Novel electrode technologies for neural recordings.

Neural recording electrode technologies have contributed considerably to neuroscience by enabling the extracellular detection of low-frequency local field potential oscillations and high-frequency action potentials of single units. Nevertheless, several long-standing limitations exist, including low multiplexity, deleterious chronic immune responses and long-term recording instability. Driven by initiatives encouraging the generation of novel neurotechnologies and the maturation of technologies to fabricate high-density electronics, novel electrode technologies are emerging. Here, we provide an overview of recently developed neural recording electrode technologies with high spatial integration, long-term stability and multiple functionalities. We describe how these emergent neurotechnologies can approach the ultimate goal of illuminating chronic brain activity with minimal disruption of the neural environment, thereby providing unprecedented opportunities for neuroscience research in the future.

Outcomes of stereoelectroencephalography exploration at an epilepsy surgery center.

OBJECTIVES: Epilepsy surgery is offered in resistant focal epilepsy. Non-invasive investigations like scalp video EEG monitoring (SVEM) help delineate epileptogenic zone. Complex cases may require intracranial video EEG monitoring (IVEM). Stereoelectroencephalography (SEEG)-based intracerebral electrode implantation has better spatial resolution, lower morbidity, better tolerance, and superiority in sampling deep structures. Our objectives were to assess IVEM using SEEG with regard to reasoning behind implantation, course, surgical interventions, and outcomes. MATERIALS AND METHODS: Seventy-two admissions for SEEG from January 2014 to December 2018 were included in the study. Demographic and clinical data were retrospectively collected. RESULTS: The cohort comprised of 69 adults of which 34 (47%) had lesional MRI. Reasons for SEEG considering all cases included non-localizing ictal onset (76%), ictal-interictal discordance (21%), discordant semiology (17%), proximity to eloquent cortex (33%), nuclear imaging discordance (34%), and discordance with neuropsychology (19%). Among lesional cases, additional reasons included SVEM discordance (68%) and dual or multiple pathology (47%). Forty-eight patients (67%) were offered resective surgery, and 41 underwent it. Twenty-three (56%) had at least one year post-surgical follow-up of which 14 (61%) had Engels class I outcome. Of the remaining 23 who were continued on medical management, 4 (17%) became seizure-free and 12 (51%) had reduction in seizure frequency. CONCLUSION: SEEG monitoring is an important and safe tool for presurgical evaluation with good surgical and non-surgical outcomes. Whether seizure freedom following non-surgical management could be related to SEEG implantation, medication change, or natural course needs to be determined.

Long-term effects of vagus nerve stimulation in refractory pediatric epilepsy: A single-center experience.

INTRODUCTION: Vagus nerve stimulation (VNS) has been used as an adjunctive therapy for both children and adults with refractory epilepsy, over the last two decades. In this study, we aimed to evaluate the long-term effects and tolerability of VNS in the pediatric drug-resistant epilepsy (DRE) and to identify the predictive factors for responsiveness to VNS. METHODS: We retrospectively reviewed the medical records of pediatric patients who underwent VNS implantation between 1997 and 2018. Patients with ≥50% reduction of seizure frequency compared with the baseline were defined as "responders". The clinical characteristics of responders and nonresponders were compared. RESULTS: A total of 58 children (male/female: 40/18) with a mean follow-up duration of 5.7 years (3 months to 20 years) were included. The mean age at implantation was 12.4 years (4.5 to 18.5 years). Approximately half (45%) of our patients were responders, including 3 patients (5.8%) who achieved seizure freedom during follow-up. The age of seizure-onset, duration of epilepsy, age at implantation, and etiologies of epilepsy showed no significant difference between responders and nonresponders. Responders were more likely to have focal or multifocal epileptiform discharges (63%) on interictal electroencephalogram (EEG), when compared to nonresponders (36%) (p = .07). Vocal disturbances and paresthesias were the most common side effects, and in two patients, VNS was removed because of local reaction. CONCLUSION: Our series had a diverse etiological profile and patients with transition to adult care. Long-term follow-up showed that VNS is an effective and well-tolerated treatment modality for refractory childhood onset epilepsy. Age at implantation, duration of epilepsy and underlying etiology are not found to be predictors of responsiveness to VNS. Higher response rates were observed for a subset of patients with focal epileptiform discharges.

Postoperative outcomes following pediatric intracranial electrode monitoring: A case for stereoelectroencephalography (SEEG).

BACKGROUND: For patients with medically refractory epilepsy, intracranial electrode monitoring can help identify epileptogenic foci. Despite the increasing utilization of stereoelectroencephalography (SEEG), the relative risks or benefits associated with the technique when compared with the traditional subdural electrode monitoring (SDE) remain unclear, especially in the pediatric population. Our aim was to compare the outcomes of pediatric patients who received intracranial monitoring with SEEG or SDE (grids and strips). METHODS: We retrospectively studied 38 consecutive pediatric intracranial electrode monitoring cases performed at our institution from 2014 to 2017. Medical/surgical history and operative/postoperative records were reviewed. We also compared direct inpatient hospital costs associated with the two procedures. RESULTS: Stereoelectroencephalography and SDE cohorts both showed high likelihood of identifying epileptogenic zones (SEEG: 90.9%, SDE: 87.5%). Compared with SDE, SEEG patients had a significantly shorter operative time (118.7 versus 233.4 min, P < .001) and length of stay (6.2 versus 12.3 days, P < .001), including days spent in the intensive care unit (ICU; 1.4 versus 5.4 days, P < .001). Stereoelectroencephalography patients tended to report lower pain scores and used significantly less narcotic pain medications (54.2 versus 197.3 mg morphine equivalents, P = .005). No complications were observed. Stereoelectroencephalography and SDE cohorts had comparable inpatient hospital costs (P = .47). CONCLUSION: In comparison with subdural electrode placement, SEEG results in a similarly favorable clinical outcome, but with reduced operative time, decreased narcotic usage, and superior pain control without requiring significantly higher costs. The potential for an improved postoperative intracranial electrode monitoring experience makes SEEG especially suitable for pediatric patients.

Patient phenotypes and clinical outcomes in invasive monitoring for epilepsy: An individual patient data meta-analysis.

OBJECTIVE: Invasive monitoring provides valuable clinical information in patients with drug-resistant epilepsy (DRE). However, there is no clear evidence indicating either stereoelectroencephalography (SEEG) or subdural electrodes (SDE) as the optimal method. Our goal was to examine differences in postresection seizure freedom rates between SEEG- and SDE-informed resective epilepsy surgeries. Additionally, we aimed to determine potential clinical indicators for SEEG or SDE monitoring in patients with drug-resistant epilepsy. METHODS: A systematic literature review was performed in which we searched for primary articles using keywords such as "electroencephalography", "intracranial grid", and "epilepsy." Only studies containing individual patient data (IPD) were included for analysis. A one-stage IPD meta-analysis was performed to determine differences in rates of seizure freedom (International League Against Epilepsy (ILAE) guidelines and Engel classification) and resection status between SEEG and SDE patients. A Cox proportional-hazards regression was performed to determine the effect of time on seizure freedom status. Additionally, a principal component analysis was performed to investigate primary drivers of variance between these two groups. RESULTS: This IPD meta-analysis compared differences between SEEG and SDE invasive monitoring techniques in 595 patients from 33 studies. Our results demonstrate that while there was no difference in seizure freedom rates regardless of resection (p = 0.0565), SEEG was associated with a lower rate of resection compared with SDE (82.00% SEEG, 92.74% SDE, p = 0.0002). Additionally, while SDE was associated with a higher rate of postresection seizure freedom (54.04% SEEG, 64.32% SDE, p = 0.0247), the difference between seizure freedom rates following SEEG- or SDE-informed resection decreased with long-term follow-up. A principal component analysis showed that cases resulting in SEEG were associated with lower risk of morbidity than SDE cases, which were strongly collinear with multiple subpial transections, anterior temporal lobectomy, amygdalectomy, and hippocampectomy. SIGNIFICANCE: In this IPD meta-analysis of SEEG and SDE invasive monitoring techniques, SEEG and SDE were associated with similar rates of seizure freedom at latest follow-up. The former was associated with lower rates of resection. Furthermore, the clinical phenotypes of patients undergoing SEEG monitoring was associated with lower rates of complications. Future long-term prospective registries of IPD are promising options for clarifying the differences in these intracranial monitoring techniques as well as the unique patient phenotypes that may be associated with their indication.

Beyond implantation effect? Long-term seizure reduction and freedom following intracranial monitoring without additional surgical interventions.

The term 'implantation effect' is used to describe an immediate and transient improvement in seizure frequency following an intracranial study for seizure onset localization. We conducted a retrospective analysis of 190 consecutive patients undergoing intracranial electroencephalogram (EEG) monitoring, of whom 41 had no subsequent resection/ablation/stimulation; 33 had adequate data and follow-up time available for analysis. Analysis of seizure frequency following an intracranial study showed 36% (12/33) responder rate (>50% seizure reduction) at one year, decreasing and stabilizing at 20% from year 4 onwards. In addition, we describe three patients (9%) who had long term seizure freedom of more than five years following electrode implantation alone, two of whom had thalamic depth electrodes. Electrode implantation perhaps leads to a neuromodulatory effect sufficient enough to disrupt epileptogenic networks. Rarely, this may be significant enough to even result in long term seizure freedom, as seen in our three patients.

Pulse Width and Implantable Pulse Generator Longevity in Pallidal Deep Brain Stimulation for Dystonia: A Population-Based Comparative Effectiveness Study.

INTRODUCTION: A wide range of pulse widths (PWs) has been used in globus pallidus internus (GPi) deep brain stimulation (DBS) for dystonia. However, no specific PW has demonstrated clinical superiority, and the paradigm may differ among DBS centers. OBJECTIVE: To investigate how different paradigms of PWs in GPi DBS for dystonia affect implantable pulse generator (IPG) longevities and energy consumption. METHODS: Thirty-nine patients with dystonia treated with bilateral GPi DBS at 2 Swedish DBS centers from 2005 to 2015 were included. Different PW paradigms were used at the 2 centers, 60-90 µs (short PWs) and 450 µs (long PW), respectively. The frequency of IPG replacements, pulse effective voltage (PEV), IPG model, pre-/postoperative imaging, and clinical outcome based on the clinical global impression (CGI) scale were collected from the medical charts and compared between the 2 groups. RESULTS: The average IPG longevity was extended for the short PWs (1,129 ± 50 days) compared to the long PW (925 ± 32 days; χ2 = 12.31, p = 0.0005, log-rank test). IPG longevity correlated inversely with PEV (Pearson's r = -0.667, p < 0.0001). IPG longevities did not differ between Kinetra® and Activa® PC in the short (p = 0.319) or long PW group (p = 0.858). Electrode distances to the central sensorimotor region of the GPi did not differ between the short or long PW groups (p = 0.595). Pre- and postoperative CGI did not differ between groups. CONCLUSIONS: Short PWs were associated with decreased energy consumption and increased IPG longevity. These effects were not dependent on the IPG model or the anatomic location of the electrodes. PWs did not correlate with symptom severities or clinical outcomes. The results suggest that the use of short PWs might be more energy efficient and could therefore be preferred initially when programming patients with GPi DBS for dystonia.

Fixed-Life or Rechargeable Battery for Deep Brain Stimulation: A Prospective Long-Term Study of Patient's Preferences.

INTRODUCTION: Deep brain stimulation (DBS) is an established treatment for movement disorders. We have previously shown that in our practice, the majority of adult patients prefer fixed-life implantable pulse generators (IPGs), although rechargeable batteries are increasingly used. The aim of this study was to evaluate patients' long-term satisfaction with their choice of battery and factors that influence their decision. METHODS: Thirty patients with DBS were given a questionnaire to assess long-term satisfaction and experience with the type of battery they had chosen. RESULTS: Twenty-six patients completed the survey. The mean age was 67.7 ± 7.3 years, and mean follow-up was 18.0 ± 7.2 months. The indications for DBS were Parkinson's disease (76.9%), tremor (11.5%) and dystonia (11.5%). Eleven patients (42.5%) had chosen the rechargeable battery. All patients were still happy with their choices and would not change the type of battery if they had the chance to do so. However, in patients who chose the fixed-life battery, concern about the size of battery rose from 6.7% pre-operatively to 60% on long-term post-operative follow-up. In patients who chose the rechargeable battery, concern about the need to recharge the battery did not change, remaining low postoperatively. Interestingly, even though the main reason cited for choosing the fixed-life battery was the convenience and concern about forgetting to recharge the battery, patients who had chosen a rechargeable IPG did not experience this problem. CONCLUSION: Patients and caregivers should be involved in the choice of battery, as each type of IPG has its own advantages and disadvantages. Long-term evaluation of patient's experience and satisfaction with battery of choice revealed that size of the IPG, need for further replacement surgeries and need for recharging remain matters of major concern. Although preoperatively often underestimated, the size of the battery seems to be an important factor in long-term satisfaction.

Complications of epidural spinal stimulation: lessons from the past and alternatives for the future.

STUDY DESIGN: Systematic review. OBJECTIVES: Over the past decade, an increasing number of studies have demonstrated that epidural spinal cord stimulation (SCS) can successfully assist with neurorehabilitation following spinal cord injury (SCI). This approach is quickly garnering the attention of clinicians. Therefore, the potential benefits of individuals undergoing epidural SCS therapy to regain sensorimotor and autonomic control, must be considered along with the lessons learned from other studies on the risks associated with implantable systems. METHODS: Systematic analysis of literature, as well as preclinical and clinical reports. RESULTS: The use of SCS for neuropathic pain management has revealed that epidural electrodes can lose their therapeutic effects over time and lead to complications, such as electrode migration, infection, foreign body reactions, and even SCI. Several authors have also described the formation of a mass composed of glia, collagen, and fibrosis around epidural electrodes. Clinically, this mass can cause myelopathy and spinal compression, and it is only treatable by surgically removing both the electrode and scar tissue. CONCLUSIONS: In order to reduce the risk of encapsulation, many innovative efforts focus on technological improvements of electrode biocompatibility; however, they require time and resources to develop and confirm safety and efficiency. Alternatively, some studies have demonstrated similar outcomes of non-invasive, transcutaneous SCS following SCI to those seen with epidural SCS, without the complications associated with implanted electrodes. Thus, transcutaneous SCS can be proposed as a promising candidate for a safer and more accessible SCS modality for some individuals with SCI.

Direct Cortical Recordings Suggest Temporal Order of Task-Evoked Responses in Human Dorsal Attention and Default Networks.

The past decade has seen a large number of neuroimaging studies focused on the anticorrelated functional relationship between the default mode network (DMN) and the dorsal attention network (DAN). Due principally to the low temporal resolution of functional neuroimaging modalities, the fast-neuronal dynamics across these networks remain poorly understood. Here we report novel human intracranial electrophysiology data from six neurosurgical patients (four males) with simultaneous coverage of well characterized nodes of the DMN and DAN. Subjects performed an arithmetic processing task, shown previously to evoke reliable deactivations (below baseline) in the DMN, and activations in the DAN. In this cohort, we show that DMN deactivations lag DAN activations by approximately 200 ms. Our findings suggest a clear temporal order of processing across the two networks during the current task and place the DMN further than the DAN in a plausible information-processing hierarchy.SIGNIFICANCE STATEMENT The human brain contains an intrinsic and strictly organized network architecture. Our understanding of the interplay across association networks has relied primarily on the slow fluctuations of the hemodynamic response, and as such it has lacked essential evidence regarding the temporal dynamics of activity across these networks. The current study presents evidence from high spatiotemporal methods showing that well studied areas of the default mode network display delayed task-induced activity relative to divergent responses in dorsal attention network nodes. This finding provides direct and critical evidence regarding the temporal chronology of neuronal events across opposing brain networks.

Pallidal and thalamic neural oscillatory patterns in tourette's syndrome.

OBJECTIVE: Aberrant oscillatory activity has been hypothesized to play a role in the pathophysiology of Tourette's syndrome (TS). Deep brain stimulation (DBS) has recently been established as an effective treatment for severe TS. Modulation of symptom-specific oscillations may underlie the mechanism of action of DBS and could be used for adaptive neuromodulation to improve therapeutic efficacy. The objective of this study was to demonstrate a pathophysiological association of pallidal and thalamic local field potentials (LFPs) with TS. METHODS: Nine medication-refractory TS patients were included in the study. Intracerebral LFPs were recorded simultaneously from bilateral pallidal and thalamic DBS electrodes. Spectral and temporal dynamics of pallidal and thalamic oscillations were characterized and correlated with preoperative Yale Global Tic Severity Scale (YGTSS) scores. RESULTS: Peaks of activity in the theta (3-12Hz) and beta (13-35Hz) were present in pallidal and thalamic recordings from all patients (3 women/6 men; mean age, 29.8 years) and coupled through coherence across targets. Presence of prolonged theta bursts in both targets was associated with preoperative motor tic severity. Total preoperative YGTSS scores (mean, 38.1) were correlated with pallidal and thalamic LFP activity using multivariable linear regression (R² = 0.96; p = 0.02). INTERPRETATION: Our findings suggest that pallidothalamic oscillations may be implicated in the pathophysiology of TS. Furthermore, our results highlight the utility of multisite and -spectral oscillatory features in severely affected patients for future identification and clinical use of oscillatory physiomarkers for adaptive stimulation in TS. Ann Neurol 2018;84:505-514.

Low-voltage fast seizures in humans begin with increased interneuron firing.

OBJECTIVE: Intracellular recordings from cells in entorhinal cortex tissue slices show that low-voltage fast (LVF) onset seizures are generated by inhibitory events. Here, we determined whether increased firing of interneurons occurs at the onset of spontaneous mesial-temporal LVF seizures recorded in patients. METHODS: The seizure onset zone (SOZ) was identified using visual inspection of the intracranial electroencephalogram. We used wavelet clustering and temporal autocorrelations to characterize changes in single-unit activity during the onset of LVF seizures recorded from microelectrodes in mesial-temporal structures. Action potentials generated by principal neurons and interneurons (ie, putative excitatory and inhibitory neurons) were distinguished using waveform morphology and K-means clustering. RESULTS: From a total of 200 implanted microelectrodes in 9 patients during 13 seizures, we isolated 202 single units; 140 (69.3%) of these units were located in the SOZ, and 40 (28.57%) of them were classified as inhibitory. The waveforms of both excitatory and inhibitory units remained stable during the LVF epoch (p > > 0.05). In the mesial-temporal SOZ, inhibitory interneurons increased their firing rate during LVF seizure onset (p < 0.01). Excitatory neuron firing rates peaked 10 seconds after the inhibitory neurons (p < 0.01). During LVF spread to the contralateral mesial temporal lobe, an increase in inhibitory neuron firing rate was also observed (p < 0.01). INTERPRETATION: Our results suggest that seizure generation and spread during spontaneous mesial-temporal LVF onset events in humans may result from increased inhibitory neuron firing that spawns a subsequent increase in excitatory neuron firing and seizure evolution. Ann Neurol 2018;84:588-600.

Ultra-long-term subcutaneous home monitoring of epilepsy-490 days of EEG from nine patients.

OBJECTIVE: To explore the feasibility of home monitoring of epilepsy patients with a novel subcutaneous electroencephalography (EEG) device, including clinical implications, safety, and compliance via the first real-life test. METHODS: We implanted a beta-version of the 24/7 EEG SubQ (UNEEG Medical A/S, Denmark) subcutaneously in nine participants with temporal lobe epilepsy. Data on seizures, adverse events, compliance in using the device, and use of antiepileptic drugs (AEDs) were collected. EEG was recorded for up to 3 months, and all EEG data were reviewed visually to identify electrographic seizures. These were descriptively compared to seizure counts and AED changes reported in diaries from the same period. RESULTS: Four hundred ninety days of EEG and 338 electrographic seizures were collected. Eight participants completed at least 9 weeks of home monitoring, while one cancelled participation after 4 weeks due to postimplantation soreness. In total, 13 cases of device-related adverse events were registered, none of them serious. Recordings obtained from the device covered 73% of the time, on average (range 45%-91%). Descriptively, electrographic seizure counts were substantially different from diary seizure counts. We uncovered several cases of underreporting and revealed important information on AED response. Electrographic seizure counts revealed circadian distributions of seizures not visible from seizure diaries. SIGNIFICANCE: The study shows that home monitoring for up to 3 months with a subcutaneous EEG device is feasible and well tolerated. No serious adverse device-related events were reported. An objective seizure count can be derived, which often differs substantially from self-reported seizure counts. Larger clinical trials quantifying the benefits of objective seizure counting should be a priority for future research as well as development of algorithms for automated review of data.

Implementation of New Technology in Patients with Chronic Deep Brain Stimulation: Switching from Non-Rechargeable Constant Voltage to Rechargeable Constant Current Stimulation.

INTRODUCTION: Deep brain stimulation (DBS) for movement disorders has been mainly performed with constant voltage (CV) technology. More recently also constant current (CC) systems have been developed which theoretically might have additional advantages. Furthermore, rechargeable (RC) system implantable pulse generators (IPG) are increasingly being used rather than the former solely available non-rechargeable (NRC) IPGs. OBJECTIVE: To provide a systematic investigation how to proceed and adapt settings when switching from CV NRC to CC RC technology. METHODS: We prospectively collected data from 11 consecutive patients (10 men, mean age at DBS implantation 52.6 ± 14.0 years) with chronic DBS for dystonia (n = 7), Parkinson disease (n = 3), and essential tremor (n = 1) who underwent IPG replacement switching from a CV NRC system (Activa® PC; Medtronic®) to a CC RC system (Vercise® RC; Boston Scientific®). Systematic assessments before and after IPG replacement were performed. RESULTS: DBS technology switching at the time of IPG replacement due to battery depletion was at a mean of 108.5 ± 46.2 months of chronic DBS. No perioperative complications occurred. Clinical outcome was stable with overall mild improvements or deteriorations, which could be dealt with in short-term follow-up. Patients were satisfied with the new RC IPG. CONCLUSIONS: This study confirms both the safety and feasibility of switching between different DBS technologies (CV to CC, NRC to RC, different manufacturers) in patients with chronic DBS. Furthermore, it shows how the management can be planned using available information from the previous DBS settings. Individual assessment is needed and might partly be related to the DBS target and the underlying disease. MR safety might be a problem with such hybrid systems.

Advances in Penetrating Multichannel Microelectrodes Based on the Utah Array Platform.

The Utah electrode array (UEA) and its many derivatives have become a gold standard for high-channel count bi-directional neural interfaces, in particular in human subject applications. The chapter provides a brief overview of leading electrode concepts and the context in which the UEA has to be understood. It goes on to discuss the key advances and developments of the UEA platform in the past 15 years, as well as novel wireless and system integration technologies that will merge into future generations of fully integrated devices. Aspects covered include novel device architectures that allow scaling of channel count and density of electrode contacts, material improvements to substrate, electrode contacts, and encapsulation. Further subjects are adaptations of the UEA platform to support IR and optogenetic simulation as well as an improved understanding of failure modes and methods to test and accelerate degradation in vitro such as to better predict device failure and lifetime in vivo.

Behavioral Impact of Long-Term Chronic Implantation of Neural Recording Devices in the Rhesus Macaque.

BACKGROUND: Ensemble recording methods are pervasive in basic and clinical neuroscience research. Invasive neural implants are used in patients with drug resistant epilepsy to localize seizure origin, in neuropsychiatric or Parkinson's patients to alleviate symptoms via deep brain stimulation, and with animal models to conduct basic research. Studies addressing the brain's physiological response to chronic electrode implants demonstrate that the mechanical trauma of insertion is followed by an acute inflammatory response as well as a chronic foreign body response. Despite use of invasive recording methods with animal models and humans, little is known of their effect on behavior in healthy populations. OBJECTIVE: To quantify the effect of chronic electrode implantation targeting the hippocampus on recognition memory performance. METHODS: Four healthy female rhesus macaques were tested in a delayed nonmatching-to-sample (DNMS) recognition memory task before and after hippocampal implantation with a tetrode array device. RESULTS: Trials to criterion and recognition memory performance were not significantly different before vs. after chronic electrode implantation. CONCLUSION: Our results suggest that chronic implants did not produce significant impairments on DNMS performance.

Therapeutic Window of Deep Brain Stimulation Using Cathodic Monopolar, Bipolar, Semi-Bipolar, and Anodic Stimulation.

OBJECTIVES: To compare the therapeutic window (TW) of cathodic monopolar, bipolar, anodic monopolar, and a novel "semi-bipolar" stimulation in ten Parkinson's disease patients who underwent deep brain stimulation of the subthalamic nucleus. MATERIALS AND METHODS: Patients were assessed in the "OFF" L-dopa condition. Each upper limb was tested separately for therapeutic threshold, TW and side-effect threshold (SET). Battery consumption index (BCI) also was documented. RESULTS: Compared to cathodic stimulation, therapeutic threshold was significantly higher for anodic, bipolar, and semi-bipolar stimulation (3.8 ± 1.6 vs. 4.9 ± 2.1, 5.0 ± 1.9, and 5.2 ± 1.9 mA, p = 0.0006, 0.0002, and 0.008, respectively). SET was significantly higher for bipolar stimulation (10.9 ± 2.5 mA) vs. cathodic (6.8 ± 2.2 mA, p < 0.0001) and anodic stimulation (9.2 ± 2.6 mA, p = 0.005). The SET of anodic and semi-bipolar stimulation was significantly higher vs. cathodic stimulation (p < 0.0001). TW of cathodic stimulation (2.5 ± 1.5 mA) was significantly narrower vs. bipolar (5.4 ± 2.0 mA, p < 0.0001), semi-bipolar (4.6 ± 2.6 mA, p = 0.001) and anodic stimulation (4.3 ± 2.3 mA, p < 0.0001). Bipolar (p = 0.005) and semi-bipolar (p = 0.0005) stimulation had a significantly wider TW vs. anodic stimulation. BCI of cathodic stimulation (5.9 ± 1.3) was significantly lower compared to bipolar (13.7 ± 6.8, p < 0.0001), semi-bipolar (11.0 ± 4.3, p = 0.0005), and anodic stimulation (8.1 ± 3.0, p < 0.0001). Anodic BCI was significantly lower than bipolar (p = 0.005) and semi-bipolar (p = 0.0002) stimulation while semi-bipolar BCI was lower than bipolar stimulation (p = 0.0005). CONCLUSIONS: While awaiting further studies, our findings suggest that cathodic stimulation should be preferred in light of its reduced battery consumption, possibly followed by semi-bipolar in case of stimulation-induced side-effects.

Cortical Activation Elicited by Subthalamic Deep Brain Stimulation Predicts Postoperative Motor Side Effects.

OBJECTIVE: Although deep brain stimulation (DBS) is an effective treatment for movement disorders, improvement varies substantially in individuals, across clinical trials, and over time. Noninvasive biomarkers that predict the individual response to DBS could be used to optimize outcomes and drive technological innovation in neuromodulation. We sought to evaluate whether noninvasive event related potentials elicited by subthalamic DBS during surgical targeting predict the tolerability of a given stimulation site in patients with advanced Parkinson's disease. METHODS: Using electroencephalography, we measured event related potentials elicited by 20 Hz DBS over a range of stimulus intensities across the spatial extent of the implanted electrode array in 11 patients. We correlated event related potential timing and morphology with the stimulus amplitude thresholds for motor side effects during postoperative programming at ≥130 Hz. RESULTS: During surgical targeting, DBS at 20 Hz elicits large amplitude, high frequency activity (evoked HFA) with mean onset latency of 9.0 ± 0.3 msec and a mean frequency of 175.8 ± 7.8 Hz. The lowest DBS amplitude that elicits the HFA predicts thresholds for motor side effects during postoperative stimulation at ≥130 Hz (p < 0.001, ANOVA). CONCLUSION: Event related potentials elicited by DBS can predict clinically relevant corticospinal activation by stimulation after surgery. Noninvasive scalp physiology requires no patient interaction and could serve as a biomarker to guide targeting, postoperative programming, and emerging technologies such as directional and closed-loop stimulation.

Ultrasound-Guided Percutaneous Peripheral Nerve Stimulation: Neuromodulation of the Femoral Nerve for Postoperative Analgesia Following Ambulatory Anterior Cruciate Ligament Reconstruction: A Proof of Concept Study.

OBJECTIVES: The purpose of this prospective proof of concept study was to investigate the feasibility of using percutaneous peripheral nerve stimulation of the femoral nerve to treat pain in the immediate postoperative period following ambulatory anterior cruciate ligament reconstruction with a patellar autograft. MATERIALS AND METHODS: Preoperatively, an electrical lead (SPRINT, SPR Therapeutics, Inc., Cleveland, OH, USA) was percutaneously implanted with ultrasound guidance anterior to the femoral nerve caudad to the inguinal crease. Within the recovery room, subjects received 5 min of either stimulation or sham in a randomized, double-masked fashion followed by a 5-min crossover period, and then continuous active stimulation until lead removal postoperative Day 14-28. Statistics were not applied to the data due to the small sample size of this feasibility study. RESULTS: During the initial 5-min treatment period, subjects randomized to stimulation (n = 5) experienced a slight downward trajectory (decrease of 7%) in their pain over the 5 min of treatment, while those receiving sham (n = 5) reported a slight upward trajectory (increase of 4%) until their subsequent 5-min stimulation crossover, during which time they also experienced a slight downward trajectory (decrease of 11% from baseline). A majority of subjects (80%) used a continuous adductor canal nerve block for rescue analgesia (in addition to stimulation) during postoperative Days 1-3, after which the median resting and dynamic pain scores remained equal or less than 1.5 on the numeric rating scale, respectively, and the median daily opioid consumption was less than 1.0 tablet. CONCLUSIONS: This proof of concept study demonstrates that percutaneous femoral nerve stimulation is feasible for ambulatory knee surgery; and suggests that this modality may be effective in providing analgesia and decreasing opioid requirements following anterior cruciate ligament reconstruction. clinicaltrials.gov: NCT02898103.

Towards eradication of inappropriate therapies for ICD lead failure by combining comprehensive remote monitoring and lead noise alerts.

INTRODUCTION: Recognition of implantable cardioverter defibrillator (ICD) lead malfunction before occurrence of life threatening complications is crucial. We aimed to assess the effectiveness of remote monitoring associated or not with a lead noise alert for early detection of ICD lead failure. METHODS: From October 2013 to April 2017, a median of 1,224 (578-1,958) ICD patients were remotely monitored with comprehensive analysis of all transmitted materials. ICD lead failure and subsequent device interventions were prospectively collected in patients with (RMLN) and without (RM) a lead noise alert (Abbott Secure Sense™ or Medtronic Lead Integrity Alert™) in their remote monitoring system. RESULTS: During a follow-up of 4,457 patient years, 64 lead failures were diagnosed. Sixty-one (95%) of the diagnoses were made before any clinical complication occurred. Inappropriate shocks were delivered in only one patient of each group (3%), with an annual rate of 0.04%. All high voltage conductor failures were identified remotely by a dedicated impedance alert in 10 patients. Pace-sense component failures were correctly identified by a dedicated alert in 77% (17 of 22) of the RMLN group versus 25% (8 of 32) of the RM group (P = 0.002). The absence of a lead noise alert was associated with a 16-fold increase in the likelihood of initiating either a shock or ATP (OR: 16.0, 95% CI 1.8-143.3; P = 0.01). CONCLUSION: ICD remote monitoring with systematic review of all transmitted data is associated with a very low rate of inappropriate shocks related to lead failure. Dedicated noise alerts further reduce inappropriate detection of ventricular arrhythmias.