Paradoxical Modulation of STN ß-Band Activity with Medication Compared to Deep Brain Stimulation.

BACKGROUND: Excessive subthalamic nucleus (STN) ß-band (13-35 Hz) synchronized oscillations has garnered interest as a biomarker for characterizing disease state and developing adaptive stimulation systems for Parkinson's disease (PD). OBJECTIVES: To report on a patient with abnormal treatment-responsive modulation in the ß-band. METHODS: We examined STN local field potentials from an externalized deep brain stimulation (DBS) lead while assessing PD motor signs in four conditions (OFF, MEDS, DBS, and MEDS+DBS). RESULTS: The patient presented here exhibited a paradoxical increase in ß power following administration of levodopa and pramipexole (MEDS), but an attenuation in ß power during DBS and MEDS+DBS despite clinical improvement of 50% or greater under all three therapeutic conditions. CONCLUSIONS: This case highlights the need for further study on the role of ß oscillations in the pathophysiology of PD and the importance of personalized approaches to the development of ß or other biomarker-based DBS closed loop algorithms. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Reliability of visual review of intracranial electroencephalogram in identifying the seizure onset zone: A systematic review and implications for the accuracy of automated methods.

Visual review of intracranial electroencephalography (iEEG) is often an essential component for defining the zone of resection for epilepsy surgery. Unsupervised approaches using machine and deep learning are being employed to identify seizure onset zones (SOZs). This prompts a more comprehensive understanding of the reliability of visual review as a reference standard. We sought to summarize existing evidence on the reliability of visual review of iEEG in defining the SOZ for patients undergoing surgical workup and understand its implications for algorithm accuracy for SOZ prediction. We performed a systematic literature review on the reliability of determining the SOZ by visual inspection of iEEG in accordance with best practices. Searches included MEDLINE, Embase, Cochrane Library, and Web of Science on May 8, 2022. We included studies with a quantitative reliability assessment within or between observers. Risk of bias assessment was performed with QUADAS-2. A model was developed to estimate the effect of Cohen kappa on the maximum possible accuracy for any algorithm detecting the SOZ. Two thousand three hundred thirty-eight articles were identified and evaluated, of which one met inclusion criteria. This study assessed reliability between two reviewers for 10 patients with temporal lobe epilepsy and found a kappa of .80. These limited data were used to model the maximum accuracy of automated methods. For a hypothetical algorithm that is 100% accurate to the ground truth, the maximum accuracy modeled with a Cohen kappa of .8 ranged from .60 to .85 (F-2). The reliability of reviewing iEEG to localize the SOZ has been evaluated only in a small sample of patients with methodologic limitations. The ability of any algorithm to estimate the SOZ is notably limited by the reliability of iEEG interpretation. We acknowledge practical limitations of rigorous reliability analysis, and we propose design characteristics and study questions to further investigate reliability.

Deep-learning based fully automatic segmentation of the globus pallidus interna and externa using ultra-high 7 Tesla MRI.

Deep brain stimulation (DBS) surgery has been shown to dramatically improve the quality of life for patients with various motor dysfunctions, such as those afflicted with Parkinson's disease (PD), dystonia, and essential tremor (ET), by relieving motor symptoms associated with such pathologies. The success of DBS procedures is directly related to the proper placement of the electrodes, which requires the ability to accurately detect and identify relevant target structures within the subcortical basal ganglia region. In particular, accurate and reliable segmentation of the globus pallidus (GP) interna is of great interest for DBS surgery for PD and dystonia. In this study, we present a deep-learning based neural network, which we term GP-net, for the automatic segmentation of both the external and internal segments of the globus pallidus. High resolution 7 Tesla images from 101 subjects were used in this study; GP-net is trained on a cohort of 58 subjects, containing patients with movement disorders as well as healthy control subjects. GP-net performs 3D inference in a patient-specific manner, alleviating the need for atlas-based segmentation. GP-net was extensively validated, both quantitatively and qualitatively over 43 test subjects including patients with movement disorders and healthy control and is shown to consistently produce improved segmentation results compared with state-of-the-art atlas-based segmentations. We also demonstrate a postoperative lead location assessment with respect to a segmented globus pallidus obtained by GP-net.

High-Frequency Oscillations in the Pallidum: A Pathophysiological Biomarker in Parkinson's Disease?

BACKGROUND: Abnormal oscillatory neural activity in the beta-frequency band (13-35 Hz) is thought to play a role in Parkinson's disease (PD); however, increasing evidence points to alterations in high-frequency ranges (>100 Hz) also having pathophysiological relevance. OBJECTIVES: Studies have found that power in subthalamic nucleus (STN) high-frequency oscillations is increased with dopaminergic medication and during voluntary movements, implicating these brain rhythms in normal basal ganglia function. The objective of this study was to investigate whether similar signaling occurs in the internal globus pallidus (GPi), a nucleus increasingly used as a target for deep brain stimulation (DBS) for PD. METHODS: Spontaneous and movement-related GPi field potentials were recorded from DBS leads in 5 externalized PD patients on and off dopaminergic medication, as well as from 3 rhesus monkeys before and after the induction of parkinsonism with the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. RESULTS: In the parkinsonian condition, we identified a prominent oscillatory peak centered at 200-300 Hz that increased during movement. In patients the magnitude of high-frequency oscillation modulation was negatively correlated with bradykinesia. In monkeys, high-frequency oscillations were mostly absent in the naive condition but emerged after the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. In patients, spontaneous high-frequency oscillations were significantly attenuated on-medication. CONCLUSIONS: Our findings provide evidence in support of the hypothesis that exaggerated, movement-modulated high-frequency oscillations in the GPi are pathophysiological features of PD. These findings suggest that the functional role(s) of high-frequency oscillations may differ between the STN and GPi and motivate additional investigations into their relationship to motor control in normal and diseased states.

Resective epilepsy surgery: assessment of randomized controlled trials.

Epilepsy is the most common form of chronic neurologic disease. Here, we review the available randomized controlled trials (RCTs) that examined the efficacy of resective epilepsy surgery in select patients suffering from medically intractable epilepsy (defined as persistent epilepsy despite two or more antiepileptic drugs [AEDs]). Three RCTs (two adult RCTs and one pediatric RCT) consistently supported the efficacy of resective surgery as treatment for epilepsy with semiology localized to the mesial temporal lobe. In these studies, 58-100% of the patients who underwent resective surgery achieved seizure freedom, in comparison to 0-13% of medically treated patients. In another RCT, the likelihood of seizure freedom after resective surgery was independent of the surgical approach (transSylvian [64%] versus subtemporal [62%]). Two other RCTs demonstrated that hippocampal resection is essential to optimize seizure control. But, no significant gain in seizure control was achieved beyond removing 2.5 cm of the hippocampus. Across RCTs, minor complications (deficit lasting < 3 months) and major complications (deficit > 3 months) ranged 2-5% and 5-11% respectively. However, nonincapacitating superior subquadrantic visual-field defects (not typically considered a minor or major complication) were noted in up to 55% of the surgical cohort. The available RCTs provide compelling support for resective surgery as a treatment for mesial temporal lobe epilepsy and offer insights toward optimal surgical strategy.

Directional deep brain stimulation leads reveal spatially distinct oscillatory activity in the globus pallidus internus of Parkinson's disease patients.

The goal of this study was to characterize the spectral characteristics and spatial topography of local field potential (LFP) activity in the internal segment of the globus pallidus (GPi) in patients with Parkinson's disease utilizing directional (segmented) deep brain stimulation (dDBS) leads. Data were collected from externalized dDBS leads of three patients with idiopathic Parkinson's disease after overnight withdrawal of parkinsonian medication at rest and during a cued reach-to-target task. Oscillatory activity across lead contacts/segments was examined in the context of lead locations and contact orientations determined using co-registered preoperative 7 Tesla (T) MRI and postoperative CT scans. Each of the three patients displayed a unique frequency spectrum of oscillatory activity in the pallidum, with prominent peaks ranging from 5 to 35 Hz, that modulated variably across subjects during volitional movement. Despite subject-specific spectral profiles, a consistent finding across patients was that oscillatory power was strongest and had the largest magnitude of modulation during movement in LFPs recorded from segments facing the postero-lateral "sensorimotor" region of GPi, whereas antero-medially-directed segmented contacts facing the internal capsule and/or anterior GPi, had relatively weaker LFP power and less modulation in the 5 to 35 Hz. In each subject, contact configurations chosen for clinically therapeutic stimulation (following data collection and blinded to physiology recordings), were in concordance with the contact pairs showing the largest amplitude of LFP oscillations in the 5-35 Hz range. Although limited to three subjects, these findings provide support for the hypothesis that the sensorimotor territory of the GPi corresponds to the site of maximal power of oscillatory activity in the 5 to 35 Hz and provides the greatest benefit in motor signs during stimulation in the GPi. Variability in oscillatory activity across patients is likely related to Parkinson's disease phenotype as well as small differences in recording location (i.e. lead location), highlighting the importance of lead location for optimizing stimulation efficacy. These data also provide compelling evidence for the use of LFP activity for the development of predictive stimulation models that may optimize patient benefits while reducing clinic time needed for programming.

Factors Influencing Electrode Position and Bending of the Proximal Lead in Deep Brain Stimulation for Movement Disorders.

BACKGROUND: The introduction of intracranial air (ICA) during deep brain stimulation (DBS) surgery is thought to have a negative influence on targeting and clinical outcomes. OBJECTIVE: To investigate ICA volumes following surgery and other patient-specific factors as potential variables influencing translocation of the DBS electrode and proximal lead bowing. METHODS: High-resolution postoperative computed tomography scans (≤1.0 mm resolution in all directions) within 24 h following DBS surgery and 4-6 weeks of follow-up were acquired. A total of 50 DBS leads in 33 patients were available for analysis. DBS leads included Abbott/St. Jude Medical InfinityTM, Boston Scientific VerciseTM, and Medtronic 3389TM. RESULTS: Both ICA volume and anatomical target were significantly associated with measures of DBS electrode translocation. ICA volume and DBS lead model were found to be significant predictors of proximal lead bowing. Measures of proximal lead bowing and translocation along the electrode trajectory for the Medtronic 3389TM DBS lead were significantly larger than measures for the Abbott/St. Jude Medical InfinityTM and Boston Scientific VerciseTM DBS leads. CONCLUSION: The association between ICA volume and translocation of the DBS electrode is small in magnitude and not clinically relevant for DBS cases within a normal range of postoperative subdural air volumes. Differences in proximal lead bowing observed between DBS leads may reflect hardware engineering subtleties in the construction of DBS lead models.

A simple geometric analysis method for measuring and mitigating RF induced currents on Deep Brain Stimulation leads by multichannel transmission/reception.

The purpose of this work is to present a new method that can be used to estimate and mitigate RF induced currents on Deep Brain Stimulation (DBS) leads. Here, we demonstrate the effect of RF induced current mitigation on both RF heating and image quality for a variety of brain MRI sequences at 3 T. We acquired pre-scan images around a DBS lead (in-situ and ex-vivo) using conventional Gradient Echo Sequence (GRE) accelerated by parallel imaging (i.e GRAPPA) and quantified the magnitude and phase of RF induced current using the relative location of the B1+ null with respect to the lead position. We estimated the RF induced current on a DBS lead implanted in a gel phantom as well as in a cadaver head study for a variety of RF excitation patterns. We also measured the increase in tip temperature using fiber-optic probes for both phantom and cadaver studies. Using the magnitude and phase information of the current induced separately by two transmit channels of the body coil, we calculated an implant friendly (IF) excitation. Using the IF excitation, we acquired T1, T2 weighted Turbo Spin Echo (TSE), T2 weighted SPACE-Dark Fluid, and Ultra Short Echo Time (UTE) sequences around the lead. Our induced current estimation demonstrated linear relationship between the magnitude of the induced current and the square root SAR at the tip of the lead as measured in phantom studies. The "IF excitation pattern" calculated after the pre-scan mitigated RF artifacts and increased the image quality around the lead. In addition, it reduced the tip temperature significantly in both phantom and cadaver studies compared to a conventional quadrature excitation while keeping equivalent overall image quality. We present a relatively fast method that can be used to calculate implant friendly excitation, reducing image artifacts as well as the temperature around the DBS electrodes. When combined with a variety of MR sequences, the proposed method can improve the image quality and patient safety in clinical imaging scenarios.

Individualized tractography-based parcellation of the globus pallidus pars interna using 7T MRI in movement disorder patients prior to DBS surgery.

The success of deep brain stimulation (DBS) surgeries for the treatment of movement disorders relies on the accurate placement of an electrode within the motor portion of subcortical brain targets. However, the high number of electrodes requiring relocation indicates that today's methods do not ensure sufficient accuracy for all patients. Here, with the goal of aiding DBS targeting, we use 7 Tesla (T) MRI data to identify the functional territories and parcellate the globus pallidus pars interna (GPi) into motor, associative and limbic regions in individual subjects. 7 T MRI scans were performed in seventeen patients (prior to DBS surgery) and one healthy control. Tractography-based parcellation of each patient's GPi was performed. The cortex was divided into four masks representing motor, limbic, associative and "other" regions. Given that no direct connections between the GPi and the cortex have been shown to exist, the parcellation was carried out in two steps: 1) The thalamus was parcellated based on the cortical targets, 2) The GPi was parcellated using the thalamus parcels derived from step 1. Reproducibility, via repeated scans of a healthy subject, and validity of the findings, using different anatomical pathways for parcellation, were assessed. Lastly, post-operative imaging data was used to validate and determine the clinical relevance of the parcellation. The organization of the functional territories of the GPi observed in our individual patient population agrees with that previously reported in the literature: the motor territory was located posterolaterally, followed anteriorly by the associative region, and further antero-ventrally by the limbic territory. While this organizational pattern was observed across patients, there was considerable variability among patients. The organization of the functional territories of the GPi was remarkably reproducible in intra-subject scans. Furthermore, the organizational pattern was observed consistently by performing the parcellation of the GPi via the thalamus and via a different pathway, going through the striatum. Finally, the active therapeutic contact of the DBS electrode, identified with a combination of post-operative imaging and post-surgery DBS programming, overlapped with the high-probability "motor" region of the GPi as defined by imaging-based methods. The consistency, validity, and clinical relevance of our findings have the potential for improving DBS targeting, by increasing patient-specific knowledge of subregions of the GPi to be targeted or avoided, at the stage of surgical planning, and later, at the stage when stimulation is adjusted.

Representation of individual forelimb muscles in primary motor cortex.

Stimulus-triggered averaging (StTA) of forelimb muscle electromyographic (EMG) activity was used to investigate individual forelimb muscle representation within the primary motor cortex (M1) of rhesus macaques with the objective of determining the extent of intra-areal somatotopic organization. Two monkeys were trained to perform a reach-to-grasp task requiring multijoint coordination of the forelimb. EMG activity was simultaneously recorded from 24 forelimb muscles including 5 shoulder, 7 elbow, 5 wrist, 5 digit, and 2 intrinsic hand muscles. Microstimulation (15 µA at 15 Hz) was delivered throughout the movement task and individual stimuli were used as triggers for generating StTAs of EMG activity. StTAs were used to map the cortical representations of individual forelimb muscles. As reported previously (Park et al. 2001), cortical maps revealed a central core of distal muscle (wrist, digit, and intrinsic hand) representation surrounded by a horseshoe-shaped proximal (shoulder and elbow) muscle representation. In the present study, we found that shoulder and elbow flexor muscles were predominantly represented in the lateral branch of the horseshoe whereas extensors were predominantly represented in the medial branch. Distal muscles were represented within the core distal forelimb representation and showed extensive overlap. For the first time, we also show maps of inhibitory output from motor cortex, which follow many of the same organizational features as the maps of excitatory output.NEW & NOTEWORTHY While the orderly representation of major body parts along the precentral gyrus has been known for decades, questions have been raised about the possible existence of additional more detailed aspects of somatotopy. In this study, we have investigated this question with respect to muscles of the arm and show consistent features of within-arm (intra-areal) somatotopic organization. For the first time we also show maps of how inhibitory output from motor cortex is organized.

Copper deficiency myelopathy in the setting of advanced degenerative cervical spondylosis.

When presenting conjointly, degenerative cervical spondylosis and copper deficiency myelopathy may be difficult to differentiate providing the potential for mismanagement and unnecessary surgery. We present a case of a 69-year-old female with copper deficiency myelopathy secondary to previous bowel resection in the setting of advanced degenerative cervical spondylotic disease.

Neural signal data collection and analysis of Percept™ PC BrainSense recordings for thalamic stimulation in epilepsy.

Deep brain stimulation (DBS) using Medtronic's Percept™ PC implantable pulse generator is FDA-approved for treating Parkinson's disease (PD), essential tremor, dystonia, obsessive compulsive disorder, and epilepsy. Percept™ PC enables simultaneous recording of neural signals from the same lead used for stimulation. Many Percept™ PC sensing features were built with PD patients in mind, but these features are potentially useful to refine therapies for many different disease processes. When starting our ongoing epilepsy research study, we found it difficult to find detailed descriptions about these features and have compiled information from multiple sources to understand it as a tool, particularly for use in patients other than those with PD. Here we provide a tutorial for scientists and physicians interested in using Percept™ PC's features and provide examples of how neural time series data is often represented and saved. We address characteristics of the recorded signals and discuss Percept™ PC hardware and software capabilities in data pre-processing, signal filtering, and DBS lead performance. We explain the power spectrum of the data and how it is shaped by the filter response of Percept™ PC as well as the aliasing of the stimulation due to digitally sampling the data. We present Percept™ PC's ability to extract biomarkers that may be used to optimize stimulation therapy. We show how differences in lead type affects noise characteristics of the implanted leads from seven epilepsy patients enrolled in our clinical trial. Percept™ PC has sufficient signal-to-noise ratio, sampling capabilities, and stimulus artifact rejection for neural activity recording. Limitations in sampling rate, potential artifacts during stimulation, and shortening of battery life when monitoring neural activity at home were observed. Despite these limitations, Percept™ PC demonstrates potential as a useful tool for recording neural activity in order to optimize stimulation therapies to personalize treatment.

Implantation accuracy of novel polyimide stereotactic electroencephalographic depth electrodes-a human cadaveric study.

Introduction: Stereoelectroencephalography (sEEG) is a minimally invasive procedure that uses depth electrodes stereotactically implanted into brain structures to map the origin and propagation of seizures in epileptic patients. Implantation accuracy of sEEG electrodes plays a critical role in the safety and efficacy of the procedure. This study used human cadaver heads, simulating clinical practice, to evaluate (1) neurosurgeon's ability to implant a new thin-film polyimide sEEG electrode according to the instructions for use (IFU), and (2) implantation accuracy. Methods: Four neurosurgeons (users) implanted 24 sEEG electrodes into two cadaver heads with the aid of the ROSA robotic system. Usability was evaluated using a questionnaire that assessed completion of all procedure steps per IFU and user errors. For implantation accuracy evaluation, planned electrode trajectories were compared with post-implantation trajectories after fusion of pre- and postoperative computer tomography (CT) images. Implantation accuracy was quantified using the Euclidean distance for entry point error (EPE) and target point error (TPE). Results: All sEEG electrodes were successfully placed following the IFU without user errors, and post-implant survey of users showed favorable handling characteristics. The EPE was 1.28 ± 0.86 mm and TPE was 1.61 ± 0.89 mm. Long trajectories (>50 mm) had significantly larger EPEs and TPEs than short trajectories (<50 mm), and no differences were found between orthogonal and oblique trajectories. Accuracies were similar or superior to those reported in the literature when using similar experimental conditions, and in the same range as those reported in patients. Discussion: The results demonstrate that newly developed polyimide sEEG electrodes can be implanted as accurately as similar devices in the marker without user errors when following the IFU in a simulated clinical environment. The human cadaver ex-vivo test system provided a realistic test system, owing to the size, anatomy and similarity of tissue composition to that of the live human brain.

Neurosurgery residency match for international medical graduates in the United States.

OBJECTIVE: Training of international medical graduates (IMGs) offers opportunities for the US neurosurgery community to engage the global talent pool and impact national and international healthcare. Here, the authors analyzed the time trend of IMGs matching into US neurosurgery programs and identified potential opportunities for enhancing IMG engagement. METHODS: The authors analyzed the National Resident Matching Program (NRMP) match results, NRMP program director (PD) surveys, and applicant surveys from 2013 to 2022. Regression methods were used to analyze time trends. RESULTS: Between 2013 and 2022, the number of US neurosurgery residency positions increased by 17.6% (from 204 to 240). During this period, the percentage of IMGs matching into neurosurgery increased from 3.5% to 7%, translating into a 6.8% increase in the likelihood of a successful IMG match per year (95% CI 0.3%-13.8%, p = 0.042). The likelihoods of a successful match for US MDs and IMGs scoring > 260 on the USMLE Step 1 were > 90% and approximately 55%, respectively. In PD surveys, approximately 90% of PDs indicated that they seldom/never interview or rank IMGs. In terms of factors that influenced the PD decision for interviewing/ranking, IMGs are disadvantaged in several categories, including the ability to secure an audition elective/rotation, and proper letters of recommendation, as well as the influence of the culture on the preconceived perception of poor interpersonal skills. CONCLUSIONS: The number of IMGs matching successfully in neurosurgery has increased marginally during the past decade. The authors outline the challenges that IMGs encounter in this process and suggest strategies for considerations of IMG training in NRMP-associated institutions.

Assessing expert reliability in determining intracranial EEG channel quality and introducing the Automated Bad Channel Detection algorithm.

OBJECTIVES: To evaluate the inter- and intra-rater reliability for the identification of bad channels among neurologists, EEG Technologists, and naïve research personnel, and to compare their performance with the automated bad channel detection (ABCD) algorithm for detecting bad channels. Methods: Six Neurologists, ten EEG Technologists, and six naïve research personnel (22 raters in total) were asked to rate 1440 real intracranial EEG channels as good or bad. Intra- and interrater kappa statistics were calculated for each group. We then compared each group to the ABCD algorithm which uses spectral and temporal domain features to classify channels as good or bad. Results: Analysis of channel ratings from our participants revealed variable intra-rater reliability within each group, with no significant differences across groups. Inter-rater reliability was moderate among neurologists and EEG Technologists but minimal among naïve participants. Neurologists demonstrated a slightly higher consistency in ratings than EEG Technologists. Both groups occasionally misclassified flat channels, and participants generally focused on low-frequency content for their assessments. The ABCD algorithm, in contrast, relied more on high-frequency content. A logistic regression model showed a linear relationship between the algorithm's ratings and user responses for predominantly good channels, but less so for channels rated as bad. Sensitivity and specificity analyses further highlighted differences in rating patterns among the groups, with neurologists showing higher sensitivity and naïve personnel higher specificity. Significance: Our study reveals the bias in human assessments of iEEG data quality and the tendency of even experienced professionals to overlook certain bad channels, highlighting the need for standardized, unbiased methods. The ABCD algorithm, outperforming human raters, suggests the potential of automated solutions for more reliable iEEG interpretation and seizure characterization, offering a reliable approach free from human biases. .

Clinical Benefit of Vagus Nerve Stimulation for Epilepsy: Assessment of Randomized Controlled Trials and Prospective Non-Randomized Studies.

We examined the efficacy of vagal nerve stimulation (VNS) for patients suffering from medically intractable epilepsy. Four randomized controlled trials (RCTs - 3 adult RCTs and 1 pediatric RCT) were identified in our comprehensive literature search. Across the 4 studies, high frequency VNS stimulation (frequency >20 Hz) consistently achieved a greater seizure frequency reduction (23.4-33.1%) relative to low frequency VNS stimulation (1 Hz, .6-15.2%). We identified 2 RCTs examining whether the parameters of stimulation influenced seizure control. These studies reported that VNS achieved seizure control comparable to those reported by the first 4 RCTs (22-43% seizure frequency reduction), irrespective of the parameters utilized for VNS stimulation. In terms of VNS associated morbidity, these morbidities were consistently higher in adults who underwent high frequency VNS stimulation (eg dysphonia 37-66%, dyspnea 6-25.3%). However, no such differences were observed in the pediatric population. Moreover, <2% of patients withdrew from the RCTs/prospective studies due to intolerable symptoms. To provide an assessment of how the risks and benefits of VNS impact the patient experience, 1 study assessed the well-being of enrolled patients (as a secondary end point) and found VNS was associated with an overall improvement in well-being. Consistent with this observation, we identified a prospective, non-randomized study that demonstrated improved quality of life for epilepsy patients managed with VNS and best medical practice relative to best medical practice alone. In aggregate, these RCT studies support the efficacy and benefit of VNS as a neuro-modulatory platform in the management of a subset of medically refractory epilepsy patients.

Frequency settings of subthalamic nucleus DBS for Parkinson's disease: A systematic review and network meta-analysis.

INTRODUCTION: Deep Brain Stimulation (DBS) is an effective treatment for the motor symptoms of Parkinson's Disease. The targeted physiological structure for lead location is commonly the subthalamic nucleus (STN). The efficacy of DBS for improving motor symptoms is assessed via the Unified Parkinson's Disease Rating III Scale (UPDRS-III). In this study, we sought to compare the efficacy of frequency settings utilized for STN-DBS. METHODS: Following PRISMA Guidelines, a search on PUBMED and MEDLINE was performed to include full-length randomized controlled trials evaluating STN-DBS. The frequency stimulation parameters and Unified Parkinson's Disease Rating Scale (UPDRS-III) outcomes were extracted in the search. High-frequency stimulation (HFS) was defined as ≥100 Hz and low-frequency stimulation (LFS) was defined as <100 Hz. A frequentist network meta-analysis was performed with odds ratios (OR) and pooling performed using the Mantel-Haenszel method. Statistics are presented as OR [95% CI]. RESULTS: 15 studies consisting of 298 patients were included for analysis. Bilateral HFS -0.68 [-0.89; -0.46] was associated with better UPDRS-III scores compared to bilateral LFS. On the other hand, bilateral LFS with medications (MEDS) was favored over HFS with MEDS (-0.28 [-0.63; 0.07]). Bilateral LFS and MEDS, HFS and MEDS, stimulation (STIM) OFF MEDS ON, HFS, LFS, STIM OFF MEDS OFF UPDRS outcomes were ranked from best to worst outcomes. DISCUSSION: The outcomes of this study suggest that bilateral HFS has better utility for those with no response to medication, while LFS has additive benefits to medication by improving unique symptoms via different neurophysiological mechanisms.

WITHDRAWN: Laterality and frequency settings of subthalamic nucleus DBS for Parkinson's disease: A systematic review and network meta-analysis.

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Low-frequency deep brain stimulation reveals resonant beta-band evoked oscillations in the pallidum of Parkinson's Disease patients.

Introduction: Evidence suggests that spontaneous beta band (11-35 Hz) oscillations in the basal ganglia thalamocortical (BGTC) circuit are linked to Parkinson's disease (PD) pathophysiology. Previous studies on neural responses in the motor cortex evoked by electrical stimulation in the subthalamic nucleus have suggested that circuit resonance may underlie the generation of spontaneous and stimulation-evoked beta oscillations in PD. Whether these stimulation-evoked, resonant oscillations are present across PD patients in the internal segment of the globus pallidus (GPi), a primary output nucleus in the BGTC circuit, is yet to be determined. Methods: We characterized spontaneous and stimulation-evoked local field potentials (LFPs) in the GPi of four PD patients (five hemispheres) using deep brain stimulation (DBS) leads externalized after DBS implantation surgery. Results: Our analyses show that low-frequency (2-4 Hz) stimulation in the GPi evoked long-latency (>50 ms) beta-band neural responses in the GPi in 4/5 hemispheres. We demonstrated that neural sources generating both stimulation-evoked and spontaneous beta oscillations were correlated in their frequency content and spatial localization. Discussion: Our results support the hypothesis that the same neuronal population and resonance phenomenon in the BGTC circuit generates both spontaneous and evoked pallidal beta oscillations. These data also support the development of closed-loop control systems that modulate the GPi spontaneous oscillations across PD patients using beta band stimulation-evoked responses.

Mapping spreading depolarisations after traumatic brain injury: a pilot clinical study protocol.

INTRODUCTION: Cortical spreading depolarisation (CSD) is characterised by a near-complete loss of the ionic membrane potential of cortical neurons and glia propagating across the cerebral cortex, which generates a transient suppression of spontaneous neuronal activity. CSDs have become a recognised phenomenon that imparts ongoing secondary insults after brain injury. Studies delineating CSD generation and propagation in humans after traumatic brain injury (TBI) are lacking. Therefore, this study aims to determine the feasibility of using a multistrip electrode array to identify CSDs and characterise their propagation in space and time after TBI. METHODS AND ANALYSIS: This pilot, prospective observational study will enrol patients with TBI requiring therapeutic craniotomy or craniectomy. Subdural electrodes will be placed for continuous electrocorticography monitoring for seizures and CSDs as a research procedure, with surrogate informed consent obtained preoperatively. The propagation of CSDs relative to structural brain pathology will be mapped using reconstructed CT and electrophysiological cross-correlations. The novel use of multiple subdural strip electrodes in conjunction with brain morphometric segmentation is hypothesised to provide sufficient spatial information to characterise CSD propagation across the cerebral cortex and identify cortical foci giving rise to CSDs. ETHICS AND DISSEMINATION: Ethical approval for the study was obtained from the Hennepin Healthcare Research Institute's ethics committee, HSR 17-4400, 25 October 2017 to present. Study findings will be submitted for publication in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT03321370.