BACKGROUND:Psychological stress shapes brain-body interactions through bidirectionally signaling between central neural circuits and peripheral systems. Central amygdala corticotropin-releasing hormone (CeACRH) neurons are key regulators of stress response and immune function. However, their chronic impact on the brain-gut-immune axis and gut microbiota remains poorly understood. METHODS:We established a chronic stress model in mice by 14-day chemogenetic activating CRH neurons in the CeA. Behavioral assays were conducted to evaluate anxiety and depressive-like phenotypes. mRNA expression level of cytokines, tight junction proteins and antimicrobial peptide were compared in spleen or colon using qPCR between CeACRH activated group and control. In addition, 16S rRNA sequencing was performed to characterize changes in the microbial composition. RESULTS:Chronic activation of CeACRH neurons showed a tendency toward anxiety-like behavior and significantly disrupts splenic and colonic immune homeostasis. Notably, the colonic interleukin-22 (IL-22)/regenerating islet‑derived protein 3 gamma (Reg3g) mucosal defense axis was suppressed. Microbiota analysis revealed a shift toward a depression-associated profile, characterized by an increase in potentially pathogenic taxa (e.g., Eggerthella and Actinomycetota) and a reduction in short-chain fatty acid producers (e.g., Ruminococcaceae and Roseburia). These microbial alterations are consistent with clinical observations in patients with depression, supporting the translational relevance of mental disorders and gut microbiota. CONCLUSIONS:Chronic activation of CeACRH neurons drives coordinated immune, gut barrier, and microbiota alterations, including Claudin-2 upregulation and suppression of the IL-22/Reg3g axis, with IL-22 significantly reduced and Reg3g showing only a decreasing trend. These findings suggest a neuro-immune-microbiota pathway linking central stress circuits to peripheral dysfunction. Targeting IL-22 signaling, epithelial barrier integrity, or microbiota composition may represent promising therapeutic strategies for chronic stress-related disorders.
Cardiovascular modulation mediated by adenine-based purines is a very complicated and dynamic process driven by adenosine, adenosine diphosphate (ADP), and adenosine triphosphate (ATP). It is orchestrated through the interaction of these molecules with specific purinergic P1, P2Y, and P2X receptors, located throughout the central and peripheral nervous systems. This, along with the constant enzymatic interconversion of these compounds by ectonucleotidases, results in overlapping and highly variable cardiovascular responses. Activation of G protein-coupled purinergic P2Y receptors plays a fundamental role in cardiovascular homeostasis, modulating autonomic integration, neurogenic transmission, and vascular function. Within this context, ADP-sensitive P2Y receptors, particularly the P2Y1, P2Y12, and P2Y13 subtypes, participate in distinct sensory, autonomic, and functional cardiovascular mechanisms, as identified in several in vitro and in vivo experimental models. Accordingly: (i) the stable and non-hydrolysable ADP analogue, adenosine 5'-O-(β-thio)-diphosphate (ADPβS), has been widely used as a pharmacological tool to investigate P2Y receptor-mediated cardiovascular responses; and (ii) the specific role of P2Y receptors has been confirmed using selective P2Y receptor antagonists, including MRS2500 (P2Y1), PSB0739 (P2Y12) or MRS2211 (P2Y13). The cardiovascular effects of ADP are complex; depending on the experimental conditions, it can either decrease or increase heart rate, myocardial contractility, vascular tone, and/or systemic blood pressure. These effects are mediated by several P2Y receptors that act at different levels of cardiovascular control, encompassing crucial integration sites within the central nervous system, as well as peripheral autonomic and cardiovascular effector mechanisms such as preganglionic nerves, autonomic ganglia, postganglionic nerves, sensory fibres, vascular smooth muscle, vascular endothelium, and cardiac tissues. In this review, we: (i) summarize the pharmacological profile of the P2Y receptors that mediate cardiovascular responses, with special emphasis on peripheral autonomic, sensory, and vascular mechanisms, revealed in in vivo experimental models; and (ii) highlight the potential of P2Y receptors as therapeutic targets for the treatment of cardiovascular pathologies, including hypertension, coronary vasospasm, ischemic injury, and coagulation problems.
BACKGROUND:High-density micro-electrocorticography (µECoG) provides the spatiotemporal resolution necessary to probe columnar-level cortical architecture. However, chronic multimodal interfacing is fundamentally challenged by aggressive post-surgical tissue responses that rapidly obscure optical access, in addition to localization uncertainties due to brain shift. In this study, established a transparent cranial window interface on the macaque visual cortex. To evaluate the feasibility of this approach, we primarily focused on assessing strategies to mitigate dural tissue regrowth and documenting the inherent biological complications (e.g., hemorrhage), while exploring the potential for direct, in vivo visual localization of µECoG arrays. METHODS:A custom transparent chamber assembly integrated with a 64-channel µECoG array was implanted in the visual cortex of two rhesus macaques (n = 2). We compared two dural interface designs-a floating Tecoflex sheet versus a bonded silicone ring-to optimize optical clarity and interface stability. Physical stability of the electrodes relative to vascular landmarks was quantified. Electrophysiological performance was longitudinally evaluated using impedance monitoring, visual evoked potentials, and support vector machine (SVM) neural decoding to discriminate between red-green and black-white grating stimuli, with statistical significance assessed via bootstrap tests. RESULTS:Regarding the biological and electrical interfaces, while long-term optical maintenance proved challenging due to tissue regrowth or hemorrhage, the bonded silicone ring design effectively mitigated peripheral tissue invasion. Electrophysiologically, array performance captured the dynamic biological transitions of the interface. Stable impedance profiles and statistically significant gamma-band (30-80 Hz) responses-modulating from initial widespread coverage (up to 100%) to restricted subsets (e.g., 16% at five months)-alongside robust SVM classification accuracy (p < 0.001) were tracked longitudinally. Additionally, as a preliminary observation in a single subject, the transparent window permitted the precise identification of electrode positions relative to cortical vasculature, revealing minor physical displacements (median = 0.20 mm) within the initial two weeks post-implantation. CONCLUSIONS:Comparing two dural interface designs highlights the mechanical and biological trade-offs required for chronic optical access, emphasizing that optimizing the mechanical compliance of the dural seal is a critical consideration for long-term multimodal interfaces. Furthermore, this interface shows the potential to overcome conventional localization limitations through early-stage visual co-registration. Although maintaining permanent optical clarity remains a fundamental challenge due to aggressive tissue responses, the system supports longitudinal high-density recording, providing a critical platform for multimodal studies bridging macroscopic network dynamics and microscopic cellular activity.
BACKGROUND:Distractive spinal cord injury (DSCI), a severe complication of spinal deformity correction surgery, is characterized by rapid neuronal loss. However, the molecular mechanisms linking mechanical distraction to apoptosis remain unclear. Here, we tested whether sodium rutin (NaR), a water-soluble rutin derivative with improved oral bioavailability, mitigates DSCI. METHODS:We employed an in vivo rat DSCI model and an in vitro mechanical distraction (DIS) model using neuronal cells. The therapeutic efficacy of NaR was evaluated using locomotor function assessments (Basso-Beattie-Bresnahan score and footprint analysis), histopathology, and transmission electron microscopy. Molecular docking simulations were performed to predict the binding affinity of NaR to Erb-B2 receptor tyrosine kinase 4 (ErbB4). Mechanistic investigations targeting the ErbB4/protein kinase B (Akt) axis, reactive oxygen species (ROS), and apoptotic pathways were conducted using western blot analysis and immunofluorescence. RESULTS:DIS suppressed ErbB4 phosphorylation and downstream Akt signaling, accompanied by the activation of B-cell lymphoma 2/Bcl-2-associated X protein/Caspase-3 (Bcl-2/Bax/Caspase-3) apoptotic pathways after DSCI. Simultaneously, DIS induced a decrease in the mitochondrial membrane potential (ΔΨm) and accumulation of mitochondrial ROS, along with a significant reduction in superoxide dismutase 2 (SOD2) and glutathione peroxidase 4 (GPX4) levels. NaR treatment engaged ErbB4 to restore ErbB4/Akt signaling, inhibited mitochondrial ROS signaling, ameliorated ΔΨm, and reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic neurons, thereby inhibiting neuronal apoptosis. However, the inhibition of ErbB4 phosphorylation along with NaR treatment significantly reversed these therapeutic effects. Furthermore, the pharmacological administration of NaR ameliorated histopathological and neuronal ultrastructural damage in the spinal cord tissues, increased the number of surviving neurons, and facilitated locomotor recovery after DSCI. CONCLUSIONS:These findings identify ErbB4 and ROS signaling as key regulators of neuronal survival during DSCI and establish NaR as a candidate therapeutic strategy for DSCI associated with spinal deformity correction surgery.
BACKGROUND:Multiple object tracking (MOT) tasks are widely used to examine attention impairments in autism spectrum disorder (ASD); however, existing research has predominantly relied on behavioral measures and has barely incorporated physiological data, such as electroencephalography (EEG). Additionally, how cognition and emotion interact in individuals with ASD during MOT tasks remains unclear. METHODS:In this study we addressed these gaps using a publicly available dataset containing EEG recordings and clinical measurement from 28 children with ASD and 28 typically developing (TD) individuals. Participants listened to speech recordings reflecting prosodic happiness and sadness while completing three attention-level tasks: neutral image viewing (low-attention), one-target four-disc MOT-4 (intermediate-attention), and one-target eight-disc MOT-8 (high-attention). For each participant's EEG data, we calculated the theta-beta ratio (TBR) for each channel and then extracted five EEG features: averaged TBR for all channels (allTBR), averaged TBR for channels in the frontal brain region (fTBR), averaged TBR for channels in the temporal brain region (tTBR), averaged TBR for channels in the central brain region (cTBR), and averaged TBR for channels in the parietal brain region (pTBR). Correlation analysis was also conducted to explore the association between EEG features and clinical measures. RESULTS:Findings showed that: (1) the interaction effect between attentional level and emotion was significant for allTBR and tTBR; (2) Significant main effects of group were observed for all five TBR metrics (allTBR, fTBR, tTBR, cTBR, and pTBR), with the ASD group showing higher values than the TD group; (3) only tTBR showed a significant difference between happiness and sadness stimuli during the MOT-8 task after Bonferroni correction; (4) during the MOT-4 task, the TD group had higher correlations between five EEG features and clinical measures than the ASD group; and (5) the tTBR finding during the MOT-8 task suggests that emotional valence may modulate neural processing in the temporal region under high cognitive load. CONCLUSIONS:These findings could provide new insights into attentional impairments and cognition-emotion interactions in ASD, offering potential implications for the development of clinical intervention strategies.
BACKGROUND:Extensive neuroimaging abnormalities in multiple brain regions constitute the neural basis of preterm infants (PTIs). However, the function of the brain and its spatial coupling with brain structure remain unknown, leaving a considerable gap in understanding the neural mechanism underlying atypical neurodevelopment in PTIs. METHODS:Combining structural magnetic resonance imaging (MRI) and resting-state functional magnetic resonance imaging (fMRI) data from 14 PTIs and 14 term infants (TEIs), we quantified gray matter volume (GMV) via voxel-based morphometry, estimated intrinsic timescales from fMRI signals via autocorrelation function (ACF) analysis, and further assessed spatial structure-function coupling across individuals. RESULTS:PTIs exhibited GMV alterations in multiple brain regions encompassing high-order cortical and subcortical regions (p < 0.001, corrected by family-wise error (FWE)), which were significantly associated with clinical variables such as gestational age (R = 0.716, p < 0.0001), postnatal age (R = -0.698, p < 0.0001) and birth weight (R = 0.727, p < 0.0001). Alterations in intrinsic timescales were revealed at both the spatial distribution (voxel-level p < 0.001, Gaussian random field (GRF)-corrected p < 0.05) and local regional levels, highlighting functional alterations of the medial frontal gyrus in PTIs (voxel-level p < 0.001, GRF-corrected p < 0.05). Furthermore, alterations in spatial structure-function coupling were also found in both high-order cortical and subcortical regions, with ACF decay in these regions significantly correlated with serum iron levels (R = -0.664, p = 0.0096) in PTIs. CONCLUSIONS:These findings suggest that preterm birth-related neurodevelopmental alterations may be associated with differences in the coordination between brain structure and function, which could be related to variations in neurobehavioral outcomes, and indicate that neuroimaging may provide useful insights into early neurodevelopmental differences in PTIs.
BACKGROUND:Caffeine, a widely consumed psychoactive substance, has known effects on physiological and behavioral processes. Recent studies report that caffeine can influence the circadian rhythm, which is linked to many aspects of physiology, energy metabolism, and homeostasis. Therefore, we examined the arousal effects of caffeine via behavioral tests and assessed its impact on the circadian rhythm by measuring clock gene and clock-controlled gene expression in the brains of mice and Neuro 2a (N2a) cells. METHODS:Male C57BL/6 mice from two age groups, young (1 month 2 weeks) and mature (10 months 2 weeks), were randomly divided into four subgroups: control, vehicle, caffeine, and caffeine with adenosine (n = 8 each). After inducing fatigue through forced treadmill exercise, we performed balance beam and foot fault tests, and measured the mRNA expression and protein levels of circadian genes (circadian locomotor output cycles kaput (Clock), brain and muscle ARNT-like 1 (Bmal1), period circadian regulator 2 (Per2), cryptochrome circadian regulator 1 (Cry1), and Cry2) in the brain and N2a cells treated with caffeine. RESULTS:Caffeine treatment showed a trend toward reduced body weight gain in both young and mature mice. Behavioral tests indicated improvements in balance and coordination across both age groups. After 16 days of treatment, circadian genes showed significant differences in expression, and adenosine receptor levels changed notably, especially after long-term exposure. In N2a cells, caffeine decreased viability in a dose-dependent manner and affected circadian gene expression. CONCLUSIONS:The study demonstrates that caffeine influences body weight, behavior, circadian rhythms, and adenosine receptor protein levels, with age-related variations. These findings deepen the understanding of caffeine's effects on physiological and molecular functions and suggest possible age-specific therapeutic implications or precautions related to caffeine intake.
BACKGROUND:Major depressive disorder is a disabling psychiatric illness with a growing global burden. Neuroinflammation, particularly microglial polarization, is increasingly recognized as a key pathogenic factor and is closely linked to lipid metabolic regulation. Shikonin, a bioactive naphthoquinone from Lithospermum erythrorhizon, exhibits anti-inflammatory and antioxidant properties, yet its antidepressant effects remain unclear. This study examined whether shikonin alleviates depressive-like behaviors by suppressing neuroinflammation. METHODS:Mice were orally treated with shikonin for two weeks before the induction of learned helplessness (LH). A series of behavioral paradigms tail suspension test (TST), forced swim test (FST), sucrose preference test (SPT), and escapable shocks test (EST) was employed to evaluate depression-related behaviors. Following behavioral testing, inflammatory mediators, activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, microglial lipid droplet accumulation, autophagic status, and M1/M2 polarization markers were evaluated. In vitro, mouse microglial cell line BV2 (BV2) microglia were activated by lipopolysaccharide (LPS). A cell counting kit-8 (CCK-8) assay was conducted to screen non-cytotoxic shikonin concentrations, with subsequent in vitro verification of in vivo outcomes. The role of lipophagy in microglial polarization was further examined through pharmacological modulation of autophagy using chloroquine and rapamycin. RESULTS:Shikonin markedly alleviated depression-like behaviors in LH mice, accompanied by decreased interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression and inhibition of the cGAS-STING pathway. Mechanistically, shikonin suppressed M1 microglial polarization and lipid droplet accumulation in the hippocampus by restoring autophagic flux. Shikonin exerted anti-inflammatory effects in vitro by inhibiting cGAS-STING-dependent M1 polarization and restoring lipophagy in LPS-stimulated BV2 cells. CONCLUSIONS:Our findings show that shikonin suppresses cGAS-STING activation, shifts microglia away from the M1 phenotype, and promotes autophagy, thereby reducing lipid droplet accumulation and alleviating neuroinflammation and depressive-like symptoms.
The triple network model has become a widely adopted framework for studying large-scale brain organization in basic and clinical neuroscience; however, accumulating evidence complicates this taxonomy. The default mode network, once labelled "task-negative", is now recognized as dynamically engaged across both internally directed and task-related processes. The salience network, often described as a "switching" hub, exerts context-dependent modulatory influences on both default mode and central executive network activity, supported by oscillatory coupling and directed connectivity. The central executive and frontoparietal networks, traditionally viewed as a unitary task-positive network, display heterogeneity across parcellations and frequency bands, suggesting finer-grained functional subdivisions than previously assumed. Multimodal studies integrating electroencephalography, functional magnetic resonance imaging, and other approaches converge on the view that networks interact through flexible, frequency-specific dynamics, but diverge in their anatomical assignments depending on atlas, modality, and task. In this scoping review synthesizes evidence on network definitions, methodological inconsistencies, and putative modulatory mechanisms, highlighting the heterogeneity of control networks and underscoring the need to incorporate temporal dynamics into future taxonomies. We propose that geometric hypotheses of neural control describing the global coordination of local activities, such as those used in neural manifolds, may improve our understanding of disordered cognition by integrating the many existing methodologically constrained maps into a coherent stable atlas that is more robust to approximating biases and errors associated with sampled population variability.
Ischemic stroke disrupts cerebral metabolism and initiates a cascade of pathological events, including excitotoxicity, mitochondrial dysfunction, and neuroinflammation. These interconnected processes drive neuronal apoptosis, necrosis, and synaptic loss, ultimately leading to irreversible brain injury, persistent neurological deficits, and high rates of long-term disability and mortality. Ketone bodies, including β-hydroxybutyrate, acetoacetate, and acetone, have demonstrated neuroprotective properties through multiple mechanisms. These include sustaining cerebral energy supply and mitochondrial stability, attenuating excitotoxicity and calcium overload, suppressing inflammatory responses, and promoting neural remodeling and functional recovery. Accordingly, ketone bodies are increasingly recognized as a promising therapeutic strategy for ischemic stroke. However, evidence supporting their clinical application and systematic implementation in humans remains limited. In this review we summarize ketone body metabolism and the mechanisms underlying its neuroprotective effects, evaluate the evidence supporting translation from preclinical studies to clinical application, and highlight key challenges that must be addressed in future investigations. Based on the current evidence, we also propose priorities for short-term clinical research and outline future perspectives.
BACKGROUND:Epileptic seizures exhibit distinct circadian rhythms. Disruption of this rhythm creates a vicious cycle that further exacerbates the seizures. Rev-Erbα is a key circadian regulator that plays a significant role in epilepsy. In this study we aimed to investigate the expression and effects of Rev-Erbα and its agonist SR9009 across different brain regions during acute status epilepticus (SE) and chronic epilepsy (CE). METHODS:C57BL/6J mice were randomly divided into control, epilepsy (SE and CE), and SR9009+epilepsy (SR9009-E) groups. The distribution and expression of Rev-Erbα in the medial prefrontal cortex (mPFC), hippocampus (HP), and occipital visual cortex (V2M) of mice with SE and CE mice were detected using immunofluorescence and western blotting. Electroencephalography (EEG), the open-field test, and the Y-maze test were applied to evaluate epileptic activity, anxiety, and spatial memory. RESULTS:Rev-Erbα expression differed significantly across cerebral regions among the control, epilepsy (SE and CE), and the SR9009-E groups (p < 0.05). SR9009-E mice had fewer seizures and less abnormal EEG discharge (p < 0.05) and showed better behavioral outcomes, including reduced anxiety-related behaviors and improved spatial memory, compared with epileptic mice (p < 0.05). Immunofluorescence showed higher neuronal numbers in the SR9009-E group than in the epilepsy group (p < 0.05). CONCLUSIONS:Rev-Erbα dysregulation is tightly linked to epilepsy progression. Activation of Rev-Erbα exerts antiepileptic and neuroprotective effects and improves epilepsy-related neurobehavioral deficits, thereby offering a novel strategy for epilepsy treatment.
BACKGROUND:Traumatic brain injury (TBI) often leads to long-term cognitive deficits. High-definition transcranial direct current stimulation (HD-tDCS) is a non-invasive neuromodulation approach with potential to enhance cognitive recovery. However, the underlying mechanisms by which tDCS influences neural synapses following mild TBI remain unclear. In this study, we aimed to identify the optimal HD-tDCS intervention cycle for improving cognition after repetitive mild TBI (rmTBI) in mice and to elucidate synaptic mechanisms. METHODS:Male C57BL/6J mice underwent mild closed-head injury and received HD-tDCS (0.5 mA, 20 min/day) over the right parietal cortex. Cognitive performance was evaluated after 5, 10, and 15 days of stimulation using Y-maze and novel object recognition tests. Synaptic protein expression (PSD-95, SYN, NMDAR, GluA1) and BDNF/TrkB/CREB signaling pathway components were assessed via Western blot, while c-Fos expression was examined by immunofluorescence staining. Dendritic spine density was examined using Golgi staining. In addition, exploratory molecular modeling was performed to assess potential interactions between electric fields and the BDNF-TrkB complex. Separately, to contextualize our experimental findings, we also analyzed the public single-cell RNA-sequencing dataset GSE180862 as part of the study design. RESULTS:HD-tDCS improved learning and memory performance, with the 15-day protocol showing the most robust effects among the tested schedules at the same post-injury endpoint. Behavioral improvements were accompanied by increased expression of BDNF-associated signaling proteins, elevated synaptic marker levels, and enhanced dendritic spine density in the hippocampus. In the 15-day stimulation group, a numerical trend toward sustained cognitive benefit was observed at 2 weeks after the end of stimulation, although the difference did not reach statistical significance. Molecular modeling suggested potential field-protein interactions but did not establish direct conformational modulation in vivo. CONCLUSIONS:Cognitive recovery improved following HD-tDCS intervention, accompanied by upregulation of BDNF/TrkB/CREB pathway-related proteins, synaptic markers, and dendritic spine density. These findings suggest a close association between repeated HD-tDCS and plasticity-related molecular changes after brain injury, although causal evidence for pathway activation requires further investigation.
BACKGROUND:Previous neuroimaging studies of patients with chronic neck pain (CNP) have revealed abnormal functional activity and structure of brain regions. However, these results often exhibit variability. Therefore, we have integrated existing research findings using a multimodal meta-analysis to obtain consistent and reliable results on brain functional activity and structural changes in CNP patients. METHODS:Studies of the amplitude of low frequency fluctuations, regional homogeneity, or voxel-based morphometry that investigated the differences in brain function and structure between CNP patients and healthy controls were searched for in seven Chinese and English databases up to November 12, 2025. Meta-analysis of the relevant neuroimaging data from the eligible literature was performed using anisotropic effect size signed differential mapping. RESULTS:This meta-analysis included a total of 36 datasets from 33 articles. The analytic results of resting-state functional magnetic resonance imaging indicate that the CNP patients exhibited abnormal functional activity in the right superior frontal gyrus (SFG), left median cingulate gyrus, right calcarine fissure cortex, right middle temporal gyrus (MTG), and left inferior parietal gyrus. Further, CNP patients exhibit abnormal gray matter volume (GMV) of the left paracentral lobule, right superior temporal gyrus (STG), right middle frontal gyrus (MFG), bilateral SFG, right cerebellum, right cuneus cortex, and left MTG. Additionally, the meta-regression analysis revealed that age is associated with increased functional activity in the right MTG, while disease duration is associated with decreased functional activity in the left median cingulate gyrus, as well as increased GMV in both the right MFG and STG. CONCLUSIONS:CNP patients exhibit widespread neuroimaging abnormalities, mainly involving pain perception, advanced cognition, and emotion regulation. These results may offer additional ideas for understanding the central mechanisms of CNP and the exploration of potential targets for CNP treatment.The PROSPERO Registration:CRD420251018254, https://www.crd.york.ac.uk/PROSPERO/view/CRD420251018254.
BACKGROUND:Prospective memory (PM) relies on the ability to form, maintain, and retrieve intentions during an ongoing activity. In this study we examined the neural oscillatory dynamics underlying distinct PM stages: intention formation (Cue trials), intention retention (Ongoing trials), and intention retrieval (PM Retrieval trials). These stages were investigated using two newly developed PM tasks: the Animal-cued Prospective Retrieval Task (Ac-PRT) and the Object-cued Prospective Retrieval Task (Oc-PRT). METHODS:In this cross-sectional observational study, twenty-three young adults (mean age = 20.50 years, standard deviation = 2.35) completed the tasks while electroencephalography (EEG) data were recorded. RESULTS:Behavioral results showed that participants responded more slowly during the Ongoing trials compared with the Cue and PM Retrieval trials and were less accurate during PM Retrieval trials across both tasks. Event-related spectral perturbation (ERSP) analyses revealed differences in PM stages in both tasks. PM Retrieval trials had significantly greater alpha (8-12 Hz) and low beta (12-20 Hz) desynchronization within 350-650 ms relative to the Ongoing trials, potentially reflecting increased attentional control and task-set reconfiguration during intention retrieval. Cue trials showed enhanced alpha and low beta desynchronization relative to Ongoing trials, suggesting preparatory attentional engagement triggered by the cue. Task-specific effects included lower theta synchronization in addition to greater alpha and beta desynchronization in the Oc-PRT compared with the Ac-PRT, which may reflect differential engagement of cognitive control and semantic processing mechanisms. CONCLUSIONS:The observed patterns in theta, alpha, and beta activity suggest that these oscillations are associated with task demands that vary across PM stages. Together, these findings identify neurophysiological signatures that may guide future research on age-related changes in prospective memory.
BACKGROUND:Gamma and beta oscillations of electroencephalography (EEG) are involved in multiple perceptual information processing. Neurofeedback training (NFB) is a non-invasive neuromodulation approach that provides an endogenous paradigm to investigate the causal relationship between brain oscillations and cognitive abilities. In this study we investigated the effectiveness and specificity of gamma and combined gamma-beta NFB training for improving visual perception in healthy adults. METHODS:A total of 48 healthy participants were recruited and randomly assigned into three groups. Four participants withdrew during the study, leaving 44 participants for final analysis : a sham group (n = 14), a gamma NFB training group (n = 16) targeting parieto-occipital (PO) gamma rhythms, and a gamma-beta training group (n = 14) targeting both PO gamma and central beta rhythms. All participants underwent six NFB sessions, each containing nine blocks. Baseline tasks for resting state and visual perception measurements were conducted before and after NFB training. RESULTS:Both training groups showed significant improvements in reaction time and accuracy. Importantly, EEG data obtained during the training process and baseline tests showed that relative PO gamma rhythms were increased in both groups, while relative central beta rhythms were enhanced only in the gamma-beta group. EZ-diffusion model analysis revealed that these improvements were primarily driven by increased drift rates and reduced non-decision times, suggesting enhanced efficiency in perceptual evidence accumulation. CONCLUSIONS:The current results validate the effectiveness of NFB training and demonstrate clear spectral and regional specificity, revealing different functional contributions of the two oscillations during visual perception. In the context of a randomized, sham-controlled design, these results provide preliminary causal evidence for the involvement of gamma- and beta-band activity in visual processing. CLINICAL TRIAL REGISTRATION:No: ChiCTR2600124537. https://www.chictr.org.cn/showproj.html?proj=292703.
Concepts are cognitive constructs that are fundamental to neuroscience. Superordinate concepts such as world, life, and person are widely used in common language but typically ill-defined. In an interdisciplinary approach we present superordinate concepts as three-part accounts that encompass the articulated concepts of objects, events, and narratives. Thereby, superordinate concepts integrate the physical, relational, and narrated nature of our environmental information into comprehensive verbal expressions. Owing to their distributed representations in large-scale neural networks that in addition to the prefrontal cortex involve the temporoparietal cortex and subcortical structures such as the amygdala, superordinate concepts evolve in relation to language development in childhood. They may gain prominent emotional relevance and continue to mature throughout a person's lifetime. Conversely, they are susceptible to neuropsychiatric disorders of the brain that affect cortico-cortical connectivity. In conclusion, superordinate concepts are metastable descriptors of integrated verbalized information that provide a novel perspective on the mind-brain relationship.
BACKGROUND:Protein p62 interacts with Kelch-like ECH-associated protein 1 (Keap1) competitively, triggering the oxidative stress response mediated by NF-E2-related factor 2 (Nrf2) and preventing ferroptosis in SH-SY5Y cells. Emerging evidence implicates that this regulatory axis may confer neuroprotection against cerebral ischemia-reperfusion injury (CIRI). The current investigation was designed to elucidate whether the p62/Keap1/Nrf2 signaling pathway contributes to the amelioration of CIRI through modulation of ferroptosis. METHODS:In SH-SY5Y cells, we used an oxygen-glucose deprivation/reperfusion (OGD/R) paradigm. In Sprague-Dawley rats, we used a middle cerebral artery occlusion/reperfusion (MCAO/R) model. Through these models, we investigated the effects of p62/Keap1/Nrf2 pathway activation. Additionally, we used in vitro experiments to analyze ferroptosis markers, cell damage, and the expression of pathway proteins. We injected the p62-overexpressing lentivirus into SH-SY5Y cells and the lateral ventricle of rats subjected to MCAO/R. Finally, we investigated the effects of an Nrf2 activator and a ferroptosis inhibitor. RESULTS:Nrf2 negatively regulated OGD/R-triggered ferroptosis in SH-SY5Y cells by increasing glutathione peroxidase 4 (GPX4) expression and decreasing acyl-CoA synthetase long-chain family member 4 (ACSL4) levels. p62 overexpression in cells enhanced the interaction between Keap1 and p62, activating Nrf2 and protecting against OGD/R-triggered ferroptosis. Activating the p62/Keap1/Nrf2 signaling pathway in vivo reduced the brain injury area, decreased neuromotor functional impairment, and decreased the expression of ferroptosis markers in rats. CONCLUSIONS:Activation of the p62/Keap1/Nrf2 signaling pathway reduces ferroptosis and alleviates CIRI. This protective mechanism provides novel directions for investigating the pathological mechanisms of CIRI.
Digital twins are increasingly promoted in neurology as an advancement beyond conventional artificial intelligence, yet the term is often applied without conceptual or methodological rigor. Strict definitions describe digital twins as dynamically updated, bidirectionally linked models that generate predictive, decision-relevant value, criteria rarely met by current neurological applications. This Opinion critically examines the state of digital twins across major neurological domains, including dementia, multiple sclerosis, Parkinson's disease, epilepsy, stroke, pain, and migraine. We argue that most existing systems are more accurately described as twin-inspired longitudinal decision-support or trial-analytics models rather than true clinical digital twins. While neurology is well-suited to digital twin approaches due to disease heterogeneity, multimodal data, and iterative care pathways, progress is limited by gaps in measurement validity, uncertainty handling, prospective evaluation, and governance. A pragmatic path forward is proposed, emphasizing question-specific, validated neurological digital twins over overgeneralized brain twin narratives, and suggesting that much of the current field is better understood as twin-inspired modeling rather than true clinical digital twin implementation.
Diabetic cognitive impairment (DCI) affects approximately 25%–35% of patients with diabetes and is characterized by progressive cognitive decline. Dysfunction of mitochondria—the energy factories within neurons—is considered a potential pathogenic factor of DCI, involving processes such as oxidative stress, calcium overload, autophagic dysfunction, and genetic mutations, ultimately disrupting normal neuronal function. Maintaining mitochondrial quality and function is critical for neuronal health. Recent studies have shown that there are multiple ways in which cells can communicate signals, such as extracellular vesicles (EVs), tunneling nanotubes and gap junctions, which can repair and replace damaged mitochondria within receptor cells. Notably, EV-mediated mitochondrial transplantation has demonstrated significant potential by transferring healthy mitochondria to impaired neurons and restoring energy metabolism and antioxidant defences, thereby offering novel therapeutic strategies for intervening in DCI progression with valuable clinical translation potential. This review systematically elucidates multimodal signalling strategies targeting mitochondrial homeostasis, with a focused analysis on the role of EV-mediated mitochondrial transplantation in restoring neuronal energy balance, providing a theoretical foundation for the development of innovative DCI interventions.
