Limbic System Research Papers - Academia.edu (original) (raw)

2025, Journal of the Neurological Sciences

The aim of this cross-sectional study was to investigate the frequency and factors associated with impulse control disorder (ICD) symptoms, including personality characteristics, in Czech youngonset Parkinson's disease (PD) patients. Subjects and methods: We examined 49 young-onset PD patients and 38 age-matched control subjects. ICD symptoms were identified using the South Oaks Gambling Screen and modified Minnesota Impulse Disorders Interview. Results: A higher prevalence of pathological gambling and hypersexuality was found in PD patients than in control subjects. A higher frequency of pathological gambling in our sample of young-onset PD patients was found in patients using dopamine agonists and in patients with dyskinesias lasting 5 or more years. The frequency of any ICD symptom was associated with coffee consumption, higher reported anxiety, and somatization. ICD symptoms were also related to personality characteristics in PD patients; specifically, patients who manifested any ICD symptom scored significantly higher on Self-assertive/ Antisocial and Reserved/Schizoid personality styles and pathological gambling was associated with lower reported Conscientiousness. Conclusion: Our results demonstrate that ICD presents a real problem in young-onset PD patients. Knowledge about the factors associated with ICD symptoms might be helpful in the proactive search for these pathological behaviours in this specific subgroup of PD patients.

2025, Surgical Neurology International

However, before we understand the current brain anatomical division, it is important to know the nature of scientific knowledge and how it was recorded in a socio-historical context. In antiquity, the search for knowledge of the brain anatomy was marked by several protagonists who, over the centuries, produced proposals to justify the clinical findings of the period and define the functioning of the organ. e purpose of this article is to report, through temporal ABSTRACT is article reports the evolution and consolidation of the knowledge of neuroanatomy through the analysis of its history. us, we propose to describe in a historical review to summarize the main theories and concepts that emerged throughout brain anatomy history and understand how the socio-historical context can reflect on the nature of scientific knowledge. erefore, among the diverse scientists, anatomists, doctors, and philosophers who were part of this history, there was a strong influence of the studies of Claudius Galen (AD 129-210),

2025, Social Cognitive and Affective Neuroscience

The neural underpinnings of repetitive behaviors (RBs) in autism spectrum disorders (ASDs), ranging from cognitive to motor characteristics, remain unknown. We assessed RB symptomatology in 50 ASD and 52 typically developing (TD) children and adolescents (ages 8-17 years), examining intrinsic functional connectivity (iFC) of corticostriatal circuitry, which is important for reward-based learning and integration of emotional, cognitive and motor processing, and considered impaired in ASDs. Connectivity analyses were performed for three functionally distinct striatal seeds (limbic, frontoparietal and motor). Functional connectivity with cortical regions of interest was assessed for corticostriatal circuit connectivity indices and ratios, testing the balance of connectivity between circuits. Results showed corticostriatal overconnectivity of limbic and frontoparietal seeds, but underconnectivity of motor seeds. Correlations with RBs were found for connectivity between the striatal motor seeds and cortical motor clusters from the whole-brain analysis, and for frontoparietal/limbic and motor/limbic connectivity ratios. Division of ASD participants into high (n ¼ 17) and low RB subgroups (n ¼ 19) showed reduced frontoparietal/limbic and motor/limbic circuit ratios for high RB compared to low RB and TD groups in the right hemisphere. Results suggest an association between RBs and an imbalance of corticostriatal iFC in ASD, being increased for limbic, but reduced for frontoparietal and motor circuits.

2025, Journal of Neural Transmission

Hypoxia, with or without hypercapnia, was induced by exposing rats to various gas mixtures for 45 min. In addition, some of the rats were exposed to electrical foot sho&s for 15 min. Rats were either untreated by drugs or received inhibitors of cate&olamine synthesis or metabolism. The adrenals and blood plasma were analyzed for dopa, and the adrenals for dopamine (DA) and adrenaline + noradrenaline. Adrenal DA was elevated by severe (6 % 02) but was slightly decreased by moderate hypoxia (8 % O~). The addition of 5 °/0 COs to 8 °/00.~ caused a moderate increase in DA. Foot shock stress raised adrenal DA under normoxia and the effect was markedly potentiated by moderate hypoxia. The accumulation of dopa in the adrenals of animals treated with 3-hydroxybenzylhydrazine (NSD 1015), an inhibitor of the aromatic amino acid decarboxylase, was closely correlated to the levels of adrenal DA in the corresponding experimental groups receiving no drug treatment, supporting the usefulness of adrenal DA as an indicator of catecholamine synthesis. In NSD 1015-treated rats dopa was found in the plasma and levels were increased atter foot shock stress. The data indicate that moderate hypoxia may retard the conversion of tyrosine to dopa, which may be related to the O~ requirement of this reaction. However, this effect can be overcome by neurogenic stimuli, presumably via an activation of adrenal tyrosine hydroxylase. Apparently such stimuli are induced by foot shock stress, severe hypoxia, hypercarbia and most markedly, by the combination of shock stress and hypoxia.

2025, American Journal of Psychiatry

Objective: Dopamine is an important mediator of the reinforcing effects of cocaine, and alterations in dopamine function might be involved in cocaine dependence. The goals of the present study were to characterize pre-and postsynaptic dopamine function in recently detoxified cocaine-dependent subjects. Specifically, dopamine response to an acute amphetamine challenge was assessed in striatal subregions in cocaine-dependent and healthy comparison participants using positron emission tomography (PET). Furthermore, the relationship between this dopamine response and the choice to self-administer cocaine in a laboratory model of relapse was investigated. Method: Twenty-four cocaine-depende nt participants an d 24 match ed healthy subjects underwent [ 11 C]raclopride scans under a baseline condition and following intravenous amphetamine administration (0.3 mg/kg).

2025, NeuroImage

In Parkinson's disease (PD) the demonstration of neuropathological disturbances in nigrostriatal and extranigral brain pathways using magnetic resonance imaging remains a challenge. Here, we applied a novel diffusionweighted imaging approach-track density imaging (TDI). Twenty-seven non-demented Parkinson's patients (mean disease duration: 5 years, mean score on the Hoehn & Yahr scale = 1.5) were compared with 26 elderly controls matched for age, sex, and education level. Track density images were created by sampling each subject's spatially normalized fiber tracks in 1 mm isotropic intervals and counting the fibers that passed through each voxel. Whole-brain voxel-based analysis was performed and significance was assessed with permutation testing. Statistically significant increases in track density were found in the Parkinson's patients, relative to controls. Clusters were distributed in disease-relevant areas including motor, cognitive, and limbic networks. From the lower medulla to the diencephalon and striatum, clusters encompassed the known location of the locus coeruleus and pedunculopontine nucleus in the pons, and from the substantia nigra up to medial aspects of the posterior putamen, bilaterally. The results identified in brainstem and nigrostriatal pathways show a large overlap with the known distribution of neuropathological changes in non-demented PD patients. Our results also support an early involvement of limbic and cognitive networks in Parkinson's disease.

2025, Research Square (Research Square)

Protocadherin-19 (PCDH19) developmental and epileptic encephalopathy causes an early-onset epilepsy syndrome with limbic seizures, typically occurring in clusters and variably associated with intellectual disability and a range of psychiatric disorders including hyperactive, obsessive-compulsive and autistic features. Previous quantitative neuroimaging studies revealed abnormal cortical areas in the limbic formation (parahippocampal and fusiform gyri) and underlying white-matter bers. In this study, we adopted morphometric, network-based and multivariate statistical methods to examine the cortex and substructure of the hippocampus and amygdala in a cohort of 20 PCDH19-mutated patients and evaluated the relation between structural patterns and clinical variables at individual level. We also correlated morphometric alterations with known patterns of PCDH19 expression levels. We found patients to exhibit high-signi cant reductions of cortical surface area at a whole-brain level (left/right p value =0.045/0.084), and particularly in the regions of the limbic network (left/right parahippocampal gyri p value =0.230/0.016; left/right entorhinal gyri p value =0.002/0.327), and bilateral atrophy of several subunits of the amygdala and hippocampus, particularly in the CA regions (head of the left CA3 p value =0.002; body of the right CA3 p value =0.004), and differences in the shape of hippocampal structures. More severe psychiatric comorbidities correlated with more signi cant altered patterns, with the entorhinal gyrus (p value =0.013) and body of hippocampus (p value =0.048) being more severely affected. Morphometric alterations correlated signi cantly with the known expression patterns of PCDH19 (r value =-0.26, p value =0.034). PCDH19 encephalopathy represents a model of genetically determined neural network based neuropsychiatric disease in which quantitative MRI-based ndings correlate with the severity of clinical manifestations and had have a potential predictive value if analyzed early.

2025, American Journal of Neuroradiology

Tract-based analysis can be used to investigate required tracts extracted from other fiber tracts. However, the fractional anisotropy (FA) threshold influences tractography analysis. The current study evaluated the influence of the FA threshold in measuring diffusion tensor parameters for tract-based analysis of the uncinate fasciculus in subjects with Alzheimer disease (AD). MATERIALS AND METHODS: Subjects included 30 patients with AD and 10 healthy controls. We acquired tractographies of the uncinate fasciculus by using different FA thresholds. We measured mean FA and the apparent diffusion coefficient (ADC) along the uncinate fasciculus for different FA thresholds and evaluated the correlation between diffusion tensor parameters (FA, ADC) and the Mini-Mental State Examination (MMSE) scores. The uncinate fasciculus showed lower mean FA and higher mean ADC values in cases with more severe AD. A higher FA threshold led to a lower mean ADC value and a higher mean FA value along the uncinate fasciculus, whereas the relative order of measured values according to the severity of AD was not influenced by the FA threshold. An FA threshold of 0.2 showed higher correlation between mean ADC values and MMSE scores. FA thresholds of 0.15 and 0.20 showed higher correlation between mean FA values and MMSE scores. CONCLUSIONS: Appropriate selection of the FA threshold leads to higher correlation between diffusion tensor parameters and the severity of AD. For tract-based analysis of degenerative diseases such as AD, appropriate selection of the FA threshold for tractography is important.

2025, American Journal of Neuroradiology

2025, Biological Psychiatry

Background: A decrease in dopamine type 2 receptors (D 2 ) and mesolimbic dopamine transmission predisposes animals to consume alcohol. This study measured D 2 receptors and dopamine transmission in human alcohol-dependent (AD) subjects using positron emission tomography (PET) and [ 11 C]raclopride. Methods: Fifteen AD and 15 healthy control (HC) subjects were scanned before and after a psychostimulant challenge (amphetamine .3 mg/kg intravenous). The outcome measures for baseline D 2 receptor availability were binding potential (BP) and the equilibrium partition coefficient (V 3 Љ). Amphetamine-induced [ 11 C]raclopride displacement was measured as the difference in V 3 Љ between the two scans. Results: [ 11 C]raclopride BP was significantly reduced by 16.6% in the limbic striatum, 19.2% in the associative striatum, and 21.3% in the sensorimotor striatum in AD subjects compared with HC. The alcohol-dependent subjects showed a blunting of amphetamineinduced dopamine release in the limbic striatum: [ 11 C]raclopride displacement was Ϫ5.2% Ϯ 3.6% in AD subjects compared with Ϫ13.0% Ϯ 8.8% in HC. However, no significant difference in [ 11 C]raclopride displacement was seen in the associative (Ϫ4.6% Ϯ 5.8% in AD subjects vs. Ϫ6.7 Ϯ 5.4% in HC) and sensorimotor (Ϫ12.3% Ϯ 7.3% in AD subjects vs. Ϫ13.7 Ϯ 7.5% in HC) subdivisions of the striatum between the two groups. Conclusions: Alcohol dependence was associated with a decrease in D 2 receptors in each striatal subdivision, whereas amphetamineinduced dopamine release was reduced in the limbic striatum only.

2025, Acta Neurochirurgica

Clinical manifestations, findings, management and outcome of a series of 177 cases with tumours of the limbic and paralimbic systems are presented. There was no operative mortality. Postoperatively 95% of them had no or only minor neurological deficits. Most of them were able to resume work. Pre-operativety 77% of the patients had epilepsy, but 84% became seizure-free after turnout removal. All 77 cases with malignant tumours died within 1-5 years. In the past many neurosurgeons were reluctant to attempt complete tumour removal in these areas. This series demonstrates the efficacy of highly skilled microneurosurgery.

2025, Physiology & Behavior

Alcohol possesses complex sensory attributes that are first detected by the body via sensory receptors and afferent fibers that promptly transmit signals to brain areas involved in mediating ingestive motivation, reinforcement, and addictive behavior. Given that the chemosensory cues accompanying alcohol consumption are among the most intimate, consistent, and immediate predictors of alcohol's postabsorptive effects, with experience these stimuli also gain powerful associative incentive value to elicit craving and related physiologic changes, maintenance of ongoing alcohol use, and reinstatement of drug seeking after periods of abstinence. Despite the above, preclinical research has traditionally dichotomized alcohol's taste and postingestive influences as independent regulators of motivation to drink. The present review summarizes current evidence regarding alcohol's ability to directly activate peripheral and central oral chemosensory circuits, relevance for intake of the drug, and provides a framework for moving beyond a dissociation between the sensory and postabsorptive effects of alcohol to understand their neurobiological integration and significance for alcohol addiction.

2025, Neuropsychopharmacology

Olfactory dysfunction in patients with schizophrenia has been a topic of increasing interest, with deficits in odor identification, detection threshold sensitivity, discrimination, and memory being reported. Despite increasing knowledge, controversy has existed about possible differential deficits among olfactory tests as well as the influences of gender, smoking, and medication status on olfactory measures. To help elucidate some of this controversy, we conducted a qualitative and quantitative (meta-analytic) review of the English language literature on olfaction in schizophrenia. Moderator variables such as gender, medication status, and smoking history were also examined. Results indicated that substantial olfactory deficits, across all domains, are observed in patients with schizophrenia. No differential deficits were observed across domains of odor identification, detection threshold sensitivity, discrimination, and memory. The influences of gender, medication status, and smoking on effect sizes were not significant across studies. This supports the hypothesis of primary dysfunction in the olfactory system that is regulated by brain regions where structural and functional abnormalities have also been reported in neuroimaging studies.

2025, Physiology & Behavior

The partial reinforcement extinction effect in rats with medial septal lesions. PHYSIOL. BEHAV. 8 (3) 491496, 1972.--Rats, which had sustained electrolytic lesions in the medial septal area (disrupting hippocampal theta rhythms) or sham operations either before acquisition or between acquisition and extinction, were given either 50 % random partial reinforcement (PR) or continuous reinforcement (CRF) during acquisition of a running response for water reward in a straight alley. The magnitude of the partial reinforcement extinction effect (PREE) was reduced in animals lesioned prior to acquisition and probably also in animals lesioned between acquisition and extinction. This reduction in the PREE was about equally due to an increase in resistance to extinction after CRF and a decrease in resistance to extinction after PR. The septal lesions disrupted vibrissae movement and also caused PR animals to be particularly disturbed by a change of environment during acquisition.

2025, The Journal of Clinical Psychiatry

2025, Frontiers in Pharmacology

The studies performed in laboratory animals and psychiatric patients suggest a possible role of limbic system-associated membrane protein (LAMP) in the mechanisms of psychiatric disorders. Stressful manipulations and genetic invalidation have revealed a role of the Lsamp gene in the regulation of anxiety in rodents. Besides that, Lsamp-deficient mice display reduced aggressiveness and impaired adaptation in novel and stressful environments. The behavioral effects of amphetamine were blunted in genetically modified mice. Recent pharmacological and biochemical studies point toward altered function of GABA-, 5-hydroxytryptamine-, and dopaminergic systems in Lsamp-deficient mice. Moreover, we found an association between the gene polymorphisms of LSAMP and major depressive disorder (MDD). Patients suffering from MDD had significantly increased ratio between risk and protective haplotypes of the LSAMP gene compared to healthy volunteers. However, the impact of these haplotypes for the function of LAMP is not clear and remains to be elucidated in future studies.

2025, Neuropsychopharmacology

Serotonin (5-HT) is thought to play an important role in the regulation of behavioral inhibition. Studies manipulating 5-HT function in the rodent brain indicate that 5-HT receptors regulate distinct forms of impulsive behavior, including impulsive responding in the 5-choice serial reaction time task (5CSRTT). The present study investigates the loci of effects mediated by 5-HT 2A and 5-HT 2C receptors in attention and inhibitory response control using microinfusions targeted at the nucleus accumbens (NAc), prelimbic cortex (PL) and infralimbic cortex (IL). Rats were implanted with bilateral guide cannulas and received infusions of the selective 5-HT 2A receptor antagonist M100907 (0.1 and 0.3 mg) or selective 5-HT 2C receptor antagonist SB242084 (0.1 and 0.5 mg) immediately prior to testing. The results show that intra-NAc infusions of M100907 significantly decrease impulsive responding on the 5CSRTT and at the highest dose increased omissions as well. By contrast, infusions of SB242084 into the NAc selectively and dose-dependently increased impulsivity. Neither M100907 nor SB242084 significantly altered impulsive responding following either intra-PL or intra-IL administration. However, SB242084 significantly decreased omissions following intra-PL administration (0.5 mg only). These data reveal opposing effects on impulsivity following 5-HT 2A and 5-HT 2C blockade in the NAc. Our results suggest that the NAc, but not the PL or IL, is implicated in the mediation of the effects of M100907 and SB242084 on inhibitory response control during baseline 5CSRTT performance.

2025, Journal of Neurology

We present a PD patient in whom dopamine agonists awoke a hidden creativity that led to a gradual increase in painting productivity evolving to a disruptive impulsive behaviour that shared many features with punding. A dramatic change in painting style related to a more emotional experience during the process of creation developed after treatment onset. This case suggests that changes in creativity in PD seem to be related to dopaminergic imbalance in the limbic system.

2025, Ódor Antal

The Emotion–Stress–Behavior (ESV) model is a new psychobiological systems theory framework that interprets human behavior as a dynamic interaction of emotional states, stress responses, and behavioral patterns. Its central thesis is that activity in the limbic system (amygdala, hippocampus, hypothalamus) plays a key regulatory role in these components, and that imbalances lead to psychological disorders, such as addictions, chronic stress, or ambivalence. The ESV model aims to integrate insights from different psychological schools (psychoanalysis, behaviorism, cognitive therapy) into a unified theoretical and practical tool for understanding and enhancing mental functioning. Its practical applications include identifying and addressing psychological compulsion loops, addiction mechanisms, and ambivalence. The model emphasizes the importance of self-awareness and self-regulation as core therapeutic goals.

2025, Brain Research

Synaptic responses of commissurally activated rat subicular and entorhinal neurons were studied intracellularly in vivo by stimulating the contralateral dentate gyrus. The most prominent synaptic responses in both subicular and entorhinal neurons were inhibitory postsynaptic potentials (IPSPs). IPSPs were generated in combination with antidromic spikes and/or excitatory postsynaptic potentials (EPSPs) and orthodromic spikes. No dependency between any two response types was found. Commissurally projecting subicular neurons (identified by the presence of antidromic spikes evoked by contralateral stimulation) were found, extending previous anatomical studies. Commissurally projecting entorhinal neurons were found in layer II, confirming previous anatomical studies. Positive correlations between antidromic spike latency and depth of recording sites supported the interpretation that axons projected along the fiber bundles of the hippocampal commissures and angular bundle to distribute to their targets. Possible circuits that could have mediated the excitatory and inhibitory responses of these retrohippocampal neurons are considered.

2025, Brain Research

2025, Human Brain Mapping

Background: Recent studies have shown that response inhibition is impaired in patients with obsessive-compulsive disorder and their unaffected siblings, suggesting that these deficits may be considered a cognitive endophenotype of obsessive-compulsive disorder. Structural and functional neural correlates of altered response inhibition have been identified in patients and siblings. This study aims to examine the functional integrity of the response inhibition network in patients with obsessive-compulsive disorder and their unaffected siblings. Methods: Forty-one unmedicated patients with obsessive-compulsive disorder, 17 of their unaffected siblings and 37 healthy controls performed a stop signal task during functional magnetic resonance imaging. Psycho-physiological interaction analysis was used to examine functional connectivity between the following regions of interest: the bilateral inferior frontal gyri, presupplementary motor area, subthalamic nuclei, inferior parietal lobes, anterior cingulate cortex, and amygdala. We then used dynamic causal modeling to investigate the directionality of the networks involved. Results: Patients, and to a lesser extent also their unaffected siblings, show Additional Supporting Information may be found in the online version of this article.

2025, Neurotoxicity Research

Prenatal stress exerts a strong impact on fetal brain development in rats impairing adaptation to stressful conditions, subsequent vulnerability to anxiety, altered sexual function, and enhanced propensity to self-administer drugs. Most of these alterations have been attributed to changes in the neurotransmitter dopamine (DA). In humans; dysfunction of dopaminergic system is associated with development of several neurological disorders, such as Parkinson disease, schizophrenia, attention-deficit hyperactivity disorder, and depression. Evidences provided by animal research, as well as retrospective studies in humans, pointed out that exposure to adverse events in early life can alter adult behaviors and neurochemical indicators of midbrain DA activity, suggesting that the development of the DA system is sensitive to disruption by exposure to early stressors. The purpose of this article is to provide a general overview of published studies and our own study related to the effect of prenatal insults on the development of DA metabolism and biology, focusing mainly in articles involving prenatal-restraint stress protocols in rats. We will also attempt to make a correlation between theses alterations and DA-related pathological processes in humans.

2025, Addictive Behaviors

Link between DRD4 polymorphism and comorbid marijuana use and depression is examined. • Those with DRD4 risk allele (≥7R/≥7R) are at 2.5 times greater risk of comorbidity. • This study is the first to link DRD4 to comorbid high marijuana... more

2025, PLOS ONE

The goal of this study was to assess the relationship between Ab deposition and white matter pathology (i.e., white matter hyperintensities, WMH) on microstructural integrity of the white matter. Fifty-seven participants (mean age: 7867 years) from an ongoing multi-site research program who spanned the spectrum of normal to mild cognitive impairment (Clinical dementia rating 0-0.5) and low to high risk factors for arteriosclerosis and WMH pathology (defined as WMH volume .0.5% total intracranial volume) were assessed with positron emission tomography (PET) with Pittsburg compound B (PiB) and magnetic resonance and diffusion tensor imaging (DTI). Multivariate analysis of covariance were used to investigate the relationship between Ab deposition and WMH pathology on fractional anisotropy (FA) from 9 tracts of interest (i.e., corona radiata, internal capsule, cingulum, parahippocampal white matter, corpus callosum, superior longitudinal, superior and inferior front-occipital fasciculi, and fornix). WMH pathology was associated with reduced FA in projection (i.e., internal capsule and corona radiate) and association (i.e., superior longitudinal, superior and inferior fronto-occipital fasciculi) fiber tracts. Ab deposition (i.e., PiB positivity) was associated with reduced FA in the fornix and splenium of the corpus callosum. There were interactions between PiB and WMH pathology in the internal capsule and parahippocampal white matter, where Ab deposition reduced FA more among subjects with WMH pathology than those without. However, accounting for apoE e4 genotype rendered these interactions insignificant. Although this finding suggests that apoE4 may increase amyloid deposition, both in the parenchyma (resulting in PiB positivity) and in blood vessels (resulting in amyloid angiopathy and WMH pathology), and that these two factors together may be associated with compromised white matter microstructural integrity in multiple brain regions, additional studies with a longitudinal design will be necessary to resolve this issue.

2025, Psychoneuroendocrinology

Behavioral adaptation to an anxiogenic environment involves the activity of various interconnected limbic regions, such as the amygdala, hippocampus and prefrontal cortex. Prenatal stress (PS) in rats affects the ability to cope with environmental challenges and alters brain plasticity, leading to long-lasting behavioral and neurobiological alterations. We examined in PS and control animals whether behavioral reactivity was correlated to neuronal activation by assessing Fos protein expression in limbic regions of rats exposed to a low or high anxiogenic environment (the closed and open arms of an elevated plus maze, respectively). A negative correlation was found between behavioral and neuronal activation, with a lower behavioral reactivity and a higher neuronal response observed in rats exposed to the more anxiogenic environment (the open arm) with respect to the less anxiogenic environment (the closed arm). Interestingly, the variation in the neurobehavioral response between the two arms of the maze was less pronounced in rats that had been subjected to PS. This study provides a remarkable example of how

2025, Neuroscience Research

Neuropeptide B/W receptor 1 (NPBWR1) is a G-protein coupled receptor, which was initially reported as an orphan receptor, and whose ligands were identified by this and other groups in 2002 and 2003. To examine the physiological roles of NPBWR1, we examined phenotype of Npbwr1 2/2 mice. When presented with an intruder mouse, Npbwr1 2/2 mice showed impulsive contact with the strange mice, produced more intense approaches toward them, and had longer contact and chasing time along with greater and sustained elevation of heart rate and blood pressure compared to wild type mice. Npbwr1 2/2 mice also showed increased autonomic and neuroendocrine responses to physical stress, suggesting that impairment of NPBWR1 leads to stress vulnerability. We also observed that these mice show abnormality in the contextual fear conditioning test. These data suggest that NPBWR1 plays a critical role in limbic system function and stress responses. Histological and electrophysiological studies showed that NPBWR1 acts as an inhibitory regulator on a subpopulation of GABAergic neurons in the lateral division of the CeA and terminates stress responses. These findings suggest important roles of NPBWR1 in regulating amygdala function during physical and social stress.

2025, Psychoneuroendocrinology

In view of the greater prevalence of depression and anxiety disorders in women than in men, functional magnetic resonance imaging (fMRI) studies have examined sex-differences in brain activations during emotion processing. Comparatively, sex-differences in brain connectivity received little attention, despite evidence for important fronto-limbic connections during emotion processing across sexes. Here, we investigated sex-differences in fronto-limbic connectivity during negative emotion processing. Forty-six healthy individuals (25 women, 21 men) viewed negative, positive and neutral images during an fMRI session. Effective connectivity between significantly activated regions was examined using Granger causality and psychophysical interaction analyses. Sex steroid hormones and feminine-masculine traits were also measured. Subjective ratings of negative emotional images were higher in women than in men. Across sexes, significant activations were observed in the dorso-medial prefrontal cortex (dmPFC) and the right amygdala. Granger connectivity from right amygdala was significantly greater than that from dmPFC during the &amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;high negative&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; condition, an effect driven by men. Magnitude of this effect correlated negatively with highly negative image ratings and feminine traits and positively with testosterone levels. These results highlight critical sex differences in brain connectivity during negative emotion processing and point to the fact that both biological (sex steroid hormones) and psychosocial (gender role and identity) variables contribute to them. As the dmPFC is involved in social cognition and action planning, and the amygdala-in threat detection, the connectivity results suggest that compared to women, men have a more evaluative, rather than purely affective, brain response during negative emotion processing.

2025, Brain connectivity

Background: Major depressive disorder (MDD) is a mood disorder associated with disruptions in emotional control. Previous studies have investigated abnormal regional activity and connectivity within the fronto-limbic circuit. However, condition-specific connectivity changes and their association with the pathophysiology of MDD remain unexplored. This study investigated effective connectivity in the fronto-limbic circuit induced by negative emotional processing from patients with MDD. Methods: Thirty-four unmedicated female patients with MDD and 28 healthy participants underwent event-related functional magnetic resonance imaging at 7T while viewing emotionally negative and neutral images. Brain regions whose dynamics are driven by experimental conditions were identified by using statistical parametric mapping. Effective connectivity among regions of interest was then estimated by using dynamic causal modeling. Results: Patients with MDD had lower activation of the orbitofrontal cortex (OFC) and higher activation of the parahippocampal gyrus (PHG) than healthy controls (HC). In association with these regional changes, we found that patients with MDD did not have significant modulatory connections from the primary visual cortex (V1) to OFC, whereas those connections of HC were significantly positively modulated during negative emotional processing. Regarding the PHG activity, patients with MDD had greater modulatory connection from the V1, but reduced negative modulatory connection from the OFC, compared with healthy participants. Conclusions: These results imply that disrupted effective connectivity among regions of the OFC, PHG, and V1 may be closely associated with the impaired regulation of negative emotional processing in the female patients with MDD.

2025, Brain Connectivity

2025, Frontiers in Neural Circuits

Chronic stress impairs cognitive function, namely on tasks that rely on the integrity of cortico-limbic networks. To unravel the functional impact of progressive stress in cortico-limbic networks we measured neural activity and spectral coherences between the ventral hippocampus (vHIP) and the medial prefrontal cortex (mPFC) in rats subjected to short term stress (STS) and chronic unpredictable stress (CUS). CUS exposure consistently disrupted the spectral coherence between both areas for a wide range of frequencies, whereas STS exposure failed to trigger such effect. The chronic stress-induced coherence decrease correlated inversely with the vHIP power spectrum, but not with the mPFC power spectrum, which supports the view that hippocampal dysfunction is the primary event after stress exposure. Importantly, we additionally show that the variations in vHIP-to-mPFC coherence and power spectrum in the vHIP correlated with stress-induced behavioral deficits in a spatial reference memory task. Altogether, these findings result in an innovative readout to measure, and follow, the functional events that underlie the stress-induced reference memory impairments.

2025, Archives of General Psychiatry

Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder of childhood. There is considerable evidence that brain dopamine is involved in ADHD, but it is unclear whether dopamine activity is enhanced or depressed. Objective: To test the hypotheses that striatal dopamine activity is depressed in ADHD and that this contributes to symptoms of inattention. Design: Clinical (ADHD adult) and comparison (healthy control) subjects were scanned with positron emission tomography and raclopride labeled with carbon 11 (D 2 /D 3 receptor radioligand sensitive to competition with endogenous dopamine) after placebo and after intravenous methylphenidate hydrochloride (stimulant that increases extracellular dopamine by blocking dopamine transporters). The difference in [ 11 C]raclopride's specific binding between placebo and methylphenidate was used as marker of dopamine release. Symptoms were quantified using the Conners Adult ADHD Rating Scales.

2025, JAMA

Context Loss of the capacity to experience pleasure (anhedonia) is a core clinical feature of schizophrenia. Although functional imaging techniques have been successful in identifying the neural basis of cognitive impairments in schizophrenia, no attempts to date have been made to investigate neural systems underlying emotional disturbances. Objective To study the neural basis of emotional processing in schizophrenia by exploring the pattern of brain responses to olfactory stimuli in patients and healthy volunteers.

2025, The Journal of Neuroscience

Neonatal, bilateral lesion of the ventral hippocampus (VH) in rats recently has been proposed as a model of schizophrenia because these animals show postpubertal hypersensitivity to stress and to dopamine (DA) agonists that can be reversed by neuroleptic treatment. In search of the mechanisms of postpubertal emergence of hyperdopaminergic behavior in this model, we investigated developmental expressions of DA D1, D2, and D3 receptors in various striatal and limbic subregions of rats that had received bilateral ibotenic acid lesion of the VH at postnatal day 7 (PD7). D-Amphetamine-, apomorphine-, and stress-induced changes in locomotor activity were measured and, in accordance with previous reports, we observed an increased locomotor activity at PD56 in the hippocampal-lesioned group. The expression of DA D1, D2, and D3 receptors was then estimated in these rats by ligand autoradiography at PD41 and PD62. We observed that the levels of DA D3 receptors, as measured by tritiated 7-hydr...

2025, Personality Disorders: Theory, Research, and Treatment

Although psychopathy has consistently been shown to distribute as a dimension, all prior studies have examined behavioral indicators that may be phenotypically distant from core biological correlates of the syndrome. The current studies attempted to determine whether biomarkers from a high-resolution structural magnetic resonance imaging (MRI) scan of selected limbic and paralimbic structures identified the latent structure of psychopathy as continuous. Participants were 254 adult male medium/maximum security inmates (Study 1) and 191 adolescent male maximum security inmates (Study 2) who volunteered to undergo research MRI scans. Indicators of gray matter concentration (GMC) in the adult sample and of gray matter volume (GMV) in the adolescent sample were subjected to taxometric analysis using three non-redundant taxometric procedures: mean above minus below a cut (MAMBAC), maximum covariance (MAXCOV), and latent-mode factor analysis (L-Mode). Evidence of continuous latent structure was found across samples (adults, adolescents), measures (GMV, GMC, Psychopathy Checklist-Revised [PCL-R], Psychopathy Checklist: Youth Version [PCL: YV]) and procedures (MAMBAC, MAXCOV, L-Mode). Continuous latent structure was also noted when biomarker (GMV, GMC) and behavioral (PCL) indicators were included in the same analysis. The current results support the view that psychopathy is a quantitative construct on which people differ in degree ("more of" or "less of") rather than a qualitative construct that assigns people to distinct categories ("either or"). Continued development of the psychopathy construct may depend on our ability to identify, understand, and make effective use of its apparent continuous latent structure.

2025, Psychiatry Research: Neuroimaging

The basal ganglia are recognized as putative mediators of certain cognitive and behavioral symptoms of major depression. Moreover, patients with basal ganglia lesions have repeatedly exhibited significant affective symptomatology, including apathy, depressive mood, and psychosis. Using high resolution, axial T, intermediate magnetic resonance images, and a systematic sampling stereologic method, we assessed putamen nuclei volumes in 41 patients with major depression (DSM-III) and 44 healthy volunteer controls of similar age. Depressed patients had significantly smaller putamen nuclei compared with controls. Age was negatively correlated with putamen size in both groups. These results are the first demonstration of diminished putamen volumes in depression and further support a role for basal ganglia structures in the etiopathogenesis of depression.

2025, Network Neuroscience

Beyond the established effects of subthalamic nucleus deep brain stimulation (STN-DBS) in reducing motor symptoms in Parkinson’s disease, recent evidence has highlighted the effect on non-motor symptoms. However, the impact of STN-DBS on disseminated networks remains unclear. This study aimed to perform a quantitative evaluation of network-specific modulation induced by STN-DBS using Leading Eigenvector Dynamics Analysis (LEiDA). We calculated the occupancy of resting-state networks (RSNs) in functional MRI data from 10 patients with Parkinson’s disease implanted with STN-DBS and statistically compared between ON and OFF conditions. STN-DBS was found to specifically modulate the occupancy of networks overlapping with limbic RSNs. STN-DBS significantly increased the occupancy of an orbitofrontal limbic subsystem with respect to both DBS OFF (p = 0.0057) and 49 age-matched healthy controls (p = 0.0033). Occupancy of a diffuse limbic RSN was increased with STN-DBS OFF when compared wit...

2025, Neurology

Objective: To investigate functional connectivity between the default mode network (DMN) and other networks in disorders of consciousness. We analyzed MRI data from 11 patients in a vegetative state and 7 patients in a minimally conscious state along with age-and sex-matched healthy control subjects. MRI data analysis included nonlinear spatial normalization to compensate for disease-related anatomical distortions. We studied brain connectivity data from resting-state MRI temporal series, combining noninferential (independent component analysis) and inferential (seed-based general linear model) methods. In DMN hypoconnectivity conditions, a patient's DMN functional connectivity shifts and paradoxically increases in limbic structures, including the orbitofrontal cortex, insula, hypothalamus, and the ventral tegmental area. Conclusions: Concurrently with DMN hypoconnectivity, we report limbic hyperconnectivity in patients in vegetative and minimally conscious states. This hyperconnectivity may reflect the persistent engagement of residual neural activity in self-reinforcing neural loops, which, in turn, could disrupt normal patterns of connectivity. Neurology â 2013;81:1417-1424 GLOSSARY ACC 5 anterior cingulate cortex; DMN 5 default mode network; GLM 5 general linear model; ICA 5 independent component analysis; MCS 5 minimally conscious state; PCC 5 posterior cingulate cortex; ROI 5 region of interest; VS 5 vegetative state; VTA 5 ventral tegmental area.

2025, Frontiers in Neural Circuits

2025

In the field of communication studies the preeminent forms of explanation of human behavior have been the social and psychological, but biological :origins may be as important to understanding human communication as are social origins. Communication research suggests a biological basis for certain patterns of adult interaction. Although these patterns of interaction do not exhaust all or even the most important aspects of huran interaction, there is ample evidence that they are functionay important to the adult and to the infant-adult relationship. The patterns of interaction may wen be the mechanism for defining caretaker-infant bonding. An appreciation of the intrica4.e relationship between social and biological behavior and the common biological bases of human communication is one result of looking for the biological sources of ultimate causation for patterns of human communication. The emphasis on learning, culture, and socialization, the emphasis on higher-level cognitive processes and on highly deliberate linguistic exchanges have had a central place in the study of human communication. But it is time to recognize that part of what makes communication human is its biological commonness across peoples and even species. (One hundred-and-two references are attached.) (RS)

2025, "Zenodo Repository"

The amygdala, a key structure in the limbic system of the human brain, is responsible for processing emotions such as fear, anger, and the need for survival. Throughout evolutionary history, this part of the brain has played an important role in maintaining human life, but today in modern societies, its constant presence in a state of alert and defense has led to consequences such as anxiety, unhealthy competition, and violence. This article examines the role of the amygdala with an interdisciplinary approach; from a scientific perspective, its function in the nervous system is examined; from a philosophical perspective, issues such as ownership, territory, and will are analyzed; and from a spiritual perspective, the possibility of humans freeing themselves from the dominance of fear and moving toward higher consciousness is analyzed. Finally, strategies are presented to balance the functioning of the amygdala and strengthen the prefrontal cortex so that humans can achieve peace, empathy, and self-knowledge.

2025, The Journal of neuroscience : the official journal of the Society for Neuroscience

Chronic pain attenuates midbrain dopamine (DA) transmission, as evidenced by a decrease in opioid-evoked DA release in the ventral striatum, suggesting that the occurrence of chronic pain impairs reward-related behaviors. However, mechanisms by which pain modifies DA transmission remain elusive. Using in vivo microdialysis and microinjection of drugs into the mesolimbic DA system, we demonstrate in mice and rats that microglial activation in the VTA compromises not only opioid-evoked release of DA, but also other DA-stimulating drugs, such as cocaine. Our data show that loss of stimulated extracellular DA is due to impaired chloride homeostasis in midbrain GABAergic interneurons. Treatment with minocycline or interfering with BDNF signaling restored chloride transport within these neurons and recovered DA-dependent reward behavior. Our findings demonstrate that a peripheral nerve injury causes activated microglia within reward circuitry that result in disruption of dopaminergic sign...

2025, Neuro endocrinology letters

The goal of the study was an evaluation of differences in working memory effectiveness between patients with type 1 and type 2DM. It was also attempted to ascertain whether the level of diabetes control is associated with working memory effectiveness. 62 subjects were enrolled into the study. All patients were divided into two groups: patients with type 1DM (n=31) and with type 2DM (n=31). The Trail Making Test (TMT) and the Stroop Test were used for evaluation of working memory effectiveness. Diabetes control indicators included: glycated haemoglobin (HbA1C) level, total cholesterol concentration, HDL and LDL cholesterol concentration and body mass index (BMI). The patients with type 1DM obtained a significantly lower time in the execution of TMT, part B (p=0.01) and of RCNb (p=0.01) and NCWd (p=0.01) versions of the Stroop Test, while making significantly less errors in NCWd version (p=0.01). Significant correlations were demonstrated between BMI values and the rate of execution o...

2025, Annals of neurology

To determine whether the frequency of TDP-43 deposition in Alzheimer's disease (AD) differs across pathologically defined AD subtypes (Hippocampal sparing [HpSp]; Typical and Limbic), and to further examine the relationship between TDP-43, pathological subtype, and clinical features in AD. We identified all cases with pathologically-confirmed AD (NIA-Reagan intermediate-high probability, Braak stage IV-VI) independent of cognitive status (n=188). Neurofibrillary tangle counts were performed using thioflavin-S microscopy in hippocampus and three neocortical regions, and all cases were subtyped: HpSp AD Pathology (n=19); Typical AD Pathology (n=136); Limbic AD Pathology (n=33). TDP-43 immunoreactivity was performed in multiple brain regions to assess for the presence of TDP-43 and TDP-43 stage. All cases were clinically sub-classified at presentation as Amnestic AD Dementia versus Atypical AD Dementia. Statistical analysis was performed using linear and penalized logistic regressi...

2025, Journal of Neuroscience Research

The midbrain central gray (periaqueductal gray; PAG) mediates defensive behaviors and is implicated in the rewarding effects of opiate drugs. Projections from the PAG to the ventral tegmental area (VTA) suggest that this region might also regulate behaviors involving motivation and cognition. However, studies have not yet examined the morphological features of PAG axons in the VTA or whether they synapse onto dopamine (DA) or GABA neurons. In this study, we injected anterograde tracers into the rat PAG and used immunoperoxidase to visualize the projections to the VTA. Immunogold-silver labeling for tyrosine hydroxylase (TH) or GABA was then used to identify the phenotype of innervated cells. Electron microscopic examination of the VTA revealed axons labeled anterogradely from the PAG, including myelinated and unmyelinated fibers and axon varicosities, some of which formed identifiable synapses. Approximately 55% of these synaptic contacts were of the symmetric (presumably inhibitory) type; the rest were asymmetric (presumably excitatory). These findings are consistent with the presence of both GABA and glutamate projection neurons in the PAG. Some PAG axons contained dense-cored vesicles indicating the presence of neuropeptides in addition to classical neurotransmitters. PAG projections synapsed onto both DA and GABA cells with no obvious selectivity, providing the first anatomical evidence for these direct connections. The results suggest a diverse nature of PAG physiological actions on midbrain neurons. Moreover, as both the VTA and PAG are implicated in the reinforcing actions of opiates, our findings provide a potential substrate for some of the rewarding effects of these drugs.

2025

Background: The occipital cortex is positioned on the back of the brain, and it is responsible for processing visual information. Ketamine is a drug used as an anesthetic. Common anesthetics can cause neurotoxicity, with the occipital cortex being one of the most vulnerable areas. Aim: To estimate the histological alteration in the occipital cortices of newborn mice receiving ketamine injections at therapeutic doses during pregnancy. Methodology: This study involved 30 pregnant female mice (8-12 weeks old), who are split into two groups: the experimental group, given 50 mg/kg ketamine hydrochloride intraperitoneally, and the control group, given distal water intraperitoneally. The mice were then subjected to a paraffin wax embedding procedure, and their neural tissue was examined using a Cresyl violet stain. The results were analyzed using the Spss software and the independent t-test. Results: Significant variability was seen when the number of cells in the mice's occipital cerebral cortex after ketamine injection during pregnancy was compared. In the control group, the difference between the mean of the superficial layer and the deep layer is 85.4%, while in the experimental group, the difference between the two layers is 85.1%. In this study, there was significant variability in the number of cells between the control groups (Mean ± SD) is 1326±14.4 cells and the experimental group (Mean ± SD) is798.06 ±26.9 cells in the occipital cortex. In calculation, the experimental newborn mice's occipital cortex showed apoptotic alterations following a ketamine injection during pregnancy. Conclusion: The experimental newborn mice's occipital cortex showed apoptotic alterations following a ketamine injection during pregnancy. These results are in line with growing concerns regarding the neurotoxic effects of anesthetic drugs on the developing brain.

2025, Behavioural Brain Research

Immunohistochemical Fos staining has proven to be a method to identify the neurons that are activated by stimulation. Although methamphetamine (MA)-conditioned place preference (CPP) memory was longlasting, how this memory was established and retrieved remained unknown. We used the vehicle-and MA-conditioned environment (including cues and context) to reactivate the MA-CPP memory in mice. In the limbic system, Fos-positive neurons were examined following retrieval of the MA-CPP memory. We demonstrated that the current conditioning procedure produced reliable MA-CPP performance. Moreover, enhanced Fos expressions were found in the medial prefrontal cortex and the core of the nucleus accumbens after reactivation of the MA-CPP memory. Furthermore, familiarity with the environmental cues/context was found to significantly enhance Fos expressions in dorsal striatum and dentate gyrus. Nucleus accumbens shell, basolateral or lateral amygdala, in this regard, did not seem to be involved in retrieval of the MA-CPP memory. These results, taken together, suggest that the medial prefrontal cortex and the core of the nucleus accumbens are anatomical substrates responsible for reactivation of the MA-CPP memory.