Search Results (44)

Background/Objectives: Chemogenetic excitation of a distinct subset of “effector-neurons” in the brainstem mesopontine tegmental anesthesia area (MPTA) is pro-anesthetic. GABAergic general anesthetics are believed to engage these neurons by disinhibition, thereby inducing loss-of-consciousness (LOC) and enabling pain-free surgery. The transition from wakefulness to LOC, however, does not occur intrinsically within the MPTA. Rather, evidence indicates that LOC is brought about (effected) by ascending and descending axonal projections of MPTA effector-neurons that terminate in a variety of downstream brain targets which, together, generate the various components of anesthesia. Previously we used anterograde and retrograde tracing to delineate the overall axonal trajectories of MPTA projection-neurons, to which targets they project. Effector-neurons, however, represent only a fraction of this neuronal pool. Which of these targets are also innervated by MPTA projecting effector-neurons? Methods: Here we marked MPTA effector-neurons with the adeno-associated virus (AAV) used in the discovery of this neuronal type, with retrograde labelling from the previously identified MPTA target structures, to establish which downstream brain structures receive direct input from effector-neurons. Results: Effector-neurons proved to contribute to all six of the major MPTA projection-targets: the prefrontal cortex, basal forebrain, intralaminar thalamus, zona incerta, rostro-ventromedial medulla and spinal cord. Conclusions: We conclude that a discrete population of projecting effector-neurons, probably representing only about 6% of all MPTA neurons, drive the multiple functional endpoints of surgical anesthesia: analgesia, atonia, amnesia and LOC. Further, we propose that these same neurons, via their associated axonal pathways, may also contribute to endogenous instances of LOC such as natural sleep, fainting, concussion, coma and hibernation. Full article

Depressive spectrum disorders are considered among the most common in the general population. Major depressive disorder and persistent depressive disorder (or dysthymia) are the most recognized, but other depressive disorders exist with varying or no specificity. The main difference between major depressive disorder and dysthymia lies in the duration and intensity of symptoms. Improving our understanding of its etiology and pathogenesis must be a priority for health and safety. Given the complexity of the evidence in the literature, it was deemed useful to provide a comprehensive summary of the neuroanatomical dysfunctions currently identified, with particular attention to the anterior and medial cingulate cortex, dorsolateral and ventromedial prefrontal cortex, posterior parietal cortex, insula, amygdala, and hippocampus. Significant neural network alterations include hyperconnectivity of the default mode network (DMN), impairment of the executive control network (ECN), and dysfunction of the salience network (Salience Network). Neurophysiological markers reveal frontal alpha asymmetries and front-striatal metabolic alterations. Studying neural correlates is essential to deepen our understanding of the depressive spectrum and the development of personalized therapeutic interventions, including noninvasive neurostimulation techniques and target-specific pharmacological therapies, opening new avenues for translational research in neuropsychiatric settings. Full article

Occupational burnout is ubiquitous yet still debated as a disease entity. Previous reviews surveyed multiple biomarkers but left their neural substrate unclear. We therefore asked: What, if any, reproducible magnetic-resonance signature characterises burnout? Following PRISMA principles adapted for mechanistic synthesis, two reviewers searched PubMed, Scopus, Google Scholar, ResearchGate and Cochrane from January 2000 to May 2025 using “MRI/fMRI” AND “burnout”. After duplicate removal and multi-stage screening, 17 clinical studies met predefined inclusion criteria (English language, MRI outcomes, validated burnout diagnosis). In total, ≈1365 participants were scanned, 880 with clinically significant burnout and 470 controls. Uniform Maslach Burnout Inventory thresholds defined cases; most studies matched age and sex, and all excluded primary neurological disease. Structural morphometry (8/17 studies) revealed consistent amygdala enlargement—predominantly in women—and grey-matter loss in dorsolateral/ventromedial prefrontal cortex and striatal caudate–putamen, while hippocampal volume remained unaffected, distinguishing burnout from PTSD or depression. Resting-state and task fMRI (9/17 studies) showed fronto-cortical hyper-activation, weakened amygdala–ACC coupling, and progressive fragmentation of rich-club networks, collectively indicating compensatory executive overdrive and global inefficiency. Two longitudinal cohorts and several intervention sub-studies demonstrated partial reversal of cortical thinning and limbic hyper-reactivity after mindfulness, exercise, cognitive-behavioural therapy, neurofeedback, or rTMS, underscoring plasticity. Across heterogeneous paradigms and populations, MRI converges on a coherent, sex-modulated but reversible brain-networkopathy that satisfies objective disease criteria. These findings justify early neuro-imaging-based triage, circuit-targeted therapy, and formal nosological recognition of burnout as a mental disorder, with policy ramifications for occupational health and insurance parity. Full article

Background: Emotion regulation (ER) plays a vital role in mental health, spanning mood, anxiety, and personality disorders. Cognitive reappraisal (CR) is one of the most common ER strategies and depends on prefrontal brain areas, but its success varies, and its neural basis is not fully clear. Interest is growing in using transcranial direct current stimulation (tDCS) to support ER, yet most studies have focused only on the dorsolateral prefrontal cortex (dlPFC) and used simple tasks. Objective: This study explored whether tDCS applied to either the dlPFC or the ventromedial prefrontal cortex (vmPFC) could shape autonomic responses during CR while people watched emotionally engaging film clips. Methods: Participants were randomly assigned to receive either active or sham tDCS over the dlPFC or vmPFC. While stimulated, they used CR strategies (positive reappraisal, fictional reappraisal, or distancing) to manage their reactions to negative film scenes. Heart rate (HR), skin conductance (SC), and respiratory rate (RR) were tracked throughout as physiological indicators. Results: Active dlPFC tDCS combined with CR led to significantly greater reductions in HR toward the end of emotional exposure, compared to sham or non-CR conditions. dlPFC stimulation also lowered HR even without explicit CR, pointing to possible effects on automatic regulation. vmPFC effects were inconsistent, and no reliable effects were observed for SC or RR. Conclusions: These results suggest that tDCS effects on autonomic ER depend on the brain region and timing. dlPFC stimulation may strengthen both intentional and automatic emotion regulation, especially when combined with reappraisal, highlighting the value of realistic emotional tasks in neuromodulation studies. Full article

Depression and obesity are comorbid conditions linked through shared neuroinflammatory and immune mechanisms. This study examined the effects of chronic cannabidiol (CBD) treatment on behavior and neuroinflammatory gene expression in female rats exposed to a combined model of high-fat diet (HFD) and unpredictable chronic mild stress (UCMS). Rats were subjected to an acute HFD for 2 weeks, followed by 4 weeks of UCMS. CBD (10 mg/kg, i.p.) or vehicle was administered during the final 2 weeks of UCMS. Specifically, mRNA levels of nuclear factor kappa B1 (NF-κB1), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 were measured in the ventromedial prefrontal cortex (vmPFC) and CA1. CBD’s effects varied depending on the type of stressor. It promoted coping behavior, increased locomotion, reduced freezing, and restored UCMS-induced depressive-like behavior in a splash test. In the vmPFC, CBD normalized the HFD- and UCMS-induced increase in il1β, and downregulated nfkb1 and tnfa expression. In the CA1, it normalized stress-induced downregulation in nfkb1 expression. These findings suggest that the efficacy of CBD in modulating both behavior and neuroinflammation is contingent upon the nature of the stress exposure, highlighting its potential as a targeted treatment for stress-related neuropsychiatric disorders in females. Full article

Emotional attunement, or emotional co-regulation in a relationship, can manifest as interpersonal neural synchrony, where partners exhibit similar anti-phase or phase-shifted brain activity. In adult romantic relationships, emotional attunement may differ according to relationship satisfaction. No study has examined how relationship satisfaction difference influences interpersonal neural synchrony. This exploratory pilot study on 17 couples (unmarried Chinese undergraduate couples in a Southeast Asian university) investigated whether relationship satisfaction difference influenced interpersonal neural synchrony during a shared emotive experience. Each couple wore an fNIRS cap to measure brain activity in their prefrontal cortex (PFC) while co-viewing seven videos intended to evoke positive, negative or neutral emotions. We found preliminary evidence that relationship satisfaction difference modulated interpersonal neural synchrony in the right ventral PFC regions, including the right ventromedial PFC (involved in the encoding of emotional values to stimuli and emotional regulation), right ventrolateral PFC (involved in voluntary emotional regulation) and the right orbitofrontal cortex (involved in processing of emotional experiences and regulation of emotions). This suggested that couples with mismatched relationship satisfaction displayed greater interpersonal neural synchrony, possibly due to mutual social cognitive processes when viewing emotive videos together. Further studies can replicate the findings with larger, diverse samples. Full article

Background: Chronic insomnia (CID) is a highly prevalent sleep disorder, yet the precise mechanisms underlying it remain incompletely understood. The aim of this study is to analyze effective connectivity between key regions of the default mode network (DMN), executive control network (ECN), and salience network (SN) in patients with CID as potential neurologic correlates of the hyperarousal state. Methods: Thirty-one CID patients and 24 healthy controls (HC) were recruited. All the subjects filled out the Insomnia severity index scale (ISI), Beck depression inventory (BDI), and Epworth sleepiness scale (ESS), underwent polysomnography, and were scanned on functional magnetic resonance imaging. Statistical Parametric Mapping 12 was used to analyze the results. Spectral dynamic causal modeling was applied to the chosen regions of interest. Results: There were three significant connections present in the CID group—inhibitory from the dorsolateral prefrontal cortex (DLPFC) to the right hippocampus (Hippocamp R); excitatory from the dorsomedial prefrontal cortex to the ventromedial prefrontal cortex; and excitatory from the common medial prefrontal cortex to the right anterior insula (AIR). Two statistically significant excitatory connections were lacking in the patients’ group—from the posterior cingulate cortex (PCC) to AIR, and from precuneus to PCC. CID patients scored higher on the ISI and BDI. Significant negative correlations between DLPFC-Hippocamp R connectivity and both ISI and BDI scores were identified. Conclusions: Disruptions within the DMN and between the DMN, SN, and ECN reflect an impaired ability to appropriately shift between internally and externally directed cognitive states—an imbalance that potentially underlies the hyperarousal state of CID. Full article

Social and environmental influences are important for learning. However, the influence of reward and competition during social learning is less understood. The literature suggests that the ventromedial prefrontal cortex is implicated in hot executive functioning (EF), while the dorsolateral prefrontal cortex is related to cool EF. In addition, reward processing deficits are associated with atypical connectivity between the nucleus accumbens and the dorsofrontal regions. Here, we used functional magnetic resonance imaging (fMRI) to determine the role of hot and cool EF in reward processing and their relationship to performance under social competition. We adapted a reward-based n-back task to examine the neural correlates of hot and cool EF and the reward influence on performance during competition. A total of 29 healthy adults showed cortical activation associated with individual differences in EF abilities during fMRI scans. Hot and cool EF activated distinct networks in the right insula, hippocampus, left caudate nucleus, and superior parietal gyrus during the no-competition task, while they differentially activated the right precuneus and caudate nucleus in the competition condition. Further analysis revealed correlations between the Hot–Cool network and reward sensitivity and risk-taking behaviour. The findings provided further insights into the neural basis of hot and cool EF engagement in the socio-emotional regulation for learning. Full article

Evidence indicates a bidirectional link between depressive symptoms and neuroinflammation. This study evaluated chronic cannabidiol (CBD) treatment effects in male and female rats subjected to the unpredictable chronic mild stress (UCMS) model of depression. We analyzed the gene expression related to neuroinflammation, cannabinoid signaling, estrogen receptors, and specific microRNAs in the ventromedial prefrontal cortex (vmPFC), CA1, and ventral subiculum (VS). UCMS influenced immobility in a sex-specific manner, increasing it in males and decreasing it in females, effects that were reversed by CBD. CBD also normalized the UCMS-induced upregulation of tumor necrosis factor α (TNF-α) in the CA1 and VS in males. In both sexes, UCMS induced the upregulation of the nuclear factor kappa B subunit 1 (NF-κB1) gene in the VS, which was unaffected by CBD. Additionally, CBD reversed CB1 downregulation in the VS of males but not in the vmPFC of either sex. In males, CBD restored the UCMS-induced downregulation of VS estrogen receptor genes ERα and ERβ. UCMS also altered miR-146a-5p expression, downregulating it in females (VS) and upregulating it in males (CA1), with no CBD effect. These findings highlight the sex-specific mechanisms of CBD’s antidepressant effect, with hippocampal neuroinflammatory and estrogenic pathways playing a key role in males. Full article

Background: Problematic social media (SM) use is a growing concern, particularly among adolescents who are drawn to these platforms for social interactions important to their age group. SM dependence is characterized by excessive, uncontrolled usage that impairs personal, social, and professional aspects. Despite the ongoing debate over recognizing SM addiction as a distinct diagnostic category, the impact of social feedback, particularly through the “like” button, on brain activity remains under scrutiny. Objective: This systematic review aims to study the neural correlates of online social feedback, focusing on the effects of the “like” feedback on brain activity using fMRI and EEG. Methods: The review followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA). Results: The review included 11 studies with 504 participants, identifying key brain structures such as the amygdala, ventromedial prefrontal cortex (vmPFC), and ventral striatum involved in reward processing. Positive feedback (“likes”) activates areas like the nucleus accumbens (NACC), vmPFC, and amygdala, with NACC correlating with increased SM use intensity. Negative feedback activates the ventrolateral prefrontal cortex (vlPFC) and left medial prefrontal cortex (mPFC). Behavioral data indicates that positive feedback influences subsequent social interactions. Conclusions: The review highlights disparities in the literature regarding the neural response to social feedback, emphasizing the need for further research to clarify the roles of sex, personality traits, and the person giving feedback. Overall, understanding the neurobiological underpinnings of SM engagement is essential for developing effective interventions to prevent or address the negative effects of excessive SM use. Full article

To elucidate the potential roles of presynaptic and postsynaptic serotonergic activity in impulsivity traits, we investigated the relationship between self-reported impulsiveness and serotonin transporter (5-HTT) and 5-HT2A receptors in healthy individuals. In this study, 26 participants completed 3-Tesla magnetic resonance imaging and positron emission tomography with [¹¹C]DASB and [¹¹C]MDL100907. To quantify 5-HTT and 5-HT2A receptor availability, the binding potential (BP_ND) of [¹¹C]DASB and [¹¹C]MDL100907 was derived using the simplified reference tissue model with cerebellar gray matter as the reference region. The participants’ impulsivity levels were assessed using the Barratt Impulsiveness Scale-11 (BIS-11). The region of interest (ROI)-based partial correlation analysis with age, sex, and temperament traits as covariates revealed a significant positive correlation between non-planning impulsiveness and [¹¹C]MDL100907 BP_ND in the caudate (CAU) at Bonferroni-corrected p < 0.0045. Non-planning impulsiveness was also positively correlated with [¹¹C]MDL100907 BP_ND in the prefrontal cortex (PFC), ventromedial PFC, orbitofrontal cortex (OFC), insula (INS), amygdala (AMYG), putamen, ventral striatum, and thalamus, and the total score of BIS-11 was positively correlated with [¹¹C]MDL100907 BP_ND in the OFC, INS, AMYG, and CAU at uncorrected p < 0.05. Motor impulsiveness had a positive correlation with [¹¹C]DASB BP_ND in the CAU at uncorrected p < 0.05. Our results suggest that impulsivity traits, characterized by focusing on the present moment without considering future consequences, may be involved in serotonergic neurotransmission, particularly 5-HT2A receptor-mediated postsynaptic signaling in the CAU, which plays an important role in cognitive processes related to executive function, judgment of alternative outcomes, and inhibitory control. Full article

Aggression is a fundamental behavior with essential roles in dominance assertion, resource acquisition, and self-defense across the animal kingdom. However, dysregulation of the aggression circuitry can have severe consequences in humans, leading to economic, emotional, and societal burdens. Previous inconsistencies in aggression research have been due to limitations in techniques for studying these neurons at a high spatial resolution, resulting in an incomplete understanding of the neural mechanisms underlying aggression. Recent advancements in optogenetics, pharmacogenetics, single-cell RNA sequencing, and in vivo electrophysiology have provided new insights into this complex circuitry. This review aims to explore the aggression-provoking stimuli and their detection in rodents, particularly through the olfactory systems. Additionally, we will examine the core regions associated with aggression, their interactions, and their connection with the prefrontal cortex. We will also discuss the significance of top-down cognitive control systems in regulating atypical expressions of aggressive behavior. While the focus will primarily be on rodent circuitry, we will briefly touch upon the modulation of aggression in humans through the prefrontal cortex and discuss emerging therapeutic interventions that may benefit individuals with aggression disorders. This comprehensive understanding of the neural substrates of aggression will pave the way for the development of novel therapeutic strategies and clinical interventions. This approach contrasts with the broader perspective on neural mechanisms of aggression across species, aiming for a more focused analysis of specific pathways and their implications for therapeutic interventions. Full article

Background: Humans perceive and interpret the world through the lens of self-reference processes, typically facilitating enhanced performance for the task at hand. However, this research has predominantly emphasized the automatic facet of self-reference processing, overlooking how it interacts with control processes affecting everyday situations. Methods: We investigated this relationship between automatic and control self-reference processing in neuropsychological patients performing self-face perception tasks and the Birmingham frontal task measuring executive functions. Results: Principal component analysis across tasks revealed two components: one loaded on familiarity/orientation judgments reflecting automatic self-reference processing, and the other linked to the cross task and executive function indicating control processing requirements. Voxel-based morphometry and track-wise lesion-mapping analyses showed that impairments in automatic self-reference were associated with reduced grey matter in the ventromedial prefrontal cortex and right inferior temporal gyrus, and white matter damage in the right inferior fronto-occipital fasciculus. Deficits in executive control were linked to reduced grey matter in the bilateral inferior parietal lobule and left anterior insula, and white matter disconnections in the left superior longitudinal fasciculus and arcuate fasciculus. Conclusions: The causal evidence suggests that automatic and control facets of self-reference processes are subserved by distinct yet integrated ventral prefrontal–temporal and dorsal frontal–parietal networks, respectively. Full article

Fear-related disorders, including post-traumatic stress disorder (PTSD), and anxiety disorders are pervasive psychiatric conditions marked by persistent fear, stemming from its dysregulated acquisition and extinction. The primary treatment for these disorders, exposure therapy (ET), relies heavily on fear extinction (FE) principles. Adolescence, a vulnerable period for developing psychiatric disorders, is characterized by neurobiological changes in the fear circuitry, leading to impaired FE and increased susceptibility to relapse following ET. Ketamine, known for relieving anxiety and reducing PTSD symptoms, influences fear-related learning processes and synaptic plasticity across the fear circuitry. Our study aimed to investigate the effects of ketamine (10 mg/kg) on FE in adolescent male C57 BL/6 mice at the behavioral and molecular levels. We analyzed the protein and gene expression of synaptic plasticity markers in the hippocampus (HPC) and prefrontal cortex (PFC) and sought to identify neural correlates associated with ketamine’s effects on adolescent extinction learning. Ketamine ameliorated FE in the adolescent males, likely affecting the consolidation and/or recall of extinction memory. Ketamine also increased the Akt and mTOR activity and the GluA1 and GluN2A levels in the HPC and upregulated BDNF exon IV mRNA expression in the HPC and PFC of the fear-extinguished mice. Furthermore, ketamine increased the c-Fos expression in specific brain regions, including the ventral HPC (vHPC) and the left infralimbic ventromedial PFC (IL vmPFC). Providing a comprehensive exploration of ketamine’s mechanisms in adolescent FE, our study suggests that ketamine’s effects on FE in adolescent males are associated with the activation of hippocampal Akt-mTOR-GluA1 signaling, with the vHPC and the left IL vmPFC as the proposed neural correlates. Full article

Neuroeconomics merges neuroscience, economics, and psychology to investigate the neural basis of decision making. Decision making involves assessing outcomes with subjective value, shaped by emotions and experiences, which are crucial in economic decisions. Functional MRI (fMRI) reveals key areas of the brain, including the ventro-medial prefrontal cortex, that are involved in subjective value representation. Collaborative interdisciplinary efforts are essential for advancing the field of neuroeconomics, with implications for clinical interventions and policy design. This review explores subjective value in neuroeconomics, highlighting brain regions identified through fMRI studies. Full article