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This paper reports findings on the respiratory/phonatory subsystems from an on-going study investigating the effect of unilateral electrostimulation of the subthalamic nucleus (STN) on different speech subsystems in people with Parkinson's disease (PD). Speech recordings were made in the medication-off state at baseline, three months post surgery with stimulation-on, and with stimulation-off, in six right-handed PD patients. Subjects completed several speech tasks. Acoustic analyses of the maximally sustained vowel phonation were reported. The results were compared to the scores of the motor section of the Unified Parkinson's Disease Rating Scale III) obtained under the same conditions. Results showed that stimulation-on improved UPDRS-III scores in all six subjects. While mild improvement was observed for all subjects in the Stimulation-on condition, three subjects received left-STN stimulation showed a significant decline in vocal intensity and vowel duration from their baseline indicating the speech function was very susceptible to micro lesions due to the surgical procedure itself when the surgical site was in the dominant hemisphere. [ABSTRACT FROM AUTHOR]

Objective: Mutations in the glucocerebrosidase (GBA1) gene and subthalamic nucleus deep brain stimulation (STN-DBS) are independently associated with cognitive dysfunction in persons with Parkinson's disease (PwP). We hypothesized that PwP with both GBA1 mutations and STN-DBS are at greater risk of cognitive dysfunction than PwP with only GBA1 mutations or STN-DBS, or neither. In this study, we determined the pattern of cognitive dysfunction in PwP based on GBA1 mutation status and STN-DBS treatment., Methods: PwP who are GBA1 mutation carriers with or without DBS (GBA1+DBS+, GBA1+DBS-), and noncarriers with or without DBS (GBA1-DBS+, GBA1-DBS-) were included. Using the NIH Toolbox, cross-sectional differences in response inhibition, processing speed, and episodic memory were compared using analysis of variance with adjustment for relevant covariates., Results: Data were available for 9 GBA1+DBS+, 14 GBA1+DBS-, 17 GBA1-DBS+, and 26 GBA1-DBS- PwP. In this cross-sectional study, after adjusting for covariates, we found that performance on the Flanker test (measure of response inhibition) was lower in GBA1+DBS+ PwP compared with GBA1-DBS+ PwP (P = 0.030)., Interpretation: PwP who carry GBA1 mutations and have STN-DBS have greater impaired response inhibition compared with PwP with STN-DBS but without GBA1 mutations. Longitudinal data, including preoperative scores, are required to definitively determine whether GBA1 mutation carriers respond differently to STN-DBS, particularly in the domain of response inhibition., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Genetic subtyping of patients with Parkinson's disease (PD) may assist in predicting the cognitive and motor outcomes of subthalamic deep brain stimulation (STN-DBS). Practical questions were recently raised with the emergence of new data regarding suboptimal cognitive outcomes after STN-DBS in individuals with PD associated with pathogenic variants in glucocerebrosidase gene (GBA1-PD). However, a variety of gaps and controversies remain. (1) Does STN-DBS truly accelerate cognitive deterioration in GBA1-PD? If so, what is the clinical significance of this acceleration? (2) How should the overall risk-to-benefit ratio of STN-DBS in GBA1-PD be established? (3) If STN-DBS has a negative effect on cognition in GBA1-PD, how can this effect be minimized? (4) Should PD patients be genetically tested before STN-DBS? (5) How should GBA1-PD patients considering STN-DBS be counseled? We aim to summarize the currently available relevant data and detail the gaps and controversies that exist pertaining to these questions. In the absence of evidence-based data, all authors strongly agree that clinicians should not categorically deny DBS to PD patients based solely on genotype (GBA1 status). We suggest that PD patients considering DBS may be offered genetic testing for GBA1, where available and feasible, so the potential risks and benefits of STN-DBS can be properly weighed by both the patient and clinician. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

There is growing appreciation of the importance of the intestinal microbiota in Parkinson's disease (PD), and one potential mechanism by which the intestinal microbiota can communicate with the brain is via bacteria-derived metabolites. In this study, plasma levels of bacterial-derived metabolites including trimethylamine-N-oxide (TMAO), short chain fatty acids (SCFA), the branched chain fatty acid isovalerate, succinate, and lactate were evaluated in PD subjects (treatment naïve and treated) which were compared to (1) population controls, (2) spousal / household controls (similar lifestyle to PD subjects), and (3) subjects with multiple system atrophy (MSA). Analyses revealed an increase in the TMAO pathway in PD subjects which was independent of medication status, disease characteristics, and lifestyle. Lactic acid was decreased in treated PD subjects, succinic acid positively correlated with disease severity, and the ratio of pro-inflammatory TMAO to the putative anti-inflammatory metabolite butyric acid was significantly higher in PD subjects compared to controls indicating a pro-inflammatory shift in the metabolite profile in PD subjects. Finally, acetic and butyric acid were different between PD and MSA subjects indicating that metabolites may differentiate these synucleinopathies. In summary, (1) TMAO is elevated in PD subjects, a phenomenon independent of disease characteristics, treatment status, and lifestyle and (2) metabolites may differentiate PD and MSA subjects. Additional studies to understand the potential of TMAO and other bacterial metabolites to serve as a biomarker or therapeutic targets are warranted., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease (PD) can have detrimental effects on eye movement inhibitory control. To investigate this detrimental effect of bilateral STN DBS, we examined the effects of manipulating STN DBS amplitude on inhibitory control during the antisaccade task. The prosaccade error rate during the antisaccade task, that is, directional errors, was indicative of impaired inhibitory control. We hypothesized that as stimulation amplitude increased, the prosaccade error rate would increase., Materials and Methods: Ten participants with bilateral STN DBS completed the antisaccade task on six different stimulation amplitudes (including zero amplitude) after a 12-hour overnight withdrawal from antiparkinsonian medication., Results: We found that the prosaccade error rate increased as stimulation amplitude increased (p < 0.01). Additionally, prosaccade error rate increased as the modeled volume of tissue activated (VTA) and STN overlap decreased, but this relationship depended on stimulation amplitude (p = 0.04)., Conclusions: Our findings suggest that higher stimulation amplitude settings can be modulatory for inhibitory control. Some individual variability in the effect of stimulation amplitude can be explained by active contact location and VTA-STN overlap. Higher stimulation amplitudes are more deleterious if the active contacts fall outside of the STN resulting in a smaller VTA-STN overlap. This is clinically significant as it can inform clinical optimization of STN DBS parameters. Further studies are needed to determine stimulation amplitude effects on other aspects of cognition and whether inhibitory control deficits on the antisaccade task result in a meaningful impact on the quality of life., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: High-frequency (130-185 Hz) deep brain stimulation (DBS) of the subthalamic nucleus is more effective for appendicular than axial symptoms in Parkinson's disease (PD). Low-frequency (60-80 Hz) stimulation (LFS) may reduce gait/balance impairment but typically results in worsening appendicular symptoms. We created a "dual-frequency" programming paradigm (interleave-interlink, IL-IL) to address both axial and appendicular symptoms. In IL-IL, 2 overlapping LFS programs are applied to the DBS lead, with the overlapping area focused on the optimal cathode. The nonoverlapping area (LFS) is thought to reduce gait/balance impairment, whereas the overlapping area (high-frequency stimulation, HFS) aims to control appendicular symptoms., Methods: We performed a randomized, double-blind crossover trial comparing patients' previously optimized IL-IL and conventional HFS paradigms. Each arm was 2 weeks in duration. The primary outcome measure was the patient/caregiver Modified Clinical Global Impression Severity (CGI-S). Secondary outcome measures included blinded motor evaluations, timed tests, patient/caregiver questionnaires, and Personal KinetiGraphs (PKG)., Results: Twenty-five patients were enrolled, and 20 completed. The patient/caregiver CGI-S for gait/balance (P = 0.01) and appendicular symptom control (P = 0.001), and the blinded rater MDS-UPDRS-III (-5.22, P = 0.02), CGI-S gait/balance (P = 0.01), and CGI-S speech (P = 0.02) were better while on IL-IL. Scores on Parkinson's Disease Quality of Life (P = 0.002) and Freezing-of-Gait Questionnaires (P = 0.04) were better on IL-IL. The Timed-Up-and-Go was 9.8% faster (P = 0.01), with 11.8% reduction in steps (P = 0.001) on IL-IL. There was no difference in PKG bradykinesia (P = 0.18) or tremor (P = 0.23) between paradigms., Conclusions: Our results prompt consideration of this novel programming paradigm (IL-IL) for PD patients with axial symptom impairment as a new treatment option for both axial and appendicular symptoms. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Background: Deep brain stimulation (DBS) surgery in patients with pre-existing cochlear implants (CIs) poses various challenges. We previously reported successful magnetic resonance imaging (MRI)-based, microelectrode recording (MER)-guided subthalamic DBS surgery in a patient with a pre-existing CI. Other case reports have described various DBS procedures in patients with pre-existing CIs using different techniques, leading to varying issues to address. A standardized operative technique and workflow for DBS surgery in the setting of pre-existing CIs is much needed., Objective: To provide a standardized operative technique and workflow for DBS lead placement in the setting of pre-existing CIs., Methods: Our operative technique is MRI-based and MER-guided, following a workflow involving coordination with a neurotology team to remove and re-implant the internal magnets of the CIs in order to safely perform DBS lead placement, altogether within a 24-h time frame. Intraoperative nonverbal communication with the patient is easily possible using a computer monitor., Results: A 65-yr old woman with a 10-yr history of craniocervical dystonia and pre-existing bilateral CIs underwent successful bilateral pallidal DBS surgery at our institution. No merging errors or difficulties in targeting globus pallidus internus were experienced. Also, inactivated CIs do not interfere with MER nor with stimulation, and intraoperative communication with the patient using a computer monitor proved feasible and satisfactory., Conclusion: DBS procedures are safe and feasible in patients with pre-existing CIs if precautions are taken following our workflow., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Objective: During deep brain stimulation (DBS) surgery, microelectrode recording (MER) leads to target refinement from the initial plan in 30% to 47% of hemispheres; however, it is unclear whether the DBS lead ultimately resides within the MER-optimized target in relation to initial radiographic target coordinates in these hemispheres. This study aimed to determine the frequency of discordance between radiographic and neurophysiologic nucleus and whether target optimization with MER leads to a significant change in DBS lead location away from initial target., Methods: Consecutive cases of DBS surgery with MER using intraoperative computed tomography were included. Coordinates of initial anatomic target (AT), MER-optimized target (MER-O) and DBS lead were obtained. Hemispheres were categorized as "discordant" (D) if there was a suboptimal neurophysiologic signal despite accurate targeting of AT. Hemispheres where the first MER pass was satisfactory were deemed "concordant" (C). Coordinates and radial distances between 1) AT/MER-O; 2) MER-O/DBS; and 3) AT/DBS were calculated and compared., Results: Of the 273 hemispheres analyzed, 143 (52%) were D, and 130 (48%) were C. In C hemispheres, DBS lead placement error (mean ± standard error of the mean) was 0.88 ± 0.07 mm. In D hemispheres, MER resulted in significant migration of DBS lead (mean AT-DBS error 2.11 ± 0.07 mm), and this distance was significantly greater than the distance between MER-O and DBS (2.11 vs. 1.09 mm, P < 0.05). Directional assessment revealed that the DBS lead migrated in the intended direction as determined by MER-O in D hemispheres, except when the intended direction was anterolateral., Conclusions: Discordance between radiographic and neurophysiologic target was seen in 52% of hemispheres, and MER resulted in appropriate deviation of the DBS lead toward the appropriate target. The actual value of the deviation, when compared with DBS lead placement error in C hemispheres, was, on average, small., (Copyright © 2019 Elsevier Inc. All rights reserved.)

People with Parkinson's disease (PD) exhibit an increase in fixational saccades during the preparatory period prior to target onset in the antisaccade task and this increase is related to an increase in prosaccade errors in the antisaccade task. It was previously shown that bilateral, but not unilateral, subthalamic nucleus deep brain stimulation (STN DBS) in people with PD further increases the prosaccade error rate on the antisaccade task. We investigated whether bilateral STN DBS also increases the number of fixational saccades in the preparatory period of the antisaccade task and if this increase in the number of fixational saccades is related to prosaccade errors. We found that: (1) there were a greater number of fixational saccades during the preparatory period of the antisaccade task during bilateral STN DBS compared to no STN DBS (p < 0.001), unilateral STN DBS (p < 0.001), and healthy controls (p = 0.02), and (2) the increase in the number of fixational saccades increased the probability of a prosaccade error for the antisaccade task during bilateral STN DBS (p = 0.005). This association between number of fixational saccades and probability of a prosaccade error was similar across no STN DBS, unilateral stimulation, and healthy controls. In addition, we found that the proportion of express prosaccade errors and prosaccade error latency were similar across stimulation conditions. We propose that bilateral STN DBS disrupts the integrated activity of cortico-basal ganglia-collicular processes underlying antisaccade preparation and that this disruption manifests as an increase in both fixational saccades and prosaccade error rate.

In 2015, the US Food and Drug Administration approved levodopa-carbidopa intestinal gel (LCIG; also known as carbidopa-levodopa enteral suspension in the US) for the treatment of motor fluctuations in patients with advanced Parkinson's disease. LCIG provides a continuous infusion of levodopa and carbidopa by means of a portable pump and percutaneous endoscopic gastrojejunostomy tube. The delivery system has a two-fold pharmacokinetic advantage over orally administered carbidopa/levodopa. First, levodopa is delivered in a continuous rather than intermittent, pulsatile fashion. Second, delivery to levodopa's site of absorption in the jejunum bypasses the stomach, thereby avoiding issues with erratic gastric emptying. In blinded prospective clinical trials and observational studies, LCIG has been shown to significantly decrease "off" time, increase "on" time without troublesome dyskinesia, and reduce dyskinesia. Consistent with procedures in previous studies, LCIG initiation and titration in the pivotal US clinical trial were performed in the inpatient setting and followed a standardized protocol. In clinical practice, however, initiation and titration of LCIG have a great degree of flexibility and, in the US, almost always take place in the outpatient setting. Nonetheless, there remains a significant amount of clinician uncertainty regarding titration in outpatient clinical practice. This review aims to shed light on and provide guidance as to the current methods of titration in the outpatient setting, as informed by the medical literature and the authors' experiences. FUNDING: AbbVie, Inc. Plain language summary available for this article.

Objectives: As genetic testing is becoming more widely commercially available for Parkinson's disease (PD) and may have implications regarding clinical outcomes for deep brain stimulation (DBS) and other therapies, we aimed to determine patient knowledge and attitudes towards genetic testing., Methods: A sample of 88 PD subjects with bilateral STN-DBS completed a Genetic Attitudes Questionnaire (GAQ). Knowledge and attitudes towards genetic testing were assessed., Results: The mean percent of correct responses regarding genetic testing knowledge was 58.5%. Nearly 90% of subjects were unfamiliar with Genetic Information Nondiscrimination Act (GINA). The most important reasons subjects cited in deciding whether to undergo genetic testing included (1) to be a candidate for clinical trials if positive, (2) to learn that they do not carry a mutation, and (3) because a healthcare provider had recommended it. Individuals who influence decision-making include spouses and children. About 88% of subjects would share results with spouses, children, and siblings., Discussion: These results reveal that there is a major knowledge gap regarding genetic testing in PD and the implications of testing results on treatment, work, insurance, and privacy. Also, subjects would mainly seek genetic testing to participate in clinical trials, with spouses and children being the key stakeholders in decision-making.

Deep brain stimulation of the subthalamic nucleus (STN DBS) significantly improves clinical motor symptoms, as well as intensive aspects of movement like velocity and amplitude in patients with Parkinson's disease (PD). However, the effects of bilateral STN DBS on integrative and coordinative aspects of motor control are equivocal. The aim of this study was to investigate the effects of bilateral STN DBS on integrative and coordinative aspects of movement using a memory-guided sequential reaching task. The primary outcomes were eye and finger velocity and end-point error. We expected that bilateral STN DBS would increase reaching velocity. More importantly, we hypothesized that bilateral STN DBS would increase eye and finger end-point error and this would not simply be the result of a speed accuracy trade-off. Ten patients with PD and bilaterally implanted subthalamic stimulators performed a memory-guided sequential reaching task under four stimulator conditions (DBS-OFF, DBS-LEFT, DBS-RIGHT, and DBS-BILATERAL) over 4 days. DBS-BILATERAL significantly increased eye velocity compared to DBS-OFF, DBS-LEFT, and DBS-RIGHT. It also increased finger velocity compared to DBS-OFF and DBS-RIGHT. DBS-BILATERAL did not change eye end-point error. The novel finding was that DBS-BILATERAL increased finger end-point error compared to DBS-OFF, DBS-LEFT, and DBS-RIGHT even after adjusting for differences in velocity. We conclude that bilateral STN DBS may facilitate basal ganglia-cortical networks that underlie intensive aspects of movement like velocity, but it may disrupt selective basal ganglia-cortical networks that underlie certain integrative and coordinative aspects of movement such as spatial accuracy.

Background: Microelectrode recording (MER) is used to confirm targeting accuracy during deep brain stimulation (DBS) surgery. We describe a technique using intraoperative computed tomography (CT) extrapolation (iCTE) to predetermine and adjust the trajectory of the guide tube to improve microelectrode targeting accuracy. We hypothesized that this technique would decrease the number of MER tracks and operative time, while increasing the recorded length of the subthalamic nucleus (STN)., Methods: Thirty-nine patients with Parkinson's disease who underwent STN DBS before the iCTE method were compared with 33 patients undergoing STN DBS using iCTE. Before dural opening, a guide tube was inserted and rested on dura. Intraoperative computed tomography (iCT) was performed, and a trajectory was created along the guide tube and extrapolated to the target using targeting software. If necessary, headstage adjustments were made to correct for error. The guide tube was inserted, and MER was performed. iCT was performed with the microelectrode tip at the target. Coordinates were compared with planned/adjusted track coordinates. Radial error between the MER track and the planned/adjusted track was calculated. Cases before and after implementation of iCTE were compared to determine the impact of iCTE on operative time, number of MER tracks and recorded STN length., Results: The use of iCTE reduced the average radial MER track error from 1.90 ± 0.12 mm (n = 54) to 0.84 ± 0.09 mm (n = 49) (P < 0.001) while reducing the operative time for bilateral lead placement from 272 ± 9 minutes (n = 30) to 233 ± 10 minutes (n = 24) (P < 0.001). The average MER tracks per hemisphere was reduced from 2.24 ± 0.13 mm (n = 66) to 1.75 ± 0.09 mm (n = 63) (P < 0.001), whereas the percentage of hemispheres requiring a single MER track for localization increased from 29% (n = 66) to 43% (n = 63). The average length of recorded STN increased from 4.01 ± 0.3 mm (n = 64) to 4.75 ± 0.28 mm (n = 56) (P < 0.05)., Conclusion: iCTE improves microelectrode accuracy and increases the first-pass recorded length of STN, while reducing operative time. Further studies are needed to determine whether this technique leads to less morbidity and improved clinical outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia., Methods: PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2-week double-blind, crossover treatment periods, with intervening 2-week washout. After 14 days, a 2-hour intravenous levodopa-infusion was administered. Patient examinations were videotaped before infusion ("off" state) and every 30 minutes during and afterwards until patients returned to "off." The primary endpoint was dyskinesia-severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area-under-curve scores (blinded expert rated). Additional endpoints included other dyskinesia/motor assessments, global measures of clinical-change, and adverse-events., Results: A total of 13 patients were randomized and completed the study (efficacy-evaluable population). Dyskinesia-severity was nonsignificantly lower with dextromethorphan/quinidine than placebo during infusion (area-under-curve 966.5 vs 1048.8; P = .191 [efficacy-evaluable patients]), and significantly lower in a post-hoc sensitivity analysis of the per-protocol-population (efficacy-evaluable patients with ≥ 80% study-drug-compliance, n = 12) when measured from infusion start to 4-hours post-infusion completion (area-under-curve 1585.0 vs 1911.3; P = .024). Mean peak dyskinesia decreased significantly from infusion-start to return to "off" (13.3 vs 14.9; P = .018 [efficacy-evaluable patients]). A total of 9 patients rated dyskinesia "much/very much improved" on dextromethorphan/quinidine versus 1-patient on placebo. Dextromethorphan/quinidine did not worsen PD-motor scores, was generally well tolerated, and was associated with more frequent adverse events., Conclusion: This study provides preliminary evidence of clinical benefit with dextromethorphan/quinidine for treating levodopa-induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. © 2017 International Parkinson and Movement Disorder Society., (© 2017 International Parkinson and Movement Disorder Society.)

Microelectrode recording (MER) is used to confirm electrophysiological signals within intended anatomic targets during deep brain stimulation (DBS) surgery. We describe a novel technique called intraoperative CT-guided extrapolation (iCTE) to predict the intended microelectrode trajectory and, if necessary, make corrections in real-time before dural opening. Prior to dural opening, a guide tube was inserted through the headstage and rested on dura. Intraoperative CT (iCT) was obtained, and a trajectory was extrapolated along the path of the guide tube to target depth using targeting software. The coordinates were recorded and compared to initial plan coordinates. If needed, adjustments were made using the headstage to correct for error. The guide tube was then inserted and MER ensued. At target, iCT was performed and microelectrode tip coordinates were compared with planned/adjusted track coordinates. Radial error between MER track and planned/adjusted track was calculated. For comparison, MER track error prior to the iCTE technique was assessed retrospectively in patients who underwent MER using iCT, whereby iCT was performed following completion of the first MER track. Forty-seven MER tracks were analyzed prior to iCTE (pre-iCTE), and 90 tracks were performed using the iCTE technique. There was no difference between radial error of pre-iCTE MER track and planned trajectory (2.1±0.12mm) compared to iCTE predicted trajectory and planned trajectory (1.76±0.13mm, p>0.05). iCTE was used to make trajectory adjustments which reduced radial error between the newly corrected and final microelectrode tip coordinates to 0.84±0.08mm (p<0.001). Inter-rater reliability was also tested using a second blinded measurement reviewer which showed no difference between predicted and planned MER track error (p=0.53). iCTE can predict and reduce trajectory error for microelectrode placement compared with the traditional use of iCT post MER., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Patients with previously implanted cranial devices pose a special challenge in deep brain stimulation (DBS) surgery. We report the implantation of bilateral DBS leads in a patient with a cochlear implant. Technical nuances and long-term interdevice functionality are presented., Case Description: A 70-year-old patient with advancing Parkinson's disease and a previously placed cochlear implant for sensorineural hearing loss was referred for placement of bilateral DBS in the subthalamic nucleus (STN). Prior to DBS, the patient underwent surgical removal of the subgaleal cochlear magnet, followed by stereotactic MRI, frame placement, stereotactic computed tomography (CT), and merging of imaging studies. This technique allowed for successful computational merging, MRI-guided targeting, and lead implantation with acceptable accuracy. Formal testing and programming of both the devices were successful without electrical interference., Conclusion: Successful DBS implantation with high resolution MRI-guided targeting is technically feasible in patients with previously implanted cochlear implants by following proper precautions., Competing Interests: There are no conflicts of interest.

Background: The aim of this postmortem study was to compare, in Parkinson's disease subjects with and without bilateral subthalamic nucleus deep brain stimulation (STN-DBS), the loss of pigmented neurons within the substantia nigra and pathological alpha-synuclein density within the SN and other brain regions., Methods: PD subjects were identified from the Arizona Study of Aging and Neurodegenerative Disorders database (STN-DBS = 11, non-DBS = 156). Pigmented neuron loss scores within the substantia nigra as well as alpha-synuclein density scores within the substantia nigra and 9 other brain regions were compared, the latter individually and in summary as the Lewy body brain load score., Results: DBS subjects had higher alpha-synuclein density scores within the substantia nigra, olfactory bulb, and locus ceruleus, as well as higher total Lewy body brain load scores when compared with non-DBS subjects. No differences in substantia nigra pigmented neuron loss scores were found., Conclusions: STN-DBS subjects tend to have higher alpha-synuclein density scores, but do not have a differential loss of substantia nigra pigmented neurons. © 2016 International Parkinson and Movement Disorder Society., (© 2016 International Parkinson and Movement Disorder Society.)

Unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease improves skeletomotor function assessed clinically, and bilateral STN DBS improves motor function to a significantly greater extent. It is unknown whether unilateral STN DBS improves oculomotor function and whether bilateral STN DBS improves it to a greater extent. Further, it has also been shown that bilateral, but not unilateral, STN DBS is associated with some impaired cognitive-motor functions. The current study compared the effect of unilateral and bilateral STN DBS on sensorimotor and cognitive aspects of oculomotor control. Patients performed prosaccade and antisaccade tasks during no stimulation, unilateral stimulation, and bilateral stimulation. There were three sets of findings. First, for the prosaccade task, unilateral STN DBS had no effect on prosaccade latency and it reduced prosaccade gain; bilateral STN DBS reduced prosaccade latency and increased prosaccade gain. Second, for the antisaccade task, neither unilateral nor bilateral stimulation had an effect on antisaccade latency, unilateral STN DBS increased antisaccade gain, and bilateral STN DBS increased antisaccade gain to a greater extent. Third, bilateral STN DBS induced an increase in prosaccade errors in the antisaccade task. These findings suggest that while bilateral STN DBS benefits spatiotemporal aspects of oculomotor control, it may not be as beneficial for more complex cognitive aspects of oculomotor control. Our findings are discussed considering the strategic role the STN plays in modulating information in the basal ganglia oculomotor circuit.

Background: Erectile dysfunction (ED) is a common nonmotor feature in patients with Parkinson's disease (PD). Data regarding the tolerability and efficacy of anti-ED medication in the PD population are limited. The aim of this work was to assess the safety and efficacy of sildenafil in treatment of ED in men with PD., Methods: This was a double-blind, placebo-controlled, cross-over study consisting of two 4-week arms separated by a 2-week washout period. Treatment sequence (placebo-sildenafil vs. sildenafil-placebo) was randomized. Sildenafil was started at 50 mg and adjusted to 25, 50, or 100 mg after 2 weeks, depending upon side effects. The Erectile Function domain of the International Index of Erectile Function (IIEF-EF; primary outcome measure) and the Parkinson's Disease Quality of Life (secondary outcome measure) were obtained at baseline and end of each treatment period. The UPDRS was obtained at each study visit. The difference between group means was tested for statistical significance using t tests., Results: Twenty men participated and completed both treatment arms of the study. There was one instance of headache as a side effect. There was a significant effect of sildenafil on sexual functioning as measured by the IIEF-EF domain ( P < 0.0001; mean for sildenafil = 23.2 ± 7.0; mean for placebo = 12.3 ± 7.5). There were no treatment effects for quality of life ( P = 0.3) or PD symptoms ( P = 0.86)., Conclusions: Sildenafil was safe and improved ED in this sample of men with PD. Overall, PD symptoms and quality of life were not impacted by use of sildenafil.

Objectives: Intraoperative computed tomography (iCT) is currently used to confirm the target location of the microelectrode (ME) during microelectrode recording (MER) and ultimate location of deep brain stimulation (DBS) leads at our institution. We evaluated whether iCT can be used to predict the trajectory and accuracy of the ME track., Patients and Methods: Intraoperative imaging profiles of ten consecutive patients who had undergone DBS surgery were retrospectively reviewed. We found that cranial iCT, in addition to visualizing the target, also visualizes the extra-cranial segment of the guide tube (ECGT) used to insert the ME. We propose a hypothetical technique that extrapolates the trajectory of only the ECGT down to target depth using planning software. In order to provide a proof of concept analysis of this hypothetical technique, we retrospectively assessed post MER placement iCT studies and used planning software to visualize only the ECGT. An extrapolated vector was drawn along the long axis of the ECGT down to the same depth (z) as the ME. The obtained x and y coordinates were subsequently recorded and compared to the x and y coordinates of the ME tip to validate this technique., Results: The average radial error between ECGT trajectory coordinates and final ME tip coordinates was 0.93±0.1mm (mean±SEM)., Conclusion: The use of iCT to predict accuracy of microelectrode location is feasible. In the future, performing iCT before guide tube penetration of dura can allow for trajectory prediction and if needed, correction of the ME, thereby potentially improving accuracy and reducing the number of MER tracks., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Symptomatic edema around a deep-brain stimulation (DBS) lead is a rare complication of DBS surgery. Although this phenomenon is not fully understood, clinical presentation of DBS lead edema can be severe enough to prompt treatment. There is a paucity of literature on the clinical course and treatment of DBS lead edema., Case Report: We present a 65-year-old man with Parkinson disease who developed unilateral DBS lead edema after bilateral subthalamic nucleus lead placement. Infectious, inflammatory, and ischemic causes were thoroughly investigated and ruled out. Clinical symptoms and radiographic changes all returned to normal with supportive care alone., Conclusions: Lead edema is a rare complication after DBS surgery. It is important to recognize the benign clinical course of DBS lead edema to counsel patients and avoid unnecessary treatment such as hardware removal.

Functional neurosurgery for Parkinson's disease has become a mainstream concept with DBS as the prime modality. This article reviews the latest and, in the eyes of the authors, the most important developments in DBS, lesioning and gene therapy. In DBS, emerging advances have focused on the timing of surgery relative to disease duration and severity, and new targets, technologies, and equipment. For lesions, new ultrasound techniques are emerging based on successes in other movement disorders. Gene and cellular therapies, including stem cells, remain only in the research realm., (© 2015 International Parkinson and Movement Disorder Society.)

Objective: We present a proof of concept for a novel method of predicting the onset of pathological tremor using non-invasively measured surface electromyogram (sEMG) and acceleration from tremor-affected extremities of patients with Parkinson's disease (PD) and essential tremor (ET)., Approach: The tremor prediction algorithm uses a set of spectral (Fourier and wavelet) and nonlinear time series (entropy and recurrence rate) parameters extracted from the non-invasively recorded sEMG and acceleration signals., Main Results: The resulting algorithm is shown to successfully predict tremor onset for all 91 trials recorded in 4 PD patients and for all 91 trials recorded in 4 ET patients. The predictor achieves a 100% sensitivity for all trials considered, along with an overall accuracy of 85.7% for all ET trials and 80.2% for all PD trials. By using a Pearson's chi-square test, the prediction results are shown to significantly differ from a random prediction outcome., Significance: The tremor prediction algorithm can be potentially used for designing the next generation of non-invasive closed-loop predictive ON-OFF controllers for deep brain stimulation (DBS), used for suppressing pathological tremor in such patients. Such a system is based on alternating ON and OFF DBS periods, an incoming tremor being predicted during the time intervals when DBS is OFF, so as to turn DBS back ON. The prediction should be a few seconds before tremor re-appears so that the patient is tremor-free for the entire DBS ON-OFF cycle and the tremor-free DBS OFF interval should be maximized in order to minimize the current injected in the brain and battery usage.

Background: Dopamine agonist therapy and deep brain stimulation (DBS) of the subthalamic nucleus (STN) are antiparkinsonian treatments that act on a different part of the basal ganglia-thalamocortical motor circuitry, yet produce similar symptomatic improvements., Objective/hypothesis: The purpose of this study was to identify common and unique brain network features of these standard treatments., Methods: We analyzed images produced by H(2)(15)O positron emission tomography (PET) of patients with Parkinson's disease (PD) at rest. Nine patients were scanned before and after injection of apomorphine, and 11 patients were scanned while bilateral stimulators were off and while they were on., Results: Both treatments produced common deactivations of the neocortical sensorimotor areas, including the supplementary motor area, precentral gyrus, and postcentral gyrus, and in subcortical structures, including the putamen and cerebellum. We observed concomitant activations of the superior parietal lobule and the midbrain in the region of the substantia nigra/STN. We also detected unique, treatment-specific changes with possible motor-related consequences in the basal ganglia, thalamus, neocortical sensorimotor cortex, and posterolateral cerebellum. Unique changes in nonmotor regions may reflect treatment-specific effects on verbal fluency and limbic functions., Conclusions: Many of the common effects of these treatments are consistent with the standard pathophysiologic model of PD. However, the common effects in the cerebellum are not readily explained by the model. Consistent deactivation of the cerebellum is interesting in light of recent reports of synaptic pathways directly connecting the cerebellum and basal ganglia, and may warrant further consideration for incorporation into the model., (Published by Elsevier Inc.)

Object: Insight may be gained into the physiological mechanisms of deep brain stimulation (DBS) by analyzing local and contralateral subthalamic nucleus (STN) single-unit activity during activation of previously placed DBS electrodes. Special techniques are required to perform such analysis due to the presence of a large stimulus artifact. The purpose of this study was to determine the effects of DBS stimulation on single unit activity acquired from patients undergoing new or revised DBS placements., Methods: Subthalamic nucleus single unit activity was acquired from awake patients during activation of a previously implanted STN DBS electrode. Stimulation was contralateral to the recording site in 4 cases and ipsilateral in 3. Data were acquired at stimulation frequencies of 30, 60, and 130 Hz and with other stimulation parameters at clinically effective settings. Cells were included if they showed kinesthetic activity before and after the stimulation paradigm and if their action potential morphology was maintained throughout the experiment. Analysis of single-unit activity acquired before, during, and after stimulation was performed employing a time-domain algorithm to overcome the stimulus artifact., Results: Both ipsilateral and contralateral acute stimulation resulted in reversible STN firing rate suppression. The degree of suppression became greater as stimulus frequency increased and was significant at 60 Hz (t-test, p < 0.05) and 130 Hz (p < 0.01). Suppression with ipsilateral 130-Hz stimulation ranged between 52.8% and 99.8%, whereas with similar contralateral STN stimulation, the range was lower (1.9%-50.3%). Return to baseline activity levels typically occurred within seconds after stimulation ended., Conclusions: Stimulation of the STN at clinically effective frequencies has an acute suppressive rather than an excitatory effect on STN single-unit activity. The effect is bilateral, even though the degree of suppression is greater on the ipsilateral than the contralateral STN. The authors' algorithm helps reveal this effect in human patients.

Background: One of the most common symptoms of speech deficits in individuals with Parkinson's disease (PD) is significantly reduced vocal loudness and pitch range. The present study investigated whether abnormal vocalizations in individuals with PD are related to sensory processing of voice auditory feedback. Perturbations in loudness or pitch of voice auditory feedback are known to elicit short latency, compensatory responses in voice amplitude or fundamental frequency., Methodology/principal Findings: Twelve individuals with Parkinson's disease and 13 age- and sex-matched healthy control subjects sustained a vowel sound (/α/) and received unexpected, brief (200 ms) perturbations in voice loudness (±3 or 6 dB) or pitch (±100 cents) auditory feedback. Results showed that, while all subjects produced compensatory responses in their voice amplitude or fundamental frequency, individuals with PD exhibited larger response magnitudes than the control subjects. Furthermore, for loudness-shifted feedback, upward stimuli resulted in shorter response latencies than downward stimuli in the control subjects but not in individuals with PD., Conclusions/significance: The larger response magnitudes in individuals with PD compared with the control subjects suggest that processing of voice auditory feedback is abnormal in PD. Although the precise mechanisms of the voice feedback processing are unknown, results of this study suggest that abnormal voice control in individuals with PD may be related to dysfunctional mechanisms of error detection or correction in sensory feedback processing.

Deep brain stimulation (DBS) of the subthalamic nucleus improves the motor symptoms of Parkinson's disease, but may produce a worsening of speech and language performance at rates and amplitudes typically selected in clinical practice. The possibility that these dissociated effects might be modulated by selective stimulation of left and right STN has never been systematically investigated. To address this issue, we analyzed motor, speech and language functions of 12 patients implanted with bilateral stimulators configured for optimal motor responses. Behavioral responses were quantified under four stimulator conditions: bilateral DBS, right-only DBS, left-only DBS and no DBS. Under bilateral and left-only DBS conditions, our results exhibited a significant improvement in motor symptoms but worsening of speech and language. These findings contribute to the growing body of literature demonstrating that bilateral STN DBS compromises speech and language function and suggests that these negative effects may be principally due to left-sided stimulation. These findings may have practical clinical consequences, suggesting that clinicians might optimize motor, speech and language functions by carefully adjusting left- and right-sided stimulation parameters.

The objective of the study was to compare the pharmacokinetics, motor effects, and safety of IPX066, a novel extended-release formulation of carbidopa-levodopa, with an immediate-release carbidopa-levodopa formulation in advanced Parkinson's disease. We performed an open-label crossover study in 27 subjects with advanced Parkinson's disease experiencing motor fluctuations on levodopa therapy. Subjects were randomized 1:1 to 8 days' treatment with either immediate-release carbidopa-levodopa followed by IPX066 or IPX066 followed by immediate-release carbidopa-levodopa. Pharmacokinetic and motor assessments were undertaken on day 1 for 8 hours (following a single dose) and on day 8 for 12 hours (during multiple-dose administration). Following a single dose of IPX066 or immediate-release carbidopa-levodopa, plasma levodopa concentrations increased at a similarly rapid rate and were sustained above 50% of peak concentration for 4 hours with IPX066 versus 1.4 hours with immediate-release carbidopa-levodopa (P < .0001). Multiple-dose data showed IPX066 substantially reduced variability in plasma levodopa concentrations despite a lower dosing frequency (mean, 3.5 vs 5.4 administrations per day). In addition, total levodopa exposure during IPX066 treatment was approximately 87% higher, whereas the increase in levodopa C(max) was approximately 30% compared with immediate-release carbidopa-levodopa. Both products were well tolerated. IPX066 provided more sustained plasma levodopa concentrations than immediate-release carbidopa-levodopa. Larger, longer-term, well-controlled studies should be conducted to provide rigorous assessment of the clinical effects of IPX066., (Copyright © 2011 Movement Disorder Society.)

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) has been demonstrated to be an effective therapy for the treatment of primary dystonia as well as tardive dystonia. Results for other forms of secondary dystonia have been less consistent. Although a number of target sites have been explored for the treatment of dystonia, most notably the motor thalamus, the target of choice remains the sensorimotor portion of the GPi. Although the optimal site within the GPi has not been determined, most centers agree that the optimal site involves the posteroventral lateral "sensorimotor" portion of the GPi. Microelectrode recording (MER) can be used to identify boundaries of the GPi and nearby white matter tracts, including the corticospinal tract and optic tract, and the sensorimotor GPi. However, whether or not the use of MER leads to improved outcomes compared with procedures performed without MER has not been determined. Currently, there is no evidence to support or refute the hypothesis that mapping structures with MER provides better short- or long-term outcomes. Centers using MER do not report a preference of one system over another, but there have not been any studies to compare the relative benefits or risks of using more than 1 electrode simultaneously. Comparison studies of different target structures and targeting techniques in dystonia have not been performed. Additional research, which includes comparative studies, is needed to advance our understanding and optimization of DBS targets, techniques, and approaches along with their relative benefits and risks in dystonia., (Copyright © 2011 Movement Disorder Society.)

This article reviews the available literature related to the surgical technique for implantation of deep brain stimulation (DBS) hardware for the treatment of dystonia. Topics covered include stereotactic targeting, selection of specific hardware components, site of placement of the cable connectors and pulse generators, and postoperative documentation of electrode location. Techniques in stereotactic neurosurgery are rapidly evolving, and there is no Class I evidence to unequivocally validate any specific technique described. Nevertheless, the guidelines provided may assist surgical teams in tailoring a rational approach to DBS implantation in dystonia., (Copyright © 2011 Movement Disorder Society.)

A 13-year old girl presented with slowly progressive rest tremor of the hands, bradykinesia, and rigidity. The symptoms improved with dopaminergic medications, but severe drug-induced dyskinesias developed early. She subsequently developed cognitive slowing and difficulty initiating saccadic eye movements. She went on to have deep brain stimulation surgery. Experts discuss the syndromal diagnosis and predict the underlying pathology. The pathological diagnosis is given and clinical learning points are considered., (© 2010 Movement Disorder Society.)

This study examined the long-term effects of chronic subthalamic nucleus (STN) deep brain stimulation (DBS) using both clinical evaluation and laboratory motor control measures. Over a 5-year time period, changes in the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) and movement speed and strength at the ankle joint were evaluated on and off STN DBS in eight patients with Parkinson's disease (PD). Four patients were also studied at the elbow joint. Patients with PD originally received unilateral STN DBS between years 2001 and 2003. They were re-evaluated after 5 years of long-term STN DBS between years 2006-2008. At baseline (year 0) and after 5 years, patients with PD were tested off treatment and on STN DBS. In each testing condition, patients performed ballistic, single degree of freedom ankle dorsiflexion and ankle plantarflexion movements and peak velocity was calculated. Patients also performed maximal voluntary contractions at the ankle joint in both directions, and peak torque was calculated. Results showed increased motor UPDRS scores from year 0 to year 5, but STN DBS was efficacious in reducing them. In contrast to the increase in motor UPDRS scores, motor control results showed a marked improvement in peak velocity and peak torque over the 5-year time period in the off treatment condition, and STN DBS was efficacious by improving both peak velocity and peak torque. The current findings suggest that 5 years of chronic STN DBS can have beneficial effects on the motor system over the long term in discrete motor tasks in which maximal effort and maximal neural output is required.

The authors report on a patient with craniocervical dystonia who was treated with bilateral GPi stimulation, with excellent improvement in dystonia but at the cost of stimulation-induced, reversible parkinsonism. Stimulation through ventral contacts resulted in maximal relief of craniocervical dystonia but induced considerable hypophonia, bradykinesia, rigidity, freezing, and impaired postural reflexes. Stimulation through dorsal contacts alleviated parkinsonism, but resulted in the return of dystonia. No stimulation parameters could alleviate the dystonia without inducing parkinsonism over the course of his 4-year follow-up.

Object: Although nucleus ventralis intermedius stimulation has been shown to be safe and efficacious in the treatment of essential tremor, there is a subset of patients who eventually lose benefit from their stimulation. Proposed causes for this phenomenon include tolerance, disease progression, and suboptimal location. The goal of this study was to assess the factors that may lead to both stimulation failure, defined as loss of meaningful tremor relief, and less satisfactory outcomes, defined as leads requiring voltages>3.6 V for effective tremor control., Methods: The authors present their clinical outcomes from 31 leads in 27 patients who had effective tremor control for >1 year following nucleus ventralis intermedius stimulation. All patients postoperatively had a mean decrease in both the writing and drawing subscales of the Fahn-Tolosa-Marin Tremor Rating Scale (p<0.001)., Results: After a mean follow-up of 40 months, 22 patients continued to have tremor control with stimulation. Four patients eventually lost efficacy of their stimulation at a mean of 39 months. There was no difference in age, duration of disease, or disease severity between the groups. Examination of perioperative factors revealed that suboptimal anteroposterior positioning as evidenced on intraoperative fluoroscopy occurred significantly more frequently in patients with stimulation failure (p=0.018). In patients with less satisfactory outcomes, no difference was seen between group demographics. Fluoroscopy again revealed suboptimal positioning more frequently in these patients (p=0.005)., Conclusions: This study provides further evidence that suboptimal lead position in combination with disease progression or tolerance may result in less satisfactory long-term outcomes.

Currently, no study of subthalamic nucleus (STN) stimulation has compared continuous stimulation with a period of short-term stimulation, which is frequently employed in the clinic and in research studies. Therefore, this study examined the effects of STN stimulation over 90 min (short) and greater than 3 months (long) on the cardinal signs of Parkinson's disease. The 90 min time period immediately followed a 12 hour withdrawal from both STN stimulation and medication. Ten PD patients who received STN stimulation were studied. Bradykinesia, rigidity, and tremor were evaluated using the UPDRS and motor control measures which included peak velocity (bradykinesia), work (rigidity), and amplitude (tremor). Results showed no difference between 90 min and greater than 3 months of STN stimulation for the UPDRS or motor control measures. This finding confirms that the treatment efficacy that is derived from a relatively short time course of stimulation generalizes to longer time periods of high frequency STN stimulation that patients experience in their daily lives. As such, it is reasonable to evaluate the effect of DBS after 90 min of stimulation in clinical trials and research studies., ((c) 2008 Movement Disorder Society.)

Deep brain stimulation (DBS) has assumed a prominent role in the treatment of Parkinson's disease (PD). In this manuscript, we attempt to estimate the prevalence and categorize adverse events (AEs) of DBS in PD, based on efficacy studies published over the last decade. We conclude that reliable categorization and quantification of AEs based on available data poses many challenges and argue that a standardized scheme for reporting AEs should be created. This would provide a foundation for a meaningful risk/benefit analysis, for comparison of results between centers and, ultimately, for a well informed decision by physicians and patients as to whether surgery should be pursued., (2007 Movement Disorder Society)

This study examined the efficacy of subthalamic nucleus (STN), deep brain stimulation (DBS), and medication for resting tremor during performance of secondary tasks. Hand tremor was recorded using accelerometry and electromyography (EMG) from 10 patients with Parkinson's disease (PD) and ten matched control subjects. The PD subjects were examined off treatment, on STN DBS, on medication, and on STN DBS plus medication. In the first experiment, tremor was recorded in a quiet condition and during a cognitive task designed to enhance tremor. In the second experiment, tremor was recorded in a quiet condition and during isometric finger flexion (motor task) with the contralateral limb at 5% of the maximal voluntary contraction (MVC) that was designed to suppress tremor. Results showed that: (1) STN DBS and medication reduced tremor during a cognitive task that exacerbated tremor, (2) STN DBS normalized tremor frequency in both the quiet and cognitive task conditions, whereas tremor amplitude was only normalized in the quiet condition, (3) a secondary motor task reduced tremor in a similar manner to STN DBS. These findings demonstrate that STN DBS still suppresses tremor in the presence of a cognitive task. Furthermore, a secondary motor task of the opposite limb suppresses tremor to levels comparable to STN DBS.

This study examined the control of elbow force in nine patients with Parkinson's disease when visual feedback was available and when visual feedback was removed to determine how medication (Meds) and unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) affect memory guided force control. Patients were examined in each of four treatment conditions: 1) off treatment; 2) Meds; 3) STN DBS; and 4) Meds plus STN DBS. With visual feedback available, there was no difference in force output across treatment conditions. When visual feedback was removed force output drifted under the target in both the off-treatment and the Meds conditions. However, when on STN DBS or Meds plus STN DBS force output drifted above the target. As such, only STN DBS had a significant effect on force output in the vision removed condition. Increased force output when on STN DBS may have occurred due to disruptions in the basal ganglia-thalamo-cortical circuitry. We suggest that modulation of output of the internal segment of the globus pallidus by STN DBS may drive the effect of STN DBS on memory guided force control.

We quantified the effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and medication on Parkinsonian rigidity using an objective measure of work about the elbow joint during a complete cycle of imposed 1-Hz sinusoidal oscillations. Resting and activated rigidity were analyzed in four experimental conditions: 1) off treatment; 2) on DBS; 3) on medication; and 4) on DBS plus medication. Rigidity at the elbow joint was also assessed using the Unified Parkinson's Disease Rating Scale (UPDRS). We tested ten patients who received STN DBS and ten age-matched neurologically healthy control subjects. The activated rigidity condition increased work in both Parkinson's disease (PD) patients and control subjects. In PD patients, STN DBS reduced both resting and activated rigidity as indicated by work and the UPDRS rigidity score. This is the first demonstration that STN stimulation reduces rigidity using an objective measure such as work. In contrast, the presurgery dose of antiparkinsonian medication did not significantly improve the UPDRS rigidity score and reduced work only in the activated rigidity condition. Our results suggest that STN DBS may be more effective in alleviating rigidity in the upper limb of PD patients than medications administered at presurgery dosage level.

This study tested the hypothesis that left versus right deep brain stimulation (DBS) of the subthalamic nucleus (STN) would have differential effects on speech. Twenty right-handed individuals with advanced Parkinson's disease (PD) underwent unilateral STN DBS. Ten were operated on the right and 10 on the left hemisphere as indicated by severity of nonspeech motor function. Speech was evaluated before surgery and 3 to 6 months after surgery with stimulator-off and with stimulator-on, with all participants off anti-parkinsonian medication for 12 hours before evaluation. Evaluators and patient speakers were blinded to the stimulator status at the postsurgery evaluations. Motor performance was assessed with UPDRS-III. Each participant produced three samples of diadochokinetic syllables. Syllable rate, syllable and vowel duration, VOT, and F0 were obtained. The diadochokinetic syllables were rated for articulatory accuracy and speaking rate. Twenty graduate clinicians served as judges. The samples were randomly presented via headphones. A mixed ANOVA with repeated measures was used to assess the significance of the changes in UPRS-III scores and speech measures. The results indicated that unilateral STN DBS produced improvement in nonspeech motor function regardless of the side of stimulation. In contrast, the changes in articulatory accuracy and syllable rate associated with the STN DBS were hemisphere specific.