INTRODUCTION:Referred sensation (RS) is described as the sensation evoked in the skin areas distinct from the site of stimulation. The study sought to identify and map RS in participants with traumatic brachial plexus injury (TBPI) through a standardised assessment. METHODS:Conducted as an observational study, Experiment 1 involved 19 participants who underwent RS screening by stimulating 22 specific skin areas across both upper limbs, the neck and the face with a cotton swab. In Experiment 2, a comprehensive RS mapping was performed using Semmes-Weinstein monofilaments on the reinnervated forearm of three subjects who exhibited upper limb-chest RS. One participant underwent RS mapping over 6.3 years. RESULTS:RSs were reported in three of four participants who underwent intercostal-to-musculocutaneous nerve (ICN-MCN) transfer and in two participants who underwent ulnar-to-musculocutaneous nerve (UN-MCN) transfer. RS within the original donor's nerve territory ('right-way') was observed following ICN-MCN transfer. Systematic mapping of 'right-way' RS after ICN-MCN transfer revealed a distinctive distribution pattern in the forearm and chest, lacking clear topographical organisation. Remarkably, longitudinal assessment of a single participant revealed a gradual, scattered expansion of RS over time. DISCUSSION:To our knowledge, this study provides the first systematic mapping of RS in TBPI participants. Persistent 'right-way' RS following ICN-MCN transfer suggested that the significant distance between donor and recipient nerve representations in the primary somatosensory cortex (S1) may limit plastic reorganisation and restrict the disentangling of sensations between the forearm and chest. This insight underscores the complexity of nerve regeneration and opens new avenues for therapeutic approaches focused on sensory function.
BACKGROUND:Irritable bowel syndrome (IBS) is a common disorder of brain-gut interaction frequently co-occurs with depressive symptoms (dIBS). The amygdala is a critical hub for emotion-visceral integration and exhibits functional heterogeneity across its subregions. However, subregion-specific network alterations in dIBS remain unclear. METHODS:Forty-nine IBS patients and 36 demographically matched healthy controls (HCs) completed resting-state functional magnetic resonance imaging (rs-fMRI) and clinical assessments. Patients were stratified into dIBS (n = 28) and nondepressive IBS (ndIBS, n = 21) groups. Bilateral lateral amygdala (lAmyg) and medial amygdala (mAmyg) were selected as seeds for graph-theoretical nodal metrics and seed-based functional connectivity (FC) analyses. One-way analysis of covariance with post hoc comparisons was performed to assess intergroup differences. Correlation, mediation, and receiver operating characteristic (ROC) analyses were further conducted. RESULTS:Compared with ndIBS patients, dIBS patients exhibited increased degree centrality (DC) and nodal efficiency (Ne) in the left lAmyg, which were positively associated with depressive symptom severity. In addition, dIBS patients showed widespread hypoconnectivity between amygdala subregions and prefrontal and sensorimotor regions, including the medial superior frontal gyrus, postcentral gyrus, and thalamus. These FC alterations were correlated with clinical symptoms severity. Notably, the mAmyg-related FC in superior frontal gyrus and thalamus showed mediation effects linking gastrointestinal symptoms and depressive symptoms and exhibited high accuracy in distinguishing dIBS from ndIBS (area under the curves, AUCs > 0.8). CONCLUSION:Aberrant nodal properties and disrupted connectivity of amygdala subregions may reflect altered emotion-visceral integration in dIBS. These findings provide neuroimaging evidence for brain-gut interaction abnormalities in dIBS and suggest that amygdala subregional networks may serve as potential markers for symptom stratification and targeted interventions.
BACKGROUND:Acute ischemic stroke (AIS) remains a leading cause of long-term disability, with approximately 70% of survivors suffering from motor, sensory, and language impairments that significantly affect their daily functioning and quality of life. Recent advances in neuroimaging have provided a more precise assessment of changes in brain gray matter volume (GMV) and functional connectivity (FC), both of which are closely correlated with disease severity, prognosis, and rehabilitation outcomes. Acupuncture, as a complementary therapy, has demonstrated potential in alleviating motor and language deficits following stroke. By integrating structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) data with comprehensive clinical evaluations, this research aims to objectively investigate the neural mechanisms underlying acupuncture-induced brain plasticity. Our goal is to explore how acupuncture may augment conventional AIS treatments by promoting neuroplasticity, offering a scientific basis for its integration into standard therapeutic protocols. The findings aim to advance our understanding of the neurobiological basis for integrative rehabilitation strategies, ultimately contributing to improved prognostic evaluation and optimized recovery trajectories for AIS patients. METHODS:A total of 54 AIS patients with motor dysfunction were allocated to receive either acupuncture combined with western medicine treatment (AWT) group or WT group alone. The acupuncture points used included: Neiguan (PC6), Renzhong (DU26), Sanyinjiao (SP6), Weizhong (BL40), Zusanli (ST36), Fenglong (ST40), Taichong (LR3), and Yanglingquan (GB34). Patients in AWT groups received treatment 5 times per week for 8 weeks. National Institutes of Health Stroke Scale (NIHSS), the Fugl-Meyer assessment (FMA) and structural and fMRI data were collected at three time points: baseline (on the day of enrollment), week 8 (at the end of the acupuncture intervention), and week 12 (after a 12-week follow-up period post-intervention). GMV and FC analysis was performed to investigate the potential mechanism of acupuncture treatment by comparing differences in brain cortical structure and function between treatments. RESULTS:GMV: The AWT group manifested an increased GMV in the ipsilesional supplementary motor area (SMA) and contralesional anterior cingulate gyrus (ACG) by week 8. In contrast, the WT group witnessed a substantial decline in GMV within the ipsilesional median cingulate and paracingulate gyrus (DCG). At the 12-week follow-up, the AWT group further demonstrated a significantly greater increase in GMV in the ipsilesional superior temporal gyrus (STG) when compared to week 8. The between-group comparisons at week 8 disclosed that the AWT group had a significantly elevated GMV in the postcentral gyrus (PoCG) and contralesional inferior temporal gyrus (ITG) (p = 0.005) in contrast to the WT group. By week 12, the AWT group also presented a marked increase in GMV in the ipsilesional ITG relative to the WT group. In the spearman correlation analysis, a positive correlation was identified in the AWT group between the GMV of the ipsilesional SMA at 8 weeks post-enrollment and the FMA score at week 12 (p = 0.016, R = 0.487). Moreover, the GMV in the contralesional ACG exhibited a positive correlation with the FMA score at week 12 (p = 0.006, R = 0.540). Additionally, a negative correlation was also detected in the WT group between the GMV of contralesional PoCG and the NIHSS score at week 8 (p = 0.004, R = -0.540). FC: At 8 weeks post-enrollment, the AWT group exhibited significantly increased FC between the ipsilesional SMA and the contralesional middle temporal gyrus (MTG), between the contralesional PoCG and the ACG, and between the contralesional PoCG and the ipsilesional pallidum (PAL). In the WT group, increased FC was observed between the ipsilesional SMA and the contralesional STG, and between the contralesional PoCG and the ipsilesional middle occipital gyrus (MOG). No significant positive FC regions were identified in the between-group comparisons at either 8 weeks post-enrollment or the 12-week follow-up. In the spearman correlation analysis, the enhanced FC between the ipsilesional SMA and the contralesional MTG in the AWT group was positively correlated with the post-acupuncture FMA score (p = 0.043, R = 0.417). In the WT group, the enhanced FC between the contralesional PoCG and the ipsilesional MOG was positively correlated with the FMA score (p = 0.003, R = 0.567). CONCLUSIONS:The increased in GMV and enhanced FC in AIS patients following acupuncture intervention are correlated with improvements in neurological and motor functions. Acupuncture may promote neural network remodeling and the coordinate of brain structure and function. These findings suggest potential neurobiological mechanisms through which acupuncture can improve clinical outcomes in patients.
Sleep disturbances (SD) are not merely symptoms of posttraumatic stress disorder (PTSD), but also amplify and perpetuate all other PTSD phenotypes. Ginsenoside Rg1 is extensively applied in managing neuropsychiatric diseases. Nevertheless, its impact on PTSD-like SD and mechanisms remain largely unknown. In this study, the PTSD model in mice was produced using single-prolonged stress (SPS) and the improvement effect of ginsenoside Rg1 on PTSD-like behavior in mice, especially the sleep-wake phase was detected. The potential targets and signaling pathways of ginsenoside Rg1 as an intervention for treatment of PTSD with sleep disturbances (PTSD-SD) were predicted using bioinformatics analysis. Thereafter, in vivo experiments were further used to verify the results. Our data showed that 14 days after SPS, the sleep architecture of mice was significantly disturbed, while ginsenoside Rg1 could treat PTSD-like SD in SPS mice. The results of bioinformatics analysis suggested that NLRP-related pathways and apoptosis may be the key factors for ginsenoside Rg1 to treat PTSD-like sleep disturbances. Meanwhile, animal experiments also showed that the NLRP3 inflammasome, oxidative stress and apoptosis-related markers were abnormally expressed in the hippocampus of SPS mice, but the administration of ginsenoside Rg1 could counteract the dysregulated expression of the above proteins in SPS mice. Finally, the results of docking revealed that ginsenoside Rg1 had favorable binding affinity with verified targets including NF-κB, NLRP3, ASC, GFAP, HO-1, and cleaved caspase-3. Collectively, ginsenoside Rg1 is effective to prevent PTSD-like SD, likely by regulating systemic comprehensive responses.
Tuina is a traditional Chinese manual therapy distinguished from generic massage by its acupoint- and meridian-based manipulations, and it is commonly used in the management of neurological and musculoskeletal disorders, although its underlying biological mechanisms remain incompletely defined. This review summarizes current experimental and clinical evidence on the neurobiological processes associated with Tuina therapy, with a focus on pain modulation and neural repair. Available evidence suggests that mechanical stimulation during Tuina may engage mechanosensitive ion channels, including transient receptor-potential vanilloid (TRPV)1, transient receptor-potential ankyrin 1 (TRPA1), and Piezo channels, thereby modulating nociceptive signaling, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) and toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB)-related inflammatory pathways, Piezo1/Piezo2- and YAP/TAZ-associated mechanotransduction, neurotransmitters and neuropeptides, and descending pain inhibitory circuits involving the periaqueductal gray (PAG)-rostral ventromedial medulla (RVM) system. In addition, emerging evidence indicates that Tuina may affect peripheral and central neuroplastic processes, including modulation of neuronal excitability, glial activity, and functional brain networks. While these findings provide a mechanistic framework for understanding reported clinical effects in conditions such as neuropathic pain (NP), low back pain (LBP), cervical disorders, and headache, heterogeneity in study design and intervention protocols limits definitive conclusions. Further well-designed mechanistic studies and standardized clinical trials are required to clarify the role of Tuina in pain regulation and neuroplasticity and to support its evidence-based application in clinical practice.
BACKGROUND:Robot-assisted upper-limb rehabilitation is widely used after stroke, but links to neuroplasticity biomarkers remain uncertain. OBJECTIVE:To synthesize biomarker evidence after robot-assisted upper-limb training and quantify post-intervention effects versus non-robot comparators. METHODS:We searched PubMed, Web of Science, Embase, Cochrane Library, EBSCOhost, and Scopus from inception to December 31, 2025. Randomized controlled trials (RCTs) and nonrandomized intervention studies enrolling adults with stroke were eligible if they reported at least one neuroplasticity biomarker. Prespecified comparison classes were used; only the primary contrast (robot-assisted training vs. non-robot control) was pooled at post using DerSimonian-Laird random-effects models. Effects were expressed as standardized mean differences (SMDs; Hedges' g) or mean differences (MDs) with 95% confidence intervals (CIs). RESULTS:Fifty-five studies, including 24 RCTs, were included. Four RCTs contributed to the primary quantitative synthesis, and each pooled endpoint included two or three trials. Robot-assisted training was associated with improved ipsilesional resting motor threshold (RMT; SMD 1.77, 95% CI: 0.46-3.08; k = 2) and upper-limb impairment (Fugl-Meyer assessment-upper extremity [FMA-UE]; MD 4.48 points, 95% CI: 0.33-8.62; k = 3). Effects were uncertain for ipsilesional motor-evoked potential (MEP) amplitude (SMD 0.52, 95% CI: -0.31-1.34; k = 2) and activities of daily living (ADL). Heterogeneity was moderate to substantial, prediction intervals crossed the null, and certainty was low or very low. CONCLUSIONS:Robot-assisted training may improve impairment and corticospinal excitability, but randomized biomarker evidence remains sparse and heterogeneous. Biomarkers should be interpreted as exploratory observations, not validated surrogates or causal evidence of cortical restitution.
BACKGROUND:The primary motor (M1) and somatosensory (S1) cortices play a key role in motor learning (ML), but the physiological mechanisms underlying learning in these regions remain unclear. This study aimed to evaluate the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over S1 or M1 to enhance use-dependent and reinforcement-like ML in healthy participants. METHODS:A single-blind, randomized controlled trial (RCT) was conducted with 60 healthy participants, randomly assigned to receive rTMS over M1, S1, or sham. Participants underwent a 10-day motor training protocol involving an arbitrary visuomotor association (AVMA) task to promote reinforcement learning and the Purdue Pegboard Test (PPT) to promote use-dependent learning, always after rTMS. The primary outcome measure was the number of pegs placed in the PPT, and the secondary outcome was the response accuracy during a forced response (FR) version of the AVMA. Assessments were conducted at baseline, mid-intervention (t1), postintervention (t2), and at 1-month follow-up (t3). RESULTS:For use-dependent learning on the PPT, S1 stimulation outperformed sham at t1 (right hand), t2 (both hands), and t3 (both hands). M1 stimulation showed no significant differences versus sham. For reinforcement learning on the forced response-AVMA (FR-AVMA), no active group differed from sham; however, S1 and M1 showed opposite numerical tendencies at t3 (S1 trending better, M1 worse), yielding a significant S1-M1 contrast. CONCLUSION:These findings suggest that rTMS over S1 may enhance use-dependent ML, while the divergent S1 and M1 tendencies in reinforcement-like learning warrant further, adequately powered investigation, with implications for future research in both healthy and clinical populations. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT06262425.
Rumination, characterized by repetitive and self-referential thinking, is closely linked to depression and a broad range of psychiatric disorders. However, previous research has predominantly relied on task activation or network-level approaches, leaving critical gaps in our understanding of local brain activity dynamics during ruminative states. To address this, we employed brain entropy (BEN), a novel functional magnetic resonance imaging (fMRI)-based neuroimaging measure, to quantify the temporal irregularity and complexity of local brain activity during rumination. We analyzed a publicly available dataset comprising 41 healthy adults who completed identical fMRI tasks across three MRI scanners. Each scanning session included four conditions: resting state, sad memory, rumination, and distraction. Voxel-wise BEN analyses were conducted to examine condition-related differences, with brain regions showing consistent patterns across all three scanners at p < 0.05 considered statistically significant. Our findings revealed distinct neural signatures associated with different cognitive states. Compared to sad memory, rumination was associated with decreased BEN in the visual cortex (VC), whereas distraction was associated with decreased BEN in the posterior cingulate cortex/precuneus (PCC/PCu). Furthermore, rumination exhibited significantly increased BEN in the PCC/PCu relative to distraction. These results suggest that rumination is characterized by heightened temporal irregularity in regions supporting internal self-referential processing, accompanied by reduced engagement with external environmental information. The present study demonstrates the utility of BEN in elucidating the neural mechanisms of rumination, providing novel insights into how cognitive states are reflected in local brain activity patterns. These findings carry implications for both theoretical frameworks of ruminative cognition and the development of neuroimaging biomarkers for clinical applications in depression and related disorders.
BACKGROUND:Nurr1, an orphan nuclear receptor that lacks an endogenous ligand, plays a key role in hippocampal function, synaptic plasticity, and cognitive processes. It is linked to various central nervous system diseases; however, its association with chronic cerebral hypoperfusion (CCH)-induced cognitive impairment remains unclear. This study investigated whether the Nurr1 agonist, amodiaquine (AQ), can enhance synaptic plasticity and alleviate cognitive deficits caused by CCH. METHODS:A CCH rat model was created using the bilateral common carotid arterial occlusion method, followed by a 2-week AQ treatment (20 mg/kg, every 12 h, through intraperitoneal injection). Learning and spatial memory were assessed using the Morris water maze (MWM), Y-maze, and object recognition tests. Cerebral blood flow (CBF) in the cortex and hippocampus was measured using arterial spin labeling (ASL) with 3.0T magnetic resonance imaging (MRI), and white matter fiber density was assessed using diffusion tensor imaging (DTI). Hippocampal neuron morphology and count were examined using Nissl and NeuN staining, while dendritic spine morphology and density in CA1 and CA3 hippocampal regions were analyzed using Golgi staining. RESULTS:Experiments with the water maze, Y-maze, and object recognition tests demonstrated that CCH rats treated with AQ exhibited improved long-term and short-term memory and spatial recognition compared to the control group, with benefits persisting after two and 6 weeks. MRI DTI sequences revealed that AQ reversed the decline in white matter fiber density observed in CCH model rats compared to the sham group. Golgi staining confirmed that AQ protected the dendritic spines of the neurons damaged in the CCH model. CONCLUSION:Administrating Nurr1 agonist AQ demonstrated a sustained ameliorative effect on cognitive deficits in CCH rats. This effect is potentially mediated through the mitigation of hippocampal neuronal loss and improvement of dendritic spine integrity.
BACKGROUND:Acute single subcortical infarction (ASSI) is a prevalent cerebrovascular disorder in clinical practice. Although progress has been made in understanding its central mechanisms, the patterns of white matter (WM) microstructural damage in early-stage unilateral lesions remain poorly characterized. OBJECTIVE:This study aimed to examine WM microstructural alterations in ASSI patients using Tract-Based Spatial Statistics (TBSS) and Atlas-Based Analysis (ABA), and to assess the clinical utility of this combined approach. METHODS:This prospective study enrolled 44 participants (20 patients with ASSI and 24 healthy control [HC] group). WM microstructure was evaluated using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). TBSS was employed for voxel-wise analysis of the WM skeleton, while ABA was used to extract regions of interest (ROIs). Correlation analyses assessed associations between microstructural changes and Fugl-Meyer Assessment (FMA) scores. RESULTS:Relative to the HC group, patients with ASSI showed significantly reduced FA in multiple bilateral WM tracts (p < 0.05), including bilaterally in the corticospinal tract (CST), cingulate gyrus, hippocampus, and inferior fronto-occipital fasciculus, as well as the right inferior longitudinal fasciculus (ILF), right superior longitudinal fasciculus, right superior longitudinal fasciculus (temporal part), and forceps major. ASSI patients also showed higher MD in several major WM tracts (p < 0.05), involving bilaterally in the anterior thalamic radiation and hippocampus, as well as the right CST, right cingulate gyrus, forceps major, right inferior fronto-occipital fasciculus, right ILF, right superior longitudinal fasciculus, and right superior longitudinal fasciculus (temporal part). The changes in AD and RD values were not statistically significant. FMA scores are closely correlated with the MD and FA of the right cingulate gyrus. The MD of the right hippocampus and right ILF is also associated with FMA scores (p < 0.05). CONCLUSION:The combined TBSS-ABA approach provides a reliable means to evaluate WM damage in ASSI. It not only identifies lesion clusters but also precisely localizes impaired WM regions, facilitating motor dysfunction assessment. TRIAL REGISTRATION:Chinese Clinical Trial Registry: ChiCTR2400085342.
We investigated the temporal dynamics of resting-state brain activity associated with language reorganization in patients with left-hemisphere brain tumors using coactivation pattern (CAP) analysis of functional MRI. This retrospective study included 106 right-handed patients who underwent both resting-state and task-based fMRI before surgery. Language dominance was determined using a phonemic fluency task, and CAP analysis identified recurring whole-brain activation patterns. Dynamic properties of CAPs, including persistence, transitions, in-degree, and out-degree, were compared between patients with typical and atypical language dominance and between those with and without postoperative aphasia. Six distinct CAPs corresponding to known functional networks were identified. Patients with atypical language dominance showed higher out-degree (p=0.004) and transitions (p=0.006) in the dorsal default mode network (DMN; CAP2) and lower persistence in the visuospatial network (VSN; CAP3; p=0.002) compared with patients with typical dominance. Patients without postoperative aphasia demonstrated higher transitions in VSN CAP6 (p=0.024). Logistic regression analyses were performed to evaluate the prediction of postoperative aphasia. A model including CAP metrics and the language laterality index (LI) demonstrated good predictive performance (area under the curve [AUC] = 0.851, accuracy = 82.4%, sensitivity = 71.9%, and specificity = 88.1%), outperforming a model based on LI alone (AUC = 0.640 and accuracy = 67.0%). No significant differences were observed by tumor type or volume. These findings indicate that CAP dynamics capture distinct neural states associated with language dominance and postoperative outcomes. Specific CAP metrics may serve as potential imaging biomarkers of functional reorganization, supporting prognostic evaluation and surgical planning in patients with brain tumors.
In adults with acquired hearing loss, cortical reorganization and cross-modal plasticity critically influence the timing and outcomes of cochlear implantation. This study examined the effects of 2 weeks of bilateral auditory deprivation-induced by intense broadband noise-on the structure and gene expression in the primary auditory (A1) and visual (V1) cortices of adult rats. The results revealed that the total neuronal counts in both the A1 and V1 remained unchanged compared to controls. Morphological analysis showed no significant change in mature dendritic spine density in either region, but immature spine density was significantly reduced in the V1 cortex. Ultrastructural examination demonstrated notable synaptic alterations in the A1 cortex, including significant reductions in postsynaptic density (PSD) length, thickness, area, and synaptic vesicle number-changes that were not observed in the V1 cortex. Transcriptomic profiling indicated a region-specific response, with 197 differentially expressed genes (DEGs) in the A1 cortex, compared to a broader alteration of 545 DEGs in the V1 cortex, which were significantly involved in neuronal signaling and synaptic transmission. These findings demonstrate that auditory deprivation induces distinct molecular and synaptic remodeling in the A1 and V1 cortices, identifying neuronal plasticity and synaptic regulation as central mechanisms for cross-modal reorganization in the adult brain.
Absence of sensory input is associated with alterations in brain morphology; mainly in or near cerebral regions normally devoted to processing of the missing sense. However, multiple recent studies demonstrate that the only consistent morphological finding within the gray matter of individuals born without the sense of smell (isolated congenital anosmia [ICA]), are changes in or near the olfactory sulcus. In contrast, for the connecting tissue of the brain, the white matter (WM), previous studies have yielded inconsistent findings. Here, we show that individuals with ICA (n = 49) exhibit clear alterations in WM volume when compared to age- and sex-matched controls. Consistent evidence from both voxel-based morphometry and multivoxel pattern analysis shows that individuals with ICA show decreased WM in areas surrounding the olfactory sulcus. Critically, no WM alterations were found in areas surrounding the olfactory (piriform) cortex. In contrast to congenital sensory loss in other sensory systems, we show that morphological alterations due to lifelong olfactory deprivation are limited, primarily localized around the olfactory sulcus, and likely due to the absence of olfactory bulbs. A possible explanation for the lack of major morphological alterations in individuals with congenital anosmia is that the olfactory regions may be recruited for nonolfactory functions.
BACKGROUND:Electroacupuncture (EA) is widely used for analgesia, but its central mechanisms remain unclear. We investigated whether EA alleviates neuropathic pain by suppressing metabotropic glutamate receptor 5 (mGluR5) signaling in the anterior cingulate cortex (ACC). METHODS:In naïve mice, we manipulated ACC pyramidal neurons using adeno-associated viral (AAV) vectors encoding calcium/calmodulin-dependent protein kinase II (CaMKII)-driven opsins-channelrhodopsin-2 (ChR2) or halorhodopsin (NpHR3.0)-followed by blue- or yellow-light stimulation to assess behavioral responses. In a chronic constriction injury (CCI) model, mice received EA and were evaluated for mechanical and thermal withdrawal thresholds. Western blotting (WB) and immunofluorescence (IF) quantified ACC mGluR5 expression. Then CaMKII-targeted adeno-associated viruses expressing chemogenetic receptors, such as hM3Dq or hM4Di, were injected into the ACC. Two weeks later, CCI was induced, and mice received either EA or intraperitoneal clozapine-N-oxide (CNO) while pain behaviors were monitored. Finally, proteomic profiling of ACC tissue compared CCI and EA groups. RESULTS:Optogenetic activation of ACC pyramidal neurons in naïve mice reduced both mechanical and thermal withdrawal thresholds, indicating a pronociceptive effect, whereas optogenetic inhibition increased thresholds. In CCI mice, EA significantly attenuated hypersensitivity and downregulated ACC mGluR5 protein levels by WB and IF. Chemogenetic inhibition of ACC pyramidal neurons similarly elevated thresholds in CCI mice, imitating EA. Notably, combining chemogenetic inhibition with EA produced no additional improvement, suggesting convergence on a common ACC mGluR5-dependent pathway. CONCLUSIONS:EA relieves neuropathic pain in mice, at least in part, by suppressing ACC pyramidal neuron activity via inhibition of mGluR5 signaling.
Dexmedetomidine (Dex), an α2-adrenergic receptor agonist, and apigenin (Api), a naturally occurring bioflavonoid, have recently shown neuroprotective effects in experimental models of methotrexate (MTX)-induced neurotoxicity; however, the impact of their combined administration has not yet been elucidated. This study investigated the effects of Dex on microglial activation, neuroinflammation, and apoptosis, and the role of Api in hippocampal neurogenesis, along with its combined effects via the miR-15a/ROCK-1/ERK1/2/CREB/BDNF signaling cascade. Male Sprague Dawley rats were randomly assigned into: a normal control group, Dex and Api-control groups, which received Dex or Api daily for 30 days, an MTX-only group that received MTX and leucovorin (LCV), Dex or Api cotreated groups received either Dex or Api with MTX and LCV, and a Dex + Api cotreated group received both drugs with MTX and LCV. Dex improved cognitive function by attenuating microglial activation. Api mitigated hippocampal neurogenesis, as shown by decreased Ki-67 and doublecortin (DCX) expression. Compared with Dex or Api alone, the combined treatment had more favorable effects on novel object recognition (NOR), miR-15a, ROCK-1, ERK1/2, histopathological changes, and Ki-67 neurogenesis marker over Api or Dex monotherapy, and improved CREB/BDNF signaling over Dex alone. However, no additional favorable effects on microglial activation, redox balance, IL-1β, or apoptosis were observed. The combination of Dex and Api exhibits more pronounced neuroprotective effects by potentiating modulation of the miR-15a/ROCK-1/ERK1/2/CREB/BDNF signaling cascade, improving cognitive behavior, and enhancing hippocampal neurogenesis.
Dysregulation of serotonin 1A receptor (5-HT1A), a G protein-coupled inhibitory receptor, is implicated in the pathogenesis of both autism spectrum disorder (ASD) and epilepsy. The prefrontal cortex (PFC) is particularly vulnerable to the factors that affect neuronal and synaptic development, with abnormal PFC development leading to increased epilepsy susceptibility. This study used 8-OH-DPAT to activate PFC 5-HT1A to investigate its role in attenuating epileptic susceptibility in a valproic acid (VPA)-induced rat model of ASD and potential mechanisms involving Kir3 channel-mediated hyperpolarization. Rats were prenatally exposed to VPA to induce autism-like behaviors, and successful induction was verified through behavioral, morphological, and electrophysiological assessments. Neuronal loss, dendritic complexity, and spine density in the PFC were evaluated using Nissl and Golgi staining. Pentylenetetrazol (PTZ) was used to induce chemical kindling for assessing seizure susceptibility in the ASD model. Spontaneous action potential (sAP) and miniature excitatory postsynaptic current (mEPSC) frequencies were electrophysiologically recorded. The selective 5-HT1A receptor (5-HT1AR) agonist 8-OH-DPAT was used to investigate its anticonvulsant effects. ASD rats exhibited significant neuronal loss, reduced dendritic complexity, and lower dendritic spine density in the PFC. The PTZ-treated ASD group showed reduced seizure onset latency, prolonged stage IV seizure duration, and higher seizure incidence, indicating increased susceptibility to epilepsy. Untreated rats displayed reduced sAP and mEPSC frequencies in PFC pyramidal neurons, suggesting E/I imbalance. However, PTZ treatment increased sAP and mEPSC frequencies, reflecting enhanced neuronal excitability. Treatment with 8-OH-DPAT significantly delayed seizure onset, shortened seizure duration, and reduced seizure incidence. Furthermore, 8-OH-DPAT decreased sAP and mEPSC frequencies. These effects were attenuated after applying tertiapin-Q (TQ), underscoring the role of inwardly rectifying potassium (Kir3) channels in mediating 8-OH-DPAT-induced anticonvulsant effects. In conclusion, PFC 5-HT1AR activity alleviated epileptic activity through Kir3 channel-mediated hyperpolarization. These findings highlight 5-HT1ARs and Kir3 channels as promising therapeutic targets for epilepsy associated with ASD.
Structural and functional brain reorganization can occur after long-term physical activity and lower limb amputation (LLA). A previous study suggested that activation of the primary motor cortex (M1) ipsilateral to the amputated leg during rectus femoris contraction is associated with the amount of sports participation in individuals with LLA. However, the structural basis of ipsilateral M1 activation remains unclear. The aim of this study was to investigate whether ipsilateral M1 activation is associated with white matter microstructure in descending motor pathways. We hypothesized that ipsilateral M1 activation would be related to microstructural properties of the corticoreticular tract (CRT) rather than the corticospinal tract (CST). Twenty-three individuals with LLA who had participated in sports for varying durations underwent functional magnetic resonance imaging (fMRI) and diffusion-weighted imaging. During fMRI, percent signal change (PSC) during rectus femoris contraction in the amputated leg was quantified. White matter microstructure was assessed using fixel-based analysis (FBA). Ipsilateral M1 PSC during contraction of the amputated leg was positively correlated with fiber cross-section (FC) in the CRT within the same hemisphere, whereas no significant correlation was observed for the CST. No significant correlations were found in control analyses using PSCs during contraction of the rectus femoris in the nonamputated leg, during motor imagery of ankle movements of the amputated leg, or in the visual cortex. These findings indicate a task- and hemisphere-specific functional-structural association between ipsilateral M1 activation and the CRT. Although FC in the CRT was not directly correlated with the amount of sports participation, it may constrain the extent of ipsilateral M1 functional reorganization associated with long-term sports involvement. Our results highlight a potential role of the CRT, in addition to the CST, in motor plasticity and rehabilitation in individuals with LLA.
Dance integrates bodily movement, rhythmic perception, and emotional expression, engaging complex sensorimotor and affective systems. However, its impact on the structural organization of empathy-related brain networks remains insufficiently understood. In this study, we adopted a data-driven approach to construct a structural empathy network based on neuroimaging data from 80 healthy university students and applied Granger causality analysis (GCA) to identify the directional impact of empathy on regional gray matter changes. Empathy ability was assessed using the interpersonal reactivity index (IRI) scale. To further examine training-induced neuroplasticity, we employed an independent sample consisting of 25 dancers and 25 musicians, alongside 40 matched controls without formal artistic experience. Inter-regional structural similarity, based on gray matter probability distributions, was calculated to capture modality-specific plasticity due to dance/music training. Compared to musicians and controls, dancers exhibited significantly higher gray matter probability distributions, which indicates enhanced structural similarity between the left superior temporal gyrus and the left precuneus, left postcentral gyrus, and right paracentral lobule. Notably, this increased structural similarity was also associated with the empathy score (r = -0.87, p < 0.05, family-wise error [FWE] corrected). These findings suggest strengthened cross-modal integration between perceptual and sensorimotor systems, potentially underpinning affective resonance. Our findings highlight the domain-specific neuroplasticity of the structural empathy network induced by dance training and provide novel insights into how embodied practices shape socio-emotional brain circuits. Chinese Clinical Trials Register: ChiCTR2200059526.
Persistent postural-perceptual dizziness (PPPD) is a disabling functional vestibular disorder characterized by chronic dizziness and visually and motion-induced unsteadiness that markedly impairs daily activities, yet it lacks objective neurobiological markers. We acquired resting-state functional MRI (rs-fMRI) in 52 patients with PPPD and 50 age- and sex-matched healthy controls (HCs) and analyzed the data using a three-tier approach: (i) functional network connectivity (FNC) of independent component analysis (ICA-FNC), (ii) voxel-wise measures of spontaneous amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF), and (iii) seed-based connectivity using a priori vestibular and subcortical regions of interest (ROIs; e.g., cerebellar (CB) nodulus, parafascicular thalamus, and caudate). Integrating these analytic tiers, we observed a coherent pattern: broadly increased connectivity of CB and primary visual (VIS) networks together with selective hypoconnectivity between a brainstem-cerebellar (BSC) component and the multimodal vestibular cortex (MVC), oculomotor (frontal eye field [FEF]), and default-mode networks (DMN). Voxel metrics revealed decreased ALFF in parietal and frontal opercular cortices-key vestibular integration regions-contrasting with increased fALFF in mid-cingulate, lateral occipital, and premotor areas. Seed-based mapping identified strengthened thalamo-VIS, striato-limbic, and nodulus-hippocampal connectivity. Importantly, increased BSC-to-VIS coupling correlated positively with depressive symptom severity and state anxiety, but negatively with balance confidence and psychological resilience, linking network imbalance to the biopsychosocial phenotype of PPPD. These findings support a multiscale signature of vestibular cortical disengagement accompanied by maladaptive VIS-CB reinforcement and motivate multicenter validation of network-level markers as adjuncts to symptom-based diagnosis.
Parkinson’s disease (PD) is a neurodegenerative disorder characterised primarily by motor symptoms. However, non-motor symptoms (NMS) also substantially affect patients’ quality of life. In recent years, exercise therapy has attracted increasing attention as a complementary treatment for PD and is regarded as a promising strategy for alleviating neuropsychiatric symptoms. A substantial body of evidence suggests that exercise improves multiple NMS domains in PD, and this effect may be achieved through several mechanisms. Despite the growing recognition of its benefits, the evidence base is limited by small sample sizes, heterogeneous interventions and inconsistent outcome measures. This underscores the necessity for further research to be conducted into the distinct effects of various forms of exercise. The present review synthesises the clinical evidence relating the impact of different exercise modalities on mood symptoms (anxiety and depression), cognitive dysfunction, sleep disturbances, pain and autonomic dysfunction in PD. It also discusses how exercise parameters such as intensity and duration can regulate NMS, exploring their potential mechanisms and clinical applications. These insights may inform new approaches to the comprehensive management of PD and future therapeutic strategies targeting NMS.
