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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.)

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: 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: 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.

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.