Subthalamic nucleus stimulation affects incentive salience attribution in Parkinson's disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can induce nonmotor side effects such as behavioral and mood disturbances or body weight gain in Parkinson's disease (PD) patients. We hypothesized that some of these problems could be related to an altered attribution of incentive salience (ie, emotional relevance) to rewarding and aversive stimuli. Twenty PD patients (all men; mean age ± SD, 58.3 ± 6 years) in bilateral STN DBS switched ON and OFF conditions and 18 matched controls rated pictures selected from the International Affective Picture System according to emotional valence (unpleasantness/pleasantness) and arousal on 2 independent visual scales ranging from 1 to 9. Eighty‐four pictures depicting primary rewarding (erotica and food) and aversive fearful (victims and threat) and neutral stimuli were selected for this study. In the STN DBS ON condition, the PD patients attributed lower valence scores to the aversive pictures compared with the OFF condition (P < .01) and compared with controls (P < .01). The difference between the OFF condition and controls was less pronounced (P < .05). Furthermore, postoperative weight gain correlated with arousal ratings from the food pictures in the STN DBS ON condition (P < .05 compensated for OFF condition). Our results suggest that STN DBS increases activation of the aversive motivational system so that more relevance is attributed to aversive fearful stimuli. In addition, STN DBS–related sensitivity to food reward stimuli cues might drive DBS‐treated patients to higher food intake and subsequent weight gain. © 2011 Movement Disorder Society     

Subthalamic nucleus stimulation affects subjective emotional experience in Parkinson's disease patients

A number of studies have reported impaired facial emotion recognition following subthalamic nucleus (STN) stimulation in Parkinson's disease (PD), and have related these changes to a limbic dysfunction induced by STN stimulation. The present study examined the effect of STN stimulation in PD patients on a specific component of emotion, namely the subjective experience of emotion. Thirteen post-operative PD patients, 13 pre-operative PD patients matched on clinical and neuropsychological characteristics, and 16 controls matched on age and education, were administered a validated battery of film excerpts known to primarily induce specific emotional feelings (anger, happiness, sadness, fear, disgust, and neutral), and self-rated the intensity of their emotional feelings on a discrete emotions questionnaire. The post-operative group showed a significant lower level of differentiation between the target feeling (i.e., the more likely to be reported) and non-target feelings for the film excerpts intended to induce “sadness” and “fear” respectively, as compared with the pre-operative and healthy control groups. Moreover, the post-operative group reported significantly less intense feelings of fear, anxiety and disgust for the excerpt intended to induce “fear” as compared with the pre-operative and the control groups, while no significant difference was observed between the pre-operative and control groups. Finally, the post-operative group reported significantly less intense feelings of sadness and anxiety during the excerpt intended to induce “sadness” as compared to the control group, although the differences between the pre- and post-operative groups and between the pre-operative and the control groups did not reach significance. Our study suggests that STN stimulation affects the subjective experience of emotion, thus providing a preliminary account of the modulation induced by STN stimulation of a distributed neuronal network underlying the subjective experience of emotion, although the exact contribution of the STN within such network remains to be specified.     

丘脑底核与电刺激术效果关系的研究

目的 研究脑深部电刺激（DBS）对帕金森病（PD）的治疗作用，观察术中丘脑底核（STN）刺激对PD震颤、肌僵直、运动的缓解效果以及对语言的影响，探讨电极在丘脑底核内的解剖位置与刺激效果的关系，以寻找植入刺激电极至STN的最佳位置。方法 26例帕金森病患者，利用MRI及微电极导向立体定向方法将刺激电极植入丘脑底核，其靶点：X＝11mm-13mm,Y=-1mm--3mm,Z=-7mm。术中予以高频刺激（频率为130Hz－150Hz，脉宽为90μs-150μs，电压自0.5V开始，逐渐增至8V）；利用电极的不同触点分别进行刺激，根据刺激效果和副反应的出现情况，确定电极在STN中的最佳位置。其中有3例进行了STN电极永久性植入，术后随访6－14月。结果 26例术中刺激发现，STN背外侧部是电刺激的最佳位置，而电极过深及过外铡易引起言语障碍。结论 STN的高频刺激能改善PD的震颤、僵直、运动缓慢等主要症状，是PD慢性刺激的最理想靶点，其背外侧部是刺激效果的最佳位置。     

丘脑底核高频刺激治疗帕金森病

目的：研究脑深部刺激（DBS）对帕金森病（PD）的治疗作用。观察术中丘脑底核（STN）刺激对PD震颤,肌僵直、运动缓慢的缓解效果及对语言的影响,探讨植入刺激电极的最佳位置。方法：17例帕金森病患者,利用MRI及微电极导向立体定向方法将刺激电极植入丘脑底核,其靶点：X=11mm,Y=-1mm,Z=-7mm。术中予以高频刺激（频率为150Hz,脉宽为150μz,脉宽为150μs,电压自0.5V开始,逐渐增至6-8V）;其中有2例进行了STN电极永久性植入慢性电刺激,术后随访6-8月,结果：17例术中刺激发现,STN中上部是其刺激、改善病人症状的最佳位置,而电极过深及过外则易引起言语障碍,2例永久性植入慢性电刺激经随访观察对肌僵直的控制非常满意,对运动缓慢有明显改善,并减少美多巴的服药量,UPDRS运动评分下降50%。结论：STN的高频刺激能改善PD的震颤,僵直,运动缓慢等主要症状,是PD慢性刺激的最理想靶点,其中上部是刺激效果的最佳位置。     

Subthalamic nucleus stimulation: improvements in outcome with reprogramming

BACKGROUND: Deep brain stimulation (DBS) is currently the most effective surgical treatment for advanced Parkinson disease (PD). Even when the electrode is well positioned in the target, the optimization of clinical results depends on careful programming of electrical parameters and changes in antiparkinsonian drug dosages. OBJECTIVE: To determine whether stable outcomes from subthalamic nucleus DBS for PD can be improved by revising stimulation parameters and drug dosages through "hands-on" involvement of a neurologist expert in both movement disorders and DBS programming. METHODS: In 44 consecutive patients with PD with long-term stable response to subthalamic nucleus DBS (mean +/- SD, 3.5 +/- 1.7 years), we compared scores from the Unified Parkinson's Disease Rating Scale parts II through IV obtained immediately before and following a formal reprogramming of their stimulation. The reprogramming was performed by a neurologist expert in both PD and DBS and accompanied by further medication adjustments. The patients were subsequently followed up for as long as 14 months. RESULTS: In 24 patients (54.6%), the scores on the Unified Parkinson's Disease Rating Scale parts II and III significantly improved by 15.0% and 25.9%, respectively. Anti-PD drugs were significantly reduced (by 25.9%). No improvement was observed in 16 patients (36.4%), and the conditions of 4 patients (9.1%) worsened. CONCLUSIONS: Further improvement of parkinsonian signs can be achieved in the majority of patients even after long-term stable stimulation. Improved patient outcomes from subthalamic nucleus DBS are obtained when postoperative care is personally managed by a neurologist expert in movement disorders and DBS who is directly responsible for stimulation programming and simultaneous drug adjustments based on observed clinical responses to changing stimulation parameters.     

双侧丘脑底核电刺激治疗原发性肌张力障碍

目的 研究双侧丘脑底核（STN）脑深部电刺激术（DBS）治疗原发性肌张力障碍的长期疗效：方法 比较15例行舣侧STN—DBS治疗的原发性肌张力障碍患者，手术前后的Burke—Fahn—Marsden肌张力障碍评分改善程度及长期改善效果。结果 15例原发性肌张力障碍患者中12例在开启刺激器后症状即刻得到部分缓解，以不自主运动、异常姿势及躯体的扭转改善为主，其中9例在刺激1—3d后、3例刺激1，周后改善75％以上，6个月后平均改善92％；1例在2个月后开始改善，6个月后改善90％以上；2例在1个月开始出现轻微改善，6个月后改善了76％：15例患者的长期随访结果显示其疗效稳定，经过1—3次程控后不需经常调整刺激参数：所有患者未出现手术相关并发症及永久性副作用。结论 双侧丘脑底核脑深部电刺激术对原发性肌张力障碍有显著的治疗效果，且疗效持久、稳定，无并发症及永久性副作用。比较GPi—DBS而言，STN—DBS起效快、最件刺激化点及参数易于确定、刺激参数水平低、长期疗效稳定，可能是原发性肌张力障碍DBS治疗的理想靶点。     

Subthalamic nucleus stimulation in Parkinson’s disease

Deep brain stimulation (DBS) is an effective surgical treatment for advanced Parkinson’s disease (PD), with significant advantages in morbidity-mortality and quality of life when compared to lesion techniques such as thalamotomy and/or pallidotomy. The procedure is indicated in patients with severe resting tremor, unresponsive to conventional medical treatment or with motor complications. The most commonly reported complications in the intra- and post-surgical period are aborted procedure, misplaced leads, intracranial haemorrhage, seizures and hardware complications, whereas in the long-term period, cognitive and psychiatric complications can be observed. The most important eligibility criteria for DBS are: a correct diagnosis of idiopathic PD, severity of illness, a consistent levodopa response and absence of cognitive impairment. Chronological age and mood disorders may be relative contraindications to be individually evaluated. Tremor, rigidity dystonias and dyskinesias improve dramatically after DBS; freezing, postural instability and falls remain unchanged, whereas verbal fluency and dysarthria are known to worsen.     

Subthalamic nucleus stimulation in Parkinson’s disease

Breathing disturbances in Rett syndrome were reported almost entirely during wakefulness, with normal respiration during sleep. We studied a case of a proven MECP2 mutation in a girl, whose videopolygraphic and polysomnographic monitoring suggested the evidence of central apnoeas not only during awake, but also during sleep. Apart from prevalent awake respiratory dysfunction, central apnoeas in Rett syndrome may be also present during sleep.     

Subthalamic nucleus deep brain stimulation improves sleep in Parkinson's disease patients: a retrospective study and a meta-analysis

BackgroundMost Parkinson's patients suffered from sleep problems. There is increasing evidence that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has a positive effect on several sleep parameters, improving overall sleep quality in patients with PD. However, the results are controversial.MethodsWe performed a retrospective study and meta-analysis to assess the Parkinson's disease sleep scale (PDSS) in Parkinson's patients.ResultsWe reviewed our data of patients who underwent STN-DBS, and then extracted five other trials to perform a meta-analysis. The pooled results showed an advantage on post-operative PDSS in both our medical center and pooled results (MD = 20.41, 95% CI = [13.03, 27.79], I² = 61%, P < 0.001). There was a significant difference in Unified Parkinson's Disease Rating Scale (UPDRS)-Ⅲ score between pre and post-operation (MD = −12.59, 95% CI = [−14.70, −10.49], I² = 90%, P < 0.001). What's more, Parkinsonian medication was significantly lower in the post-operative groups after DBS (MD = −314.71, 95% CI = [−468.13, −161.28], I² = 53%, P < 0.001).ConclusionIn the retrospective study and meta-analysis of 6 trials, we found that DBS can significantly increase sleep quality. Furthermore, motor function improved and Parkinsonian medication was significantly decreased postoperatively. The sample size was enough and no further investigations would change the conclusion.     

Subthalamic nucleus stimulation restores corticospinal facilitation in Parkinson's disease

We have previously shown that in patients with Parkinson's disease (PD), high‐frequency stimulation (HFS) of the subthalamic nucleus (STN) modifies spinal excitability via subcortical reticulospinal routes. To investigate whether STN‐HFS also modifies spinal excitability via transcortical routes in PD, 10 patients with PD (9 men, 1 woman; 58.3 ± 8.3 years) were investigated in the medical OFF‐state with or without STN‐HFS. The H‐reflex of the right soleus muscle was recorded during slight plantar flexion at 20% of maximum force. A conditioning transcranial stimulus was applied at 95% of active motor threshold to the contralateral primary motor leg area (M1) 0–5 ms after eliciting the H‐reflex. The same paradigm was applied to 8 healthy individuals (5 men, 3 women; 50.8 ± 3.0 years). Transcranial magnetic stimulation (TMS) facilitated the H‐reflex amplitude in healthy controls. A facilitatory effect of the corticospinal input on the H‐reflex was also found in patients with PD, but only with STN‐HFS switched on. When STN‐HFS was discontinued, the H‐reflex was no longer facilitated by the TMS pulse. Accordingly, analysis of variance showed a main effect of stimulation (F = 11.15; P = 0.005), ISI (F = 6.1; P = 0.003), and an interaction between stimulation and group (PD vs. control) (F = 8.9; P = 0.01). STN‐HFS restores the normal facilitatory drive of a transcranially evoked motor cortical response to the spinal motoneuron pool. In addition to subcortical routes, STN‐DBS also alters spinal excitability via transcortical pathways. © 2008 Movement Disorder Society.     

Subthalamic nucleus deep brain stimulation evokes resonant neural activity

Deep brain stimulation (DBS) is a rapidly expanding treatment for neurological and psychiatric conditions; however, a target‐specific biomarker is required to optimize therapy. Here, we show that DBS evokes a large‐amplitude resonant neural response focally in the subthalamic nucleus. This response is greatest in the dorsal region (the clinically optimal stimulation target for Parkinson disease), coincides with improved clinical performance, is chronically recordable, and is present under general anesthesia. These features make it a readily utilizable electrophysiological signal that could potentially be used for guiding electrode implantation surgery and tailoring DBS therapy to improve patient outcomes. Ann Neurol 2018;83:1027–1031     

Subthalamic nucleus stimulation in Parkinson's disease: clinical evaluation of 18 patients

The aim of the present study was to assess the efficacy and safety of chronic subthalamic nucleus deep-brain stimulation (STN-DBS) in patients with Parkinson's disease (PD). 18 consecutive severely affected PD patients were included (mean age, SD: 56.9+/-6 years; mean disease duration: 13.5+/-4.4 years). All the patients were evaluated clinically before and 6 months after the surgical procedure using the Unified Parkinson's Disease Rating Scale (UPDRS). Additionally, a 12 months follow-up was available in 14 patients. The target coordinates were determined by ventriculography under stereotactic conditions, followed by electrophysiology and intraoperative stimulation. After surgery, continuous monopolar stimulation was applied bilaterally in 17 patients at 2.9+/-0.4 V through 1 (n = 31) or 2 contacts (n = 3). One patient had bilateral bipolar stimulation. The mean frequency of stimulation was 140+/-16 Hz and pulse width 68+/-13 micros. Off medication, the UPDRS part III score (max = 108) was reduced by 55 % during on stimulation (score before surgery: 44.9+/-13.4 vs at 6 months: 20.2+/-10; p < 0.001). In the on medication state, no difference was noted between the preoperative and the postoperative off stimulation conditions (scores were respectively: 17.9+/-9.2 and 23+/-12.6). The severity of motor fluctuations and dyskinesias assessed by UPDRS IV was reduced by 76 % at 6 months (scores were respectively: 10.3+/-3 and 2.5+/-3; p < 0.001). Off medication, the UPDRS II or ADL score was reduced by 52.8 % during on stimulation (26.9+/-6.5 preop versus 12.7+/-7 at 6 months). The daily dose of antiparkinsonian treatment was diminished by 65.5 % (levodopa equivalent dose -- mg/D -- was 1045 +/- 435 before surgery and 360 +/- 377 at 6 months; p < 0.01). These results remained stable at 12 months for the 14 patients studied. Side effects comprised lower limb phlebitis (n = 2), pulmonary embolism (n = 1), depression (n = 6), dysarthria and freezing (n = 1), sialorrhea and drooling (n = 1), postural imbalance (n = 1), transient paresthesias and dyskinesias. This study confirms the great value of subthalamic nucleus stimulation in the treatment of intractable PD. Some adverse events such as depression may be taken into account in the inclusion criteria and also in the post-operative outcome.     

Subthalamic nucleus stimulation and levodopa-resistant postural instability in Parkinson's disease

We examined the effect of bilateral subthalamic nucleus stimulation on levodopa-resistant balance impairment in 14 patients with Parkinson's disease and 18 matched controls. Instability was quantitatively assessed using standardized multidirectional dynamic posturography. Patients were tested after taking a suprathreshold dose of levodopa, both with stimulators turned on and off. Patients with stimulators turned off were more unstable than controls following backward directed perturbations. Overall, patients' instability did not improve with STN stimulation, and considerable inter-individual variability was noted. Of note, marked levodopa- resistant axial motor symptoms before surgery correlated with an adverse treatment effect. We conclude that STN stimulation does not alleviate levodopa-resistant postural instability in Parkinson's disease.     

Subthalamic nucleus deep brain stimulation improves deglutition in Parkinson's disease

Relatively little is known about the role of the basal ganglia in human deglutition. Deep brain stimulation (DBS) affords us a model for examining deglutition in humans with known impairment of the basal ganglia. The purpose of this study was to examine the effects of subthalamic nuclei (STN) DBS on the oral and pharyngeal stages of deglutition in individuals with Parkinson's Disease (PD). It was hypothesized that DBS would be associated with improved deglutition. Within participant, comparisons were made between DBS in the ON and OFF conditions using the dependent variables: pharyngeal transit time, maximal hyoid bone excursion, oral total composite score, and pharyngeal total composite score. Significant improvement occurred for the pharyngeal composite score and pharyngeal transit time in the DBS ON condition compared with DBS OFF. Stimulation of the STN may excite thalamocortical or brainstem targets to sufficiently overcome the bradykinesia/hypokinesia associated with PD and return some pharyngeal stage motor patterns to performance levels approximating those of “normal” deglutition. However, the degree of hyoid bone excursion and oral stage measures did not improve, suggesting that these motor acts may be under the control of different sensorimotor pathways within the basal ganglia. © 2007 Movement Disorder Society