Memory improvements by face-based RPE could be involved in functional networks between the extended VS (representing RPE) and the hippocampus, and the interaction could be modulated by RPE values in a social context.

The right superior temporal gyrus plays a role in semantic-rule learning: Evidence supporting a reinforcement learning model

In real-life communication, individuals use language that carries evident rewarding and punishing elements, such as praise and criticism. A common trend is to seek more praise while avoiding criticism. Furthermore, semantics is crucial for conveying information, but such semantic access to native and foreign languages is subtly distinct. To investigate how rule learning occurs in different languages and to highlight the importance of semantics in this process, we investigated both verbal and non-verbal rule learning in first (L1) and second (L2) languages using a reinforcement learning framework, including a semantic rule and a color rule. Our computational modeling on behavioral and brain imaging data revealed that individuals may be more motivated to learn and adhere to rules in an L1 compared to L2, with greater striatum activation during the outcome phase in the L1. Additionally, results on the learning rates and inverse temperature in the two rule learning tasks showed that individuals tend to be conservative and are reluctant to change their judgments regarding rule learning of semantic information. Moreover, the greater the prediction errors, the greater activation of the right superior temporal gyrus in the semantic-rule learning condition, demonstrating that such learning has differential neural correlates than symbolic rule learning. Overall, the findings provide insight into the neural mechanisms underlying rule learning in different languages, and indicate that rule learning involving verbal semantics is not a general symbolic learning that resembles a conditioned stimulus-response, but rather has its own specific characteristics.

Development and cadherin-mediated control of prefrontal corticostriatal projections in mice

Action-outcome associations depend on prefrontal cortex (PFC) projections to the dorsal striatum. To assess how these projections form, we measured PFC axon patterning, synapse formation, and functional maturation in the postnatally developing mouse striatum. Using Hotspot analysis, we show that PFC axons form an adult-like pattern of clustered terminations in the first postnatal week that remains largely stable thereafter. PFC-striatal synaptic strength is adult-like by P21, while excitatory synapse density increases until adulthood. We then tested how the targeted deletion of a candidate adhesion/guidance protein, Cadherin-8 (Cdh8), from corticostriatal neurons regulates pathway development. Mutant mice showed diminished PFC axon targeting and reduced spontaneous glutamatergic synaptic activity in the dorsal striatum. They also exhibited impaired behavioral performance in action-outcome learning. The data show that PFC-striatal axons form striatal territories through an early, directed growth model and they highlight essential contributions of Cdh8 to the anatomical and functional features critical for the formation of action-outcome associations.

Reward expectation enhances action-related activity of nigral dopaminergic and two striatal output pathways

Neurons comprising nigrostriatal system play important roles in action selection. However, it remains unclear how this system integrates recent outcome information with current action (movement) and outcome (reward or no reward) information to achieve appropriate subsequent action. We examined how neuronal activity of substantia nigra pars compacta (SNc) and dorsal striatum reflects the level of reward expectation from recent outcomes in rats performing a reward-based choice task. Movement-related activity of direct and indirect pathway striatal projection neurons (dSPNs and iSPNs, respectively) were enhanced by reward expectation, similarly to the SNc dopaminergic neurons, in both medial and lateral nigrostriatal projections. Given the classical basal ganglia model wherein dopamine stimulates dSPNs and suppresses iSPNs through distinct dopamine receptors, dopamine might not be the primary driver of iSPN activity increasing following higher reward expectation. In contrast, outcome-related activity was affected by reward expectation in line with the classical model and reinforcement learning theory, suggesting purposive effects of reward expectation.

Chronic alcohol exposure differentially alters calcium activity of striatal cell populations during actions.

Alcohol Use Disorder (AUD) can induce long lasting alterations to executive function. This includes altered action control, which can manifest as dysfunctional goal-directed control. Cortical and striatal circuits mediate goal-directed control over behavior, and prior research has found chronic alcohol disrupts these circuits. In particular, prior in vivo and ex vivo work have identified alterations to function and activity of dorsal medial striatum (DMS), which is necessary for goal-directed control. However, unknown is whether these alterations manifest as altered activity of select DMS populations during behavior. Here we examine effects of prior chronic alcohol exposure on calcium activity modulation during action-related behaviors via fiber photometry of genetically-identified DMS populations including the direct and indirect output pathways, and fast-spiking interneurons. We find that prior chronic alcohol exposure leads to increased calcium modulation of the direct pathway during action related behavior. In contrast, prior chronic alcohol exposure led to decreased calcium activity modulation of the indirect pathway and the fast-spiking interneuron population around action-related events. Together, our findings suggest an imbalance in striatal activity during action control. This disruption may contribute to the altered goal-directed control previously reported.

Biopsychosocial Determinants of Problematic Pornography Use: A Systematic Review.

Although some studies have examined the determinants of problematic pornography use (PPU), few systematic comparisons of risk profiles have been conducted so far. Research on risk profiles can shed a bright light on our knowledge of both the early diagnosis and etiology of such highly prevalent disorders. Accordingly, the present study aimed to provide a comprehensive overview of the determinants of PPU. Scopus, Web of Science, PubMed, and PsycINFO databases were systematically searched, and relevant English articles, including longitudinal and cross-sectional studies on risk factors published from January 2000 to February 2022 were reviewed. The determinants of PPU extracted from the investigated studies (n=66) were summarized and clustered into biological, psychological, and social categories. The findings indicated that ventral striatum activity is a consistent biological factor which plays a key role in the development of PPU, while there were other psychological factors influencing PPU as mentioned in several studies, including craving, low self-esteem, sexual arousal, coping styles, stress, frequent pornography watching, avoidance, negative beliefs, and emotional deficiency. In addition, the social factors affecting PPU have been reported to be male gender, age, religion, moral incompatibility, and loneliness. According to these results, the identified factors could be considered in preventive treatment. This systematic review provided a comprehensive overview of the biopsychosocial determinants of PPU by analyzing 66 articles mostly from Europe and North America. Most studies showed that ventral striatum activity, craving, self-esteem, stress, frequent pornography watching, gender, age, and religion are related to PPU.

Brain functional alterations in patients with anorexia nervosa: A meta-analysis of task-based functional MRI studies

The goal of this study was to discern the neural activation patterns associated with anorexia nervosa (AN) in response to tasks related to body-, food-, emotional-, cognitive-, and reward- processing. A meta-analysis was performed on task-based fMRI studies, revealing that patients with AN showed increased activity in the left superior temporal gyrus and bilaterally in the ACC during a reward-related task. During cognitive-related tasks, patients with AN also showed increased activity in the left superior parietal gyrus, right middle temporal gyrus, but decreased activity in the MCC. Additionally, patients with AN showed increased activity bilaterally in the cerebellum, MCC, and decreased activity bilaterally in the bilateral precuneus/PCC, right middle temporal gyrus, left ACC when they viewed food images. During emotion-related tasks, patients with AN showed increased activity in the left cerebellum, but decreased activity bilaterally in the striatum, right mPFC, and right superior parietal gyrus. Patients with AN also showed increased activity in the right striatum and decreased activity in the right inferior temporal gyrus and bilaterally in the mPFC during body-related tasks. The present meta-analysis provides a comprehensive overview of the patterns of brain activity evoked by task stimuli, thereby augmenting the current comprehension of the pathophysiology in AN.

Differential local field potential oscillations in the dorsal striatum and locomotor activity induced by morphine and haloperidol in mice.

Dopamine (DA) depletion in the dorsal striatum underlies symptoms of basal ganglia pathologies, including Parkinson's disease (PD). Various drug compounds are used to enhance DA levels for therapeutic purposes. Understanding neural signaling and movement patterns associated with over‑ and under‑stimulation of the DA system is essential. This study investigated striatal local field potential (LFP) oscillation and locomotor activity following treatments with morphine, a DA release enhancer, and haloperidol (HAL), a DA D2 receptor (D2R) antagonist in mice. After intracranial electrodes were placed into the dorsal striatum of male Swiss albino ICR mice, intraperitoneal injections of morphine or HAL were administered. LFP signals and spontaneous motor activity were recorded simultaneously. The results showed that morphine significantly increased locomotor speed, both low (30.3-44.9 Hz) and high (60.5-95.7 Hz) LFP gamma powers and delta (1-4 Hz)‑gamma (30.3-95.7 Hz) phase‑amplitude coupling. In contrast, HAL treatments were found to significantly decrease these parameters. Moreover, regression analyses also revealed significant positive correlations between locomotor speed and high gamma powers. Taken together, these results demonstrate opposite LFP oscillations in the dorsal striatum with low and high gamma activities, and delta‑gamma couplings in response to a DA release enhancer and D2R antagonist by morphine and HAL, respectively. These parameters reflect fluctuation of neuronal activity in the dorsal striatum that might be useful for pathological research and drug discovery for PD.

The longitudinal role offamily conflict andneural reward sensitivity inyouth's internalizing symptoms.

Adolescence is often associated with an increase in psychopathology. Although previous studies have examined how family environments and neural reward sensitivity separately play a role in youth's emotional development, it remains unknown how they interact with each other in predicting youth's internalizing symptoms. Therefore, the current research took a biopsychosocial approach to examine this question using two-wave longitudinal data of 9353 preadolescents (mean age = 9.93 years at T1; 51% boys) from the Adolescent Brain Cognitive Development study. Using mixed-effects models, results showed that higher family conflict predicted youth's increased internalizing symptoms 1 year later, whereas greater ventral striatum (VS) activity during reward receipt predicted reduced internalizing symptoms over time. Importantly, there was an interaction effect between family conflict and VS activity. For youth who showed greater VS activation during reward receipt, high family conflict was more likely to predict increased internalizing symptoms. In contrast, youth with low VS activation during reward receipt showed high levels of internalizing symptoms regardless of family conflict. The findings suggest that youth's neural reward sensitivity is a marker of susceptibility to adverse family environments and highlight the importance of cultivating supportive family environments where youth experience less general conflict within the family.

Methamphetamine enhances neural activation during anticipation of loss in the monetary incentive delay task.

Stimulants like methamphetamine (MA) affect motivated behaviors via actions on circuits mediating mood, attention, and reward. Few studies examined the effects of single doses of stimulants on reward circuits during anticipation and receipt of rewards and losses. Here, we examined the effects of MA (20mg) or placebo in a within-subject, double-blind study with healthy adults (n = 43). During 2 fMRI sessions, participants completed the monetary incentive delay task. Primary outcome measures were BOLD activation in selected regions of interest during anticipation and receipt of monetary rewards and losses. Secondary analyses included behavioral measures, whole brain analysis, and arterial spin labeling. MA produced its expected behavioral effects and increased neural activation in the ventral striatum and anterior insula during anticipation of monetary loss versus non-loss. MA did not affect activation during anticipation of gains, or during receipt of wins or losses. MA significantly reduced cerebral blood flow in the striatum and insula. The present finding that a stimulant enhances the responses of striatal and insular regions to upcoming loss suggests that this system may be sensitive to the salience of upcoming events. The finding adds to a complex body of evidence regarding the effects of stimulant drugs on neural processes during motivated behaviors.

Routing states transition during oscillatory bursts and attentional selection

Brain-wide information routing relies on the spatio-temporal dynamics of neural activity, but it remains unclear how routing states emerge at fast spiking timescales and relate to slower activity dynamics during cognitive processes. Here, we show that localized spiking events participate in directional routing states with spiking activity in distant brain areas that dynamically switch or amplify states during oscillatory bursts, attentional selection, and decision-making. Modeling and neural recordings from lateral prefrontal cortex (LPFC), anterior cingulate cortex (ACC), and striatum of nonhuman primates revealed that cross-regional routing states arise within 20ms following individual neuron spikes, with LPFC spikes leading the activity in ACC and striatum. The baseline routing state amplified during LPFC beta bursts between LPFC and striatum and switched direction during ACC theta/alpha bursts between ACC and LPFC. Selective attention amplified theta-/alpha-band-specific lead ensembles in ACC, while decision-making increased the lead of ACC and LPFC spikes to the striatum.

Neural substrates on the judgment of sequential benefits and losses.

People need to adapt to situations where they experience sequential benefits (or losses) to ensure survival. This study investigated the neural substrates involved in judgments of sequential benefits and losses. A total of 29 healthy volunteers participated in this study, in which they were asked to participate in a game of purchasing stocks while a magnetic resonance imaging scan was performed. This game had two main types of trials: (1) participants received four sequential financial benefits (or losses), and (2) participants received an equal amount of benefits (or losses) immediately. The results showed greater activation of the orbitofrontal cortex (OFC) when fourbenefits werereceived sequentially thanwhenan equal amount of benefits wasreceived immediately. This indicates that the OFC plays a crucial role in the process of mental integration of sequential benefits and interpretation oftheir valuations. It also showed greater activation of the dorsal striatum when four sequentallosses werereceived than whenan equal amount of losses wasreceived immediately. However, it cannot be concluded that activation of the dorsal striatum reflects the differences between sequential and immediate losses, because previous studies have not confirmed this perspective. Therefore, it is necessary to clarify the function of the striatum in processingthese losses.