STN-DBS In Parkinson's Disease Research Articles

Subthalamic nucleus local field potential stability in patients with Parkinson's disease

BackgroundDespite the large body of work on local field potentials (LFPs), a measure of oscillatory activity in patients with Parkinson's disease (PD), the longitudinal evolution of LFPs is less explored. ObjectiveTo determine LFP fluctuations collected in clinical settings in patients with PD and STN deep brain stimulation (DBS). MethodsTwenty-two STN-DBS patients (age: 67.6 ± 8.3 years; 9 females; disease duration: 10.3 ± 4.5 years) completed bilateral LFP recordings over three visits in the OFF-stimulation setting. Peak and band power measures were calculated from each recording. ResultsAfter bilateral LFP recordings, at least one peak was detected in 18 (81.8%), 20 (90.9%), and 22 (100%) patients at visit 1, 2, and 3, respectively. No significant differences were seen in primary peak amplitude (F = 2.91, p = 0.060) over time. Amplitude of the second largest peak (F = 5.49, p = 0.006) and low-beta (F = 6.89, p = 0.002), high-beta (F = 13.23, p < 0.001), and gamma (F = 12.71, p < 0.001) band power demonstrated a significant effect of time. Post hoc comparisons determined low-beta power (Visit 1–Visit 2: t = 3.59, p = 0.002; Visit 1–Visit 3: t = 2.61, p = 0.031), high-beta (Visit 1–Visit 2: t = 4.64, p < 0.001; Visit 1–Visit 3: t = 4.23, p < 0.001) and gamma band power (Visit 1–Visit 2: t = 4.65, p < 0.001; Visit 1–Visit 3: t = 4.00, p < 0.001) were significantly increased from visit 1 recordings to both follow-up visits. ConclusionOur results provide substantial evidence that LFP can reliably be detected across multiple real-world clinical visits in patients with STN-DBS for PD. Moreover, it provides insights on the evolution of these LFPs.

Subthalamic Deep Brain Stimulation in Parkinson's Disease: A Boon or Bane - A Single Centre Retrospective Observational Study from India.

Background Subthalamic deep brain stimulation (STN-DBS) for refractory Parkinson's disease (PD) is more of a modality of treatment that is empirical, for which a physiological explanation is being sought. This study was done to determine the outcome and complications of patients undergoing STN-DBS for PD. Methods This retrospective observational cohort study was conducted in an advanced neuromedicine facility in eastern India for 9 years (August 2013-August 2022), which included all patients undergoing STN-DBS. Results A total of 53 patients were operated on during the study period. The mean age group of the study population was 60.5 (standard deviation [SD]: 8.2) years with a male (33 [62.3%]) predominance. The most common presenting complaints included rigidity and hypokinesia (27), severe dyskinesia (21), and tremors (17). During the postoperative period, rigidity and hypokinesia (21), severe dyskinesia (16), and tremors (12) improved significantly in a subset of the patients. The majority (45 [84.9%]) of these cases received bilateral monopolar simulation, whereas three patients (5.7%) had bilateral bipolar stimulation. Unilateral bipolar stimulation was used in five (9.4%) patients. In the immediate postoperative period, they were initiated on limb, speech, and swallowing therapy as indicated. Surgery-related complications were seen in five (9.4%) cases. At 6 months of follow-up, a significant improvement in the Unified PD rating scale component (mainly motor examination and complication of PD therapy) was noted in the majority (36 [67.9%]) of patients. One patient developed neuroleptic malignant syndrome and succumbed to his illness on the fourth postoperative day. Conclusion Given these findings, STN-DBS appears to be a good, safe, and effective treatment for a subset of medically refractory PD with an overall improvement in two-thirds of the study cohort and less than 10% risk of complications.

Programming Algorithm for the Management of Speech Impairment in Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease

ObjectivesDeep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson’s disease (PD) has an ambiguous relation to speech. Speech impairment can be a stimulation-induced side effect, and parkinsonian dysarthria can improve with STN-DBS. Owing to the lack of an up-to-date and evidence-based approach, DBS reprogramming for speech impairment is largely blind and greatly relies on the physician’s experience. In this study, we aimed to establish an evidence- and experience-based algorithm for managing speech impairment in patients with PD treated with STN-DBS. Materials and MethodsWe performed a single-center retrospective study to identify patients with STN-DBS and speech impairment. Onset of speech impairment, lead localization, and assessment of DBS-induced nature of speech impairment were collected. When DBS settings were adjusted for improving speech, the magnitude and duration of effect were collected. We also performed a systematic literature review to identify studies describing the effects of parameter adjustments aimed at improving speech impairment in patients with PD receiving STN-DBS. ResultsIn the retrospective study, 245 of 631 patients (38.8%) with STN-DBS had significant speech impairment. The probability of sustained marked improvement upon reprogramming was generally low (27.9%). In the systematic review, 23 of 662 identified studies were included. Only two randomized controlled trials have been performed, providing evidence for interleaving-interlink stimulation only. Considerable methodologic heterogeneity precluded the conduction of a meta-analysis. ConclusionsSpeech impairment in STN-DBS for PD is frequent, but high-quality evidence regarding DBS parameter adjustments is scarce, and the probability of sustained improvement is low. To improve this outcome, we propose an evidence- and experience-based approach to address speech impairment in STN-DBS that can be used in clinical practice.

Low beta-band suppression as a tool for DBS contact selection for akinetic-rigid symptoms in Parkinson's disease

BackgroundSuppression of pathologically altered activity in the beta-band has previously been suggested as a biomarker for feedback-based neurostimulation in subthalamic deep brain stimulation (STN-DBS) for Parkinson's Disease (PD). ObjectiveTo assess the utility of beta-band suppression as a tool for contact selection in STN-DBS for PD. MethodsA sample of seven PD patients (13 hemispheres) with newly implanted directional DBS leads of the STN were recorded during a standardized monopolar contact review (MPR). Recordings were received from contact pairs adjacent to the stimulation contact. The degree of beta-band suppression for each investigated contact was then correlated to the respective clinical results. Additionally, we have implemented a cumulative ROC analysis, to test the predictive value of beta-band suppression on the clinical efficacy of the respective contacts. ResultsStimulation ramping led to frequency-specific changes in the beta-band, while lower frequencies remained unaffected. Most importantly, our results showed that the degree of low beta-band suppression from baseline activity (stimulation off) served as a predictor for clinical efficacy of the respective stimulation contact. In contrast suppression of high beta-band activity yielded no predictive power. ConclusionThe degree of low beta-band suppression can serve as a time-saving, objective tool for contact selection in STN-DBS.

Emotional symptoms and cognitive function outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts and the volume of tissue activated.

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), that can improve patients' motor and non-motor symptoms. However, there are differences in the improvement of patients' emotional symptoms and cognitive function. To investigate the impact of active contact location and the volume of tissue activated (VTA) on patients' emotional symptoms and cognitive function in STN-DBS in PD. A total of 185 PD patients were included in this study. We evaluated them using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), Montreal Cognitive Assessment (MoCA), and Mini-Mental State Examination (MMSE) scales at the preoperative, 1- and 12-month postoperative time points. Leads were positioned in standard space using the Lead-DBS toolbox, and VTA was calculated for analysis. When the lead active contact was closer to the ventral side of the STN, the patients' HAM-A improvement rate was higher, and when the active contact was closer to the anterior and dorsal sides of the STN, the patients' MoCA improvement rate was higher. Stimulation of the sensorimotor zone was more favorable to the improvement of HAM-A and HAM-D in patients. And, the stimulation of the associative zone was more favorable to the improvement of MoCA in patients. Our results provide evidence that the 12-month outcomes of cognitive function and emotional symptoms in PD patients with STN-DBS were closely related to the specific location of the active contacts in the STN and influenced by the VTA.

Application of current steering with MICC directional lead in STN-DBS for Parkinson’s disease

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely performed for medically refractory Parkinson's disease (PD). Recent new technology of the multiple independent current control (MICC) with the directional lead provides both vertical and horizontal current steering on purposes. Consequently, MICC directional lead allows fine stimulation adjustment tailoring the condition of the individual patient. It is also expected to avoid stimulation induced adverse effects. MethodsWe retrospectively investigated the situation of current steering and the reason for doing so 3-month and 1-year after surgery in 80 patients who underwent bilateral STN-DBS for PD using MICC directional lead. ResultsIn 160 leads of 80 patients, current steering was used in 39 leads (24%) 3-month after surgery, but in 80 leads (50%) 1-year after surgery. As for the reason, vertical steering was used in 7 leads (4%) and horizontal steering was used in 28 leads (18%) to explore better stimulation effect for cardinal symptoms of PD. In addition, vertical steering was used for improving dyskinesia in 40 leads (25%) and alleviating tremor in 5 leads (3%). Horizontal steering was also used for avoiding adverse effects in 15 leads (9%), most of which were used to alleviate the symptoms of excessive stimulation of pyramidal tract. ConclusionsCurrent steering with the MICC directional lead was actually utilized in STN-DBS to explore more precise control of motor symptoms and also useful to avoid stimulation-induced adverse effect. Current steering is especially used in the later period after introduction of DBS.

Genetic stratification of motor and QoL outcomes in Parkinson's disease in the EARLYSTIM study

PurposeThe decision for subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD) relies on clinical predictors. Whether genetic variables could predict favourable or unfavourable decisions is under investigation. ObjectiveFirst, we aimed to reproduce the previous observation that SNCA rs356220 was associated with favourable STN-DBS motor response. In additional exploratory analyses, we studied if other PD risk and progression variants from the latest GWAS are associated with therapeutic outcome. Further, we evaluated the predictive value of polygenic risk scores. MethodsWe comprehensively genotyped patients from the EarlyStim cohort using NeuroChip, and assessed the clinico-genetic associations with longitudinal outcome parameters. ResultsThe SNCA rs356220 variant did not predict UPDRS III outcomes. However, it was associated with quality of life improvement in secondary analyses. Several polymorphisms from previously identified GWAS hits predicted motor or quality of life outcomes in DBS patients. Polygenic risk scores did not predict any outcome parameter. ConclusionsOur findings support the hypothesis that different common genetic markers are associated with favourable quality of life outcomes of STN-DBS in PD. These findings can be the basis for further validation in larger and independent cohorts.

Limbic Stimulation Drives Mania in STN-DBS in Parkinson Disease: A Prospective Study.

In this one-year prospective study, Parkinson's disease (PD) patients with or without mania following STN-DBS were compared to investigate risk and etiological factors, clinical management and consequences. Eighteen (16.2%) out of 111 consecutive PD patients developed mania, of whom 17 were males. No preoperative risk factor was identified. Postoperative mania was related to ventral limbic subthalamic stimulation in 15 (83%) patients, and resolved as stimulation was relocated to the sensorimotor STN, besides discontinuation or reduction of dopamine agonists and use of low-dose clozapine in 12 patients, while motor and nonmotor outcomes were similar. These findings underpin the prominent role of limbic subthalamic stimulation in postoperative mania. ANN NEUROL 2022;92:411-417.

818 Association Between Intraoperative LFP, Lead Location, and Outcomes in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease

INTRODUCTION: Imaging-based, LFP-based and empirical programming strategies can be used to determine the optimal therapeutic contact for deep brain stimulation, but the most efficient strategy is unclear. METHODS: In this prospective, IRB-approved study, 10 awake patients were implanted with bilateral STN DBS using both an electrophysiologically- and imaged-confirmed technique. Once the DBS lead had been secured, LFP signals were recorded with a Grapevine Neural Amplifier (Ripple Neuro, UT) at 30 KHz and 16-bit A/D resolution, and LFPs were down-sampled to 2 KHz before further processing. Stereotactic CTs acquired two weeks postoperatively were fused to the pre-operative 3T, T2 weighted MRI and processed using the SureTune platform (Medtronic, MN). Therapeutic DBS programming parameters were obtained 6 months post-implantation, along with pre- and post-operative UPDRS Part III scores. RESULTS: There was a 54% reduction in the UPDRS score when comparing the preoperative OFF score, to the 6 month postoperative OFF Meds/ON Stimulation Score. 50% of the chosen contacts were in the STN only, 10% in the ZI only, and 35% in both. One lead was found to be outside the segmented STN and ZI; this patient did not experience clinical improvement based on their Part III UPDRS score. Beta (8-30Hz) power was 4.1 times higher for electrodes within the STN versus out, 1.4 times for ZI versus out, and 5.9 times higher for both versus neither. The average beta power was 15% higher in the chosen therapeutic contacts over those contacts not used. Lastly, we found that the number of electrodes within the STN correlated with the decrease in the UPDRS score (r=0.27). CONCLUSIONS: There is a strong correlation between image-based electrode localization, LFP characteristics, and clinical outcomes in patients undergoing STN DBS for Parkinson Disease. Focused programming strategies based on either imaging or LFP data can facilitate identification of the optimal therapeutic contact.

Atlas-independent, N-of-1 tissue activation modeling to map optimal regions of subthalamic deep brain stimulation for Parkinson disease

BackgroundMotor outcomes after subthalamic deep brain stimulation (STN DBS) for Parkinson disease (PD) vary considerably among patients and strongly depend on stimulation location. The objective of this retrospective study was to map the regions of optimal STN DBS for PD using an atlas-independent, fully individualized (N-of-1) tissue activation modeling approach and to assess the relationship between patient-level therapeutic volumes of tissue activation (VTAs) and motor improvement. MethodsThe stimulation-induced electric field for 40 PD patients treated with bilateral STN DBS was modeled using finite element analysis. Neurostimulation models were generated for each patient, incorporating their individual STN anatomy, DBS lead position and orientation, anisotropic tissue conductivity, and clinical stimulation settings. A voxel-based analysis of the VTAs was then used to map the optimal location of stimulation. The amount of stimulation in specific regions relative to the STN was measured and compared between STNs with more and less optimal stimulation, as determined by their motor improvement scores and VTA. The relationship between VTA location and motor outcome was then assessed using correlation analysis. Patient variability in terms of STN anatomy, active contact position, and VTA location were also evaluated. Results from the N-of-1 model were compared to those from a simplified VTA model. ResultsTissue activation modeling mapped the optimal location of stimulation to regions medial, posterior, and dorsal to the STN centroid. These regions extended beyond the STN boundary towards the caudal zona incerta (cZI). The location of the VTA and active contact position differed significantly between STNs with more and less optimal stimulation in the dorsal-ventral and anterior-posterior directions. Therapeutic stimulation spread noticeably more in the dorsal and posterior directions, providing additional evidence for cZI as an important DBS target. There were significant linear relationships between the amount of dorsal and posterior stimulation, as measured by the VTA, and motor improvement. These relationships were more robust than those between active contact position and motor improvement. There was high variability in STN anatomy, active contact position, and VTA location among patients. Spherical VTA modeling was unable to reproduce these results and tended to overestimate the size of the VTA. ConclusionAccurate characterization of the spread of stimulation is needed to optimize STN DBS for PD. High variability in neuroanatomy, stimulation location, and motor improvement among patients highlights the need for individualized modeling techniques. The atlas-independent, N-of-1 tissue activation modeling approach presented in this study can be used to develop and evaluate stimulation strategies to improve clinical outcomes on an individual basis.

The impact of dispositional optimism and depression on post-operative motor functioning following deep brain stimulation surgery for Parkinson's disease

IntroductionThe primary goal of subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) is to improve motor function. Dispositional optimism has been associated with better physical outcomes following a rehabilitation program in PD but has not been investigated in relation to STN-DBS. This study investigated the influence of dispositional optimism on motor outcomes following STN-DBS in individuals with PD. MethodsA retrospective data analysis of 33 individuals with PD who underwent STN-DBS was conducted. Linear regression was used to determine whether dispositional optimism, measured by the Life Orientation Test-Revised questionnaire, predicted change in motor symptoms following DBS surgery, as assessed by the Movement Disorder Society-sponsored revision of the Unified PD Rating Scale, Part III. Self-reported levels of depressive and anxiety symptoms were included as co-variates. ResultsHigher pre-operative dispositional optimism combined with less self-reported depressive symptoms predicted greater post-operative improvement in motor symptoms from the baseline OFF-medication to post-operative ON-medication/ON-stimulation state, accounting for 38.8% of the variance in post-operative change. ConclusionThe large percentage of variance in post-STN-DBS motor change predicted by pre-operative dispositional optimism and depressive symptoms suggests that assessment of these variables prior to surgery may provide valuable information for clinicians regarding the surgery's ultimate initial motor benefit for individuals with PD. If modifiable, these variables may provide cost-effective targets to improve motor outcomes of STN-DBS in PD.

Deep Brain Stimulation in Parkinson's Disease: Still Effective After More Than 8 Years.

ABSTRACTBackgroundDeep brain stimulation of the subthalamic nucleus (STN‐DBS) is well established and the most effective treatment for advanced Parkinson's disease (PD). However, little is known of the long‐term effects.ObjectivesThe aim of this study was to examine the long‐term effects of STN‐DBS in PD and evaluate the effect of reprogramming after more than 8 years of treatment.MethodsA total of 82 patients underwent surgery in Copenhagen between 2001 and 2008. Before surgery and at 8 to 15 years follow‐up, the patients were rated with the Unified Parkinson's Disease Rating Scale (UPDRS) with and without stimulation and medicine. Furthermore, at long‐term follow‐up, the patients were offered a systemic reprogramming of the stimulation settings. Data from patients' medical records were collected. The mean (range) age at surgery was 60 (42–78) years, and the duration of disease was 13 (5–25) years. A total of 30 patients completed the long‐term follow‐up.ResultsThe mean reduction of the motor UPDRS by medication before surgery was 52%. The improvement of motor UPDRS with stimulation alone compared with motor UPDRS with neither stimulation nor medication was 61% at 1 year and 39% at 8 to 15 years after surgery (before reprogramming). Compared with before surgery, medication was reduced by 55% after 1 year and 44% after 8 to 15 years. After reprogramming, most patients improved.ConclusionsSTN‐DBS remains effective in the long run, with a sustained reduction of medication in the 30 of 82 patients available for long‐term follow‐up. Reprogramming is effective even in the late stages of PD and after many years of treatment.

Correspondence of optimal stimulation and beta power varies regionally in STN DBS for Parkinson disease

IntroductionSubthalamic nucleus deep brain stimulation (STN DBS) for Parkinson disease (PD) normalizes neuronal hypersynchrony in the beta frequency range (13–30 Hz). The spatial correspondence of maximal beta power to the site of optimal stimulation along the DBS lead trajectory has been debated. MethodsWe determined the trajectory locations of the active contact, maximal beta power, and the dorsal border of the STN (DB-STN) in DBS patients. Beta power profiles were measured during intraoperative microelectrode recording (MER). Active contact locations were assigned during blinded, postoperative DBS programming. The DB-STN was identified both electrophysiologically during MER and anatomically on MRI. After grouping DBS trajectories into quadrants relative to the anatomic STN midpoint, we examined regional variations in the relative trajectory locations of the three entities. ResultsSTN DBS significantly improved motor performance for all 13 DBS patients, with active contacts at the DB-STN. Along trajectories passing posterior-medial to the STN midpoint, maximal beta power co-localized with active contacts at the DB-STN (difference Δ = 0.4 ± 1.6 mm, p = 0.57). By contrast, in posterior-lateral trajectories, maximal beta arose within the STN, ventral to active contacts (Δ = 1.9 ± 1.3 mm, p = 0.002). For trajectories anterior to the STN midpoint, maximal beta power co-localized with the DB-STN, while active contacts were ventral to peak beta power (p = 0.05). ConclusionOur findings indicate that co-localization of optimal stimulation and beta power varies by anatomical region in STN DBS for Parkinson disease.

Stimulation challenge test after STN DBS improves satisfaction in Parkinson's disease patients

ObjectiveAlthough subthalamic Deep Brain Stimulation (STN DBS) is proven effective in improving symptoms of Parkinson's Disease (PD), previous literature demonstrates a discrepancy between objective improvement and patients' perception thereof. We aimed to examine whether postoperative stimulation challenge tests (SCT) alters patients' satisfaction after STN DBS for PD. MethodsFifty-four PD patients underwent preoperative levodopa challenge tests and were routinely invited for SCT 1-2 years postoperatively. SEverity of predominantly Nondopaminergic Symptoms in PD (SENS-PD) scores quantified non-dopaminergic disease severity. Motor functioning was quantified using Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III scores; a ratio between conditions ON and OFF (preoperative Med-ON vs. Med-OFF, and postoperative Med-ON/Stim-ON vs. Med-OFF/Stim-OFF) reflected treatment benefit. ‘Global Impression of Change’ (GIC) and ‘Global Satisfaction with Surgery’ (GSS) Likert scales were filled out before and immediately after SCT. ResultsPostoperative Med-ON/Stim-ON severity was lower than preoperative ON severity. Disease severity scores were not different between assessments. GIC and GSS scores were higher after SCT versus before (GIC: Z = -3.80, r = 0.37, subjects indicating maximum scores before SCT: 32.1%, after SCT: 57.1%; GSS: Z = -3.69, r = 0.35, maximum scores before SCT: 25.0%, after SCT: 46.4%). Higher non-dopaminergic disease severity was associated with lower GIC and GSS scores (GIC: OR 1.2 (95%CI 1.0–1.3); GSS: OR 1.2 (95%CI 1.1–1.3), while motor-scores and magnitude of DBS-effects were not. ConclusionSCT improves patients’ satisfaction and is recommended especially in case of suboptimal subjective valuations. This information should be considered in clinical practice and in the context of clinical trials.

Subthalamic Nucleus Stimulation Does Not Have Any Acute Effects on Verbal Fluency or on Speed of Word Generation in Parkinson's Disease.

Background Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been shown to be generally safe from a cognitive perspective, with consistent evidence that the major impact of STN-DBS in Parkinson's disease (PD) is on verbal fluency. Objective The aim of this study was first to identify the influence of acute manipulation of STN-DBS in PD on the number and time pattern of word generation on different verbal fluency (VF) tasks, phonemic, switching, and cued switching, and second to determine whether cueing improved VF and if cueing effects interacted with STN-DBS effects. Methods Parallel versions of these three verbal fluency tasks were completed by 31 patients with Parkinson's disease who had had bilateral DBS of the STN, twice, with DBS On and Off, with the order counterbalanced across patients. Results There was no effect of acute STN-DBS on the total number of words generated during verbal fluency. As expected, the number of words generated significantly declined over the six 10-second intervals of the verbal fluency tasks, but this time pattern of word generation was not altered by STN-DBS. External cueing significantly increased the number of words generated relative to an uncued switching verbal fluency task, but the cueing effect on VF was not altered by STN-DBS. Conclusion In conclusion, (i) acute STN-DBS manipulation did not alter either verbal fluency performance or the time pattern of word generation and (ii) external cueing significantly improved verbal fluency performance both with STN-DBS On and Off.

Comparison of Awake vs. Asleep Surgery for Subthalamic Deep Brain Stimulation in Parkinson’s Disease

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. 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. 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. 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. 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.

Non-motor outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts

BackgroundSubthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in Parkinson's disease (PD). Few studies have investigated the influence of the location of neurostimulation on NMS. ObjectiveTo investigate the impact of active contact location on NMS in STN-DBS in PD. MethodsIn this prospective, open-label, multicenter study including 50 PD patients undergoing bilateral STN-DBS, we collected NMSScale (NMSS), NMSQuestionnaire (NMSQ), Hospital Anxiety and Depression Scale (anxiety/depression, HADS-A/-D), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD-motor examination, motor complications, activities of daily living (ADL), and levodopa equivalent daily dose (LEDD) preoperatively and at 6 months follow-up. Changes were analyzed with Wilcoxon signed-rank/t-test and Bonferroni-correction for multiple comparisons. Although the STN was targeted visually, we employed an atlas-based approach to explore the relationship between active contact locations and DBS outcomes. Based on fused MRI/CT-images, we identified Cartesian coordinates of active contacts with patient-specific Mai-atlas standardization. We computed linear mixed-effects models with x-/y-/z-coordinates as independent, hemispheres as within-subject, and test change scores as dependent variables. ResultsNMSS, NMSQ, PDQ-8, motor examination, complications, and LEDD significantly improved at follow-up. Linear mixed-effect models showed that NMS and QoL improvement significantly depended on more medial (HADS-D, NMSS), anterior (HADS-D, NMSQ, PDQ-8), and ventral (HADS-A/-D, NMSS, PDQ-8) neurostimulation. ADL improved more in posterior, LEDD in lateral neurostimulation locations. No relationship was observed for motor examination and complications scores. ConclusionsOur study provides evidence that more anterior, medial, and ventral STN-DBS is significantly related to more beneficial non-motor outcomes.

Fluency-Enhancing Strategies for Hypokinetic Dysarthria Exacerbated by Subthalamic Nucleus Brain Stimulation: A Case Study

Introduction Speech disorders associated with Parkinson's disease (PD) and the pharmaceutical treatments of PD are well documented. A relatively recent treatment alternative for PD is deep brain stimulation (DBS) of the subthalamic nucleus (STN), which is used to manage the symptoms of PD as the disease progresses. This case study documented the speech characteristics of a unique client with PD STN-DBS and reported initial findings on a variety of fluency- and intelligibility-enhancing strategies. Method A speech-language pathologist referred a 63-year-old man, previously diagnosed by a speech-language pathologist with neurogenic stuttering as a result of an STN-DBS battery change, for a speech evaluation, reporting lack of success with traditional stuttering treatment strategies. The client's speech was assessed, and a variety of fluency- and intelligibility-enhancing techniques were tested during trial therapy. Results The client's speech exhibited the hallmark characteristics of hypokinetic dysarthria, including speech disfluencies. A variety of pacing and prosthetic strategies were tested, revealing that auditory and tactile prosthetic speech feedback provided optimal improvements in fluency and intelligibility. Discussion These results suggest that the prosthetic speech feedback provided optimal intelligibility and fluency enhancement and could potentially improve articulation and speech volume, which are also common in cases of hypokinetic dysarthria.

Pyramidal tract activation due to subthalamic deep brain stimulation in Parkinson's disease.

Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), but can have side effects caused by stimulus spread to structures outside the target volume such as the pyramidal tract. To assess the relevance of pyramidal tract activation with STN-DBS in PD. In a multimodal, blinded study in 20 STN-DBS patients, we measured stimulation thresholds for evoking electromyographic activity in orbicularis oris and first dorsal interosseous muscles at each of 150 electrode sites. We also modeled the electric field spread and calculated its overlap with the estimated anatomical location of corticospinal and corticobulbar tracts from primary motor cortex using 3 Tesla MRI probabilistic tractography. Mean resting motor thresholds were significantly lower for the contralateral orbicularis oris (3.5 ± 1.0 mA) compared with ipsilaterally (4.1 ± 1.1 mA) and with the contralateral first dorsal interosseous (4.0 ± 1.2 mA). The modeled volumes of corticobulbar and corticospinal tract activated correlated inversely with the resting motor threshold of the contralateral orbicularis oris and first dorsal interosseous, respectively. Active motor thresholds were significantly lower compared with resting motor thresholds by around 30% to 35% and correlated with the clinically used stimulation amplitude. Backward multiple regression in 12 individuals with a "lateral-type" speech showed that stimulation amplitude, levodopa equivalent dose reduction postsurgery, preoperative speech intelligibility, and first dorsal interosseous resting motor thresholds explained 79.9% of the variance in postoperative speech intelligibility. Direct pyramidal tract activation can occur at stimulation thresholds that are within the range used in clinical routine. This spread of current compromises increase in stimulation strengths and is related to the development of side effects such as speech disturbances with chronic stimulation. © 2017 International Parkinson and Movement Disorder Society.

Toward an electrophysiological "sweet spot" for deep brain stimulation in the subthalamic nucleus.

Enhanced beta-band activity recorded in patients suffering from Parkinson's Disease (PD) has been described as a potential physiomarker for disease severity. Beta power is suppressed by Levodopa intake and STN deep brain stimulation (DBS) and correlates with disease severity across patients. The aim of the present study was to explore the promising signature of the physiomarker in the spatial domain. Based on local field potential data acquired from 54 patients undergoing STN-DBS, power values within alpha, beta, low beta, and high beta bands were calculated. Values were projected into common stereotactic space after DBS lead localization. Recorded beta power values were significantly higher at posterior and dorsal lead positions, as well as in active compared with inactive pairs. The peak of activity in the beta band was situated within the sensorimotor functional zone of the nucleus. In contrast, higher alpha activity was found in a more ventromedial region, potentially corresponding to associative or premotor functional zones of the STN. Beta- and alpha-power peaks were then used as seeds in a fiber tracking experiment. Here, the beta-site received more input from primary motor cortex whereas the alpha-site was more strongly connected to premotor and prefrontal areas. The results summarize predominant spatial locations of frequency signatures recorded in STN-DBS patients in a probabilistic fashion. The site of predominant beta-activity may serve as an electrophysiologically determined target for optimal outcome in STN-DBS for PD in the future. Hum Brain Mapp 38:3377-3390, 2017. © 2017 Wiley Periodicals, Inc.