Indication of surgical therapy for Parkinson's disease

We review the current status of surgical treatment of Parkinson's disease (PD). The advantages of deep brain stimulation (DBS) over ablative surgery include reversibility and controllability of stimulation. In addition, DBS carries a smaller risk of side effects, especially when employed bilaterally. DBS of the thalamus is useful to control tremor which is unresponsive to medication. DBS of the globus pallidus internus (GPi) or the subthalamic nucleus (STN) is useful to control wearing off of motor symptoms which is difficult to manage with medication alone. DBS of STN and GPi improves motor function mainly during the off-period. DBS of STN attenuates levodopa-induced dyskinesia through reduction of dopa requirement, whereas DBS of GPi attenuates dopa-induced dyskinesia directly. DBS of STN is also useful to control symptoms of PD in patients who are intolerant to dopa. However, DBS of either STN or GPi cannot reverse advanced symptoms of PD, which are unresponsive to dopa.     

Free-living energy expenditure reduced after deep brain stimulation surgery for Parkinson's disease

Background: The clinical picture in Parkinson’s disease (PD) is characterized by bradykinesia, rigidity, resting tremor and postural instability. In advanced stages of the disease, many patients will experience reduced efficacy of medication with fluctuations in symptoms and dyskinesias. Surgical treatment with deep brain stimulation in the subthalamic nucleus (STN‐DBS) is now considered the gold standard in fluctuating PD. Many patients experience a gain of weight following the surgery. The aim of this study was to identify possible mechanisms, which may contribute to body weight gain in patients with PD following bilateral STN‐DBS surgery. Methods: Ten patients with PD were studied before bilateral STN‐DBS surgery, and seven patients were studied again 3 and 12 months postoperatively. Clinical examination and resting metabolic rate with and without medical treatment was measured before and after STN‐DBS. Furthermore, free‐living energy expenditure, body composition, energy intake, peak oxygen consumption, maximal workload and leisure time physical activity were measured before and 3 and 12 months after surgery. Results: The STN‐DBS operated patients had a significant weight gain of 4·7 ± 1·6 kg (mean ± SE) 12 months postoperatively, and the weight gain was in the fat mass. The free‐living energy expenditure decreased postoperatively 13 ± 4% even though the reported dietary intake was reduced. A decreased energy expenditure took place in the non‐resting energy expenditure. The reported daily leisure time activity, peak oxygen consumption and maximal workload were unchanged. Conclusion: The STN‐DBS operated patients have a significant postoperative weight gain, as a result of a decrease in free‐living energy expenditure concomitant with an insufficient decrease in energy intake.     

深部脑电刺激治疗帕金森病的FDGPET研究

目的研究双侧丘脑底核慢性电刺激术对晚期帕金森病患者脑局部糖代谢的影响及作用机制.方法对7例进行双侧STN DBS的晚期帕金森病患者,在术前和术后1个月电刺激条件下,分别进行18F-脱氧葡萄糖(18F-FDG)PET显像和UPDRS评分,通过SPM进行数据分析.结果 7例患者临床症状明显改善,同时FDG PET显像提示双侧豆状核、脑干、顶枕部、运动前区(BA6)及扣带回的脑代谢增加,而前额叶底部及海马的脑代谢减少(P<0.05).结论双侧STN DBS可使PD患者临床症状改善.FDG PET可作为PD进行STN治疗适应证选择的方法之一.     

Subthalamic GAD gene transfer in Parkinson disease patients who are candidates for deep brain stimulation

This gene transfer experiment is the first Parkinson's Disease (PD) protocol to be submitted to the Recombinant DNA Advisory Committee. The principal investigators have uniquely focused their careers on both pre-clinical work on gene transfer in the brain and clinical expertise in management and surgical treatment of patients with PD. They have extensively used rodent models of PD for proof-of-principle experiments on the utility of different vector systems. PD is an excellent target for gene therapy, because it is a complex acquired disease of unknown etiology (apart from some rare familial cases) yet it is characterized by a specific neuroanatomical pathology, the degeneration of dopamine neurons of the substantia nigra (SN) with loss of dopamine input to the striatum. This pathology results in focal changes in the function of several deep brain nuclei, which have been well-characterized in humans and animal models and which account for many of the motor symptoms of PD. Our original approaches, largely to validate in vivo gene transfer in the brain, were designed to facilitate dopamine transmission in the striatum using an AAV vector expressing dopamine-synthetic enzymes. Although these confirmed the safety and potential efficacy of AAV, complex patient responses to dopamine augmenting medication as well as poor results and complications of human transplant studies suggested that this would be a difficult and potentially dangerous clinical strategy using current approaches. Subsequently, we and others investigated the use of growth factors, including GDNF. These showed some encouraging effects on dopamine neuron survival and regeneration in both rodent and primate models; however, uncertain consequences of long-term growth factor expression and question regarding timing of therapy in the disease course must be resolved before any clinical study can be contemplated. We now propose to infuse into the subthalamic nucleus (STN) recombinant AAV vectors expressing the two isoforms of the enzyme glutamic acid decarboxylase (GAD-65 and GAD-67), which synthesizes the major inhibitory neurotransmitter in the brain, GABA. The STN is a very small nucleus (140 cubic mm or 0.02% of the total brain volume, consisting of approximately 300,000 neurons) which is disinhibited in PD, leading to pathological excitation of its targets, the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNpr). Increased GPi/SNpr outflow is believed responsible for many of the cardinal symptoms of PD, i.e., tremor, rigidity, bradykinesia, and gait disturbance. A large amount of data based on lesioning, electrical stimulation, and local drug infusion studies with GABA-agonists in human PD patients have reinforced this circuit model of PD and the central role of the STN. Moreover, the closest conventional surgical intervention to our proposal, deep brain stimulation (DBS) of the STN, has shown remarkable efficacy in even late stage PD, unlike the early failures associated with recombinant GDNF infusion or cell transplantation approaches in PD. We believe that our gene transfer strategy will not only palliate symptoms by inhibiting STN activity, as with DBS, but we also have evidence that the vector converts excitatory STN projections to inhibitory projections. This additional dampening of outflow GPi/SNpr outflow may provide an additional advantage over DBS. Moreover, of perhaps the greatest interest, our preclinical data suggests that this strategy may also be neuroprotective, so this therapy may slow the degeneration of dopaminergic neurons. We will use both GAD isoforms since both are typically expressed in inhibitory neurons in the brain, and our data suggest that the combination of both isoforms is likely to be most beneficial. Our preclinical data includes three model systems: (1) old, chronically lesioned parkinsonian rats in which intraSTN GAD gene transfer results not only in improvement in both drug-induced asymmetrical behavior (apomorphine symmetrical rotations), but also in spontaneous behaviors. In our second model, GAD gene transfer precedes the generation of a dopamine lesion. Here GAD gene transfer showed remarkable neuroprotection. Finally, we carried out a study where GAD-65 and GAD-67 were used separately in monkeys that were resistant to MPTP lesioning and hence showed minimal symptomatology. Nevertheless GAD gene transfer showed no adverse effects and small improvements in both Parkinson rating scales and activity measures were obtained. In the proposed clinical trial, all patients will have met criteria for and will have given consent for STN DBS elective surgery. Twenty patients will all receive DBS electrodes, but in addition they will be randomized into two groups, to receive either a solution containing rAAV-GAD, or a solution which consists just of the vector vehicle, physiological saline. Patients, care providers, and physicians will be blind as to which solution any one patient receives. All patients, regardless of group, will agree to not have the DBS activated until the completion and unblinding of the study. Patients will be assessed with a core clinical assessment program modeled on the CAPSIT, and in addition will also undergo a preop and several postop PET scans. At the conclusion of the study, if any patient with sufficient symptomatic improvement will be offered DBS removal if they so desire. Any patients with no benefit will simply have their stimulators activated, which would normally be appropriate therapy for them and which requires no additional operations. If any unforeseen symptoms occur from STN production of GABA, this might be controlled by blocking STN GABA release with DBS, or STN lesioning could be performed using the DBS electrode. Again, this treatment would not subject the patient to additional invasive brain surgery. The trial described here reflects an evolution in our thinking about the best strategy to make a positive impact in Parkinson Disease by minimizing risk and maximizing potential benefit. To our knowledge, this proposal represents the first truly blinded, completely controlled gene or cell therapy study in the brain, which still provides the patient with the same surgical procedure which they would normally receive and should not subject the patient to additional surgical procedures regardless of the success or failure of the study. This study first and foremost aims to maximally serve the safety interests of the individual patient while simultaneously serving the public interest in rigorously determining in a scientific fashion if gene therapy can be effective to any degree in treating Parkinson's disease.     

Deep brain stimulation(DBS) therapy for parkkinson,s disease

During the last decade, it has become increasingly clear that DBS represents a useful adjunct for therapies to control various symptoms of Parkinson's disease. The stimulation sites include the thalamic nucleus ventralis intermedius(Vim), globus pallidus internus(GPi) and subthalamic nucleus (STN). The clinical data of DBS therapy currently available from the literature, together with our own experience, are reviewed. The results of our double blinded evaluation of the effects of GPi and STN stimulation are also summarized. DBS therapy affords the best effect on tremor when the Vim is selected as the stimulation site. DBS therapy is also useful for controlling rigidity when the GPi or STN is stimulated. Improvement of bradykinesia may often be induced by DBS therapy involving the GPi or STN. Dopa-induced dyskinesia can be attenuated effectively by the direct and/or indirect effects of DBS therapy. Two advantages of GPi and STN stimulation were identified in our double blinded evaluation. Firstly, the stimulation can supplement a reduced action of levodopa during the off-period. It thus improves the patient's daily activities through attenuation of the motor fluctuations. Secondly, the stimulation can replace part of the action of levodopa during the on-period. It thus attenuates dopa-induced dyskinesia through a reduced dose of medication. More importantly, the stimulation improves the daily activities in dopa-intolerant patients who are being administered a small dose of levodopa because of unbearable side effects. In addition, GPi stimulation has its own inhibitory effect on dopa-induced dyskinesia.     

Deep brain stimulation for advanced Parkinson's disease

Deep brain stimulation (DBS) is a new and promising technique for the treatment of movement disorders. Medically intractable Parkinson's disease (PD) is one of the most common indications for DBS. There are three possible subcortical targets for PD, depending on the symptomatology (i.e., the motor subdivision of the thalamus, the globus pallidus internus, the subthalamic nucleus [STN]). Thalamic stimulation has been well established as a safe and effective treatment for essential tremor and the tremor associated with PD. Globus pallidus internus and STN DBS are being investigated for the treatment of all the cardinal signs of PD. This article describes the pathophysiology of PD, the surgical treatment history of PD, surgical techniques used for DBS implants, and the role the perioperative nurse has in the care of the patients undergoing these procedures.     

Frequency-correlated decreases of motor cortex activity associated with subthalamic nucleus stimulation in Parkinson's disease

According to the classical model of basal ganglia organization, deep brain stimulation (DBS) in the subthalamic nucleus (STN) for the treatment of Parkinson's disease (PD) blocks overactive excitatory projections to inhibitory basal ganglia output structures. This would release the break on thalamofrontal neurons alleviating the poverty of movement, the hallmark of PD. Such parallels to a functional lesion certainly simplify the mechanism of STN DBS. Here, we applied parametric analyses of H2(15)O positron emission tomography (PET) scans at rest while systematically varying stimulation frequency in 6 patients with STN DBS for akinetic PD. A strong positive correlation of rCBF to increasing stimulation frequency was detected around the STN bilaterally. More importantly, we show that gradual increases in STN stimulation frequency are tightly correlated with decreases in motor cortex activity. This demonstrates an active modulation of resting activity within the subcortical stimulation target and within motor cortex by STN DBS. Rather than a possible downstream effect, we propose to consider the tight correlations between DBS frequency and motor cortex activity in the context of an upstream modulation of direct efferents to the STN from primary motor and premotor cortices.     

脑慢性深部电刺激治疗难治性帕金森病及特发性震颤

目的 应用脑慢性深部电刺激 (DBS)治疗难治性帕金森病 (PD)及特发性震颤 (ET),并对其疗效作出评价。方法 对 6例 PD患者及 2例 ET患者采用磁共振导向立体定向及术中电生理验证方法。将刺激电极分别植入丘脑腹中间核及丘脑底核,并同期植入刺激发生器。结果 6例患者术后获得了显著的疗效,震颤完全消失,肌张力恢复正常,步态、姿势明显改善,未出现任何并发症。结论 DBS作为目前最理想的手术方法治疗药物难治性 PD、 ET,具有极少副作用、可逆转性的优点,能完全控制震颤,明显改善肌张力障碍、步态、姿势等运动障碍。     

Modulation of subthalamic T-type Ca(2+) channels remedies locomotor deficits in a rat model of Parkinson disease

An increase in neuronal burst activities in the subthalamic nucleus (STN) is a well-documented electrophysiological feature of Parkinson disease (PD). However, the causal relationship between subthalamic bursts and PD symptoms and the ionic mechanisms underlying the bursts remain to be established. Here, we have shown that T-type Ca(2+) channels are necessary for subthalamic burst firing and that pharmacological blockade of T-type Ca(2+) channels reduces motor deficits in a rat model of PD. Ni(2+), mibefradil, NNC 55-0396, and efonidipine, which inhibited T-type Ca(2+) currents in acutely dissociated STN neurons, but not Cd(2+) and nifedipine, which preferentially inhibited L-type or the other non–T-type Ca(2+) currents, effectively diminished burst activity in STN slices. Topical administration of inhibitors of T-type Ca(2+) channels decreased in vivo STN burst activity and dramatically reduced the locomotor deficits in a rat model of PD. Cd(2+) and nifedipine showed no such electrophysiological and behavioral effects. While low-frequency deep brain stimulation (DBS) has been considered ineffective in PD, we found that lengthening the duration of the low-frequency depolarizing pulse effectively improved behavioral measures of locomotion in the rat model of PD, presumably by decreasing the availability of T-type Ca(2+) channels. We therefore conclude that modulation of subthalamic T-type Ca(2+) currents and consequent burst discharges may provide new strategies for the treatment of PD.     

脑深部电刺激治疗帕金森病患者的护理配合

目的：探讨脑深部电刺激（ DBS）治疗帕金森病（ PD）患者手术配合的要点,以期提高临床疗效,减少并发症。方法对2011年3月至2012年10月行DBS手术的187例帕金森病患者,进行缜密、细致的手术配合,并对部分手术方法进行改进。结果187例患者共植入325侧电极,单侧49例,双侧138例,全部患者术后均无颅内血肿和永久神经系统并发症出现。187例患者随访3～27个月,开机不服药和开机服药患者的UPDRSⅢ评分改善率分别为51％和63％,与术前相比,患者术后服用多巴胺类药物的剂量明显减少,平均减少62％。结论 DBS是治疗PD的有效手段。周到细致的手术护理配合对DBS治疗帕金森病的疗效提高具有重要作用。     

脑深部电刺激治疗帕金森病的围手术期护理

目的 探讨脑深部电刺激（DBS）治疗帕金森病的护理方法及效果.方法 对我院2006年8月至2008年11月脑深部电刺激治疗的12例原发性帕金森病患者进行严谨的围手术期护理,重点加强患者的心理护理和知识宣教,严密观察病情,积极防范并发症的发生.结果 12例共植入22根电极（单侧2例,双侧10例）,刺激电极植入靶点均为丘脑底核（STN）,全部术后无颅内血肿出现,无感染及永久神经系统并发症,无刺激相关的不良反应;12例患者随访时间2～28个月,术后6个月UPDRSⅢ评分在开机不服药和开机服药的改善率分别是50%和67%.结论 周到细致的围手术期护理是STN-DBS治疗帕金森病良好疗效的保障.     

Probabilistic analysis of activation volumes generated during deep brain stimulation

Deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson's disease (PD) and shows great promise for the treatment of several other disorders. However, while the clinical analysis of DBS has received great attention, a relative paucity of quantitative techniques exists to define the optimal surgical target and most effective stimulation protocol for a given disorder. In this study we describe a methodology that represents an evolutionary addition to the concept of a probabilistic brain atlas, which we call a probabilistic stimulation atlas (PSA). We outline steps to combine quantitative clinical outcome measures with advanced computational models of DBS to identify regions where stimulation-induced activation could provide the best therapeutic improvement on a per-symptom basis. While this methodology is relevant to any form of DBS, we present example results from subthalamic nucleus (STN) DBS for PD. We constructed patient-specific computer models of the volume of tissue activated (VTA) for 163 different stimulation parameter settings which were tested in six patients. We then assigned clinical outcome scores to each VTA and compiled all of the VTAs into a PSA to identify stimulation-induced activation targets that maximized therapeutic response with minimal side effects. The results suggest that selection of both electrode placement and clinical stimulation parameter settings could be tailored to the patient's primary symptoms using patient-specific models and PSAs.     

Sensory abnormalities and pain in Parkinson disease and its modulation by treatment of motor symptoms

Pain and sensory abnormalities are present in a large proportion of Parkinson disease (PD) patients and have a significant negative impact in quality of life. It remains undetermined whether pain occurs secondary to motor impairment and to which extent it can be relieved by improvement of motor symptoms. The aim of this review was to examine the current knowledge on the mechanisms behind sensory changes and pain in PD and to assess the modulatory effects of motor treatment on these sensory abnormalities. A comprehensive literature search was performed. We selected studies investigating sensory changes and pain in PD and the effects of levodopa administration and deep brain stimulation (DBS) on these symptoms. PD patients have altered sensory and pain thresholds in the off‐medication state. Both levodopa and DBS improve motor symptoms (i.e.: bradykinesia, tremor) and change sensory abnormalities towards normal levels. However, there is no direct correlation between sensory/pain changes and motor improvement, suggesting that motor and non‐motor symptoms do not necessarily share the same mechanisms. Whether dopamine and DBS have a real antinociceptive effect or simply a modulatory effect in pain perception remain uncertain. These data may provide useful insights into a mechanism‐based approach to pain in PD, pointing out the role of the dopaminergic system in pain perception and the importance of the characterization of different pain syndromes related to PD before specific treatment can be instituted.     

Patient-specific analysis of the relationship between the volume of tissue activated during DBS and verbal fluency

Deep brain stimulation (DBS) for the treatment of advanced Parkinson's disease involves implantation of a lead with four small contacts usually within the subthalamic nucleus (STN) or globus pallidus internus (GPi). While generally safe from a cognitive standpoint, STN DBS has been commonly associated with a decrease in the speeded production of words, a skill referred to as verbal fluency. Virtually all studies comparing presurgical to postsurgical verbal fluency performance have detected a decrease with DBS. The decline may be attributable in part to the surgical procedures, yet the relative contributions of stimulation effects are not known. In the present study, we used patient-specific DBS computer models to investigate the effects of stimulation on verbal fluency performance. Specifically, we investigated relationships of the volume and locus of activated STN tissue to verbal fluency outcome. Stimulation of different electrode contacts within the STN did not affect total verbal fluency scores. However, models of activation revealed subtle relationships between the locus and volume of activated tissue and verbal fluency performance. At ventral contacts, more tissue activation inside the STN was associated with decreased letter fluency performance. At optimal contacts, more tissue activation within the STN was associated with improved letter fluency performance. These findings suggest subtle effects of stimulation on verbal fluency performance, consistent with the functional nonmotor subregions/somatotopy of the STN.     

Topography of cortical and subcortical connections of the human pedunculopontine and subthalamic nuclei

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the most common surgical therapy for Parkinson' s disease (PD). DBS of the pedunculopontine nucleus (PPN) is emerging as a promising surgical therapy for PD as well. In order to better characterize these nuclei in humans, we determined the anatomical connections of the PPN and STN and the topography of these connections using probabilistic diffusion tractography. Diffusion tractography was carried out in eight healthy adult subjects using diffusion data acquired at 1.5 T MRI (60 directions, b=1000 s/mm(2), 2 x 2 x 2 mm(3) voxels). The major connections that we identified from single seed voxels within STN or PPN were present in at least half the subjects and the topography of these connections within a 36-voxel region surrounding the initial seed voxel was then examined. Both the PPN and STN showed connections with the cortex, basal ganglia, cerebellum, and down the spinal cord, largely matching connections demonstrated in primates. The topography of motor and associative brain areas in the human STN was strikingly similar to that shown in animals. PPN Topography has not been extensively demonstrated in animals, but we showed significant topography of cortical and subcortical connections in the human PPN. In addition to demonstrating the usefulness of PDT in determining the connections and topography of small grey matter structures in vivo, these results allow for inference of optimal DBS target locations and add to our understanding of the role of these nuclei in PD.     

Distinct oscillatory STN-cortical loops revealed by simultaneous MEG and local field potential recordings in patients with Parkinson's disease

Neuronal oscillations are assumed to play a pivotal role in the pathophysiology of Parkinson's disease (PD). Neurons in the subthalamic nucleus (STN) generate oscillations which are coupled to rhythmic population activity both in other basal ganglia nuclei and cortical areas. In order to localize these cortical areas, we recorded local field potentials (LFPs) and magnetoencephalography (MEG) simultaneously in PD patients undergoing surgery for deep brain stimulation (DBS). Patients were withdrawn from antiparkinsonian medication and recorded at rest. We scanned the entire brain for oscillations coherent with LFPs recorded from the STN with a frequency domain beamformer. Coherent activity in the low (12-20 Hz) and high (20-35 Hz) beta range was found in the ipsilateral sensorimotor and the premotor cortex. Coherence in the alpha range (7-12 Hz) was observed at various locations in the ipsilateral temporal lobe. In a subset of subjects, the superior temporal gyrus consistently showed coherent alpha oscillations. Our findings provide new insights into patterns of frequency-specific functional connectivity between basal ganglia and cortex and suggest that simultaneous inter-regional interactions may be segregated in the frequency domain. Furthermore, they demonstrate that simultaneous MEG-LFP recordings are a powerful tool to study interactions between brain areas in PD patients undergoing surgery for DBS.     

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease

Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted tool for the treatment of Parkinson's disease (PD). Although the precise mechanism of action of this intervention is unknown, its effectiveness has been attributed to the modulation of pathological network activity. We examined this notion using positron emission tomography (PET) to quantify stimulation-induced changes in the expression of a PD-related covariance pattern (PDRP) of regional metabolism. These metabolic changes were also compared with those observed in a similar cohort of patients undergoing STN lesioning. We found that PDRP activity declined significantly (P < 0.02) with STN stimulation. The degree of network modulation with DBS did not differ from that measured following lesioning (P = 0.58). Statistical parametric mapping (SPM) revealed that metabolic reductions in the internal globus pallidus (GPi) and caudal midbrain were common to both STN interventions (P < 0.01), although declines in GPi were more pronounced with lesion. By contrast, elevations in posterior parietal metabolism were common to the two procedures, albeit more pronounced with stimulation. These findings indicate that suppression of abnormal network activity is a feature of both STN stimulation and lesioning. Nonetheless, these two interventions may differ metabolically at a regional level.     

The effects of high frequency subthalamic stimulation on balance performance and fear of falling in patients with Parkinson's disease

Background  

Balance impairment is one of the most distressing symptoms in Parkinson's disease (PD) even with pharmacological treatment (levodopa). A complementary treatment is high frequency stimulation in the subthalamic nucleus (STN). Whether STN stimulation improves postural control is under debate. The aim of this study was to explore the effects of STN stimulation alone on balance performance as assessed with clinical performance tests, subjective ratings of fear of falling and posturography.     

Surgical approaches to treatment of Parkinson's disease: Implications for speech function

Although neurosurgical procedures have been reported to be successful in relieving many of the motor symptoms of Parkinson's disease (PD) (e.g., tremor, rigidity, bradykinesia) in the limb musculature, their effect on speech is much less consistent. This paper will review and evaluate reports in the literature on the effects of various surgical interventions for PD, including thalamotomy, pallidotomy, and DBS, on speech. In particular the paper will focus on the implications of these findings for one's understanding of the neurological control of the speech mechanism. As a foundation, contemporary models of the neuropathophysiology of PD and hypokinetic dysarthria will be outlined and explained. The various neurosurgical treatments for PD will be described and their theoretical underpinning discussed with regard to their proposed effects on subcortical and cortical motor control systems. Evidence suggestive of the need to reconsider contemporary thinking in relation to the neurology of speech and the need to differentiate it from limb neurology will be highlighted.     

Speech motor program maintenance,but not switching,is enhanced by left-hemispheric deep brain stimulation in Parkinson's disease

Speech reaction time (SRT) was measured in a response priming protocol in 12 participants with Parkinson's disease (PD) and hypokinetic dysarthria “on” and “off” left-hemispheric deep brain stimulation (DBS). Speech preparation was measured during speech motor programming in two randomly ordered speech conditions: speech maintenance and switching. Double blind testing was completed in participants with DBS of globus pallidus pars interna (GPi) (n?=?5) or subthalamic nucleus (STN) (n?=?7). SRT was significantly faster in the maintenance vs switch task, regardless of DBS state. SRT was faster in the speech maintenance task “on” stimulation, while there was no difference in speech switching “on” and “off” DBS. These data suggest that left-hemispheric DBS may have differential effects on aspects of speech preparation in PD. It is hypothesized that speech maintenance improvements may result from DBS-induced cortical enhancements, while the lack of difference in switching may be related to inhibition deficits mediated by the right-hemisphere. Alternatively, DBS may have little influence on the higher level motor processes (i.e., motor planning) which it is believed the switch task engaged to a greater extent than the maintenance task.