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Objectives: Target localization for deep brain stimulation (DBS) is a crucial step that influences the clinical benefit of the DBS procedure together with the reduction of side effects. In this work, we address the feasibility of DBS target localization in the globus pallidus internus (GPi) aided by intraoperative motor evoked potentials (MEP) with emphasis on the reduction of capsular side effects., Material and Methods: Micro-macroelectrode recordings were performed intraoperatively on 20 patients that underwent DBS treatment of the GPi (GPi-DBS). MEP were elicited intraoperatively by microelectrode stimulation during stereotactic DBS surgery. We studied the relationship between MEP thresholds and the internal capsule (IC) proximity., Results: We found a significant correlation between intraoperative MEP thresholds and IC proximity., Conclusions: We provide further evidence of the role of MEPs for DBS target localization in the GPi, which extends and confirms the usefulness of MEPs as previously reported by DBS target localization studies dealing with the subthalamic and thalamic nuclei. Our approach is advantageous in that it provides criteria to determine the DBS target without the need to rely on a patient's response while avoiding capsular effects., Competing Interests: Declaration of competing interest CT reports no conflict of interest. PN received travel expenses from Abbott Medical and Boston Scientific, manufacturers of DBS devices. PJS received speaker honoraria and travel reimbursement from Abbott Medical. JV received consultant fees and/or travel grants and/or research grants from Abbott, Boston Scientific, Medtronic, UniQure. AS reports grants from German Research Council; personal fees from Medtronic Inc., Boston Scientific, Abbott Medical, UCB, and Teva Pharma. SJG received honoraria and/or travel expenses from Abbott Medical, Boston Scientific, Inomed and Medtronic., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: One of the main challenges posed by the surgical deep brain stimulation (DBS) procedure is the successful targeting of the structures of interest and avoidance of side effects, especially in asleep surgery. Here, intraoperative motor evoked potentials (MEPs) might serve as tool to identify the pyramidal tract. We hypothesized that intraoperative MEPs are useful to define the distance to the pyramidal tract and reduce the occurrence of postoperative capsular side effects., Materials and Methods: Motor potentials were evoked through both microelectrode and DBS-electrode stimulation during stereotactic DBS surgery on 25 subthalamic nuclei and 3 ventral intermediate thalamic nuclei. Internal capsule proximity was calculated for contacts on microelectrode trajectories, as well as for DBS-electrodes, and correlated with the corresponding MEP thresholds. Moreover, the predictivity of intraoperative MEP thresholds on the probability of postoperative capsular side effects was calculated., Results: Intraoperative MEPs thresholds correlated significantly with internal capsule proximity, regardless of the stimulation source. Furthermore, MEPs thresholds were highly accurate to exclude the occurrence of postoperative capsular side effects., Conclusions: Intraoperative MEPs provide additional targeting guidance, especially in asleep DBS surgery, where clinical value of microelectrode recordings and test stimulation may be limited. As this technique can exclude future capsular side effects, it can directly be translated into clinical practice., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Published reports on directional deep brain stimulation (DBS) have been limited to small, single-center investigations. Therapeutic window (TW) is used to describe the range of stimulation amplitudes achieving symptom relief without side effects. This crossover study performed a randomized double-blind assessment of TW for directional and omnidirectional DBS in a large cohort of patients implanted with a DBS system in the subthalamic nucleus for Parkinson's disease., Materials and Methods: Participants received omnidirectional stimulation for the first three months after initial study programming, followed by directional DBS for the following three months. The primary endpoint was a double-blind, randomized evaluation of TW for directional vs omnidirectional stimulation at three months after initial study programming. Additional data recorded at three- and six-month follow-ups included stimulation preference, therapeutic current strength, Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score, and quality of life., Results: The study enrolled 234 subjects (62 ± 8 years, 33% female). TW was wider using directional stimulation in 183 of 202 subjects (90.6%). The mean increase in TW with directional stimulation was 41% (2.98 ± 1.38 mA, compared to 2.11 ± 1.33 mA for omnidirectional). UPDRS part III motor score on medication improved 42.4% at three months (after three months of omnidirectional stimulation) and 43.3% at six months (after three months of directional stimulation) with stimulation on, compared to stimulation off. After six months, 52.8% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, and 25.9% (50/193) preferred the omnidirectional period. The directional period was preferred by 58.5% of clinicians (113/193) vs 21.2% (41/193) who preferred the omnidirectional period., Conclusion: Directional stimulation yielded a wider TW compared to omnidirectional stimulation and was preferred by blinded subjects and clinicians., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Deep brain stimulation (DBS), an effective treatment for movement disorders, usually involves lead implantation while the patient is awake and sedated. Recently, there has been interest in performing the procedure under general anesthesia (asleep). This report of a consecutive cohort of DBS patients describes anesthesia protocols for both awake and asleep procedures., Methods: Consecutive patients with Parkinson's disease received subthalamic nucleus (STN) implants either moderately sedated or while intubated, using propofol and remifentanil. Microelectrode recordings were performed with up to five trajectories after discontinuing sedation in the awake group, or reducing sedation in the asleep group. Clinical outcome was compared between groups with the UPDRS III., Results: The awake group (n = 17) received 3.5 mg/kg/h propofol and 11.6 μg/kg/h remifentanil. During recording, all anesthesia was stopped. The asleep group (n = 63) initially received 6.9 mg/kg/h propofol and 31.3 μg/kg/h remifentanil. During recording, this was reduced to 3.1 mg/kg/h propofol and 10.8 μg/kg/h remifentanil. Without parkinsonian medications or stimulation, 3-month UPDRS III ratings (ns = 16 and 52) were 40.8 in the awake group and 41.4 in the asleep group. Without medications but with stimulation turned on, ratings improved to 26.5 in the awake group and 26.3 in the asleep group. With both medications and stimulation, ratings improved further to 17.6 in the awake group and 15.3 in the asleep group. All within-group improvements from the off/off condition were statistically significant (all ps < 0.01). The degree of improvement with stimulation, with or without medications, was not significantly different in the awake vs. asleep groups (ps > 0.05)., Conclusion: The above anesthesia protocols make possible an asleep implant procedure that can incorporate sufficient microelectrode recording. Together, this may increase patient comfort and improve clinical outcomes., (© 2022. The Author(s).)

Objective: The effect of anesthesia type in terms of asleep vs. awake deep brain stimulation (DBS) surgery on therapeutic window (TW) has not been investigated so far. The objective of the study was to investigate whether asleep DBS surgery of the subthalamic nucleus (STN) improves TW for both directional (dDBS) and omnidirectional (oDBS) stimulation in a large single-center population., Materials and Methods: A total of 104 consecutive patients with Parkinson's disease (PD) undergoing STN-DBS surgery (80 asleep and 24 awake) were compared regarding TW, therapeutic threshold, side effect threshold, improvement of Unified PD Rating Scale motor score (UPDRS-III) and degree of levodopa equivalent daily dose (LEDD) reduction., Results: Asleep DBS surgery led to significantly wider TW compared to awake surgery for both dDBS and oDBS. However, dDBS further increased TW compared to oDBS in the asleep group only and not in the awake group. Clinical efficacy in terms of UPDRS-III improvement and LEDD reduction did not differ between groups., Conclusions: Our study provides first evidence for improvement of therapeutic window by asleep surgery compared to awake surgery, which can be strengthened further by dDBS. These results support the notion of preferring asleep over awake surgery but needs to be confirmed by prospective trials., (© 2020 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals LLC. on behalf of International Neuromodulation Society.)

Objectives: Deep brain stimulation (DBS) of the posterior subthalamic area (PSA) and the ventral intermediate thalamic nucleus (VIM) is a well-established therapy for essential tremor (ET), but it is frequently associated with side effects like dysarthria or gait ataxia. Directional DBS (dDBS) may be a way to activate fiber tracts more selectively. Is dDBS for ET superior to omnidirectional DBS (oDBS) regarding therapeutic window and clinically as effective as oDBS?, Materials and Methods: Ten patients with ET treated with PSA/VIM-DBS were recruited. Therapeutic window served as primary outcome parameter; clinical efficacy, volume of neuronal activation, and total electrical energy delivered (TEED) served as secondary outcome parameters. Therapeutic window was calculated for all three dDBS directions and for oDBS by determining therapeutic thresholds and side effect thresholds. Clinical efficacy was assessed by comparing the effect of best dDBS and oDBS on tremor and ataxia rating scales, and accelerometry. Volume of neural activation and TEED were also calculated for both paradigms., Results: For best dDBS, therapeutic window was wider and therapeutic threshold was lower compared to oDBS. While side effect threshold did not differ, volume of neural activation was larger for dDBS. In terms of clinical efficacy, dDBS was as effective as oDBS., Conclusions: dDBS for ET widens therapeutic window due to reduction of therapeutic threshold. Larger volume of neural activation for dDBS at side effect threshold supports the notion of persistent directionality even at higher intensities. dDBS may compensate for slightly misplaced leads and should be considered first line for PSA/VIM-DBS., (© 2020 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals LLC. on behalf of International Neuromodulation Society.)

Deep brain stimulation is an established and evidence-based therapeutic option for the treatment of advanced Parkinson's disease. Main indication and inclusion criteria are the presence of idiopathic Parkinsonism with motor fluctuations and / or dyskinesias and / or with medication refractory tremor, a significant improvement of akinesia / rigidity in response to dopaminergic medication, the absence of relevant cognitive deficits and other significant comorbidities. DBS neurosurgery has a low risk of complications. The clinical programming should follow an established monopolar review algorithm. Regular follow-up visits are required for stimulation monitoring., Competing Interests: Erklärung zu finanziellen InteressenForschungsförderung erhalten: nein; Honorar / geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater / interner Schulungsreferent / Gehaltsempfänger: nein; Patent / Geschäftsanteile / Aktien (Autor / Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent /Geschäftsanteile / Aktien (Autor / Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein.Erklärung zu nichtfinanziellen InteressenDie Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Shorter pulse widths than conventional pulse width settings may lead to reduction of side effects and therefore be a valuable therapeutic option for deep brain stimulation (DBS) in patients with essential tremor (ET)., Objective: To compare the DBS effect of shorter pulse width at 40 μs (DBS-40 μs) to conventional pulse width at 60 μs (DBS-60 μs) on the therapeutic window in ET patients., Methods: For this prospective, randomized, double-blind, crossover study 9 ET patients with chronic DBS of the ventral intermediate nucleus (VIM)/posterior subthalamic area (PSA) were recruited. Therapeutic window was calculated by determining efficacy and side effect thresholds for DBS-40 μs and DBS-60 μs. Tremor Rating Scales and Kinesia tremor analyses were used to compare clinical efficacy between the considered settings and deactivated DBS (DBS-OFF). Volume of neural activation (VNA) was calculated for both efficacy and side effect thresholds at each pulse width., Results: DBS-40 μs showed a significantly larger therapeutic window than DBS-60 μs mainly due to higher side-effect thresholds. Both conditions significantly improved tremor compared to DBS-OFF, while efficacy was comparable between DBS-40 μs and DBS-60 μs. Moreover, VNA at efficacy threshold was smaller and less energy was required for tremor suppression with DBS-40 μs compared to DBS-60 μs., Conclusions: VIM/PSA-DBS with short pulse width represents a promising programming option for DBS in ET as it reduces side effects while maintaining efficient tremor suppression. Furthermore, our data support the notion of pulse width dependent selective modulation of distinct fiber tracts leading to widening of the therapeutic window., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Target localization for deep brain stimulation (DBS) is a challenging step that determines not only the correct placement of stimulation electrodes, but also influences the success of the DBS procedure as reflected in the desired clinical outcome of a patient., Objective: We report on the feasibility of DBS target localization in the subthalamic nucleus (STN) by long-latency somatosensory evoked potentials (LL-SSEPs) (>40 msec) in Parkinson's disease (PD) patients., Methods: Micro-macroelectrode recordings were performed intraoperatively on seven PD patients (eight STN hemispheres) who underwent DBS treatment. LL-SSEPs were elicited by ipsi- and contralateral median nerve stimulation to the wrist., Results: Four distinctive LL-SSEP components were elicited ("LL-complex" consisting of P80, N100, P140, and N200). The P80 appeared as the most visible and reliable intraoperative component. Localization of the "LL-complex" within the target was approved with typical microelectrode firing activity patterns, atlas visualization of recording electrodes, and postoperative CT-based visualization of final DBS electrodes., Conclusions: LL-SSEPs represent a promising approach for DBS target localization in the STN, provided deeper understanding on their anesthesia effect is obtained. This approach is advantageous in that it does not require the patient's participation in an intraoperative setting., (© 2017 International Neuromodulation Society.)

Background: Deep brain stimulation (DBS) surgery for Parkinson's disease (PD) is usually performed as awake surgery allowing sufficient intraoperative testing. Recently, outcomes after asleep surgery have been assumed comparable. However, direct comparisons between awake and asleep surgery are scarce., Objective: To investigate the difference between awake and asleep surgery comparing motor and nonmotor outcome after subthalamic nucleus (STN)-DBS in a large single center PD population., Methods: Ninety-six patients were retrospectively matched pairwise (48 asleep and 48 awake) and compared regarding improvement of Unified PD Rating Scale Motor Score (UPDRS-III), cognitive function, Levodopa-equivalent-daily-dose (LEDD), stimulation amplitudes, side effects, surgery duration, and complication rates. Routine testing took place at three months and one year postoperatively., Results: Chronic DBS effects (UPDRS-III without medication and with stimulation on [OFF/ON]) significantly improved UPDRS-III only after awake surgery at three months and in both groups one year postoperatively. Acute effects (percentage UPDRS-III reduction after activation of stimulation) were also significantly better after awake surgery at three months but not at one year compared to asleep surgery. UPDRS-III subitems "freezing" and "speech" were significantly worse after asleep surgery at three months and one year, respectively. LEDD was significantly lower after awake surgery only one week postoperatively. The other measures did not differ between groups., Conclusions: Overall motor function improved faster in the awake surgery group, but the difference ceased after one year. However, axial subitems were worse in the asleep surgery group suggesting that worsening of axial symptoms was risked improving overall motor function. Awake surgery still seems advantageous for STN-DBS in PD, although asleep surgery may be considered with lower threshold in patients not suitable for awake surgery., (© 2018 International Neuromodulation Society.)

Background: Recently, therapeutic attempts to control motor choreatic hyperkinesia of Huntington's disease (HD) by means of pallidal deep brain stimulation (Gp-DBS) were successful. With respect to the clinical effects of Gp-DBS in juvenile hypokinetic-rigid HD (jHD; Westphal variant), only one single-case has been reported up to date. Oscillatory patterns of the Gp in jHD are not known., Objectives and Methods: This work aimed to analyse pallidal local field potential oscillations (LFP) in two patients with jHD treated with Gp-DBS. Safety data and clinical scores up to 12 months after DBS-electrode implantation were collected in the framework of a prospective trial (ClinicalTrials.gov; NCT00902889)., Results: Intraoperative LFP revealed local alpha and beta oscillations similar to those found in other movement disorders with akinetic rigid and dystonic presentation. Significant motor improvement was not found. There were no treatment-related complications or unresolved long-term adverse events., Conclusions: In spite of similar intraoperative LFP patterns of jHD with those of movement disorders benefitting from DBS, clinical results were not convincing in our patients, so that Gp-DBS in jHD cannot be generally recommended.

Background: Stimulation parameters in deep brain stimulation (DBS) of the subthalamic nucleus for Parkinson's disease (PD) are rarely tested in double-blind conditions. Evidence-based recommendations on optimal stimulator settings are needed. Results from the CUSTOM-DBS study are reported, comparing 2 pulse durations., Methods: A total of 15 patients were programmed using a pulse width of 30 µs (test) or 60 µs (control). Efficacy and side-effect thresholds and unified PD rating scale (UPDRS) III were measured in meds-off (primary outcome). The therapeutic window was the difference between patients' efficacy and side effect thresholds., Results: The therapeutic window was significantly larger at 30 µs than 60 µs (P = ·0009) and the efficacy (UPDRS III score) was noninferior (P = .00008)., Interpretation: Subthalamic neurostimulation at 30 µs versus 60 µs pulse width is equally effective on PD motor signs, is more energy efficient, and has less likelihood of stimulation-related side effects. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society., (© 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)

Somatosensory evoked potentials (SSEPs) are a viable way to measure processing of somatosensory information. SSEPs have been described at the scalp and the cortical level by electroencephalographic, magnetoencephalographic and intracranial cortical recordings focusing on short-latency (SL; latency<40 ms) and long-latency (LL; latency>40 ms) SSEPs as well as by deep brain stimulation (DBS) electrode studies targeting SL-SSEPs. Unfortunately, LL-SSEPs have not been addressed at the subcortical level aside from the fact that studies targeting the characteristics and generators of SSEPs have been neglected for the last ten years. To cope with these issues, we investigated LL-SSEPs of the subthalamic nucleus (STN) in twelve patients with Parkinson's disease (PD) that underwent deep brain stimulation (DBS) treatment. In a postoperative setting, LL-SSEPs were elicited by median nerve stimulation (MNS) to the patient's wrists. Ipsilateral or contralateral MNS was applied with a 3 s inter-stimulus interval. Here, we report about four distinctive LL-SSEPs ("LL-complex" consisting of P80, N100, P140 and N200 component), which were recorded by using monopolar/bipolar reference and ipsi/contralateral MNS. Phase reversal and/or maximum amplitude provided support for the generation of such LL-SSEPs within the STN, which also underscores a role of this subcortical structure in sensory processing., Competing Interests: LW, JV, SJG, AS have received—unrelated to the current project—honoraria and travel expenses in the past from Inomed, Medtronic and/or St. Jude Medical and/or Boston Scientific, companies that manufacture microelectrode recordings and/or deep brain stimulation hardware. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Huntington's disease (HD) is a hereditary neurodegenerative disorder which is associated with severe disturbances of motor function, especially choreatic movements, cognitive decline and psychiatric symptoms. Various brain stimulation methods have been used to study brain function in patients with HD. Moreover, brain stimulation has evolved as an alternative or additive treatment option, besides current symptomatic medical treatment. This article summarizes the results of brain stimulation to better understand the characteristics of cortical excitability and plasticity in HD and gives a perspective on the therapeutic role for noninvasive and invasive neuromodulatory brain stimulation methods.

Background: This study was conducted to better understand the development of clinical efficacy and impedance levels in the long-term course of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD)., Methods: In this retrospective study of twenty PD patients, the motor part of the Unified Parkinson's Disease Rating Scale was periodically assessed i) after withdrawal of medication and inactivated stimulation, ii) after withdrawal of medication with activated stimulation and iii) after challenge with l-Dopa during activated stimulation up to 13 years after surgery., Results: STN-DBS with or without medication significantly improved motor function up to 13 years after surgery. The contribution of axial symptoms increased over time. While the stimulation parameters were kept constant, the therapeutic impedances progressively declined., Conclusion: STN-DBS in PD remains effective in the long-term course of the disease. Constant current stimulation might be preferable over voltage-controlled stimulation, as it would alleviate the impact of impedance changes on the volume of tissue activated., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background and Study Aims: The use of multiple trajectories microelectrode recording (MER) during implantation of deep brain stimulation (DBS) electrodes into the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) is discussed controversially because of possible risks and unclear benefits. The aim of the study is to investigate whether MER combined with intraoperative evaluation of stimulation effects improve clinical outcome in PD patients undergoing STN DBS surgery., Material and Methods: Prior to final DBS electrode implantation, we performed multiple trajectories MER and intraoperative test stimulations after magnetic resonance imaging (MRI)-guided planning in 32 PD patients. In further 10 patients no MER (only intraoperative test stimulation) was used., Results: We found a significantly better clinical outcome (Unified Parkinson's Disease Rating Scale [UPDRS] III) in patients undergoing MER compared with non-MER patients. In MER patients, DBS electrode placement was performed using the central trajectory in 73%. Another than the central trajectory was taken in 27% of the patients. No difference in clinical outcome between DBS electrodes implanted on the central or a decentral trajectory was observed., Conclusions: DBS surgery based on intraoperative multiple trajectories MER and test stimulation improves clinical outcome if compared with intraoperative test stimulation alone. The data suggest that DBS surgery solely based on MRI and intraoperative test stimulation without MER may lead to nonoptimal placement of DBS electrodes and consequently poorer clinical outcome., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The mechanism and time course of emotional side effects of subthalamic deep brain stimulation in Parkinson's disease are a matter for discussion. We report a 53-month follow-up of a patient with affective lability. Postoperative lesion plus bilateral stimulation strongly influenced mood in the first week in terms of laughing behavior, while voltage changes had only minor long-term impact up to 37 months on negative emotion, possibly caused by the right electrode stimulating the subthalamic nucleus and adjacent fiber tracts involving the internal capsule. Thus we conclude that affective lability can occur with different temporal dynamics of microlesion, and early and chronic stimulation.

Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥ 130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥ 130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds.