Deep Brain Stimulation System Research Articles

A method for the synchronization of inertial sensor signals and local field potentials from deep brain stimulation systems

Objective. Recent innovative neurostimulators allow recording local field potentials (LFPs) while performing motor tasks monitored by wearable sensors. Inertial sensors can provide quantitative measures of motor impairment in people with subthalamic nucleus deep brain stimulation. To the best of our knowledge, there is no validated method to synchronize inertial sensors and neurostimulators without an additional device. This study aims to define a new synchronization method to analyze disease-related brain activity patterns during specific motor tasks and evaluate how LFPs are affected by stimulation and medication. Approach. Fourteen male subjects treated with subthalamic nucleus deep brain stimulation were recruited to perform motor tasks in four different medication and stimulation conditions. In each condition, a synchronization protocol was performed consisting of taps on the implanted neurostimulator, which produces artifacts in the LFPs that a nearby inertial sensor can simultaneously record. Main results. In 64% of the recruited subjects, induced artifacts were detected at least in one condition. Among those subjects, 83% of the recordings could be synchronized offline analyzing LFPs and wearables data. The remaining recordings were synchronized by video analysis. Significance. The proposed synchronization method does not require an external system (e.g., TENS electrodes) and can be easily integrated into clinical practice. The procedure is simple and can be carried out in a short time. A proper and simple synchronization will also be useful to analyze subthalamic neural activity in the presence of specific events (e.g., freezing of gait events) to identify predictive biomarkers.

Beta Burst-Driven Adaptive Deep Brain Stimulation Improves Gait Impairment and Freezing of Gait in Parkinson's Disease.

Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) that is often refractory to medication. Pathological prolonged beta bursts within the subthalamic nucleus (STN) are associated with both worse impairment and freezing behavior in PD, which are improved with deep brain stimulation (DBS). The goal of the current study was to investigate the feasibility, safety, and tolerability of beta burst-driven adaptive DBS (aDBS) for FOG in PD. Seven individuals with PD were implanted with the investigational Summit™ RC+S DBS system (Medtronic, PLC) with leads placed bilaterally in the STN. A PC-in-the-loop architecture was used to adjust stimulation amplitude in real-time based on the observed beta burst durations in the STN. Participants performed either a harnessed stepping-in-place task or a free walking turning and barrier course, as well as clinical motor assessments and instrumented measures of bradykinesia, OFF stimulation, on aDBS, continuous DBS (cDBS), or random intermittent DBS (iDBS). Beta burst driven aDBS was successfully implemented and deemed safe and tolerable in all seven participants. Gait metrics such as overall percent time freezing and mean peak shank angular velocity improved from OFF to aDBS and showed similar efficacy as cDBS. Similar improvements were also seen for overall clinical motor impairment, including tremor, as well as quantitative metrics of bradykinesia. Beta burst driven adaptive DBS was feasible, safe, and tolerable in individuals with PD with gait impairment and FOG.

Effect of surgical modification of deep brain stimulation lead trajectories on radiofrequency heating during MRI at 3T: from phantom experiments to clinical implementation.

Radiofrequency (RF) tissue heating around deep brain stimulation (DBS) leads is a well-known safety risk during MRI, resulting in strict imaging guidelines and limited allowable protocols. The implanted lead's trajectory and orientation with respect to the MRI electric fields contribute to variations in the magnitude of RF heating across patients. Currently, there are no surgical requirements for implanting the extracranial portion of the DBS lead, resulting in substantial variations in clinical lead trajectories and consequently RF heating. Recent studies have shown that incorporating concentric loops in the extracranial lead trajectory can reduce RF heating. However, optimal positioning of the loops and the quantitative benefit of trajectory modification in terms of added safety margins during MRI remain unknown. In this study, the authors systematically evaluated the characteristics of DBS lead trajectories that minimize RF heating during 3T MRI to develop the best surgical practices for safe access to postoperative MRI, and they present the first surgical implementation of these modified trajectories. The authors performed experiments to assess the maximum temperature increase of 244 distinct lead trajectories. They investigated the effect of the position, number, and size of the concentric loops on the skull. Experiments were performed in an anthropomorphic phantom implanted with a commercial DBS system, and RF exposure was generated by applying a high specific absorption rate sequence (B1+rms = 2.7 µT). The authors conducted test-retest experiments to assess the reliability of measurements. Additionally, they evaluated the effect of imaging landmarks and perturbations to the DBS device configuration on the efficacy of low-heating trajectories. Finally, two neurosurgeons implanted the recommended modified trajectories in patients, and the authors characterized their RF heating in comparison with unmodified trajectories. The maximum temperature increase ranged from 0.09°C to 7.34°C. The authors found that increasing the number of loops and positioning them closer to the surgical burr hole, particularly for the contralateral lead, substantially reduced RF heating. These trajectory modifications were easily incorporated during the surgical procedure and resulted in a threefold reduction in RF heating. Surgically modifying the extracranial portion of the DBS lead trajectory can substantially reduce RF heating during 3T MRI. The authors' results indicate that simple adjustments to the lead's configuration, such as small, concentric loops near the burr hole, can be readily adopted during DBS lead implantation to improve patient safety during MRI.

How Accurate Is Frameless Fiducial—Free Deep Brain Stimulation?

BACKGROUND AND OBJECTIVES: Frameless deep brain stimulation (DBS) offers advantages in terms of patient comfort and reduced operative time. However, the need for bony fiducial markers for localization remains a drawback due to the time-consuming and uncomfortable procedure. An alternative localization method involves the direct tracking of an intraoperative 3-dimensional scanner. This study aims to assess the accuracy of the NexFrame frameless DBS system in conjunction with the O-Arm (Medtronic Inc.), both with and without fiducial markers. METHODS: The locations of 100 DBS leads were determined, with 50 cases using fiducial-free localization and 50 involving fiducial markers. The coordinates were compared with the expected intraoperative targets. Absolute errors in the X, Y, and Z coordinates (ΔX, ΔY, and ΔZ) were calculated, along with the vector error (Euclidean) (vector error ). RESULTS: The vector error averaged 1.61 ± 0.49 mm (right) and 1.52 ± 0.60 mm (left) for the group without fiducial bone markers and 1.66 ± 0.69 (right) and 1.44 ± 0.65 mm (left) for the other cohort (P = .76 right; P = .67 left). Absolute errors in the X, Y, and Z coordinates for the fiducial-free group were 0.88 ± 0.55, 0.79 ± 0.45, and 0.79 ± 0.57 mm (right) and 0.72 ± 0.37, 0.78 ± 0.56, and 0.77 ± 0.71 mm (left). For the group with fiducial markers, these errors were 0.87 ± 0.72, 0.92 ± 0.39, and 0.86 ± 0.50 mm (right) and 0.75 ± 0.33, 0.80 ± 0.51, and 0.73 ± 0.64 mm (left) with no statistically significant difference. CONCLUSION: Our analysis of the accuracy of NexFrame DBS, both with and without fiducial markers, using an intraoperative navigable cone-beam computed tomography, demonstrates that both techniques provide sufficient and equivalent 3-dimensional accuracy.

Model-based closed-loop control of thalamic deep brain stimulation.

Introduction: Closed-loop control of deep brain stimulation (DBS) is beneficial for effective and automatic treatment of various neurological disorders like Parkinson's disease (PD) and essential tremor (ET). Manual (open-loop) DBS programming solely based on clinical observations relies on neurologists' expertise and patients' experience. Continuous stimulation in open-loop DBS may decrease battery life and cause side effects. On the contrary, a closed-loop DBS system uses a feedback biomarker/signal to track worsening (or improving) of patients' symptoms and offers several advantages compared to the open-loop DBS system. Existing closed-loop DBS control systems do not incorporate physiological mechanisms underlying DBS or symptoms, e.g., how DBS modulates dynamics of synaptic plasticity. Methods: In this work, we propose a computational framework for development of a model-based DBS controller where a neural model can describe the relationship between DBS and neural activity and a polynomial-based approximation can estimate the relationship between neural and behavioral activities. A controller is used in our model in a quasi-real-time manner to find DBS patterns that significantly reduce the worsening of symptoms. By using the proposed computational framework, these DBS patterns can be tested clinically by predicting the effect of DBS before delivering it to the patient. We applied this framework to the problem of finding optimal DBS frequencies for essential tremor given electromyography (EMG) recordings solely. Building on our recent network model of ventral intermediate nuclei (Vim), the main surgical target of the tremor, in response to DBS, we developed neural model simulation in which physiological mechanisms underlying Vim-DBS are linked to symptomatic changes in EMG signals. By using a proportional-integral-derivative (PID) controller, we showed that a closed-loop system can track EMG signals and adjust the stimulation frequency of Vim-DBS so that the power of EMG reaches a desired control target. Results and discussion: We demonstrated that the model-based DBS frequency aligns well with that used in clinical studies. Our model-based closed-loop system is adaptable to different control targets and can potentially be used for different diseases and personalized systems.

Role of electrophysiological activity and interactions of lateral habenula in the development of depression-like behavior in a chronic restraint stress model

Closed-loop deep brain stimulation (DBS) system offers a promising approach for treatment-resistant depression, but identifying universally accepted electrophysiological biomarkers for closed-loop DBS systems targeting depression is challenging. There is growing evidence suggesting a strong association between the lateral habenula (LHb) and depression. Here, we took LHb as a key target, utilizing multi-site local field potentials (LFPs) to study the acute and chronic changes in electrophysiology, functional connectivity, and brain network characteristics during the formation of a chronic restraint stress (CRS) model. Furthermore, our model combining the electrophysiological changes of LHb and interactions between LHb and other potential targets of depression can effectively distinguish depressive states, offering a new way for developing effective closed-loop DBS strategies.

1137 Prospective, Multicenter, International Registry of Deep Brain Stimulation for Dystonia: A Sub-analysis of Cervical Dystonia Patients

INTRODUCTION: Management of dystonia using Deep Brain Stimulation (DBS) is a well-established therapeutic approach. However, optimal DBS target sites in patients with cervical (focal) versus generalized dystonia are thought to diverge and be specific for particular connections (Horn 2022). DBS devices equipped with capabilities such as directionality and Multiple Independent Current Control (MICC) may offer potential for improved clinical outcomes. METHODS: This is a sub-analysis of patients with focal (cervical) dystonia only or cervical dystonia in the context of segmental or generalized dystonia assessed as part of a prospective, multicenter, international dystonia registry (NCT02686125). All patients receive an MICC-based, directional DBS system (Vercise, Boston Scientific). Patients are followed up to 3-years (post-implant). Several study assessments are being collected to evaluate their dystonia symptoms (e.g., TWSTRS), quality of life, and overall satisfaction. Adverse Events are also collected. RESULTS: A total of 43-patients (mean age 56.9-years, 58% females) with focal (cervical) dystonia only and 83 patients (mean 41.95-years, 61% females) with cervical dystonia in context of segmental or generalized dystonia have been evaluated. Both groups reported significant improvement in overall TWSTRS scores – however the extent varied. In the cervical-only cohort, a 19.9-point improvement was noted at 6-months (n = 25) and sustained up to 1-year (23.2-point improvement, n = 20). In those with cervical dystonia within frame of segmental or generalized dystonia, a 9.7-point and 7.3-point improvement in overall TWSTRS scores was noted at 6- (n = 50) and 12-months (n = 38), respectively. Updated data will be reported. CONCLUSIONS: This registry represents the first comprehensive, large-scale collection of real-world outcomes associated with dystonia patients implanted with a directional DBS system capable of MICC. Preliminary results demonstrate significant improvement in patients with cervical dystonia (alone or in context of segmental or generalized dystonia) following DBS.

Local field potentials: Therapeutic implications for DBS in dystonia including adaptive DBS for dystonia

Local field potentials (LFPs) are signals generated primarily by the result of the synchronous discharge of post-synaptic potentials. Detection of LFPs from intracranial electrodes sited within the basal ganglia has led to the recognition that there are specific features of the LFP that could serve as neurophysiological biomarkers of different disease states. For example, in Parkinson’s disease peaks in the beta frequency range of the power spectrum are known to correlate with the degree of bradykinesia and rigidity, whereas low frequency, alpha-theta peaks are increasingly considered a biomarker of dystonic activity. The introduction of newer deep brain stimulation (DBS) devices capable of simultaneous stimulation and LFP detection creates opportunities to investigate new strategies for treating patients with dystonia. This review aims to summarise the LFP findings seen in patients with dystonia undergoing DBS with a particular focus on the potential implications for future clinical practice and the development of adaptive DBS systems.

Coating of Neural Electrodes with Platinum Nanoparticles Reduces and Stabilizes Impedance In Vitro and In Vivo in a Rat Model

The efficacy of electrodes that are chronically implanted and used in the context of deep brain stimulation (DBS) for the treatment of neurological disorders critically depends on stable impedance. Platinum–iridium electrodes were coated with laser-generated platinum nanoparticle colloids (PtNPs) via electrophoretic deposition using pulsed direct currents (DC-EPD). Uncoated electrodes were used as controls. In vitro, electrodes were stimulated for four weeks in a 0.9% NaCl solution. For the in vivo (rats) study, coated electrodes were implanted in the left and uncoated control electrodes in the right subthalamic nucleus (STN). After two weeks of recovery, electrodes were stimulated for four weeks. Impedance measurements were conducted after each week of stimulation, both in vivo and in vitro. NP-coating resulted in a significant and long-lasting reduction in electrode impedance (p < 0.05) over four weeks of in vitro stimulation. Despite an initial increase in impedance after intracranial implantation, the impedance of the NP-coated electrodes was also reduced during in vivo stimulation over four weeks. NP-coated electrodes had a lower fluctuation of impedance during stimulation compared to uncoated electrodes both in vitro and in vivo (p < 0.05). Laser-generated PtNPs applied to electrodes by pulsed DC-EPD lead to lower and more stable electrode impedance during chronic stimulation, with the potential to enhance the performance of DBS systems during chronic use.

Do Antibiotic-Impregnated Envelopes Prevent Deep Brain Stimulation Implantable Pulse Generator Infections? A Prospective Cohort Study

Introduction: Infection after deep brain stimulation (DBS) implanted pulse generator (IPG) replacement is uncommon but when it occurs can cause significant clinical morbidity, often resulting in partial or complete DBS system removal. An antibiotic absorbable envelope developed for cardiac implantable electronic devices (IEDs), which releases minocycline and rifampicin for a minimum of 7 days, was shown in the WRAP-IT study to reduce cardiac IED infections for high-risk cardiac patients. We aimed to assess whether placing an IPG in the same antibiotic envelope at the time of IPG replacement reduced the IPG infection rate. Methods: Following institutional ethics approval (UnitingCare HREC), patients scheduled for IPG change due to impending battery depletion were prospectively randomised to receive IPG replacement with or without an antibiotic envelope. Patients with a past history of DBS system infection were excluded. Patients underwent surgery with standard aseptic neurosurgical technique [J Neurol Sci. 2017;383:135–41]. Subsequent infection requiring antibiotic therapy and/or IPG removal or revision was recorded. Results: A total of 427 consecutive patients were randomised from 2018 to 2021 and followed for a minimum of 12 months. No patients were lost to follow-up. At the time of IPG replacement, 200 patients received antibiotic envelope (54 female, 146 male, mean age 72 years), and 227 did not (43 female, 184 male, mean age 71 years). The two groups were homogenous for risk factors of infection. The IPG replacement infection rate was 2.1% (9/427). There were six infections, which required antibiotic therapy and/or IPG removal, in the antibiotic envelope group (6/200) and three in the non-envelope group (3/227) (p = 0.66). Conclusion: This prospective randomised study did not find that an antibiotic envelope reduced the IPG infection rate in our 427 patients undergoing routine DBS IPG replacement. Further research to reduce IPG revisions and infections in a cost-effective manner is required.

Safety and feasibility clinical trial of nucleus accumbens deep brain stimulation for treatment-refractory opioid use disorder.

There were more than 107,000 drug overdose deaths in the US in 2021, the most ever recorded. Despite advances in behavioral and pharmacological treatments, over 50% of those receiving treatment for opioid use disorder (OUD) experience drug use recurrence (relapse). Given the prevalence of OUD and other substance use disorders (SUDs), the high rate of drug use recurrence, and the number of drug overdose deaths, novel treatment strategies are desperately needed. The objective of this study was to evaluate the safety and feasibility of deep brain stimulation (DBS) targeting the nucleus accumbens (NAc)/ventral capsule (VC) and potential impact on outcomes in individuals with treatment-refractory OUD. A prospective, open-label, single-arm study was conducted among participants with longstanding treatment-refractory OUD (along with other co-occurring SUDs) who underwent DBS in the NAc/VC. The primary study endpoint was safety; secondary/exploratory outcomes included opioid and other substance use, substance craving, and emotional symptoms throughout follow-up and 18FDG-PET neuroimaging. Four male participants were enrolled and all tolerated DBS surgery well with no serious adverse events (AEs) and no device- or stimulation-related AEs. Two participants sustained complete substance abstinence for > 1150 and > 520 days, respectively, with significant post-DBS reductions in substance craving, anxiety, and depression. One participant experienced post-DBS drug use recurrences with reduced frequency and severity. The DBS system was explanted in one participant due to noncompliance with treatment requirements and the study protocol. 18FDG-PET neuroimaging revealed increased glucose metabolism in the frontal regions for the participants with sustained abstinence only. DBS of the NAc/VC was safe, feasible, and can potentially reduce substance use, craving, and emotional symptoms in those with treatment-refractory OUD. A randomized, sham-controlled trial in a larger cohort of patients is being initiated.

Structural and microstructural predictors of cognitive decline in deep brain stimulation of subthalamic nucleus in Parkinson’s disease

Background and objectivesThe intricate relationship between deep brain stimulation (DBS) in Parkinson’s disease (PD) and cognitive impairment has lately garnered substantial attention. The presented study evaluated pre-DBS structural and microstructural cerebral patterns as possible predictors of future cognitive decline in PD DBS patients. MethodsPre-DBS MRI data in 72 PD patients were combined with neuropsychological examinations and follow-up for an average of 2.3 years after DBS implantation procedure using a screening cognitive test validated for diagnosis of mild cognitive impairment in PD in a Czech population – Dementia Rating Scale 2. ResultsPD patients who would exhibit post-DBS cognitive decline were found to have, already at the pre-DBS stage, significantly lower cortical thickness and lower microstructural complexity than cognitively stable PD patients. Differences in the regions directly related to cognition as bilateral parietal, insular and cingulate cortices, but also occipital and sensorimotor cortex were detected. Furthermore, hippocampi, putamina, cerebellum and upper brainstem were implicated as well, all despite the absence of pre-DBS differences in cognitive performance and in the position of DBS leads or stimulation parameters between the two groups. ConclusionsOur findings indicate that the cognitive decline in the presented PD cohort was not attributable primarily to DBS of the subthalamic nucleus but was associated with a clinically silent structural and microstructural predisposition to future cognitive deterioration present already before the DBS system implantation.

A workflow for predicting radiofrequency-induced heating around bilateral deep brain stimulation electrodes in MRI.

Heating around deep brain stimulation (DBS) in magnetic resonance imaging (MRI) occurs when the time-varying electromagnetic (EM) fields induce currents in the electrodes which can generate heat and potentially cause tissue damage. Predicting the heating around the electrode contacts is important to ensure the safety of patients with DBS implants undergoing an MRI scan. We previously proposed a workflow to predict heating around DBS contacts and introduced a parameter, equivalent transimpedance, that is independent of electrode trajectories, termination, and radiofrequency (RF) excitations. The workflow performance was validated in a unilateral DBS system. To predict RF heating around the contacts of bilateral (DBS) electrodes during an MRI scan in an anthropomorphic head phantom. Bilateral electrodes were fixed in a skull phantom filled with hydroxyethyl cellulose (HEC) gel. The electrode shafts were suspended extracranially, in a head and torso phantom filled with the same gel material. The current induced on the electrode shaft was experimentally measured using an MR-based technique 3cm above the tip. A transimpedance value determined in a previous offline calibration was used to scale the shaft current and calculate the contact voltage. The voltage was assigned as a boundary condition on the electrical contacts of the electrode in a quasi-static (EM) simulation. The resulting specific absorption rate (SAR) distribution became the input for a transient thermal simulation and was used to predict the heating around the contacts. RF heating experiments were performed for eight different lead trajectories using circularly polarized (CP) excitation and two linear excitations for one trajectory. The measured temperatures for all experiments were compared with the simulated temperatures and the root-mean-squared errors (RMSE) were calculated. The RF heating around the contacts of both bilateral electrodes was predicted with ≤ 0.29°C of RMSE for 20 heating scenarios. The workflow successfully predicted the heating for different bilateral DBS trajectories and excitation patterns in an anthropomorphic head phantom.

Early brain imaging changes and its influence on electrode impedance after implantation of 3.0 T MRI-compatible deep brain stimulation system in Parkinson's disease subthalamic nucleus

Objective: To analyze the imaging changes of in the early period after subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson's disease (PD) and its impact on electrode impedance by the application of 3.0T MRI-compatible devices. Methods: A retrospective analysis was performed for the data of 43 PD patients who underwent 3.0T MRI-compatible STN-DBS surgery from October 2022 to April 2023 at the First Affiliated Hospital of USTC(Anhui Provincial Hospital), including 27 males and 16 females, aged 43-68 (56±5) years. All patients underwent postoperative 3.0T MRI, CT scans,and impedance measurements 1 week postoperatively.Fifteen patients underwent 3.0T MRI and impedance measurements 1 month postoperatively. The differences in impedance of electrode contacts before and after the 3.0T MRI scans were compared. The occurrence of peri-lead cerebral edema (PLE) in patients was analyzed, as well as the differences in PLE detection rates between the two imaging methods, and the differences in the incidence and volume of PLE at different microelectrode recordings, the occurrence and detection of postoperative PLE, and different microelectrode recording (MER) times and different time nodes were compared. The correlation between electrode impedance and the volume of edema around the nucleus was analyzed. Results: All 43 patients successfully underwent surgery, with a total of 86 electrodes implanted. There was no significant difference in electrode impedance values before and after the 3.0T MRI examinations at 1 week and 1 month postoperatively. The PLE detection rate with 3.0T MRI was 95.12%(39/43), which is significantly higher than that of CT imaging 17.07% (7/43)(χ2=50.705, P<0.001). One week after surgery, the incidence and volume of PLE were higher in the multiple MER group compared with the single MER group, but the difference was not statistically significant. The volume of PLE [M(Q1, Q3) 0 (0, 1.211) cm3] at 1 month was significantly smaller than that at 1 week [0.243 (0, 2.914) cm3] (Z=-3.408, P=0.001). The impedance of electrode contacts within 1 month postoperatively showed a trend of initial decrease followed by an increase, which was negatively correlated with SE volume(r=-0.317, P=0.014). Conclusions: The application of 3.0T MRI-compatible DBS devices in the surgical treatment of PD patients improves the accuracy of early postoperative imaging assessment. The electrode impedance is more stable as the edema around the nucleus subsided at 1 month after surgery, which is suitable for the first program control.

Rescuing Infected Deep Brain Stimulation Therapies in Severely Affected Patients.

(1) Background: Infections in deep brain stimulation (DBS) hardware, while an undesired complication of DBS surgeries, can be effectively addressed. Minor infections are typically treated with wound revision and IV antibiotics. However, when visible hardware infection occurs, most centers opt for complete removal, leaving the patient in a preoperative state and necessitating post-removal care. To avoid the need for such care, a novel technique was developed. (2) Methods: The electrodes are placed at the exact same spot and then led to the contralateral side. new extensions and a new generator contralateral to the infection as well. Subsequently, the infected system is removed. This case series includes six patients. (3) Results: The average duration of DBS system implantation before the second surgery was 272 days. Only one system had to be removed after 18 months due to reoccurring infection; the others remained unaffected. Laboratory alterations and pathogens were identified in only half of the patients. (4) Conclusions: The described surgical technique proves to be safe, well tolerated, and serves as a viable alternative to complete system removal. Importantly, it effectively prevents the need of post-removal care for patients.

Parkinsonian rest tremor can be distinguished from voluntary hand movements based on subthalamic and cortical activity

ObjectiveTo distinguish Parkinsonian rest tremor and different voluntary hand movements by analyzing brain activity. MethodsWe re-analyzed magnetoencephalography and local field potential recordings from the subthalamic nucleus of six patients with Parkinson’s disease. Data were obtained after withdrawal from dopaminergic medication (Med Off) and after administration of levodopa (Med On). Using gradient-boosted tree learning, we classified epochs as tremor, fist-clenching, forearm extension or tremor-free rest. ResultsSubthalamic activity alone was insufficient for distinguishing the four different motor states (balanced accuracy mean: 38%, std: 7%). The combination of cortical and subthalamic features, in contrast, allowed for a much more accurate classification (balanced accuracy mean: 75%, std: 17%). Adding a single cortical area improved balanced accuracy by 17% on average, as compared to classification based on subthalamic activity alone. In most patients, the most informative cortical areas were sensorimotor cortical regions. Decoding performance was similar in Med On and Med Off. ConclusionsElectrophysiological recordings allow for distinguishing several motor states, provided that cortical signals are monitored in addition to subthalamic activity. SignificanceBy combining cortical recordings, subcortical recordings and machine learning, adaptive deep brain stimulation systems might be able to detect tremor specifically and to respond adequately to several motor states.

Liquid Crystal Polymer-Based Miniaturized Fully Implantable Deep Brain Stimulator.

A significant challenge in improving the deep brain stimulation (DBS) system is the miniaturization of the device, aiming to integrate both the stimulator and the electrode into a compact unit with a wireless charging capability to reduce invasiveness. We present a miniaturized, fully implantable, and battery-free DBS system designed for rats, using a liquid crystal polymer (LCP), a biocompatible and long-term reliable material. The system integrates the simulator circuit, the receiver coil, and a 20 mm long depth-type microelectrode array in a dome-shaped LCP package that is 13 mm in diameter and 5 mm in height. Wireless powering and control via an inductive link enable device miniaturization, allowing for full implantation and, thus, the free behavior of untethered animals. The eight-channel stimulation electrode array was microfabricated on an LCP substrate to form a multilayered system substrate, which was monolithically encapsulated by a domed LCP lid using a specialized spot-welding process. The device functionality was validated via an in vivo animal experiment using a neuropathic pain model in rats. This experiment demonstrated an increase in the mechanical withdrawal threshold of the rats with microelectrical stimulation delivered using the fully implanted device, highlighting the effectiveness of the system.

Local Field Potentials Predict Motor Performance in Deep Brain Stimulation for Parkinson's Disease.

Deep brain stimulation (DBS) is an effective treatment option for patients with Parkinson's disease (PD). However, clinical programming remains challenging with segmented electrodes. Using novel sensing-enabled neurostimulators, we investigated local field potentials (LFPs) and their modulation by DBS to assess whether electrophysiological biomarkers may facilitate clinical programming in chronically implanted patients. Sixteen patients (31 hemispheres) with PD implanted with segmented electrodes in the subthalamic nucleus and a sensing-enabled neurostimulator were included in this study. Recordings were conducted 3 months after DBS surgery following overnight withdrawal of dopaminergic medication. LFPs were acquired while stimulation was turned OFF and during a monopolar review of both directional and ring contacts. Directional beta power and stimulation-induced beta power suppression were computed. Motor performance, as assessed by a pronation-supination task, clinical programming and electrode placement were correlated to directional beta power and stimulation-induced beta power suppression. Better motor performance was associated with stronger beta power suppression at higher stimulation amplitudes. Across directional contacts, differences in directional beta power and the extent of stimulation-induced beta power suppression predicted motor performance. However, within individual hemispheres, beta power suppression was superior to directional beta power in selecting the contact with the best motor performance. Contacts clinically activated for chronic stimulation were associated with stronger beta power suppression than non-activated contacts. Our results suggest that stimulation-induced β power suppression is superior to directional β power in selecting the clinically most effective contact. In sum, electrophysiological biomarkers may guide programming of directional DBS systems in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Investigation of a Deep Brain Stimulator (DBS) System.

A deep brain stimulator (DBS) device is a surgically implanted system that delivers electrical impulses to specific targets in the brain to treat abnormal movement disorders. A DBS is like a cardiac pacemaker, but instead of sending electrical signals to the heart, it sends them to the brain instead. When DBS leads and extension wires are exposed in the biological environment, this can adversely affect impedance and battery life, resulting in poor clinical outcomes. A posthumously extracted DBS device was evaluated using visual inspection and optical microscopy as well as electrical and mechanical tests to quantify the damage leading to its impairment. The implantable pulse generator (IPG) leads, a component of the DBS, contained cracks, delamination, exfoliations, and breakage. Some aspects of in vivo damage were observed in localized areas discussed in this paper. The duration of the time in months that the DBS was in vivo was estimated based on multiple regression analyses of mechanical property testing from prior research of pacemaker extensions. The test results of three DBS extensions, when applied to the regressions, were used to estimate the in vivo duration in months. This estimation approach may provide insight into how long the leads can function effectively before experiencing mechanical failure. Measurements of the extension coils demonstrated distortion and stretching, demonstrating the changes that may occur in vivo. These changes can alter the impedance and potentially reduce the effectiveness of the clinical treatment provided by the DBS system. Ultimately, as both DBSs and pacemakers use the same insulation and lead materials, the focus of this paper is to develop a proof of concept demonstrating that the mechanical properties measured from pacemaker extensions and leads extracted posthumously of known duration, measured in months while in vivo, can be used to predict the duration of DBS leads of unknown lifespan. The goal is to explore the validity of the proposed model using multiple regression of mechanical properties.

Anthropology of Deep Brain Stimulation; the 30th Anniversary of STN DBS in 2023.

The year 2023 marks the 30th anniversary of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD). This procedure prompted a universal interest in DBS for various brain disorders and resulted in a unique expansion of clinical and scientific collaboration between many disciplines, with impact on many aspects of society. To study the anthropology of DBS, that is, its ethno-geographic origins, its evolution, its impact on clinicians and scientists, and its influence on society at large. The authors scrutinized the geo-ethnic origins of the pioneers of modern DBS, and they evaluated, based on the literature and on a long-term praxis, the development of DBS and its impact on clinicians, on healthcare, and on society. Scientists and clinicians from various geo-ethnic origins pioneered modern DBS, leading to worldwide spread of this procedure and to the establishment of large multidisciplinary teams in many centers. Neurologists became actively involved in surgery and took on new laborious tasks of programming ever more complicated DBS systems. Publications sky-rocketed and the global spread of DBS impacted positively on several aspects of society, including healthcare, awareness of neurological diseases, interdisciplinary relations, conferences, patient organizations, unemployment, industry, etc. STN DBS has boosted the field of deep brain electrotherapy for many neurological and psychiatric illnesses, and DBS has generated a global benefit on many aspects of society, well beyond its clinical benefits on symptoms of diseases. With the ever-increasing indications for DBS, more positive global impact is expected.