Background: Obsessive-compulsive disorder (OCD) remains refractory to conventional pharmacological and psychotherapeutic treatments in a substantial proportion of patients. Neuromodulation has emerged as a promising intervention, but optimal neural circuit targets remain unclear. This systematic review and meta-analysis aimed to evaluate the efficacy of invasive and non-invasive neuromodulation for OCD using a circuit-based framework and to translate these findings into clinical practice. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials investigating neuromodulation for OCD. PubMed/MEDLINE, Web of Science, and the Cochrane Library were searched from database inception to December 2023. Eligible studies included adult patients with a primary diagnosis of OCD receiving invasive or non-invasive neuromodulation, with symptom outcomes assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Random-or fixed-effects meta-analyses were performed using mean differences or standardized mean differences, depending on heterogeneity. The review was registered in PROSPERO (CRD42024518326). Results: Twenty-seven randomized controlled trials involving 868 patients met inclusion criteria. Overall, neuromodulation significantly reduced OCD symptoms compared with control conditions. Circuit-based subgroup analyses indicated that modulation of the fronto-limbic circuit--primarily via invasive deep brain stimulation--was associated with the largest and most consistent Y-BOCS improvements, while sensorimotor, dorsal cognitive, and ventral affective circuits also demonstrated significant but more heterogeneous effects. Invasive neuromodulation showed greater efficacy than non-invasive approaches. These findings informed a translational multi-target deep brain stimulation case, demonstrating clinically meaningful symptom improvement (Y-BOCS decreased from 25 to 16 after 6 months). Limitations: Heterogeneity across non-invasive studies, short follow-up durations, and limited circuit-specific data constrain interpretation of long-term and symptom-domain-specific effects. Conclusions: This systematic review, meta-analysis, and case study suggest that circuit-based neuromodulation--particularly targeting the fronto-limbic circuit--may offer the most consistent benefit for treatment-refractory OCD. Larger, longer-term, and circuit-informed trials are needed to optimize individualized neuromodulation strategies.

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.

We investigated the impact of visual states on basal ganglia oscillatory biomarkers, comparing local field potentials (LFPs) dynamics between Parkinson’s disease (PD) and dystonia and developing a decoding model for state identification. Simultaneous LFPs recordings from the subthalamic nucleus (STN) or globus pallidus internus (GPi), and cortex were obtained from 18 PD and 18 dystonia patients. In the eyes-closed state, theta and alpha power increased in the basal ganglia, with stronger coherence to the central cortex, more pronounced in the STN than in the GPi. Machine learning models identified the eyes-closed state with 88% accuracy for STN and 77% for GPi. The sensorimotor STN and GPi were most informative. The present findings provide proof-of-concept that basal ganglia LFPs can reliably predict a physiological state, highlighting the potential influence of physiological oscillatory activity on pathological bands and its relevance for adaptive stimulation paradigms.

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.

AimDeep brain stimulation of the nucleus basalis of Meynert (NBM-DBS) represents an emerging therapeutic strategy for Alzheimer’s disease (AD), yet clinical outcomes have been inconsistent and its mechanistic underpinnings are not fully elucidated. This study aimed to assess the cognitive and psychobehavioral effects of NBM-DBS and to explore its potential impact on systemic inflammatory markers.MethodsIn this open-label trial, nine individuals with moderate-to-severe AD underwent bilateral NBM-DBS. Six participants (four with moderate and two with severe AD) completed the full 12-month protocol, which included serial neuropsychiatric assessments and serum cytokine profiling.ResultsStratification by baseline disease severity revealed divergent cognitive trajectories. Patients with moderate AD (CDR = 2) maintained their preoperative performance on the Montreal Cognitive Assessment (MoCA) and Boston Naming Test (BNT) over the 12-month follow-up. In contrast, patients with severe AD (CDR = 3) experienced significant decline on these measures. Serum analyses demonstrated a significant immunomodulatory effect, characterized by elevated levels of the anti-inflammatory cytokines IL-10 and IL-27, and reduced levels of the pro-inflammatory chemokines CXCL10 and RANTES at the 12-month timepoint.ConclusionOur findings indicate that NBM-DBS may be associated with stabilization of cognitive function in patients with moderate AD, potentially through the modulation of inflammation. The therapeutic benefit appears to be more pronounced in the moderate stage of the disease.

Background:Stroke remains the leading cause of long-term disability worldwide. Approximately 60% of individuals with chronic ischemic stroke experience persistent upper limb impairment that limits daily activities. The Repair Study aims to evaluate the safety and efficacy of vagus nerve stimulation (VNS) paired with rehabilitation in patients with chronic ischemic stroke in developing countries, including those with severe upper limb dysfunction, thereby generating evidence to support broader global application. Methods:It is a multicenter, triple-blinded, randomized controlled trial conducted across 13 centers in China. Up to 99 participants with upper limb motor impairment, 9 months to 10 years post-stroke, will be enrolled. All participants will undergo VNS implantation (Model G115R/G115, PINS Medical, Beijing, China) and be randomized 2:1 by a central randomization system to active stimulation (0.8 mA) or sham stimulation (0 mA) paired with standardized upper limb rehabilitation. The blinded phase includes 6 weeks of clinical therapy (three sessions/week, 90-120 min/session, ≥300 stimulation-movement repetitions) followed by 6 weeks of home-based therapy (30 min/day). Post-unblinding, the active VNS group continues home-based therapy, while the sham group receives 6 weeks of clinic-based therapy. Discussion:The primary outcome is the between-group difference in Fugl-Meyer Assessment for Upper Extremity scores at the end of 6 weeks of clinical therapy. Secondary outcomes include additional motor, functional, and quality-of-life measures. Safety will be assessed through adverse event monitoring. The Repair Study is a multicenter randomized controlled trial targeting chronic ischemic stroke populations in developing countries. It supplements the existing clinical evidence by enrolling patients with more servere motor dysfunction and being conducted in a developing country. Trial Registration:ClinicalTrials.gov: NCT06722677.

BACKGROUND:Cognitive decline in Parkinson's disease (PD) is associated with pathological alterations within the thalamus. Nevertheless, volumetric changes in the specific subnuclei of the thalamus in PD patients with dementia (PD-D) remain inadequately characterized. Furthermore, the clinical challenges of diagnosing PD-D at an individual level and forecasting the trajectory of cognitive decline persist. METHODS:This study acquired structural magnetic resonance imaging (MRI) data from 60 healthy normal controls (NC), 63 PD patients without dementia (PD-nD), and 57 PD-D patients. The volumes of 25 thalamic subnuclei were quantified using FreeSurfer and a novel thalamic segmentation algorithm. Subsequently, individual PD-D diagnosis and severity prediction of cognitive impairment were performed using support vector machines (SVMs). RESULTS:Our findings demonstrated atrophy in seven out of 25 left and two out of 25 right thalamic subnuclei in PD-D patients relative to PD-nD patients. When compared to NC subjects, the PD-D group exhibited volume reductions in two left and one right subnuclei, alongside enlargement in several others. Within the PD cohort, the volumes of four left thalamic subnuclei showed a negative correlation with cognitive impairment severity. Machine learning models achieved high accuracy in differentiating PD-nD from NC (89.19%), PD-D from NC (94.29%), and PD-D from PD-nD (83.33%). Moreover, the prediction of Mini-Mental State Examination (MMSE) scores yielded a Pearson correlation coefficient of 0.7568. CONCLUSION:Specific thalamic subnuclei undergo atrophy in PD-D, and these morphological changes are linked to cognitive deficit severity. Leveraging these features with machine learning enables accurate individual diagnosis and severity prediction.

ABSTRACT Objective Deep brain stimulation offers a unique opportunity to record neural activity of the basal ganglia. While much work in dystonia has focused on the globus pallidus internus, expanding research to investigate subthalamic nucleus (STN) activity in various dystonia types is critical to provide a comprehensive understanding of dystonia pathophysiology. Methods STN and cortex activity were recorded from 17 patients with cervical dystonia (CD), 19 with Meige syndrome, and 9 with generalized dystonia (GD) during the lead externalized period. We investigated local and network oscillatory characteristics, including power, bursts, and coherence. Additionally, we explored the relationship between these features and the severity of dystonic symptoms within each group and conducted a comparative analysis across the different dystonia types. Results Peaks of low‐frequency (4–13 Hz) and beta (14–30 Hz) power were present in the STN of all patients; most of the beta peaks are distributed in the high beta range (20–30 Hz). The CD and GD groups showed longer low‐frequency bursts and greater high beta power in STN than the Meige group. Interestingly, the CD group showed stronger STN‐cortex low‐frequency coherence, while the GD group had stronger STN‐cortex high beta coherence. Combined, low‐frequency and beta features could predict symptom severity with a performance of 73% in the CD group and 82% in the GD group. Interpretation Low‐frequency and high‐beta oscillations are present in the STN across all three types of dystonia. The distinct patterns may be associated with different underlying pathological mechanisms.

Introduction: Subthalamic deep brain stimulation (STN-DBS) is an established treatment for Parkinson's disease (PD); however, long-term motor outcomes vary, affecting patients' quality of life. Identifying the factors that influence these heterogeneous motor outcomes is essential. This study investigated the factors influencing heterogeneous motor outcomes in patients with PD after STN-DBS and developed predictive models using preoperative demographic and clinical factors. Methods: We studied 92 patients with PD who underwent bilateral STN-DBS at the Beijing Tiantan Hospital between 2020 and 2022. Motor outcomes were assessed preoperatively and 1 and 12 months postoperatively. Patients were grouped based on different motor outcomes (change in Unified Parkinson's Disease Rating Scale Part III scores) between the 12- and 1-month assessments: those achieving minimal clinically significant motor improvement (MCID+) and those who did not (MCID-). Machine-learning models were used to predict outcomes based on preoperative factors. Results: The MCID+ group (n = 46) showed significantly better motor outcomes at the 1-year follow-up than the MCID- group (n = 46, mean difference 10.47, p < 0.001). A lower levodopa equivalent daily dose (p < 0.01), reduced anxiety (p < 0.05), reduced depression (p < 0.001), and milder freezing of gait (p < 0.05) were associated with better motor outcomes. Predictive models using logistic regression and XGBoost achieved a high accuracy (82%) in forecasting motor outcomes. Conclusions: Preoperative non-motor factors, particularly emotional status, significantly affected motor outcomes following STN-DBS. Machine-learning models enhance prognostic accuracy and offer the potential for personalized treatment strategies.

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.

Obsessive-Compulsive Disorder (OCD) is characterized by persistent intrusive thoughts and compulsive behaviors that are often resistant to traditional treatment methods such as medication and psychotherapy. Neuromodulation, targeting specific brain circuits, has emerged as a promising alternative for treating refractory OCD. This study aims to synthesize the effectiveness of various neuromodulation techniques, focusing particularly on their impact on neural circuitry based on existing symptom and treatment taxonomies. Through a systematic search of major databases, randomized controlled trials of both invasive and non-invasive neuromodulation techniques targeting different brain circuits were analyzed. The primary outcome was measured by changes in the Yale-Brown Obsessive-Compulsive Scale. The comprehensive search included 868 patients and demonstrated significant improvement in OCD symptoms through neuromodulation. The most substantial improvements were observed when targeting the fronto-limbic circuit. Additional significant symptom relief was noted in interventions affecting the sensorimotor and ventral affective circuits, with invasive methods outperforming non-invasive ones. In addition, a detailed case study of Deep Brain Stimulation from our center targeting the subthalamic nucleus, nucleus accumbens, and anterior limb of the internal capsule (ALIC) highlighted substantial symptom relief by specifically modulating the fronto-limbic circuit (targeting ALIC), aligning with the results of the meta-analysis. The findings underline the importance to tailor neuromodulation treatments to individual patients’ needs on the circuitry basis, optimizing outcomes in OCD management.

Background: Previous studies have revealed the existence of electrode displacement during subthalamic nucleus deep brain stimulation (STN-DBS). However, the effect of electrode displacement on treatment outcomes is still unclear. In this study, we aimed to analyze the related factors of electrode displacement and assess postoperative electrode displacement in relation to the motor outcomes of STN-DBS. Methods: A total of 88 patients aged 62.73 ± 6.35 years (55 males and 33 females) with Parkinson’s disease undergoing STN-DBS, with comprehensive clinical characterization before and 1 month after surgery, were involved retrospectively and divided into a cross-incision group and cannula puncture group according to different dura opening methods. The electrode displacement, unilateral pneumocephalus volume percent (uPVP), and brain volume percent were estimated. Results: A significant anterior and lateral electrode displacement was observed among all implanted electrodes after pneumocephalus absorption (p < 0.0001). The degree of electrode displacement was positively correlated with the uPVP (p = 0.005) and smaller in females than males (p = 0.0384). Electrode displacement was negatively correlated with motor improvement following STN-DBS in both on-medication and off-medication conditions (p < 0.05). Dural puncture reduced the uPVP (p < 0.0001) and postoperative electrode displacement (p = 0.0086) compared with dural incision. Conclusions: Electrode displacement had a negative impact on the therapeutic efficacy of STN-DBS. Opening the dura via cannula puncture is recommended to increase the accuracy of the lead implantation.

Background:Subthalamic nucleus deep brain stimulation (STN-DBS) improves sleep qualities in Parkinson's disease (PD) patients; however, it remains elusive whether STN-DBS improves sleep by directly influencing the sleep circuit or alleviates other cardinal symptoms such as motor functions, other confounding factors including stimulation intensity may also involve. Studying the effect of microlesion effect (MLE) on sleep after STN-DBS electrode implantation may address this issue. Objective:To examine the influence of MLE on sleep quality and related factors in PD, as well as the effects of regional and lateral specific correlations with sleep outcomes after STN-DBS electrode implantation. Study Design:Case-control study; Level of evidence, 3. Data Sources and Methods:In 78 PD patients who underwent bilateral STN-DBS surgery in our center, we compared the sleep qualities, motor performances, anti-Parkinsonian drug dosage, and emotional conditions at preoperative baseline and postoperative 1-month follow-up. We determined the related factors of sleep outcomes and visualized the electrodes position, simulated the MLE-engendered volume of tissue lesioned (VTL), and investigated sleep-related sweet/sour spots and laterality in STN. Results:MLE improves sleep quality with Pittsburgh Sleep Quality Index (PSQI) by 13.36% and Parkinson's Disease Sleep Scale-2 (PDSS-2) by 17.95%. Motor (P = 0.014) and emotional (P = 0.001) improvements were both positively correlated with sleep improvements. However, MLE in STN associative subregions, as an independent factor, may cause sleep deterioration (r = 0.348, P = 0.002), and only the left STN showed significance (r = 0.327, P = 0.004). Sweet spot analysis also indicated part of the left STN associative subregion is the sour spot indicative of sleep deterioration. Conclusion:The MLE of STN-DBS can overall improve sleep quality in PD patients, with a positive correlation between motor and emotional improvements. However, independent of all other factors, the MLE in the STN associative subregion, particularly the left side, may cause sleep deterioration.

There are many documented sex differences in the clinical course, symptom expression profile, and treatment response of Parkinson’s disease, creating additional challenges for patient management. Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease, the effects of sex on treatment outcome are still unclear. The aim of this retrospective observational study, was to examine sex differences in motor symptoms, non-motor symptoms, and quality of life after subthalamic nucleus deep brain stimulation. Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00 ± 8.01 years (55 men and 35 women). Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test, and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex. We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation. Restless legs syndrome was alleviated to a greater extent in men than in women. Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation. Furthermore, Hoehn-Yahr stage was positively correlated with the treatment response in men, while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women. In conclusion, women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms, non-motor symptoms, and quality of life. We found sex-specific factors, i.e., Hoehn-Yahr stage and levodopa equivalent dose, that were related to motor improvements. These findings may help to guide subthalamic nucleus deep brain stimulation patient selection, prognosis, and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.

During surgery for foci-related epilepsy, neurosurgeons face significant difficulties in identifying and resecting MRI-negative or deep-seated epileptic foci. Here, we present a neuro-robotic navigation system that is specifically designed for resection of MRI negative epileptic foci. We recruited 52 epileptic patients, and randomly assigned them to treatment group with either neuro-robotic navigation or conventional neuronavigation system. For each patient, in the neuro-robotic navigation group, we integrated multimodality imaging including MRI and PET-CT into the robotic workstation and marked the boundary of foci from the fused image. During surgery, this boundary was delineated by the robotic laser device with high accuracy, guiding resection for the surgeon. For deeply seated foci, we exploited the neuro-robotic navigation system to localize the deepest point with biopsy needle insertion and methylene dye application to locate the boundary of the foci. Our results show that, compared with the conventional neuronavigation, the neuro-robotic navigation system performs equally well in MRI positive epilepsy patients (ENGEL I ratio: 71.4% vs 100%, p = 0.255) systems and show better performance in patients with MRI-negative focal cortical dysplasia (ENGEL I ratio: 88.2% vs 50%, p = 0.0439). At present, there are no documented neurosurgery robots with similar function and application in the field of epilepsy. Our research highlights the added value of using neuro-robotic navigation systems in resection surgery for epilepsy, particularly in cases that involve MRI-negative or deep-seated epileptic foci.

Aim Subthalamic nucleus deep brain stimulation (STN-DBS) has been reported to be effective in treating motor symptoms in Parkinson's disease (PD), which may be attributed to changes in the brain network. However, the association between brain morphology and initial STN-DBS efficacy, as well as the performance of prediction using neuroimaging, has not been well illustrated. Therefore, we aim to investigate these issues. Methods In the present study, 94 PD patients underwent bilateral STN-DBS, and the initial stimulation efficacy was evaluated. Brain morphology was examined by magnetic resonance imaging (MRI). The volume of tissue activated in the motor STN was measured with MRI and computed tomography. The prediction of stimulation efficacy was achieved with a support vector machine, using brain morphology and other features, after feature selection and hyperparameter optimization. Results A higher stimulation efficacy was correlated with a thicker right precentral cortex. No association with subcortical gray or white matter volumes was observed. These morphological features could estimate the individual stimulation response with an r value of 0.5678, an R-2 of 0.3224, and an average error of 11.4%. The permutation test suggested these predictions were not based on chance. Conclusion Our results indicate that changes in morphology are associated with the initial stimulation motor response and could be used to predict individual initial stimulation-related motor responses.

Subthalamic nuclei deep brain stimulation (STN-DBS) is a well-established treatment for Parkinson’s disease (PD). Some studies have confirmed the long-term efficacy is associated with brain connectivity; however, whether the initial outcome is associated with brain connectivity and efficacy of prediction based on these factors has not been well investigated. In the present study, a total of 98 patients were divided into a training set ( n = 78) and a test set ( n = 20). The stimulation and medication responses were calculated based on the motor performance. The functional and structural connectomes were established based on a public database and used to measure the association between stimulation response and brain connectivity. The prediction of initial outcome was achieved via a machine learning algorithm-support vector machine based on the model established with the training set. It was found that the initial outcome of STN-DBS was associated with functional/structural connectivities between the volume of tissue activated and multiple brain regions, including the supplementary motor area, precentral and frontal areas, cingulum, temporal cortex, and striatum. These factors could be used to predict the initial outcome, with an r value of 0.4978 ( P = 0.0255). Our study demonstrates a correlation between a specific connectivity pattern and initial outcome of STN-DBS, which could be used to predict the initial outcome of DBS.

Abstract Objective To examine the influence of the microlesion effect (MLE) after subthalamic nucleus (STN) deep brain stimulation (DBS) on sleep quality in Parkinson’s disease (PD) patients and the correlates of sleep changes. Methods In 78 PD patients who underwent bilateral STN-DBS surgery, we assessed and compared the sleep qualities, motor performances, anti-parkinsonian drug dosage, emotional conditions at preoperative baseline and before implantable pulse generator activation (i.e., 1-month postoperatively). We determined the possible related factors of sleep outcomes using Spearman correlations and visualized the electrodes via Lead-DBS toolbox, simulated and extracted the MLE-engendered volume of tissue lesioned (VTL) based on uniform settings, and conducted sweet-spot analysis within the STN. Results Significant improvements induced by MLE were observed in sleep (P < 0.001), motor performances (P < 0.001), and emotions (P < 0.001). Motor and emotional improvements were both positively correlated with sleep changes. The VTL in STN associative sub-regions was positively correlated with sleep deterioration (r = 0.348, P = 0.002), and that only the left STN showed statistical significance (r = 0.327, P = 0.004), which was further corroborated by the sweet-spot analysis. Stepwise regression analysis showed that the VTL in associative sub-regions was an independent factor that negatively influenced sleep outcomes. Conclusion The MLE of STN-DBS can overall improve sleep quality in PD patients, with the change correlating with motor and emotional improvement. However, independent of these two factors and other demographics, the MLE in the associative sub-region of the STN, left particularly, may result in worsened sleep outcomes.

BACKGROUND:Previous studies have reported the effects of age and disease duration on the efficacy of subthalamic nuclei deep brain stimulation (STN-DBS) of Parkinson's disease (PD) patients. However, available data involving these issues are not consistent. In particular, the effect of age and disease duration on the initial efficacy of STN-DBS has not been established.METHODS:A total of 51 patients with PD treated with bilateral STN-DBS were involved in the present study. They received clinical symptom evaluation during the preoperative, initial, and chronic stages of surgery. The correlations between age when undergoing surgery/age at disease onset/disease duration and outcomes of STN-DBS were measured.RESULTS:The preoperative levodopa response was negatively associated with age. During the initial stage, the age when undergoing surgery and age at disease onset were negatively correlated with the effect on bradykinesia, with better symptom control of general symptoms in long-term disease patients. Similarly, patients with an early time of surgery and disease onset and long-term disease duration showed better control of bradykinesia and axial symptoms at the chronic stage. Furthermore, a long-term disease duration and early disease onset benefited from an increase of therapeutic efficacy in general, rigid, and axial symptoms with STN-DBS after a long period. Nevertheless, patients with late disease onset achieved a better relief of stigma.CONCLUSION:Age and disease durations played a unique role in controlling the symptoms of PD patients treated with STN-DBS. These results may contribute to patient selection and adjustments of expectations of surgery, based on the age, disease duration, and different symptoms.

Background Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has shown potential for the treatment of mild-to-moderate Alzheimer’s disease (AD). However, there is little evidence of whether NBM-DBS can improve cognitive functioning in patients with advanced AD. In addition, the mechanisms underlying the modulation of brain networks remain unclear. This study was aimed to assess the cognitive function and the resting-state connectivity following NBM-DBS in patients with advanced AD. Methods Eight patients with advanced AD underwent bilateral NBM-DBS and were followed up for 12 months. Clinical outcomes were assessed by neuropsychological examinations using the Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale. Resting-state functional magnetic resonance imaging and positron emission tomography data were also collected. Results The cognitive functioning of AD patients did not change from baseline to the 12-month follow-up. Interestingly, the MMSE score indicated clinical efficacy at 1 month of follow-up. At this time point, the connectivity between the hippocampal network and frontoparietal network tended to increase in the DBS-on state compared to the DBS-off state. Additionally, the increased functional connectivity between the parahippocampal gyrus (PHG) and the parietal cortex was associated with cognitive improvement. Further dynamic functional network analysis showed that NBM-DBS increased the proportion of the PHG-related connections, which was related to improved cognitive performance. Conclusion The results indicated that NBM-DBS improves short-term cognitive performance in patients with advanced AD, which may be related to the modulation of multi-network connectivity patterns, and the hippocampus plays an important role within these networks. Trial registration ChiCTR, ChiCTR1900022324. Registered 5 April 2019—Prospective registration. https://www.chictr.org.cn/showproj.aspx?proj=37712