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.

Alpha-band activity is the most prominent neurobiological feature of scalp electroencephalography (EEG) signals, recent findings showed that there is more than one alpha rhythm coexisted in this 8-13 Hz band, but the generation mechanism of them was not fully understood. To address this question, we collected local field potential (LFP) in 32 brain regions of human brain with stereo-EEG (SEEG), with simultaneously recording with EEG during the process from awaked state (eyes-closed) to loss of consciousness (LOC) state with anesthesia. Our study revealed a prominent low-alpha (LA) rhythm (8-10 Hz) localized in the occipital region during the awake, eyes-closed state. As anesthetic depth increased leading to the LOC, this low-alpha rhythm gradually diminished and was replaced by a globally distributed high-alpha (HA) rhythm (10-13 Hz). This phenomenon was consistently observed at both LFP and EEG levels. Furthermore, we demonstrated that state-dependent changes of oscillatory property in alpha band were primarily driven by periodic rather than aperiodic activities, which could be also effectively explained by a simple dynamical model. This work provides the first evidence of anesthetic-induced modulation mechanisms underlying the generation and regulation of distinct alpha oscillations, offering valuable insights for future research in anesthesia, consciousness studies, and potential clinical applications.

Histamine functions as a neurotransmitter regulating multiple neural processes, whereas interleukin-10 (IL-10) is an anti-inflammatory cytokine with recognized neuroprotective properties. Previous research suggests that histamine can stimulate the release of various inflammatory mediators, including IL-10. However, the precise molecular mechanisms governing the interaction between histamine and IL-10, particularly their role in safeguarding dopaminergic neurons in Parkinson's disease (PD), have not been fully elucidated. The current findings suggest that, within the context of PD, histamine levels are elevated in the substantia nigra pars compacta (SNc) microglia, leading to an upregulation of IL-10 expression through activation of the H2 receptor and the downstream cAMP/PKA/p38β/CREB signaling cascade. However, the increased histamine concentration was negatively regulated by the IL-10 expression, allowing a limited increase in its concentration. Furthermore, the H2R-IL-10 pathway activation inhibited microglial activation and the production of inflammatory factors. Moreover, the H2R-IL-10 signaling axis modulated both membrane resistance and the expression of cleaved caspase-3 mRNA in dopaminergic neurons, contributing to the improvement of motor deficits in LPS-induced mouse models. These observations suggest that, in the pathological context of PD, microglia in the SNc exhibit increased production of histamine and IL-10 in a mutually regulatory manner. Elevated histamine levels further enhance IL-10 expression, which confers neuroprotection to dopaminergic neurons through its anti-inflammatory actions, ultimately alleviating motor impairments associated with PD.

Background Theory of mind (ToM), the ability to infer others' mental state, is essential for social interaction among human beings. It has been widely reported that both cognitive (inference of knowledge) and affective (inference of emotion) components of ToM are disrupted in Parkinson's disease (PD). Previous studies usually focused on the involvement of the prefrontal cortex. Objective This study investigated the causal role of the subthalamic nucleus (STN), a key hub of the fronto-basal ganglia loops, in ToM. Methods Thirty-four patients with idiopathic PD (15 women, aged 62.2 +/- 8.3 years) completed a Yoni task with deep brain stimulation (DBS) ON and OFF. The Yoni task was designed to separate the cognitive and affective components of ToM. Volumes of tissue activated (VTA) were computed for three subregions of the STN. Results DBS showed insignificant effects on ToM inference costs at the group level, which may be due to the large interindividual variability. The associative VTA correlated with the cognitive inference cost change but not the affective inference cost change. Patients with greater associative STN stimulation infer more slowly on cognitive ToM. Stimulating associative STN can adversely affect cognitive ToM in PD patients, especially in patients with a wide range of stimulation (>= 0.157) or cognitive decline (Montreal Cognitive Assessment < 26). Conclusions The associative STN plays a causal role in cognitive ToM in patients with PD. However, stimulating the associative STN likely impairs cognitive ToM and potentially leads to social interaction deficits in PD. (c) 2024 International Parkinson and Movement Disorder Society.

BACKGROUND:Ventral hippocampus (vHipp) in schizophrenia is in a state of hyperactivity and hypermetabolism, where the glutamate/gamma-aminobutyric acid (GABA) imbalance leads to downstream dopamine hyperactivity in the midbrain-limbic system. High-frequency deep brain stimulation (DBS) can disrupt the abnormal synchronization of functional circuits and modulate local brain networks. METHODS:The DBS-HITS study is a crossover randomized controlled trial. DBS will be applied to bilateral vHipp in six patients. They will be randomly assigned to receive 3-month high-frequency active stimulation and then 3-month sham stimulation, or vice versa. After 6-month crossover trial phase, all participants will undergo personalized active stimulation. Researchers will assess clinical symptoms and neurocognition, collect EEG and PET-CT data during planned follow-ups. Adverse event will be researcher-assessed or participant self-reported throughout the trial. DISCUSSION:To our knowledge, the DBS-HITS study is the first hippocampal DBS randomized controlled trial for schizophrenia. The goal of the DBS-HITS study is to assess the efficacy and safety of hippocampal DBS in treatment-resistant schizophrenia (TRS) and to investigate its impact on hippocampal activity and glutamate/GABA metabolism. The study is expected to deepen our understanding of the effects and side-effects of neuromodulation in TRS to facilitate individualized DBS treatment. TRIAL REGISTRATION:NCT05694000 in ClinicalTrial.gov, registered on January 23, 2023.

Graph theory enables a direct quantification of topological properties of any arbitrary network. Its application in neuroscience has unveiled topological changes of brain networks associated with various neurodegenerative diseases. This study used the graph theory to understand speech deficits in patients with Parkinson’s disease (PD). In particular, this study investigated the effect of subthalamic nucleus deep brain stimulation (STN-DBS) on the topology of speech graphs. Sixty patients with PD completed a standard semantic fluency test with DBS switched ON and OFF. A control group of sixty matched nonsurgical PD patients completed the test once. All verbal responses were recorded, transcripted, and transformed into directed speech graphs. Volumes of tissue activated (VTA) were estimated for three STN subregions, including sensorimotor, associative, and limbic parts. First, the patients with DBS OFF produced smaller and denser speech graphs than nonsurgical patients, showing fewer nodes, higher density, shorter diameter, and shorter average shortest path. Second, DBS partially reversed the effect of surgery, leading to larger and sparser speech graphs with more nodes, lower density, longer diameter, and longer average shortest path (ON versus OFF). Third, however, the left associative VTA negatively correlated with the DBS-induced diameter and average shortest path changes (ON versus OFF), suggesting that the patients with greater left associative STN stimulation tended to produce smaller and denser speech graphs. This study demonstrates that STN-DBS can partially restore the topological structure of speech graphs in PD patients. However, stimulating the left associative STN appears to disrupt speech graphs.

Accurate and rapid segmentation of the hippocampus can help doctors perform intractable temporal lobe epilepsy (TLE) preoperative evaluations to identify good surgical candidates. This study aims to establish a radiomics system for the automatic diagnosis of hippocampal sclerosis with the help of machine learning. A total of 240 cases were analysed to develop a diagnostic model. First, an automatic hippocampal segmentation process was established that exploits a priori knowledge of the relatively fixed location of the hippocampus in brain partitions, as well as a deep-learning segmentation network based on an Attention U-net. Then, we extracted 527 radiomics features from each side of the segmented hippocampus. The iterative sparse representation based on feature selection and a support vector machine classifier were finally used to establish the diagnostic model of hippocampal sclerosis. The diagnostic model consists of two consecutive steps: distinguish hippocampal sclerosis (HS) from normal control (NC) and detect whether the HS is located on the left or right side. When the automatic diagnosis model identified HS and NC, the sensitivity and specificity reached 0.941 and 0.917 in the 10-fold cross-validation set and 0.920 and 0.909 in the independent testing set. When the diagnostic model detected HS lateralization, the sensitivity and specificity reached 0.923 and 0.920 in cross-validation and 0.909 and 0.929 in independent testing. Our results show that the developed radiomics model can help detect TLE patients with hippocampal sclerosis and has the potential to simplify preoperative evaluations and select surgical candidates.

BackgroundThe levodopa challenge test (LCT) has been routinely used in Parkinson disease (PD) evaluation and predicts the outcome of deep brain stimulation (DBS). Guidelines recommend that patients with an improvement in Unified Parkinson's Disease Rating Scale (UPDRS)-III score > 33% in the LCT receive DBS treatment. However, LCT results are affected by many factors, and only provide information on the immediate effectiveness of dopamine. The aim of the present study was to investigate the relationship between LCT outcome and brain imaging features of PD patients to determine whether the latter can be used to identify candidates for DBS. MethodsA total of 38 PD patients were enrolled in the study. Based on improvement in UPDRS-III score in the LCT, patients were divided into low improvement (PD-LCT-L) and high improvement (PD-LCT-H) groups. Each patient's neural network was reconstructed based on T1-weighted magnetic resonance imaging data using the Jensen-Shannon divergence similarity estimation method. The network was established with the multiple kernel support vector machine technique. We analyzed differences in individual morphologic brain networks and their global and local metrics to determine whether there were differences in the connectomes of PD-LCT-L and PD-LCT-H groups. ResultsThe 2 groups were similar in terms of demographic and clinical characteristics. Mean +/- SD levodopa responsiveness was 26.52% +/- 3.47% in the PD-LCT-L group (N = 13) and 58.66% +/- 4.09% in the PD-LCT-H group (N = 25). There were no significant differences between groups in global and local metrics. There were 43 consensus connections that were affected in both groups; in PD-LCT-L patients, most of these connections were decreased whereas those related to the dorsolateral superior frontal gyrus and left cuneus were significantly increased. ConclusionMorphologic brain network assessment is a valuable method for predicting levodopa responsiveness in PD patients, which can facilitate the selection of candidates for DBS.

Drug-resistant epilepsy (DRE) is a chronic condition derived from spontaneous changes and regulatory effects in the epileptic brain. As demethylation factors, ten-eleven translocation (TET) family members have become a focus in recent studies of neurological disorders. Here, we quantified and localized TET1, TET2 and 5-hydroxymethylcytosine (5-hmC) in the temporal lobe cortex of DRE patients (n = 27) and traumatic brain hemorrhage controls (n = 10) by immunochemical staining. TET2 and ATP binding cassette subfamily B member 1 (ABCB1) expression patterns were determined in the isolated brain capillaries of DRE patients. TET2 expression was significantly increased in the temporal cortical tissue of DRE patients with or without hippocampal sclerosis (HS) compared to control patients, while TET1 and 5-hmC showed no differences in expression. We also found that a particularly strong expression of TET2 in the vascular tissue of DRE patients. ABCB1 and TET2 have evidently higher expression in the vascular endothelium from the neocortex of DRE patients. In blood-brain barrier (BBB) model, TET2 depletion can cause attenuated expression and function of ABCB1. Data from a cohort study and experiments in a BBB model suggest that TET2 has a specific regulatory effect on ABCB1, which may serve as a potential mechanism and target in DRE.

Microvascular decompression (MVD) surgery is the only potential curative method for hemifacial spasm (HFS). Little attention is paid to those recurrent/residual HFS cases. We want to study the potential etiology of those recurrent/residual HFS cases and evaluate the value of reoperation. We retrospectively reviewed reoperation hemifacial spasm patients in our hospital. Intraoperative videos or images were carefully reviewed, and the etiology of recurrent/residual HFS is roughly divided into three categories. Intraoperative findings, surgical outcomes, and complications were carefully studied to assess the value of reoperation for recurrent/residual HFS patients. A total of 28 cases were included in our case series. Twenty-three of them are recurrent HFS cases, and 5 of them are residual HFS cases. The mean follow-up duration is 24.96 months. There are seventeen patients with missed culprit vessels or insufficient decompression of root exit zone (REZ), eight patients with Teflon adhesion, and three patients with improper application of decompression materials in our case series. The final reoperation outcome with 17 excellent, seven good, and four fair, respectively. Eight (28.57

BACKGROUND: Surgical removal of lesions around the rolandic cortex remains a challenge for neurosurgeons owing to the high risk of neurological deficits. Evaluating the risk factors associated with motor deficits after surgery in this region may help reduce the occurrence of motor deficits. OBJECTIVE: To report our surgical experience in treating epileptic lesions involving the rolandic and perirolandic cortices. METHODS: We performed a single-center retrospective review of patients undergoing epilepsy surgeries with lesions located in the rolandic and perirolandic cortices. Patients with detailed follow-up information were included. The lesion locations, resected regions, and invasive exploration techniques were studied to assess their relationship with postoperative motor deficits. RESULTS: Forty-one patients were included. Twenty-three patients suffered from a transient motor deficit, and 2 had permanent disabilities after surgery. Six patients with lesions at the posterior bank of the precentral sulcus underwent resection, and 5 experienced short-term motor deficits. Two patients with lesions adjacent to the anterior part of the precentral gyrus, in whom the adjacent precentral gyrus was removed, experienced permanent motor deficits. Lesions located at the bottom of the central sulcus and invading the anterior bank of the central sulcus were observed in 3 patients. The patients did not experience permanent motor deficits after surgery. CONCLUSION: The anterior bank of the central sulcus is indispensable for motor function, and destruction of this region would inevitably cause motor deficits. The anterior bank of the precentral gyrus can also be removed without motor impairment if there is a preexisting epileptogenic lesion.

Abstract BackgroundDrug-resistant epilepsy (DRE) is a chronic condition derived from spontaneous changes and regulatory effects in the epileptic brain. DNA methylation, an inheritable but reversible epigenetic change, may participate in this complicated regulatory network. As demethylation factors, ten-eleven translocation (TET) family members have become a focus in recent studies of neurological disorders. Thus, we aimed to unravel their role in DRE and their function related to the possible refractory factor ABCB1 in a blood-brain barrier (BBB) model.MethodsWe quantified and localized TET1, TET2 and 5-hydroxymethylcytosine (5-hmC) in the temporal lobe cortex of DRE patients (n = 27) and traumatic brain haemorrhage controls (n = 10) by immunochemical staining. TET2 and ABCB1 expression patterns were determined in the temporal cortex and isolated brain capillaries of DRE patients using immunohistological detection and Western blot analysis, respectively. A BBB model constructed with hCMEC/D3 cells was used to verify the demethylation and regulatory effects of TET2 on ABCB1.ResultsTET2 expression was significantly increased in the temporal cortical tissue of DRE patients with or without hippocampal sclerosis (HS) compared to control patients, while TET1 and 5-hmC showed differences in expression. We also discovered that the vascular endothelium of DRE patients has a strong affinity for TET2. ABCB1 and TET2 have identical densities in the DRE temporal cortex, and they both have evidently higher expression in the vascular endothelium from the neocortex of DRE patients. In the BBB, TET2 depletion can cause attenuated expression and function of ABCB1, as well as a pattern of higher methylation in CpG islands of the ABCB1 promoter.ConclusionsThrough a cohort study performed on the temporal cortex and brain vessels of DRE patients, we identified a novel epigenetic marker, TET2. Data from experiments in a BBB model suggest that TET2 has a specific regulatory effect on ABCB1, which may serve as a potential mechanism and target in DRE and requires further research.

PurposeTo evaluate the risk factors associated with motor deficit following surgeries involving rolandic & peri-rolandic cortex and to introduce our surgical experiences dealing with lesions in this region.MethodsWe retrospectively reviewed patients who experienced drug-refractory epilepsies and received surgeries in our hospital. Medical records were carefully studied, and patients with lesions located in the rolandic & peri-rolandic cortex were screened. Those with detailed follow-up information were included. Lesion locations, resected regions, and invasive exploration techniques were studied to assess their relationship with the postoperative motor deficit.ResultsA total of 41 patients with lesions located in the rolandic or peri-rolandic cortex were included in this study. Of all these patients, 23 (56.10%) patients suffered from a transient motor deficit and 2 (4.88%) with a permanent disability after surgery. All eight patients with the anterior bank of precentral sulcus resected experienced motor deficit, and six of them gradually recovered within half a year. Seven patients with the anterior half of precentral gyrus resected did not experience permanent disability. A total of 14 (34.15%) patients received invasive exploration, and one of them had a permanent disability.ConclusionsThe anterior bank of the central sulcus is indispensable for motor functions, and the destruction of this region would inevitably cause a motor deficit. The upper part of the central sulcus could also be removed without significant neurological impairment if there is an epileptogenic lesion.

BACKGROUND:The inflammatory response is closely related to cancer progression and prognosis. The aim of this study was to determine the prognostic value of preoperative inflammatory markers among different molecular subtypes of lower-grade glioma (LGG). METHODS:We performed a retrospective analysis of 214 patients with LGG from 2001 to 2013, evaluating the effect of the neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR) and derived NLR (dNLR) on prognosis among different molecular subtypes. Isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promotor mutations were detected by gene sequencing, and Chromosome arms 1p and 19q (1p/19q) codeletion was estimated via fluorescence in situ hybridization. RESULTS:Survival analysis showed that a high NLR, low LMR, and high dNLR were associated with poor prognosis, while the PLR had no prognostic significance. The subsequent molecular subtype analysis indicated that a high NLR and dNLR predicted worse survival in the IDH mutation only group, a high NLR and PLR predicted worse survival in the IDH and TERT promoter mutation group, and a high PLR was associated with shorter survival in the triple-positive group. Furthermore, univariate and multivariate Cox regression analysis suggested that the dNLR was an independent prognostic factor for LGG. Finally, the prognostic nomogram was developed by integrating the inflammatory marker dNLR and independent clinical risk factors. CONCLUSION:The results of this study indicated that a high dNLR was an independent risk factor for overall survival rates in patients with LGG, which may increase prognostic accuracy and improve patient outcomes.

Purpose: This study was conducted to explore the cerebellar substructure volumetric alterations in refractory unilateral temporal lobe epilepsy (TLE) patients and the relationship with clinical factors and cognitive scores. Methods: A total of 48 unilateral refractory TLE patients and 48 age- and gender-matched normal controls (NCs) were retrospectively studied. All subjects underwent high-resolution magnetic resonance imaging (MRI) and automatically segmented volumetric brain information was obtained using volBrain and Data Processing Assistant for Resting-State fMRI (DPARSF) separately. Clinical seizure features and cognitive scores were acquired by a structured review of medical records. Results: The total volumes (TVs) of bilateral crus I, crus II, and IX were significantly smaller in the refractory unilateral TLE epilepsy patients. The gray matter volumes (GMVs) of cerebellar lobules showed lateralized reduction in ipsilateral III, IX, and contralateral crus II. Contralateral crus II GMV showed significant negative correlation with the duration of epilepsy (r = -0.31, p = 0.035) and positive association with the cognitive scores including long-term memory (LTM) (r = 0.39, p = 0.017), short-term memory (STM) (r = 0.51, p = 0.001) verbal comprehension index (VCI) (r = 0.37, p = 0.024), and perceptual organization index (POI) (r = 0.36, p = 0.030). The voxel-based morphometry (VBM) analysis proved similar results. The contralateral crus I GMV was significantly smaller in the generalized onset group (t= 2.536, p = 0.015). Conclusions: The lobules of the cerebellar in refractory TLE patients manifest different volumetric change characteristics. Crus II contralateral GMV is negatively correlated with the duration of epilepsy and positively associated with the cognitive scores. (C) 2020 Elsevier Inc. All rights reserved.

目的 分析影响脑深部电刺激(DBS)术治疗原发性帕金森病(PD)患者疗效的因素.方法 采用自身对照方法,收集40例以丘脑底核为靶标的DBS术治疗PD患者的运动功能、生活质量和临床相关资料进行回顾性分析,应用运动量表和神经心理量表对患者进行术后评估,对可能的疗效影响因素进行相关性分析.结果 术后1年刺激器开机未服药(DBS-ON/MED-OFF)状态下的运动评分(UPDRS Ⅲ)与术前药物关期(MED-OFF)比较,运动功能总分和震颤、强直、少动、PIGD分项得分均显著下降(P＜0.05),术后生活质量(PDQ-39)较术前明显提升(P＜0.05).其中,合并快眼动期睡眠行为障碍(RBD)患者与无RBD患者的症状比较,术后PDQ-39得分更高;4个主要非运动症状、PD病程、术前PDQ-39和自主神经功能评分均与术后PDQ-39评分相关(P＜0.05);女性和术前MMSE得分与术后PDQ-39变化值具有相关性(P＜0.05).结论 DBS治疗可整体改善PD患者运动功能;但PDQ-39改善受非运动症状尤其是RBD、性别和病程的影响;基于生活质量的DBS疗效评价应更多关注RBD等因素的影响.