Ventral striatum

High-penetrance mutations affecting mental health can involve genes ubiquitously expressed in the brain. Whether the specific patterns of dysfunctions result from ubiquitous circuit deficits or might reflect selective vulnerabilities of targetable subnetworks has remained unclear. Here, we determine how loss of ubiquitously expressed fragile X mental retardation protein (FMRP), the cause of fragile X syndrome, affects brain networks in Fmr1y/- mice. We find that in wild-type mice, area-specific knockout of FMRP in the adult mimics behavioral consequences of area-specific silencing...

The understanding of the pathophysiology of schizophrenia as well as the mechanisms of action of antipsychotic drugs remains a challenge for psychiatry. The demonstration of the therapeutic efficacy of several new atypical drugs targeting multiple different receptors apart from the classical dopamine D2 receptor as initially postulated unique antipsychotic target, complicated even more conceptualization efforts. Here we discuss results suggesting a main role of the islands of Calleja, still poorly studied GABAergic granule cell clusters in the ventral striatum, as cellular targets of several innovative atypical antipsychotics (clozapine, cariprazine and xanomeline/emraclidine) effective in treating also negative symptoms of schizophrenia...

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...

A growing literature links socioeconomic disadvantage and adversity to brain function, including disruptions in reward processing. Less research has examined exposure to community violence 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 exposure to community violence was associated with reward-related ventral striatum activation after accounting for familial factors associated with differences in reward-related activation (e...

Reinforcement learning (RL) engages a network of areas, including the orbitofrontal cortex (OFC), ventral striatum (VS), amygdala (AMY), and mediodorsal thalamus (MDt). This study examined RL mediated by gains and losses of symbolic reinforcers across this network. Monkeys learned to select options that led to gaining tokens and avoid options that led to losing tokens. Tokens were cashed out for juice rewards periodically. We found that task-relevant information was distributed across the network. However, examination of the way in which information was encoded differed, with VS showing increased responses to appetitive outcomes, OFC differentiating primary and symbolic reinforcers, and AMY responding to the salience of outcomes...

Humans frequently interact with agents whose intentions can fluctuate between competition and cooperation over time. It is unclear how the brain adapts to fluctuating intentions of others when the nature of the interactions (to cooperate or compete) is not explicitly and truthfully signaled. Here, we use model-based fMRI and a task in which participants thought they were playing with another player. In fact, they played with an algorithm that alternated without signaling between cooperative and competitive strategies...

Environmental cues, through Pavlovian learning, become conditioned stimuli that invigorate and guide animals toward acquisition of rewards. Dopamine neurons in the ventral tegmental area (VTA) and substantia nigra (SNC) are crucial for this process. Dopamine neurons are embedded in a reciprocally connected network with their striatal targets, the functional organization of which remains poorly understood. Here, we investigated how learning during optogenetic Pavlovian cue conditioning of VTA or SNC dopamine neurons directs cue-evoked behavior and shapes subregion-specific striatal dopamine dynamics...

INTRODUCTION: Alzheimer's disease (AD) requires novel therapeutic approaches due to limited efficacy of current treatments. AREAS COVERED: This article explores AD as a manifestation of neurocircuit dysfunction and evaluates deep brain stimulation (DBS) as a potential intervention. Focusing on fornix-targeted stimulation (DBS-f), the article summarizes safety, feasibility, and outcomes observed in phase 1/2 trials, highlighting findings such as cognitive improvement, increased metabolism, and hippocampal growth...

BACKGROUND: Altered neural haemodynamic activity during decision making and learning has been linked to the effects of inflammation on mood and motivated behaviours. So far, it has been reported that blunted mesolimbic dopamine reward signals are associated with inflammation-induced anhedonia and apathy. Nonetheless, it is still unclear whether inflammation impacts neural activity underpinning decision dynamics. The process of decision making involves integration of noisy evidence from the environment until a critical threshold of evidence is reached...

Multiple Sclerosis (MS) is an autoimmune disease affecting the central nervous system, characterised by neuroinflammation and neurodegeneration. Fatigue and depression are common, debilitating, and intertwined symptoms in people with relapsing-remitting MS (pwRRMS). An increased understanding of brain changes and mechanisms underlying fatigue and depression in RRMS could lead to more effective interventions and enhancement of quality of life. To elucidate the relationship between depression and fatigue and brain connectivity in pwRRMS we conducted a systematic review...

Motor learning is a prominent and extensively studied subject in rehabilitation following various types of neurological disorders. Motor repair and rehabilitation often extend over months and years post-injury with a slow pace of recovery, particularly affecting the fine movements of the distal extremities. This extended period can diminish the motivation and persistence of patients, a facet that has historically been overlooked in motor learning until recent years. Reward, including monetary compensation, social praise, video gaming, music, and virtual reality, is currently garnering heightened attention for its potential to enhance motor motivation and improve function...

BACKGROUND: Mild cognitive impairment (MCI), the prodromal stage of Alzheimer's disease, has two distinct subtypes: stable MCI (sMCI) and progressive MCI (pMCI). Early identification of the two subtypes has important clinical significance. OBJECTIVE: We aimed to compare the cortico-striatal functional connectivity (FC) differences between the two subtypes of MCI and enhance the accuracy of differential diagnosis between sMCI and pMCI. METHODS: We collected resting-state fMRI data from 31 pMCI patients, 41 sMCI patients, and 81 healthy controls...

Obsessive Compulsive Disorder (OCD) is a debilitating psychiatric disorder characterized by intrusive obsessive thoughts and compulsive behaviors. Multiple studies have shown association of polymorphisms in the SLC1A1 gene with OCD. The most common of these OCD-associated polymorphisms increases expression of the encoded protein, Excitatory Amino Acid Transporter 3 (EAAT3), a neuronal glutamate transporter. Previous work has shown that increased EAAT3 expression results in OCD-relevant behavioral phenotypes in rodent models...

Chronic, low-grade inflammation has been associated with motivational deficits in patients with major depression (MD). In turn, impaired motivation has been linked to poor quality of life across psychiatric disorders. We thus determined effects of the anti-inflammatory drug infliximab-a potent tumor necrosis factor (TNF) antagonist-on behavioral and neural measures of motivation in 42 medically stable, unmedicated MD patients with a C-reactive protein > 3mg/L. All patients underwent a double-blind, placebo-controlled, single-dose, randomized clinical trial with infliximab (5mg/kg) versus placebo...

Inhibition is implicated across virtually all human experiences. As a trade-off of being very efficient, this executive function is also prone to many errors. Rodent and computational studies show that midbrain regions play crucial roles during errors by sending dopaminergic learning signals to the basal ganglia for behavioural adjustment. However, the parallels between animal and human neural anatomy and function are not determined. We scanned human adults while they performed an fMRI inhibitory task requiring trial-and-error learning...

The ventral pallidum (VP) is a central hub in the reward circuitry with diverse projections that have different behavioral roles attributed mostly to the connectivity with the downstream target. However, different VP projections may represent, as in the striatum, separate neuronal populations that differ in more than just connectivity. In this study we performed in mice of both sexes a multimodal dissection of four major projections of the VP - to the lateral hypothalamus (VP→LH ), ventral tegmental area (VP→VTA ), lateral habenula (VP→LHb ) and mediodorsal thalamus (VP→MDT ) - with physiological, anatomical, genetic and behavioral tools...

The cortico-basal ganglia circuit mediates decision making. Here, we generated transgenic tools for adult zebrafish targeting specific subpopulations of the components of this circuit and utilized them to identify evolutionary homologs of the mammalian direct- and indirect-pathway striatal neurons, which respectively project to the homologs of the internal and external segment of the globus pallidus (dorsal entopeduncular nucleus [dEN] and lateral nucleus of the ventral telencephalic area [Vl]) as in mammals...

The analysis of RNA-Sec data from murine bulk tissue samples taken from five brain regions associated with behavior and stress response was conducted. The focus was on the most contrasting brain region-specific genes (BRSG) sets in terms of their expression rates. These BRSGs are identified as genes with a distinct outlying (high) expression rate in a specific region compared to others used in the study. The analysis suggested that BRSG sets form non-randomly connected compact gene networks, which correspond to the major neuron-mediated functional processes or pathways in each brain region...

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...

Dysfunction of the cortico-basal circuitry - including its primary input nucleus, the striatum - contributes to neuropsychiatric disorders, including autism and Tourette Syndrome (TS). These conditions show marked sexual dimorphism, occurring more often in males than in females. Regulatory interneurons, including cholinergic interneurons (CINs) and parvalbumin-expressing GABAergic fast spiking interneurons (FSIs), are implicated in human neuropsychiatric disorders such as TS, and ablation of these interneurons produces relevant behavioral pathology in male mice, but not in females...