Activity In Nucleus Accumbens Research Articles

Brain activity of professional investors signals future stock performance

A major aspiration of investors is to better forecast stock performance. Interestingly, emerging "neuroforecasting" research suggests that brain activity associated with anticipatory reward relates to market behavior and population-wide preferences, including stock price dynamics. In this study, we extend these findings to professional investors processing comprehensive real-world information on stock investment options while making predictions of long-term stock performance. Using functional MRI, we sampled investors' neural responses to investment cases and assessed whether these responses relate to future performance on the stock market. We found that our sample of investors could not successfully predict future market performance of the investment cases, confirming that stated preferences do not predict the market. Stock metrics of the investment cases were not predictive of future stock performance either. However, as investors processed case information, nucleus accumbens (NAcc) activity was higher for investment cases that ended up overperforming in the market. These findings remained robust, even when controlling for stock metrics and investors' predictions made in the scanner. Cross-validated prediction analysis indicated that NAcc activity could significantly predict future stock performance out-of-sample above chance. Our findings resonate with recent neuroforecasting studies and suggest that brain activity of professional investors may help in forecasting future stock performance.

Non-invasive suppression of the human nucleus accumbens (NAc) with transcranial focused ultrasound (tFUS) modulates the reward network: a pilot study.

The nucleus accumbens (NAc) is a key node of the brain reward circuit driving reward-related behavior. Dysregulation of NAc has been demonstrated to contribute to pathological markers of addiction in substance use disorder (SUD) making it a potential therapeutic target for brain stimulation. Transcranial focused ultrasound (tFUS) is an emerging non-invasive brain stimulation approach that can modulate deep brain regions with a high spatial resolution. However, there is currently no evidence showing how the brain activity of NAc and brain functional connectivity within the reward network neuromodulated by tFUS on the NAc. In this pilot study, we carried out a single-blind, sham-controlled clinical trial using functional magnetic resonance imaging (fMRI) to investigate the underlying mechanism of tFUS neuromodulating the reward network through NAc in ten healthy adults. Specifically, the experiment consists of a 20-min concurrent tFUS/fMRI scan and two 24-min resting-state fMRI before and after the tFUS session. Firstly, our results demonstrated the feasibility and safety of 20-min tFUS on NAc. Additionally, our findings demonstrated that bilateral NAc was inhibited during tFUS on the left NAc compared to sham. Lastly, increased functional connectivity between the NAc and medial prefrontal cortex (mPFC) was observed after tFUS on the left NAc, but no changes for the sham group. Delivering tFUS to the NAc can modulate brain activations and functional connectivity within the reward network. These preliminary findings suggest that tFUS could be potentially a promising neuromodulation tool for the direct and non-invasive management of the NAc and shed new light on the treatment for SUD and other brain diseases that involve reward processing.

The regulation of social factors on anxiety and microglial activity in nucleus accumbens of adolescent male mice: Influence of social interaction strategy

BackgroundAdolescence is a period characterized by a high vulnerability to emotional disorders, which are modulated by biological, psychological, and social factors. However, the underlying mechanisms remain poorly understood. MethodsCombining physical or emotional social defeat stress (PS and ES) and pair or isolation rearing conditions, we investigated the effects of stress type and social support on emotional behavior and central immune molecules in adolescent mice, including anxiety, social fear, and social interaction strategies, as well as changes in microglia-specific molecules (ionized calcium-binding adaptor molecule 1 (Iba1) and a cluster of differentiation molecule 11b (CD11b)) in the medial prefrontal cortex (mPFC), hippocampus (HIP), amygdala (AMY), and nucleus accumbens (NAc). ResultsMice exposed to both physical stress and isolated rearing condition exhibited the highest levels of anxiety, social fear, and microglial CD11b expression in the NAc. In terms of social support, pair-housing with siblings ameliorated social fear and NAc molecular changes in ES mice, but not in PS mice. The reason for the differential benefit from social support was attributed to the fact that ES mice exhibited more active and less passive social strategies in social environment compared to PS mice. Further, the levels of stress-induced social fear were positively associated with the expression of microglial CD11b in the NAc. ConclusionThese findings offer extensive evidence regarding the intricate effects of multiple social factors on social anxiety and immune alteration in the NAc of adolescent mice. Additionally, they suggest potential behavioral and immune intervention strategies for anxiety-related disorders in adolescents.

Melanocortin agonism in a social context selectively activates nucleus accumbens in an oxytocin-dependent manner

Social deficits are debilitating features of many psychiatric disorders, including autism. While time-intensive behavioral therapy is moderately effective, there are no pharmacological interventions for social deficits in autism. Many studies have attempted to treat social deficits using the neuropeptide oxytocin for its powerful neuromodulatory abilities and influence on social behaviors and cognition. However, clinical trials utilizing supplementation paradigms in which exogenous oxytocin is chronically administered independent of context have failed. An alternative treatment paradigm suggests pharmacologically activating the endogenous oxytocin system during behavioral therapy to enhance the efficacy of therapy by facilitating social learning. To this end, melanocortin receptor agonists like Melanotan II (MTII), which induces central oxytocin release and accelerates formation of partner preference, a form of social learning, in prairie voles, are promising pharmacological tools. To model pharmacological activation of the endogenous oxytocin system during behavioral therapy, we administered MTII prior to social interactions between male and female voles. We assessed its effect on oxytocin-dependent activity in brain regions subserving social learning using Fos expression as a proxy for neuronal activation. In non-social contexts, MTII only activated hypothalamic paraventricular nucleus, a primary site of oxytocin synthesis. However, during social interactions, MTII selectively increased oxytocin-dependent activation of nucleus accumbens, a site critical for social learning. These results suggest a mechanism for the MTII-induced acceleration of partner preference formation observed in previous studies. Moreover, they are consistent with the hypothesis that pharmacologically activating the endogenous oxytocin system with a melanocortin agonist during behavioral therapy has potential to facilitate social learning.

Neuronal activation of nucleus accumbens by local methamphetamine administration induces cognitive impairment through microglial inflammation in mice

More than half of methamphetamine (METH) users present with cognitive impairment, making it difficult for them to reintegrate into society. However, the mechanisms of METH-induced cognitive impairment remain unclear. METH causes neuronal hyperactivation in the nucleus accumbens (NAc) by aberrantly releasing dopamine, which triggers dependence. In this study, to clarify the involvement of hyperactivation of NAc in METH-induced cognitive impairment, mice were locally microinjected with METH into NAc (mice with METH (NAc)) and investigated their cognitive phenotype. Mice with METH (NAc) exhibited cognitive dysfunction in behavioral analyses and decreased long-term potentiation in the hippocampus, with NAc activation confirmed by expression of FosB, a neuronal activity marker. In the hippocampus of mice with METH (NAc), activated microglia, but not astroglia, and upregulated microglia-related genes, Il1b and C1qa were observed. Finally, administration of minocycline, a tetracycline antibiotic with suppressive effect on microglial activation, to mice with METH (NAc) ameliorated cognitive impairment and synaptic dysfunction by suppressing the increased expression of Il1b and C1qa in the hippocampus. In conclusion, activation of NAc by injection of METH into NAc elicited cognitive impairment by facilitating immune activation in mice. This study suggests that immunological intervention could be a therapeutic strategy for addiction-related cognitive disturbances.

Sex-Specific Vulnerability to Externalizing Problems: Sensitivity to Early Stress and Nucleus Accumbens Activation Over Adolescence

BackgroundExposure and sensitivity to early-life stress (ELS) are related to increased risk for psychopathology in adolescence. While cross-sectional studies have reported blunted nucleus accumbens (NAcc) activation in the context of these associations, researchers have not yet assessed the effects of ELS on developmental trajectories of activation. We examined whether trajectories are affected by stress and the moderating role of biological sex in predicting vulnerability to symptoms of psychopathology. MethodsAdolescents (n = 173) completed 3 assessments at 2-year intervals across puberty (ages 9–18 years). At baseline, we assessed objective ELS and stress sensitivity using the Traumatic Events Screening Inventory for Children. At all time points, we assessed NAcc activation using the Monetary Incentive Delay task and externalizing, internalizing, and total problems using the Youth Self-Report. We examined correlations between NAcc trajectories (extracted using linear mixed-effects models) with ELS and stress sensitivity and conducted multivariate regression analysis to examine the interaction of NAcc trajectories and biological sex in predicting symptoms of psychopathology. ResultsSymptoms increased over adolescence. Stress sensitivity, but not objective ELS, was associated with decreasing trajectories of NAcc activation. Biological sex interacted with NAcc trajectories to predict psychopathology; boys, but not girls, with decreasing NAcc activation had more severe externalizing problems in adolescence. These findings were replicated in the putamen and caudate but not in the medial prefrontal cortex or control brain regions. ConclusionsNAcc activation may be a sex-specific marker of externalizing problems in adolescence. Efforts to reduce stress sensitivity may help to decrease symptoms of psychopathology in adolescent boys.

Cultural variation inneural responses to social but not monetary reward outcomes.

European Americans view high-intensity, open-mouthed 'excited' smiles more positively than Chinese because they value excitement and other high arousal positive states more. This difference is supported by reward-related neural activity, with European Americans showing greater Nucleus Accumbens (NAcc) activity to excited (vs calm) smiles than Chinese. But do these cultural differences generalize to all rewards, and are they related to real-world social behavior? European American (N = 26) and Chinese (N = 27) participants completed social and monetary incentive delay tasks that distinguished between the anticipation and receipt (outcome) of social and monetary rewards while undergoing Functional Magnetic Resonance Imaging (FMRI). The groups did not differ in NAcc activity when anticipating social or monetary rewards. However, as predicted, European Americans showed greater NAcc activity than Chinese when viewing excited smiles during outcome (the receipt of social reward). No cultural differences emerged when participants received monetary outcomes. Individuals who showed increased NAcc activity to excited smiles during outcome had friends with more intense smiles on social media. These findings suggest that culture plays a specific role in modulating reward-related neural responses to excited smiles during outcome, which are associated with real-world relationships.

Acquired alterations in nucleus accumbens responsiveness to a cocaine-paired discriminative stimulus preceding rats’ daily cocaine consumption

Resumption of drug taking is a primary focus for substance use disorder research and can be triggered by drug-associated environmental stimuli. The Nucleus Accumbens (NAc) is a key brain region which guides motivated behavior and is implicated in resumption. Yet, there remains a pressing need to characterize NAc neurons’ responsiveness to drug associated stimuli during withdrawal and abstinence. We recorded discriminative stimulus (DS) induced NAc activity via in vivo single-unit electrophysiology in rats that self-administered cocaine. Male and female rats implanted with a jugular catheter and a microwire array in NAc Core and Shell self-administered cocaine under control of a 30s auditory DS for 6 hours per session across 14 consecutive days. Rats acquired tone discrimination within 4 sessions. To exclude pharmacological effects of circulating cocaine from all neuronal analyses, we studied changes in DS-induced firing only for trials preceding the first infusion of cocaine in each of the 14 sessions, which were defined as “pre-drug trials.” NAc neuron responses were assessed prior to tone-evoked movement onset. Responsiveness to the DS tone was exhibited throughout all sessions by the NAc Core population, but only during Early sessions by the NAc Shell population. Both Core and Shell responded selectively to the DS, i.e., more strongly on drug taking trials, or Hits, than on Missed opportunities. These findings suggest that NAc Core and Shell play distinct roles in initiating cocaine seeking prior to daily cocaine consumption, and align with reports suggesting that as drug use becomes chronic, cue-evoked activity shifts from NAc Shell to NAc Core.

Selective Activation of NAc D1R-VP/LH Circuits Promotes Reanimation From Sevoflurane Anesthesia in Mice.

Emerging evidence has uncovered a vital role of nucleus accumbens (NAc) neurons that express the dopamine D1 receptor (D1R) and its upstream neural circuit in general anesthesia (GA) regulation. However, the underlying downstream neural basis of the modulation of GA emergence by NAc D1R neurons remains unknown. In the present study, we explored the downstream neural mechanism of NAc D1R neurons in the modulation of emergence from sevoflurane GA. We traced the axonal projections of NAc D1R neurons using a cell type-specific anterograde tracing method and immunohistochemical techniques in D1R-Cre mice. Optogenetic stimulations combined with electroencephalogram/electromyogram recordings and behavioral tests were used to determine the effects of optogenetic activation of the axonal terminals of NAc D1R neurons on sevoflurane emergence during sevoflurane-induced continuous, steady-state general anesthesia (CSSGA) or burst-suppression oscillations. Labeled efferent fibers of NAc D1R neurons were highly distributed in the ventral pallidum (VP), lateral hypothalamus (LH), and substantia nigra pars compacta. Optogenetic activation of the NAc D1R -VP circuit during CSSGA with sevoflurane induced cortical activation (mean ± standard deviation [SD]; delta power: prestimulation versus during stimulation, 48.7% ± 5.7% vs 35.1% ± 3.3%, P < .0001; beta power: 7.1% ± 2.7% vs 14.2% ± 3.3%, P = .0264) and behavioral emergence, and restored the righting reflex in 66.7% of ChR2 mice. Optogenetic stimulation of the NAc D1R -LH circuit also produced cortical activation (delta power: prestimulation versus during stimulation, 45.0% ± 6.5% vs 36.1% ± 4.6%, P = .0016) and behavioral emergence, and restored the righting reflex in 100% of the ChR2 mice during CSSGA with sevoflurane. Under a sevoflurane-induced burst-suppression state, NAc D1R -VP/LH circuit activation produced evidence of cortical activation (burst-suppression ratio [BSR]: NAc D1R -VP circuit, prestimulation versus during stimulation, 42.4% ± 4.0% vs 26.3% ± 6.0%, P = .0120; prestimulation versus poststimulation, 42.4% ± 4.0% vs 5.9% ± 5.6%, P = .0002; BSR: NAc D1R -LH circuit, prestimulation versus during stimulation, 33.3% ± 13.4% vs 5.1% ± 4.9%, P = .0177; prestimulation vs poststimulation, 33.3% ± 13.4% vs 3.2% ± 4.0%, P = .0105) and behavioral emergence. Both NAc D1R -VP and NAc D1R -LH circuits are sufficient to promote reanimation from sevoflurane GA by simultaneously inducing cortical and behavioral emergence.

Neural correlates of immediate versus delayed extinction when simultaneously varying the time of the test in humans.

Anxiety disorders are effectively treated with exposure therapy based on the extinction of Pavlovian fear conditioning. Animal research indicates that both the timing of extinction and test are important factors to reduce the return of fear. However, empirical evidence in humans is incomplete and inconsistent. In this neuroimaging study, we, therefore, tested 103 young, healthy participants in a 2-factorial between-subjects design with the factors extinction group (immediate, delayed) and test group (+1day and +7days). Immediate extinction led to greater retention of fear memory at the beginning of extinction training indicated by increased skin conductance responses. A return of fear was observed in both extinction groups, with a trend toward a greater return of fear in immediate extinction. The return of fear was generally higher in groups with an early test. Neuroimaging results show successful cross-group fear acquisition and retention, as well as activation of the left nucleus accumbens during extinction training. Importantly, the delayed extinction group showed a larger bilateral nucleus accumbens activation during test. This nucleus accumbens finding is discussed in terms of salience, contingency, relief, and prediction error processing. It may imply that the delayed extinction group benefits more from the test as a new learning opportunity.

The motivation to flock correlates with vocal-social behaviors and dopamine-related gene expression in male European starlings

It is proposed that songbird flocks are partly reinforced by positive social interactions, however not all flock mate interactions are positive. The combination of both positive and negative social interactions with flock mates may play a role in the motivation for birds to flock. The nucleus accumbens (NAc), medial preoptic area (POM), and ventral tegmental area (VTA) are implicated in vocal-social behaviors in flocks, including singing. Dopamine (DA) within these regions modifies motivated, reward-directed behaviors. Here, we begin to test the hypothesis that individual social interactions and DA within these regions are involved in the motivation to flock. Vocal-social behaviors were recorded in eighteen male European starlings in mixed-sex flocks in fall, when starlings are highly social and form large flocks. Males were then singly removed from their flock and the motivation to flock was quantified as the amount of time spent attempting to join a flock following separation. We used quantitative real-time polymerase chain reaction to measure expression of DA-related genes in the NAc, POM, and VTA. Birds producing high levels of vocal behaviors were more highly motivated to flock and had higher tyrosine hydroxylase (the rate-limiting enzyme in DA synthesis) expression in the NAc and VTA. Birds that received high levels of agonistic behaviors were less motivated to flock and had higher DA receptor subtype 1 expression in the POM. Overall, our findings suggest that interplay between social experience and DA activity in NAc, POM, and VTA plays a key role in social motivation in flocking songbirds.

0610 The effects of wakefulness promoting agents on neuronal activity in nucleus accumbens

Abstract Introduction Both modafinil and methylphenidate are frequently utilized for maintenance of wakefulness in narcolepsy and other sleep disorders. Both have been demonstrated to affect dopamine transporter, leading to an increase extracellular dopamine. Subsequent functional connectivity changes between nucleus accumbens and pallidum are noted. Animal studies demonstrate changes in neuronal activity with methylphenidate in nucleus accumbens. To our knowledge there has been no direct examination of human neural activity in nucleus accumbens after administration of modafinil or methylphenidate, compared to baseline. Methods Two subjects with placement of stereotactic electroencephalographic (sEEG) electrodes to identify optimal location for permanent deep brain stimulation electrodes in nucleus accumbens were given wakefulness promoting agents to optimize testing of stimulation sites during inpatient hospitalization. Assessment occurred at least 48 hours following surgical electrode insertion under inhaled general anesthesia. Retrospective analysis was performed on neural activity in nucleus accumbens during rest on and off medication. Frequency content was calculated in the following bands: delta (1-3 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (13-30 Hz), gamma (30-50 Hz), and high gamma (70-100 Hz). Power in each band is reported as the percentage contribution of each band to summed power across all bands. Results Total power was noted to be lower with both modafinil and methylphenidate. With modafinil, the beta band ratio was decreased (22.3% vs. 30.5%), the gamma band ratio was increased (24% vs. 22.4%), and the high gamma band was increased (39.5% vs. 32.9%). With methylphenidate, only the high gamma band was increased (40.3% vs. 22.9%). Conclusion Both methylphenidate and modafinil increase high gamma band neural activity in nucleus accumbens, while modafinil has additional effects on beta and gamma bands. Further assessment of modafinil and methylphenidate’s effects on neural activity are indicated to help better understand their mechanism of action and appropriate use as wakefulness promoting agents. Support (if any)

Developing Biomarkers for Chronic Low Back Pain Using Arterial Spin Labeling (P9-6.005)

<h3>Objective:</h3> In this study, we aim to 1) utilize Arterial Spin Labeling (ASL) to develop neurophysiological characterization of the subjective chronic pain experience, and 2) explore the feasibility of incorporating ASL in routine clinical scans. <h3>Background:</h3> Over 100 million people in the US suffer from chronic pain. This leads to tremendous burden on individuals and society. However, as the mechanisms for chronic pain are unclear, robust diagnostic and prognostic methods remain limited. Our previous research using resting-state fMRI revealed changes in low-frequency fluctuations in nucleus accumbens (NAc) when low back pain became chronic. We hypothesize that physiological changes in NAc in chronic pain also affect local blood perfusion. <h3>Design/Methods:</h3> ASL is a non-invasive perfusion-based MRI technique that can quantify cerebral blood flow (CBF). We collected resting-state ASL data from 43 patients with chronic low back pain (CLBP) and 33 healthy controls (HC) on a research scanner, as well as 11 CLBP patients and 10 HC on a clinical scanner. Brain perfusion maps were generated to quantify the CBF and relative CBF (rCBF). <h3>Results:</h3> Compared to HC, CLBP patients had significantly higher rCBF in the NAc (<i>p</i>=0.046). However, multivariate analysis revealed sex and age as main contributors to this difference in our preliminary clinical dataset. NAc rCBF increased with age and decreased with female sex. We also observed linear correlation between CBF from the clinical scanner and the research scanner in grey matter and white matter (<i>p</i>=0.0008 and 0.001; <i>r</i>₂=0.57 and 0.55, respectively). <h3>Conclusions:</h3> Our preliminary ASL results show consistency with prior fMRI findings in identifying NAc as a biomarker for chronic pain. Altered NAc activity in chronic pain may be involved in the motivational and hedonic aspect of chronic pain. This pilot study also supports the potential of utilizing ASL in clinical care for chronic pain patients. <b>Disclosure:</b> Ms. Yuan has nothing to disclose. Madalina Tivarus has nothing to disclose. Miss Tahsin has nothing to disclose. Mr. Alldritt has nothing to disclose. Dr. Geha has nothing to disclose.

Motherhood and DREADD manipulation of the nucleus accumbens weaken established pair bonds in female prairie voles

Monogamous pair bonding has evolved to enhance reproductive success and ensure offspring survival. Although the behavioral and neural mechanisms regulating the formation of pair bonds have been relatively well outlined, how these relationships are regulated and maintained across the lifetime of an individual remains relatively unexplored. One way to explore this is to study the maintenance of a social bond across a major life-history transition. The transition to motherhood is among the most poignant moments in the life history of a female, and is associated with significant neural and behavioral changes and shifting priorities. The nucleus accumbens (NAc) is known to modulate social valence and is central to mammalian pair bonding. In this study, we investigated two mechanisms driving variation in bond strength in the socially monogamous prairie vole (Microtus ochrogaster). We manipulated neural activity of the NAc at two distinct stages of life-history, before and after the birth of offspring, to assess how neural activity and social contexts modulate female pair bond strength. Our results showed DREADD (Designer Receptor Exclusively Activated by Designer Drugs) inhibition of the NAc decreases affiliative behavior towards the mating partner, whereas DREADD activation of the NAc increases affiliative behavior of strangers, thereby decreasing social selectivity. We also found a robust “birth effect” on pair bond strength, such that bonds with partners were weakened after the birth of offspring, an effect not attributable to the amount of cohabitation time with a partner. Overall, our data support the hypotheses that NAc activity modulates reward/saliency within the social brain in different ways, and that motherhood comes with a cost for the bond strength between mating partners.

Puberty and risky decision-making in male adolescents

Pubertal development is a potential trigger for increases in risk-taking behaviours during adolescence. Here, we sought to investigate the relationship between puberty and neural activation during risky decision-making in males using functional magnetic resonance imaging (fMRI). Forty-seven males aged 12.5–14.5 years completed an fMRI risk-taking task (BART) and reported their tendencies for risky decision-making using a self-report questionnaire. Puberty was assessed through self-reported pubertal status and salivary testosterone levels. Testosterone concentration, but not physical pubertal status, was positively correlated with self-reported risk-taking behaviour, while neither was correlated with BART performance. Across the whole sample, participants had greater activation of the bilateral nucleus accumbens and right caudate on trials when they made a successful risky decision compared to trials when they made a safe choice or when their risky decision was unsuccessful. There was a negative correlation between pubertal stage and brain activation during unsuccessful risky decision-making trials compared within unsuccessful control trials. Males at a lower stage of pubertal development showed increased activation in the left insula, right cingulate cortex, dorsomedial prefrontal cortex (dmPFC), right putamen and right orbitofrontal cortex (OFC) relative to more pubertally mature males during trials when they chose to take a risk and the balloon popped compared to when they watched the computer make an unsuccessful risky decision. Less pubertally mature males also showed greater activation in brain regions including the dmPFC, right temporal and frontal cortices, right OFC, right hippocampus and occipital cortex in unsuccessful risky trials compared to successful risky trials. These results suggest a puberty-related shift in neural activation within key brain regions when processing outcomes of risky decisions, which may reduce their sensitivity to negative feedback, and in turn contribute to increases in adolescent risk-taking behaviours.

Aberrant reward-related neural activation: Dimensional correlate of binge-eating severity or categorical marker of binge eating?

Binge eating (BE) is characterized by consuming an objectively large amount of food in a short period of time and experiencing loss of control over one's eating. The neural underpinnings of monetary reward anticipation and their association with BE severity remain poorly understood. Fifty-nine women aged 18 to 35 (M = 25.67, SD = 5.11) with a range of average weekly BE frequency (M = 1.96, SD = 1.89, range = 0–7) completed the Monetary Incentive Delay Task during fMRI scanning. Mean percent signal change within the left and right nucleus accumbens (NAc) during anticipation of monetary gain (versus non-gain) was extracted from a priori-defined functional 5 mm spheres and correlated with average weekly BE frequency. Exploratory voxel-wise whole-brain analyses examined the association between neural activation during anticipation of monetary reward and average weekly BE frequency. Body mass index and depression severity were covariates of non-interest in analyses. Mean percent signal change in the left and right NAc inversely correlated with average weekly BE frequency. Whole-brain analysis revealed no significant associations between neural activation during reward anticipation and average weekly BE frequency. In exploratory case-control analyses, mean percent signal change in the right NAc was significantly lower in women with BE (n = 41) versus women without BE (n = 18), but whole-brain analyses revealed no significant group differences in neural activation during reward anticipation. Decreased right NAc activity during monetary reward anticipation may distinguish women with and without BE.

Excitatory Projections from the Prefrontal Cortex to Nucleus Accumbens Core D1-MSNs and κ Opioid Receptor Modulate Itch-Related Scratching Behaviors.

Itch is an uncomfortable and complex sensation that elicits the desire to scratch. The nucleus accumbens (NAc) activity is important in driving sensation, motivation, and emotion. Excitatory afferents from the medial prefrontal cortex (mPFC), amygdala, and hippocampus are crucial in tuning the activity of dopamine receptor D1-expressing and D2-expressing medium spiny neurons (Drd1-MSN and Drd2-MSN) in the NAc. However, a cell-type and neural circuity-based mechanism of the NAc underlying acute itch remains unclear. We found that acute itch induced by compound 48/80 (C48/80) decreased the intrinsic membrane excitability in Drd1-MSNs, but not in Drd2-MSNs, in the NAc core of male mice. Chemogenetic activation of Drd1-MSNs alleviated C48/80-induced scratching behaviors but not itch-related anxiety-like behaviors. In addition, C48/80 enhanced the frequency of spontaneous EPSCs (sEPSCs) and reduced the paired-pulse ratio (PPR) of electrical stimulation-evoked EPSCs in Drd1-MSNs. Furthermore, C48/80 increased excitatory synaptic afferents to Drd1-MSNs from the mPFC, not from the basolateral amygdala (BLA) or ventral hippocampus (vHipp). Consistently, the intrinsic excitability of mPFC-NAc projecting pyramidal neurons was increased after C48/80 treatment. Chemogenetic inhibition of mPFC-NAc excitatory synaptic afferents relieved the scratching behaviors. Moreover, pharmacological activation of κ opioid receptor (KOR) in the NAc core suppressed C48/80-induced scratching behaviors, and the modulation of KOR activity in the NAc resulted in the changes of presynaptic excitatory inputs to Drd1-MSNs in C48/80-treated mice. Together, these results reveal the neural plasticity in synapses of NAc Drd1-MSNs from the mPFC underlying acute itch and indicate the modulatory role of the KOR in itch-related scratching behaviors.SIGNIFICANCE STATEMENT Itch stimuli cause strongly scratching desire and anxiety in patients. However, the related neural mechanisms remain largely unclear. In the present study, we demonstrated that the pruritogen compound 48/80 (C48/80) shapes the excitability of dopamine receptor D1-expressing medium spiny neurons (Drd1-MSNs) in the nucleus accumbens (NAc) core and the glutamatergic synaptic afferents from medial prefrontal cortex (mPFC) to these neurons. Chemogenetic activation of Drd1-MSNs or inhibition of mPFC-NAc excitatory synaptic afferents relieves the scratching behaviors. In addition, pharmacological activation of κ opioid receptor (KOR) in the NAc core alleviates C48/80-induced itch. Thus, targeting mPFC-NAc Drd1-MSNs or KOR may provide effective treatments for itch.

Methylphenidate Enhances Spontaneous Fluctuations in Reward and Cognitive Control Networks in Children With Attention-Deficit/Hyperactivity Disorder

BackgroundMethylphenidate, a first-line treatment for attention-deficit/hyperactivity disorder (ADHD), is thought to influence dopaminergic neurotransmission in the nucleus accumbens (NAc) and its associated brain circuitry, but this hypothesis has yet to be systematically tested. MethodsWe conducted a randomized, placebo-controlled, double-blind crossover trial including 27 children with ADHD. Children with ADHD were scanned twice with resting-state functional magnetic resonance imaging under methylphenidate and placebo conditions, along with assessment of sustained attention. We examined spontaneous neural activity in the NAc and the salience, frontoparietal, and default mode networks and their links to behavioral changes. Replicability of methylphenidate effects on spontaneous neural activity was examined in a second independent cohort. ResultsMethylphenidate increased spontaneous neural activity in the NAc and the salience and default mode networks. Methylphenidate-induced changes in spontaneous activity patterns in the default mode network were associated with improvements in intraindividual response variability during a sustained attention task. Critically, despite differences in clinical trial protocols and data acquisition parameters, the NAc and the salience and default mode networks showed replicable patterns of methylphenidate-induced changes in spontaneous activity across two independent cohorts. ConclusionsWe provide reproducible evidence demonstrating that methylphenidate enhances spontaneous neural activity in NAc and cognitive control networks in children with ADHD, resulting in more stable sustained attention. Our findings identified a novel neural mechanism underlying methylphenidate treatment in ADHD to inform the development of clinically useful biomarkers for evaluating treatment outcomes.

Chronic high-fat diet induces overeating and impairs synaptic transmission in feeding-related brain regions.

Obesity is linked to overeating, which can exacerbate unhealthy weight gain. However, the mechanisms for mediating such linkages are elusive. In the current study, we hypothesized that synaptic remodeling occurs in feeding-related brain regions of obese mice. To investigate this, we established a high-fat diet (HFD)-induced obese mouse model and observed that these mice consumed excessive calories. The effect of chronic HFD feeding on lipid droplet accumulation in different brain structures was also investigated. We found that lipid droplets accumulated on the ependyma of the third ventricle (3V), which is surrounded by key areas of the hypothalamus that are involved in feeding. Then, the spontaneous synaptic activity of miniature excitatory postsynaptic current (mEPSC) and miniature inhibitory postsynaptic current (mIPSC) was recorded in these hypothalamic areas. HFD induced a decreased amplitude of mEPSC in the arcuate nucleus (ARC) and the ventromedial hypothalamus (VMH), meanwhile, increased the frequency in the VMH. In addition, HFD reduced the frequency of mIPSC in the lateral hypothalamus (LH) and increased the amplitude of mIPSC in the paraventricular nucleus of the hypothalamus (PVH). Subsequently, we also measured the synaptic activity of nucleus accumbens (NAc) neurons, which play a vital role in the hedonic aspect of eating, and discovered that HFD diminished the frequency of both mEPSC and mIPSC in the NAc. These findings suggest that chronic HFD feeding leads to lipid accumulation and synaptic dysfunction in specific brain regions, which are associated with energy homeostasis and reward regulation, and these impairments may lead to the overeating of obesity.

The Association of Non–Drug-Related Pavlovian-to-Instrumental Transfer Effect in Nucleus Accumbens With Relapse in Alcohol Dependence: A Replication

BackgroundThe Pavlovian-to-instrumental transfer (PIT) paradigm measures the effects of Pavlovian conditioned cues on instrumental behavior in the laboratory. A previous study conducted by our research group observed activity in the left nucleus accumbens (NAcc) elicited by a non–drug-related PIT task across patients with alcohol dependence (AD) and healthy control subjects, and the left NAcc PIT effect differentiated patients who subsequently relapsed from those who remained abstinent. In this study, we aimed to examine whether such effects were present in a larger sample collected at a later date. MethodsA total of 129 recently detoxified patients with AD (21 females) and 74 healthy, age- and gender-matched control subjects (12 females) performing a PIT task during functional magnetic resonance imaging were examined. After task assessments, patients were followed for 6 months. Forty-seven patients relapsed and 37 remained abstinent. ResultsWe found a significant behavioral non–drug-related PIT effect and PIT-related activity in the NAcc across all participants. Moreover, subsequent relapsers showed stronger behavioral and left NAcc PIT effects than abstainers. These findings are consistent with our previous findings. ConclusionsBehavioral non–drug-related PIT and neural PIT correlates are associated with prospective relapse risk in AD. This study replicated previous findings and provides evidence for the clinical relevance of PIT mechanisms to treatment outcome in AD. The observed difference between prospective relapsers and abstainers in the NAcc PIT effect in our study is small overall. Future studies are needed to further elucidate the mechanisms and the possible modulators of neural PIT in relapse in AD.