Neuropsychological changes between "off" and "on" STN or GPi stimulation in Parkinson's disease

BACKGROUND: In a previous study on a consecutive series of 62 patients with PD, the authors showed that bilateral subthalamic or pallidal continuous high-frequency deep brain stimulation (DBS) affects neither memory nor executive functions 3 to 6 months after surgery. OBJECTIVE: To investigate the specific effects of DBS by comparing the performance of patients with the stimulator turned "on" and "off." METHODS: The performance of 56 patients on clinical tests of executive function was compared after 3 and 12 months of DBS of the subthalamic nucleus (STN; n = 48) or the internal globus pallidus (GPi; n = 8) with the stimulator "on" or "off." Global intellectual efficiency, verbal learning, and mood were also evaluated with the stimulator "on." The performance of another group of 20 patients was compared after 6 months of DBS of the STN (n = 15) or the GPi (n = 5) with the stimulator "on" or "off" on more experimental tests recently shown to be more sensitive to l-dopa therapy. RESULTS: When the stimulator was "on," STN patients showed a mild but significant improvement in psychomotor speed and working memory. In comparison with the presurgical state, STN patients had no cognitive deficit at 12 months, except for lexical fluency. There was no differential effect of STN or GPi stimulation. CONCLUSIONS: 1) The specific effect of DBS seems to mimic the action of l-dopa treatment in the cognitive as in the motor domain; 2) the surgery associated with DBS does not appear to affect the cognitive performance of patients with PD 12 months later, except for a mild deficit in lexical fluency.     

Neurophysiological identification of the subthalamic nucleus in surgery for Parkinson's disease

Microelectrode recording methods for stereotactic localization of the subthalamic nucleus (STN) and surrounding structures are described. These methods accurately define targets for chronic deep brain stimulation in the treatment of Parkinson's disease. Mean firing rates and a burst index were determined for all recorded neurons, and responses to active and passive limb and orofacial movements were tested. STN neurons had a mean firing rate of 37 ± 17 Hz (n = 248) and an irregular firing pattern (median burst index, 3.3). Movement-related activity and tremor cells were identified in the STN. Ventral to the STN, substantia nigra pars reticulata neurons had a mean rate of 71 ± 23 Hz (n = 56) and a more regular firing pattern (median burst index, 1.7). Short trains (1–2 seconds) of electrical microstimulation of STN could produce tremor arrest but were and found to be useful for localization. Compared with data from normal monkeys our findings suggest that STN neuronal activity is elevated in Parkinson's disease.     

Does bilateral stimulation of the subthalamic nucleus aggravate apathy in Parkinson's disease?

OBJECTIVE: High frequency stimulation of the subthalamic nucleus (STN) dramatically decreases motor disability in patients with Parkinson"s disease (PD), but has been reported to aggravate apathy. The aim of this study was to analyse the effect of STN stimulation on motivation and reward sensitivity in a consecutive series of PD patients. METHODS: Apathy and reward sensitivity (Apathy Scale, Stimulus-Reward Learning, Reversal, Extinction, and Gambling tasks) were assessed in 18 PD patients treated by bilateral STN stimulation ("on" and "off" conditions) compared with 23 matched patients undergoing long term treatment with levodopa ("on" and "off" conditions). RESULTS: Apathy decreased under both STN stimulation and levodopa treatment, whereas explicit and implicit stimulus reward learning was unchanged. CONCLUSIONS: Bilateral STN stimulation in PD patients does not necessarily have a negative effect on motivation and reward sensitivity and can even improve apathy provided patients have been appropriately selected for neurosurgery.     

Modifications of local cerebral metabolic rates for glucose and motor behavior in rats with unilateral lesion of the subthalamic nucleus.

Inactivation of the subthalamic nucleus (STN) has attracted interest as a therapeutic tool in Parkinson's disease. The functional consequences of the inactivation, however, are uncertain. In this study definition of the pattern of changes of cerebral functional activity associated with lesion of the STN and dopaminergic stimulation, by using the [14C]deoxyglucose method, was sought. Six or 7 days following unilateral lesion of the STN, the animals were divided into two groups: One group (n = 10) was administered apomorphine (1 mg/kg) subcutaneously; the second group (n = 10) received saline. The [14C]deoxyglucose procedure was initiated 10 minutes following the drug or saline injection. The results show that systemic administration of apomorphine to rats with unilateral lesion of the STN causes ipsiversive rotational behavior and asymmetries of glucose utilization of defined brain areas, including the substantia nigra reticulata, globus pallidus, and entopeduncular nucleus. These nuclei are the main targets of the subthalamic excitatory projections. Lesion of the nucleus per se (without challenge with apomorphine) has no significant consequences on glucose utilization. The findings indicate that the STN is involved in the activation of the basal ganglia output nuclei induced by systemic dopaminergic stimulation.     

Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson's disease.

OBJECTIVE: To reduce antiparkinsonian medication in parkinsonian patients with bilateral high frequency subthalamic nucleus (STN) stimulation. BACKGROUND: Parkinsonian syndromes are characterized by hyperactivity of the STN. Preliminary data indicate that functional inactivation of the STN may reduce the requirement for dopaminergic therapy in PD. METHODS: Bilateral quadripolar leads were implanted stereotactically in the STN of seven patients with advanced PD (mean age, 57.4 years; mean disease duration, 15.4 years). High-frequency stimulation was applied for 24 hours a day. Following implantation, antiparkinsonian medication was reduced to the minimum possible and stimulation was gradually increased. The patients were evaluated in the practically defined "off" and "on" conditions using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Schwab & England scale. The average follow-up was 16.3+/-7.6 months. A battery of neuropsychological tests was applied before and 9 months after the implant. RESULTS: Parkinsonian features improved in all patients--the greatest change seen in rigidity, then tremor, followed by bradykinesia. Compared with the presurgical condition, off-drug UPDRS motor scores improved by 41.9% on the last visit (p = 0.0002), UPDRS activities of daily living (ADL) scores improved by 52.2% (p = 0.0002), and the Schwab & England scale score improved by 213% (p = 0.0002). The levodopa-equivalent daily dose was reduced by 65%. Night sleep improved in all patients due to increased mobility at night, and in five patients insomnia was resolved. All patients gained weight after surgery and their appetite increased. The mean weight gain at the last follow-up was 13% compared with before surgery. During the last visit, the stimulation amplitude was 2.9+/-0.5 V and the total energy delivered per patient averaged 2.7+/-1.4 W x10(-6). The results of patient self-assessment scales indicated a marked improvement in five patients and a moderate improvement in the other two. The neuropsychological data showed no changes. Side effects were mild and tolerable. In all cases, a tradeoff between the optimal voltage and the severity of side effects made it possible to control parkinsonian signs effectively. The most marked side effects directly related to STN stimulation consisted of ballistic or choreic dyskinesias of the neck and the limbs elicited by contralateral STN stimulation above a given threshold voltage, which varied depending on the individual. CONCLUSIONS: Parkinsonian signs can be controlled by bilateral high-frequency STN stimulation. The procedure is well tolerated. On-state dyskinesias were greatly reduced, probably due to the reduction of total antiparkinsonian medication. Bilateral high-frequency STN stimulation compensated for drug reduction and elicited dyskinesias, which differ from those observed following dopaminergic medication. ADL improved significantly, suggesting that some motor tasks performed during everyday chores, and that are not taken into account in the UPDRS motor score, also improved.     

Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation

OBJECTIVE: To assess the effects of high frequency stimulation of the subthalamic nucleus (STN) on axial symptoms occurring in advanced stages of Parkinson's disease (PD). METHODS: The efficacy of STN stimulation on total motor disability score (unified Parkinson's disease rating scale (UPDRS) part III) were evaluated in 10 patients with severe Parkinson's disease. The subscores were then studied separately for limb akinesia, rigidity, and tremor, which are known to respond to levodopa, and axial signs, including speech, neck rigidity, rising from a chair, posture, gait, and postural stability, which are known to respond less well to levodopa. Patients were clinically assessed in the "off" and "on" drug condition during a levodopa challenge test performed before surgical implantation of stimulation electrodes and repeated 6 months after surgery under continuous STN stimulation. A complementary score for axial symptoms from the "activities of daily living" (ADL)-that is, speech, swallowing, turning in bed, falling, walking, and freezing-was obtained from each patient's questionnaire (UPDRS, part II). RESULTS: Improvements in total motor disability score (62%), limb signs (62%), and axial signs (72%) obtained with STN stimulation were statistically comparable with those obtained with levodopa during the preoperative challenge (68%, 69%, and 59%, respectively). When levodopa and STN stimulation were combined there was a further improvement in total motor disability (80%) compared with preoperative levodopa administration. This consisted largely of an additional improvement in axial signs (84%) mainly for posture and postural stability, no further improvement in levodopa responsive signs being found. Axial symptoms from the ADL showed similar additional improvement when levodopa and STN stimulation were combined. CONCLUSION: These findings suggest that bilateral STN stimulation improves most axial features of Parkinson's disease and that a synergistic effect can be obtained when stimulation is used in conjunction with levodopa treatment.     

丘脑底核与苍白球内侧部电刺激术治疗帕金森病疗效的Meta分析

目的 系统评价脑深部电刺激术（DBS）作用丘脑底核（STN）与苍白球内侧部（GPi）治疗帕金森病（PD）的疗效。方法 计算机检索2015年6月之前在PubMed、Cochrane Library、Embase、CNKI及VIP等数据库中DBS作用STN或GPi治疗PD的随机临床对照研究,按纳入排除标准进行资料的筛选和提取,利用RevMan 5.3软件进行Meta分析。结果 纳入7个研究共613例患者,其中STN组331例,GPi组282例。Meta分析显示,STN-DBS与GPi-DBS治疗后,患者运动症状改善效果（SMD=0.36;95% CI为-0.07~0.78;P=0.10）及生活质量改善（SMD=-0.20,95%CI为-0.78~0.39;P=0.51）相似,且术后3年均效果稳定。STN组较GPi组能明显减少术后药物用量（SMD=0.37;95% CI为0.19~0.55;P<0.0001）;gpi组抑郁发生率较stn组明显减少（rr ci为="" 1.28~2.27;p="0.0003）。结论 STN-DBS与GPi-DBS治疗PD后,患者运动症状改善效果与生活质量改善效果相似,STN -DBS能有效减少术后用药量,GPi-DBS术后抑郁发生率更低。     

Effects of subthalamic nucleus stimulation and levodopa on the autonomic nervous system in Parkinson's disease

Dysfunctions of the autonomic nervous system (ANS) are common in Parkinson's disease (PD). Regarding motor disability, deep brain stimulation of the subthalamic nucleus (STN) is an effective treatment option in long lasting PD. The aims of this study were to examine whether STN stimulation has an influence on functions of the ANS and to compare these effects to those induced by levodopa. Blood pressure (BP) and heart rate (HR) during rest and orthostatic conditions, HR variability (HRV) and breathing-induced cutaneous sympathetic vasoconstriction (CVC) were tested in 14 PD patients treated with STN stimulation during "ON" and "OFF" condition of the stimulator. The effects of a single dose of levodopa on ANS were tested in 15 PD patients without DBS. STN stimulation had no influence on cardiovascular ANS functions, whereas CVC was significantly increased. In contrast, levodopa significantly lowered BP and HR at rest and enhanced orthostatic hypotension. Further, HRV, skin perfusion and temperature increased after administration of levodopa. Our results suggest that in contrast to levodopa, STN stimulation has only minor effects on autonomic functions. Since less pharmacotherapy is needed after STN stimulation, reduced levodopa intake results in relative improvement of autonomic function in deep brain stimulated PD patients.     

Multicenter study on deep brain stimulation in Parkinson's disease: An independent assessment of reported adverse events at 4 years

Ongoing adverse events (AEs) at 4‐years postsurgery in 69 patients with advanced Parkinson′s disease (PD) who received deep brain stimulation (DBS) of the subthalamic nucleus (STN) (n = 49) or the internal globus pallidus (GPi) (n = 20), in the framework of a subset of eight centers of a multicenter study, were analyzed by an independent ad hoc committee. At baseline, the patients' age, sex, disease duration, and clinical condition were virtually identical, as was the duration of follow‐up. There were 64 AEs reported in 53% of STN DBS patients and eight AEs reported in 35% of GPi DBS patients. Most of the AEs were not deemed severe and were reported to be present “both with and without stimulation.” The majority of the AEs affected patients' cognitive, psychiatric and behavioral status, as well as speech, gait, and balance, and most of these AEs occurred in STN DBS patients. When comparing patients who exhibited AEs with those who did not, it was found that in the STN DBS group, the patients with AEs had a longer disease duration, as well as more gait disorders and psychiatric disturbances at baseline. © 2007 Movement Disorder Society     

Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in PD

Abstract Objective To compare the cognitive and behavioural effects of unilateral pallidotomy and bilateral subthalamic nucleus (STN) stimulation. Methods After baseline examination 34 patients were randomly assigned to unilateral pallidotomy (4 left-sided, 10 right-sided) or bilateral STN stimulation (n=20). At baseline and six and twelve months after surgery we administered neuropsychological tests of language, memory, visuospatial function, mental speed and executive functions. Also a depression rating scale, and self and proxy ratings of memory and dysexecutive symptoms were administered. Results Six months after surgery, the STN group and the pallidotomy group differed significantly in change from baseline in number of errors on two tests of executive functioning. After 12 months the STN group reported less positive affect compared with baseline than the pallidotomy group. One patient in the STN group showed an overall cognitive deterioration due to complications. Conclusions Although we need larger groups to draw firm conclusions, our results suggest that bilateral STN stimulation has slightly more negative effects on executive functioning than unilateral pallidotomy.     

Feedback loop between locus coeruleus and spinal trigeminal nucleus neurons responding to tooth pulp stimulation in the rat

IGARASHI, S., M. SASA AND S. TAKAORI. Feedback loop between locus coeruleus and spinal trigeminal nucleusneurons responding to tooth pulp stimulation in the rat. BRAIN RES. BULL. 4(1) 75–83, 1979.—Studies were performed to elucidate reciprocal relationships between locus coeruleus (LC) and spinal trigeminal nucleus (STN) neurons responding to tooth pulp (TP) stimulation using rats anesthetized with α-chloralose. LC conditioning stimulation inhibited STN field potential as well as orthodromic spike generation of STN neurons produced by ipsilateral TP stimulation, confirming the previous findings in cats that LC neurons played an inhibitory role in the orthodromic transmission in STN neurons. Forty-one out of 56 LC neurons were activated by ipsilateral TP stimulation and 12 neurons by stimulation of both ipsi- and contralateral TP. STN stimulation usually excited LC neurons with a significantly shorter latency than did TP stimulation, including three LC neurons with a latency of less than 2.0 msec. These results indicate the existence of input from TP to LC neurons via multisynapses. In addition, neurons antidromically activated by STN stimulation were found in LC. It is highly probable, therefore, that there is a feedback loop between LC and STN, which might control input from TP to STN.     

MRI verified STN stimulation site – gait improvement and clinical outcome

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in alleviating Parkinson’s disease (PD) symptoms (tremor, rigidity and bradykinesia) and may improve gait and postural impairment associated with the disease. However, improvement of gait is not always as predictable as the clinical outcome. This may relate to the type of gait impairment or localization of the active DBS contact. Methods: The active contact was visualized on peri‐operative magnetic resonance imaging in 22 patients with idiopathic PD, consecutively treated with bilateral STN DBS. Stimulation site was grouped as either in the dorsal/ventral STN or medial/lateral hereof and anterior/posterior STN or medial/lateral hereof. The localization was compared with relative improvement of clinical outcome (UPDRS‐III). In 10 patients, quantitative gait analyses were performed, and the improvement in gait performance was compared with stimulation site in the STN. Results: Of 44 active contacts, 77% were inside the nucleus, 23% were medial hereof. Stimulation of the dorsal half improved UPDRS‐III significantly more than ventral STN DBS (P = 0.02). However, there were no differences between anterior and posterior stimulation in the dorsal STN. Step velocity and length improved significantly more with dorsal stimulation compared with ventral stimulation (P = 0.03 and P = 0.02). Balance during gait was also more improved with dorsal stimulation compared with ventral stimulation. Conclusions: Deep brain stimulation of the dorsal STN is superior to stimulation of the ventral STN. Possible different effects of stimulation inside the nucleus underline the need for exact knowledge of the active stimulation site position to target the most effective area.     

Double blinded evaluation of the effects of pallidal and subthalamic nucleus stimulation on daytime activity in advanced Parkinson's disease

The results of a double blinded evaluation of the effects of globus pallidus (GPi; n=7) and subthalamic nucleus (STN; n=11) stimulation in patients with advanced Parkinson's disease are summarized. The patients were evaluated at 6-8months after surgery. In order to determine the benefits afforded by the stimulation to the actual daily activities, the patients were maintained on-medication with optimal doses and schedules. The stimulation was turned off overnight for at least 12h. It was turned on in the morning (or maintained turned off), and the best and worst scores during daytime activity were recorded, as on-period and off-period scores, respectively. A reduction in total motor score on the Unified Parkinson's Disease Rating Scale was clearly elicited by GPi and STN stimulation at both the off-period (-57 and -29%, respectively) and the on-period (-36 and -25%, respectively). The difference in effects between GPi and STN stimulation appeared to be due largely to an unintended difference in the patients' preoperative symptoms. The benefits provided by stimulation to the actual daily activities appears to be limited in patients who have become unresponsive to a large dose of levodopa. Two advantages of GPi and STN stimulation were identified. 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. Clinically important improvement was observed in severe gait freezing in 2 patients following unilateral anterodorsal GPi stimulation on the right side alone.     

Comparison of weight gain and energy intake after subthalamic versus pallidal stimulation in Parkinson's disease

To compare body mass index (BMI) and daily energy intake (DEI) after subthalamic versus pallidal deep brain stimulation (DBS). Weight gain following DBS in Parkinson's disease patients remains largely unexplained and no comparison of subthalamic and pallidal (GPi) stimulation has yet been performed. BMI and DEI, dopaminergic drug administration and motor scores were recorded in 46 patients with PD before STN (n = 32) or GPi (n = 14) DBS and 3 and 6 months after. At M6, BMI had increased by an average of 8.4% in the STN group and 3.2% in the GPi group. BMI increased in 28 STN and 9 GPi patients. This increase was significantly higher in the STN group (P < 0.048) and the difference remained significant after adjustment for reduced dopaminergic medication; 28.6% of GPi patients were overweight at 6 months (14.3% preoperatively) versus 37.5% of STN patients (21.9% preoperatively). Changes in BMI were negatively correlated with changes in dyskinesia in the GPi–DBS group. Food intake did not change in the two groups, either quantitatively or qualitatively. Frequent weight gain, inadequately explained by motor improvement or reduced dopaminergic drug dosage, occurred in subthalamic DBS patients. The difference between groups suggests additional factors in the STN group, such as homeostatic control center involvement. © 2009 Movement Disorder Society     

Electrophysiology of subthalamic nucleus in normal and Parkinson's disease

Subthalamic nucleus (STN) has been known to play an important role in the regulation of cortico-basal ganglia-thalamo-cortical loop. STN neurons have pacemaking activitiy and their firing pattern can switch from spike mode to bursting mode when membrane potential becomes hyperpolarized. Recent study has shown that STN neurons show marked increase in burst and oscillatory activity during the dopamine-depleting state of Parkinson's disease (PD). This electrophysiological change in activity is now considered as an characterstic pathophysiological feature of PD. High frequency stimulation of STN can modify and "normalize" the activity of STN neurons in the pathophysiologial state. This electrophysiological treatment applied to STN, known as deep brain stimulation (DBS) clinically, ameliorates the symptoms of PD effectively, and is becoming a standard treatment in patients with advanced PD. This article would review the basic researches concerning electrical activities of STN and try to extend the basic knowledge into clinical applications.     

Low-frequency subthalamic oscillations increase after deep brain stimulation in Parkinson's disease

This work is the second of a series of papers in which we investigated the neurophysiological basis of deep brain stimulation (DBS) clinical efficacy using post-operative local field potential (LFP) recordings from DBS electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease. We found that low-frequency (1-1.5Hz) oscillations in LFP recordings from the STN of patients with Parkinson's disease dramatically increase after DBS of the STN itself (log power change=0.93+/-0.62; Wilcoxon: p=0.0002, n=13), slowly decaying to baseline levels after turning DBS off. The DBS-induced increase of low-frequency LFP oscillations is highly reproducible and appears only after the delivery of DBS for a time long enough to induce clinical improvement. This increase of low-frequency LFP oscillations could reflect stimulation-induced modulation of network activity or could represent changes of the electrochemical properties at the brain-electrode interface.     

Deep brain stimulation of the subthalamic nucleus improves cognitive flexibility but impairs response inhibition in Parkinson disease

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease. Although several studies have assessed cognitive functions before surgery and after long-term STN stimulation, only a few have assessed patients while stimulation is on and off to more specifically address the short-term cognitive effects of STN deep brain stimulation. OBJECTIVE: To examine the short-term effects of STN stimulation on several tests sensitive to executive function and the long-term effects of STN stimulation on a global cognitive scale. DESIGN: Twenty-three patients with Parkinson disease were tested 6 to 12 months after surgery with STN stimulation switched on and off in a random order while taking their regular medication. The Unified Parkinson's Disease Rating Scale motor score was also rated in the on and off stimulation condition. The neuropsychological battery included digit span, verbal fluency, Stroop color test, and random number generation in a single- and dual-task condition. RESULTS: Short-term stimulation improved the results on the Random Number Generation Task, requiring suppression of habitual responses, but induced more errors in the interference task of the Stroop color test. Digit span, verbal fluency, and dual-task performance results did not change. There was a significant correlation (r = 0.47, P =.02) between improved performance on the Random Number Generation Task and impaired response inhibition in the Stroop interference condition. A preoperative to postoperative comparison showed no changes in global cognitive function with long-term STN deep brain stimulation. CONCLUSIONS: Short-term STN stimulation improves cognitive flexibility (giving up habitual responses) but impairs response inhibition. Long-term STN stimulation does not change global cognitive function.     

Apomorphine test: a predictor for motor responsiveness to deep brain stimulation of the subthalamic nucleus

The value of the apomorphine test as a predictor of the clinical outcome of deep brain stimulation of the subthalamic nucleus (STN) was evaluated in patients with advanced idiopathic Parkinson’s disease (IPD) or multiple system atrophy (MSA). Thirteen IPD patients with severe diurnal fluctuations and one MSA patient not responding to dopaminergic drugs were assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS) and the timed finger tapping test (FTT), measured preoperatively on and off apomorphine and postoperatively on and off STN stimulation. UPDRS motor items 20–25 were assessed intraoperatively on and off STN stimulation when the clinically effective target was approached. The motor response to immediate intraoperative and long-term STN stimulation was correlated with results of the apomorphine test. The response to immediate intraoperative STN stimulation was accurately predicted by apomorphine challenge in all 13 IPD patients. Clinical outcome following long-term STN stimulation was correlated significantly with preoperative changes due to apomorphine measured with the UPDRS motor scores (r = 0.7125, P < 0.01) and FTT (r = 0.9276, P < 0.001). Moreover, comparison of long-term STN stimulation to preoperative drug treatment displayed a significant reduction in the duration of off-phases and a significant increase in the duration of on-phases. However, in the single patient with MSA no beneficial response was obtained either to apomorphine or to STN stimulation intraoperatively and during the postoperative externalized test period. Our results indicate that the apomorphine test can predict the outcome of immediate and long-term STN stimulation and may help in the selection of candidates for surgery. Received: 3 April 1998 Received in revised form: 19 January 1999 Accepted: 16 February 1999     

MEP latency shift after implantation of deep brain stimulation systems in the subthalamic nucleus in patients with advanced Parkinson's disease.

Deep brain stimulation (DBS) into the subthalamic nucleus (STN) is a highly effective treatment for advanced Parkinson's disease (PD). The consequences of STN stimulation on intracortical and corticospinal excitability have been addressed in a few studies using transcranial magnetic stimulation (TMS). Although excitability measurements were compared between the STN stimulation OFF and ON condition, in these experiments, there are no longitudinal studies examining the impact of electrode implantation per se on motor excitability. Here, we explored the effects of STN electrode implantation on resting motor thresholds (RMT), motor evoked potential (MEP) recruitment curves, and MEP onset latencies on 2 consecutive days before and shortly after STN surgery with the stimulator switched off, thus avoiding the effects of chronic DBS on the motor system, in 8 PD patients not taking any dopaminergic medication. After surgery, RMT and MEP recruitment curves were unchanged. In contrast, MEP onset latencies were significantly shorter when examined in relaxed muscles but were unchanged under preactivation. We hypothesize that postoperatively TMS pulses induced small currents in scalp leads underneath the TMS coil connecting the external stimulator with STN electrodes leading to inadvertent stimulation of fast-conducting descending neural elements in the vicinity of the STN, thereby producing submotor threshold descending volleys. These "conditioning" volleys probably preactivated spinal motor neurons leading to earlier suprathreshold activation by the multiple corticospinal volleys produced by TMS of the motor cortex. These TMS effects need to be considered when interpreting results of excitability measurements in PD patients after implantation of STN electrodes.