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Background and Objectives: Frameless deep brain stimulation (DBS) offers advantages in terms of patient comfort and reduced operative time. However, the need for bony fiducial markers for localization remains a drawback due to the time-consuming and uncomfortable procedure. An alternative localization method involves the direct tracking of an intraoperative 3-dimensional scanner. This study aims to assess the accuracy of the NexFrame frameless DBS system in conjunction with the O-Arm (Medtronic Inc.), both with and without fiducial markers., Methods: The locations of 100 DBS leads were determined, with 50 cases using fiducial-free localization and 50 involving fiducial markers. The coordinates were compared with the expected intraoperative targets. Absolute errors in the X, Y, and Z coordinates (ΔX, ΔY, and ΔZ) were calculated, along with the vector error (Euclidean) (vector error )., Results: The vector error averaged 1.61 ± 0.49 mm (right) and 1.52 ± 0.60 mm (left) for the group without fiducial bone markers and 1.66 ± 0.69 (right) and 1.44 ± 0.65 mm (left) for the other cohort (P = .76 right; P = .67 left). Absolute errors in the X, Y, and Z coordinates for the fiducial-free group were 0.88 ± 0.55, 0.79 ± 0.45, and 0.79 ± 0.57 mm (right) and 0.72 ± 0.37, 0.78 ± 0.56, and 0.77 ± 0.71 mm (left). For the group with fiducial markers, these errors were 0.87 ± 0.72, 0.92 ± 0.39, and 0.86 ± 0.50 mm (right) and 0.75 ± 0.33, 0.80 ± 0.51, and 0.73 ± 0.64 mm (left) with no statistically significant difference., Conclusion: Our analysis of the accuracy of NexFrame DBS, both with and without fiducial markers, using an intraoperative navigable cone-beam computed tomography, demonstrates that both techniques provide sufficient and equivalent 3-dimensional accuracy., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Purpose: Due to brain shift during bilateral deep brain stimulation (DBS) surgery, placement of the second electrode may be subjected to more error than that of the first electrode. The authors aimed to investigate the accuracy of second electrode placement in this setting., Materials and Methods: Fifty-five patients with Parkinson's disease who underwent bilateral DBS surgery (110 electrodes) were retrospectively evaluated. The targets were subthalamic nucleus (STN) and globus pallidus interna (GPi) in 40 and 15 cases, respectively. Preoperative planning and postoperative electrode images were co-registered to compare the error margin between the two sides., Results: There is a statistically significant difference in the directional axis error along the y axis only when comparing each laterality (posterior 0.04 ± 1.21 mm vs anterior 0.41 ± 1.07 mm, p  = 0.006). There is no significant difference of other error parameters, final track location, and number of microelectrode recording passes between the two sides. In a subgroup analysis, there is a significant difference in directional axis error along the y axis only in the STN subgroup (posterior 0.40 ± 1.05 mm vs anterior 0.18 ± 1.04 mm, p  = 0.003)., Conclusion: Although a statistically significant difference in directional axis error along the y axis was found between first and second electrode placements in the STN group but not in the GPi group, its magnitude is well below the clinically significant threshold.

Objective: Neuromodulation is a viable option for patients with drug-resistant epilepsies. We reviewed the management of patients with two deep brain neurostimulators. In addition, patients implanted with a device targeting the centromedian-parafascicular (CM-Pf) nuclear complex supplements this report to provide an illustrative case to implantation and programming a patient with three active devices., Methods: A narrative review using PubMed and Embase identified patients with drug-resistant epilepsy implanted with more than one neurostimulator was performed. Combinations of vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS) were identified. We provide a background of a newly reported case of an adult with a triple implant eventually responding to CM-Pf DBS as the third implant following suboptimal benefit from VNS and RNS., Results: In review of the literature, dual-device therapy is increasing in reports of use with combinations of VNS, RNS, and DBS to treat patients with drug-resistant epilepsy. We review dual-device implants with thalamic DBS device combinations, functional neural networks, and programming patients with dual devices. CM-Pf is a new target for DBS and has shown a variable response in focal epilepsy. We report the unique case of 28-year-old male with drug-resistant focal epilepsy who experienced a 75% seizure reduction with CM-Pf DBS as his third device after suboptimal responses to VNS and RNS. After 9 months, he also experienced seizure freedom from recurrent focal to bilateral tonic-clonic seizures. No medical or surgical complications or safety issues were encountered., Conclusion: We demonstrate safety and feasibility in an adult combining active VNS, RNS, and CM-Pf DBS. Patients with dual-device therapy who experience a suboptimal response to initial device use at optimized settings should not be considered a neuromodulation "failure." Strategies to combine devices require a working knowledge of brain networks., (© 2024 International League Against Epilepsy.)

Introduction: Deep Brain Stimulation (DBS) is an established therapeutic approach for the treatment of dystonia. However, to date, no large-scale or comprehensive DBS dystonia patient registry has been yet undertaken. Here, we describe the protocol for a world-wide registry of clinical outcomes in dystonia patients implanted with DBS., Methods and Analysis: This protocol describes a multicenter, international clinical outcomes registry consisting of up to 200 prospectively enrolled participants at up to 40 different sites to be implanted with a constant-current, multiple independent current controlled (MICC) DBS device (Vercise DBS Systems, Boston Scientific) for treatment of dystonia. Key inclusion criteria for registry candidates include the following: understanding of study requirements and treatment procedures, a signed written informed consent form prior to participation, and meeting all criteria established in the locally applicable Instructions for Use (IFU) for the implanted DBS system. Key clinical endpoints include (but are not limited to) the evaluation of disease state (Burke-Fahn-Marsden Dystonia Rating Scale [BFMDRS], Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), quality of life (Short Form Health Survey-36, Short Form Health Survey-10), and treatment satisfaction (Clinical Global Impression of Change [CGI-Clinician; CGI-Subject; CGI-Caregiver]) at 6-months, 12-months, 2-years, and 3-years post-lead placement. Adverse events are documented and reported using structured questionnaires., Perspectives: Treatment of patients with dystonia using DBS has progressed considering recent technological advances. This international dystonia outcomes registry aims to collect and evaluate real-world clinical data derived from patients who have been implanted with a constant-current, MICC-equipped DBS system (with available directional capabilities), per standard of care., Competing Interests: No authors have competing interests., (Copyright: © 2024 Albanese et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Non-invasive deep brain modulation (DBM) stands as a promising therapeutic avenue to treat brain diseases. Acoustic DBM represents an innovative and targeted approach to modulate the deep brain, employing techniques such as focused ultrasound and shock waves. Despite its potential, the optimal mechanistic parameters, the effect in the brain and behavioral outcomes of acoustic DBM remains poorly understood., Objective: To establish a robust protocol for the shock wave DBM by optimizing its mechanistic profile of external stimulation, and to assess its efficacy in preclinical settings., Methods: We used shockwaves due to their capacity to leverage a broader spectrum of peak intensity (10-127 W/mm 2 ) in contrast to ultrasound (0.1-5.0 W/mm 2 ), thereby enabling a more extensive range of neuromodulation effects. We established various types of shockwave pressure profiles of DBM and compared neural and behavioral responses. To ascertain the anticipated cause of the heightened neural activity response, numerical analysis was employed to examine the mechanical dynamics within the brain., Results: An optimized profile led to an enhancement in neuronal activity within the hypothalamus of mouse models. The optimized profile in the hippocampus elicited a marked increase in neurogenesis without neuronal damage. Behavioral analyses uncovered a noteworthy reduction in locomotion without significant effects on spatial memory function., Conclusions: The present study provides an optimized shock wave stimulation protocol for non-invasive DBM. Our optimized stimulation profile selectively triggers neural functions in the deep brain. Our protocol paves the way for new non-invasive DBM devices to treat brain diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Parkinsonian motor symptoms are linked to pathologically increased beta oscillations in the basal ganglia. Studies with externalised deep brain stimulation electrodes showed that Parkinson patients were able to rapidly gain control over these pathological basal ganglia signals through neurofeedback. Studies with fully implanted deep brain stimulation systems duplicating these promising results are required to grant transferability to daily application., Methods: In this study, seven patients with idiopathic Parkinson's disease and one with familial Parkinson's disease were included. In a postoperative setting, beta oscillations from the subthalamic nucleus were recorded with a fully implanted deep brain stimulation system and converted to a real-time visual feedback signal. Participants were instructed to perform bidirectional neurofeedback tasks with the aim to modulate these oscillations., Results: While receiving regular medication and deep brain stimulation, participants were able to significantly improve their neurofeedback ability and achieved a significant decrease of subthalamic beta power (median reduction of 31% in the final neurofeedback block)., Conclusion: We could demonstrate that a fully implanted deep brain stimulation system can provide visual neurofeedback enabling patients with Parkinson's disease to rapidly control pathological subthalamic beta oscillations., Significance: Fully-implanted DBS electrode-guided neurofeedback is feasible and can now be explored over extended timespans., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Neuromodulation technologies are crucial for investigating neuronal connectivity and brain function. Magnetic neuromodulation offers wireless and remote deep brain stimulations that are lacking in optogenetic- and wired-electrode-based tools. However, due to the limited understanding of working principles and poorly designed magnetic operating systems, earlier magnetic approaches have yet to be utilized. Furthermore, despite its importance in neuroscience research, cell-type-specific magnetic neuromodulation has remained elusive. Here we present a nanomaterials-based magnetogenetic toolbox, in conjunction with Cre-loxP technology, to selectively activate genetically encoded Piezo1 ion channels in targeted neuronal populations via torque generated by the nanomagnetic actuators in vitro and in vivo. We demonstrate this cell-type-targeting magnetic approach for remote and spatiotemporal precise control of deep brain neural activity in multiple behavioural models, such as bidirectional feeding control, long-term neuromodulation for weight control in obese mice and wireless modulation of social behaviours in multiple mice in the same physical space. Our study demonstrates the potential of cell-type-specific magnetogenetics as an effective and reliable research tool for life sciences, especially in wireless, long-term and freely behaving animals., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective. Understanding the generative mechanism between local field potentials (LFP) and neuronal spiking activity is a crucial step for understanding information processing in the brain. Up to now, most approaches have relied on simply quantifying the coupling between LFP and spikes. However, very few have managed to predict the exact timing of spike occurrence based on LFP variations. Approach. Here, we fill this gap by proposing novel spiking Laguerre-Volterra network (sLVN) models to describe the dynamic LFP-spike relationship. Compared to conventional artificial neural networks, the sLVNs are interpretable models that provide explainable features of the underlying dynamics. Main results. The proposed networks were applied on extracellular microelectrode recordings of Parkinson's Disease patients during deep brain stimulation (DBS) surgery. Based on the predictability of the LFP-spike pairs, we detected three neuronal populations with unique signal characteristics and sLVN model features. Significance. These clusters were indirectly associated with motor score improvement following DBS surgery, warranting further investigation into the potential of spiking activity predictability as an intraoperative biomarker for optimal DBS lead placement., (Creative Commons Attribution license.)

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

Introduction: The current approach to assessing bradykinesia in Parkinson's Disease relies on the Unified Parkinson's Disease Rating Scale (UPDRS), which is a numeric scale. Inertial sensors offer the ability to probe subcomponents of bradykinesia: motor speed, amplitude, and rhythm. Thus, we sought to investigate the differential effects of high-frequency compared to low-frequency subthalamic nucleus (STN) deep brain stimulation (DBS) on these quantified facets of bradykinesia., Methods: We recruited advanced Parkinson's Disease subjects with a chronic bilateral subthalamic nucleus (STN) DBS implantation to a single-blind stimulation trial where each combination of medication state (OFF/ON), electrode contacts, and stimulation frequency (60 Hz/180 Hz) was assessed. The Kinesia One sensor system was used to measure upper limb bradykinesia. For each stimulation trial, subjects performed extremity motor tasks. Sensor data were recorded continuously. We identified STN DBS parameters that were associated with improved upper extremity bradykinesia symptoms using a mixed linear regression model., Results: We recruited 22 subjects (6 females) for this study. The 180 Hz STN DBS (compared to the 60 Hz STN DBS) and dopaminergic medications improved all subcomponents of upper extremity bradykinesia (motor speed, amplitude, and rhythm). For the motor rhythm subcomponent of bradykinesia, ventral contacts yielded improved symptom improvement compared to dorsal contacts., Conclusion: The differential impact of high- and low-frequency STN DBS on the symptoms of bradykinesia may advise programming for these patients but warrants further investigation. Wearable sensors represent a valuable addition to the armamentarium that furthers our ability to conduct objective, quantitative clinical assessments.

Background: DBS entails the insertion of an electrode into the patient brain, enabling Subthalamic nucleus (STN) stimulation. Accurate delineation of STN borders is a critical but time-consuming task, traditionally reliant on the neurosurgeon experience in deciphering the intricacies of microelectrode recording (MER). While clinical outcomes of MER have been satisfactory, they involve certain risks to patient safety. Recently, there has been a growing interest in exploring the potential of local field potentials (LFP) due to their correlation with the STN motor territory., Method: A novel STN detection system, integrating LFP and wavelet packet transform (WPT) with stacking ensemble learning, is developed. Initial steps involve the inclusion of soft thresholding to increase robustness to LFP variability. Subsequently, non-linear WPT features are extracted. Finally, a unique ensemble model, comprising a dual-layer structure, is developed for STN localization. We harnessed the capabilities of support vector machine, Decision tree and k-Nearest Neighbor in conjunction with long short-term memory (LSTM) network. LSTM is pivotal for assigning adequate weights to every base model., Results: Results reveal that the proposed model achieved a remarkable accuracy and F1-score of 89.49% and 91.63%., Comparison With Existing Methods: Ensemble model demonstrated superior performance when compared to standalone base models and existing meta techniques., Conclusion: This framework is envisioned to enhance the efficiency of DBS surgery and reduce the reliance on clinician experience for precise STN detection. This achievement is strategically significant to serve as an invaluable tool for refining the electrode trajectory, potentially replacing the current methodology based on MER., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Integration of bioelectronic devices in clinical practice is expanding rapidly, focusing on conditions ranging from sensory to neurological and mental health disorders. While platinum (Pt) electrodes in neuromodulation devices such as cochlear implants and deep brain stimulators have shown promising results, challenges still affect their long-term performance. Key among these are electrode and device longevity in vivo, and formation of encapsulating fibrous tissue. To overcome these challenges, organic conductors with unique chemical and physical properties are being explored. They hold great promise as coatings for neural interfaces, offering more rapid regulatory pathways and clinical implementation than standalone bioelectronics. This study provides a comprehensive review of the potential benefits of organic coatings in neuromodulation electrodes and the challenges that limit their effective integration into existing devices. It discusses issues related to metallic electrode use and introduces physical, electrical, and biological properties of organic coatings applied in neuromodulation. Furthermore, previously reported challenges related to organic coating stability, durability, manufacturing, and biocompatibility are thoroughly reviewed and proposed coating adhesion mechanisms are summarized. Understanding organic coating properties, modifications, and current challenges of organic coatings in clinical and industrial settings is expected to provide valuable insights for their future development and integration into organic bioelectronics., (© 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Precise assessment of wakefulness states during sevoflurane anesthesia and timely arousal are of paramount importance to refine the control of anesthesia. To tackle this issue, a bidirectional implantable microelectrode array (MEA) is designed with the capability to detect electrophysiological signal and perform in situ deep brain stimulation (DBS) within the dorsomedial hypothalamus (DMH) of mice. The MEA, modified with platinum nanoparticles/IrOx nanocomposites, exhibits exceptional characteristics, featuring low impedance, minimal phase delay, substantial charge storage capacity, high double-layer capacitance, and longer in vivo lifetime, thereby enhancing the sensitivity of spike firing detection and electrical stimulation (ES) effectiveness. Using this MEA, sevoflurane-inhibited neurons and sevoflurane-excited neurons, together with changes in the oscillation characteristics of the local field potential within the DMH, are revealed as indicative markers of arousal states. During the arousal period, varying-frequency ESs are applied to the DMH, eliciting distinct arousal effects. Through in situ detection and stimulation, the disparity between these outcomes can be attributed to the influence of DBS on different neurons. These advancements may further our understanding of neural circuits and their potential applications in clinical contexts.

Precise neurostimulation can revolutionize therapies for neurological disorders. Electrode-based stimulation devices face challenges in achieving precise and consistent targeting due to the immune response and the limited penetration of electrical fields. Ultrasound can aid in energy propagation, but transcranial ultrasound stimulation in the deep brain has limited spatial resolution caused by bone and tissue scattering. Here, we report an implantable piezoelectric ultrasound stimulator (ImPULS) that generates an ultrasonic focal pressure of 100 kPa to modulate the activity of neurons. ImPULS is a fully-encapsulated, flexible piezoelectric micromachined ultrasound transducer that incorporates a biocompatible piezoceramic, potassium sodium niobate [(K,Na)NbO 3 ]. The absence of electrochemically active elements poses a new strategy for achieving long-term stability. We demonstrated that ImPULS can i) excite neurons in a mouse hippocampal slice ex vivo, ii) activate cells in the hippocampus of an anesthetized mouse to induce expression of activity-dependent gene c-Fos, and iii) stimulate dopaminergic neurons in the substantia nigra pars compacta to elicit time-locked modulation of nigrostriatal dopamine release. This work introduces a non-genetic ultrasound platform for spatially-localized neural stimulation and exploration of basic functions in the deep brain., (© 2024. The Author(s).)

A CMOS analog front-end (AFE) local-field potential (LFP) chopper amplifier with stimulation artifact tolerance, improved right-leg driven (RLD) circuit, and improved auxiliary path is proposed. In the proposed CMOS AFE LFP chopper amplifier, common-mode artifact voltage (CMAV) and differential-mode artifact voltage (DMAV) removal using the analog template removal method are proposed to achieve good signal linearity during stimulation. An improved auxiliary path is employed to boost the input impedance and allow the negative stimulation artifact voltage passing through. The common-mode noise is suppressed by the improved RLD circuit. The chip is implemented in 0.18- μm CMOS technology and the total chip area is 5.46-mm 2 . With the improved auxiliary path, the measured input impedance is larger than 133 M[Formula: see text] in the signal bandwidth and reaches 8.2 G[Formula: see text] at DC. With the improved RLD circuit, the measured CMRR is 131 - 144 dB in the signal bandwidth. Under 60-μs pulse width and 130-Hz constant current stimulation (CCS) with ±1-V CMAV and ±50-mV DMAV, the measured THD at the SC Amp output of fabricated AFE LFP chopper amplifier is 1.28%. The measurement results of In vitro agar tests have shown that with ±1.6-mA CCS pulses injecting to agar, the measured THD is 1.69%. Experimental results of both electrical and agar tests have verified that the proposed AFE LFP chopper amplifier has good stimulation artifact tolerance. The proposed CMOS AFE LFP chopper amplifier with analog template removal method is suitable for real-time closed-loop deep drain stimulation (DBS) SoC applications.

Objectives: We have previously proposed that Tourette syndrome (TS) is the clinical expression of the hyperactivity of globus pallidus externus (GPe) and various cortical areas. This study was designed to test this hypothesis by verifying the efficacy and safety of bilateral GPe deep brain stimulation (DBS) for treating refractory TS., Materials and Methods: In this open clinical trial, 13 patients were operated on. Target coordinates (center of GPe) were obtained by direct visualization. Physiological mapping was performed with macrostimulation and microrecording. Primary and secondary outcome measures were, respectively, responder and improvement rates of TS and comorbidities, according to pre- and postoperative scores on the following assessment instruments: Yale Global Tic Severity Scale, Yale-Brown Obsessive Compulsive Scale, Beck Depression Inventory/Hamilton Depression Rating Scale, Beck Anxiety Inventory/Hamilton Anxiety Rating Scale, and Concentrated Attention test., Results: Intraoperative stimulation (100 Hz/5.0V) did not produce any adverse effects or impact on tics. Microrecording revealed bursting cells discharging synchronously with tics in the central part of the dorsal half of GPe. Patients were followed up for a mean of 61.46±48.50 months. Responder rates were 76.9%, 75%, 71.4%, 71.4%, and 85.7%, respectively, for TS, obsessive-compulsive disorder (OCD), depression, anxiety, and attention deficit hyperactivity disorder. Mean improvements among responders in TS, OCD, depression, and anxiety were 77.4%, 74.7%, 89%, and 84.8%, respectively. After starting stimulation, tic improvement was usually delayed, taking up to ten days to manifest. Afterward, it increased over time, usually reaching its maximum at approximately one year postoperatively. The best stimulation parameters were 2.3V to 3.0V, 90 to 120 μsec, and 100 to 150 Hz, and the most effective contacts were the two dorsal ones. Two complications were registered: reversible impairment of previous depression and transient unilateral bradykinesia., Conclusions: Bilateral GPe-DBS proved to be low risk and quite effective for treating TS and comorbidities, ratifying the pathophysiological hypothesis that led to this study. Moreover, it compared favorably with DBS of other targets currently in use., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Ultrasound-driven bioelectronics could offer a wireless scheme with sustainable power supply; however, current ultrasound implantable systems present critical challenges in biocompatibility and harvesting performance related to lead/lead-free piezoelectric materials and devices. Here, we report a lead-free dual-frequency ultrasound implants for wireless, biphasic deep brain stimulation, which integrates two developed lead-free sandwich porous 1-3-type piezoelectric composite elements with enhanced harvesting performance in a flexible printed circuit board. The implant is ultrasonically powered through a portable external dual-frequency transducer and generates programmable biphasic stimulus pulses in clinically relevant frequencies. Furthermore, we demonstrate ultrasound-driven implants for long-term biosafety therapy in deep brain stimulation through an epileptic rodent model. With biocompatibility and improved electrical performance, the lead-free materials and devices presented here could provide a promising platform for developing implantable ultrasonic electronics in the future., (© 2024. The Author(s).)

Implantable brain recording and stimulation devices apply to a broad spectrum of conditions, such as epilepsy, movement disorders and depression. For long-term monitoring and neuromodulation in epilepsy patients, future extracranial subscalp implants may offer a promising, less-invasive alternative to intracranial neurotechnologies. To inform the design and assess the safety profile of such next-generation devices, we estimated extracranial complication rates of deep brain stimulation (DBS), cranial peripheral nerve stimulation (PNS), responsive neurostimulation (RNS) and existing subscalp EEG devices (sqEEG), as proxy for future implants. Pubmed was searched systematically for DBS, PNS, RNS and sqEEG studies from 2000 to February 2024 (48 publications, 7329 patients). We identified seven categories of extracranial adverse events: infection, non-infectious cutaneous complications, lead migration, lead fracture, hardware malfunction, pain and hemato-seroma. We used cohort sizes, demographics and industry funding as metrics to assess risks of bias. An inverse variance heterogeneity model was used for pooled and subgroup meta-analysis. The pooled incidence of extracranial complications reached 14.0%, with infections (4.6%, CI 95% [3.2 - 6.2]), surgical site pain (3.2%, [0.6 - 6.4]) and lead migration (2.6%, [1.0 - 4.4]) as leading causes. Subgroup analysis showed a particularly high incidence of persisting pain following PNS (12.0%, [6.8 - 17.9]) and sqEEG (23.9%, [12.7 - 37.2]) implantation. High rates of lead migration (12.4%, [6.4 - 19.3]) were also identified in the PNS subgroup. Complication analysis of DBS, PNS, RNS and sqEEG studies provides a significant opportunity to optimize the safety profile of future implantable subscalp devices for chronic EEG monitoring. Developing such promising technologies must address the risks of infection, surgical site pain, lead migration and skin erosion. A thin and robust design, coupled to a lead-anchoring system, shall enhance the durability and utility of next-generation subscalp implants for long-term EEG monitoring and neuromodulation., Competing Interests: Declaration of Competing Interest M.O.B. and G.K. hold shares with Epios, Ltd., a medical device company based in Geneva, Switzerland that develops a sub-scalp EEG system; C.P. is co-founder of Aleva Neurotherapeutics, a medical device company based in Lausanne Switzerland, currently without any active role in the company. The other authors report no conflict of interest. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Transcranial ultrasound stimulation (TUS) is a non-invasive brain stimulation technique; when skull aberrations are compensated for, this technique allows, with millimetric accuracy, circumvention of the invasive surgical procedure associated with deep brain stimulation (DBS) and the limited spatial specificity of transcranial magnetic stimulation., Objective: /hypothesis: We hypothesize that MR-guided low-power TUS can induce a sustained decrease of tremor power in patients suffering from medically refractive essential tremor., Methods: The dominant hand only was targeted, and two anatomical sites were sonicated in this exploratory study: the ventral intermediate nucleus of the thalamus (VIM) and the dentato-rubro-thalamic tract (DRT). Patients (N = 9) were equipped with MR-compatible accelerometers attached to their hands to monitor their tremor in real-time during TUS., Results: VIM neurostimulations followed by a low-duty cycle (5 %) DRT stimulation induced a substantial decrease in the tremor power in four patients, with a minimum of 89.9 % reduction when compared with the baseline power a few minutes after the DRT stimulation. The only patient stimulated in the VIM only and with a low duty cycle (5 %) also experienced a sustained reduction of the tremor (up to 93.4 %). Four patients (N = 4) did not respond. The temperature at target was 37.2 ± 1.4 °C compared to 36.8 ± 1.4 °C for a 3 cm away control point., Conclusions: MR-guided low power TUS can induce a substantial and sustained decrease of tremor power. Follow-up studies need to be conducted to reproduce the effect and better to understand the variability of the response amongst patients. MR thermometry during neurostimulations showed no significant thermal rise, supporting a mechanical effect., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: IR and YS are employees of Insightec. JFA received a research grant from Insightec for preclinical work on transcranial ultrasound., (Copyright © 2024. Published by Elsevier Inc.)

While The Big medical device makers may have a deep-pockets advantage in the neurostimulation space, many smaller players are innovating their way to advances that offer tantalizing hope for changing patients' lives.

Ingestible electronic pills can be used for targeted noninvasive neuromodulation.

Importance: Establishing a formal definition for neurological device abandonment has the potential to reduce or to prevent the occurrence of this abandonment., Objective: To perform a systematic review of the literature and develop an expert consensus definition for neurological device abandonment., Evidence Review: After a Royal Society Summit on Neural Interfaces (September 13-14, 2023), a systematic English language review using PubMed was undertaken to investigate extant definitions of neurological device abandonment. Articles were reviewed for relevance to neurological device abandonment in the setting of deep brain, vagal nerve, and spinal cord stimulation. This review was followed by the convening of an expert consensus group of physicians, scientists, ethicists, and stakeholders. The group summarized findings, added subject matter experience, and applied relevant ethics concepts to propose a current operational definition of neurological device abandonment. Data collection, study, and consensus development were done between September 13, 2023, and February 1, 2024., Findings: The PubMed search revealed 734 total articles, and after review, 7 articles were found to address neurological device abandonment. The expert consensus group addressed findings as germane to neurological device abandonment and added personal experience and additional relevant peer-reviewed articles, addressed stakeholders' respective responsibilities, and operationally defined abandonment in the context of implantable neurotechnological devices. The group further addressed whether clinical trial failure or shelving of devices would constitute or be associated with abandonment as defined. Referential to these domains and dimensions, the group proposed a standardized definition for abandonment of active implantable neurotechnological devices., Conclusions and Relevance: This study's consensus statement suggests that the definition for neurological device abandonment should entail failure to provide fundamental aspects of patient consent; fulfill reasonable responsibility for medical, technical, or financial support prior to the end of the device's labeled lifetime; and address any or all immediate needs that may result in safety concerns or device ineffectiveness and that the definition of abandonment associated with the failure of a research trial should be contingent on specific circumstances.

Background and Objectives: Robotic assistance has garnered increased use in neurosurgery. Recently, this has expanded to include deep brain stimulation (DBS). Several studies have reported increased accuracy and improved efficiency with robotic assistance, but these are limited to individual robotic platforms with smaller sample sizes or are broader studies on robotics not specific to DBS. Our objectives are to report our technique for robot-assisted, minimally invasive, asleep, single-stage DBS surgery and to perform a meta-analysis comparing techniques from previous studies., Methods: We performed a single-center retrospective review of DBS procedures using a floor-mounted robot with a frameless transient fiducial array registration. We compiled accuracy data (radial entry error, radial target error, and 3-dimensional target error) and efficiency data (operative time, setup time, and total procedure time). We then performed a meta-analysis of previous studies and compared these metrics., Results: We analyzed 315 electrodes implanted in 160 patients. The mean radial target error was 0.9 ± 0.5 mm, mean target 3-dimensional error was 1.3 ± 0.7 mm, and mean radial entry error was 1.1 ± 0.8 mm. The mean procedure time (including pulse generator placement) was 182.4 ± 47.8 minutes, and the mean setup time was 132.9 ± 32.0 minutes. The overall complication rate was 8.8% (2.5% hemorrhagic/ischemic, 2.5% infectious, and 0.6% revision). Our meta-analysis showed increased accuracy with floor-mounted over skull-mounted robotic platforms and with fiducial-based registrations over optical registrations., Conclusion: Our technique for robot-assisted, minimally invasive, asleep, single-stage DBS surgery is safe, accurate, and efficient. Our data, combined with a meta-analysis of previous studies, demonstrate that robotic assistance can provide similar or increased accuracy and improved efficiency compared with traditional frame-based techniques. Our analysis also suggests that floor-mounted robots and fiducial-based registration methods may be more accurate., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Prader-Willi syndrome (PWS) is a complex, genetic disorder characterized by multisystem involvement, including hyperphagia, maladaptive behaviors and endocrinological derangements. Recent developments in advanced neuroimaging have led to a growing understanding of PWS as a neural circuit disorder, as well as subsequent interests in the application of neuromodulatory therapies. Various non-invasive and invasive device-based neuromodulation methods, including vagus nerve stimulation (VNS), transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS) have all been reported to be potentially promising treatments for addressing the major symptoms of PWS. In this systematic literature review, we summarize the recent literature that investigated these therapies, discuss the underlying circuits which may underpin symptom manifestations, and cover future directions of the field. Through our comprehensive search, there were a total of 47 patients who had undergone device-based neuromodulation therapy for PWS. Two articles described VNS, 4 tDCS, 1 rTMS and 2 DBS, targeting different symptoms of PWS, including aberrant behavior, hyperphagia and weight. Multi-center and multi-country efforts will be required to advance the field given the low prevalence of PWS. Finally, given the potentially vulnerable population, neuroethical considerations and dialogue should guide the field., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Aysegul Gunduz reports a relationship with Medtronic Inc that includes: funding grants. Casey H. Halpern reports a relationship with Boston Scientific Corp that includes: consulting or advisory and speaking and lecture fees. Casey H. Halpern reports a relationship with Insightec that includes: consulting or advisory and speaking and lecture fees. Casey H. Halpern reports a relationship with SynchNeuro Inc that includes: board membership and equity or stocks. Michael S. Okun reports a relationship with Parkinson's Foundation that includes: consulting or advisory and funding grants. Michael S. Okun reports a relationship with National Institutes of Health that includes: funding grants. Michael S. Okun reports a relationship with Michael J. Fox Foundation, Parkinson Alliance, Smallwood Foundation, Bachmann-Strauss Foundation, Tourette Syndrome Association, UF Foundation that includes: funding grants. Casey H. Halpern has patent #USPTO serial number: 63/170,404 and 63/220,432 issued to Stanford University. Casey H. Halpern has patent #USPTO serial number: 63/210,472 pending to SynchNeuro. Michael S. Okun has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford and Cambridge (movement disorders books). M.S.O. is an associate editor for New England Journal of Medicine Journal Watch Neurology and JAMA Neurology. He has participated in CME and educational activities (past 12–24 months) on movement disorders sponsored by WebMD/Medscape, RMEI Medical Education, American Academy of Neurology, Movement Disorders Society, Mediflix and by Vanderbilt University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Conventional frame-based stereotactic systems have circumferential base frames, often necessitating deep brain stimulation (DBS) surgery in two stages: intracranial electrode insertion followed by surgical re-preparation and pulse generator implantation. Some patients do not tolerate awake surgery, underscoring the need for a safe alternative for asleep DBS surgery. A frame-based stereotactic system with a skull-mounted "key" in lieu of a circumferential base frame received US FDA clearance. The authors describe the system's application for single-stage, asleep DBS surgery in 8 patients at their institution and review its workflow and technical considerations., Methods: Eight patients underwent DBS lead insertion and IPG implantation in a single surgical preparation under general anesthesia using the system. Postoperative CT imaging confirmed lead placement., Results: Eight patients underwent implantation of 15 total leads targeting the ventral intermediate nucleus (4 patients), globus pallidus internus (GPi; 3 patients), and subthalamic nucleus (STN; 1 patient). Intraoperative microelectrode recording was conducted for GPi and STN targets. Postoperative CT imaging revealed a mean ± SD radial error of 1.24 ± 0.45 mm (n = 15 leads), without surgical complications., Conclusions: The stereotactic system facilitated safe and effective asleep, single-stage DBS surgery, maintaining traditional lead accuracy standards.

Deep brain stimulation (DBS), including optical stimulation and electrical stimulation, has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders. Advances in DBS microsystems based on implantable microelectrode array (MEA) probes have opened up new opportunities for closed-loop DBS (CL-DBS) in situ. This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously. Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems, key challenges, including excessive wired communication, need to be urgently resolved. In this review, we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field. This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.

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.

Introduction: DBS efficacy depends on accuracy. CT-MRI fusion is established for both stereotactic registration and electrode placement verification. The desire to streamline DBS workflows, reduce operative time, and minimize patient transfers has increased interest in portable imaging modalities such as the Medtronic O-arm® and mobile CT. However, these remain expensive and bulky. 3D C-arm fluoroscopy (3DXT) units are a smaller and less costly alternative, albeit incompatible with traditional frame-based localization and without useful soft tissue resolution. We aimed to compare fusion of 3DXT and CT with pre-operative MRI to evaluate if 3DXT-MRI fusion alone is sufficient for accurate registration and reliable targeting verification. We further assess DBS targeting accuracy using a 3DXT workflow and compare radiation dosimetry between modalities., Methods: Patients underwent robot-assisted DBS implantation using a workflow incorporating 3DXT which we describe. Two intra-operative 3DXT spins were performed for registration and accuracy verification followed by conventional CT post-operatively. Post-operative 3DXT and CT images were independently fused to the same pre-operative MRI sequence and co-ordinates generated for comparison. Registration accuracy was compared to 15 consecutive controls who underwent CT-based registration. Radial targeting accuracy was calculated and radiation dosimetry recorded., Results: Data were obtained from 29 leads in 15 consecutive patients. 3DXT registration accuracy was significantly superior to CT with mean error 0.22 ± 0.03 mm (p < 0.0001). Mean Euclidean electrode tip position variation for CT to MRI versus 3DXT to MRI fusion was 0.62 ± 0.40 mm (range 0.0 mm-1.7 mm). In comparison, direct CT to 3DXT fusion showed electrode tip Euclidean variance of 0.23 ± 0.09 mm. Mean radial targeting accuracy assessed on 3DXT was 0.97 ± 0.54 mm versus 1.15 ± 0.55 mm on CT with differences insignificant (p = 0.30). Mean patient radiation doses were around 80% lower with 3DXT versus CT (p < 0.0001)., Discussion: Mobile 3D C-arm fluoroscopy can be safely incorporated into DBS workflows for both registration and lead verification. For registration, the limited field of view requires the use of frameless transient fiducials and is highly accurate. For lead position verification based on MRI co-registration, we estimate there is around a 0.4 mm discrepancy between lead position seen on 3DXT versus CT when corrected for brain shift. This is similar to that described in O-arm® or mobile CT series. For units where logistical or financial considerations preclude the acquisition of a cone beam CT or mobile CT scanner, our data support portable 3D C-arm fluoroscopy as an acceptable alternative with significantly lower radiation exposure., (© 2024 S. Karger AG, Basel.)

Introduction: We present our surgical complications resulting in neurological deficit or additional surgery during 25 years of DBS of the subthalamic nucleus (STN) for Parkinson's disease (PD)., Methods: We conducted a retrospective chart review of all PD patients that received STN DBS in our DBS center between 1998 and 2023. Outcomes were complications resulting in neurological deficit or additional surgery. Potential risk factors (number of microelectrode recording tracks, age, anesthesia method, hypertension, and sex) for symptomatic intracerebral hemorrhage (ICH) were analyzed. Furthermore, lead fixation techniques were compared., Results: Eight hundred PD patients (507 men, 293 women) received unilateral (n = 11) or bilateral (n = 789) implantation of STN electrodes. Neurological deficit due to ICH, edema, delirium, or infarction was seen in 8.4% of the patients (7.4% transient, 1.0% permanent). Twenty-two patients (2.8%) had a symptomatic ICH following STN DBS, for which we did not find any risk factors, and five had permanent sequelae due to ICH (0.6%). Of all patients, 18.4% required additional surgery; the proportion was reduced from 27% in the first 300 cases to 13% in the last 500 cases (p < 0.001). The infection rate was 3.5%, which decreased from 5.3% in the first 300 cases to 2.2% in the last 500 cases. The use of a lead anchoring device led to significantly less lead migrations than miniplate fixation., Conclusion: STN DBS leads to permanent neurological deficit in a small number of patients (1.0%), but a substantial proportion needs some additional surgical procedure after the first DBS system implantation. The risk of revision surgery was reduced over time but remained significant. These findings need to be discussed with the patient in the preoperative informed consent process in addition to the expected health benefit., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Infection after deep brain stimulation (DBS) implanted pulse generator (IPG) replacement is uncommon but when it occurs can cause significant clinical morbidity, often resulting in partial or complete DBS system removal. An antibiotic absorbable envelope developed for cardiac implantable electronic devices (IEDs), which releases minocycline and rifampicin for a minimum of 7 days, was shown in the WRAP-IT study to reduce cardiac IED infections for high-risk cardiac patients. We aimed to assess whether placing an IPG in the same antibiotic envelope at the time of IPG replacement reduced the IPG infection rate., Methods: Following institutional ethics approval (UnitingCare HREC), patients scheduled for IPG change due to impending battery depletion were prospectively randomised to receive IPG replacement with or without an antibiotic envelope. Patients with a past history of DBS system infection were excluded. Patients underwent surgery with standard aseptic neurosurgical technique [J Neurol Sci. 2017;383:135-41]. Subsequent infection requiring antibiotic therapy and/or IPG removal or revision was recorded., Results: A total of 427 consecutive patients were randomised from 2018 to 2021 and followed for a minimum of 12 months. No patients were lost to follow-up. At the time of IPG replacement, 200 patients received antibiotic envelope (54 female, 146 male, mean age 72 years), and 227 did not (43 female, 184 male, mean age 71 years). The two groups were homogenous for risk factors of infection. The IPG replacement infection rate was 2.1% (9/427). There were six infections, which required antibiotic therapy and/or IPG removal, in the antibiotic envelope group (6/200) and three in the non-envelope group (3/227) (p = 0.66)., Conclusion: This prospective randomised study did not find that an antibiotic envelope reduced the IPG infection rate in our 427 patients undergoing routine DBS IPG replacement. Further research to reduce IPG revisions and infections in a cost-effective manner is required., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Deep brain stimulation (DBS) requires a consistent electrical supply from the implantable pulse generator (IPG). Patients may struggle to monitor their IPG, risking severe complications in battery failure. This review assesses current literature on DBS IPG battery life management and proposes a protocol for healthcare providers., Methods: A literature search using four databases identified best practices for DBS IPG management. Studies were appraised for IPG management guidelines, categorized as qualitative, quantitative, or both., Results: Of 408 citations, only seven studies were eligible, none providing clear patient management strategies. Current guidelines lack specificity, relying on clinician suggestions., Conclusion: Limited guidelines exist for IPG management. Specificity and adaptability to emerging technology are crucial. The findings highlight the need for specificity in patients' needs and adaptability to emerging technology in future studies. To address this need, we developed a protocol for DBS IPG management that we have implemented at our own institution. Further research is needed for effective DBS IPG battery life management, preventing therapy cessation complications., (© 2024 S. Karger AG, Basel.)

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

Introduction: Deep brain stimulation (DBS) has become a well-established treatment modality for a variety of conditions over the last decades. Multiple surgeries are an essential part in the postoperative course of DBS patients if nonrechargeable implanted pulse generators (IPGs) are applied. So far, the rate of subclinical infections in this field is unknown. In this prospective cohort study, we used sonication to evaluate possible microbial colonization of IPGs from replacement surgery., Methods: All consecutive patients undergoing IPG replacement between May 1, 2019 and November 15, 2020 were evaluated. The removed hardware was investigated using sonication to detect biofilm-associated bacteria. Demographic and clinical data were analyzed., Results: A total of 71 patients with a mean (±SD) of 64.5 ± 15.3 years were evaluated. In 23 of these (i.e., 32.4%) patients, a positive sonication culture was found. In total, 25 microorganisms were detected. The most common isolated microorganisms were Cutibacterium acnes (formerly known as Propionibacterium acnes) (68%) and coagulase-negative Staphylococci (28%). Within the follow-up period (5.2 ± 4.3 months), none of the patients developed a clinical manifest infection., Discussions/conclusions: Bacterial colonization of IPGs without clinical signs of infection is common but does not lead to manifest infection. Further larger studies are warranted to clarify the impact of low-virulent pathogens in clinically asymptomatic patients., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Deep brain stimulation (DBS) is an established clinical therapy, and directional DBS electrode designs are now commonly used in clinical practice. Directional DBS leads have the ability to increase the therapeutic window of stimulation, but they also increase the complexity of clinical programming. Therefore, computational models of DBS have become available in clinical software tools that are designed to assist in the identification of therapeutic settings. However, the details of how the DBS model is implemented can influence the predictions of the software. The goal of this study was to compare different methods for representing directional DBS electrodes within finite element volume conductor (VC) models. We evaluated 15 different DBS VC model variants and quantified how their differences influenced estimates on the spatial extent of axonal activation from DBS. Each DBS VC model included the same representation of the brain and head, but the details of the current source and electrode contact were different for each model variant. The more complex VC models explicitly represented the DBS electrode contacts, while the more simple VC models used boundary condition approximations. The more complex VC models required 2-3 times longer to mesh, build, and solve for the DBS voltage distribution than the more simple VC models. Differences in individual axonal activation thresholds across the VC model variants were substantial (-24% to +47%). However, when comparing total activation of an axon population, or estimates of an activation volume, the differences between model variants decreased (-7% to +8%). Nonetheless, the technical details of how the electrode contact and current source are represented in the DBS VC model can directly affect estimates of the voltage distribution and electric field in the brain tissue., Competing Interests: CCM is a paid consultant for Boston Scientific Neuromodulation, receives royalties from Hologram Consultants, Neuros Medical, Qr8 Health, and is a shareholder in the following companies: Hologram Consultants, Surgical Information Sciences, CereGate, Autonomic Technologies, Cardionomic, Enspire DBS. AMN is a paid consultant for Hologram Consultants. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To investigate the effects on the blink reflex (BR) of single stimuli applied to the pedunculopontine tegmental nucleus (PPTg)., Methods: The BR was evoked by stimulating the supraorbital nerve (SON) in fifteen patients suffering from idiopathic Parkinson's disease (PD) who had electrodes monolaterally or bilaterally implanted in the PPTg for deep brain stimulation (DBS). Single stimuli were delivered to the PPTg through externalized electrode connection wires 3-4 days following PPTg implantation., Results: PPTg stimuli increased the latency and reduced duration, amplitude and area of the R2 component of the BR in comparison to the response recorded in the absence of PPTg stimulation. These effects were independent of the side of SON stimulation and were stable for interstimulus interval (ISI) between PPTg prepulse and SON stimulus from 0 to 110 ms. The PPTg-induced prepulse inhibition of the BR was bilaterally present in the brainstem. The R1 component was unaffected., Conclusions: The prepulse inhibition of the R2 component may be modulated by the PPTg., Significance: These findings suggest that abnormalities of BR occurring in PD may be ascribed to a reduction of basal ganglia-mediated inhibition of brainstem excitability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Deep brain stimulation (DBS) is used to treat the motor symptoms of Parkinson's disease patients by stimulating the subthalamic nucleus. However, optimization of DBS is still needed since the performance of the neural electrodes is limited by the body's response to the implant. This review discusses the issues with DBS, such as placement of electrodes, foreign body response, and electrode degradation. The current solutions to these technical issues include modifications to electrode material, coatings, and geometry., (© 2021 American Institute of Chemical Engineers.)

There has been a significant rise in robotic trajectory guidance devices that have been utilised for stereotactic neurosurgical procedures. These devices have significant costs and associated learning curves. Previous studies reporting devices usage have not undertaken prospective parallel-group comparisons before their introduction, so the comparative differences are unknown. We study the difference in stereoelectroencephalography electrode implantation time between a robotic trajectory guidance device (iSYS1) and manual frameless implantation (PAD) in patients with drug-refractory focal epilepsy through a single-blinded randomised control parallel-group investigation of SEEG electrode implantation, concordant with CONSORT statement. Thirty-two patients (18 male) completed the trial. The iSYS1 returned significantly shorter median operative time for intracranial bolt insertion, 6.36 min (95% CI 5.72-7.07) versus 9.06 min (95% CI 8.16-10.06), p = 0.0001. The PAD group had a better median target point accuracy 1.58 mm (95% CI 1.38-1.82) versus 1.16 mm (95% CI 1.01-1.33), p = 0.004. The mean electrode implantation angle error was 2.13° for the iSYS1 group and 1.71° for the PAD groups (p = 0.023). There was no statistically significant difference for any other outcome. Health policy and hospital commissioners should consider these differences in the context of the opportunity cost of introducing robotic devices.Trial registration: ISRCTN17209025 ( https://doi.org/10.1186/ISRCTN17209025 )., (© 2021. The Author(s).)

The extent to which functional MRI (fMRI) reflects direct neuronal changes remains unknown. Using 160 simultaneous electrical stimulation (es-fMRI) and intracranial brain stimulation recordings acquired in 26 individuals with epilepsy (with varying electrode locations), we tested whether brain networks dynamically change during intracranial brain stimulation, aiming to establish whether switching between brain networks is reduced after intracranial brain stimulation. As the brain spontaneously switches between a repertoire of intrinsic functional network configurations and the rate of switching is likely increased in epilepsy, we hypothesised that intracranial stimulation would reduce the brain's switching rate, thus potentially normalising aberrant brain network dynamics. To test this hypothesis, we quantified the rate that brain regions changed networks over time in response to brain stimulation, using network switching applied to multilayer modularity analysis of time-resolved es-fMRI connectivity. Network switching and synchrony was decreased after the first brain stimulation, followed by a more consistent pattern of network switching over time. This change was commonly observed in cortical networks and adjacent to the electrode targets. Our results suggest that neuronal perturbation is likely to modulate large-scale brain networks, and multilayer network modelling may be used to inform the clinical efficacy of brain stimulation in epilepsy., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Pallidal deep brain stimulation (DBS) is an important option for patients with severe dystonias, which are thought to arise from a disturbance in striatal control of the globus pallidus internus (GPi). The mechanisms of GPi-DBS are far from understood. Although a disturbance of striatal function is thought to play a key role in dystonia, the effects of DBS on cortico-striatal function are unknown. We hypothesised that DBS, via axonal backfiring, or indirectly via thalamic and cortical coupling, alters striatal function. We tested this hypothesis in the dt sz hamster, an animal model of inherited generalised, paroxysmal dystonia. Hamsters (dystonic and non-dystonic controls) were bilaterally implanted with stimulation electrodes in the GPi. DBS (130 Hz), and sham DBS, were performed in unanaesthetised animals for 3 h. Synaptic cortico-striatal field potentials, as well as miniature excitatory postsynaptic currents (mEPSC) and firing properties of medium spiny striatal neurones were recorded in brain slice preparations obtained immediately after EPN-DBS. The main findings were as follows: a. DBS increased cortico-striatal evoked responses in healthy, but not in dystonic tissue. b. Commensurate with this, DBS increased inhibitory control of these evoked responses in dystonic, and decreased inhibitory control in healthy tissue. c. Further, DBS reduced mEPSC frequency strongly in dystonic, and less prominently in healthy tissue, showing that also a modulation of presynaptic mechanisms is likely involved. d. Cellular properties of medium-spiny neurones remained unchanged. We conclude that DBS leads to dampening of cortico-striatal communication, and restores intrastriatal inhibitory tone., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Deep brain stimulation (DBS) is known to interfere with electrocardiographic (ECG) examinations. In emergency situations, such electrical interferences can not only thwart ECG diagnostics, but even induce an ECG pattern that causes the emergency medical service to initiate inadequate or even harmful therapy. Aim of this prospective study was to evaluate factors influencing ECG interpretation in DBS and to evaluate the susceptibility of ECG criteria 'frequency', 'rhythm', 'regularity', 'QRS-configuration', and 'ST-segment' on neurostimulation., Patients and Methods: In 33 DBS patients (17 male, 16 female, mean age 64 years), limb-, 12 channel-, Nehb, and adhesive paddle-lead ECG were performed in activated (n = 33) and deactivated (n = 31) stimulation mode during outpatient follow-up examinations. The examinations were carried out using three different ECG devices (two portable emergency ECG-monitor/defibrillation/pacer-devices, one stationary hospital device), resulting in 4096 ECG leads. Statistics have been based on regression analyses and on a maximum likelihood estimation regression model., Results: Monopolar settings were found to be a relevant factor interfering significantly more often with ECG recording than bipolar parameters (p < 0.0001). Due to recurring movement artefacts, deactivation of bipolar stimulation might even significantly worsen ECG quality (p < 0.0001). Interpretability of 'rhythm' (β = -0.088, p = 0.03) and 'frequency' (β = -0.110, p = 0.02) revealed significant negative correlation to the applied neurostimulation voltage. Nehb lead yielded in highest ECG interpretability., Conclusion: Bipolar neurostimulation mode barely affected the ECGs; furthermore, the suppression of motion artefacts by neurostimulation can improve ECG quality. If monopolar neurostimulation is required, at least, stimulation voltage should be as low as possible to obtain good stimulation results., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Several software and hardware advances in the field of deep brain stimulation (DBS) have been realized in recent years and devices from three manufacturers are available. The Percept™ PC platform (Medtronic, Inc.) enables brain sensing, the latest innovation. Clinicians should be familiar with the differences in devices, and with the latest technologies to deliver optimized patient care. Areas covered : In this device profile, the sensing capabilities of the Percept™ PC platform are described, and the system capabilities are differentiated from other available platforms. The development of the preceding Activa™ PC+S research platform, an investigational device to simultaneously sense brain signals and provide therapeutic stimulation, is provided to place Percept™ PC in the appropriate context. Expert opinion : Percept™ PC offers unique sensing and diary functions as a means to refine therapeutic stimulation, track symptoms and correlate them to neurophysiologic characteristics. Additional features enhance the patient experience with DBS, including 3 T magnetic resonance imaging compatibility, wireless telemetry, a smaller and thinner battery profile, and increased battery longevity. Future work will be needed to illustrate the clinical utility and added value of using sensing to optimize DBS therapy. Patients implanted with Percept™ PC will have ready access to future technology developments.

Deep brain stimulation (DBS) has evolved into an approved and efficacious treatment for movement, obsessive-compulsive, and epilepsy disorders that are refractory to medical therapy, with current investigation into other disease conditions. However, there are unintentional and intentional sources of external electromagnetic interference (EMI) that can lead to either malfunctioning or damaged DBS devices, as well as injury to human tissue. Comprehensive studies and guidelines on such topics in the medical literature are scarce. Herein, we review the principles behind EMI, as well as the various potential sources of interference, both unintentional (e.g. stray EMI fields) and intentional (e.g. MRI scans, "brainjacking"). Additionally, we employ the Manufacturer and User Device Facility Experience (MAUDE) database to assess real-world instances of EMI (e.g., airport body scanners, magnetic resonance imaging (MRI), and electrosurgery) affecting DBS devices commonly implanted in the United States (US)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Deep brain stimulation (DBS) is an important treatment for patients with advanced Parkinson's disease (PD). Patients after DBS implantation need specialized programming to get optimal outcomes. However, access to timely and economical postoperative programming for many patients living in remote areas is limited. Teleprogramming, which refers to deliver real-time remote programming through Internet, can help to address this gap., Objective: We aimed to evaluate the clinical application of remote programming for PD patients with DBS., Methods: We retrospectively studied 90 patients with PD who received remote DBS programming after implantation at Yuquan Hospital (Beijing, China) between March 2016 and June 2018. Patients' medical records were reviewed in an electronic database. A self-designed questionnaire was performed on all patients by phone., Results: Over a mean follow-up period of 27.0 months, 90 patients underwent a total of 386 remote programming visits, of which the average frequency within 6 months after DBS was 2.27 times/person. The average distance between the patients' residences and Yuquan Hospital was 1243.8 ± 746.5 km. The questionnaire survey showed that each remote programming visit saved ≥2000¥ for 76.7% of the patients and ≥12 hours for 90.0% of the patients, compared with the on-site programming visit. The acceptability of the remote programming platform was highly rated. Transient side effects related to programming were reported and were relieved after adjustments of parameters., Conclusions: Remote programming may offer a feasible and acceptable approach to timely and economic management in patients with PD after DBS implantation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. DBS is a standard of care in Parkinson disease, essential tremor and dystonia, and is also under active investigation for other conditions linked to pathological circuitry, including major depressive disorder and Alzheimer disease. Modern DBS systems, borrowed from the cardiac field, consist of an intracranial electrode, an extension wire and a pulse generator, and have evolved slowly over the past two decades. Advances in engineering and imaging along with an improved understanding of brain disorders are poised to reshape how DBS is viewed and delivered to patients. Breakthroughs in electrode and battery designs, stimulation paradigms, closed-loop and on-demand stimulation, and sensing technologies are expected to enhance the efficacy and tolerability of DBS. In this Review, we provide a comprehensive overview of the technical development of DBS, from its origins to its future. Understanding the evolution of DBS technology helps put the currently available systems in perspective and allows us to predict the next major technological advances and hurdles in the field.