The subjective limitations of neurobehavioral assessment cause a high misdiagnosis rate for disorders of consciousness (DoC). The purpose of this study was to identify the DoC level based on an analysis of multi-dimensional electroencephalogram (EEG) signals to assist with establishing a clinical diagnosis.
Sixty-seven patients with DoC [coma, n = 19; vegetative state (VS), n = 23; and minimally conscious state (MCS), n = 25] were included to analyze resting state EEG characteristics. The EEG features were statistically compared among five band powers (delta, theta, alpha, beta, and gamma) and five brain regions (prefrontal, frontal, parietal, temporal, and occipital) by multidimensional analyses, including time-domain analysis, spectral analysis, and functional brain connectivity.
Amplitude-integrated electroencephalography (aEEG) center amplitude showed significant differences between coma and MCS (p = 0.02688), with no significant differences observed for the other comparison. Spectral analysis revealed that delta and theta power decreased with higher consciousness levels, whereas alpha, beta, and gamma power increased. Relative power differed among groups across specific brain regions (prefrontal, frontal, parietal, temporal, and occipital) and frequency bands. Weighted Phase Lag Index (wPLI) based functional connectivity demonstrated frequency-specific network reorganization with theta band connectivity strongest in VS and alpha/beta/gamma band connectivity enhanced in MCS. Absolute power topographic maps showed expanding high-power regions from coma-to-MCS in high-frequency bands and the left dorsolateral prefrontal cortex (DLPFC) (F3 electrode) exhibited a consistent power gradient of coma < MCS < VS across all bands.
Multidimensional EEG features have significant value in differentiating the levels of consciousness disorders. aEEG center amplitude discriminated MCS from coma; delta/gamma relative power separated VS from MCS, and alpha/beta relative power separated coma, VS, and MCS. Parieto-occipital connectivity matrix in the theta band distinguishes coma from VS, while absolute power topography of the left DLPFC shows potential for grading levels of impaired consciousness. These electrophysiologic biomarkers complement behavioral assessments, enhancing diagnostic accuracy.
Premature ejaculation (PE) accompanied by anxiety or depression is a complex clinical condition at the intersection of male reproductive dysfunction and emotional disorders. Increasing evidence suggests that serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) play central and interrelated roles in its pathogenesis. In this review we examine the bidirectional functions of 5-HT and BDNF in both the reproductive and nervous systems, highlighting their importance in regulating ejaculation, emotional stability, and synaptic plasticity. A comprehensive literature search (2010–2025) was conducted across multiple databases using relevant Medical Subject Headings (MeSH) terms, including pertinent original research and review articles, to synthesize the roles and regulatory pathways of 5-HT and BDNF in PE with comorbid anxiety or depression. We summarize the shared and distinct roles of 5-HT and BDNF in maintaining physiological balance across these systems and focus on their involvement in the major pathological processes underlying PE with anxiety or depression, including neurotransmitter imbalance, neuroendocrine dysregulation, inflammation, and oxidative stress. Furthermore, we outline the related signaling pathways through which 5-HT and BDNF exert their effects and interact. We also evaluate current pharmacological and non-pharmacological interventions targeting these molecules, demonstrating their potential to improve both ejaculatory control and emotional symptoms, and critically appraise selective serotonin reuptake inhibitor (SSRI)-related risks and highlighted the need for individualized dosing and monitoring. Emerging evidence suggests that Traditional Chinese Medicine formulations can extend intravaginal ejaculatory latency and mitigate mood symptoms and may serve as stand-alone or adjunctive options to reduce reliance on selective serotonin reuptake inhibitors (SSRIs). Overall, 5-HT and BDNF are not only deeply involved in the biological mechanisms of PE with comorbid psychological disorders, but also represent promising biomarkers and therapeutic targets, and their integrative neuro-reproductive regulatory functions provide new insights into the diagnosis and treatment of this multifaceted condition.
Cognitive impairment (CI) is recognized as a debilitating complication of Parkinson’s disease (PD). This study was designed to develop a diagnostic classification model by integrating substantia nigra hyperechogenicity (SNH) and inflammationassociated biomarkers to evaluate its diagnostic performance in distinguishing PD CI stages.
Between January, 2023 and May, 2024, 184 patients with PD who underwent transcranial sonography were prospectively enrolled. Based on Montreal Cognitive Assessment (MoCA) scores, participants were categorized into three groups: cognitive impairment (PD-CI, MoCA <26), mild cognitive impairment (PD-MCI, MoCA 22–25), and dementia (PD-dementia, MoCA ≤21). Ultrasound features and inflammationassociated biomarkers were screened with univariate analyses. Multivariate logistic regression was used to identify independent diagnostic factors, and receiver operating characteristic (ROC) curve analysis was used to assess model discrimination.
Multivariate regression analysis indicated that age <50 years and more years of education were significantly associated factors for CI (OR = 0.170, p = 0.0350; OR = 0.8780, p = 0.0020, respectively), whereas Unified Parkinson’s Disease Rating Scale Part III (UPDRSIII) score (OR = 1.024, p = 0.0270), SNH (OR = 2.550, p = 0.0030), elevated C-reactive protein (CRP) (OR = 2.038, p = 0.0350), and elevated homocysteine (Hcy) (OR = 2.830, p = 0.0020) were independent risk factors. The area uinder the curves (AUCs) for the combined SNH+CRP+Hcy model in predicting PD-CI, PD-MCI, and PD-dementia were 0.783, 0.729, and 0.823, respectively; these values were significantly superior to those for single or dual marker combinations (p < 0.05), with the strongest performance for distinguishing PD-dementia.
An SNH and inflammationassociated biomarkerbased model was developed for predicting the stage of cognitive impairment in PD. Clinical targets for individualized intervention can be provided, and clinical risk stratification and care pathways can be optimized. Furthermore, the model supports the iron deposition-neuroinflammation-CI pathway hypothesis, providing a mechanistic rationale for ultrasoundbased PD-CI diagnosis.
A high-fat diet (HFD) has been implicated in the induction of depressive-like behaviors, yet the underlying mechanisms remain incompletely elucidated. Growing evidence indicates that microglia-mediated neuroinflammation plays a critical role in the pathogenesis of depression, with excessive lipid droplet (LD) accumulation emerging as an early trigger for neuroinflammatory cascades. The aim of this study was to investigate microglial LD accumulation and the associated neuroinflammatory response in a model of HFD-induced depression.
Diet-induced obese (DIO) mice were compared with normal control (Con) mice. Depressive-like behaviors were evaluated through a battery of behavioral tests. Hippocampal neuronal damage and microglial activation were assessed using histological and immunofluorescence techniques. A co-culture system of glial cell-enriched isolates and hippocampal neurons was employed to evaluate the neurotoxic potential of DIO microglia. LD accumulation in microglia was quantified in vivo and in vitro using Bodipy staining, Oil Red O staining, and electron microscopy. Untargeted lipidomics was performed on glial cells to characterize alterations in lipid metabolism.
Compared with Con mice, DIO mice exhibited significant depressive-like behaviors and hippocampal neuronal damage, accompanied by enhanced microglia-mediated neuroinflammation. In the co-culture system, microglia from DIO mice demonstrated increased neurotoxicity toward hippocampal neurons. Bodipy staining and electron microscopy revealed increased accumulation of LDs in the hippocampal microglia of DIO mice. This was further confirmed in glial cells in vitro. Lipidomic profiling identified substantial disturbances in lipid metabolism in DIO microglia.
Diet-induced obesity leads to depressive-like behaviors and hippocampal neuronal damage, which is associated with microglia-mediated neuroinflammation and intracellular accumulation of LDs. The enhanced neurotoxicity of DIO microglia, coupled with pronounced lipid metabolic dysregulation, suggests that lipid-laden microglia may contribute to the link between obesity and depression via neuroinflammatory mechanisms.
Secondary cerebral oedema following traumatic brain injury (TBI) is a major cause of poor prognosis, primarily driven by neuroinflammation. High-mobility group box 1 (HMGB1) is a key damage-associated molecular pattern that initiates a potent inflammatory cascade, yet targeted pharmacological interventions face clinical translation challenges. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has shown anti-inflammatory potential, but its efficacy and specific mechanisms in treating traumatic cerebral oedema remain unclear.
A controlled cortical impact (CCI) model was established in male C57BL/6 mice. The animals were randomly divided into five groups: sham, TBI, TBI + taVNS, TBI + HMGB1 agonist (high glucose), and TBI + HMGB1 antagonist (glycyrrhizic acid). taVNS was administered daily for 7 days. Cerebral oedema volume was quantified via magnetic resonance imaging (MRI) on days 3 and 10 post-injury. Neurological function was assessed using the open field test and modified neurological sign score (mNSS). Molecular mechanisms were investigated through transcriptomic sequencing, enzyme-linked immunosorbent assay (ELISA), western blotting, and immunofluorescence to analyze HMGB1 and downstream inflammatory factors (interleukin-1β (IL-1β), interleukin-6 (IL-6)).
Transcriptomic analysis revealed that taVNS reversed TBI-induced dysregulation of genes enriched in HMGB1-related pathways (e.g., Ras-associated protein-1 (Rap1), mitogen-activated protein kinase (MAPK)). Compared with the TBI group, taVNS significantly accelerated the resolution of cerebral oedema (reduction rate: 74.7 ± 12.1% vs 53.5 ± 16.2%, p < 0.05) and improved neurological function. Mechanistically, taVNS markedly suppressed the upregulation of HMGB1, IL-1β, and IL-6 in both serum and brain tissue. Crucially, the therapeutic effects of taVNS were abolished by HMGB1 agonism (high glucose), while HMGB1 antagonism (glycyrrhizic acid) alone mimicked the benefits of taVNS.
This study demonstrates that taVNS effectively promotes the resolution of post-traumatic cerebral oedema and facilitates neurological recovery by specifically inhibiting the HMGB1-mediated inflammatory pathway. These findings position taVNS as a promising, non-invasive therapeutic strategy for the early management of secondary brain injury.
To investigate whether the common clinical practice of setting transcranial magnetic stimulation (TMS) parameters by scaling from the motor threshold (MT) measured at the primary motor cortex (M1) can be expected to yield comparable stimulation at complex brain regions such as the dorsolateral prefrontal cortex (DLPFC).
Personalized head models were constructed from T1- and T2-weighted magnetic resonance imaging (MRI) scans from 20 healthy elderly adults from a public Chinese dataset. SimNIBS 4.1 was used for tissue segmentation, mesh generation, and TMS electric field (E-field) simulations. A MagVenture MC-B70 figure-of-eight coil was used to simulate stimulation over the M1 and DLPFC (C3/F3, 10–10 electroencephalography (EEG) system). First, both targets were simulated at a fixed intensity of 60% of maximum stimulator output (MSO) to isolate anatomical contributions. Second, an MT-equivalent reference output framework was implemented by calibrating subject-specific output to an M1 reference E-field level of 60 mV/mm, using two calibration tracks (Mean-based and Max-based), and the DLPFC was evaluated at 80–120% of the subject-specific reference output.
Under fixed-output stimulation, the mean and robust maximum E-field magnitudes on the gray matter surface and within gray matter volume were significantly lower in the DLPFC region of interest (ROI) than in the M1 ROI (PFDR < 0.05). The normal (surface-perpendicular) component did not differ significantly between targets (PFDR > 0.05), whereas the tangential (surface-parallel) component was significantly weaker at the DLPFC (PFDR < 0.05). Under MT-equivalent scaling, increasing intensity reduced the overall magnitude gap, with approximate parity around 110% of the reference output, but a component trade-off persisted: scaling that brought tangential fields closer to the M1 reference tended to increase normal fields beyond the M1 reference.
Fixed-output simulations show target-wise differences in both E-field magnitude and component balance between the M1 and DLPFC. An M1-referenced, MT-equivalent scaling framework can reduce magnitude differences but does not necessarily align component balance at the DLPFC. These findings support target-specific, E-field–informed parameter selection and should be tested in prospective studies linking modeled E-fields to experimental readouts and clinical outcomes.
Intracranial space-occupying lesions (IOLs) often require precise surgical resection. Intraoperative neurophysiological monitoring (IONM), including somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs), is widely used to preserve neurological function. However, interpretation of IONM data still relies heavily on the experience of the surgeon. The aim of this study was to develop machine-learning (ML) models based on IONM data to support the assessment of lesion location relative to functional brain areas and surgical outcomes.
We initially screened 377 patients undergoing microsurgical resection of IOLs. The clinical data on these patients included demographic characteristics, quantitative IONM parameters (SEP and MEP amplitude and latency), lesion localization, and postoperative adverse events. Four ML models were developed: support vector machine (SVM), decision tree, random forest, and naïve Bayes. Model performance was evaluated using several metrics, including accuracy, sensitivity, specificity, precision, F1-score, and the area under the curve (AUC).
Significant differences in SEP and MEP parameters were observed between patient groups with lesions located in functional and non-functional brain areas (all p < 0.05). SEP and MEP parameters were both associated with lesion localization and postoperative adverse events, with differential correlation patterns observed between the two modalities. The ML models demonstrated moderate discriminative performance in predicting lesion involvement in functional areas, with the highest accuracy of 79.2% in the training set and 65.00% in the test set. The models showed good performance in predicting serious adverse events, with the best accuracy of >78% in both datasets.
ML models based on IONM data may help to assess lesion location relative to functional brain areas, as well as the prediction of postoperative outcomes. These findings suggest that ML-assisted analysis of IONM data may provide an exploratory framework for understanding lesion localization and postoperative outcomes, rather than a clinically deployable decision-support tool.
The cortex and cerebellum have a closely connected closed-loop circuit. Intermittent theta burst stimulation (iTBS) targeting the cerebellum has shown promise in improving balance function and inducing neuroplasticity. This study investigates whether cerebellar iTBS can elicit cortical responses.
One hundred healthy volunteers were randomly assigned to a real or sham iTBS stimulation group. Functional near-infrared spectroscopy (fNIRS) measured cortical activation during resting, walking, and unilateral support tasks.
During the unilateral support task, graph theory analysis revealed significant changes in brain network properties, suggesting a deviation from optimal small-world organization and reduced global integration. No significant changes were observed during the walking and resting-state tasks.
These findings suggest that cerebellar iTBS can modulate cortical activity, though further studies are needed to confirm its clinical effects.
ChiCTR2300077916, https://www.chictr.org.cn/showproj.html?proj=207394.
Multiple sclerosis is a chronic immune-mediated disease of the central nervous system, marked by demyelination, axonal damage, and progressive neurological decline. T lymphocytes—particularly CD4+, T helper (Th)1 and Th17 cells, as well as cytotoxic CD8+ cells—play a pivotal role in initiating and sustaining central nervous system inflammation. Acute inflammation is driven by peripheral immune activation, while progressive disease reflects compartmentalized, smouldering inflammation within the central nervous system, dominated by CD8+ T cells and microglia. A relative deficiency or dysfunction of regulatory T cells contributes to immune tolerance loss and ongoing neurodegeneration. Although T lymphocytes play a central role, the pathogenesis of multiple sclerosis involves a broader cellular network, including antigen-presenting cells, B lymphocytes, microglia, and astrocytes. While recent therapeutic strategies have increasingly focused on B lymphocytes, most disease-modifying therapies—and many emerging ones—exert at least partial effects by modulating T cell–mediated mechanisms. These insights underpin current T cell-targeted therapies and highlight unmet needs in multiple sclerosis.
Parkinson’s disease (PD) is the second most common neurodegenerative disorder among the elderly. Although pharmacological therapies can alleviate symptoms, they often fail to provide sustained or complete symptom control, underscoring the need for alternative therapeutic strategies. Neuromodulation techniques, particularly cortical electrical stimulation (CES), have shown promise in modulating cortical plasticity. However, the therapeutic efficacy of CES in PD remains to be fully elucidated. In this study we investigated the long-term therapeutic potential of a novel CES protocol in a transgenic MitoPark mouse model of PD.
MitoPark mice received CES beginning at 8 weeks of age (one session per day, 2 days per week) for a total of 12 weeks. Motor function was assessed using a comprehensive behavioral battery, including beam walking, open-field, and gait performance tests. Neuroprotective effects were evaluated by quantifying dopaminergic neuronal survival and striatal fiber density using tyrosine hydroxylase (TH) immunohistochemistry.
Long-term CES treatment significantly ameliorated motor impairments in MitoPark mice, improving locomotor activity, gait coordination, and beam walking performance compared with sham controls. Immunohistochemical analyses further revealed enhanced survival of nigrostriatal dopaminergic neurons and fibers in the CES-treated group, indicating pronounced neuroprotective effects.
These findings demonstrate that early and sustained CES intervention mitigates motor deficits and enhances dopaminergic neuron survival in the MitoPark PD model. The results provide compelling preclinical evidence supporting CES as a potential adjunctive neuromodulatory therapy for Parkinson’s disease.
Emotional variability in healthy individuals may reflect underlying neurochemical processes relevant to mental health. Proton magnetic resonance spectroscopy (1H-MRS) enables in vivo quantification of metabolites linked to neuronal integrity and glial activity, yet data on nonclinical Middle Eastern populations remain scarce.
Eighty-four healthy young women from Saudi Arabia underwent 3T 1H-MRS of the basal ganglia. Metabolite ratios ((N-acetylaspartate/Creatine (NAA/Cr), Choline/Creatine (Cho/Cr), Myo-Inositol/ Creatine (Myo-In/Cr), Glutamate/Creatine (Glx/Cr)) were quantified using LCModel. Mood and anxiety were assessed with validated self-reported scales. Correlation and regression analyses examined associations between metabolite ratios and emotional scores.
Higher Cho/Cr and Myo-In/Cr ratios correlated positively with mood (r = 0.35, p < 0.001; r = 0.29, p = 0.004) and anxiety (r = 0.32, p = 0.002; r = 0.27, p = 0.009). NAA/Cr showed small negative associations, while Glx/Cr was nonsignificant. Regression confirmed Cho/Cr and Myo-In/Cr as significant predictors of both mood and anxiety, explaining up to 31% of variance.
Basal ganglia metabolite ratios, particularly Cho/Cr and Myo-In/Cr, are associated with affective variability in healthy young women. These findings underscore the potential of 1H-MRS neurochemical profiles as early indicators of emotional vulnerability, supporting integration into precision mental health frameworks for preventive care.
The objective identification of potential neurophysiological markers of schizotypal personality traits represents a major step toward improving early diagnostic strategies in psychiatry. In this study, we investigated the influence of schizotypal personality traits on the neural mechanisms underlying literal and figurative language comprehension, aiming to contribute to the development of neurophysiological markers of schizophrenia spectrum pathology.
A total of 121 university students were assessed using the Schizotypal Personality Questionnaire (SPQ) and categorized into three groups: low-SPQ (scores <21; n = 60), intermediate-SPQ (scores 21–40; n = 44), and high-SPQ (scores ≥41; n = 16). Participants evaluated 60 literal, 60 idiomatic, and 60 semantically incongruent phrases for meaningfulness, while event-related potentials (ERPs)—specifically N400 and post-N400 Positivity (PNP)—were recorded.
The low-SPQ group showed clear N400 differentiation between idiomatic expressions and both incongruent and literal conditions, whereas intermediate-SPQ and high-SPQ groups demonstrated reduced N400 distinctions in the frontal area. At central and parietal sites, participants with increased SPQ scores retained partial differentiation between idiomatic and incongruent phrases, but they failed to differentiate between idiomatic and literal ones. Moreover, participants with intermediate SPQ scores exhibited larger frontal PNP differences between incongruent and idiomatic conditions relative to the low-SPQ group.
These findings indicate that schizotypal traits are associated with poorly regulated semantic processing at the N400 stage, which is accompanied by compensatory activity at later stages of stimulus processing. These findings highlight ERP markers that may support early detection of vulnerability to schizophrenia spectrum disorders.
Circadian rhythms and emotional health are fundamentally interconnected. Circadian rhythms are characterized by self-sustaining oscillations within biological systems that synchronize sleep-wake cycles and related physiological and biochemical processes with periodic environmental changes. Clinical observations have demonstrated the significant role of the biological clock in the regulation of mood and anxiety, indicating that disruptions in circadian pacemaker control may contribute to the development of mood disorders and psychopathology. Conversely, therapeutic interventions aimed at correcting circadian misalignment have been shown to alleviate symptoms of mood disorders. The mechanistic involvement of astrocytes in mood disorders has been well-established. Recent research indicates that astrocytes possess the ability to autonomously regulate circadian rhythms, independent of pacemaker neurons. In addition to modulating rhythmicity in the central pacemaker, the suprachiasmatic nucleus (SCN), astrocytes are involved in circadian regulation within emotion-related brain regions, such as the nucleus accumbens (NAc) and amygdala. Nonetheless, the precise mechanisms by which astrocytes influence mood through circadian pathways, and the potential for their rhythmic alterations to serve as therapeutic targets for mood disorders, remain incompletely understood. In this review we synthesizes contemporary evidence regarding the role of astrocytes as pivotal regulators of circadian rhythms, focusing on how their intrinsic transcriptional–translational feedback loop (TTFL) oscillations influence mood disorders. Additionally, we investigate the role of astrocytic neurotransmitters, such as glutamate, γ-aminobutyric acid (GABA), and purinergic signaling, in the circadian-mediated amelioration of mood pathologies. These insights offer novel perspectives for identifying chronotherapeutic intervention targets for mood disorders.
Cerebral ischemia-reperfusion injury (CIRI) is a severe neurological condition where restoring neuronal mitochondrial function critically impacts prognosis. While electroacupuncture (EA) has demonstrated neuroprotective effects by improving mitochondrial function, the precise underlying mechanisms remain unclear. Emerging evidence suggests that astrocyte-to-neuron mitochondrial transfer, facilitated by mitochondrial Rho-GTPase 1 (Miro1), serves as a vital neuroprotective pathway. Therefore, this study investigates whether astrocytic Miro1 participates in the neuroprotective effects of EA against CIRI in mice by regulating the expression of the mitochondrial marker translocase of the outer mitochondrial membrane 40 (TOM40) and adenosine triphosphate (ATP) levels in damaged neurons.
126 C57BL/6 mice were randomly allocated into seven experimental groups (n = 18 per group): Sham-operated (Sham), middle cerebral artery occlusion (MCAO) model, EA, sham electroacupuncture (SEA), EA combined with astrocyte-specific Miro1 knockdown (GFAP: glial fibrillary acidic protein, EA+AAV-GFAP-shMiro1), astrocyte-specific Miro1 over-expression (AAV-GFAP-hiMiro1), and adenoviral empty vector control (AAV-GFAP-control). The CIRI model was induced using MCAO. Prior to model induction, the EA group received pretreatment with EA at the Baihui (GV20) acupoint. The SEA group underwent identical procedures to the EA group except for electrical stimulation. For the EA+AAV-GFAP-shMiro1, AAV-GFAP-hiMiro1, and AAV-GFAP-control groups, mice received intracerebroventricular injections of AAV-GFAP-shMiro1, AAV-GFAP-hiMiro1, or AAV-GFAP-control, respectively, 48 hours prior to EA treatment, with other procedures matching the EA group. At 24 hours post-reperfusion, neurological deficit scores, cerebral infarct volume, and neuronal survival in the peri-infarct penumbra were assessed. Astrocytes and neurons from the peri-infarct penumbra were isolated to measure ATP levels and expression of the mitochondrial-specific protein TOM40 in neurons, as well as ATP levels, TOM40, and Miro1 protein expression in astrocytes.
Relative to the Sham group, the MCAO group displayed a significant increase in cerebral infarct volume and neurological deficit scores, accompanied by a marked reduction in neuronal viability, TOM40 expression, and ATP levels (p < 0.01). In contrast to the MCAO and SEA groups, the EA and AAV-GFAP-hiMiro1 groups demonstrated improved neurological scores, reduced infarct volume, enhanced neuronal viability, elevated neuronal ATP levels and TOM40 expression, as well as decreased astrocytic ATP and TOM40 levels, but significantly increased Miro1 expression in astrocytes (p < 0.01). When compared to the EA group, the EA+AAV-GFAP-shMiro1 group exhibited a reversal of all the aforementioned improvements (p < 0.01), while the AAV-GFAP-hiMiro1 group showed no significant changes (p > 0.05).
EA exerts neuroprotective effects in MCAO mice by upregulating Miro1 protein expression in astrocytes and upregulating the mitochondrial marker TOM40 alongside ATP levels in neurons. Silencing Miro1 abolished the neuroprotective effects of EA and reduced neuronal TOM40 expression, while Miro1 overexpression increased this mitochondrial marker and mimicked EA-mediated neuroprotection. These findings identify Miro1 as a key effector of EA-induced neuroprotection, although the upstream signaling pathways linking EA to Miro1 upregulation require further investigation.
Migraine with aura (MwA) and migraine without aura (MwoA) are believed to have distinct pathophysiological mechanisms. However, differences in their neuromagnetic activity are currently unclear. To address this knowledge gap, this study employed magnetoencephalography (MEG) to examine alterations in magnetic source strength and functional connectivity (FC) between MwA and MwoA patients.
Resting-state MEG data were recorded for 18 MwA and 18 MwoA patients during the interictal period and compared with 18 matched healthy controls (HCs). The spectral power and FC of the visual network were estimated using minimum norm estimation (MNE) combined with the Welch technique and corrected amplitude envelope correlation.
Spectral power analysis revealed distinct frequency-dependent alterations in MwA in the left lateral occipital cortex (LOC), bilateral lingual cortices, and right transverse temporal cortex within the theta band compared with the MwoA and HCs groups. FC analysis revealed a distinct pattern of weakened FC in MwA in the low-frequency band between the visual cortex and several key regions, including the right entorhinal cortex, right rostral anterior cingulate cortex (ACC), right superior parietal cortex (SPC), left precentral cortex, and right precuneus cortex compared with the MwoA and HCs groups. The MwoA group exhibited significantly stronger FC within the ACC-visual cortex circuit in the gamma1 band compared with the MwA and HCs groups. Several abnormal FC metrics were significantly correlated with headache attack frequency in both migraine groups.
This study revealed the distinct neuromagnetic signatures of MwA and MwoA, linking specific connectivity patterns to clinical features. These findings could potentially support the development of subtype-specific, targeted neuromodulation therapies for migraine.
Whole-body vibration (WBV) has emerged as a promising non-pharmacological intervention for chronic neurological disorders; however, its underlying mechanisms remain incompletely understood. In this study, we investigated the therapeutic efficacy and mechanistic basis of WBV in subarachnoid hemorrhage (SAH), a severe condition characterized by high mortality and long-term neurological deficits.
SAH was induced in mice via chiasmatic cistern injection. WBV intervention (frequency: 28 Hz, amplitude: 0.3 mm) was initiated 7 days post-SAH and continued for 3 consecutive weeks. Neurological function was assessed using the open field test, Morris water maze, Y-maze, and gait analysis. Meningeal lymphatic vessel (MLV)-mediated drainage was evaluated through in vivo fluorescence imaging of Evans blue and Alexa Fluor 647-conjugated ovalbumin clearance. The expression of podoplanin (Pdpn) and lymphatic vessel endothelial hyaluronan receptor 1 (Lyve-1), specific markers of meningeal lymphatic endothelial cells, was analyzed in MLVs and deep cervical lymph nodes (dCLNs) using quantitative real-time polymerase chain reaction (qRT-PCR). Peripheral immunomodulatory changes were assessed by quantifying cluster of differentiation 4 and forkhead box protein P3 positive (CD4+Foxp3+) regulatory T cells (Tregs) in peripheral blood mononuclear cells via flow cytometry.
WBV treatment significantly improved learning and memory deficits, emotional disturbances, and motor dysfunction in SAH mice. Mechanistically, WBV enhanced the drainage capacity of MLVs by promoting lymphangiogenesis. Furthermore, WBV increased the proportion of peripheral Tregs, indicating an enhanced immunomodulatory effect.
This study demonstrates that WBV facilitates neurological recovery post-SAH by enhancing meningeal lymphatic drainage and expanding the peripheral Treg population. These findings highlight WBV as a promising, non-invasive therapeutic strategy for SAH rehabilitation.
Global cerebral ischemia remains a major cause of neurological morbidity and mortality, yet effective neuroprotective strategies have shown limited translational success. Experimental studies frequently rely on ischemic duration as a primary determinant of injury severity, implicitly assuming equivalence across global brain ischemia–reperfusion (IR) and cardiac arrest with return of spontaneous circulation (CA/ROSC) models. However, increasing experimental evidence indicates that identical ischemic durations can lead to substantially different neuronal outcomes depending on the physiological and systemic context of ischemia. In brain-restricted global IR models, partial preservation of systemic circulation allows residual metabolic activity, delayed stress responses, and region-specific neuronal vulnerability, most notably delayed neuronal death in the hippocampal cornu ammonis 1 region. By contrast, CA/ROSC is characterized by complete systemic circulatory arrest followed by a biologically hostile reperfusion phase that includes profound mitochondrial dysfunction, heterogeneous reperfusion, blood–brain barrier disruption, and amplification of systemic inflammatory responses. As a result, these qualitative differences shift ischemic injury thresholds toward earlier onset and broader neuronal damage in CA/ROSC, even when ischemic durations are nominally comparable. This review integrates experimental evidence from rat models to examine how energy failure, reperfusion biology, proteostasis disruption, and brain–body interactions collectively determine neuronal vulnerability beyond ischemic duration alone. Through direct comparison of global IR and CA/ROSC paradigms, we highlight limitations of duration-centric interpretations and outline implications for experimental design and translational neuroprotection. Recognition of context-dependent ischemic mechanisms is essential for improving model selection and advancing therapeutic strategies for global cerebral ischemia.