Objectives This study aims to characterize the gut microbiota in arteriosclerotic cerebral small vessel disease and idiopathic normal pressure hydrocephalus (aCSVD-iNPH) patients, investigate its correlation with cerebral small vessel disease imaging markers, and develop a diagnostic model based on differential microbial profiles. Methods This study enrolled 95 subjects. Fresh fecal samples were collected for microbial DNA extraction. Gut microbiota composition was analyzed using 16S rDNA sequencing, and Spearman’s correlation analysis was performed to investigate the association between microbial abundance and imaging indicators. Results An analysis of gut microbiota diversity revealed no statistically significant differences in α -diversity among the three groups, but there were significant differences in β -diversity. Compared to the aCSVD group, the relative abundances of Clostridium_Innocuum_group, Dietzia, Lachnospira, Pedobacter, Romboutsia, Saccharomyces, Solobacterium, Thermus, and TM7x were significantly higher in the aCSVD-iNPH group (all p < 0.05). Among these, the relative abundance of Solobacterium was negatively correlated with the number of cerebral microbleeds (CMBs) in the basal ganglia ( r = −0.292, FDR-adjusted p = 0.019) and deep regions ( r = −0.296, FDR-adjusted p = 0.018). Additionally, the relative abundance of Thermus was positively correlated with the deep medullary vein (DMV) score ( r = 0.271, FDR-adjusted p = 0.031). The ROC analysis yielded AUC values ranging from 0.666 to 0.716, indicating limited discriminative ability between aCSVD-iNPH and aCSVD (Thermus, AUC = 0.716, 95% CI 0.569–0.864, p = 0.006; Saccharomyces, AUC = 0.688, 95% CI 0.535–0.842, p = 0.017; Dietzia, AUC = 0.666, 95% CI 0.512–0.821, p = 0.034). Conclusion This study identifies distinct changes in gut microbiota among patients with aCSVD-iNPH and their associations with aCSVD imaging markers, suggesting that certain microbial taxa may serve as potential diagnostic biomarkers to distinguish aCSVD-iNPH from aCSVD, although these preliminary findings require validation in independent cohorts.

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, significantly impacting patients’ quality of life. Although extensive research has focused on identifying biomarkers, PD diagnosis still relies heavily on clinical features. Current treatments are primarily symptomatic and fail to halt disease progression. Emerging evidence suggests that abnormal bilirubin (BR) levels correlate with PD severity and motor outcomes, highlighting BR’s potential as both a biomarker and a therapeutic target. This review elucidates the dual role of BR in PD pathogenesis—modulating oxidative stress, neuroinflammation, and mitochondrial dysfunction—and discusses novel BR-based therapeutic strategies.

Contactin 6 (CNTN6) is a recently discovered member of the contactins family, which belongs to a group of cell adhesion molecules. This review summarizes the current knowledge about the possible functions of CNTN6 in the organism and its manifestations in animal models and human diseases. Histological, cellular, and molecular studies in rodents have shown the involvement of this protein in neurite guidance, neural network development, and oligodendrocytogenesis. The expression levels in the cerebellum, hippocampus, and visual cortex of rodents vary depending on the period of neurodevelopment. Animal models with a deletion of the Cntn6 gene have shown impaired spatial orientation and memory patterns. In humans, copy number variation (CNV) analysis and genome-wide association studies (GWAS) found allele-phenotype relationship of this gene with autism spectrum disorder (ASD), intellectual disability (ID), Tourette syndrome (TS), schizophrenia (SCZ), anorexia, and other mental and neurodevelopmental diseases.

Acupuncture has been increasingly applied as an adjunctive treatment for major depressive disorder (MDD), yet its central neurobiological mechanisms remain insufficiently understood. Cerebral blood flow (CBF) and functional connectivity strength (FCS) provide complementary perspectives on regional metabolic activity and large-scale functional integration, and their coupling may reflect neurovascular coordination relevant to depression. Twenty patients with MDD and twenty matched healthy controls (HC) underwent resting-state MRI. Patients received intradermal acupuncture (IA) and were scanned before and immediately after stimulation, while healthy controls were scanned once. Voxel-wise analyses of CBF, FCS, and their ratio (CBF/FCS) were performed to characterize acupuncture-related changes in neurovascular coupling. Group comparisons and pre-post acupuncture effects were assessed at the whole gray matter level. Acupuncture induced significant alterations in CBF/FCS coupling across widespread brain regions, including the bilateral precuneus, postcentral gyrus, superior temporal pole, superior frontal gyrus, occipital cortex, and cerebellum. These regions are primarily involved in sensorimotor processing, cognitive control, and emotional regulation. Overall, IA was associated with an immediate increase in CBF/FCS coupling, suggesting enhanced coordination between cerebral perfusion and functional network integration. This study provides evidence that intradermal acupuncture modulates neurovascular coupling in patients with MDD, offering neuroimaging-based insights into its antidepressant mechanisms. The findings support the notion that acupuncture may facilitate more efficient brain function by optimizing the balance between neural activity and metabolic supply.

Multiple sclerosis (MS) affects different cognitive domains, including social cognition. Immersive Virtual Reality (VR) may provide a novel rehabilitative approach to treat motor and cognitive symptoms of MS. This exploratory pilot study evaluated the effects of immersive VR rehabilitation on social cognition in MS patients and explored related cortical neurophysiological signatures. Seven MS patients underwent immersive VR rehabilitation with the CAREN system (3 sessions/week, approximately 45 min of active training per session, about 1 h including preparation, 8 weeks), while seven healthy controls (HC) did not undergo any intervention. Patients were evaluated at baseline (T0) and post-treatment (T1) with standardized measures of cognitive, emotional, and motor functioning. EEG data were acquired from all participants, and, after artifact removal, spectral parameterization decomposed signals into aperiodic (exponent, offset) and periodic oscillatory components (alpha and beta power). Power spectral density was analyzed using group comparisons and Pearson correlations with neuropsychological measures. Compared with HC, MS patients showed reduced alpha-band power, mainly over frontal and parieto-occipital regions, whereas aperiodic parameters did not differ between groups. In patients, alpha and beta power correlated with the Positive Emotions Self-Efficacy Scale (alpha: r = 0.92, p = 0.003; beta: r = 0.83, p = 0.020). Alpha power is also correlated with RAO SRT-LTS (r = 0.85, p = 0.016), and beta with EQ-CE (r = 0.82, p = 0.023). Overall, alpha and beta power were correlated with emotional self-efficacy, balance, memory, and empathy, suggesting that oscillatory markers are potential indicators of clinical outcomes. Rehabilitation via immersive VR has shown promising clinically significant effects in the cognitive, emotional, and motor domains, supported by convergent EEG spectral signatures. Future studies employing predictive modeling approaches will be required to assess their prognostic value.

To explore the temporal and causal relationships underlying brain structural changes in post-radiotherapy (RT) nasopharyngeal carcinoma (NPC) patients. A total of 38 post-radiotherapy NPC patients (33 males, 5 females; median age: 50.0 years, range: 27-63 years; median time post-RT: 17.2 months, range: 0.5-108 months) and 23 healthy controls (16 males, 7 females; median age: 37 years, range: 24-61 years) underwent T1-weighted magnetic resonance (MR) images, and their images were evaluated. The causal structural covariance network (CaSCN) analysis approach was applied to assess the causal relationships underlying radiation-induced brain structural alterations in these patients. Granger causality (GC) analysis was employed to morphometric data derived from T1-weighted MR images, which were ordered by the time elapsed post-RT. The source-like directed associations were observed in the bilateral parahippocampal gyrus (PHG), the right gyrus rectus (REC.R), and the right caudate nucleus (CAU.R). The directed network analysis revealed that the parahippocampal gyrus (PHG), REC.R and CAU.R exhibited typical source-like characteristics, and their structural changes exerted a key regulatory effect on GM volume alterations across multiple brain regions. While the left precuneus (PCUN.L), left temporal pole: middle temporal gyrus (TPOmid.L) and the left inferior temporal gyrus (ITG.L) were typical sink-like brain region that mainly received regulatory effects from source-like brain regions, acting as major target regions of structural damage. Over time, post-radiotherapy NPC patients exhibited progressive changes in GM volume, where the PHG.L, PHG.R, REC.R and CAU.R were core source-like brain regions. The PCUN.L, TPOmid.L, and ITG.L show distinct sink-like features, which mainly receive regulatory effects from source-like brain regions.

Internet addiction (IA) is associated with impaired cognitive control and altered large-scale brain dynamics. Electroencephalogram (EEG) microstates provide a sensitive index of rapid neural network organization; however, whether acute aerobic exercise can modulate abnormal microstate dynamics in individuals with IA remains unclear. Forty young adults [IA: n = 20; healthy controls (HC): n = 20] completed resting-state EEG recordings before and after a single 30-min bout of moderate-intensity aerobic cycling. Microstate duration, occurrence, contribution, and transition probabilities were analyzed using mixed-design repeated-measures with time (pre/post) and Microstate (A-D) as within-subject factors and group (IA/HC) as a between-subject factor. Spearman correlations examined associations between exercise-induced microstate changes and IA severity. For microstate duration, the IA group exhibited longer duration of Microstate A than HC group at baseline (t = 2.47, p = 0.018). IA group showed reduced Microstate D occurrence at baseline compared with HC (t = 4.23, p < 0.001), followed by a significant post-exercise increase (t = -4.23, p = 0.001), eliminating group differences. Microstate contribution showed a significant Time × Group interaction [F (1, 38) = 4.68, p = 0.037, η2 = 0.110], with Microstate D contribution increasing selectively in the IA group (t = -3.71, p = 0.001). Changes in Microstate D occurrence were negatively correlated with IA severity (ρ = -0.55, p = 0.012). A single session of aerobic exercise rapidly normalizes aberrant microstate dynamics in IA, particularly within Microstate D, highlighting exercise as an effective acute neuromodulatory intervention.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique with promising application in the treatment of neurological and psychiatric disorders. However, its effectiveness is often limited by the high inter-subject variability of the induced effects, mainly attributable to individual anatomical differences, which are not considered in the design of the stimulation protocols. Among these, structural connectivity plays a crucial role but remains often overlooked in tDCS research. Objective-This study aims to evaluate how variations in structural connectivity influence the distribution of the electric field (EF) during tDCS session. In particular, we analyse how the inclusion of white matter anisotropy affects the EF distribution and spread compared to classical isotropic models, and how the strength of connection across cortical parcels affects the EF spread. Approach-The study proposes an advancement in the computational modelling of tDCS through the integration of white matter anisotropy into finite element method (FEM) simulations. By combining advanced computational approaches, we explore the relationship between EF strength and cortical connectivity. Main results-Neglecting white matter anisotropy in electromagnetic simulations lead to a relative error in EF magnitude greater than 10% and to an orientation error of the EF vector of almost 20 degrees. The DTI-informed simulations lead to a more focalized EF distribution, moreover it was found a positive and significant (p < 0.05) correlation between EF focality and the strength of connectivity between cortical areas below P2 and P1 electrodes. Significance-These findings highlight the importance of including white matter anisotropy into tDCS simulation to prevent distortions in EF distribution and suggest the need to integrate structural connectivity information into the definition of subject-specific dose in tDCS protocols.

[This corrects the article DOI: 10.3389/fnins.2026.1744871.].

BackgroundType 2 diabetes mellitus (T2DM) is often accompanied by cognitive dysfunction, though its underlying mechanisms remain unclear. Impaired glymphatic system function may contribute to cognitive impairment. Herein, we aimed to evaluate glymphatic activity in patients with T2DM using diffusion tensor imaging analysis along perivascular spaces (DTI-ALPS) and to explore its mediating role between white matter hyperintensities (Fazekas score) and Montreal Cognitive Assessment (MoCA) scores.MethodsThirty-eight patients with T2DM and 54 age- and sex-matched healthy controls underwent 3.0 T magnetic resonance imaging (MRI) and MoCA testing. The DTI-ALPS index was derived from diffusion tensor imaging data. Clinical variables included demographics, disease duration, metabolic indicators, and the homeostatic model assessment of insulin resistance (HOMA-IR) index. Group differences were analyzed using ANCOVA, correlations were assessed using Pearson analysis, and mediation analysis was used to evaluate the role of the DTI-ALPS index between Fazekas score and MoCA.ResultsThe DTI-ALPS index was significantly lower in patients with T2DM having cognitive impairment compared to both healthy controls and patients with T2DM without cognitive impairment (p < 0.001). MoCA scores positively correlated with the DTI-ALPS index (r = 0.860, p < 0.001), while HOMA-IR showed a negative correlation (r = −0.326, p < 0.05). Longer disease duration and higher Fazekas scores were associated with reduced DTI-ALPS index (p < 0.05). Mediation analysis indicated that the association between Fazekas score and MoCA was significantly and partially accounted for by the DTI-ALPS index in patients with T2DM (effect = −0.344, p < 0.05).ConclusionThe DTI-ALPS index was strongly associated with cognitive performance in patients with T2DM. Mediation analysis suggests that this relationship may reflect a mechanism in which impaired glymphatic function mediates the impact of white matter lesions on cognitive decline.