BACKGROUND:Depression in Parkinson's disease (dPD) is common and heterogeneous, impairs quality of life, and may accelerate disease progression. Tools that predict long-term dPD progression are lacking. METHODS:We retrospectively analyzed de novo, drug-naïve Parkinson's disease (PD) participants in the Parkinson's Progression Markers Initiative (PPMI; 2011-2024). The primary outcome was depressive progression, defined as a sustained worsening in Geriatric Depression Scale-15 (GDS-15) category over 12 months. Candidate predictors included demographic, motor, and non-motor variables at both total and sub-item levels. Four survival machine learning models, Random Survival Forests (RSF), Extreme Gradient Boosting, Support Vector Survival Machines, and Gradient Boosting Survival Analysis, were evaluated using concordance index (C-index). Shapley Additive exPlanations were applied to identify key predictors and construct an integer-based risk score. RESULTS:Of 1819 eligible participants, 496 met inclusion criteria (median age 62 years [IQR: 55-69]; 61.3% male); 94 (19.0%) progressed over a median 6 year follow-up. RSF achieved the best discrimination (test-set C-index 0.744). Key predictors included age, baseline GDS-15; SCOPA-AUT subscores (thermoregulatory, gastrointestinal, cardiovascular); cognition (BJLOT, SDMT); impulse control disorder (QUIP-CS score), and MDS-UPDRS I (sleep problems night, pain and other sensations). The SHAP-derived score stratified patients into low (progression 7.3%), moderate (14.7%), and high-risk (36.5%) groups with clear Kaplan-Meier separation (log-rank p < 0.001). Time-dependent AUCs were 0.721, 0.770, 0.794, 0.792, and 0.812 at 2, 4, 6, 8, and 10 years. CONCLUSIONS:An explainable survival model and integer-based risk score using routinely collected measures predicted long-term dPD progression and enabled pragmatic risk stratification to support early, personalized management.

Neuroinflammation plays a key role in exacerbating dopaminergic neuron loss in Parkinson's disease (PD). We identified TAB2 as an early-stage biomarker, which was elevated in PD patients' microglia. However, the role of TAB2 in the pathogenesis of PD remains unknown. In this study, we found that Tab2 knockdown inhibited the activation of microglia and protected neurons in PD models. STAT3, as a transcription factor for TAB2, regulated TAB2 expression. Mechanistically, TAB2 interacted with α-synuclein and facilitated the recognition of K63-linked ubiquitin chains, leading to the formation of the TAK1-TABs complex and activation of TAK1, which was ultimately followed by activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, microglia-specific knockdown of Tab2 significantly inhibited microglia activation, protected dopaminergic neurons, improved motor function, and attenuated anxiety-like behaviors in PD mouse model. We further showed that the FDA-approved drug, lumacaftor, suppressed microglial TAB2 expression and had potent anti-inflammatory and neuroprotective effects in PD models. Taken together, our study reveals that the STAT3-TAB2-NF-κB-IL-1β positive feedback axis in microglia is a crucial checkpoint that exacerbates neuroinflammation in PD. Therefore, these findings identify a pivotal role of TAB2 in regulating microglia-mediated neuroinflammation, suggesting that targeting TAB2 may be a possible therapeutic strategy for PD.

Deep brain stimulation (DBS) has emerged as a transformative neuromodulation therapy for a variety of neurological and psychiatric disorders, including Parkinson’s disease, epilepsy, and obsessive-compulsive disorder. Despite its widespread clinical use, the precise mechanisms underlying these therapeutic effects remain incompletely understood. This review provides a comprehensive examination of DBS, from its historical development and underlying mechanisms to its diverse clinical applications in 16 diseases. The historical context traces the evolution of DBS technology from early stereotactic techniques to contemporary advances that allow for more precise targeting and adaptive stimulation. Mechanistically, DBS influences neural activity through a combination of depolarization block, informational lesion, and network reconfiguration via induced neuroplasticity. Each mechanism may contribute uniquely to symptom mitigation and therapeutic outcome. The most advanced and widely studied clinical applications of DBS are alleviating motor symptoms in Parkinson’s disease, managing refractory epilepsy, and addressing treatment-resistant psychiatric conditions. While highlighting these three major application conditions, we also map therapeutic interventions across a broader spectrum of emerging indications. The future of DBS lies in adaptive systems that optimize stimulation based on real-time neural feedback, as well as in expanding applications to other disorders and targets. Continued research and technological advancements are crucial for enhancing the efficacy, precision, and accessibility of DBS, thereby broadening its therapeutic potential.

Theta-burst stimulation, including intermittent (iTBS) and continuous (cTBS) protocols, is a promising neuromodulatory intervention for autism spectrum disorder (ASD). This study aims to elucidate the therapeutic mechanisms of iTBS and cTBS for ASD. Prenatal valproic acid-induced ASD rats were established and were randomized into VPA, VPA + iTBS, and VPA + cTBS groups, with a saline group as control. Core and comorbid ASD behaviors in rats were assessed. Multi-omics analyses included 16 S rRNA sequencing of cecal contents, non-targeted fecal metabolomics, and prefrontal cortex transcriptomics. Key pathways were validated via Western blot, ELISA, and immunofluorescence. Integrative analyses correlated multi-omics data with neuroendocrine findings. Behavioral assessments demonstrated that both iTBS and cTBS significantly ameliorated social deficits and repetitive behaviors in VPA-exposed rats. However, protocol-specific effects on comorbidities were observed: cTBS, but not iTBS, effectively alleviated anxiety-like behaviors, whereas iTBS, but not cTBS, significantly improved learning and memory. The multi-omics approach demonstrated that iTBS primarily modulated inflammatory immune responses and energy metabolism, while cTBS predominantly regulated oxidative stress, lipid metabolism, and nucleotide metabolism. Both interventions suppressed the hyperactivated PI3K/AKT/mTOR signaling pathway, an effect potentially linked to the normalization of hypothalamic-pituitary axis function. Furthermore, we identified a potential interplay between the GH/IGF-1 axis and the gut microbiome in ASD, which was differentially modulated by iTBS and cTBS. iTBS modulated inflammatory-immune responses and energy metabolism, while cTBS regulated oxidative stress, lipid metabolism, and nucleotide metabolism. The inhibition of the central GH/PI3K/AKT/mTOR pathway by both protocols may involve their specific regulation of distinct gut microbiota communities.

Infantile Epileptic Spasms Syndrome (IESS) is associated with brain network dysfunction during seizures, though the underlying mechanisms remain incompletely characterized. This study implemented an integrated multi-modal framework to examine how epileptic spasms impact developing functional brain networks in pediatric patients. Scalp EEG data from 25 patients were analyzed across five seizure phases, combining canonical microstate dynamics, multi-band source localization, and power spectral density analysis of eight large-scale functional networks. Results showed that microstates C and D displayed distinct dynamic patterns, with global microstate transition probabilities peaking in the interictal period and declining significantly during ictal events. These microstate patterns were aligned with findings from source localization and spectral analysis, which identified α₁–γ band PSD changes within core cognitive and motor networks, alongside marked hemispheric asymmetry in sensorimotor and attention networks. These observations indicate that epileptic spasms may disproportionately affect developing core functional networks in IESS, with α/β/γ band spectral variations representing potential candidate markers for IESS-related brain dysfunction.

Recent evidence suggests that temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is not merely a focal brain disorder but a network-based disease involving widespread structural alterations. Patients with TLE-HS commonly experience a decline in cognitive function, which significantly impacts their quality of life. To improve therapeutic effect of TLE-HS and protect their cognitive function, it is crucial to elucidate the underlying pathophysiological mechanisms of TLE-HS.In this study, structural magnetic resonance imaging (sMRI) data and Wechsler Intelligence Scale scores were collected from 62 patients with TLE-HS and 61 healthy controls at Beijing Tiantan Hospital. Individual morphological brain networks were constructed based on multiple cortical morphological features, and graph-theoretical analysis was performed to characterize network topology. Between-group differences in network properties were assessed, and the relationships between topological metrics and cognitive performance were further examined using correlation analysis and support vector regression (SVR).Compared with healthy controls, TLE-HS patients exhibited significant alterations in multiple nodal topological properties, including betweenness centrality, degree centrality, clustering coefficient, and nodal efficiency (P<0.05, FDR-corrected). A disease-related subnetwork primarily involving frontal and temporal regions was identified. Importantly, nodal betweenness measures showed significant associations with cognitive scores, and SVR models based on network features achieved consistent predictive performance for cognitive outcomes.These findings demonstrate that individual morphological brain networks are significantly disrupted in TLE-HS and network topological alterations are closely associated with cognitive impairment. The results highlight the potential of brain network topology as an imaging biomarker for cognitive function and provide new insights into the network-based mechanisms underlying TLE-HS.

BACKGROUND AND OBJECTIVES:Deep brain stimulation of the subthalamic nucleus (STN-DBS) is effective for medication-refractory Parkinson's disease (PD) motor symptoms, but clinical response varies across symptom domains, particularly tremor and gait. Accurate preoperative stratification is clinically important, especially for early post-programming outcomes. METHODS:We retrospectively enrolled 155 patients with PD undergoing bilateral STN-DBS and 43 healthy controls. Preoperative structural magnetic resonance imaging and diffusion-weighted imaging were used to quantify brain morphometry and glymphatic markers, including diffusion tensor imaging along the perivascular space (DTI-ALPS) and choroid plexus volume (CPV). Total motor response was evaluated in all 155 patients, tremor response in 133 patients with complete tremor subscores, and an exploratory data-driven gait-improvement phenotype in 66 patients with paired instrumented gait assessments. Machine-learning models were developed using fold-wise feature selection and hyperparameter tuning and were evaluated by fivefold cross-validation. RESULTS:Best-performing trimodal models yielded AUCs of 0.850 ± 0.045 (95% CI, 0.794-0.906) for total motor response, 0.861 ± 0.047 (95% CI, 0.803-0.919) for tremor response, and 0.970 ± 0.019 (95% CI, 0.946-0.994) for the exploratory gait-improvement phenotype. Morphometric-only models retained substantial predictive performance, with maximum AUCs of 0.830, 0.849, and 0.955 for the motor, tremor, and gait-related endpoints, respectively. For the exploratory gait phenotype, clinical-plus-morphometric and trimodal models performed similarly, suggesting limited incremental value of glymphatic variables in this subgroup. CONCLUSION:Preoperative cerebral morphometry, complemented by selected glymphatic markers and baseline clinical variables, may help stratify short-term post-programming STN-DBS response in PD. These findings support further development of imaging-informed DBS outcome prediction, while external validation and longer-term follow-up remain necessary before clinical implementation.

BackgroundMigraine is a common comorbidity in patients with epilepsy, with a comorbidity rate ranging from 9.3 to 34.7%. Transcutaneous auricular vagus nerve stimulation (taVNS) is an emerging therapy used in both epilepsy and migraine treatment. However, there are currently no randomized controlled studies (RCTs) using taVNS for epilepsy complicated with migraine.ObjectiveIn this study, we evaluated the effect of taVNS as an adjuvant therapy on patients with comorbid epilepsy and migraine.MethodsForty comorbid patients (taVNS n = 20, tanVNS n = 20) were recruited and randomly grouped. The taVNS group received the true stimulus, whereas the tanVNS group received a pseudostimulus. Outcome assessment was performed at baseline and 24 weeks after initiation. We used t-test and non-parametric tests to analyse the data.ResultsThe frequencies of migraine attacks and seizures significantly decreased in the taVNS group from baseline to 24 weeks (migraine attack frequency, p = 0.002; seizure frequency, p = 0.004), and so did in Self-Rating Anxiety Scale (SAS) score (p < 0.001) and Self-Rating Depression Scale (SDS) score (p < 0.001). The QOLIE-31 scores increased after 24 weeks of taVNS treatment (p = 0.028). Moreover, taVNS reduced the EEG power spectrum in four frequency bands at 16 electrode locations in comparison between groups (p < 0.05).ConclusionIn comorbid patients in our groups, taVNS can decrease the frequency of seizures, improve mood and quality of life, and reduce the EEG power spectrum.

Motor dysfunction and muscle atrophy are typical symptoms of patients with spinal cord injury (SCI). Exercise training is a conventional physical therapy after SCI, but exercise intervention alone may have limited efficacy in reducing secondary injury and promoting nerve regeneration and functional remodeling. Our previous research found that intramedullary pressure after SCI is one of the key factors affecting functional prognosis. It has been reported that GsMTx-4, a specific blocker of the mechanosensitive ion channels Piezo1, can protect the integrity of the neuromuscular junction and promote nerve regeneration, and thus has the potential as a therapeutic agent for SCI. In this study, we observed the combined and separate therapeutic effect of GsMTx-4 and exercise on the structure of the soleus muscle and motor function in rats with SCI. At 42 days post-injury, compared with SCI rats, the Basso-Beattie-Bresnahan score (P = 0.0007) and Gait Symmetry (P = 0.0002) were significantly improved after combination therapy. On histology of rat soleus muscle, compared with SCI rats, the combined treatment significantly increased the wet weight ratio, muscle fiber cross-sectional area and acetylcholinesterase (all P<0.0001). On histology of rat spinal tissue, compared with SCI rats, the combined treatment significantly increased neuron counts and BDNF levels, and significantly reduced the percentage of TUNEL-positive cells (all P<0.0001). On physiology of rat soleus muscle, compared with SCI rats, the combined treatment increased the succinate dehydrogenase expression (P<0.0001), while the expression of α-glycerophosphate dehydrogenase (P<0.0001) and GDF8 protein (P = 0.0008) decreased. Results indicate the combination therapy effectively improves histopathology of spinal cord and soleus muscle in SCI rats, enhancing motor function. This study was conducted on animal models, it offers insights for SCI treatment, advancing understanding of lower limb muscle pathology post-SCI. Further research is needed for clinical validation in the future.

Freezing of gait (FOG) in Parkinson’s disease (PD) is a debilitating motor symptom linked to executive dysfunction, particularly impaired conflict resolution. However, the underlying neural mechanisms and optimal treatment remain unclear. We assessed conflict resolution using a modified Flanker task in 90 PD patients (52 with FOG) and 37 healthy controls. PD-FOG patients exhibited significantly greater conflict costs than patients without FOG and healthy controls. Task-based fMRI revealed enhanced frontal cortical activation associated with conflict processing deficits in PD-FOG, positively correlating with FOG severity. In a subgroup of 18 PD-FOG patients undergoing fMRI during subthalamic nucleus deep brain stimulation (STN-DBS), theta-frequency (5 Hz) stimulation improved conflict resolution and increased frontal activation, whereas high-frequency (130 Hz) stimulation primarily activated motor regions without cognitive benefit. These findings indicate that frontal dysfunction contributed to the conflict resolution deficits in PD-FOG and support theta-frequency STN-DBS as a promising therapeutic approach for enhancing cognitive function.

Surgical decompression after spinal cord injury (SCI) is a conventional treatment. Although it has been proven to have clinical effects, there are certain limitations, such as the surgical conditions that must be met and the invasive nature of the treatment. Therefore, there is an urgent need to develop a simple and maneuverable therapy for the emergency treatment of patients with SCI before surgery. Rapamycin (RAPA) has been reported to have potential as a therapeutic agent for SCI. In this study, we observed the therapeutic effects of rapamycin and surgical decompression, in combination or separately, on the histopathology in rabbits with SCI. After combination therapy, intramedullary pressure (IMP) decreased significantly, autophagic flux increased, and apoptosis and demyelination were significantly reduced. Compared with RAPA/surgical decompression alone, the combination therapy had a significantly better effect. In addition, we evaluated the effects of mechanical pressure on autophagy after SCI by assessing changes in autophagic initiation, degradation, and flux. Increased IMP after SCI inhibited autophagic degradation and impaired autophagic flux. Decompression improved autophagic flux after SCI. Our findings provide novel evidence of a promising strategy for the treatment of SCI in the future. The combination therapy may effectively improve emergency treatment after SCI and promote the therapeutic effect of decompression. This study also contributes to a better understanding of the effects of mechanical pressure on autophagy after neurotrauma.

BACKGROUND:Subthalamic nucleus (STN) deep brain stimulation (DBS) is used to treat Parkinson's disease (PD), yet neither high-frequency stimulation (HFS) nor low frequency stimulation (LFS) fully resolves gait issues. Previous studies indicate that STN-DBS modulates motor-related brain networks. Given that PD patients with gait disturbances exhibit cognitive deficits-and considering the extensive projections between the STN and cerebral cortex-we hypothesized that varying STN stimulation frequencies may improve gait by modulating distinct brain networks. METHODS:We collected gait data, cortical electrophysiological signals, and resting-state fMRI from 44 PD patients and 32 healthy controls. Multi-network cortical activity and functional connectivity were c ompared under three conditions: DBS OFF, HFS, and LFS. Additionally, the connectivity values were correlated to the gait behaviors and clinical assessment scores. RESULTS:We found that: (1) HFS improved both motor and gait performance, while LFS enhanced gait but may not be optimal for long-term use; (2) STN-DBS induced widespread modulation across sensorimotor, frontoparietal, salience, dorsal attention, and default mode networks. HFS improved motor and gait functions via network modulation related to motor control, whereas LFS may enhance gait by boosting executive-related cortical activities and connections; (3) Relative to healthy controls, PD exhibited widespread reductions in functional connectivity, with DBS modulation trending toward normalization. CONCLUSIONS:These results reveal distinct brain network responses to different STN-DBS frequencies in PD, offering a theoretical basis for optimizing DBS treatment for gait impairments. These findings provide critical insights for tailoring DBS parameters to maximize both motor and cognitive benefits in PD patients.

Abstract Background Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. Methods This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive–compulsive disorder (OCD), depression, and quality of life, respectively. Results Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). Conclusions DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

MicroRNAs play an important role in the occurrence and development of ischemic stroke(IS).A lot of researches have shown that acupuncture intervention can improve IS-induced neural dysfunction by regulating miRNA.In the present paper,we summarized the current progress of researches on the mechanisms of acupuncture underlying improvement of IS via regulation of miRNA from 1)promoting angiogenesis and increasing cerebral blood flow,2)inhibiting inflammatory response,3)maintaining blood-brain barrier homeostasis and relieving brain edema,4)regulating programmed cell death,5)promoting neuron regeneration,and 6)improving synaptic plasticity.These miRNA-related mechanisms may provide a reference for the follow-up research.

Subthalamic nucleus deep brain stimulation (STN-DBS) has the potential to delay Parkinson’s disease (PD) progression. Whether oxidative stress participates in the neuroprotective effects of DBS and related signaling pathways remains unknown. To address this, we applied STN-DBS to mice and monkey models of PD and collected brain tissue to evaluate mitophagy, oxidative stress, and related pathway. To confirm findings in animal experiments, a cohort of PD patients was recruited and oxidative stress was evaluated in cerebrospinal fluid. When PD mice received STN stimulation, the mTOR pathway was suppressed, accompanied by elevated LC3 II expression, increased mitophagosomes, and a decrease in p62 expression. The increase in mitophagy and balance of mitochondrial fission/fusion dynamics in the substantia nigra caused a marked enhancement of the antioxidant enzymes superoxide dismutase and glutathione levels. Subsequently, fewer mitochondrial apoptogenic factors were released to the cytoplasm, which resulted in a suppression of caspase activation and reservation of dopaminergic neurons. While interfaced with an mTOR activator, oxidative stress was no longer regulated by STN-DBS, with no neuroprotective effect. Similar results to those found in the rodent experiments were obtained in monkeys treated with chronic STN stimulation. Moreover, antioxidant enzymes in PD patients were increased after the operation, however, there was no relation between changes in antioxidant enzymes and motor impairment. Collectively, our study found that STN-DBS was able to increase mitophagy via an mTOR-dependent pathway, and oxidative stress was suppressed due to removal of damaged mitochondria, which was attributed to the dopaminergic neuroprotection of STN-DBS in PD.

OBJECTIVE:Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has demonstrated efficacy against multiple types of dystonia, but only a few case reports and small-sample studies have investigated the clinical utility of STN-DBS for Meige syndrome, a rare but distressing form of craniofacial dystonia. Furthermore, the effects of DBS on critical neuropsychological sequelae, such as depression and anxiety, are rarely examined. In this study, the authors investigated the therapeutic efficacy of STN-DBS for both motor and psychiatric symptoms of Meige syndrome. METHODS:The authors retrospectively reviewed consecutive patients with Meige syndrome receiving bilateral STN-DBS at their institution from January 2016 to June 2023. Motor performance and nonmotor features including mood, cognitive function, and quality of life (QOL) were evaluated using standardized rating scales at baseline and at final postoperative follow-up. Clinical and demographic factors influencing postoperative motor outcome were evaluated by uni- and multivariable linear regression models. RESULTS:Fifty-one patients were ultimately included, with a mean ± SD follow-up duration of 27.3 ± 18.0 months. The mean Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score improved from 12.9 ± 5.2 before surgery to 5.3 ± 4.2 at the last follow-up (mean improvement 58.9%, p < 0.001) and the mean BFMDRS disability score improved from 5.6 ± 3.3 to 2.9 ± 2.9 (mean improvement 44.6%, p < 0.001). Hamilton Depression and Anxiety Rating Scale scores also improved by 35.3% and 34.2%, respectively, and the postoperative 36-item Short-Form Health Survey score indicated substantial QOL enhancement. Global cognition remained stable after treatment. Multiple linear regression analysis identified disease duration (β = -0.241, p = 0.027), preoperative anxiety severity (β = -0.386, p = 0.001), and volume of activated tissue within the dorsolateral (sensorimotor) STN (β = 0.483, p < 0.001) as independent predictors of motor outcome. CONCLUSIONS:These findings support STN-DBS as an effective and promising therapy for both motor and nonmotor symptoms of Meige syndrome. Timely diagnosis, treatment of preoperative anxiety, and precise electrode placement within the dorsolateral STN are essential for optimal clinical outcome.

BACKGROUND:Upper extremity (UE) motor function impairment is a major poststroke complication whose recovery remains one of the most challenging tasks in neurological rehabilitation. This study examined the efficacy and safety of the personalized neuroimaging-guided high-dose theta-burst stimulation (TBS) for poststroke UE motor function recovery. METHODS:Patients after stroke with UE motor impairment from a China rehabilitation center were randomly assigned to receive high-dose intermittent TBS (iTBS) to ipsilesional UE sensorimotor network, continuous TBS (cTBS) to contralesional UE sensorimotor network, or sham stimulation, along with conventional therapy for 3 weeks. The primary outcome was the score changes on the Fugl-Meyer assessment-UE from baseline to 1 and 3 weeks. The secondary outcomes included the response rate on Fugl-Meyer assessment-UE scores posttreatment (≥9-point improvement) and score changes in multidimensional scales measuring UE, lower extremity, and activities and participation. RESULTS:From June 2021 to June 2022, 45 participants were randomized and 43 were analyzed. The iTBS and continuous TBS groups showed significantly greater improvement in Fugl-Meyer assessment-UE (mean improvement, iTBS: 10.73 points; continuous TBS: 10.79 points) than the sham group (2.43 points) and exhibited significantly greater response rates on Fugl-Meyer assessment-UE (iTBS, 60.0%; continuous TBS, 64.3%) than the sham group (0.0%). The active groups consistently exhibited superior improvement on the other 2 UE assessments at week 3. However, only the iTBS group showed greater efficacy on 1 lower extremity assessment than the sham group at week 3. Both active groups showed significant improvements in activities and participation assessments. CONCLUSIONS:The study provides evidence for the efficacy and safety of high-dose TBS in facilitating poststroke UE rehabilitation. REGISTRATION:URL: www.chictr.org.cn; Unique identifier: ChiCTR2100047340.

The pathophysiology of affective disorders-particularly circuit -level mechanisms underlying bidirectional, periodic affective state transitions-remains poorly understood. In patients, disruptions of sleep and circadian rhythm can trigger transitions to manic episodes, whereas depressive states are reversed. Here, we introduce a hybrid automated sleep deprivation platform to induce transitions of affective states in mice. Acute sleep loss causes mixed behavioral states, featuring hyperactivity, elevated social and sexual behaviors, and diminished depressive -like behaviors, where transitions depend on dopamine (DA). Using DA sensor photometry and projection -targeted chemogenetics, we reveal that elevated DA release in specific brain regions mediates distinct behavioral changes in affective state transitions. Acute sleep loss induces DA -dependent enhancement in dendritic spine density and uncaging-evoked dendritic spinogenesis in the medial prefrontal cortex, whereas optically mediated disassembly of enhanced plasticity reverses the antidepressant effects of sleep deprivation on learned helplessness. These findings demonstrate that brainwide dopaminergic pathways control sleep -loss -induced polymodal affective state transitions.

Spinal cord injury is a severe and devastating disease, and spasticity is a common and severe complication that is notoriously refractory to treatment. However, the pathophysiological mechanisms underlying spasticity and its development remain largely unknown. The goal of the present study was to find differences, if any, in metabolites of the left precentral gyrus and basal ganglia of patients who have spinal cord injury with or without spasticity, and to explore the relationship between the brain metabolite concentrations and clinical status. Thirty-six participants were recruited for magnetic resonance spectroscopic examination: 23 with spinal cord injury (12 with spasticity and 11 without spasticity) and 13 healthy controls. We acquired localized proton spectra from the precentral gyrus and basal ganglia via 10 mm3 voxels. Notably, univariate linear regression analysis demonstrated that the lower that the N-acetylaspartate concentration (a marker for neuronal loss) was in the precentral gyrus of the patients, the lower their ASIA (American Spinal Injury Association) light-touch scores, pinprick scores, and motor scores. Additionally, longer durations of injury were associated with higher N-acetylaspartate levels in the precentral gyrus. Compared with the healthy participants and patients without spasticity, N-acetylaspartate levels in the patients with spasticity were significantly lower in both the precentral gyrus and basal ganglia. Lower N-acetylaspartate levels also correlated with greater sensory and motor dysfunction in the patients who had spinal cord injury with spasticity.

Postural instability/gait disturbance (PIGD) is very common in advanced Parkinson's disease, and associated with cognitive dysfunction. Research suggests that low frequency (5-12 Hz) subthalamic nucleus-deep brain stimulation (STN-DBS) could improve cognition in patients with Parkinson's disease (PD). However, the clinical effectiveness of low frequency stimulation in PIGD patients has not been explored. This study was designed in a double-blinded randomized cross-over manner, aimed to verify the effect of low frequency STN-DBS on cognition of PIGD patients. Twenty-nine PIGD patients with STN-DBS were tested for cognitive at off (no stimulation), low frequency (5 Hz), and high frequency (130 Hz) stimulation. Neuropsychological tests included the Stroop Color-Word Test (SCWT), Verbal fluency test, Symbol Digital Switch Test, Digital Span Test, and Benton Judgment of Line Orientation test. For conflict resolution of executive function, low frequency stimulation significantly decreased the completion time of SCWT-C (p = 0.001) and Stroop interference effect (p < 0.001) compared to high frequency stimulation. However, no significant differences among stimulation states were found for other cognitive tests. Here we show, low frequency STN-DBS improved conflict resolution of executive function compared to high frequency. Our results demonstrated the possibility of expanding the treatment coverage of DBS to cognitive function in PIGD, which will facilitate integration of low frequency stimulation into future DBS programming.