Comparison of children and adults in deep brain stimulation for Tourette Syndrome: a large-scale multicenter study of 102 cases with long-term follow-up.

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

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.

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.

Cortical phase-amplitude coupling is key to the occurrence and treatment of freezing of gait.

Freezing of gait is a debilitating symptom in advanced Parkinson's disease and responds heterogeneously to treatments such as deep brain stimulation. Recent studies indicated that cortical dysfunction is involved in the development of freezing, while evidence depicting the specific role of the primary motor cortex in the multi-circuit pathology of freezing is lacking. Since abnormal beta-gamma phase-amplitude coupling recorded from the primary motor cortex in patients with Parkinson's disease indicates parkinsonian state and responses to therapeutic deep brain stimulation, we hypothesized this metric might reveal unique information on understanding and improving therapy for freezing of gait. Here, we directly recorded potentials in the primary motor cortex using subdural electrocorticography and synchronously captured gait freezing using optoelectronic motion-tracking systems in 16 freely-walking patients with Parkinson's disease who received subthalamic nucleus deep brain stimulation surgery. Overall, we recorded 451 timed up-and-go walking trials and quantified 7073 s of stable walking and 3384 s of gait freezing in conditions of on/off-stimulation and with/without dual-tasking. We found that (i) high beta-gamma phase-amplitude coupling in the primary motor cortex was detected in freezing trials (i.e. walking trials that contained freezing), but not non-freezing trials, and the high coupling in freezing trials was not caused by dual-tasking or the lack of movement; (ii) non-freezing episodes within freezing trials also demonstrated abnormally high couplings, which predicted freezing severity; (iii) deep brain stimulation of subthalamic nucleus reduced these abnormal couplings and simultaneously improved freezing; and (iv) in trials that were at similar coupling levels, stimulation trials still demonstrated lower freezing severity than no-stimulation trials. These findings suggest that elevated phase-amplitude coupling in the primary motor cortex indicates higher probabilities of freezing. Therapeutic deep brain stimulation alleviates freezing by both decoupling cortical oscillations and enhancing cortical resistance to abnormal coupling. We formalized these findings to a novel 'bandwidth model,' which specifies the role of cortical dysfunction, cognitive burden and therapeutic stimulation on the emergence of freezing. By targeting key elements in the model, we may develop next-generation deep brain stimulation approaches for freezing of gait.

Low-frequency oscillations link frontal and parietal cortex with subthalamic nucleus in conflicts.

Low-frequency oscillations (LFOs, 28 Hz) in the subthalamic nucleus(STN) are known to reflect cognitive conflict. However, it is unclear if LFOs mediate communication and functional interactions among regions implicated in conflict processing, such as the motor cortex (M1), premotor cortex (PMC), and superior parietal lobule (SPL). To investigate the potential contribution of LFOs to cognitive conflict mediation, we recorded M1, PMC, and SPL activities by right subdural electrocorticography (ECoG) simultaneously with bilateral STN local field potentials (LFPs) by deep brain stimulation electrodes in 13 patients with Parkinson's disease who performed the arrow version of the Eriksen flanker task. Elevated cue-related LFO activity was observed across patients during task trials, with the earliest onset in PMC and SPL. At cue onset, LFO power exhibited a significantly greater increase or a trend of a greater increase in the PMC, M1, and STN, and less increase in the SPL during high-conflict (incongruent) trials than in low-conflict (congruent) trials. The local LFO power increases in PMC, SPL, and right STN were correlated with response time, supporting the notion that these structures are critical hubs for cognitive conflict processing. This power increase was accompanied by increased functional connectivity between the PMC and right STN, which was correlated with response time across subjects. Finally, ipsilateral PMC-STN Granger causality was enhanced during high-conflict trials, with direction from STN to PMC. Our study indicates that LFOs link the frontal and parietal cortex with STN during conflicts, and the ipsilateral PMC-STN connection is specifically involved in this cognitive conflict processing.

Neuromodulation in drug-resistant epilepsy: A review of current knowledge.

Nearly 1% of the global population suffers from epilepsy. Drug-resistant epilepsy (DRE) affects one-third of epileptic patients who are unable to treat their condition with existing drugs. For the treatment of DRE, neuromodulation offers a lot of potential. The background, mechanism, indication, application, efficacy, and safety of each technique are briefly described in this narrative review, with an emphasis on three approved neuromodulation therapies: vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS), and closed-loop responsive neurostimulation (RNS). Neuromodulatory approaches involving direct or induced electrical currents have been developed to lessen seizure frequency and duration in patients with DRE since the notion of electrical stimulation as a therapy for neurologic diseases originated in the early nineteenth century. Although few people have attained total seizure independence for more than 12 months using these treatments, more than half have benefitted from a 50% drop in seizure frequency over time. Although promising outcomes in adults and children with DRE have been achieved, challenges such as heterogeneity among epilepsy types and etiologies, optimization of stimulation parameters, a lack of biomarkers to predict response to neuromodulation therapies, high-level evidence to aid decision-making, and direct comparisons between neuromodulatory approaches remain. To solve these existing gaps, authorize new kinds of neuromodulation, and develop personalized closed-loop treatments, further research is needed. Finally, both invasive and non-invasive neuromodulation seems to be safe. Implantation-related adverse events for invasive stimulation primarily include infection and pain at the implant site. Intracranial hemorrhage is a frequent adverse event for DBS and RNS. Other stimulation-specific side-effects are mild with non-invasive stimulation.

Ultra-high magnetic resonance imaging (MRI): a potential examination for deep brain stimulation devices and the limitation study concerning MRI-related heating injury.

Nowadays, the patients with deep brain stimulation (DBS) devices are restricted to undertake 1.5T magnetic resonance imaging (MRI) according to the guideline. Nevertheless, we conducted an experiment to test pathological change near the leads in different field-strength MRI. Twenty-four male New Zealand rabbits were assigned to Group 1 (G1, n = 6, 7.0T, DBS), Group 2 (G2, n = 6, 3.0T, DBS), Group 3 (G3, n = 6, 1.5T, DBS), and Group 4 (G4, n = 6, 1.5T, paracentesis). DBS leads were implanted in G1, G2 and G3, targeting left nucleus ventralis posterior thalami. Paracentesis was performed in G4. 24 h after MRI scan, all animals were killed for examining pathological alternation (at different distance from lead) via transmission electron microscopy. Our results suggest that the severity of tissue injury correlates with the distance to electrode instead of field strength of MRI. Up to now, the reason for the restriction of MRI indicated no significantly different pathological change.

The ability of anterior thalamic signals to predict seizures in temporal lobe epilepsy in kainate-treated rats.

OBJECTIVE: To analyze the local field potential (LFP) of the anterior nucleus of the thalamus (ANT) of epileptic rats using the Generic Osorio-Frei algorithm (GOFA), and to determine the ability of the ANT LFP to predict clinical seizures in temporal lobe epilepsy. METHODS: GOFA is an advanced real-time technique used to detect and predict seizures. In this article, GOFA was utilized to process the electrical signals of ANT and the motor cortex recorded in 12 rat models of temporal lobe epilepsy (TLE) induced via the injection of kainic acid into the unilateral hippocampus. The electroencephalography (EEG) data included (1) 161 clinical seizures (each contained a 10-min segment) involving the ANT and cortical regions and (2) one hundred three 10-min segments of randomly selected interictal (no seizure) data. RESULTS: Minimal false-positives (0.51 ± 0.36/h) and no false-negatives were detected based on the ANT LFP data processed using GOFA. In ANT LFP, the delay from electrographic onset (EO) to automated onset (AO) was 1.24 ± 0.47 s, and the delay from AO to clinical onset (CO) was 7.73 ± 3.23 s. The AO time occurred significantly earlier in the ANT than in the cortex (p = 0.001). In 75.2% of the clinical onsets predicted by ANT LFP, it was 1.37 ± 0.82 s ahead of the prediction of cortical potentials (CPs), and the remainder were 0.84 ± 0.31 s slower than the prediction of CPs. SIGNIFICANCE: ANT LFP appears to be an optimal option for the prediction of seizures in temporal lobe epilepsy. It was possible to upgrade the responsive neurostimulation system to emit electrical stimulation in response to the prediction of epileptic seizures based on the changes in the ANT LFP.

Transcutaneous vagus nerve stimulation for refractory epilepsy: a randomized controlled trial.

This trial was designed to test the safety and effectiveness of transcutaneous auricular vagus nerve stimulation (ta-VNS) for patients with refractory epilepsy.Pre-trial：144 patients were randomly assigned to ta-VNS group (n=98) or transcutaneous auricular non-vagus nerve stimulation (tn-VNS) control group (n=46). Treatment was conducted twice per day for 24 weeks. After 8, 16 and 24 weeks of treatment，the patients were evaluated according to the Modified Engel Scale (four classes). After 8 weeks，according to the medical ethic design, patients in tn-VNS group were switched into ta-VNS group uniquely. After 8 weeks' treatment 41.0% and 27.5% of patients from ta-VNS and tn-VNS groups, respectively, experienced reduction in seizure frequency that reached I, II and III levels according to the standards of the Modified Engel Scale compared with the baselines, indicating significant difference in seizure reduction between the two groups. After 24 weeks of treatment, ta-VNS patients had a 47.7% reduction, and tn-VNS, with an additional 16 weeks of treatment, reached 47.5% in reduction. After 8 weeks' treatment, the percentages of average seizure frequency in ta-VNS and tn-VNS were reduced by 42.6% and 11.5% respectively, providing a statistically significant difference in the results between the two groups (P<0.05). In addition, there were significant improvements in electroencephalograph (EEG) and the quality of daily life of the patients after treatment.The results show that this ta-VNS treatment can effectively reduce the frequency of seizures and improve the patient's quality of life. This may be an effective treatment for refractory epilepsy. At the same time，it is also safe，economic, and widely applicable.

Individual Structural Covariance Network Predicts Long-Term Motor Improvement in Parkinson Disease with Subthalamic Nucleus Deep Brain Stimulation.

BACKGROUND AND PURPOSE: The efficacy of long-term chronic subthalamic nucleus deep brain stimulation (STN-DBS) in treating Parkinson disease (PD) exhibits substantial variability among individuals. The preoperative identification of suitable deep brain stimulation (DBS) candidates through predictive means becomes crucial. Our study aims to investigate the predictive value of characterizing individualized structural covariance networks for long-term efficacy of DBS, offering patients a precise and cost-effective preoperative screening tool. MATERIALS AND METHODS: We included 138 patients with PD and 40 healthy controls. We developed individualized structural covariance networks from T1-weighted images utilizing network template perturbation, and computed the networks' topological characteristics. Patients were categorized according to their long-term motor improvement following STN-DBS. Intergroup analyses were conducted on individual network edges and topological indices, alongside correlation analyses with long-term outcomes for the entire patient cohort. Finally, machine learning algorithms were employed for regression and classification to predict post-DBS motor improvement. RESULTS: Among the patients with PD, 6 edges (left middle frontal and left caudate nucleus, right olfactory and right insula, left superior medial frontal gyrus and right insula, right middle frontal and left paracentral lobule, right middle frontal and cerebellum, left lobule VIIb of the cerebellum and the vermis of the cerebellum) exhibited significant results in intergroup comparisons and correlation analyses. Increased degree centrality and local efficiency of the cerebellum, parahippocampal gyrus, and postcentral gyrus were associated with DBS improvement. A regression model constructed from these 6 edges revealed a significant correlation between predicted and observed changes in the unified PD rating scale (R = 0.671, P < .001) and receiver operating characteristic analysis demonstrated an area under the curve of 0.802, effectively distinguishing between patients with good and moderate improvement post-DBS. CONCLUSIONS: Our findings reveal the link between individual structural covariance network fingerprints in patients with PD and long-term motor outcome following STN-DBS. Additionally, binary and continuous cerebellum-basal ganglia-frontal structural covariance network edges have emerged as potential predictive biomarkers for DBS motor outcome.

Acoustic assessment in mandarin-speaking Parkinson's disease patients and disease progression monitoring and brain impairment within the speech subsystem.

Approximately 90% of Parkinson's patients (PD) suffer from dysarthria. However, there is currently a lack of research on acoustic measurements and speech impairment patterns among Mandarin-speaking individuals with PD. This study aims to assess the diagnosis and disease monitoring possibility in Mandarin-speaking PD patients through the recommended speech paradigm for non-tonal languages, and to explore the anatomical and functional substrates. We examined total of 160 native Mandarin-speaking Chinese participants consisting of 80 PD patients, 40 healthy controls (HC), and 40 MRI controls. We screened the optimal acoustic metric combination for PD diagnosis. Finally, we used the objective metrics to predict the patient's motor status using the Naïve Bayes model and analyzed the correlations between cortical thickness, subcortical volumes, functional connectivity, and network properties. Comprehensive acoustic screening based on prosodic, articulation, and phonation abnormalities allows differentiation between HC and PD with an area under the curve of 0.931. Patients with slowed reading exhibited atrophy of the fusiform gyrus (FDR p = 0.010, R = 0.391), reduced functional connectivity between the fusiform gyrus and motor cortex, and increased nodal local efficiency (NLE) and nodal efficiency (NE) in bilateral pallidum. Patients with prolonged pauses demonstrated atrophy in the left hippocampus, along with decreased NLE and NE. The acoustic assessment in Mandarin proves effective in diagnosis and disease monitoring for Mandarin-speaking PD patients, generalizing standardized acoustic guidelines beyond non-tonal languages. The speech impairment in Mandarin-speaking PD patients not only involves motor aspects of speech but also encompasses the cognitive processes underlying language generation.

Subthalamic nucleus deep brain stimulation alleviates oxidative stress via mitophagy in Parkinson's disease.

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.

Efficacy and safety of combined deep brain stimulation with capsulotomy for comorbid motor and psychiatric symptoms in Tourette's syndrome: Experience and evidence.

OBJECTIVES: To evaluate the efficacy and safety of combined deep brain stimulation (DBS) with capsulotomy for comorbid motor and psychiatric symptoms in patients with Tourette's syndrome (TS). METHODS: This retrospective cohort study consecutively enrolled TS patients with comorbid motor and psychiatric symptoms who were treated with combined DBS and anterior capsulotomy at our center. Longitudinal motor, psychiatric, and cognitive outcomes and quality of life were assessed. In addition, a systematic review and meta-analysis were performed to summarize the current experience with the available evidence. RESULTS: In total, 5 eligible patients in our cohort and 26 summarized patients in 6 cohorts were included. After a mean 18-month follow-up, our cohort reported that motor symptoms significantly improved by 62.4 % (P = 0.005); psychiatric symptoms of obsessive-compulsive disorder (OCD) and anxiety significantly improved by 87.7 % (P < 0.001) and 78.4 % (P = 0.009); quality of life significantly improved by 61.9 % (P = 0.011); and no significant difference was found in cognitive function (all P > 0.05). Combined surgery resulted in greater improvements in psychiatric outcomes and quality of life than DBS alone. The synthesized findings suggested significant improvements in tics (MD: 57.92, 95 % CI: 41.28-74.56, P < 0.001), OCD (MD: 21.91, 95 % CI: 18.67-25.15, P < 0.001), depression (MD: 18.32, 95 % CI: 13.26-23.38, P < 0.001), anxiety (MD: 13.83, 95 % CI: 11.90-15.76, P < 0.001), and quality of life (MD: 48.22, 95 % CI: 43.68-52.77, P < 0.001). Individual analysis revealed that the pooled treatment effects on motor symptoms, psychiatric symptoms, and quality of life were 78.6 %, 84.5-87.9 %, and 83.0 %, respectively. The overall pooled rate of adverse events was 50.0 %, and all of these adverse events were resolved or alleviated with favorable outcomes. CONCLUSIONS: Combined DBS with capsulotomy is effective for relieving motor and psychiatric symptoms in TS patients, and its safety is acceptable. However, the optimal candidate should be considered, and additional experience is still necessary.

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.

Generalized sleep decoding with basal ganglia signals in multiple movement disorders.

Sleep disturbances profoundly affect the quality of life in individuals with neurological disorders. Closed-loop deep brain stimulation (DBS) holds promise for alleviating sleep symptoms, however, this technique necessitates automated sleep stage decoding from intracranial signals. We leveraged overnight data from 121 patients with movement disorders (Parkinson's disease, Essential Tremor, Dystonia, Essential Tremor, Huntington's disease, and Tourette's syndrome) in whom synchronized polysomnograms and basal ganglia local field potentials were recorded, to develop a generalized, multi-class, sleep specific decoder - BGOOSE. This generalized model achieved 85% average accuracy across patients and across disease conditions, even in the presence of recordings from different basal ganglia targets. Furthermore, we also investigated the role of electrocorticography on decoding performances and proposed an optimal decoding map, which was shown to facilitate channel selection for optimal model performances. BGOOSE emerges as a powerful tool for generalized sleep decoding, offering exciting potentials for the precision stimulation delivery of DBS and better management of sleep disturbances in movement disorders.

Subthalamic deep brain stimulation with a new device in Parkinson's disease: an open-label trial.

OBJECTIVE: We aimed to evaluate the safety and efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) with a new stimulator (Beijing PINS Medical Co., Ltd, PNS 1101) in Parkinson's disease (PD). MATERIALS AND METHODS: Forty patients received a PINS device implantation in the subthalamic nucleus. The effects of stimulation on motor score, activities of daily living, good-quality on-time, and the levodopa-equivalent dose were analyzed for all 40 patients with PD treated with bilateral or unilateral STN-DBS. The scores were collected at baseline in two conditions (on/off medication) and at 3, 6, 9, 12, and 24 months of follow-up with stimulation in the absence or presence of medication. The patients were followed up for two years. RESULTS: At 3, 6, 9, 12, and 24 months of follow-up, our results showed a significant increase from baseline in both activities of daily living and motor scores (p < 0.001) and good-quality on-time (p < 0.001); the daily levodopa-equivalent dose decreased compared with baseline (p < 0.01). No patient died during the study, and none of the adverse effects were classified as severe. All of the adverse events were resolved or improved by the end of the study. CONCLUSIONS: STN-DBS with the PINS device significantly improved the symptoms of PD when compared with baseline in this trial. This new device may be recommended for the treatment of patients with advanced PD; however, a randomized, double-blinding trial will be required.

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.

Adaptive deep brain stimulation for Parkinson's disease: looking back at the past decade on motor outcomes.

BACKGROUND: Adaptive deep brain stimulation (aDBS) has been reported to be an effective treatment for motor symptoms in patients with Parkinson's disease (PD). However, it remains unclear whether and in which motor domain aDBS provides greater/less benefits than conventional DBS (cDBS). OBJECTIVE: To conduct a meta-analysis and systematic review to explore the improvement of the motor symptoms of PD patients undergoing aDBS and the comparison between aDBS and cDBS. METHODS: Nineteen studies from PubMed, Embase, and the Cochrane Library database were eligible for the main analysis. Twelve studies used quantitative plus qualitative analysis; seven studies were only qualitatively analyzed. The efficacy of aDBS was evaluated and compared to cDBS through overall motor function improvements, changes in symptoms of rigidity-bradykinesia, dyskinesia, tremor, and speech function, and total electrical energy delivered (TEED). The overall motor improvement and TEED were investigated through meta-analyses, while other variables were investigated by systematic review. RESULTS: Quantitative analysis showed that aDBS, with a reduction of TEED (55% of that of cDBS), significantly improved motor functions (33.9%, p < 0.01) and may be superior to cDBS in overall motor improvement (p = 0.002). However, significant publication bias was detected regarding the superiority (p = 0.006, Egger's test). In the qualitative analysis, rigidity-bradykinesia, dyskinesia, and speech function outcomes after aDBS and cDBS were comparable. Beta-based aDBS may not be as efficient as cDBS for tremor control. CONCLUSIONS: aDBS can effectively relieve the clinical symptoms of advanced PD as did cDBS, at least in acute trials, delivering less stimulation than cDBS. Specific symptoms including tremor and axial disability remain to be compared between aDBS and cDBS in long-term studies.

Closed-Loop Adaptive Deep Brain Stimulation in Parkinson's Disease: Procedures to Achieve It and Future Perspectives.

Parkinson's disease (PD) is a neurodegenerative disease with a heavy burden on patients, families, and society. Deep brain stimulation (DBS) can improve the symptoms of PD patients for whom medication is insufficient. However, current open-loop uninterrupted conventional DBS (cDBS) has inherent limitations, such as adverse effects, rapid battery consumption, and a need for frequent parameter adjustment. To overcome these shortcomings, adaptive DBS (aDBS) was proposed to provide responsive optimized stimulation for PD. This topic has attracted scientific interest, and a growing body of preclinical and clinical evidence has shown its benefits. However, both achievements and challenges have emerged in this novel field. To date, only limited reviews comprehensively analyzed the full framework and procedures for aDBS implementation. Herein, we review current preclinical and clinical data on aDBS for PD to discuss the full procedures for its achievement and to provide future perspectives on this treatment.

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.