Brain Research Bulletin[JOURNAL]
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200 papers
Thalamic atrophy and its impact on cognitive function in normal aging.
Zhang X, Shi Y, Yu G … +5 more , Zhang M, Cao W, Chen Z, Jiao Q, Cui D
Brain Res Bull · 2026 Jun · PMID 42069231 · Publisher ↗
The human thalamus serves as a central integrative hub, facilitating the transmission of information among the cerebral cortex, subcortical structures, and the peripheral nervous system, while supporting a range of highe...
The human thalamus serves as a central integrative hub, facilitating the transmission of information among the cerebral cortex, subcortical structures, and the peripheral nervous system, while supporting a range of higher cognitive functions. Although significant age-related changes in thalamic volume and microstructure have been reported, the specific differences in the volumes of thalamic nuclei and their associations with cognitive functions throughout adulthood remain unclear. T-weighted MRI scans from 314 cognitively healthy individuals were categorized into four age groups: young (20-35 years), early middle-aged (36-50 years), late middle-aged (51-65 years), and older (>65 years). Thalamus volumes and cognitive function scales were compared across age groups, and associations between thalamic volume and cognitive function with age were further analyzed. Significant atrophy was observed in all ventral thalamic nuclei in older adults, as well as in the paracentral (Pc), mediodorsal medial (MDm), lateral geniculate (LGN), and anterior pulvinar (PuA) nuclei. The volumes of thalamic subnuclei, particularly those in the ventral, posterior, medial and intralaminar groups, were positively correlated with cognitive performance, especially in executive-attentional and working memory during aging. These findings underscore the importance of thalamic subnuclei in maintaining cognitive function during healthy aging.
Decreased gamma band power and increased betagamma phaseamplitude coupling are characteristic of brain activity in patients with chronic spinal cord injury.
Nishi A, Yanagisawa T, Fukuma R … +3 more , Yamamoto S, Tani N, Kishima H
Brain Res Bull · 2026 Jun · PMID 42055147 · Publisher ↗
Neurophysiological biomarkers are needed to characterize the condition of patients with spinal cord injury (SCI), for which effective symptomatic biomarkers are lacking. We recorded the resting-state magnetoencephalograp...
Neurophysiological biomarkers are needed to characterize the condition of patients with spinal cord injury (SCI), for which effective symptomatic biomarkers are lacking. We recorded the resting-state magnetoencephalography data of 22 patients with SCI and 29 healthy controls. Power spectral density and phase-amplitude coupling (PAC) were assessed for six frequency bands using source-reconstructed cortical currents. Compared with controls, SCI patients exhibited significantly reduced gamma band power and increased beta-gamma PAC in the frontal cortex, including the primary motor area (q < 0.05, FDR corrected). No significant differences were observed in alpha or beta power. These results suggest that decreased gamma power and increased beta-gamma coupling reflect altered cortical dynamics after SCI and may serve as potential neurophysiological signatures for chronic cortical adaptation.
Icariin promotes lysosomal degradation of amyloid-β precursor protein via enhanced endosome-lysosome trafficking to reduce amyloid-β accumulation and improve cognitive function in Alzheimer's disease models.
Lin C, Xu Z, Yan J … +2 more , Liu B, Li F
Brain Res Bull · 2026 Jun · PMID 42055146 · Publisher ↗
Alzheimer's disease (AD) represents a devastating global public health crisis, characterized by progressive cognitive decline and memory impairment, with its prevalence and associated disability rates rising exponentiall...
Alzheimer's disease (AD) represents a devastating global public health crisis, characterized by progressive cognitive decline and memory impairment, with its prevalence and associated disability rates rising exponentially amid global population aging. The pathological hallmarks of AD include the accumulation of amyloid-beta (Aβ) plaques and hyperphosphorylated tau protein tangles, which primarily arise from the aberrant processing of amyloid-β precursor protein (AβPP). Currently, approved therapeutic strategies for AD only provide symptomatic relief, and there is a critical unmet need for effective disease-modifying treatments-particularly those targeting the transport and degradation mechanisms of AβPP, which remain poorly understood and under-explored. This study aims to elucidate the effects of icariin on AβPP subcellular localization and degradation via the lysosomal pathway in both APP/PS1 transgenic mouse model and human-APP695-overexpressing cell line. Combining behavioral assessments with biochemical analyses and confocal microscopy, this study demonstrates that prolonged icariin treatment significantly enhances cognitive function, reduces levels of AβPP, BACE1, and Aβ, and promotes the lysosomal degradation of AβPP by facilitating its transport from early endosomes to lysosomes. The findings reveal that icariin effectively mitigates Aβ generation and cognitive deficits by shortening the residence time of AβPP in early endosomes, thereby filling a key knowledge gap in AβPP metabolism and uncovering a novel regulatory mechanism. These results not only establish icariin as a promising candidate for AD intervention but also propose a new therapeutic avenue targeting AβPP degradation mechanisms, with substantial implications for both basic research and clinical applications in AD treatment. Future investigations should focus on evaluating the translational potential of icariin and characterizing its pharmacological profile to optimize clinical efficacy and safety, addressing the urgent need for disease-modifying therapies for this devastating neurodegenerative disorder.
Cognitive function and brain structure in extreme sports athletes: Evidence from neuroimaging.
Allahmoradi Z, Ahanian I, Olamaei SA … +1 more , Maleknia L
Brain Res Bull · 2026 Jun · PMID 42055145 · Publisher ↗
Neuroimaging studies have shown that the brain structure and function of athletes engaging in professional sports can be affected even after a short period of training. However, few studies have investigated the structur...
Neuroimaging studies have shown that the brain structure and function of athletes engaging in professional sports can be affected even after a short period of training. However, few studies have investigated the structural and functional characteristics of the athletes' brains in extreme sports. A combination of psychological assessment, structural and functional MRI was performed to evaluate the effects of extreme sports on athletes' brains. The athlete group included 30 male athletes (mean age 20.5 ± 0.9 years) with at least two years of professional experience in extreme sports, while the control group consisted of 20 age-matched male non-athletes engaged in regular physical activity. Brain imaging data were acquired using a 3-Tesla MRI scanner. Psychological evaluation was conducted using internationally standardized questionnaires, including measures of personality traits, affect, anxiety, stress, emotional regulation, aggression, and attention. These assessments ensured groups were matched on key psychological traits before participating in the study. Brain volumetric analysis showed that athletes had increased gray matter in the Thalamus, Hippocampus, Middle Temporal Gyrus, Inferior Frontal Gyrus, and Anterior Cingulate Cortex-regions linked to memory, cognitive control, decision-making, and emotional regulation. Athletes also performed better on a task administered before and after exposure to aggressive, critical, and emotionally provocative extreme sports stimuli. Our findings indicate that participation in professional extreme sports is associated with structural brain differences that may be related to cognitive functions, particularly cognitive performance and emotional regulation.
Graph-theoretical analysis of EEG functional brain network development in preterm infants.
Li J, Shan Y, Ge M … +9 more , Peng T, Jiang C, Xu X, Zhang P, Lin Y, Liu M, Zhou W, Chen Y, Cheng G
Brain Res Bull · 2026 Jun · PMID 42049100 · Publisher ↗
OBJECTIVE: To investigate preterm brain network maturation using electroencephalography connectivity and graph theory. METHODS: Sixty-one preterm infants (25-36 weeks gestational age) were studied, including 40 with long...
OBJECTIVE: To investigate preterm brain network maturation using electroencephalography connectivity and graph theory. METHODS: Sixty-one preterm infants (25-36 weeks gestational age) were studied, including 40 with longitudinal electroencephalography. Resting-state recordings across δ (0.5-4 Hz), θ (4-8 Hz), α (8-13 Hz), and β (13-30 Hz) bands were analyzed using weighted phase-lag index (wPLI), with false discovery rate correction. Graph metrics (small-worldness, efficiency, degree, betweenness, clustering) were computed across 27-50% sparsity. Developmental trajectories were modeled with generalized additive models and linear mixed-effects models. RESULTS: wPLI revealed 25 significant connections, dominated by interhemispheric frontopolar synchrony. θ-band clustering at F4 peaked at 36 weeks. Between 35-38 weeks, β- and θ-band networks showed significant declines, whereas δ-band connectivity demonstrated enhanced global integration and efficiency. Longitudinal models confirmed post-menstrual age (PMA)-dependent increases in parietal hub (P4) betweenness, degree, and nodal efficiency in the θ-band. CONCLUSION: Thirty-six weeks PMA marks a critical neurodevelopmental transition, characterized by δ-band hub emergence and parietal θ-band integration, offering potential biomarkers for preterm network maturation.
Oxytocin alleviates the cognitive and memory dysfunction caused by neuroinflammation through blocking the TLR4/NLRP3/NF-κB signaling pathway.
Gong H, Wang Y, Ou Y … +12 more , Zhou M, Wu G, Che M, Li K, Chen R, Xiong Z, Ling X, Wang H, Wang X, Ye X, Feng Z, Qi S
Brain Res Bull · 2026 Jun · PMID 42049099 · Publisher ↗
Lipopolysaccharide (LPS)-induced systemic inflammation is associated with cognitive and memory impairments, neuroinflammation, and synaptic dysfunction. The neuropeptide oxytocin has anti-inflammatory and neuromodulatory...
Lipopolysaccharide (LPS)-induced systemic inflammation is associated with cognitive and memory impairments, neuroinflammation, and synaptic dysfunction. The neuropeptide oxytocin has anti-inflammatory and neuromodulatory properties; however, the underlying molecular mechanisms remain poorly understood. This study aimed to investigate the role of oxytocin in LPS-induced deficits in spatial learning, memory, and social recognition and explore the underlying mechanisms related to neuroinflammatory suppression and synaptic restoration. Adult male C57BL/6 mice were intraperitoneally injected with LPS, with or without oxytocin and the oxytocin receptor antagonist atosiban, and subjected to behavioral assessments, including the Morris water maze, three-chamber social interaction test, open field test, and elevated plus maze. LPS administration impaired social and spatial memory without affecting anxiety-related behaviors. These impairments were associated with elevated levels of pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) in the serum and hippocampus, increased microglial activation, and downregulated synaptic proteins (postsynaptic density protein 95 (PSD-95), synaptosomal-associated protein 25 (SNAP-25), and synaptophysin). LPS decreased circulating oxytocin levels and the number of oxytocinergic neurons in the hypothalamus while upregulating hippocampal oxytocin receptor expression. Exogenous oxytocin administration ameliorated LPS-induced cognitive deficits, reduced neuroinflammation, and restored synaptic protein expression, which were reversed by atosiban co-administration. Pharmacological inhibition of the nucleotide-binding oligomerization domain-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome using MCC950 mimicked the protective effects of oxytocin, whereas its activation using nigericin abolished them. These findings suggest that oxytocin alleviates LPS-induced cognitive and synaptic impairments by suppressing NLRP3 inflammasome-mediated neuroinflammation, highlighting its therapeutic potential in inflammation-associated cognitive dysfunction.
Individual morphological brain networks, systemic inflammation, and neurocognitive alterations in type 2 diabetes.
He Y, Tan J, Chen M … +8 more , Zhao Y, Yang C, Zhang H, Tian J, Huang G, Zhao Z, Yao Z, Zhao L
Brain Res Bull · 2026 Jun · PMID 42036036 · Publisher ↗
BACKGROUND: Type 2 diabetes mellitus (T2DM) is closely associated with chronic low-grade inflammation and brain impairment, but how systemic inflammation affects brain morphological networks remains unclear. This study a...
BACKGROUND: Type 2 diabetes mellitus (T2DM) is closely associated with chronic low-grade inflammation and brain impairment, but how systemic inflammation affects brain morphological networks remains unclear. This study aimed to investigate the topological organization of individual-level morphological similarity networks (MSNs) in T2DM and its relationship with systemic inflammation and neuropsychological manifestations. METHODS: This study comprised two distinct cohorts. Cohort 1 included 92 T2DM patients and 63 demographically matched healthy controls (HCs); all underwent MRI and neuropsychological assessments. Individual MSNs were constructed using cortical thickness similarity, and graph-theoretical analysis was applied. Cohort 2 included 40 T2DM and 40 well-matched HCs with plasma inflammatory cytokines measured. An overlapping subset (n = 39) further investigated the relationship between cytokines and topological metrics. RESULTS: Both groups showed small-world properties in MSNs without global differences. At the nodal level, T2DM patients exhibited decreased degree centrality in the left superior frontal gyrus (SFG) and increased degree centrality/nodal efficiency in the right cingulate gyrus (CG). The ventral attention network (VAN) had higher betweenness centrality, which negatively correlated with anxiety scores. T2DM patients showed elevated pro-inflammatory cytokines (e.g., IL-6, IL-8, TNF-α), and IL-4 levels positively correlated with depression severity. CONCLUSION: T2DM is associated with distinct alterations in the topological organization of individual morphological brain networks, where the left SFG may be a vulnerable node linked to disease progression and right CG/VAN changes may reflect compensation. Systemic inflammation, particularly IL-4, may contribute to affective symptoms, providing new network neuroscience insights into T2DM-related brain impairment.
EEG-based schizophrenia detection using handcrafted biomarkers and a TOA-optimized hybrid multi-branch CNN-Transformer framework.
Rezaee K, Dehghanpour M, Saberi Anari M
Brain Res Bull · 2026 Jun · PMID 42036035 · Publisher ↗
Schizophrenia is a chronic psychiatric disorder for which electroencephalography (EEG) offers a low-cost, non-invasive window into abnormal neural dynamics. However, many EEG-based computer-aided diagnosis (CAD) pipeline...
Schizophrenia is a chronic psychiatric disorder for which electroencephalography (EEG) offers a low-cost, non-invasive window into abnormal neural dynamics. However, many EEG-based computer-aided diagnosis (CAD) pipelines still rely on a single feature representation, heuristic tuning of model components, and window-level evaluation that may not translate to clinically meaningful subject-level decisions. We therefore developed a hybrid, calibration-aware CAD framework that fuses multi-branch deep embeddings with interpretable handcrafted EEG biomarkers and jointly optimizes feature selection and classifier hyperparameters via a Treble Opposite Algorithm with feature-search hybridization (TOA-FSH). Resting-state multi-channel EEG from two public cohorts-MSU-SZ (84 adolescents; 45 schizophrenia/39 healthy controls) and RepOD-SZ (28 adults; 14 schizophrenia/14 healthy controls)-was preprocessed under strict subject-wise protocols and converted into continuous wavelet transform (CWT) scalogram images. Deep features from EfficientNetV2-S, MobileNetV3-Large, ResNet-50, and a Swin Transformer branch were concatenated with handcrafted spectral, complexity, and connectivity features. TOA-FSH selected a sparse hybrid subset and tuned a k-nearest neighbor classifier, followed by probability calibration and subject-level fusion. On MSU-SZ, the final model achieved approximately 97.6% window-level balanced accuracy (BAC) and 100% subject-level BAC. When trained on MSU-SZ and tested without retraining on the unseen RepOD-SZ cohort, it again achieved approximately 97.6% window-level BAC and 100% subject-level BAC, indicating strong cross-cohort generalization under a harmonized preprocessing and evaluation scheme. Ablation analysis further showed incremental gains from ensembling, TOA-FSH-based selection, and handcrafted-feature fusion beyond single-backbone baselines. These findings indicate that calibration-aware hybrid modeling can provide reliable and transferable subject-level EEG markers for clinician-guided schizophrenia screening and assessment.
Longitudinal alterations in morphometric inverse divergence networks among diabetes patients with progressive cognitive decline.
Bao YW, Zhou Y, Wei DF … +4 more , Ji YQ, Shen DM, Liu YY, Guo LL
Brain Res Bull · 2026 Jun · PMID 42034128 · Publisher ↗
BACKGROUND: Diabetes mellitus (DM) is associated with an elevated risk of cognitive decline, though trajectories are heterogeneous. This study investigated whether a novel, clinically applicable measure of brain network...
BACKGROUND: Diabetes mellitus (DM) is associated with an elevated risk of cognitive decline, though trajectories are heterogeneous. This study investigated whether a novel, clinically applicable measure of brain network integrity, the Morphometric Inverse Divergence (MIND) network, could differentiate and predict cognitive progression in DM. METHODS: We retrospectively analyzed 101 DM participants (41 cognitively normal, 60 with mild cognitive impairment) from the Alzheimer's Disease Neuroimaging Initiative, classifying them into stable (DM_S, n = 64) or decline (DM_D, n = 37) group based on longitudinal diagnostic conversion. MIND networks were constructed from multiple cortical morphological features derived from T1-weighted MRI and graph theory measurements were further analyzed. Using network-based statistics (NBS) and its extension NBS-predict, we tested whether subject-level connectomes were associated with long-term DM-related cognitive worsening. RESULTS: At baseline, DM_D individuals exhibited significantly lower cognitive scores and a focal subnetwork of disrupted morphometric similarity, primarily involving temporal regions. Longitudinally, DM_D individuals showed a more targeted pattern of network change that significantly altered global efficiency, local efficiency, and path length exclusively, while stable individuals, the brain underwent more widespread changes. Crucially, baseline MIND networks significantly predicted long-term cognitive progression status (accuracy = 63.1%, p = 0.034). The predictive subnetwork was rich in transmodal connections involving the temporoparietal, default mode, and limbic networks. CONCLUSION: These findings indicate that cognitive decline in DM is preceded by specific disruptions in the brain's structural connectome. The MIND method shows promise as a network-based biomarker for identifying at-risk individuals and predicting cognitive trajectory, potentially driving advanced network analyses toward real-world applicability.
Functional adaptive longitudinal reorganization of superior parietal lobule networks in amyotrophic lateral sclerosis: Evidence suggesting compensatory mechanisms.
Ghaderi S, Mohammadi S, Kalra S … +1 more , Batouli SAH
Brain Res Bull · 2026 Jun · PMID 42034127 · Publisher ↗
PURPOSE: To investigate longitudinal changes in resting-state functional connectivity (rs-FC) of the superior parietal lobule (SPL) in limb-onset amyotrophic lateral sclerosis (ALS). METHODS: Resting-state fMRI was used...
PURPOSE: To investigate longitudinal changes in resting-state functional connectivity (rs-FC) of the superior parietal lobule (SPL) in limb-onset amyotrophic lateral sclerosis (ALS). METHODS: Resting-state fMRI was used to compare SPL connectivity between 14 ALS patients and 14 healthy controls (HCs) at baseline and during a 5-month follow-up (n = 10 ALS patients). Imaging sequences were acquired using a 3-Tesla scanner equipped with a 64-channel head coil. The data were preprocessed and analyzed using CONN and SPM12, employing FDR correction (p < 0.05) to identify significant resting-state functional connectivity (rs-FC) alterations. RESULTS: ALS patients showed significant FC alterations in both right and left SPL compared to HCs. At baseline, the right SPL exhibited increased FC with the right Lateral Visual Network, Medial Visual Network (MVN), right Occipital Fusiform Gyrus (OFG), and left Lingual Gyrus (LG). At follow-up, these increases persisted and expanded, notably to the Occipital Visual Network and left LVN. For several connections, including the right OFG and MVN, the corresponding beta values were descriptively larger at follow-up than at baseline. Conversely, at follow-up, the right SPL showed decreased FC with the left Salience Network (SN). The left SPL showed no baseline changes but, at follow-up, exhibited increased FC with visual networks and the Default Mode Network, alongside decreased FC with the SN. CONCLUSION: These findings may be suggestive of adaptive reorganization of SPL-related brain networks in response to neurodegeneration in ALS.
Exploring the toxicological impact of perfluorooctanoic acid and perfluorooctane sulfonate on glioblastoma through network toxicology, machine learning, and multi-dimensional bioinformatics analysis.
Wang J, Xu Q, Luo Y … +2 more , Zhang Z, Lu J
Brain Res Bull · 2026 Jun · PMID 42025812 · Publisher ↗
Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) has been associated with the development of various malignant tumors. However, their roles and molecular mechanisms in glioblastoma (GBM) are...
Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) has been associated with the development of various malignant tumors. However, their roles and molecular mechanisms in glioblastoma (GBM) are still unclear. This study combined network toxicology, machine learning, immune infiltration analysis, single-cell RNA sequencing (scRNA-seq), molecular docking, Mendelian randomization (MR), and molecular dynamics (MD) simulation to explore the potential toxicological targets and mechanisms of PFOA/PFOS in GBM. Five core target genes (ANXA5, AURKA, CDK2, EIF4EBP1, and ODC1) were identified. Their predictive potential was validated using three external independent datasets, with AUC values mostly above 0.90. Gene Set Enrichment Analysis (GSEA) revealed significant enrichment of the phosphatidylinositol, ErbB, and MAPK signaling pathways. Furthermore, the expression levels of core targets exhibited strong correlations with immune cell infiltration, particularly with macrophages and NK cells. ScRNA-seq analysis revealed that the core targets were predominantly expressed in MES‑like and AC‑like malignant cells, suggesting their potential roles in regulating the functional phenotypes of GBM cell subpopulations. Molecular docking confirmed the strong binding affinity of PFOA/PFOS with five core targets. MR analysis revealed a significant association between ODC1 expression and GBM risk (OR = 2.16, 95%CI: 1.129-4.115; P = 0.0198), while MD simulation further verified the sustained binding interactions between ODC1 and PFOA/PFOS. We also proposed a novel adverse outcome pathway (AOP) framework linking PFOA/PFOS exposure to GBM, offering critical toxicological insights. Overall, these findings provide valuable evidence for the potential toxicological impact of PFOA/PFOS on GBM, highlighting the necessity for further mechanistic investigations.
Impact of co-housing on anxiety- and depression-like behaviors in rats exposed to chronic unpredictable mild stress.
Maimaitiming N, Zhong W, Zhang J … +3 more , Ma Y, Shi H, Li X
Brain Res Bull · 2026 Jun · PMID 42025811 · Publisher ↗
To investigate the ameliorating effects of co-housing combined with fluoxetine intervention on anxiety- and depression-like behaviors and gut microbiota dysbiosis induced by chronic unpredictable mild stress (CUMS) in ra...
To investigate the ameliorating effects of co-housing combined with fluoxetine intervention on anxiety- and depression-like behaviors and gut microbiota dysbiosis induced by chronic unpredictable mild stress (CUMS) in rats. SD rats were randomly divided into control group, CUMS stress group, stress + normal co-housing group, stress + fluoxetine group, and stress + normal co-housing + fluoxetine group. The stress group received chronic unpredictable mild stress, the normal co-housing group was housed with normal rats, the fluoxetine group received fluoxetine during CUMS stimulation, and the combined intervention group received fluoxetine intervention during stimulation followed by co-housing intervention. Behavioral changes were assessed through sucrose preference test, forced swimming test, tail suspension test, and open field test. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Compared to the stress group, the normal co-housing group showed significantly increased sucrose preference rate, significantly reduced immobility time in forced swimming test, and significantly increased activity time in the center area of open field test. The behavioral improvement effects of combined intervention were significantly superior to individual interventions. Gut microbiota analysis showed that Monoglobus abundance was significantly elevated in the stress group and significantly reduced in the normal co-housing group. The combined intervention group not only reduced Monoglobus abundance but also simultaneously reduced the abnormal elevation of Alloprevotella and uncultured_Bacteroidales_bacterium, two other stress-related bacterial species.
Resting-state EEG networks predict individual differences in cognitive flexibility.
Xu P, Chen Y, Wei X … +3 more , Qi J, Chen Y, Li L
Brain Res Bull · 2026 Jun · PMID 42019559 · Publisher ↗
Cognitive flexibility, the ability to adapt behavior and switch between tasks in response to changing goals, is a core component of executive function. However, the multiscale resting-state mechanisms underlying individu...
Cognitive flexibility, the ability to adapt behavior and switch between tasks in response to changing goals, is a core component of executive function. However, the multiscale resting-state mechanisms underlying individual differences remain poorly understood. Here, resting-state electroencephalography (EEG) from 128 healthy participants (66 male; age 18-35 years) was analyzed to characterize frequency-specific connectivity and network topology. Results show that, delta-band fronto-temporal connectivity and associated graph metrics associated with repeat task performance, whereas beta-band fronto-parietal, fronto-occipital, and prefronto-frontal connections associated with shift task performance. Individuals with low switching costs exhibited stronger intra- and inter-hemispheric alpha-, beta-, and gamma-band connectivity, which were associated with more efficient cognitive flexibility. Multivariate models using connectivity features reliably predicted repeat RT and shift RT. Together, these findings indicate that hierarchical, frequency-specific resting-state networks constitute core neural mechanisms of cognitive flexibility and highlight the potential for resting-state EEG networks to account for individual differences in executive function.
Identifying neuroimaging-based biomarkers for obsessive-compulsive disorder: A resting-state fMRI and machine learning study in patients and unaffected first-degree relatives.
Suo X, Zhang Y, Li X … +9 more , Liu J, Xu Z, Zeng L, Lei L, Zhang M, Luo Z, Min Y, Zeng X, Hu M
Brain Res Bull · 2026 Jun · PMID 42002113 · Publisher ↗
BACKGROUND: Identifying whether brain alterations in obsessive-compulsive disorder (OCD) represent the illness itself or an underlying genetic vulnerability is challenging, primarily due to the confounding effects of med...
BACKGROUND: Identifying whether brain alterations in obsessive-compulsive disorder (OCD) represent the illness itself or an underlying genetic vulnerability is challenging, primarily due to the confounding effects of medication and chronic illness. To disentangle these disease-state and genetic-trait markers, we investigated a unique cohort of first-episode, drug-naïve patients and their unaffected first-degree relatives (UFDR). METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were acquired from 72 first-episode, drug-naïve OCD patients, 23 UFDR, and 56 healthy controls (HC). We computed the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and degree centrality (DC). Following covariate-controlled statistical comparisons, support vector machine (SVM) models with nested cross-validation were employed to evaluate the exploratory classification capacity of the identified functional features. RESULTS: No significant main effects were found for ReHo across groups. However, OCD patients exhibited significantly elevated ALFF in the left orbital middle frontal gyrus and left dorsolateral superior frontal gyrus compared to HC and UFDR, respectively. ALFF values in both regions were positively correlated with obsessive-compulsive symptom severity. Meanwhile, the UFDR group demonstrated distinct network alterations, including increased DC in the left caudate nucleus and decreased DC in the left orbital inferior frontal gyrus compared to HC. The SVM classifiers differentiated the groups with promising capacity, achieving areas under the curve of 0.834 (UFDR vs. HC), 0.791 (OCD vs. HC), and 0.801 (OCD vs. UFDR). CONCLUSIONS: This study helps separate state-dependent from trait-related functional features in OCD. Prefrontal ALFF hyperactivity characterizes the active disease state, whereas striatal-frontal DC alterations in unaffected relatives represent candidate endophenotypes for genetic vulnerability. While these neural signatures show exploratory discriminatory capacity, their clinical utility for early diagnosis and risk stratification requires strict validation in larger, multi-site, and longitudinal cohorts.
Calcitriol attenuates neuroinflammation induced by ischemia/reperfusion via modulation of the ROS/TXNIP/NLRP3 pathway: Evidence from in silico and in vivo studies.
Behdarvandy M, Shamsara A, Pourjafari F … +3 more , Sheikhbahaei F, Eftekhar-Vaghefi SH, Vahidinia Z
Brain Res Bull · 2026 Jun · PMID 42000080 · Publisher ↗
Cerebral ischemia is a major cause of death and long-term disability. NOD-like receptor protein 3 (NLRP3) inflammasome plays a central role in post-ischemic inflammation, with reactive oxygen species (ROS)-induced thiore...
Cerebral ischemia is a major cause of death and long-term disability. NOD-like receptor protein 3 (NLRP3) inflammasome plays a central role in post-ischemic inflammation, with reactive oxygen species (ROS)-induced thioredoxin-interacting protein (TXNIP) activation contributing to its assembly. Calcitriol, the active form of vitamin D3, has anti-inflammatory and antioxidant properties. Here, we investigated the neuroprotective effects of calcitriol via modulation of the ROS/TXNIP/NLRP3 pathway in cerebral ischemia. We employed a rat model of transient middle cerebral artery occlusion (tMCAO) to induce ischemia/reperfusion (I/R) injury. Adult male Wistar rats (280-320 g) were randomly assigned to three experimental groups: sham, I/R, and calcitriol-treated. Calcitriol (1 µg/kg) was administered intraperitoneally at 30 min, 24 h, and 48 h post-surgery. At 72 h, neurological deficits and infarct volume were assessed. Oxidative stress was evaluated by measuring ROS, malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC). ELISA was utilized to assay the levels of Interleukin-1 beta (IL-1β) and, Interleukin-18 (IL-18). Protein expression of TXNIP, NLRP3, ASC, and Caspase-1 was analyzed via Western blot, and neuronal injury was assessed using Nissl staining. Molecular docking was used to assess the interaction strength between calcitriol and NLRP3. Results showed that calcitriol significantly alleviated neurological impairments, reduced infarct size of stroke, lowered oxidative stress and pro-inflammatory markers, and downregulated NLRP3 inflammasome components and TXNIP. Histological analysis confirmed neuroprotection, and docking analysis revealed favorable binding of calcitriol to NLRP3's NACHT domain. The present study suggests that calcitriol mitigates I/R-induced neuroinflammation by targeting the ROS/TXNIP/NLRP3 signaling pathway.
CCR5 as a key mediator: Insights into the molecular mechanisms by which air pollutants induce Alzheimer's disease via network toxicology and molecular docking.
Zhang Y, Wu H, Peng J … +2 more , Li L, Liu Y
Brain Res Bull · 2026 Jun · PMID 41991115 · Publisher ↗
BACKGROUND: Air pollution is a critical environmental risk factor for Alzheimer's disease (AD), yet the underlying molecular mechanisms remain unclear, hindering mechanistic insights and targeted prevention METHODS: This...
BACKGROUND: Air pollution is a critical environmental risk factor for Alzheimer's disease (AD), yet the underlying molecular mechanisms remain unclear, hindering mechanistic insights and targeted prevention METHODS: This study combined network toxicology and molecular docking to explore how seven air pollutants (benzene, toluene, O₃, SO₂, NO, NO₂, CO) contribute to AD. Pollutant-related targets were retrieved from PubChem, SwissTargetPrediction, STITCH, and ChEMBL, while AD-related genes were sourced from GeneCards, OMIM, and TTD. Overlapping genes were identified, followed by GO and KEGG enrichment analyses. GEO dataset GSE122063 was used for differential expression and ROC curve-based diagnostic evaluation. Molecular docking assessed binding affinities between pollutants and core proteins. RESULTS: A total of 1349 pollutant-related targets and 495 AD-related targets were identified, with 88 overlapping genes. Enrichment analyses revealed significant involvement in neuronal apoptosis, inflammatory responses, and MAPK and PI3K-Akt signaling pathways. External validation identified CCR5, PLD3, CCL2, and RET as core targets, among which CCR5 demonstrated the highest diagnostic efficacy (AUC = 0.85). Docking simulations indicated that all seven pollutants could spontaneously bind to the core proteins (binding energy < 0 kcal/mol). Notably, benzene and toluene showed the strongest and most stable interactions with CCR5 (binding energy < -5 kcal/mol), suggesting that pollutant toxicity may be partly associated with direct binding to CCR5. CONCLUSIONS: This study supports CCR5 as a potential key molecular mediator associated with the link between air pollution and AD, providing a novel mechanistic perspective on how environmental pollutants may be involved in neurodegenerative disease. These findings offer theoretical support for further exploring CCR5-targeted preventive or therapeutic strategies.
The neuroprotective effect of guanabenz combined with α-lipoic acid in the hSOD1-G93A amyotrophic lateral sclerosis model.
Zhang W, Zhang D, Han L … +8 more , Wang D, Huo D, Tan X, Su X, Wang M, Xu J, Cheng J, Feng H
Brain Res Bull · 2026 Jun · PMID 41991114 · Publisher ↗
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, and although its pathogenesis is not yet clear, the multifactorial mechanisms that affect motor neuron death are intertwined, exacerbating the dis...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, and although its pathogenesis is not yet clear, the multifactorial mechanisms that affect motor neuron death are intertwined, exacerbating the disease. Here, we explore the effectiveness and mechanism of a combination medication that combines guanabenz with α-lipoic acid in an in vitro as well as in vivo model of ALS. In this research, we initially determined the independent action targets and synergistic action targets of the two drugs through network pharmacology and molecular docking. Subsequently, we further investigated their specific action mechanisms in both in vivo and in vitro studies. In NSC34 cells transfected with hSOD1-G93A, we observed that the combined drugs could more effectively safeguard against cell damage and the production of reactive oxygen species (ROS) generated by mutant hSOD1, superior to monotherapy. This was achieved by upregulating the p-AKT/HO-1 pathway and synergistically suppressing the GRP78/CHOP pathway. Moreover, we found that combination drugs can effectively delay the decline in motor function of hSOD1-G93A transgenic mice by synergistically inhibiting GRP78/CHOP pathway. They can protect the motor neurons in the anterior horn of the spinal cord and suppress gliosis in hSOD1-G93A transgenic mice. In summary, our research indicates that the combination therapy of guanabenz and α-lipoic acid can serve as a viable treatment option for ALS.
Emotion-dependent integration and segregation in EEG functional brain networks revealed by data-driven sparsity optimization.
Wang T, Liu W, Li G … +3 more , Hu F, Zhou B, Zhang Y
Brain Res Bull · 2026 Jun · PMID 41985789 · Publisher ↗
Functional connectivity analysis based on electroencephalogram (EEG) provides an effective window for understanding the network-level mechanisms of emotional processing. However, traditional brain network construction me...
Functional connectivity analysis based on electroencephalogram (EEG) provides an effective window for understanding the network-level mechanisms of emotional processing. However, traditional brain network construction methods typically relied on empirical thresholds, making it difficult to objectively reveal true emotion-specific connectivity patterns. This study proposed a data-driven sparsity optimization framework aimed at objectively identifying emotion-discriminative EEG connectivity patterns across multiple frequency bands. Functional networks based on Pearson Correlation Coefficient were constructed across five representative frequency bands, with network sparsity systematically varied from 10% to 100%. Utilizing ensemble learning models, we determined the optimal sparsity level by maximizing emotion classification performance. Under the optimized sparsity conditions, we further examined the graph-theoretic properties of three emotional states: neutral, sad, and happy. The proposed framework achieved peak classification accuracies of 94.28 ± 1.51% and 94.44 ± 1.89% in the Beta and Gamma bands, respectively, significantly outperforming fully connected networks. Crucially, network topology analysis revealed distinct emotion-dependent organizational patterns: the happy state exhibited higher global efficiency, indicating enhanced large-scale integration of emotional information; while neutral emotional states exhibited higher local efficiency and clustering coefficients, reflecting more pronounced small-world organization. These findings showed that sparsity-optimized networks boosted emotion recognition and revealed key differences in integration and segregation across emotions. The proposed method provided a principled framework for studying emotion-related brain network organization and contributed to a deeper understanding of the neural mechanisms underlying emotional regulation.
The dual role of microglia in neurodegenerative diseases: A review.
Zhang N, Xiong N, He Y … +1 more , Zhou L
Brain Res Bull · 2026 Jun · PMID 41985788 · Publisher ↗
BACKGROUND: Microglial activation has increasingly been recognized as a central hub in the pathogenesis of neurodegenerative diseases, where it exerts dynamic regulatory roles characterized by a contest between neuroprot...
BACKGROUND: Microglial activation has increasingly been recognized as a central hub in the pathogenesis of neurodegenerative diseases, where it exerts dynamic regulatory roles characterized by a contest between neuroprotective and neurotoxic actions. However, the precise process underlying this interplay between the two opposing effects remains incompletely elucidated. RESULTS: Moderate activation of microglia prevents the accumulation of neurotoxic substances, such as cellular debris and misfolded proteins, promotes neuronal survival by secreting neurotrophic factors, and induces self-limiting inflammation that exerts neuroprotective and repair-promoting effects. In contrast, chronic and persistent microglial activation driven by sustained elevations of pro-inflammatory cytokines, cGAS-STING-mediated DNA sensing, hyperactivation of membrane receptors (e.g., TREM2 and CX3CR1), mitochondrial dysfunction, accumulation of disease-associated proteins, and the emergence of regulatory lectins like Galectin-3, accelerates the progression of neurodegenerative diseases. Through multi-targeted and multi-mechanistic interventions aimed at enhancing microglial phagocytic activity, inhibiting aberrant complement-mediated synaptic pruning (C1q/C3/CR3), reducing neuroinflammation, modulating immune checkpoints (e.g., CD33 and TIM-3)-it is possible to preserve microglial clearance of pathological factors and support neuronal repair. These precision strategies prevent the erroneous engulfment of healthy synapses and promote M2-like polarization，thereby optimizing neuroprotective effects, and delaying or ameliorating the progression of neurodegenerative diseases. CONCLUSIONS: This review outlines the dynamic "double-edged sword" role of microglia in neurodegenerative diseases and systematically summarizes the clinical and multi-targeted intervention strategies designed to precisely modulate their functions and skew them toward a neuroprotective phenotype.
Ferulic acid promotes proliferation and angiogenesis of cerebral microvascular endothelial cells in Moyamoya disease via the SIRT1/HIF-1α/VEGF-A axis.
Gao T, Liu Z, Wang L … +2 more , Zhao L, Li C
Brain Res Bull · 2026 Jun · PMID 41980628 · Publisher ↗
BACKGROUND: Moyamoya disease (MMD) is characterized by progressive stenosis of the intracranial internal carotid arteries, resulting in chronic cerebral hypoperfusion and impaired angiogenesis. Oxidative stress, mitochon...
BACKGROUND: Moyamoya disease (MMD) is characterized by progressive stenosis of the intracranial internal carotid arteries, resulting in chronic cerebral hypoperfusion and impaired angiogenesis. Oxidative stress, mitochondrial dysfunction, and endothelial apoptosis are recognized contributors to microvascular injury in ischemic MMD. Ferulic acid (FA), a natural phenolic compound with potent antioxidant and cytoprotective properties, has shown therapeutic potential in ischemic cerebrovascular injury. However, its role in restoring endothelial function and promoting angiogenesis in the context of MMD remains unclear. This study investigated whether FA protects brain microvascular endothelial cells (Bend.3) against oxygen-glucose deprivation (OGD)-induced injury and examined the involvement of the SIRT1/HIF-1α/VEGF-A signaling axis. METHODS: OGD was applied to mouse Bend.3 to mimic the hypoxic and ischemic microenvironment of MMD. The effects of FA on cell proliferation, migration, tube formation, and apoptosis were evaluated using CCK-8, scratch assay, Transwell, and Matrigel tube formation. Oxidative stress and mitochondrial function were assessed via ROS, MDA and JC-1assays. qPCR and western blotting were used to examine the expression of SIRT1, HIF-1α, VEGF-A, eNOS, and angiogenesis-related markers. The involvement of SIRT1 signaling was validated through siRNA-mediated SIRT1 silencing and SIRT1 inhibitor treatment. RESULTS: OGD induced significant apoptosis in Bend.3 cells, which was accompanied by the accumulation of reactive oxygen species (ROS), depolarization of the mitochondrial membrane, and a reduction in angiogenesis-related capacity. Conversely, treatment with ferulic acid (FA) enhanced cell viability, improved migration and tube formation, and mitigated apoptotic injury. Furthermore, FA decreased OGD-induced oxidative stress and partially preserved the mitochondrial membrane potential. At the signaling level, FA was associated with an increase in SIRT1 expression and elevated levels of HIF-1α protein, along with an upregulation of downstream angiogenesis-related mediators, including VEGF-A and eNOS. Notably, the knockdown of SIRT1 diminished several FA-associated protective and pro-angiogenic phenotypes and reduced the corresponding HIF-1α/VEGF-A responses under OGD conditions, thereby supporting a SIRT1-dependent mechanism in FA-mediated endothelial effects in this in vitro model. CONCLUSION: FA mitigated OGD-induced oxidative and mitochondrial injury in Bend.3 cells and promoted angiogenesis-related responses through activation of the SIRT1/HIF-1α/VEGF-A axis. These data support a SIRT1-dependent endothelial protective mechanism and provide a rationale for future studies evaluating FA in neurovascular-unit systems and in vivo models relevant to Moyamoya disease.
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