PARP1 inhibition prevents oxidative stress in age-related hearing loss via PAR-Ca2+-AIF axis in cochlear strial marginal cells.

Studies have highlighted oxidative damage in the inner ear as a critical pathological basis for sensorineural hearing loss, especially the presbycusis. Poly(ADP-ribose) polymerase-1 (PARP1) activation responds to oxidative stress-induced DNA damage with pro-repair and pro-death effects resembling two sides of the same coin. PARP1-related cell death, known as parthanatos, whose underlying mechanisms are attractive research hotspots but remain to be clarified. In this study, we observed that aged rats showed stria vascularis degeneration and oxidative damage, and PARP1-dependent cell death was prominent in age-related cochlear disorganization and dysfunction. Based on oxidative stress model of primary cultured stria marginal cells (MCs), we revealed that upregulated PARP1 and PAR (Poly(ADP-ribose)) polymers are responsible for MCs oxidative death with high mitochondrial permeability transition pore (mPTP) opening and mitochondrial membrane potential (MMP) collapse, while inhibition of PARP1 ameliorated the adverse outcomes. Importantly, the PARylation of apoptosis-inducing factor (AIF) is essential for its conformational change and translocation, which subsequently causes DNA break and cell death. Concretely, the interaction of PAR and truncated AIF (tAIF) is the mainstream in the parthanatos pathway. We also found that the effects of AIF cleavage and release were achieved through calpain activity and mPTP opening, both of which could be regulated by PARP1 via mediation of mitochondria Ca2+ concentration. In conclusion, the PAR-Ca2+-tAIF signaling pathway in parthanatos contributes to the oxidative stress damage observed in MCs. Targeting PAR-Ca2+-tAIF might be a potential therapeutic strategy for the early intervention of presbycusis and other oxidative stress-associated sensorineural deafness.

Spinal cord and brain atrophy patterns in neuromyelitis optica spectrum disorder and multiple sclerosis.

BACKGROUND: Spinal cord and brain atrophy are common in neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) but harbor distinct patterns accounting for disability and cognitive impairment. METHODS: This study included 209 NMOSD and 304 RRMS patients and 436 healthy controls. Non-negative matrix factorization was used to parse differences in spinal cord and brain atrophy at subject level into distinct patterns based on structural MRI. The weights of patterns were obtained using a linear regression model and associated with Expanded Disability Status Scale (EDSS) and cognitive scores. Additionally, patients were divided into cognitive impairment (CI) and cognitive preservation (CP) groups. RESULTS: Three patterns were observed in NMOSD: (1) Spinal Cord-Deep Grey Matter (SC-DGM) pattern was associated with high EDSS scores and decline of visuospatial memory function; (2) Frontal-Temporal pattern was associated with decline of language learning function; and (3) Cerebellum-Brainstem pattern had no observed association. Patients with CI had higher weights of SC-DGM pattern than CP group. Three patterns were observed in RRMS: (1) DGM pattern was associated with high EDSS scores, decreased information processing speed, and decreased language learning and visuospatial memory functions; (2) Frontal-Temporal pattern was associated with overall cognitive decline; and (3) Occipital pattern had no observed association. Patients with CI trended to have higher weights of DGM and Frontal-Temporal patterns than CP group. CONCLUSION: This study estimated the heterogeneity of spinal cord and brain atrophy patterns in NMOSD and RRMS patients at individual level, and evaluated the clinical relevance of these patterns, which may contribute to stratifying participants for targeted therapy.

Contribution of basal ganglia activity to REM sleep disorder in Parkinson's disease.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the most common sleep problems and represents a key prodromal marker in Parkinson's disease (PD). It remains unclear whether and how basal ganglia nuclei, structures that are directly involved in the pathology of PD, are implicated in the occurrence of RBD. METHOD: Here, in parallel with whole-night video polysomnography, we recorded local field potentials from two major basal ganglia structures, the globus pallidus internus and subthalamic nucleus, in two cohorts of patients with PD who had varied severity of RBD. Basal ganglia oscillatory patterns during RBD and REM sleep without atonia were analysed and compared with another age-matched cohort of patients with dystonia that served as controls. RESULTS: We found that beta power in both basal ganglia nuclei was specifically elevated during REM sleep without atonia in patients with PD, but not in dystonia. Basal ganglia beta power during REM sleep positively correlated with the extent of atonia loss, with beta elevation preceding the activation of chin electromyogram activities by ~200 ms. The connectivity between basal ganglia beta power and chin muscular activities during REM sleep was significantly correlated with the clinical severity of RBD in PD. CONCLUSIONS: These findings support that basal ganglia activities are associated with if not directly contribute to the occurrence of RBD in PD. Our study expands the understanding of the role basal ganglia played in RBD and may foster improved therapies for RBD by interrupting the basal ganglia-muscular communication during REM sleep in PD.

Deep brain stimulation of the subthalamic nucleus for primary Meige syndrome: clinical outcomes and predictive factors.

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 (ß = -0.241, p = 0.027), preoperative anxiety severity (ß = -0.386, p = 0.001), and volume of activated tissue within the dorsolateral (sensorimotor) STN (ß = 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.

Advances in Understanding the Notch Signaling Pathway in the Cochlea.

The cochlear structure is highly complex and specific, and its development is regulated by multiple signaling pathways. Abnormalities in cochlear development can lead to different degrees of loss of function. Hair cells (HCs), which are difficult to regenerate in the mature mammalian cochlea, are susceptible to damage from noise and ototoxic drugs, and damage to HCs can cause hearing loss to varying degrees. Notch, a classical developmental signaling molecule, has been shown to be closely associated with embryonic cochlear development and plays an important role in HC regeneration in mammals, suggesting that the Notch signaling pathway may be a potential therapeutic target for cochlear development and hearing impairment due to HC damage. In recent years, the important role of the Notch signaling pathway in the cochlea has received increasing attention. In this paper, we review the role of Notch signaling in cochlear development and HC regeneration, with the aim of providing new research ideas for the prevention and treatment of related diseases.

Premature drug reduction after subthalamic nucleus deep brain stimulation leading to worse depression in patients with Parkinson's disease.

Background: Reduction of medication in Parkinson's disease (PD) following subthalamic nucleus deep brain stimulation (STN-DBS) has been recognized, but the optimal timing for medication adjustments remains unclear, posing challenges in postoperative patient management. Objective: This study aimed to provide evidence for the timing of medication reduction post-DBS using propensity score matching (PSM). Methods: In this study, initial programming and observation sessions were conducted over 1 week for patients 4-6 weeks postoperatively. Patients were subsequently categorized into medication reduction or non-reduction groups based on their dyskinesia evaluation using the 4.2-item score from the MDS-UPDRS-IV. PSM was employed to maintain baseline comparability. Short-term motor and neuropsychiatric symptom assessments for both groups were conducted 3-6 months postoperatively. Results: A total of 123 PD patients were included. Baseline balance in motor and non-motor scores was achieved between the two groups based on PSM. Short-term efficacy revealed a significant reduction in depression scores within the non-reduction group compared to baseline (P < 0.001) and a significant reduction compared to the reduction group (P = 0.037). No significant differences were observed in UPDRS-III and HAMA scores between the two groups. Within-group analysis showed improvements in motor symptoms, depression, anxiety, and subdomains in the non-reduction group, while the reduction group exhibited improvements only in motor symptoms. Conclusion: This study provides evidence for the timing of medication reduction following DBS. Our findings suggest that early maintenance of medication stability is more favorable for improving neuropsychiatric symptoms.

Focalizing regions of biomarker relevance facilitates biomarker prediction on histopathological images.

Image-based AI has thrived as a potentially revolutionary tool for predicting molecular biomarker statuses, which aids in categorizing patients for appropriate medical treatments. However, many methods using hematoxylin and eosin-stained (H&E) whole-slide images (WSIs) have been found to be inefficient because of the presence of numerous uninformative or irrelevant image patches. In this study, we introduced the region of biomarker relevance (ROB) concept to identify the morphological areas most closely associated with biomarkers for accurate status prediction. We actualized this concept within a framework called saliency ROB search (SRS) to enable efficient and effective predictions. By evaluating various lung adenocarcinoma (LUAD) biomarkers, we showcased the superior performance of SRS compared to current state-of-the-art AI approaches. These findings suggest that AI tools, built on the ROB concept, can achieve enhanced molecular biomarker prediction accuracy from pathological images.

Optimal subthalamic stimulation sites and related networks for freezing of gait in Parkinson's disease.

Freezing of gait is a common and debilitating symptom in Parkinson's disease. Although high-frequency subthalamic deep brain stimulation is an effective treatment for Parkinson's disease, post-operative freezing of gait severity has been reported to alleviate, deteriorate or remain constant. We conducted this study to explore the optimal stimulation sites and related connectivity networks for high-frequency subthalamic deep brain stimulation treating freezing of gait in Parkinson's disease. A total of 76 Parkinson's disease patients with freezing of gait who underwent bilateral high-frequency subthalamic stimulation were retrospectively included. The volumes of tissue activated were estimated based on individual electrode reconstruction. The optimal and sour stimulation sites were calculated at coordinate/voxel/mapping level and mapped to anatomical space based on patient-specific images and stimulation settings. The structural and functional predictive connectivity networks for the change of the post-operative Freezing of Gait-Questionnaire were also identified based on normative connectomes derived from the Parkinson's Progression Marker Initiative database. Leave-one-out cross-validation model validated the above results, and the model remained significant after including covariates. The dorsolateral two-thirds of the subthalamic nucleus was identified as the optimal stimulation site, while the ventrocentral portion of the right subthalamic nucleus and internal capsule surrounding the left central subthalamic nucleus were considered as the sour stimulation sites. Modulation of the fibre tracts connecting to the supplementary motor area, pre-supplementary motor area and pedunculopontine nucleus accounted for the alleviation of freezing of gait, whereas tracts connecting to medial and ventrolateral prefrontal cortices contributed to the deterioration of freezing of gait. The optimal/sour stimulation sites and structural/functional predictive connectivity networks for high-frequency subthalamic deep brain stimulation treating freezing of gait are identified and validated through sizable Parkinson's disease patients in this study. With the growing understanding of stimulation sites and related networks, individualized deep brain stimulation treatment with directional leads will become an optimal choice for Parkinson's disease patients with freezing of gait in the future.

A genome-wide transposon mutagenesis screening identifies LppB as a key factor associated with Mycoplasma bovis colonization and invasion into host cells.

Mycoplasma spp., the smallest self-replicating and genome-reduced organisms, have raised a great concern in both the medical and veterinary fields due to their pathogenicity. The molecular determinants of these wall-less bacterium efficiently use their limited genes to ensure successful infection of the host remain unclear. In the present study, we used the ruminant pathogen Mycoplasma bovis as a model to identify the key factors for colonization and invasion into host cells. We constructed a nonredundant fluorescent transposon mutant library of M. bovis using a modified transposon plasmid, and identified 34 novel adhesion-related genes based on a high-throughput screening approach. Among them, the ΔLppB mutant exhibited the most apparent decrease in adhesion to embryonic bovine lung (EBL) cells. The surface-localized lipoprotein LppB, which is highly conserved in Mycoplasma species, was then confirmed as a key factor for M. bovis adhesion with great immunogenicity. LppB interacted with various components (fibronectin, vitronectin, collagen IV, and laminin) of host extracellular matrix (ECM) and promoted plasminogen activation through tPA to degrade ECM. The 439-502 amino acid region of LppB is a critical domain, and F465 and Y493 are important residues for the plasminogen activation activity. We further revealed LppB as a key factor facilitating internalization through clathrin- and lipid raft-mediated endocytosis, which helps the Mycoplasma invade the host cells. Our study indicates that LppB plays a key role in Mycoplasma infection and is a potential new therapeutic and vaccine target for Mycoplasma species.

Utilization, surgical populations, centers, coverages, regional balance, and their influential factors of deep brain stimulation for Parkinson's disease: a large-scale multicenter cross-sectional study from 1997 to 2021.

BACKGROUND: Deep brain stimulation (DBS) is an emerging and effective therapy for Parkinson's disease (PD). However, little is known about its utilization, surgical populations, centers, coverages, regional balance, and influential factors. MATERIALS AND METHODS: This large-scale multicenter cross-sectional study was conducted using a national census involving 74 Chinese centers. National DBS populations and centers for PD were investigated in 1997-2021, and regional sociodemographic features, surgical populations, related resources, and insurance policies in 2020 were explored. RESULTS: Since the first DBS surgery in 1997, a total of 38 122 PD patients from 349 centers underwent DBS by 2021, which covered 1.118% (1.108-1.129) of patients and 0.954% (0.933-0.976) of centers. Significant upward trends in the annual surgical population and coverages were observed with rapid climbing rates, while the annual surgical centers and their coverage showed two growth peaks in 2002-2006 and 2010-2018, correlating with clinical approvals and new technologies. A total of 103 070 (51 165-154 975) PD patients [2.088% (1.351-2.825) coverage] and 603 (72-1134) centers [1.356% (1.126-1.586) coverage] are predicted to conduct DBS by 2030. The new remotely programmed DBS technology was recoded as the first application in 2015 and rapidly increased to 2771 (47.39%, 46.11-48.67) patients with 10 507 remote programming sessions annually in 2021. Provinces in the eastern and central regions had better economic status, more surgical patients, higher insurance affordability, and more related resources than those in the western and northeastern regions. Higher gross domestic product per capita ( ß =5.041, 3.324-6.758 and ß =0.008, 0.004-0.012; all P <0.001) and more functional neurosurgery doctors ( ß =3.596, 0.353-6.839; P =0.031 and ß =0.010, 0.002-0.017; P =0.013) positively influenced surgical populations and coverages, while higher insurance levels ( ß =128.888, 64.702-193.075; P <0.001) positively influenced surgical coverages. CONCLUSION: Although surgical populations, centers, and coverages of DBS for PD have rapidly improved and are predicted to show future increases, this is still insufficient to cover potential eligible patients. Regionally imbalanced health coverage should be given attention to promote coordinated development.

Pallidal activities during sleep and sleep decoding in dystonia, Huntington's, and Parkinson's disease.

BACKGROUND: Sleep disturbances are highly prevalent in movement disorders, potentially due to the malfunctioning of basal ganglia structures. Pallidal deep brain stimulation (DBS) has been widely used for multiple movement disorders and been reported to improve sleep. We aimed to investigate the oscillatory pattern of pallidum during sleep and explore whether pallidal activities can be utilized to differentiate sleep stages, which could pave the way for sleep-aware adaptive DBS. METHODS: We directly recorded over 500 h of pallidal local field potentials during sleep from 39 subjects with movement disorders (20 dystonia, 8 Huntington's disease, and 11 Parkinson's disease). Pallidal spectrum and cortical-pallidal coherence were computed and compared across sleep stages. Machine learning approaches were utilized to build sleep decoders for different diseases to classify sleep stages through pallidal oscillatory features. Decoding accuracy was further associated with the spatial localization of the pallidum. RESULTS: Pallidal power spectra and cortical-pallidal coherence were significantly modulated by sleep-stage transitions in three movement disorders. Differences in sleep-related activities between diseases were identified in non-rapid eye movement (NREM) and REM sleep. Machine learning models using pallidal oscillatory features can decode sleep-wake states with over 90% accuracy. Decoding accuracies were higher in recording sites within the internus-pallidum than the external-pallidum, and can be precited using structural (P < 0.0001) and functional (P < 0.0001) whole-brain neuroimaging connectomics. CONCLUSION: Our findings revealed strong sleep-stage dependent distinctions in pallidal oscillations in multiple movement disorders. Pallidal oscillatory features were sufficient for sleep stage decoding. These data may facilitate the development of adaptive DBS systems targeting sleep problems that have broad translational prospects.

Subthalamic nucleus stimulation attenuates motor seizures via modulating the nigral orexin pathway.

Background: Focal motor seizures that originate in the motor region are a considerable challenge because of the high risk of permanent motor deficits after resection. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a potential treatment for motor epilepsy that may enhance the antiepileptic actions of the substantia nigra pars reticulata (SNr). Orexin and its receptors have a relationship with both STN-DBS and epilepsy. We aimed to investigate whether and how STN inputs to the SNr regulate seizures and the role of the orexin pathway in this process. Methods: A penicillin-induced motor epileptic model in adult male C57BL/6 J mice was established to evaluate the efficacy of STN-DBS in modulating seizure activities. Optogenetic and chemogenetic approaches were employed to regulate STN-SNr circuits. Selective orexin receptor type 1 and 2 antagonists were used to inhibit the orexin pathway. Results: First, we found that high-frequency ipsilateral or bilateral STN-DBS was effective in reducing seizure activity in the penicillin-induced motor epilepsy model. Second, inhibition of STN excitatory neurons and STN-SNr projections alleviates seizure activities, whereas their activation amplifies seizure activities. In addition, activation of the STN-SNr circuits also reversed the protective effect of STN-DBS on motor epilepsy. Finally, we observed that STN-DBS reduced the elevated expression of orexin and its receptors in the SNr during seizures and that using a combination of selective orexin receptor antagonists also reduced seizure activity. Conclusion: STN-DBS helps reduce motor seizure activity by inhibiting the STN-SNr circuit. Additionally, orexin receptor antagonists show potential in suppressing motor seizure activity and may be a promising therapeutic option in the future.

Fronto-parieto-subthalamic activity decodes motor status in Parkinson's disease.

AIMS: Patients with Parkinson's disease (PD) have various motor difficulties, including standing up, gait initiation and freezing of gait. These abnormalities are associated with cortico-subthalamic dysfunction. We aimed to reveal the characteristics of cortico-subthalamic activity in PD patients during different motor statuses. METHODS: Potentials were recorded in the superior parietal lobule (SPL), the primary motor cortex (M1), premotor cortex (PMC), and the bilateral subthalamic nucleus (STN) in 18 freely walking patients while sitting, standing, walking, dual-task walking, and freezing in medication "off" (Moff) and "on" (Mon) states. Different motor status activities were compared in band power, and a machine learning classifier was used to differentiate the motor statuses. RESULTS: SPL beta power was specifically inhibited from standing to walking, and negatively correlated with walking speed; M1 beta power reflected the degree of rigidity and was reversed by medication; XGBoost algorithm classified the five motor statuses with acceptable accuracy (68.77% in Moff, 60.58% in Mon). SPL beta power ranked highest in feature importance in both Moff and Mon states. CONCLUSION: SPL beta power plays an essential role in walking status classification and could be a physiological biomarker for walking speed, which would aid the development of adaptive DBS.

Profiling the low-beta characteristics of the subthalamic nucleus in early- and late-onset Parkinson's disease.

Objectives: Low-beta oscillation (13-20 Hz) has rarely been studied in patients with early-onset Parkinson's disease (EOPD, age of onset ≤50 years). We aimed to explore the characteristics of low-beta oscillation in the subthalamic nucleus (STN) of patients with EOPD and investigate the differences between EOPD and late-onset Parkinson's disease (LOPD). Methods: We enrolled 31 EOPD and 31 LOPD patients, who were matched using propensity score matching. Patients underwent bilateral STN deep brain stimulation (DBS). Local field potentials were recorded using intraoperative microelectrode recording. We analyzed the low-beta band parameters, including aperiodic/periodic components, beta burst, and phase-amplitude coupling. We compared low-beta band activity between EOPD and LOPD. Correlation analyses were performed between the low-beta parameters and clinical assessment results for each group. Results: We found that the EOPD group had lower aperiodic parameters, including offset (p = 0.010) and exponent (p = 0.047). Low-beta burst analysis showed that EOPD patients had significantly higher average burst amplitude (p = 0.016) and longer average burst duration (p = 0.011). Furthermore, EOPD had higher proportion of long burst (500-650 ms, p = 0.008), while LOPD had higher proportion of short burst (200-350 ms, p = 0.007). There was a significant difference in phase-amplitude coupling values between low-beta phase and fast high frequency oscillation (300-460 Hz) amplitude (p = 0.019). Conclusion: We found that low-beta activity in the STN of patients with EOPD had characteristics that varied when compared with LOPD, and provided electrophysiological evidence for different pathological mechanisms between the two types of PD. These differences need to be considered when applying adaptive DBS on patients of different ages.

Prefrontal association of subthalamic deep brain stimulation with rapid eye movement sleep behavior disorder in Parkinson's disease.

OBJECTIVE: Subthalamic nucleus (STN)-deep brain stimulation (DBS) in Parkinson's disease (PD) patients affects not just focused target areas but also diffuse brain networks. The effect of this network modulation on nonmotor DBS effects is not fully understood. By concentrating on the sleep domain, the authors comprehensively determined the influence of electrode location and related structural/functional connections on changes in probable rapid eye movement (REM) sleep behavior disorder (pRBD) symptoms after STN-DBS, which has been reported to ameliorate, deteriorate, or remain constant. METHODS: Preoperative and postoperative pRBD symptoms were documented in 60 PD patients. The volumes of tissue activated (VTAs) were assessed on the basis of individual electrode reconstructions and merged with normative connectome data to identify structural/functional connections associated with VTAs. The entire cohort was used to construct connection models that explained changes in pRBD symptoms, as well as to perform cross-validations. RESULTS: Structural/functional connectivity was associated with pRBD symptom changes during STN-DBS. Changes in pRBD symptoms were predicted using an ideal structural connection map. Prefrontal connection was related with improved pRBD symptoms, whereas sensorimotor connectivity was associated with deterioration. CONCLUSIONS: Recovery of pRBD symptoms was predicted on the basis of the fibers connecting the STN electrode to prefrontal regions. These findings implied that the placement of STN-DBS leads influences the fibers to prefrontal regions and may be used to enhance treatment of pRBD symptoms; however, further prospective studies are needed to validate these findings.

Vagus Nerve Stimulation for Drug Resistant Epilepsy: Clinical Outcome, Adverse Events, and Potential Prognostic Factors in a Single Center Experience.

OBJECTIVE: Vagus nerve stimulation (VNS) has been used for adjunctive treatment in drug resistant epilepsy (DRE) for decades. Nevertheless, information is lacking on possible potential prognostic factors. Our study presents the efficacy and safety of VNS with a focus on prognostic factors in 45 patients with DRE. METHODS: We retrospectively evaluated the clinical outcome of 45 consecutive patients with DRE undergoing VNS implantation in The First Affiliated Hospital of Anhui Medical University between November 2016 and August 2021. Medical records were aggregated across all patient visits. Cox proportional hazards regression was used to estimate the prognostic factors. RESULTS: Significant decrease in seizure frequency was observed after intermittent stimulation of the vagus nerve. According to the modified McHugh classification, 11 patients (24.4%) were Class I, 11 patients (24.4%) were Class II, four patients (8.9%) were Class III, 10 patients (22.2%) were Class IV, and nine patients (20.0%) were Class V. Notably, 22 patients (48.9%) were responders and four patients (8.9%) were seizure-free at the final follow-up. No significant prognostic factors were found in this cohort. Furthermore, 37 patients reported improved quality of life. Of the patients, 22 (48.9%) experienced adverse events after surgery; hoarseness, discomfort at the surgical site, and coughing were the most common. CONCLUSION: The results confirmed the efficacy and safety of VNS. No prognostic factors were identified.

Deep brain stimulation of the nucleus basalis of Meynert modulates hippocampal-frontoparietal networks in patients with advanced Alzheimer's disease.

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.

Effects of Subthalamic Nucleus Deep Brain Stimulation on Depression in Patients with Parkinson's Disease.

Objective: In this study, we aimed to investigate the effects of STN-DBS on PD patients with different levels of depression and to identify predictors of the effects of STN-DBS on PD depression. Methods: We retrospectively collected data for 118 patients with PD depression who underwent STN-DBS at Beijing Tiantan Hospital. Neuropsychological, motor, and quality of life assessments were applied preoperatively and postoperatively. All patients were divided into two groups according to their HAM-D24 total scores (group I: mild depression; group Ⅱ: moderate depression). A mixed repeated-measure analysis of variance (ANOVA) was performed to investigate whether there were differences in depression scores before and after STN-DBS between the two groups. The changes in depression scores were also compared between groups using ANCOVA, adjusting for gender and preoperative HAMA scores. Logistic regression was performed to identify predictors of STN-DBS's effects on PD depression. Results: Both groups showed significant improvement in depression symptoms after STN-DBS. Compared with patients in group I, patients in group Ⅱ showed greater reductions in their HAM-D24 total scores (p = 0.002) and in HAM-D24 subitems including cognitive disturbances (p = 0.026) and hopelessness symptoms (p = 0.018). Logistic regression indicated that gender (female) (p = 0.014) and preoperative moderate depression (p < 0.001) patients had greater improvements in depression after STN-DBS. Conclusions: Patients with moderate depression showed better improvement than patients with mild depression. Gender (female) and preoperative HAMA scores are predictors of STN-DBS's effects on PD depression.

Efficacy of Neurostimulations for Upper Extremity Function Recovery after Stroke: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Neurostimulations for the post-stroke recovery of upper extremity function has been explored in previous research, but there remains a controversy about the superiority of different neurostimulations. METHODS: Randomized controlled trials (RCTs) were searched in MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov, from 1 January 2000 to 1 June 2022. A conventional pair-wise meta-analysis with a random-effect model was used to evaluate direct evidence. Bayesian random effect models were used for network meta-analysis. The grading of the recommendations assessment, development and evaluation (GRADE) approach was applied to assess the clinical quality of the results. RESULTS: A total of 88 RCTs, which enrolled 3491 participants, were included. For the Fugl-Meyer Assessment-Upper Extremity score change from the baseline to the longest follow-up, the following interventions showed a significant difference: VNS (MD = 4.12, 95%CrI: 0.54 to 7.80, moderate certainty), cNMES (MD = 3.98, 95%CrI: 1.05 to 6.92, low certainty), FES (MD = 7.83, 95%CrI: 4.42 to 11.32, very low certainty), drTMS (MD = 7.94, 95%CrI: 3.71 to 12.07, moderate certainty), LFrTMS (MD = 2.64, 95%CrI: 1.20 to 4.11, moderate certainty), HFrTMS (MD = 6.73, 95%CrI: 3.26 to 10.22, moderate certainty), and iTBS combined with LFrTMS (MD = 5.41, 95%CrI: 0.48 to 10.35, moderate certainty). CONCLUSIONS: The neurostimulations above the revealed significant efficacy for improving the upper limb function after stroke eased the suffering of the patient.