Search Results (627)

Insulin acts in the brain to promote satiety. Aging individuals may have brain insulin resistance and altered appetite perceptions. However, it is unclear if exercise impacts cerebral reward centers and appetite perception in middle-aged to older individuals. Purpose: To assess whether a single exercise bout alters cerebral blood flow (CBF) in reward centers in relation to appetite perceptions. Methods: Fifteen sedentary adults (12F; ~56 ± 2y; ~31 ± 1 kg/m²) completed a control and acute exercise condition (70% maximal oxygen consumption) in a randomized, counterbalanced order in the evening. Following an overnight fast, CBF in the accumbens, thalamus, and amygdala (pCASL MRI) was evaluated before and after intranasal insulin spray (INI, 40 IU) administration. Plasma glucose and insulin as well as an appetite visual analog scale (VAS) were assessed at fasting, 30, and 90 min post-INI, as well as at 30 min intervals of a 120 min 75 g oral glucose tolerance test (OGTT). Total area under the curve (tAUC) was calculated. Results: Exercise tended to lower blood glucose (p = 0.072) and plasma insulin (p = 0.007) tAUC, compared with rest. Exercise also raised right thalamus (p = 0.029) and left amygdala CBF (p = 0.023). The rise in fasting CBF in these regions, and the accumbens, correlated with reduced insulin tAUC (r = −0.55 to −0.73, p < 0.050). Although there was no difference in hunger, satisfaction, fullness, or prospective food consumption after exercise, changes in INI-stimulated thalamus CBF related to fullness tAUC after exercise (r = −0.57, p = 0.044). Conclusions: A single exercise bout might increase fasting CBF in some brain regions associated with appetite perception through a potential insulin-related mechanism. Full article

Fibromyalgia is a chronic nociplastic pain condition frequently accompanied by affective disturbances, particularly depression, for which effective treatments remain limited. Increasing evidence implicates central oxidative stress, maladaptive synaptic plasticity, and neuroinflammatory alterations in its pathophysiology. This study investigated the therapeutic effects of molecular hydrogen (H₂) in a reserpine-induced murine model of fibromyalgia, with emphasis on sex-dependent and region-specific mechanisms. Male and female C57BL/6 mice received repeated reserpine injections to induce fibromyalgia-like symptoms. Mechanical allodynia, thermal hyperalgesia, cold allodynia, and depressive-like behaviors were assessed, followed by molecular analyses in the spinal cord and amygdala. Reserpine induced persistent nociceptive hypersensitivity and depressive-like behaviors in both sexes, with earlier cold allodynia in females. Hydrogen-rich water (HRW) progressively reversed mechanical and thermal hypersensitivity and rapidly abolished cold allodynia, showing greater efficacy in females. HRW also normalized depressive-like behaviors in both sexes. At the molecular level, HRW reduced spinal oxidative stress and ERK-dependent plasticity without altering spinal NLRP3 expression, whereas it fully reversed NLRP3 upregulation and HO-1 downregulation in the amygdala. HRW additionally engaged sex-dependent antioxidant pathways in the spinal cord. These findings indicate that H₂ alleviates sensory and affective alterations through region- and sex-dependent central mechanisms, supporting HRW as a promising therapeutic strategy for nociplastic pain and its affective comorbidities. Full article

Objectives: This study aims to define the surgical anatomy, technical feasibility, advantages, and limitations of the TPPA through detailed cadaveric dissection and a representative clinical case, evaluating its potential as a safe and effective alternative to traditional approaches to the mesiotemporal lobe. Methods: A cadaveric dissection was performed on one adult head injected with colored latex, using standard microsurgical instruments and high-definition video documentation. Each procedural step was recorded and illustrated with cadaveric photographs. Additionally, a clinical case of mesiotemporal cavernous hemangioma resected via TPPA is presented, including an operative video. Results: The dissection demonstrated a direct and safe trajectory to the amygdala and hippocampal head, with clear identification of key vascular and white matter landmarks. In the clinical case, the lesion was completely resected with no postoperative neurological deficits. Conclusions: The TPPA represents a novel microsurgical corridor to the mesiotemporal region, minimizing cortical disruption, Sylvian fissure dissection, and manipulation of middle cerebral artery branches. Although its exposure is limited posteriorly, the TPPA could offer an optimal balance between functional preservation and surgical accessibility, constituting a valuable addition to the modern microsurgical armamentarium. Full article

This study presents the results of a Proof of Concept developed within the framework of the Amygdala Project, aimed at exploring the relationship between electronic music and emotional well-being among young people with and without a diagnosis of adjustment disorders (anxiety, depression, and distress). The fieldwork was conducted during the live concert of DJ Steve Aoki (Cosquín Rock 2024, Valladolid), combining psychophysiological measurements using Sociograph technology, self-reported questionnaires, and performative and contextual analyses. The results reveal significant differences between the two groups: participants with a diagnosis exhibited a more constant and profound emotional connection, interpreting the experience as a form of “emotional escape” and an opportunity for affective regulation; whereas those without a diagnosis experienced more fluctuating levels of attention and perceived the event primarily as entertainment. The triangulation of biometric, observational, and narrative data suggests that electronic music in collective contexts may operate as a tool for emotional containment and transformation, fostering group cohesion and reducing psychological distress. These findings open new avenues for interdisciplinary research into the biosocial effects of contemporary music and its potential in the design of cultural and educational strategies to promote psychological well-being among young people. Full article

Despite the growing interest in brain structural plasticity and the substantial body of knowledge that has accumulated over recent decades, some issues remain poorly defined, leading to confusion in the interpretation of results. In addition to stem cell-driven neurogenesis in adult neurogenic niches (adult neurogenesis), neuronal precursors in a state of arrested maturation have also been described, representing a form of neurogenesis without division based on so-called “immature” or late-maturing neurons. These processes occur in different brain regions yet share certain molecular markers and temporal windows. Recent advances in comparative neuroplasticity have further complicated our understanding. Studies reveal a reduction in adult neurogenesis in the olfactory bulb and hippocampus of large-brained, gyrencephalic mammals compared with small-brained species such as rodents. Conversely, a higher prevalence of immature neurons has been reported in the neocortex and amygdala of larger-brained mammals. It is becoming evident that evolutionary trade-offs took place in distinct plastic processes, resulting in the predominance of certain forms in particular species, while others coexist and share overlapping markers. Regardless of the approach employed (neuroanatomical, immunocytochemical, phylogenetic, or transcriptional), current evidence indicates substantial heterogeneity in cell types with different origins and fates across diverse mammalian species. These patterns appear to be sculpted by evolutionary pressures yet unified by shared transient maturational states. Full article

Background: Post-traumatic stress disorder (PTSD) affects millions globally, with 40–50% of patients not responding adequately to first-line treatments. Prism neurofeedback, an FDA-cleared electroencephalography (EEG)-based system targeting amygdala-derived biomarkers, has demonstrated efficacy in randomized controlled trials (RCTs) and multicenter studies. Real-world implementation data from community clinical practice remain limited. Objective: To evaluate clinical outcomes and patient-developed self-regulation strategies of Prism neurofeedback in patients with PTSD in community clinical practice. Methods: Retrospective case series of 28 consecutive patients with PTSD treated with Prism neurofeedback in a community psychiatry practice. The primary outcome was change in PTSD Checklist for DSM-5 (PCL-5) from baseline to end of treatment. Results: Twenty-one of 28 patients (75.0%) completed treatment. Mean PCL-5 reduction was 37.0 ± 18.2 points (Cohen’s d = 2.03). Response rates were 100% for any improvement and 90.5% for clinically significant improvement (≥10-point reduction). Five patients (23.8%) achieved excellent response with ≥50-point reduction. Limited follow-up data (1–3 months post-treatment) were available for three patients; two of three (67%) exceeded their end-of-treatment gains. Four patients receiving booster sessions showed continued improvement. Limitations: The uncontrolled, retrospective design precludes causal attribution of improvements to the intervention versus placebo effects or regression to the mean. The 25% early discontinuation rate may introduce attrition bias. Durability data are available for only three patients. Conclusions: This case series provides real-world evidence supporting the feasibility and potential clinical utility of Prism neurofeedback in community practice, with outcomes comparable to controlled studies and preliminary evidence of durable treatment effects. These findings complement existing RCT evidence by demonstrating successful implementation outside research settings. Full article

Background/Objective: Auditory and vestibular (AV) symptoms can be considered functional neurological disorders (FND) when they do not arise from structural abnormalities. These symptoms can arise as expressions of underlying neuropsychological or psychiatric conditions, yet they may also play a role in precipitating or maintaining such disorders. This systematic review aimed at exploring the prevalence of AV symptoms in post-traumatic stress disorders (PTSD) as well as to understand if they correlate with each other. Methods: We conducted a systematic review of the literature including PubMed, Scopus and Google Scholar. Articles in English published between 1985 and 2025 were screened using the following keywords: “Tinnitus”, “Ghost sound”, “Dizziness” “Vertigo”, “Persistent Postural Perceptual Dizziness”, “PPPD”, “Hearing concerns”, “Hyperacusis”, “Diplacusis”, “Auditory hallucination(s)”, “Audio and Vestibular symptom” and “Post Traumatic Stress Disorders” or “PTSD”. Risk of bias was used to evaluate the quality of the articles. Results: We found 18 studies analysing specifically these symptoms in PTSD, including a total of 598,654 subjects. We identified 123.006 patients with PTSD (20.5% of the entire analysed sample) suffering from AV symptoms, in particular tinnitus (33.8%) and a combination of hearing loss and tinnitus (29%). A very small separate percentage suffered from auditory hallucinations (0.3%) or vertigo/dizziness (0.8%). Magnetic resonance imaging studies have identified hyperactivation in various brain areas both in PTSD and in the presence of AV symptoms, with amygdala hyperactivation emerging as the most common finding. Conclusions: Based on the results of this systematic review, patients with PTSD suffer from AV symptoms in 20.5% of cases. MRI studies conducted separately on patients with PTSD and tinnitus, vertigo or dizziness showed a hyperactivation of the amygdala in all these conditions. We speculate that amygdala hyperactivation might explain the coexistence of and the relationship between PTSD and AV symptoms. Full article

Sex differences in stress-induced alcohol-seeking are well documented. The overarching goal of this study is to examine how sex may moderate the relationship between depression and anxiety symptoms and stress-induced alcohol-seeking and to identify mechanisms of this relationship. We explore subjective alcohol responses and the resting-state functional connectivity of the amygdala and the hippocampus, regions implicated in anxiety and depression, as potential sex-dependent mediators. This secondary analysis draws from a recently published trial of 84 adults aged 21 to 55 (54.8% female, mean age = 32, SD = 10.68; 58.3% White, 88.1% non-Hispanic/Latino) who endorsed moderate-to-heavy alcohol use. All participants completed two counterbalanced intravenous alcohol administration sessions, and 54 completed optional neuroimaging. Generalized anxiety symptoms were significantly associated with greater stress-induced alcohol-seeking in women but not in men. Depression symptoms showed a similar pattern, though the results did not reach statistical significance. Across men and women, blunted state stimulation, but not state anxiety, in response to alcohol was associated with greater stress-induced alcohol-seeking. In men, anxiety symptoms were linked with heightened state stimulation effects, which appeared to buffer against stress-induced alcohol-seeking. State stimulation findings may suggest a possible mechanism for sex differences concerning anxiety pathways to alcohol-seeking. Subjective alcohol responses did not mediate the relationship between depression symptoms and stress-induced alcohol-seeking. Resting-state network connectivity findings identified several potential sex-dependent neural mechanisms that warrant further investigation. Although this study was not originally designed as a direct test of competing subjective response and low-level response to alcohol theoretical models, our findings are consistent with Schuckit’s low level of response to alcohol theory. Our findings showed that blunted stimulation may contribute to stress-induced alcohol-seeking among men. Identifying mechanisms that underlie sex-specific relationships with stress-induced alcohol-seeking can inform the development of tailored intervention approaches, ultimately enhancing treatment efficacy for both men and women. Full article

Callous–unemotional (CU) traits are characterised by reduced empathy, guilt, and emotional responsiveness, and are strongly linked to atypical socioemotional processing. Eye-tracking research provides a valuable window into these processes by capturing early developing patterns of attention to emotionally salient social cues, particularly facial expressions. This narrative review examines how alterations in gaze behaviour contribute to the emergence of CU traits across neurodevelopmental disorders (NDs), with a focus on autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and conduct disorder (CD). Across studies, elevated CU traits are associated with reduced fixations on the eye region, most consistently in response to fearful faces. ASD is associated with robust eye avoidance, ADHD with inhibitory and attentional control difficulties during face processing, and CD with atypical gaze allocation to negative emotional expressions such as fear and anger. These patterns appear amplified when CU traits co-occur with NDs. Competing explanatory accounts, including aberrant amygdala functioning, oculomotor disinhibition, and hostile attribution biases, each capture aspects of these patterns but fail to provide a unified explanation. Integrating developmental, neurobiological, and environmental perspectives, we propose that CU traits reflect a transdiagnostic developmental construct shaped by early attentional–emotional mechanisms, rather than a disorder-specific identity. Full article

With the aim of identifying key proteins that play a role in the disorder tinnitus, interactions between proteins involved in thalamo-amygdala signaling under conditions of normal hearing (NH), acoustic stimulation (AS), and tinnitus (Tin) were studied. Three gene lists compiled from the GeneCards database using keywords were characterized by analyses of overlap, protein–protein interaction (PPI) networks, and by protein-enrichment analysis. Key proteins were selected on the basis of the degree and combined score value of the corresponding PPI network. In the NH process, BDNF, CASP3, and PVALB were identified as high-degree proteins (HDPs). In the AS process, BDNF, PVALB, and DLG4 are the top three HDPs; in the Tin process, these are BDNF, APP, and TNF. In the Tin process, key proteins appear that differ pre- and postsynaptically from those detectable in NH or AS. The glucocorticoid receptor NR3C1 and its interaction with FKBP5, a glucocorticoid receptor-induced co-chaperone, appear to be of particular importance for the emotional aspects of tinnitus. In tinnitus, the HDPs, together with their high-score interaction proteins, indicate processes of chronic neurodegeneration and of changes in transcription, intercellular communication, and in the survival and growth of neurons. Full article

Objectives: To evaluate regional anatomical differences in brain volume, surface area, and cortical thickness between children with breath-holding spells (BHSs) and a control group using morphometric MRI analyses. Methods: Three-dimensional T1-weighted cranial MRI data from 48 children with BHSs and 50 control children were retrospectively analyzed, yielding volumetric, surface area, and cortical thickness measures for 135 brain regions. All measurements were assessed relative to total intracranial volume (ICV). Group comparisons were performed using analysis of covariance with age, sex, and ICV as covariates, followed by Benjamini–Hochberg false discovery rate correction (q < 0.05). Results: The BHS group exhibited reduced bilateral amygdala volumes (left: q = 0.042; right: q = 0.038). Both cortical thickness and volume were reduced in the right anterior insula (thickness: q = 0.046; volume: q = 0.049). In addition, cortical thickness was reduced in the bilateral anterior cingulate cortices (left: p = 0.019, q = 0.045; right: p = 0.017, q = 0.043) as well as in the right medial frontal cortex (p = 0.009, q = 0.036). Subregional cerebellar analysis demonstrated volume reductions in the right lobule VI (q = 0.031), left lobule VIIA (Crus I) (q = 0.043), and vermis IX–X (q = 0.039). Conclusions: Detecting measurable morphometric changes in brain regions involved in autonomic and emotional regulation in children with BHSs will contribute to understanding the neurobiological characteristics associated with BHSs. Full article

The authors hypothesize that idiopathic Parkinson’s disease may result from an alteration in microvascular flow at a “critical point” in the nervous system that is characterized by pigmented cells that express neuromelanin and/or lipofuscin. “Critical points” include the olfactory epithelium/bulb, the autonomic nervous system, the enteric nervous system, the prefrontal–cortico-pontine network, and the amygdala. Hypoxia–ischemia following blood flow disturbance would recruit and activate leukocytes and induce the infiltration of peripheral immune cells into neural tissue. The excess of toxic factors produced by hyperactive immune cells, such as myeloperoxidase and its derivatives, would cause the oxidation of lipids, proteins, and biogenic monoamines such as dopamine, which in turn would facilitate the accumulation and precipitation of neuromelanin, lipofuscin, and alpha-synuclein. In addition, neuromelanin and lipofuscin precipitates may accentuate the misfolding and aggregation of alpha-synuclein. This “amplification” mechanism could help explain the crucial role of pigmented neurons in the onset of Parkinson’s disease pathology, triggering abnormal neurotoxic alpha-synuclein spread throughout the nervous system from the “critical point” of origin, and enabling a self-perpetuating degenerative process. The proposed hypothesis may have implications for the identification of new therapeutic targets, early prevention strategies, and the development of vascular and/or immune biomarkers. Full article

Bipolar affective disorder (BD) is a severe mental illness characterized by recurrent episodes of mania, hypomania, and depression, accompanied by progressive neurobiological changes that go beyond the classical concepts of neurotransmitter dysregulation. Increasing evidence points to the key role of the interaction between inflammatory processes, mitochondrial dysfunction, and disturbances within neural networks in the pathogenesis, course, and treatment response of BD. Neuroinflammatory processes, including elevated levels of pro-inflammatory cytokines, chemokines, and microglial activation, are consistently reported in patients with BD and linked to cognitive impairment, accelerated neuroprogression, and treatment resistance. At the same time, mitochondrial abnormalities—such as impaired oxidative phosphorylation, excessive production of reactive oxygen species, and disturbances in calcium homeostasis—contribute to oxidative stress, synaptic dysfunction, and increased neuronal vulnerability, forming the biological substrate of mood instability. Findings from neuroimaging studies provide consistent evidence of structural and functional alterations within the cortico-limbic networks regulating emotions, including the prefrontal cortex, anterior cingulate cortex, amygdala, and hippocampus. Importantly, a growing number of studies demonstrate correlations between neuroimaging changes and inflammatory and metabolic biomarkers, making it possible to link molecular pathology with dysfunctions at the level of neural networks. The use of multimodal methods—encompassing structural and functional magnetic resonance imaging, spectroscopy, and molecular analyses—allows for a more precise explanation of these complex interactions and the identification of biomarkers of clinical states, progression, and treatment response. This review synthesizes current knowledge on the molecular and neuroimaging correlates of BD, emphasizing the interdependence of inflammatory processes, mitochondrial function, and neural networks. The integration of molecular biomarkers with imaging-based phenotyping opens new perspectives for precision medicine in BD. Full article

Extensive research in laboratory rodents has shown that novelty exposure enhances the consolidation of memories for preceding or following low-arousal events by elevating dopamine release in the dorsal hippocampus (dHipp). Additionally, numerous studies have demonstrated that post-encoding noradrenergic activation of the basolateral amygdala (BLA) can also enhance memory consolidation in dHipp. Since the BLA is most active during emotionally arousing or stress-related situations, it was suggested that this nuclear complex mediates the effects of emotional salience on memory consolidation. However, it is presently unknown whether the reinforcement of memory storage in dHipp induced by novel and arousing environmental conditions results from the interaction between these two modulatory systems. To test the hypothesis of a functional interaction between dopaminergic and noradrenergic systems, this study assessed their combined effects on a low-arousal object-location (OL) task. Rats received post-training intra-BLA infusions of vehicle or clenbuterol (Clen), a selective β-adrenoceptor agonist. Novelty-induced dopamine release in the dHipp was enhanced by omitting habituation prior to training, and the contribution of dopamine signaling was further evaluated using pre-infusion administration of the D1/D5 receptor antagonist SCH 23390. The distribution of two important proteins for memory processing, namely the activity-regulated cytoskeleton-associated protein (Arc) and the phosphorylated form of the transcription factor, cAMP-response element-binding protein (pCREB) in the dHipp, was explored in a subset of rats perfused 60 min after the training phase. Stimulation of the BLA significantly increased the number of Arc- and pCREB-positive cells in several dHipp areas. The preceding application of SCH 23390, however, substantially decreased these effects in the same areas, i.e., the dentate gyrus (DG), CA2, and CA1 subregions for pCREB, and the CA3b, CA3c, CA2, and CA1 subregions for Arc. This interaction is considered essential for the initial stages of memory consolidation. The obtained results indicate the presence of a region-specific interaction between BLA modulatory inputs and intrahippocampal dopaminergic transmission, the mechanisms of which remain to be elucidated. Full article

Chronic post-stroke headache is a common yet understudied complication of stroke, potentially driven by maladaptive connectivity between limbic and sensorimotor brain regions. This pilot study evaluated the effects of a combined intervention using repetitive transcranial magnetic stimulation (rTMS) and moderate-intensity exercise on resting-state functional connectivity and self-reported pain outcomes in individuals with persistent post-stroke headache. Five participants completed ten sessions of rTMS targeted to the primary motor cortex followed by aerobic exercise within a 2 h window. Resting-state fMRI and behavioral data were collected at baseline and post-intervention. Seed-based analyses revealed reduced connectivity between the amygdala, insula, and thalamus and regions involved in salience, sensory, and cognitive control. Self-reported pain severity and interference (Brief Pain Inventory [BPI] and Visual Analogue Scale [VAS]) also showed mean reductions over the course of the study. These findings support the feasibility and potential neural and behavioral impact of combined neuromodulatory and behavioral interventions for managing chronic pain after stroke. Full article