Mental scene construction-the ability to generate coherent, spatially organized, and vivid internal representations-is central to episodic memory, future thinking, and social cognition. However, in behavioral-variant frontotemporal dementia (bvFTD), relatively little is known about how core components of mental scene construction, such as visual imagery, spatial imagery, imagery vividness, and visuospatial working memory, are affected. In this study, 21 bvFTD patients and 25 matched controls completed tasks assessing these processes: the Taller/Wider Task, the Clock Angles Task, the Vividness of Visual Imagery Questionnaire, and forward and backward Corsi Block-Tapping. Patients with bvFTD showed marked impairments across all tasks. In this group, general cognitive functioning was positively correlated with performance on the visual imagery, spatial imagery, and visuospatial working memory tasks, but not with imagery vividness. These findings highlight marked impairments in fundamental imagery and mental scene construction, consistent with broader disruptions in visuospatial processing and working memory processes in bvFTD.

Chemotherapy-associated behavioral deficits, including cognitive impairment and depression, collectively termed chemobrain, often persist into the chronic phase after treatment, yet their underlying cellular mechanisms remain unclear. In particular, it remains unknown whether long-lasting behavioral deficits are associated with sustained neuroinflammatory responses or other forms of microglial alteration. We therefore examined whether chronic behavioral deficits were associated with region-specific microglial morphological alterations and inflammatory gene expression changes, and how EA intervention was associated with these alterations. Male SD rats were assigned to the Control, PTX, and PTX + EA groups. Cognitive and emotional behaviors were assessed using behavioral tests. Microglial morphology in the hippocampus across the dorsoventral axis and mPFC was analyzed using skeleton analysis, and inflammatory gene expression was evaluated by qPCR. PTX induced cognitive impairment and depressive-like behavior, accompanied by a selective reduction in microglial process number and length in the dentate gyrus of the dorsal hippocampus and the infralimbic cortex of the mPFC. Microglial morphology differed between the PTX and PTX + EA groups in both regions, although the difference in the dorsal dentate gyrus was limited to process number. No significant changes in the inflammatory genes examined were detected in the hippocampus or mPFC. Thus, PTX produced chronic behavioral deficits accompanied by selective microglial remodeling in the dorsal dentate gyrus and infralimbic cortex, but not in the ventral hippocampus, with no detectable changes in inflammatory gene expression. Behavioral outcomes and microglial morphology differed between the PTX and PTX + EA groups, indicating an association between EA intervention and region-specific microglial remodeling.

Charitable giving depends both on how money is acquired and on expectations about its eventual use. However, it remains unclear how monetary source shapes the evaluation of donation-risk information after a donation decision. Twenty-six participants made repeated donation decisions using earned and windfall money while electroencephalography was recorded. After each choice, a cue indicated a 70 % probability of allocation to either a lower-credibility charity (high risk) or a higher-credibility charity (low risk). One decision and its associated allocation rule were implemented at the end of the experiment. Participants donated more from windfall than earned money and reported greater regret and lower satisfaction after high-risk than low-risk cues. Mixed-effects analysis also showed lower next-trial donations following high-risk cues. Windfall money was associated with less positive frontocentral mean voltage within the feedback-related negativity (FRN) interval, whereas low-risk information elicited a larger P3. The predicted monetary-source-by-risk interaction was not supported, and Bayesian comparisons favored the zero-interaction model over the specified alternative. These findings show that monetary acquisition context and prospective allocation information both matter for charitable giving and its neural evaluation. They extend research on donation-related feedback by demonstrating behavioral adjustment to consequential risk information before the recipient and the realized charitable outcome are known.

TAR DNA-binding protein 43 (TDP-43) pathology is a defining feature of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although TDP-43 dysfunction has traditionally been studied through a neuron-centric framework, increasing evidence demonstrates that astrocytes, microglia, and oligodendrocytes are also directly affected and actively contribute to disease progression. In this review, we examine how TDP-43 dysfunction disrupts lineage-specific glial homeostatic programs and promotes distinct pathological state transitions across major glial populations. In astrocytes, TDP-43 dysfunction impairs neurotransmitter regulation, metabolic and neuronal support, RNA homeostasis, and secretory signaling while promoting inflammatory and antiviral-like states. In microglia, altered TDP-43 disrupts inflammatory regulation, phagocytosis, lysosomal function, lipid metabolism, and stage-dependent protective responses. In oligodendrocytes, TDP-43 dysfunction compromises RNA processing, lineage maintenance, lipid metabolism, myelin integrity, and long-term axonal support. Together, these findings suggest that glial TDP-43 dysfunction cannot be reduced to a single generalized form of reactivity but instead reflects the breakdown of distinct cell type-specific identities required to maintain central nervous system homeostasis. A cross-glial framework integrating cell-autonomous dysfunction, non-cell-autonomous signaling, disease stage, and genetic context may therefore provide a more complete understanding of TDP-43 proteinopathy and its contribution to neurodegeneration across the ALS-FTD spectrum.

Cell therapy using human umbilical cord-derived mesenchymal stem cells (hUCMSCs) is attracting attention as a promising treatment strategy for ischemic stroke. This study investigated the therapeutic effects and associated biological changes following hUCMSC administration during the subacute phase using a mouse model of permanent middle cerebral artery occlusion (MCAO). Based on our previous findings showing an increase in CD163-positive brain immune cells after hUCMSC administration, we hypothesized that subacute hUCMSC treatment would be associated with changes in myeloid immune responses and high-mobility group box 1 (HMGB1) dynamics. hUCMSCs were administered intravenously two weeks after MCAO induction. Ischemic brain and systemic immune responses were evaluated at the 3[rd], 4[th], and 5[th] weeks post-MCAO using flow cytometry, RT-qPCR, immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), Evans Blue assay, Western blotting, and ELISA. Neurobehavioral outcomes were also assessed during the subacute and chronic phases after MCAO. Subacute hUCMSC administration was associated with improved neurobehavioral outcomes after ischemic stroke. Brain immune-cell analyses showed treatment-associated changes in CD163/CD204 co-expression and intracellular HMGB1 accumulation, while peripheral myeloid populations also exhibited changes in CD163 expression within Ly6C subsets. These findings indicate that neurobehavioral improvement following hUCMSC administration was accompanied by local and systemic myeloid immune changes and altered intracellular HMGB1 dynamics.

Post-stroke dysphagia is a common complication with limited treatment options. Transcutaneous auricular vagus nerve stimulation (ta-VNS) has shown neuroprotective effects. This study investigated whether ta-VNS improves swallowing function and alleviates neuroinflammation by modulating microglial M1/M2 polarization, examining the role of von Willebrand factor (VWF) in endothelial-microglial crosstalk. A rat model of transient bilateral middle cerebral artery occlusion (MCAO) was established. Rats received ta-VNS for 3 weeks, and swallowing function, neurological deficits, and inflammatory markers were assessed. Microglial M1 (CD16) and M2 (CD206) polarization in the white matter was examined by immunofluorescence. RNA-seq was used to identify candidate genes. In vitro, an oxygen-glucose deprivation/reoxygenation (OGD/R) model was applied to hCMEC/D3 endothelial cells co-cultured with HMC3 microglia, and VWF was knocked down using shRNA to evaluate its effect on microglial polarization and inflammation. ta-VNS significantly improved body weight, food/water intake, and swallowing function (reduced latency and increased swallowing frequency) in transient middle cerebral artery occlusion rats. ta-VNS reduced levels of TNF-α, IL-6, IL-1β, and IL-10, attenuated microglial activation, suppressed M1 (Iba-1[+]CD16[+]) microglia, and enhanced M2 (Iba-1[+]CD206[+]) polarization in rat whiter matter. RNA-seq revealed downregulation of VWF after ta-VNS, with enrichment in the PI3K-Akt pathway. In vitro, OGD/R upregulated VWF, ICAM-1, VCAM-1, endothelial apoptosis, and permeability. Knockdown of VWF in endothelial cells shifted co-cultured microglia from M1 toward M2 phenotype and reduced TNF-α, IL-6, and IL-1β while increasing IL-10. ta-VNS can improve post-stroke dysphagia and reduce neuroinflammation by promoting M2 microglial polarization. Endothelial VWF may be a key downstream mediator of this process.

The prelimbic division (PrL) of the medial prefrontal cortex is implicated in the pathogenesis of generalised anxiety and chronic pain disorders. This study aimed to investigate the role of PrL N-methyl-D-aspartate (NMDA) receptor signalling in the comorbidity between neuropathic pain and psychiatric disorders. Male Wistar rats were exposed to the Enriched Polygonal Arena Snake-Evoked Panic Test involving confrontation by a constrictor snake. Neuropathy was induced by chronic constriction injury (CCI) of the ischiadicus nerve. Rats subjected to a sham surgical procedure were used as controls. Electrophysiological recordings were performed to assess PrL neuronal activity in CCI and sham-operated rats. Exposure to the threatening environment was conducted 21 days after surgery for 5 min following PrL cortical treatment with vehicle or LY235959 (2, 4, and 8 nmol). Neuronal activity in the PrL cortex was reduced in CCI rats. When confronted with a potential predator, threatened CCI rats exhibited increased emotional defensive responses accompanied by a decrease in mechanical paw withdrawal threshold (MWT), whereas sham-operated animals (without neuropathy) showed an increase in MWT following snake confrontation. Furthermore, NMDA receptor blockade in the PrL cortex with LY235959 reduced both defensive behaviours and mechanical allodynia in threatened animals. These findings suggest that NMDA receptor signalling in the PrL cortex plays a key role in the potentiation and maintenance of the comorbidity between anxiety/panic-like states and chronic neuropathic pain.

This exploratory study aimed to characterize dynamic functional network connectivity (dFNC) alterations in spinal cord injury-induced neuropathic pain (SCI-NP) and dFNC-related metrics as biomarkers for treatment guidance. A total of 23 SCI individuals with NP (SCI-NP), 20 SCI individuals without NP (SCI-N), and 20 healthy controls (HCs) were enrolled. SCI-NP individuals were predominantly chronic (≥12 months post-injury), whereas SCI-N individuals were predominantly acute/subacute (<12 months post-injury). Resting-state fMRI data were analyzed using independent component analysis (ICA) combined with a sliding-window approach to characterize dFNC. Recurring connectivity states were identified using clustering algorithms. Group differences were assessed using ANCOVA, adjusting for age and sex. P values were FDR-corrected for multiple comparisons. Spearman's correlation analyses examined associations between dFNC metrics and pain and clinical scores. Twenty-two whole-brain independent components were identified, and seven functionally meaningful components were selected for dFNC analysis, which revealed six distinct connectivity states. Compared with the SCI-N group, the SCI-NP individuals showed increased State 1 connectivity between the medial visual network (mVN) and sensorimotor network (SMN) and between the default mode network (DMN) and SMN (both p < 0.05, uncorrected), reflecting enhanced cross-modal sensory integration and maladaptive plasticity commonly observed in chronic neuropathic pain. In contrast, State 6 exhibited significantly reduced DMN-visual network (VN) connectivity in the SCI-NP group (p < 0.05, uncorrected), representing a low-interaction resting configuration that may reflect preserved functional segregation preferentially maintained in the SCI-N group. The SCI-NP individuals had shorter mean dwell time (p = 0.04, uncorrected) and fraction of time (p = 0.03, uncorrected) in State 6 relative to SCI-N individuals. None of these differences survived FDR correction.These findings indicate that SCI-NP individuals exhibit state-specific dynamic connectivity disturbances, including maladaptive hyperconnectivity involving sensorimotor, visual, and default mode networks. Metrics of dFNC-including state-specific connectivity and dwell time may serve as sensitive imaging features for guiding targeted rehabilitation strategies in SCI-NP.

Cerebral small vessel disease (CSVD) is a leading cause of vascular cognitive impairment (VCI), characteristically associated with gray matter (GM) loss. However, it remains unclear whether this GM loss exhibits regional interhemispheric asymmetry and how it relates to cognitive function. In this study, 56 CSVD patients and 56 demographically matched healthy controls were included, and structural MRI as well as cognitive and clinical data were collected. Voxel-based morphometry (VBM) and the GM Asymmetry Index (GMAI; calculated as (L-R)/(L + R), higher values indicate relatively greater left-sided GM) were performed using a study-specific symmetric template. Perivascular spaces were also estimated with a deep learning framework. Partial correlations were tested against multi-domain cognitive performance. Compared with controls, CSVD patients exhibited extensive GM reduction in the right superior and middle frontal gyri as well as in the left hippocampus and putamen. Regional GMAI analyses further suggested altered hemispheric GM loss, with leftward shifts (higher GMAI) in the middle temporal gyrus, superior frontal gyrus, and precuneus, and rightward shifts (lower GMAI) in the inferior temporal and fusiform gyri. Additionally, subcortical nuclei exhibited a corresponding leftward lateralization of perivascular space burden. Association analyses showed that right prefrontal volume was positively related to global cognitive scores, whereas left temporal asymmetry tracked cognitive decline. Of note, this right-dominant pattern in prefrontal-related regions is consistent with our activation likelihood estimation meta-analytic re-synthesis of prior VBM evidence and NeuroSynth mapping. Collectively, these findings suggest a distinct topographical vulnerability of the right hemisphere in CSVD and highlight GMAI as a neuroimaging marker for vascular cognitive decline.