Deep Brain Stimulation Electrodes Research Articles

Nonlinear effects at the electrode-tissue interface of deep brain stimulation electrodes.

Objective.The electrode-tissue interface provides the critical path for charge transfer in neurostimulation therapies and exhibits well-established nonlinear properties at high applied currents or voltages. These nonlinear properties may influence the efficacy and safety of applied stimulation but are typically neglected in computational models. In this study, nonlinear behavior of the electrode-tissue interface impedance was incorporated in a computational model of deep brain stimulation (DBS) to simulate the impact on neural activation and safety considerations.Approach.Nonlinear electrode-tissue interface properties were incorporated in a finite element model of DBS electrodesin vitroandin vivo,in the rat subthalamic nucleus, using an iterative approach. The transition point from linear to nonlinear behavior was determined for voltage and current-controlled stimulation. Predicted levels of neural activation during DBS were examined and the region of linear operation of the electrode was compared with the Shannon safety limit.Main results.A clear transition of the electrode-tissue interface impedance to nonlinear behavior was observed for both current and voltage-controlled stimulation. The transition occurred at lower values of activation overpotential for simulatedin vivothanin vitroconditions (91 mV and 165 mV respectively for current-controlled stimulation; 110 mV and 275 mV for voltage-controlled stimulation), corresponding to an applied current of 30μA and 45μA, or voltage of 330 mV at 1 kHz. The onset of nonlinearity occurred at lower values of the overpotential as frequency was increased. Incorporation of nonlinear properties resulted in activation of a higher proportion of neurons under voltage-controlled stimulation. Under current-controlled stimulation, the predicted transition to nonlinear behavior and Faradaic charge transfer at stimulation amplitudes of 30μA, corresponds to a charge density of 2.29μC cm-2and charge of 1.8 nC, well-below the Shannon safety limit.Significance.The results indicate that DBS electrodes may operate within the nonlinear region at clinically relevant stimulation amplitudes. This affects the extent of neural activation under voltage-controlled stimulation and the transition to Faradaic charge transfer for both voltage- and current-controlled stimulation with important implications for targeting of neural populations and the design of safe stimulation protocols.

Directional deep brain stimulation in the management of Parkinson's disease: efficacy and constraints-an analytical appraisal.

Deep brain stimulation (DBS) is a widely employed treatment for Parkinson's disease. However, conventional DBS utilizing ring-shaped leads can often result in undesirable side effects by stimulating nearby brain structures, thus limiting its effectiveness. To address this issue, a novel DBS electrode was developed to allow for directional stimulation, avoiding neighboring structures. This literature review aims to analyze the disparities between conventional and directional DBS and discuss the benefits and limitations associated with this innovative electrode design, focusing on the stimulation-induced side effects it can or cannot mitigate. A comprehensive search was conducted in MEDLINE/PubMed, ScienceDirect, and EBSCO databases using the Boolean search criteria: "Deep brain stimulation" AND "Parkinson" AND "Directional." Following the application of inclusion and exclusion criteria, the selected articles were downloaded for full-text reading. Subsequently, the results were organized and analyzed to compose this article. Numerous studies have demonstrated that directional DBS effectively reduces side effects associated with brain stimulation, prevents the stimulation of non-targeted structures, and expands the therapeutic window, among other advantages. However, it has been observed that directional DBS may be more challenging to program and requires higher energy consumption. Furthermore, there is a lack of standardization among different manufacturers of directional DBS electrodes. Various stimulation-induced side effects, including dysarthria, dyskinesia, paresthesias, and symptoms of pyramidal tract activation, have been shown to be mitigated with the use of directional DBS. Moreover, directional electrodes offer a wider therapeutic window and a reduced incidence of undesired effects, requiring the same or lower minimum current for symptom relief compared to conventional DBS. The utilization of directional leads in DBS offers numerous advantages over conventional electrodes without significant drawbacks for patients undergoing directional DBS therapy.

Increased electrode impedance as an indicator for early detection of deep brain stimulation (DBS) hardware Infection: Clinical experience and in vitro study

BackgroundWhen deep brain stimulation (DBS) infections are identified, they are often too advanced to treat without complete hardware removal. New objective markers to promptly identify DBS infections are needed. We present a patient with GPi (globus pallidus interna) DBS for dystonia, where the electrode impedance unexpectedly increased 3-months post-operatively, followed by serologic and hematologic markers of inflammation at 6-months, prompting explantation surgery. We recreated these conditions in a laboratory environment to analyze the pattern of changing of electrical impedance across the contacts of a DBS lead following Staphylococcus biofilm formation. MethodsA stainless-steel culture chamber containing 1 % brain heart infusion agar was used. A DBS electrode was dipped in peptone water containing a strain of S. aureus and subsequently introduced into the chamber. The apparatus was incubated at 37 °C for 6 days. Impedance was measured at 24hr intervals. A control experiment without S. Aureus inoculation was used to determine changes in impedance over a period of 6-days. ResultsThe mean monopolar impedance on day-1 was 751.8 ± 23.8 Ω and on day-3 was 1004.8 ± 68.7 Ω, a 33.7 % rise (p = 0.007). A faint biofilm formation could be seen around the DBS lead by day-2 and florid growth by day-3. After addition of the linezolid solution, a 15.9 % decrease in monopolar impedance was observed from day 3–6 (p = 0.003). ConclusionThis study gives insight into impedance trends following a hardware infection in DBS. Increased impedance outside expected norms may be valuable for early prediction of infection. Furthermore, timely management using antibiotics might reduce the frequency of infection-related explant surgeries.

Single-center experience of utilization and clinical efficacy of segmented leads for subthalamic deep brain stimulation in Parkinson’s disease

BackgroundSegmented electrodes for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson’s disease (PD) enable directional current steering leading to expanded programming options. ObjectiveThis retrospective study covering a longitudinal period of up to 7 years compares the efficacy of segmented and non-segmented leads in motor symptom alleviation and reduction of dopaminergic medication in PD patients treated in a specialized center and assesses the long-term use of directional steering in clinical routine. MethodsDemographic data and clinical scores before surgery and at 12-month follow-up (12MFU) as well as stimulation parameters at 12MFU and last follow-up (LFU) were assessed in all patients implanted with segmented leads between 01/2016 and 12/2019 and non-segmented leads in a corresponding time-period. Patients were classified as very good (>60 %), good (30–60 %) and poor (<30 %) responders according to DBS-induced motor improvement. ResultsClinical data at 12MFU was available for 61/96 patients with segmented (SEG) and 42/53 with non-segmented leads (N-SEG). Mean DBS-induced motor improvement and reduction of medication at 12MFU did not differ significantly between SEG and N-SEG groups or in a subgroup analysis of steering modes. There was a lower proportion of poor responders in the SEG compared with the N-SEG group (23% vs. 31%), though not statistically significant. At LFU, the percentage of patients set at directional steering increased from 54% to 70%. ConclusionEfficacy in reduction of motor symptoms and medication does not differ between electrode types for STN-DBS at 12 months follow-up. The use of directional steering increases over time and may account for a lower proportion of poor responders.

Directional electrodes in deep brain stimulation: Results of a survey by the European Association of Neurosurgical Societies (EANS)

IntroductionDirectional Leads (dLeads) represent a new technical tool in Deep Brain Stimulation (DBS), and a rapidly growing population of patients receive dLeads. Research questionThe European Association of Neurosurgical Societies(EANS) functional neurosurgery Task Force on dLeads conducted a survey of DBS specialists in Europe to evaluate their use, applications, advantages, and disadvantages. Material and methodsEANS functional neurosurgery and European Society for Stereotactic and Functional Neurosurgery (ESSFN) members were asked to complete an online survey with 50 multiple-choice and open questions on their use of dLeads in clinical practice. ResultsForty-nine respondents from 16 countries participated in the survey (n = 38 neurosurgeons, n = 8 neurologists, n = 3 DBS nurses). Five had not used dLeads. All users reported that dLeads provided an advantage (n = 23 minor, n = 21 major). Most surgeons (n = 35) stated that trajectory planning does not differ when implanting dLeads or conventional leads. Most respondents selected dLeads for the ability to optimize stimulation parameters (n = 41). However, the majority (n = 24), regarded time-consuming programming as the main disadvantage of this technology. Innovations that were highly valued by most participants included full 3T MRI compatibility, remote programming, and closed loop technology. Discussion and conclusionDirectional leads are widely used by European DBS specialists. Despite challenges with programming time, users report that dLeads have had a positive impact and maintain an optimistic view of future technological advances.

A Review of Motor Brain-Computer Interfaces Using Intracranial Electroencephalography Based on Surface Electrodes and Depth Electrodes.

Brain-computer interfaces (BCIs) provide a communication interface between the brain and external devices and have the potential to restore communication and control in patients with neurological injury or disease. For the invasive BCIs, most studies recruited participants from hospitals requiring invasive device implantation. Three widely used clinical invasive devices that have the potential for BCIs applications include surface electrodes used in electrocorticography (ECoG) and depth electrodes used in Stereo-electroencephalography (SEEG) and deep brain stimulation (DBS). This review focused on BCIs research using surface (ECoG) and depth electrodes (including SEEG, and DBS electrodes) for movement decoding on human subjects. Unlike previous reviews, the findings presented here are from the perspective of the decoding target or task. In detail, five tasks will be considered, consisting of the kinematic decoding, kinetic decoding,identification of body parts, dexterous hand decoding, and motion intention decoding. The typical studies are surveyed and analyzed. The reviewed literature demonstrated a distributed motor-related network that spanned multiple brain regions. Comparison between surface and depth studies demonstrated that richer information can be obtained using surface electrodes. With regard to the decoding algorithms, deep learning exhibited superior performance using raw signals than traditional machine learning algorithms. Despite the promising achievement made by the open-loop BCIs, closed-loop BCIs with sensory feedback are still in their early stage, and the chronic implantation of both ECoG surface and depth electrodes has not been thoroughly evaluated.

Incidence of complications associated with deep brain stimulation surgery in patients with Parkinson's disease: An 8-year retrospective study.

Various complications occur in patients undergoing deep brain stimulation (DBS) surgery. The objective of this study was to determine the incidence of complications in patients with Parkinson's disease who underwent DBS surgery and identify the risk factors, especially anesthetic factors. A retrospective cohort study was performed between May 2015 and December 2022. Based on a review of medical charts, patients aged 18 years or older who underwent DBS surgery at a tertiary neurological center in Thailand were recruited. Univariate analysis using the Chi-square test or Fisher's exact test was performed to compare patients with and without complications. Multivariate logistic regression analysis was performed to identify the predictive factors for complications. The study included 46 patients. The most common complication during DBS electrode placement was hypertension (30/46, 65.2%), and 19 patients (41.3%) who developed hypertension did not receive antihypertensive treatment. The most common complication during battery placement was clinical hypotension (14/46, 30.4%). The most common postoperative complication was delirium (6/46, 13.0%). In the multivariate analysis, no significant independent risk factors for overall complications after DBS surgery were identified. Hypertension during DBS electrode insertion was the most common perioperative complication. Hemodynamic instability is preventable and manageable, and vigilant and prompt treatment should be provided during DBS surgery.

Directionally non-rotating electric field therapy delivered through implanted electrodes as a glioblastoma treatment platform: A proof-of-principle study.

While directionally rotating tumor-treating fields (TTF) therapy has garnered considerable clinical interest in recent years, there has been comparatively less focus on directionally non-rotating electric field therapy (dnEFT). We explored dnEFT generated through customized electrodes as a glioblastoma therapy in in vitro and in vivo preclinical models. The effects of dnEFT on tumor apoptosis and microglia/macrophages in the tumor microenvironment were tested using flow-cytometric and qPCR assays. In vitro, dnEFT generated using a clinical-grade spinal cord stimulator showed antineoplastic activity against independent glioblastoma cell lines. In support of the results obtained using the clinical-grade electrode, dnEFT delivered through a customized, 2-electrode array induced glioblastoma apoptosis. To characterize this effect in vivo, a custom-designed 4-electrode array was fabricated such that tumor cells can be implanted into murine cerebrum through a center channel equidistant from the electrodes. After implantation with this array and luciferase-expressing murine GL261 glioblastoma cells, mice were randomized to dnEFT or placebo. Relative to placebo-treated mice, dnEFT reduced tumor growth (measured by bioluminescence) and prolonged survival (median survival gain of 6.5 days). Analysis of brain sections following dnEFT showed a notable increase in the accumulation of peritumoral macrophage/microglia with increased expression of M1 genes (IFNγ, TNFα, and IL-6) and decreased expression of M2 genes (CD206, Arg, and IL-10) relative to placebo-treated tumors. Our results suggest therapeutic potential in glioblastoma for dnEFT delivered through implanted electrodes, supporting the development of a proof-of-principle clinical trial using commercially available deep brain stimulator electrodes.

Parameter-based analysis of clinical efficacy of combined bed nucleus of the stria terminalis-nucleus accumbens deep brain stimulation for treatment-resistant depression.

Treatment-resistant depression (TRD) is a severely disabling psychiatric condition that responds poorly to conventional treatments. Deep brain stimulation (DBS) has been proposed for the treatment of patients with TRD in numerous studies. Several deep brain nuclei are considered as potential targets for TRD-DBS, but their clinical efficacy needs further validation. This study carried out dual-target combined stimulation of the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAc) to investigate the effectiveness of the treatment for TRD patients. An 8-contact DBS electrode was used in the study with a surgical path that crossed the BNST and NAc targets. Stimulation parameters and the corresponding severity of symptoms evaluated by the 17-item Hamilton Depression Rating Scale (HAMD-17) and other scales were obtained at each follow-up. The accuracy of electrode positions, the effect of combined stimulation, and the corresponding stimulation parameters were evaluated. Sweet spot prediction models were used to assess the effective stimulation sites in the treatment. The study included 23 TRD patients undergoing DBS at a single center from March 2021 to May 2023. At the last follow-up (range 4-24 months), 14 patients had responded to the treatment (HAMD-17 score improved ≥ 50%), 7 of whom had achieved clinical remission (HAMD-17 score ≤ 7). Electrode position analysis suggested that the BNST may be more important for the improvement of depressive symptoms than the NAc. Overlapped volumes of volume of tissue activated (VTA) and BNST were significantly correlated with absolute (ρleft = -0.377, p < 0.001; ρright = -0.251, p < 0.001) and percent (ρleft = -0.249, p < 0.001; ρright = -0.098, p = 0.102) changes in HAMD-17 score. The sweet spot model of HAMD-17 improvement also suggested that the VTA overlap with the dorsal side of BNST was associated with the impact on depressive symptoms (t = -4.10, p < 0.05). Combined BNST-NAc stimulation of TRD can effectively improve depressive symptoms, in which the BNST seems to have a dominant therapeutic effect. The results of this study not only help to optimize the DBS programming parameters, but also offer an opportunity to further understand the differences between the two targets. In the future, larger prospective cohorts are needed to verify the results of combined BNST-NAc DBS.

Minimizing hemorrhagic and perioperative complications in deep brain stimulation surgery in a series of 191 patients operated on over 4 years.

Intracranial hemorrhage (ICH) in functional neurosurgery is a relatively rare but serious complication. One of the possible risk factors related to ICH is the number of trajectories made for microelectrode recording (MER). Authors who solely rely on macrostimulation using macroelectrodes argue that the incidence of ICH is much lower while maintaining good clinical efficacy of deep brain stimulation (DBS). The present study aimed to assess the incidence of ICH in DBS procedures by reducing to the minimum the number of brain passes and the diameter of guiding cannulas. For this reason, we used one MER guiding cannula exclusively for track making with subsequent macrostimulation done through the implanted DBS electrode. All DBS procedures performed between January 2018 and January 2022 in the Department of Neurosurgery of the Institute of Psychiatry and Neurology in Warsaw were analyzed for possible ICH and other perioperative complications. The DBS lead was implanted by an MR image-guided and intraprocedural CT-verified approach. No MER was done. During four years 191 patients underwent 267 DBS lead implantations in 252 stereotactic procedures. ICH occurred in 2 patients. Both were symptomatic. Adverse symptoms resolved within a week. Two DBS leads required replacement. There was 1 case of hematoma at the implantable pulse generator (IPG) site and 1 case of pneumothorax due to tunneling of the extension. Our surgical technique has a low incidence of ICH. Symptomatic ICH affected 2 patients. The other perioperative complications mentioned above required repeated surgery or conservative treatment. No patient suffered from permanent deficits.

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.

Subthalamic nucleus neuronal activity entropy in the effective stimulation area in patients with Parkinson’s disease

One of the most successful and promising treatments for Parkinson’s disease today is deep brain stimulation (DBS). Accurate localization of the stimulation area is critical for the outcome of surgical DBS electrode implantation in the subthalamic nucleus (STN). To achieve this, microelectrode recording is used during surgery to precisely locate the STN borders [1], while test stimulations with a macroelectrode are widely employed to enhance DBS electrode placement accuracy. Thus, through testing multiple trajectories, the most clinically effective one can be selected. However, a comprehensive and reliable description of the specific single neuron activity associated with successful DBS electrode implantation is currently lacking. A study was conducted using microelectrode recordings (MER) of single neuron activity in the STN of 21 Parkinson’s disease patients (UPDRS III off/on=46.9/12.8) to identify the neuronal activity features associated with the most favorable clinical outcome of test stimulation. A comparative analysis of 29 activity parameters, such as firing rate, oscillatory activity intensity in different frequency ranges (Oscores), coefficient of variation, burst, pause index, among others [2], was conducted for 618 identified neurons. In addition, the approach of computing the entropy of the change in interspike intervals (ISI) of the pulse sequence [3] and the process of identifying patterns of neural activity using hierarchical clustering [4] were implemented. A comparative analysis of single neuron activity indicated notable (p 0.05) variations between disregarded and selected paths for the ultimate implantation of DBS electrode, solely relying on entropy parameters. Trajectories that delivered optimal test stimulation outcomes demonstrated reduced entropy of interspike intervals. Only the patterns of neuronal activity characterized by extended periods of steady firing and brief pauses, referred to as tonic and pause activity, respectively, were found to contribute to the difference in entropy between trajectories. In contrast, there were no statistically significant differences detected in entropy values associated with neurons demonstrating burst activity. Furthermore, we observed a positive and significant correlation between entropy values and the degree of improvement in disease presentation before and after administration of medication. A comparative analysis was conducted on the activity of single neurons along different trajectories with varied test stimulation responses. The results showed a weak effectiveness of linear parameters in determining the optimal electrode insertion path for improved clinical outcomes. However, the use of non-linear activity parameters, specifically entropy, in single neurons effectively differentiated trajectories with significant versus absent/insignificant test stimulation results. Furthermore, the significance of entropy in establishing the basal ganglia functions and describing information transfer processes in movement control is emphasized by interpreting this parameter as a measure of uncertainty or unpredictability of the information system in relation to the findings of other studies [5].

Neural activity of the subthalamic nucleus during voluntary movements in patients with Parkinson’s disease

Microelectrode recording (MER) during electrode implantation for deep brain stimulation (DBS) can determine the boundaries of the subthalamic nucleus (STN), and track neural activity during rest and voluntary movement in Parkinson’s disease (PD) patients. However, the functional role of STN in motor control remains unclear, despite its effectiveness in stimulation. Single unit activity of STN was recorded in 16 patients with PD during implantation of deep brain stimulation electrodes. Electromyograms of forearm muscles and a phonogram featuring verbal commands were simultaneously recorded with MER. The patients were instructed to perform motor tests involving clenching their hand into a fist. Out of the 560 neurons studied, 93 (16.6%) responded to motor tasks. The registered neurons were classified into three patterns using the hierarchical clustering method of histograms of interspike interval density — namely, tonic, burst, and pause patterns. Sensitive neurons were classified according to their responses, with activation (76.9%) and inhibition (23.1%) being the two identified types. In 90% of cases, neuron activation preceded movement. Of the responses, 53.8% were classified as tonic and 46.2% as phasic. Two thirds of inhibitory responses were advanced, occurring 0.2–0.3 seconds before movement onset. One third of neurons were activated after movement initiation with a delay of 0.05–0.2 seconds. 83.3% of the inhibitory neurons responded tonically, while the remaining 16.7% responded phasically. Notably, all phasic reactions occurred before the onset of movement. A comparison of the parameters of sensitive and non-sensitive neurons revealed several differences. The findings suggest a potential physiological distinction between the two neuron types. All three patterns of activity were present in both types of neurons, but sensitive neurons exhibited a wider representation of pause neurons (57.9% vs. 49.5%). Additionally, burst and pause neurons responded to movements that featured significantly lower variance of multiple activity parameters, such as firing rate, burst index, mean burst length, and oscillation scores in the 8–12 and 12–20 Hz range. The distribution of sensitive neurons along the electrode trajectory through the subthalamic nucleus was analyzed. Sensitive neurons were located significantly more dorsally compared to non-sensitive neurons, and no sensitive pause cells were observed in the ventral half of the STN. Based on our findings, it is presumed that the pause pattern plays a critical role in both motor control and its related disorders in Parkinson’s disease. A diverse range of neuronal responses suggests a high degree of heterogeneity among STN neurons implicated in motor control. The presence of both delayed and advanced neural responses suggests that STN involvement in motor control encompasses both the preparation and initiation of movement, as well as the regulation of ongoing movements via afferent feedback. The range of neural responses aligns with the dynamic model of basal ganglia, which suggests that STN can perform distinct functional roles during different stages of movement, including initiation, control, and completion.

Frameless and fiducial-less, O-arm assisted navigation for deep brain stimulation placement using the Nexframe®. A technical note

O-arm® assisted navigation for placement of deep brain stimulation (DBS) electrodes using the Nexframe® device is a relatively new method that has been in use at many centers in the United States. However, no reports have described this operative technique in detail. In this technical report we describe the surgical nuances of this method in a stepwise approach. We also review and discuss the accuracy of this method in comparison to other methods of placing DBS electrodes.

Review of the targeting accuracy of frameless and frame-based robot-assisted deep brain stimulation electrode implantation in pediatric patients using the Neurolocate module.

The Neurolocate module is a 3D frameless patient registration module that is designed for use with the Neuromate stereotactic robot. Long-term electrical stimulation of the globus pallidus internus (GPi) and subthalamic nucleus (STN) via deep brain electrode implantation is particularly successful in a select group of movement disorders in pediatric patients. This study aimed to review the targeting accuracy of deep brain stimulation (DBS) electrode implantation in a single center, comparing standard frame-based techniques to the frameless Neurolocate module. Twenty-four pediatric patients underwent implantation of bilateral DBS electrodes under general anesthesia during the period of August 2018-August 2022. All patients underwent robot-assisted stereotactic implantation of DBS electrodes using an intraoperative O-arm 3D scanner to confirm the final electrode position. These coordinates were compared with the planned entry and target, with attention to depth, radial, directional, and absolute errors, in addition to Euclidean distance (ED). The primary outcome evaluated the accuracy and safety of the Neurolocate frameless technology compared with standard frame-based techniques. Of the 24 bilateral DBS electrode implantations performed, 62.5% used Neurolocate technology: 87.5% were delivered to the GPi and the remaining 12.5% to the STN. The mean patient age was 11.0 (range 4-18) years and 70.8% were male. The median absolute errors in x-, y-, and z-axes were 0.35, 0.75, and 0.9 mm, respectively, using the Neurolocate module compared with 0.30, 0.95, and 1.1 mm using the standard frame-based technique. The median ED from the planned target to the actual electrode position with the Neurolocate module was 1.28 mm versus 1.69 mm using standard frame-based techniques. No major perioperative complications occurred. Stereotactic robot-assisted DBS implantation with the frameless Neurolocate module is safe for use in the pediatric population, showing good surgical accuracy and no inferiority to standard frame-based techniques. The Neurolocate module for robotic DBS surgery has the potential to improve surgical targeting accuracy, surgical time, patient comfort, and safety.

Role of the volume conductor on simulations of local field potential recordings from deep brain stimulation electrodes.

Local field potential (LFP) recordings from deep brain stimulation (DBS) electrodes are commonly used in research analyses, and are beginning to be used in clinical practice. Computational models of DBS LFPs provide tools for investigating the biophysics and neural synchronization that underlie LFP signals. However, technical standards for DBS LFP model parameterization remain to be established. Therefore, the goal of this study was to evaluate the role of the volume conductor (VC) model complexity on simulated LFP signals in the subthalamic nucleus (STN). We created a detailed human head VC model that explicitly represented the inhomogeneity and anisotropy associated with 12 different tissue structures. This VC model represented our "gold standard" for technical detail and electrical realism. We then incrementally decreased the complexity of the VC model and quantified the impact on the simulated LFP recordings. Identical STN neural source activity was used when comparing the different VC model variants. Results Ignoring tissue anisotropy reduced the simulated LFP amplitude by ~12%, while eliminating soft tissue heterogeneity had a negligible effect on the recordings. Simplification of the VC model to consist of a single homogenous isotropic tissue medium with a conductivity of 0.215 S/m contributed an additional ~3% to the error. Highly detailed VC models do generate different results than simplified VC models. However, with errors in the range of ~15%, the use of a well-parameterized simple VC model is likely to be acceptable in most contexts for DBS LFP modeling.

SURG-19. RE-PURPOSING DEEP BRAIN STIMULATORS AS ELECTRIC FIELD THERAPY (EFT) AS TREATMENT FOR GLIOBLASTOMA

Abstract INTRODUCTION Though alternating electric field therapy (EFT) for glioblastoma received FDA approval, biophysical modeling suggests that field strength generated by scalp electrodes may not sufficiently extend to deep, subcortical regions. Objective: We explore the anti-tumor activity of electric field (EF) generated by electrode directly implanted into glioblastomas, with the goal of repurposing deep brain stimulators as a therapeutic platform. Method: Laboratory characterization and murine modeling Result: In vitro, activation of leads of a deep brain stimulator induced tumoricidal activity within the region encompassed by the EF. To further characterized this tumoricidal activity, a customized two-electrode array was designed and fabricated to allow study of glioblastoma cells seeded at the center of the EF. Consistent with the observations made using the deep brain stimulator electrode, electric field therapy (EFT) induced both necrosis and apoptosis of glioblastoma cells. To characterize this effect in vivo, a four-electrode array was designed and fabricated such that tumor cells can be implanted through a center channel equidistant the electrodes. Mice were implanted with this array, followed by luciferase labelled murine glioblastomas through the center channel. After tumor engravement, mice were randomized to EFT or placebo. EFT was associated with significant diminishment of tumor growth (measured by bio- bioluminescence) and prolonged survival. Analysis of brain sections following EFT showed a notable increase in peri-tumoral microglia accumulation, suggesting potential of EFT as an immune-modulation platform. CONCLUSION Our results suggest therapeutic potential for repurposing of deep brain stimulator as glioblastoma therapy, with opportunities for therapeutic enhancement through novel electrode design and stimulation parameter modulation.

Combining ultrasound and microelectrode recordings for postoperative localization of subthalamic electrodes in Parkinson’s disease

ObjectiveTo assess transcranial sonography (TCS) as stand-alone tool and in combination with microelectrode recordings (MER) as a method for the postoperative localization of deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN). MethodsIndividual dorsal and ventral boundaries of STN (n = 12) were determined on intraoperative MER. Postoperatively, a standardized TCS protocol was applied to measure medio-lateral, anterior-posterior and rostro-caudal electrode position using visualized reference structures (midline, substantia nigra). TCS and combined TCS-MER data were validated using fusion-imaging and clinical outcome data. ResultsTest-retest reliability of standard TCS measures of electrode position was excellent. Computed tomography and TCS measures of distance between distal electrode contact and midline agreed well (Pearson correlation; r = 0.86; p < 0.001). Comparing our “gold standard” of rostro-caudal electrode localization relative to STN boundaries, i.e. combining MRI-based stereotaxy and MER data, with the combination of TCS and MER data, the measures differed by 0.32 ± 0.87 (range, −1.35 to 1.25) mm. Combined TCS-MER data identified the clinically preferred electrode contacts for STN-DBS with high accuracy (Coheńs kappa, 0.86). ConclusionsCombined TCS-MER data allow for exact localization of STN-DBS electrodes. SignificanceOur method provides a new option for monitoring of STN-DBS electrode location and guidance of DBS programming in Parkinson’s disease.

Seeing Is Believing: Photon Counting Computed Tomography Clearly Images Directional Deep Brain Stimulation Lead Segments and Markers After Implantation

Background and ObjectivesDirectional deep brain stimulation (DBS) electrodes are increasingly used, but conventional computed tomography (CT) is unable to directly image segmented contacts owing to physics-based resolution constraints. Postoperative electrode segment orientation assessment is necessary because of the possibility of significant deviation during or immediately after insertion. Photon-counting detector (PCD) CT is a relatively novel technology that enables high resolution imaging while addressing several limitations intrinsic to CT. We show how PCD CT can enable clear in vivo imaging of DBS electrodes, including segmented contacts and markers for all major lead manufacturers. Materials and MethodsWe describe postoperative imaging and reconstruction protocols we have developed to enable optimal lead visualization. PCD CT images were obtained of directional leads from the three major manufacturers and fused with preoperative 3T magnetic resonance imaging (MRI). Radiation dosimetry also was evaluated and compared with conventional imaging controls. Orientation estimates from directly imaged leads were compared with validated software-based reconstructions (derived from standard CT imaging artifact analysis) to quantify congruence in alignment and directional orientation. ResultsHigh-fidelity images were obtained for 15 patients, clearly indicating the segmented contacts and directional markers both on CT alone and when fused to MRI. Our routine imaging protocol is described. Ionizing radiation doses were significantly lower than with conventional CT. For most leads, the directly imaged lead orientations and depths corresponded closely to those predicted by CT artifact-based reconstructions. However, unlike direct imaging, the software reconstructions were susceptible to 180° error in orientation assessment. ConclusionsHigh-resolution photon-counting CT can very clearly image segmented DBS electrode contacts and directional markers and unambiguously determine lead orientation, with lower radiation than in conventional imaging. This obviates the need for further imaging and may facilitate anatomically tailored directional programming.

Dorsal subthalamic nucleus targeting in deep brain stimulation: microelectrode recording versus 7-Tesla connectivity.

Connectivity-derived 7-Tesla MRI segmentation and intraoperative microelectrode recording can both assist subthalamic nucleus targeting for deep brain stimulation in Parkinson's disease. It remains unclear whether deep brain stimulation electrodes placed in the 7-Tesla MRI segmented subdivision with predominant projections to cortical motor areas (hyperdirect pathway) achieve superior motor improvement and whether microelectrode recording can accurately distinguish the motor subdivision. In 25 patients with Parkinson's disease, deep brain stimulation electrodes were evaluated for being inside or outside the predominantly motor-connected subthalamic nucleus (motor-connected subthalamic nucleus or non-motor-connected subthalamic nucleus, respectively) based on 7-Tesla MRI connectivity segmentation. Hemi-body motor improvement (Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III) and microelectrode recording characteristics of multi- and single-unit activities were compared between groups. Deep brain stimulation electrodes placed in the motor-connected subthalamic nucleus resulted in higher hemi-body motor improvement, compared with electrodes placed in the non-motor-connected subthalamic nucleus (80% versus 52%, P < 0.0001). Multi-unit activity was found slightly higher in the motor-connected subthalamic nucleus versus the non-motor-connected subthalamic nucleus (P < 0.001, receiver operating characteristic 0.63); single-unit activity did not differ between groups. Deep brain stimulation in the connectivity-derived 7-Tesla MRI subthalamic nucleus motor segment produced a superior clinical outcome; however, microelectrode recording did not accurately distinguish this subdivision within the subthalamic nucleus.