With the aging population, identifying the relationship between verbal fluency test (VFT) performance and brain atrophy is crucial for improving the early detection of cognitive decline. This study aimed to investigate the association between cerebral cortical volume and performance on VFTs, specifically category (CFT) and letter (LFT) fluency tests, to identify brain regions associated with verbal fluency. In this cross-sectional observational study, community-dwelling adults underwent brain magnetic resonance imaging (MRI) and completed CFTs and LFTs. Participants with organic brain anomalies on MRI were excluded. Using multiple linear regression, the relationship, adjusted for age, sex, Mini-Mental State Examination score, and total brain volume, between local gray matter volumes in 22 cortical regions in both hemispheres and VFT performance was analyzed. We included 267 community-dwelling adults (70 years and 0.8 months ± 6 years and 2.3 months; 178 men and 89 women). A significant association was found between CFT scores and volume of the left inferior frontal gyrus (R2 = 0.1765, corrected-p = 0.0027), specifically the pars orbitalis (R2 = 0.1520, corrected-p = 0.011) and pars triangularis (R2 = 0.1452, corrected-p = 0.036). No significant associations were observed between LFT scores and cortical volumes. These findings align with previous lesion and functional MRI studies highlighting the left inferior frontal gyrus' role in language production. Lower CFT performance was associated with smaller left inferior frontal gyrus volume. Longitudinal and predictive studies are required before diagnostic or prognostic utility can be inferred.
Effective stress regulation is essential for emotional health, whereas maladaptive stress responses contribute to neuropsychiatric disorders such as depression and post-traumatic stress disorder. Because neuron–microglia interactions are increasingly recognized as key modulators of neuroplasticity under physiological conditions, stress-related microglial dysregulation may contribute to aberrant neuronal responses implicated in mental health disorders. This exploratory study examined region-specific microglial morphometric responses to acute intense stress, chronic restraint stress, and social defeat stress (SDS) in the amygdala and habenula, focusing on the BLA, CeA, LHb, and MHb. Microglial morphology was assessed using animal-level morphometric comparisons and exploratory cluster-based profiling. Acute stress was associated with limited animal-level morphometric differences, while exploratory cluster distributions suggested subregion-dependent shifts, particularly in the CeA and LHb. Chronic stress was associated with larger soma-related parameters in the BLA and CeA, together with a descriptive redistribution toward large-soma/low-process profiles in both amygdalar subregions. In the habenula, chronic stress induced selective MHb morphometric changes, while cluster profiles remained comparatively constrained. SDS was associated with the most pronounced remodelling in the amygdala, including increased soma-related measures, reduced circularity/solidity in the CeA, altered spatial organization, and a strong redistribution toward large-soma/ high-process profile. SDS also shifted LHb cluster profiles, whereas the MHb showed comparatively limited sensitivity. Overall, these exploratory findings suggest that different stressors are associated with region- and subregion-dependent microglial remodelling, with the amygdala showing greater stress-related plasticity than the habenula. These patterns support further investigation of microglial morphological adaptation as a potential contributor to stress-related psychopathology.
The rapid digitalisation of design education has fundamentally altered how students collaborate; however, the cognitive and neurophysiological dynamics underlying online creative co-creation remain poorly understood. To address this, we conducted an exploratory pilot study (N = 11 dyads) employing a multimodal paradigm that integrated behavioural protocol analysis with fNIRS hyperscanning. Specifically, this study examined the effects of collaborative modality (face-to-face versus online via Zoom) and interactional behaviours between design students on neural coupling, utilising Phase Locking Value (PLV) to quantify inter-brain synchrony (IBS). The results revealed an inversion between observable behaviour and underlying neural synchrony. In face-to-face settings, dyads spent the majority of their time communicating verbally, yet their highest levels of IBS were associated with sketching. Conversely, although participants sketched significantly more often in the online environment, the neural coupling previously associated with sketching collapsed. Instead, verbal communication emerged as the primary correlate of enhanced IBS in the digital space. These initial findings indicate that online collaborative dyads may rely more heavily on explicit verbal channels to maintain cognitive alignment. Crucially, because generative “Solution Space” activities inherently demand the visual externalisation of ideas, this disruption of sketching-associated neural coupling raises the theoretical hypothesis that remote environments may leave students more susceptible to misaligned mental models or design fixation during the solution exploration phases. It also highlights a critical avenue for future outcome-based research.
Collaborative problem solving plays a central role in children’s cognitive and social development, yet how neural activity relates to real-time peer coordination remains poorly understood. Using functional near-infrared spectroscopy (fNIRS) hyperscanning, we simultaneously recorded brain activity from 15 dyads of school-aged children during a naturalistic Tangram puzzle task, including rest, solo problem-solving, observation, and collaboration. We examined task-related neural activation and inter-brain connectivity (IBC) to assess how interpersonal neural dynamics relate to task context and behavior. No prespecified region-of-interest activation effect survived correction for multiple comparisons. At the exploratory channel level, a posterior-parietal channel showed a positive HbO response during collaboration relative to baseline. The global IBC did not differ significantly across experimental conditions, indicating that inter-brain synchrony was not determined solely by collaboration or social presence. Nevertheless, an exploratory association between global HbO coupling during Duo and total manual activity showed a relevant magnitude (Spearman rho = 0.581), a bootstrap 95
Dietary patterns covary with cognitive performance during adolescence, but the structural brain features associated with this covariance remain incompletely characterized. To identify structural brain correlates of cognition-aligned dietary patterns in adolescents while addressing adiposity, ethnicity adjustment, family relatedness, and multiple testing. We analyzed 3,308 adolescents from ABCD Release 5.1. Ten food-group measures were summarized by five dietary principal components (PCs). We constructed sample-derived, cognition-aligned dietary scores (PolyIQ) and used repeated five-fold family-level cross-fitting so that each participant’s score was calculated using cognition-derived weights estimated without that participant or members of the same family. The original PCs provided an outcome-independent benchmark. Primary models adjusted for age, sex, pubertal stage, socioeconomic status, income-to-needs ratio, sleep, and age- and sex-standardized BMI; ethnicity was excluded from primary models and added in sensitivity analyses. Brain–cognition models and family-cluster bootstrap indirect-effect models examined fractional anisotropy (FA), cortical thickness, surface area, and regional volume. All pre-specified indirect-effect models, including nonsignificant results, were retained. Cross-fitted dietary scores were associated with crystallized cognition (β = 0.099, SE = 0.018, P < 0.001) and fluid cognition (β = 0.064, SE = 0.015, P < 0.001); the five original dietary PCs were jointly associated with both domains. Brain–cognition associations in the bilateral fornix and hippocampal cingulum remained after BMI adjustment. In the all-ROI analysis, indirect associations through right and left fornix FA survived false-discovery-rate correction for both crystallized cognition (right: 0.0067, 95
Auditory Verbal Hallucinations (AVH) are not exclusive to schizophrenia but also occur in other psychiatric disorders, including Borderline Personality Disorder (BPD). While AVH in SZ has been extensively studied, their neurobiological underpinnings in BPD remain poorly understood. Preliminary evidence suggests structural anomalies in auditory regions among BPD patients experiencing AVH, indicating potential neuroanatomical vulnerabilities. This study examined structural brain differences in female BPD patients with (BPD-AVH n = 20) and without (BPD-nAVH n = 27) a lifetime history of AVH, as well as healthy controls (HC, n = 30), using high-resolution structural MRI. Cortical thickness (CTh), gyrification (CG), and gray matter volume (GMV) were assessed in frontotemporal regions implicated in auditory and speech processing, including the inferior frontal gyrus and superior, middle, and transverse temporal gyri. Region-of-interest (ROI) analyses were performed via CAT12, with supplementary segmentation of Heschl’s gyrus using the TASH toolbox. Group comparisons were conducted using SPM12. Compared to both HC and BPD-nAVH, BPD-AVH patients showed significantly reduced CG in the right transverse temporal gyrus (rTTG), a region encompassing early auditory cortex. No significant group differences emerged in other ROI analyses, for GMV, CG or CTh. Reduced gyrification in the rTTG suggests aberrant cortical folding in early auditory regions among BPD patients with AVH. This may reflect disrupted neurodevelopmental processes that impair auditory signal encoding and internal vs. external sound source discrimination. These findings highlight the role of primary auditory cortex abnormalities in AVH and support transdiagnostic models emphasizing early sensory processing deficits.
Personality traits are stable individual differences linked to important life outcomes including mental health, occupational functioning, and interpersonal relationships, yet their neural bases remain poorly characterized. Prior electroencephalography (EEG) studies have mainly examined isolated features such as spectral power or frontal asymmetry and have yielded mixed results. Building on recent work in connectome based predictive modeling, this study tested whether resting state EEG connectivity can predict Big Five personality traits in a nonclinical student sample. Resting state EEG (eyes open and eyes closed; about five minutes) was recorded from 115 healthy Chinese university students aged 18 to 28 years, who completed a psychometrically validated Chinese version of the Big Five Inventory 2. The exploratory CPM analyses reported here were conducted using eyes-open connectivity matrices derived from amplitude envelope correlation (AEC) and debiased weighted phase lag index (dwPLI) across canonical frequency bands. At the model-specific level, three CPM models yielded modest cross-validated correlations between observed and predicted trait scores: alpha-band AEC for Conscientiousness (r = 0.30, 95
Axon-carrying dendrites, AcDs, have been reported in hippocampus to be privileged dendrites which can directly feed synaptic inputs into an axonal output bypassing the soma and escaping somatic inhibition. In non-primate neocortex, 15–20
Associations between patterns of brain connectivity and brain structural features have transdiagnostic relevance to psychopathology. There is considerable evidence for disruptions to the hippocampus and temporoparietal brain systems in psychotic disorders. The present study examines structure–function relationships—specifically, the relation of hippocampal volume with patterns of temporoparietal effective connectivity—in youth at clinical high-risk for psychosis (CHR-P) and healthy controls (HCs). Participants at CHR-P and HCs completed clinical symptom measures and magnetic resonance imaging at baseline (n = 388, 42.5
Response inhibition, or the ability to suppress “pre-potent” behavioral responses, is subserved by both motor and inhibitory control processes and linked to the anterior mid-cingulate cortex (aMCC). We utilized an adapted Go/No-Go paradigm combined with proton functional magnetic resonance spectroscopy (1H fMRS) of the dACC to investigate differences in glutamate level between an All-Go (non-selective motor responding) and Go/No-Go (selective motor responding) condition, both compared to a no-response condition. This allowed disambiguation of the excitatory neurochemistry underlying motor vs. inhibitory control processes. 1H fMRS (midline dACC; 4.1 cm3) was acquired in 15 participants at 3T during non-selective (response to 100
This review synthesizes current evidence on the psychological and neurological benefits of physical activity, with emphasis on mental health, Parkinson’s disease (PD), and Alzheimer’s disease (AD). Physical inactivity is increasingly recognized as a modifiable risk factor that may exacerbate neuroinflammatory and metabolic dysfunctions associated with these conditions. Structured exercise has been shown to activate muscle–brain signaling pathways, including neurotrophic factors (BDNF, IGF-1, VEGF), immune modulation (IL-6, IL-10), metabolic regulators (PGC-1α, SIRT1), and peripheral mediators such as myokines and gut-brain axis components. For mental health, exercise is associated with reductions in depressive, anxiety, and stress-related symptoms, potentially through HPA-axis recalibration, neurotransmitter remodeling (serotonin, dopamine), and enhanced endocannabinoid signaling. These changes are supported by fMRI and EEG studies showing improved prefrontal–limbic connectivity and cognitive resilience. In PD, exercise interventions are linked to improvements in motor control, balance, and mood, likely mediated by dopaminergic integrity, neurotrophic support, and anti-inflammatory effects, with multimodal programs (aerobic, resistance, and dance-based) often demonstrating superior outcomes. In AD, mid-life physical activity has been associated with reduced dementia risk in epidemiological studies; proposed mechanisms include enhanced amyloid/tau clearance, glymphatic function, and synaptic adaptation, with some RCTs reporting hippocampal volume preservation and improved network connectivity. Shared mechanisms across conditions include neurotrophic upregulation and anti-inflammatory effects, whereas distinct pathways involve dopaminergic circuit remodeling in PD and glymphatic facilitation in AD. Clinical translation through FITT principles (frequency, intensity, time, type) requires personalized prescriptions, strong adherence strategies, and multidisciplinary integration. Despite methodological heterogeneity and limitations in the existing trials, structured physical activity emerges as a scalable, non-pharmacological intervention with potential for prevention, symptom management, and neuroprotection. Larger, well-designed studies are needed to optimize its application and clarify long-term disease-modifying effects.
The Wada test is an invasive procedure used to assess language and memory lateralization. Despite the widespread use of the Wada test in the population of people with epilepsy, the two existing standardized protocols for conducting the procedure are methodologically different and do not fully account for language comprehension as a separate domain. In this study, we presented a novel, optimized Wada protocol developed and tested using Russian language stimuli, with an English adaptation provided to support crosslinguistic application. The protocol was applied to a cohort of eight patients undergoing presurgical evaluation, demonstrating consistent lateralization patterns: language comprehension was predominately bilateral, while production was unilaterally localized in most patients, and memory representation was either bilaterally and right-hemisphere organized. Postoperative outcomes available for four patients confirmed the protocol's ability to identify eloquent hemispheres, as patients with unilateral language dominance showed transient language deficits after surgery, whereas those with bilateral representation did not. Furthermore, the intraoperative mapping results also corroborate the obtained outcomes. These findings support the protocol's enhanced applicability for determining individual patterns of language and memory lateralization, offering valuable insights to improve presurgical planning and treatment strategy selection for epilepsy patients.
Sensory processing deficits in schizophrenia have been linked to dysfunction of cortical inhibitory interneurons, particularly parvalbumin-expressing (PV+) populations. NMDA receptor hypofunction during development is known to disrupt interneuron maturation, but its long-term impact on visual cortex circuitry and the potential for experience-dependent modulation in adulthood remain unclear. Here, we examined the effects of early postnatal N-methyl-D-aspartate (NMDA) receptor blockade with MK-801 on the number of PV+ and somatostatin-expressing (SST+) interneurons in the primary visual cortex (V1) and assessed whether environmental enrichment (EE) in adulthood modulates these alterations by analyzing molecular changes using Western blot. Male Long–Evans rats received MK-801 (0.5 mg/kg) or saline from postnatal day 10–20, followed by EE exposure from P55–73. Stereological analyses revealed a marked reduction of PV-immunoreactive cells in layers II/III and IV, while SST+ populations were largely preserved. EE increased the number of PV-immunoreactive cells across groups, and modestly enhanced SST+ cells in layer IV, although no treatment × housing interaction was detected, indicating a general enrichment-related effect. At the molecular level, MK-801 reduced expression of the NMDA receptor subunit NR1 and increased Akt phosphorylation, whereas EE enhanced PSD95 expression, ERK phosphorylation, and GABAA β2/3 subunit levels, without increasing NR1 levels. These findings indicate that early NMDA receptor hypofunction induces long-lasting, subtype-specific alterations in inhibitory circuitry in V1. EE in adulthood engages molecular pathways associated with synaptic plasticity and modulates interneuron immunoreactivity, suggesting that inhibitory circuits retain some capacity for experience-dependent remodeling despite persistent receptor-level deficits.
Temporal lobe epilepsy (TLE) is increasingly recognized as a distributed network disorder extending beyond mesial temporal structures. Among the brain regions implicated in epileptic network organization, the thalamus has emerged as a key hub due to its extensive structural and functional connections with cortical, limbic, and subcortical systems.This integrative review aimed to synthesize current evidence regarding nucleus-specific thalamic abnormalities and thalamocortical connectivity alterations in TLE.A literature search was conducted following PRISMA guidelines using PubMed and Google Scholar databases. Twenty-eight studies were included in the qualitative synthesis, with nineteen studies providing detailed nucleus-specific structural, functional, or electrophysiological characterization of thalamic involvement.Across structural MRI, diffusion imaging, resting-state functional MRI, magnetoencephalography, and stereo-electroencephalography studies, convergent evidence indicated preferential involvement of the anterior thalamic nucleus (ANT), mediodorsal nucleus (MD), pulvinar, and intralaminar nuclei. TLE with mesial temporal sclerosis generally exhibited more extensive thalamic atrophy and thalamotemporal disconnection, whereas MRI-negative TLE showed more heterogeneous functional and network-level abnormalities. Electrophysiological studies demonstrated dynamic thalamic participation in seizure propagation and network synchronization, supporting an active role of thalamic nuclei in epileptic processes. Emerging longitudinal evidence further suggests that thalamocortical networks may undergo postoperative reorganization following successful epilepsy surgery.Overall, the available evidence supports a transition from a predominantly hippocampocentric framework toward a distributed thalamocortical network model of TLE. Nucleus-specific thalamic dysfunction appears to contribute to seizure propagation, cognitive impairment, and large-scale network dysregulation, highlighting the importance of multimodal approaches for understanding epileptic network organization.
Border-associated macrophages (BAM) and mast cells are resident immune cells at the peripheral CNS borders, strategically located close to the brain surface, potentially influencing the homeostasis of the underlying parenchyma. Subarachnoid haemorrhage (SAH), when blood enters between the meningeal layers that cover the brain, is associated with neuroinflammation, which has been shown to play a critical role in subsequent brain damage; however, the impact of the activation of border-associated immune cells on the pathomechanism of the disease has not been investigated. Our aim was to examine inflammatory reactions that occur simultaneously at the cellular level in various compartments of the CNS: meningeal, subdural space, and parenchyma after experimental SAH in rats. Using immunohistochemistry, we performed the morphological characterisation of the BAM subpopulations in meningeal preparations. Additionally, confocal microscopy and image analysis were used to evaluate the reactive state of microglia cells and the integrity of the glial boundary in the upper fronto-parietal cortex of the rat 72 h after SAH. We demonstrated morphological alterations of BAM populations in the meninges and parallel disintegration of the astrocyte barrier due to haemorrhage. Furthermore, we confirmed the crucial role of mast cells in subsequent glial reactions. Our results suggest that activation of border-associated immune cells, contemporaneously with the early neuroinflammatory reactions that take place in the brain parenchyma, proposes a feasible signalling between these compartments following haemorrhage. Further studies are to be performed to reveal the importance of CNS meningeal border as a communication interface in the pathomechanism of SAH.
Developmental dyslexia (DD) is a common neurodevelopmental disorder, whose causes lie in genetic and neurobiological underpinnings. DCDC2 is one of the most replicated candidate genes underlying the etiology of reading (dis)abilities and has been associated with neural migration patterns. Although a deletion within intron 2 of the DCDC2, encompassing the entire READ1 (hereafter READ1d), has been reported to be linked to structural and functional brain alterations, its impact on white matter connectivity was not fully explored. In this study, we investigated how the READ1d influences white matter network organization and its relationship with reading ability. Seventy-four children (47 M/27 F, age in months: 161 ± 22) with/without a diagnosis of DD and with/without READ1d underwent diffusion MRI, from which graph-theoretical analysis was performed. Statistical analyses tested the effects of READ1d, reading proficiency, and their interaction, with age, sex, IQ, and attention scores included as covariates. Regardless of reading performance, subjects with READ1d showed nominally significant lower global efficiency, local efficiency, and clustering coefficient compared to subjects without READ1d, with consistent effect directions across metrics; the nodal analysis revealed a significant effect of READ1d on a network spanning lateral, occipital and frontal cortex. Reading performance was associated with a network in the left occipital-temporal cortex at the level of nodal degree and a scattered bilateral network for local efficiency. These findings are consistent with an association between READ1d carrier status and subtle but widespread differences in network integration and nodal connectivity, observed regardless of reading performance, and offer a framework for future multimodal investigations into the genetic architecture of reading disorders.
The functional organization of the teleost telencephalic pallium remains poorly understood, particularly regarding the presence of modality-specific sensory domains and their topographic arrangement. Here, we used in vivo wide-field voltage-sensitive dye imaging to map sensory-evoked neural activity across the dorsal surface of the telencephalic pallium of adult goldfish. Somatosensory, auditory, gustatory, and visual stimulation revealed distinct, modality-specific domains located within the dorsomedial (Dm) and dorsolateral (Dl) pallium, that closely matched cytoarchitectural boundaries. Within Dm, somatosensory and auditory stimuli activated partially overlapping territories in the caudal subregion (Dm4), exhibiting clear somatotopic and tonotopic organization along the mediolateral axis. Gustatory stimulation selectively engaged Dm3, where different tastants activated spatially distinct but partially overlapping domains. A more rostral subregion (Dm2) responded only to high-intensity somatosensory stimulation, suggesting involvement in processing negatively valenced inputs, whereas the adjacent Dm1 remained unresponsive to all sensory modalities tested. Visual stimulation activated a circumscribed area within the dorsolateral pallium (Dld2). Pharmacological blockade of ionotropic glutamate receptors markedly reduced sensory-evoked responses, indicating that these maps depend on glutamatergic synaptic transmission. Together, these findings reveal a more elaborate and functionally differentiated pallial organization than previously recognized and provide the first direct evidence for modality-specific topographic sensory maps in the teleost pallium. More broadly, they offer a new framework for understanding how sensory, affective, and mnemonic functions are organized within the teleost pallium and for comparing this organization with distributed pallial systems in other vertebrates. Voltage-sensitive dye imaging was used to map sensory responses in the goldfish pallium. Distinct sensory areas for somatosensory, auditory, gustatory, and visual modalities were identified. Some sensory regions in Dm show topographically organized maps. Functional segregation suggests a complex, non-diffuse pallial organization. Findings support a novel hypothesis linking Dm and Dld to mammalian mesocortical regions.
Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized primarily by progressive cognitive decline and tremor. While these clinical features are well-recognized, the specific structural neural substrates and morphometric alterations underlying these symptoms remain poorly understood. This prospective study included 10 genetically confirmed NIID patients and 10 age- and sex-matched controls. Following high-resolution T1-weighted MRI and MoCA-based cognitive assessment, atlas-based morphometry was utilized to characterize gray-matter alterations. The analytical workflow prioritized identifying global atrophy patterns between groups, followed by correlation analyses between identified atrophic regions and clinical markers (MoCA scores and disease onset). Additionally, subgroup comparisons were conducted within the patient cohort to identify the neural correlates of tremor. Compared with healthy controls, NIID patients exhibited widespread gray-matter atrophy primarily involving the extensive temporal and occipital cortices, limbic and paralimbic regions (including the cingulate gyri, hippocampus, and amygdala), and the thalamus (Bonferroni-corrected, p < 0.05). Notably, lower MoCA scores were significantly associated with reduced volumes in the left hippocampus and the left temporal pole (extending to the superior and middle temporal gyri) (all p < 0.05). Earlier disease onset was correlated with the relative preservation of the left thalamus (r = -0.755, p = 0.019). Finally, patients manifesting tremor displayed significantly diminished gray-matter volume in the right hippocampus compared to tremor-free patients (t = 2.472, p = 0.039). Distinct morphometric substrates underpin cognitive dysfunction and tremor in NIID. Cognitive decline is primarily associated with atrophy in the left hippocampus and temporal regions, whereas tremor manifestation is linked to right hippocampal volume loss. These findings elucidate the neuroanatomical basis of NIID’s core symptoms and highlight regional brain atrophy as a potential imaging biomarker for disease monitoring and future therapeutic trials.
The prefrontal cortex (PFC) is often treated as the anatomical seat of executive control. We defend a distributed but structurally constrained account. The PFC is not an exclusive executive locus; it is a transient and structurally tuned cortical interface in which laminar differentiation, molecular tuning, recurrent synaptic persistence, thalamocortical embedding, and long-range connectivity converge to support context-sensitive control. We review prefrontal organization across genomic and transcriptomic patterning, receptor architecture, synaptic and interneuronal organization, laminar microcircuitry, white-matter constraints, and large-scale network dynamics. We argue that canonical cortical motifs are prefrontally parameterized toward four operations: convergence, filtering, maintenance, and feedback. Inputs are selected through molecularly tuned and inhibitory-gated laminar compartments; task-relevant states are stabilized through recurrent, neuromodulation-sensitive synaptic regimes; and selected states are exported through deep-layer corticocortical, corticostriatal, and corticothalamic channels. Evidence from gradual cortical damage, particularly low-grade glioma, suggests that preserved cognition after prefrontal injury is better explained by network-constrained functional reinstantiation than by strict regional essentialism. Yet compensation should not be equated with unconstrained migration of function; whether it depends on partial microcircuital convergence, synaptic re-weighting, network redistribution, or a combination of these mechanisms remains an open empirical question. Finally, we organize these mechanisms across encoding, maintenance/manipulation, and retrieval, arguing that prefrontal participation is temporally structured rather than statically localized. Progress will require a spatiotemporal multiscale atlas linking molecularly parameterized laminar motifs, tract engagement, and network interactions across cognitive stages.
