Localization of clinically effective stimulating electrodes in the human subthalamic nucleus on magnetic resonance imaging

OBJECT: The authors sought to determine the location of deep brain stimulation (DBS) electrodes that were most effective in treating Parkinson disease (PD). METHODS: Fifty-four DBS electrodes were localized in and adjacent to the subthalamic nucleus (STN) postoperatively by using magnetic resonance (MR) imaging in a series of 29 patients in whom electrodes were implanted for the treatment of medically refractory PD, and for whom quantitative clinical assessments were available both pre- and postoperatively. A novel MR imaging sequence was developed that optimized visualization of the STN. The coordinates of the tips of these electrodes were calculated three dimensionally and the results were normalized and corrected for individual differences by using intraoperative neurophysiological data (mean 5.13 mm caudal to the midcommissural point [MCP], 8.46 mm inferior to the anterior commissure-posterior commissure [AC-PC], and 10.2 mm lateral to the midline). Despite reported concerns about distortion on the MR image, reconstructions provided consistent data for the localization of electrodes. The neurosurgical procedures used, which were guided by combined neuroimaging and neurophysiological methods, resulted in the consistent placement of DBS electrodes in the subthalamus and mesencephalon such that the electrode contacts passed through the STN and dorsally adjacent fields of Forel (FF) and zona incerta (ZI). The mean location of the clinically effective contacts was in the anterodorsal STN (mean 1.62 mm posterior to the MCP, 2.47 mm inferior to the AC-PC, and 11.72 mm lateral to the midline). Clinically effective stimulation was most commonly directed at the anterodorsal STN, with the current spreading into the dorsally adjacent FF and ZI. CONCLUSIONS: The anatomical localization of clinically effective electrode contacts provided in this study yields useful information for the postoperative programming of DBS electrodes.     

Stimulation of the subthalamic nucleus compared with the globus pallidus internus in patients with Parkinson disease

OBJECT: The authors compared the effects of deep brain stimulation (DBS) in the globus pallidus internus (GPi) with those in the subthalamic nucleus (STN) in patients with Parkinson disease (PD) in whom electrodes had been bilaterally implanted in both targets. METHODS: Eight of 14 patients with advanced PD in whom electrodes had been implanted bilaterally in both the GPi and STN for DBS were selected on the basis of optimal DBS effects and were studied 2 months postsurgery in off- and on-stimulus conditions and after at least 1 month of pharmacological withdrawal. Subcutaneous administration of an apomorphine test dose (0.04 mg/kg) was also performed in both conditions. Compared with the off status, the results showed less reduction in the Unified PD Rating Scale Section III scores during DBS in the GPi (43.1%) than during DBS of the STN (54.5%) or DBS of both the STN and GPi (57.1%). The difference between the effects of DBS in the GPi compared with that in the STN or simultaneous DBS was statistically significant (p < 0.01). In contrast, no statistical difference was found between DBS in the STN and simultaneous DBS in the STN and GPi (p < 0.9). The improvement induced by adding apomorphine administration to DBS was similar in all three stimulus modalities. The abnormal involuntary movements (AIMs) induced by apomorphine were almost abolished by DBS of the GPi, but were not affected by stimulation of the STN. The simultaneous stimulation of STN and GPi produced both antiparkinsonian and anti-AIM effects. CONCLUSIONS: The improvement of parkinsonian symptoms during stimulation of the GPi, STN, and both nuclei simultaneously may indicate a similar DBS mechanism for both nuclei in inducing antiparkinsonian effects, although STN is more effective. The antidyskinetic effects produced only by DBS of the GPi, with or without STN, may indicate different mechanisms for the antidyskinetic and antiparkinsonian activity related to DBS of the GPi or an additional mechanism in the GPi. These findings indicate that implantation of double electrodes for DBS should not be proposed as a routine procedure, but could be considered as a possible subsequent choice if electrode implantation for DBS of the STN does not control AIMs.     

Weight Change after Globus Pallidus Internus or Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease and Dystonia

Background: Weight gain has been described in Parkinson's disease (PD) patients after subthalamic nucleus (STN) deep brain stimulation (DBS). Objectives: We examined change in weight following DBS in both PD and dystonia patients to further investigate the role of disease and brain target (STN or globus pallidus internus, GPi) specificity. Methods: Data was retrospectively collected on 61 PD DBS patients (STN n = 31 or GPi n = 30) and on 36 dystonia DBS patients (STN n = 9 and GPi n = 27) before and after surgery. Annual change in body mass index (BMI) was evaluated with nonparametric tests between groups and multiple quantile regression. Results: PD patients treated with STN DBS had a small increase in median BMI while those with GPi had a small decrease in BMI. Dystonia patients treated with STN DBS had a greater increase in BMI per year compared to those treated with GPi DBS. Multivariable regression analyses for each disease showed little difference between targets in weight gain in those with PD, but STN target was strongly associated with weight gain in dystonia patients (STN vs. GPi, +7.99 kg, p = 0.012). Conclusions: Our results support previous reports of weight gain after DBS in PD. This is the first report to suggest a target-specific increase in weight following STN DBS in dystonia patients.     

Subthalamic nucleus stimulation for advanced Parkinson's disease: how to find a far medial STN.

In a patient with advanced Parkinson's disease, an anatomically deviant far medial subthalamic nucleus (STN) posed problems in the placement of DBS electrodes for chronic high frequency (HF) stimulation despite the use of multimodal targeting with 1) statistical atlas data, 2) T (2)-weighted (T (2)W) magnetic resonance imaging (MRI), 3) microelectrode recording, and 4) clinical testing with macro stimulation. Diagnostic T (2)W MRI suggested that the patient's STN was in a typical location and seemed to confirm the statistical atlas-based planning. Intraoperatively, cell activity recording (MER) with five parallel electrodes could not reveal any STN typical activity profile and electrical stimulation was not able to disclose a medial or lateral displacement of the electrodes. The operation was discontinued and postoperative stereotactic CT confirmed that the correct target area had been approached during the operation. Postoperative T (2)W MRI now disclosed a left STN which was 2 mm medial of the initial target and lead to a further medial target definition and finally to a successful DBS placement. In conclusion, finding a deep seated DBS target like the STN can be difficult in cases with an extremely deviant anatomy even if reiterative sophisticated multimodal planning is used. In the presented case we applied the integrated information from intraoperative MER, macrostimulation and postoperative imaging work-up and were able to complete DBS implantation successfully.     

Placement of deep brain stimulators into the subthalamic nucleus

We present our technique for deep brain stimulation (DBS) of the subthalamic nucleus (STN) and include information which may be helpful in general DBS. With the patient in a stereotactic head frame, the anterior and posterior commissures are identified on SPGR-sequence magnetic resonance imaging (MRI). STN coordinates are based on a stereotactic brain atlas at 12 mm lateral, 2 mm posterior and 5 mm caudal to the midcommissural point. Surgical navigation software allows for planning of the trajectory. Electromyography is used to quantitatively measure tremor responses to macrostimulation. Permanent lead placement is confirmed with intraoperative fluoroscopy and postoperative MRI.     

Variability in position of the subthalamic nucleus targeted by magnetic resonance imaging and microelectrode recordings as compared to atlas co-ordinates

BACKGROUND: Traditional methods for localisation of target nuclei for deep brain stimulation (DBS) have used brain atlas co-ordinates for initial targeting. It is now possible to visualise the subthalamic nucleus (STN) on magnetic resonance imaging (MRI) and determine the individual variability of its position. METHODS: The present study was performed in patients undergoing STN DBS for Parkinson's disease. The STN was directly targeted from axially obtained MRI and verified with microelectrode recordings. Postoperatively, the most effective contact was identified for each patient, and its position was calculated. RESULTS: Fifty electrodes were inserted in 25 patients. The target position varied considerably in relation to the mid-commissural point. The mean effective contact position lies just dorsal to the location of the STN in a standard brain atlas. CONCLUSION: The STN varies in position, and can be accurately targeted from MRI alone.     

Surgical targeting accuracy analysis of six methods for subthalamic nucleus deep brain stimulation.

A commonly adopted surgical target in deep brain stimulation (DBS) procedures, the subthalamic nucleus (STN) is located deep within the brain and is surrounded by delicate deep-brain structures. Symptoms of Parkinson's disease can be reduced by precisely implanting a multi-electrode stimulator at a specific location within the STN and delivering the appropriate signal to the target. A number of techniques have recently been proposed to facilitate STN DBS surgical targeting and thereby improve the surgical outcome. This paper presents a retrospective study evaluating the target localization accuracy and precision of six approaches in 55 STN DBS procedures. The targeting procedures were performed using a neurosurgical visualization and navigation system, which integrates normalized and standardized anatomical and functional information into the planning environment. In this study, we employed as the "gold standard" the actual surgical target locations determined by an experienced neurosurgeon using both pre-operative image-guided surgical target/trajectory planning and intra-operative electrophysiological exploration and confirmation. The surgical target locations determined using each of the six targeting methods were compared with the "gold standards". The average displacement between the actual surgical targets and those planned with targeting approaches was 3.0 +/- 1.3 mm, 3.0 +/- 1.3 mm, 3.0 +/- 1.0 mm, 2.6 +/- 1.1 mm, 2.5 +/- 0.9 mm, and 1.7 +/- 0.7 mm for approaches based on T2-weighted MRI, a brain atlas, T1 and T2 maps, an electrophysiological database, a collection of final surgical targets from previous patients, and the combination of these functional and anatomical data, respectively. The technique incorporating both anatomical and functional data provides the most reliable and accurate target position for STN DBS.     

Effect of subthalamic stimulation on mood state in Parkinson's disease: evaluation of previous facts and problems

In an attempt to clarify the effect of deep brain stimulation (DBS) to the subthalamic nucleus (STN) on mood state, previous evidence and problems were evaluated through a systematic literature search. Twenty three articles reported the effect of STN DBS on mood state in Parkinson's disease (PD), and antidepressant, depressant, and mania-induced effects were reported in 16.7-76%, 2-33.3%, and 4.2-8.1% of the patients treated with STN DBS, respectively. Most articles reported larger subgroups showing antidepressant effects than those showing depressant effects. The average depression scale score of all subjects was improved or unchanged after STN DBS. Although there was a limitation due to the varied results, it was suggested that, in general, STN DBS had an antidepressant effect in PD. However, the studies reporting severe depressant symptoms, such as suicidal attempts, after STN DBS indicated the importance of careful attention to mood state as well as to motor symptoms after STN DBS. It may be crucial to reduce the variation in the results by, for example, the use of standardized protocols and the precise verification of the stimulated region in further investigations to address this issue.     

Does deep brain stimulation improve lower urinary tract symptoms in Parkinson's disease?

Aims

To investigate whether deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) or the subthalamic nucleus (STN) improve lower urinary tract symptoms (LUTS) in advanced Parkinson's disease (PD).

Methods

An exploratory post‐hoc analysis was performed of specific LUTS items of questionnaires used in a randomized clinical trial with 128 patients (NSTAPS study). First, we compared scores on LUTS items at baseline and 12 months for the GPi DBS and STN DBS group separately. Second, we divided the group by sex, instead of DBS location; to assess a possible gender associated influence of anatomical and pathophysiological differences, again comparing scores at baseline and 12 months. Third, we reported on Foley‐catheter use at baseline and after 12 months.

Results

Urinary incontinence and frequency improved after both GPi DBS and STN DBS at 12 months, postoperatively, but this was only statistically significant for the STN DBS group (P = 0.004). The improvements after DBS were present in both men (P = 0.01) and women (P = 0.05). Nocturia and urinary incontinence did not improve significantly after any type of DBS, irrespective of sex. At 12 months, none of the patients had a Foley‐catheter.

Conclusions

Urinary incontinence and frequency significantly improved after STN DBS treatment in male and female patients with PD. Nocturia and nighttime incontinence due to parkinsonism did not improve after DBS, irrespective of gender.     

Localization of electrodes in the subthalamic nucleus on magnetic resonance imaging

OBJECT: The authors describe a new method of localizing electrodes on magnetic resonance (MR) images and focus on the positions of both the most efficient contact and the electrode related to the MR imaging target. METHODS: Thirty-one patients who had undergone bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) were included in this study. Target coordinates were calculated in the anterior commissure-posterior commissure referential. A study of the correlation between the artifact and the related contact allowed one to deduce the contact position from the identification of the distal artifact on MR imaging. The best stimulation point corresponded with the contact resulting in the best Unified Parkinson's Disease Rating Scale (UPDRS) motor score improvement. It was compared (Student t-test) with the dorsal margin of the STN (DM STN), which was determined electrophysiologically. The distance between the target and the electrode was calculated individually in each axis. The best stimulation point was located at anteroposterior -2.34 +/- 1.63 mm, lateral 12.04 +/- 1.62 mm, and vertical -2.57 +/- 1.68 mm. This point was not significantly different from the DM STN (p < 0.05). The postoperative UPDRS motor score was 28.07 +/- 12.16, as opposed to the preoperative score of 46.27 +/- 13.89. The distance between the expected and actual target in the x- and y-axes was 1.34 +/- 1.02 and 1.03 +/- 0.76 mm, respectively. In the z-axis, 39.7% of the distal contacts were located proximal to the target. CONCLUSIONS: This approach proposed for the localization of the electrodes on MR imaging shows that DBS is most effective in the dorsal and lateral part of the STN and indicates that the DBS electrode can be located more proximally than originally expected because of the caudal brain shift that may occur during the implantation procedure.     

Deep brain stimulation in Parkinson disease: a metaanalysis of patient outcomes

OBJECT: Deep brain stimulation (DBS) to treat advanced Parkinson disease (PD) has been focused on one of two anatomical targets: the subthalamic nucleus (STN) and the globus pallidus internus (GPI). Authors of more than 65 articles have reported on bilateral DBS outcomes. With one exception, these studies involved pre- and postintervention comparisons of a single target. Despite the paucity of data directly comparing STN and GPI DBS, many clinicians already consider the STN to be the preferred target site. In this study the authors conducted a metaanalysis of the existing literature on patient outcomes following DBS of the STN and the GPI. METHODS: This metaanalysis includes 31 STN and 14 GPI studies. Motor function improved significantly following stimulation (54% in patients whose STN was targeted and 40% in those whose GPI was stimulated), with effect sizes (ESs) of 2.59 and 2.04, respectively. After controlling for participant and study characteristics, patients who had undergone either STN or GPI DBS experienced comparable improved motor function following surgery (p = 0.094). The performance of activities of daily living improved significantly in patients with either target (40%). Medication requirements were significantly reduced following stimulation of the STN (ES = 1.51) but did not change when the GPI was stimulated (ES = -0.02). CONCLUSIONS: In this analysis the authors highlight the need for uniform, detailed reporting of comprehensive motor and nonmotor DBS outcomes at multiple time points and for a randomized trial of bilateral STN and GPI DBS.     

Effect of subthalamic stimulation on mood state in Parkinson’s disease: evaluation of previous facts and problems

In an attempt to clarify the effect of deep brain stimulation (DBS) to the subthalamic nucleus (STN) on mood state, previous evidence and problems were evaluated through a systematic literature search. Twenty three articles reported the effect of STN DBS on mood state in Parkinsons disease (PD), and antidepressant, depressant, and mania-induced effects were reported in 16.7–76%, 2–33.3%, and 4.2–8.1% of the patients treated with STN DBS, respectively. Most articles reported larger subgroups showing antidepressant effects than those showing depressant effects. The average depression scale score of all subjects was improved or unchanged after STN DBS. Although there was a limitation due to the varied results, it was suggested that, in general, STN DBS had an antidepressant effect in PD. However, the studies reporting severe depressant symptoms, such as suicidal attempts, after STN DBS indicated the importance of careful attention to mood state as well as to motor symptoms after STN DBS. It may be crucial to reduce the variation in the results by, for example, the use of standardized protocols and the precise verification of the stimulated region in further investigations to address this issue.     

The subthalamic nucleus at 7.0 Tesla: evaluation of sequence and orientation for deep-brain stimulation

Background

Deep-brain stimulation (DBS) of the subthalamic nucleus (STN) is an accepted neurosurgical technique for the treatment of medication-resistant Parkinson’s disease and other neurological disorders. The accurate targeting of the STN is facilitated by precise and reliable identification in pre-stereotactic magnetic resonance imaging (MRI). The aim of the study was to compare and evaluate different promising MRI methods at 7.0?T for the pre-stereotactic visualisation of the STN

Methods

MRI (T2-turbo spin-echo [TSE], T1-gradient echo [GRE], fast low-angle shot [FLASH] two-dimensional [2D] T2* and susceptibility-weighted imaging [SWI]) was performed in nine healthy volunteers. Delineation and image quality for the STN were independently evaluated by two neuroradiologists using a six-point grading system. Inter-rater reliability, contrast-to-noise ratios (CNRs) and signal-to-noise ratios (SNRs) for the STN were calculated. For the anatomical validation, the coronal FLASH 2D T2* images were co-registered with a stereotactic atlas (Schaltenbrand-Wahren).

Results

The STN was clearly and reliably visualised in FLASH 2D T2* imaging (particularly coronal view), with a sharp delineation between the STN, the substantia nigra and the zona incerta. No major artefacts in the STN were observed in any of the sequences. FLASH 2D T2* and SWI images offered significantly higher CNR for the STN compared with T2-TSE. The co-registration of the coronal FLASH 2D T2* images with the stereotactic atlas affirmed the correct localisation of the STN in all cases.

Conclusion

The STN is best and reliably visualised in FLASH 2D T2* imaging (particularly coronal orientation) at 7.0-T MRI.     

Combined pallidal and subthalamic nucleus stimulation in sporadic dystonia-parkinsonism

Multifocal deep brain stimulation (DBS) is a new technique that has been introduced recently. A 39-year-old man with dystonia-parkinsonism underwent the simultaneous implantation of subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS electrodes. While bilateral STN DBS controlled the parkinsonian symptoms well and allowed for a reduction in levodopa, the improvement of dystonia was only temporary. Additional GPi DBS also alleviated dystonic symptoms. Formal assessment at the 1-year follow-up showed that both the parkinsonian symptoms and the dystonia were markedly improved via continuous bilateral combined STN and GPi stimulation. Sustained benefit was achieved at 3 years postoperatively.     

Subthalamic nucleus stimulation in Parkinson's disease patients intolerant to levodopa

Levodopa responsiveness has been shown to be the best predictor of improvement after subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD). The objective of this study was to assess the effect of STN DBS on PD patients intolerant to levodopa due to severe acute side effects such as intolerable nausea. There were 10 patients in the study who received STN DBS for PD. Five patients who were intolerant to levodopa were matched based on age, disease duration, sex and presurgical disease severity to 5 patients taking levodopa and demonstrating a good levodopa response. Both groups had a significant improvement in Unified Parkinson's Disease Rating Scale activities of daily living and motor subscales as well as tremor, rigidity and bradykinesia scores at 3, 6 and 12 months after surgery compared to baseline, and these improvements were equivalent between the two groups. Patient global ratings also indicated significant improvements at all follow-up visits. There were no differences in stimulator settings between the two groups at the 3-, 6- or 12-month follow-up visits. In conclusion, although levodopa responsiveness is the best predictor for outcome after STN DBS, carefully selected PD patients intolerant to levodopa can have significant improvement.     

异丙酚降低帕金森病患者丘脑下核神经元放电活动

背景治疗帕金森病患者时，通常采用微电极记录仪（microelectrode recording，MER）记录丘脑下核（subthalamic nucleus，STN）神经元峰电位活动来指导实施在STN植入深部脑刺激（deep brain stimulation，DBS）电极。镇静药物对丘脑下核的微电极记录干扰程度如何目前仍不清楚。本研究监测了异丙酚镇静期间丘脑下核神经元放电活动，及对神经元电活动的影响。方法选择需要进行深部脑电刺激手术的帕金森病患者，固定电极定位于丘脑下核部位，给患者静脉输注异丙酚50μg·kg^-1·mm^-1，直到患者处于稳定镇静期。记录神经元电活动，计算异丙酚输注前、中、后神经元电活动的均方根（root mean square，RMS）。结果16例患者中记录了24次电极轨迹的活动，异丙酚注射后其中18次出现明显的丘脑下核电活动的均方根降低。异丙酚输注期间，平均均方根降低23．2％±9．1％（均数±标准差）（P〈0．001），停止输注后回到基线时间为（9．3±4．0）分钟。结论异丙酚输注导致丘脑下核神经峰电活动显著降低，说明它可能干扰丘脑下核边缘微电极记录电活动的识别。停止异丙酚输注后，神经元电活动很快恢复到基线，因此，异丙酚在微电极记录仪指导DBS前可安全地使用。     

Microelectrode recording revealing a somatotopic body map in the subthalamic nucleus in humans with Parkinson disease

OBJECT: The subthalamic nucleus (STN) is a key structure for motor control through the basal ganglia. The aim of this study was to show that the STN in patients with Parkinson disease (PD) has a somatotopic organization similar to that in nonhuman primates. METHODS: A functional map of the STN was obtained using electrophysiological microrecording during placement of deep brain stimulation (DBS) electrodes in patients with PD. Magnetic resonance imaging was combined with ventriculography and intraoperative x-ray film to assess the position of the electrodes and the STN units, which were activated by limb movements to map the sensorimotor region of the STN. Each activated cell was located relative to the anterior commissure-posterior commissure line. Three-dimensional coordinates of the cells were analyzed statistically to determine whether those cells activated by movements of the arm and leg were segregated spatially. Three hundred seventy-nine microelectrode tracks were created during placement of 71 DBS electrodes in 44 consecutive patients. Somatosensory driving was found in 288 tracks. The authors identified and localized 1213 movement-related cells and recorded responses from 29 orofacial cells, 480 arm-related cells, 558 leg-related cells, and 146 cells responsive to both arm and leg movements. Leg-related cells were localized in medial (p < 0.0001) and ventral (p < 0.0004) positions and tended to be situated anteriorly (p = 0.063) relative to arm-related cells. CONCLUSIONS: Evidence of somatotopic organization in the STN in patients with PD supports the current theory of highly segregated loops integrating cortex-basal ganglia connections. These loops are preserved in chronic degenerative diseases such as PD, but may subserve a distorted body map. This finding also supports the relevance of microelectrode mapping in the optimal placement of DBS electrodes along the subthalamic homunculus.     

Modeling parkinsonian circuitry and the DBS electrode. II. Evaluation of a computer simulation model of the basal ganglia with and without subthalamic nucleus stimulation

Treatment with deep brain stimulation (DBS) for Parkinson's disease (PD) has become routine over the past decade, particularly using the subthalamic nucleus (STN) as a target and utilizing microelectrode recordings to ensure accurate placement of the stimulating electrodes. The clinical changes seen with DBS in the STN for PD are consistently beneficial, but there continues to be only marginal understanding of the mechanisms by which DBS achieves these results. Using an analytical model of the typical DBS 4-contact electrode and software developed to simulate individual neurons and neural circuitry of the basal ganglia we compare the results of the model to those of data obtained during DBS surgery of the STN. Firing rate, interspike intervals and regularity analyses were performed on the simulated data and compared to results in the literature.     

Implantation of bilateral deep brain stimulators in patients with Parkinson disease and preexisting cardiac pacemakers. Report of two cases

Deep brain stimulation (DBS) has become an important modality in the treatment of refractory Parkinson disease (PD). In patients with comorbid arrhythmias requiring cardiac pacemakers, DBS therapy is complicated by concerns over a possible electrical interaction between the devices (or with device programming) and the inability to use magnetic resonance imaging guidance for implantation. The authors report two cases of PD in which patients with preexisting cardiac pacemakers underwent successful implantation of bilateral DBS electrodes in the subthalamic nucleus (STN). Each patient underwent computerized tomography-guided stereotactic frame-based placement of DBS electrodes with microelectrode recording. Both extension wires were passed from the right side of the head and neck (contralateral to the pacemaker) to place the cranial pulse generators subcutaneously in the left and right abdomen. The cranial pulse generators were placed farther than 6 in from the cardiac pacemaker and from each other to decrease the chance of interference between the devices during telemetry reprogramming. Postoperative management involved brain stimulator programming sessions with simultaneous cardiological monitoring of pacemaker function and cardiac rhythm. No interference was noted at any time, and proper pacemaker function was maintained throughout the follow-up period. With bilateral STN stimulation, both patients experienced a dramatic improvement in their PD symptoms, including elimination of dyskinesias, reduction of "off" severity, and increase of "on" duration. With some modifications of implantation strategy, two patients with cardiac pacemakers were successfully treated with bilateral DBS STN therapy for refractory PD. To our knowledge, this is the first report on patients with cardiac pacemakers undergoing brain stimulator implantation.