Recognition of emotional prosody is altered after subthalamic nucleus deep brain stimulation in Parkinson's disease

The recognition of facial emotions is impaired following subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD). These changes have been linked to a disturbance in the STN's limbic territory, which is thought to be involved in emotional processing. This was confirmed by a recent PET study where these emotional modifications were correlated with changes in glucose metabolism in different brain regions, including the amygdala and the orbitofrontal regions that are well known for their involvement in emotional processing. Nevertheless, the question as to whether these emotional changes induced by STN DBS in PD are modality-specific has yet to be answered. The objective of this study was therefore to examine the effects of STN DBS in PD on the recognition of emotional prosody.An original emotional prosody paradigm was administered to twenty-one post-operative PD patients, twenty-one pre-operative PD patients and twenty-one matched controls. Results showed that both the pre- and post-operative groups differed from the healthy controls. There was also a significant difference between the pre and post groups. More specifically, an analysis of their continuous judgments revealed that the performance of the post-operative group compared with that of the other two groups was characterized by a systematic emotional bias whereby they perceived emotions more strongly.These results suggest that the impaired recognition of emotions may not be specific to the visual modality but may also be present when emotions are expressed through the human voice, implying the involvement of the STN in the brain network underlying the recognition of emotional prosody.     

Specific impairment of visual spatial covert attention mechanisms in Parkinson's disease

Visual deficits in early and high level processing nodes have been documented in Parkinson's disease (PD). Non-motor high level visual integration deficits in PD seem to have a cortical basis independently of a low level retinal contribution. It is however an open question whether sensory and visual attention deficits can be separated in PD. Here, we have explicitly separated visual and attentional disease related patterns of performance, by using bias free staircase procedures measuring psychophysical contrast sensitivity across visual space under covert attention conditions with distinct types of cues (valid, neutral and invalid). This further enabled the analysis of patterns of dorsal-ventral (up-down) and physiological inter-hemispheric asymmetries. We have found that under these carefully controlled covert attention conditions PD subjects show impaired psychophysical performance enhancement by valid attentional cues. Interestingly, PD patients also show paradoxically increased visual homogeneity of spatial performance profiles, suggesting flattening of high level modulation of spatial attention. Finally we have found impaired higher level attentional modulation of contrast sensitivity in the visual periphery, where mechanisms of covert attention are at higher demands.These findings demonstrate a specific loss of attentional mechanisms in PD and a pathological redistribution of spatial mechanisms of covert attention.     

Pyramidal tract activation due to subthalamic deep brain stimulation in Parkinson's disease

Background: Subthalamic deep brain stimulation (STN‐DBS) is an effective treatment for Parkinson's disease (PD), but can have side effects caused by stimulus spread to structures outside the target volume such as the pyramidal tract. Objectives: To assess the relevance of pyramidal tract activation with STN‐DBS in PD. Methods: In a multimodal, blinded study in 20 STN‐DBS patients, we measured stimulation thresholds for evoking electromyographic activity in orbicularis oris and first dorsal interosseous muscles at each of 150 electrode sites. We also modeled the electric field spread and calculated its overlap with the estimated anatomical location of corticospinal and corticobulbar tracts from primary motor cortex using 3 Tesla MRI probabilistic tractography. Results: Mean resting motor thresholds were significantly lower for the contralateral orbicularis oris (3.5 ± 1.0 mA) compared with ipsilaterally (4.1 ± 1.1 mA) and with the contralateral first dorsal interosseous (4.0 ± 1.2 mA). The modeled volumes of corticobulbar and corticospinal tract activated correlated inversely with the resting motor threshold of the contralateral orbicularis oris and first dorsal interosseous, respectively. Active motor thresholds were significantly lower compared with resting motor thresholds by around 30% to 35% and correlated with the clinically used stimulation amplitude. Backward multiple regression in 12 individuals with a “lateral‐type” speech showed that stimulation amplitude, levodopa equivalent dose reduction postsurgery, preoperative speech intelligibility, and first dorsal interosseous resting motor thresholds explained 79.9% of the variance in postoperative speech intelligibility. Conclusions: Direct pyramidal tract activation can occur at stimulation thresholds that are within the range used in clinical routine. This spread of current compromises increase in stimulation strengths and is related to the development of side effects such as speech disturbances with chronic stimulation. © 2017 International Parkinson and Movement Disorder Society     

丘脑底核电刺激术治疗帕金森病的疗效

目的评估丘脑底核脑深部电刺激(STN-DBS)对帕金森病的临床疗效。方法回顾性分析应用STN-DBS手术治疗的32例帕金森病病人的临床资料,在术前、术后3个月分别采用统一帕金森病评定量表(UPDRS)、抑郁自评量表(SDS)和症状自评量表(SCL-90)进行随访评估、心理状况问卷调查和分析。结果脉冲发生器开启后,32例病人的UPDRS日常活动和运动功能在"关"状态,平均改善率为51.7%和60.9%;在"开"状态下,平均改善率21.4%和22.3%。20例病人术前SDS评分50分,其SCL-90的抑郁、焦虑、躯体化、人际敏感、敌对、恐怖和偏执7个因子显著高于中国常模(P0.05)。术前与术后SCL-90抑郁、躯体化、恐怖、焦虑、精神病性因子有显著性差异(P0.05),人际敏感、偏执、敌对和强迫等因子无显著性差异(P0.05)。结论 STN-DBS可以改善帕金森病病人的运动功能,提高日常生活能力,还可以明显改善帕金森病伴抑郁病人的心理状况,是安全有效的治疗方法。     

帕金森病病人脑深部电刺激器刺激参数调节策略

目的探讨帕金森（Parkinson disease，PD）病人脑深部电刺激器（brain deep stimulation,DBS）刺激参数调节的策略。方法回顾性分析82例（共141侧）PD病人的临床资料，均采用微电极记录下丘脑底核（subthalamic nucleus，STN）电刺激术治疗，双侧手术59例，单侧手术23例。采用微电极记录手术靶点区域细胞外放电信号并计算STN核团长度，术后复查MRI了解电极位置，估算出每个触点相对于STN的位置关系。每个触点采用相同刺激参数，单极刺激观察评估病人症状改善情况。刺激参数从低到高，直至病人出现副反应。选取病人最佳改善状态且副作用最小时电压值，进行4个触点比较，取最小值的触点为刺激靶点。调节并记录病人6个月、12个月和24个月所用电压、脉宽和频率大小。结果术后6个月刺激电压（2．9±0．8）V，术后12个月（3．0±0．4）V，术后24个月（3．0±0.7）V。刺激脉宽60-120μs，刺激频率130-185Hz。刺激触点共141个，其中121个（86％）个触点位于STN前背侧和周边纤维传导束，20个（14％）触点位于STN中央。结论丘脑底核前背侧部和周边纤维传导束，如未定带（zona incerta，ZI）和Forel区（fields of Forel，FF）是刺激的最佳靶点，用相对最低电量可以得到最佳疗效。刺激频率和脉宽对刺激效果影响较小，刺激电压基本不随时间推移增加。     

丘脑底核脑深部电刺激对帕金森病抑郁障碍的影响

目的探讨丘脑底核脑深部电刺激对帕金森病病人抑郁障碍的疗效及其机制。方法回顾性分析21例帕金森病合并抑郁障碍病人的临床资料,均行丘脑底核脑深部电刺激术,术前及术后3、6个月分别应用汉密尔顿抑郁量表(HAMD)评分和统一帕金森病评定量表(UPDRS)运动评分对抑郁障碍和运动功能进行临床评价并分析其相关性。结果术后UPDRS运动评分和HAMD评分均显著下降(均P0.05),但是抑郁症状的改善与运动功能的改善并没有明显的相关性(P0.05)。结论丘脑底核脑深部电刺激能够明显改善帕金森病病人的抑郁症状,其机制可能与丘脑底核受到刺激影响脑内神经递质的变化有关,术后运动功能的改善不是抑郁症状改善的主要原因。     

Operative techniques and morbidity with subthalamic nucleus deep brain stimulation in 100 consecutive patients with advanced Parkinson's disease

OBJECTIVE: Subthalamic nucleus (STN) stimulation for patients with medically refractory Parkinson disease (PD) is expanding. Reported experience has provided some indication of techniques, efficacy, and morbidity, but few centres have reported more than 50 patients. To expand this knowledge, we reviewed our experience with a large series of consecutive patients. METHODS: From March 1999 to September 2003, 191 subthalamic stimulator devices (19 unilateral) were implanted in 100 patients with PD at New York Presbyterian Hospital/Columbia University Medical Center. Sixteen patients had undergone a prior surgery for PD (pallidotomy, thalamotomy, or fetal transplant). Microelectrode guided implantations were performed using techniques similar to those described previously. Electrode implantation occurred 1-2 weeks before outpatient pulse generator implantation. RESULTS: Reductions of dyskinesias and off severity/duration were similar to prior published reports. Morbidity included: 7 device infections (3.7%), 1 cerebral infarct, 1 intracerebral haematoma, 1 subdural haematoma, 1 air embolism, 2 wound haematomas requiring drainage (1.0%), 2 skin erosions over implanted hardware (1.0%), 3 periprocedural seizures (1.6%), 6 brain electrode revisions (3.1%), postoperative confusion in 13 patients (6.8%), and 16 battery failures (8.4%). Of the 100 patients, there were no surgical deaths or permanent new neurological deficits. The average hospital stay for all 100 patients was 3.1 days. CONCLUSION: Subthalamic stimulator implantation in a large consecutive series of patients with PD produced significant clinical improvement without mortality or major neurological morbidity. Morbidity primarily involved device infections and hardware/wound revisions.     

丘脑底核电刺激治疗帕金森病

目的 探讨脑深部电刺激（DBS）对原发帕金森病（PD）的治疗作用及手术方法。方法 应用微电极导向技术和手术计划系统进行靶点定位，对20例PD病人的丘脑底核（STN）进行电极植入，术后至少6个月的评价和随访。结果 15例单侧和5例双侧STN的DBS术后病人肢体僵直、震颤和运动迟缓等症状改善明显，术前术后UPDRS运动评分和日常生活能力评分均有显著下降（P＜0.01），服药量也有不同程度的减少，无严重及永久并发症。结论 STN的DBS手术治疗PD，对症状改善非常全面，可通过参数调整达到最佳治疗效果。服药量明显减少，是一种安全、有效的治疗方法。     

Comparison of neuropathology in Parkinson's disease subjects with and without deep brain stimulation

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

双侧丘脑底核脑深部电刺激术治疗帕金森病(附33例报道)

目的总结双侧脑深部电刺激术(DBS)治疗帕金森病(PD)的手术方法和效果。方法对具有严重双侧症状和轴性症状的33例PD病人进行同期双侧丘脑底核DBS治疗。采用磁共振扫描结合微电极记录技术进行靶点定位。术后采用统一帕金森病评定量表(UPDRS)运动评分评价刺激效果。结果术后随访3个月~4年,平均7.3个月。脉冲发生器开启时,UPDRS运动评分平均改善率在“关”状态下为62.3%,在“开”状态下为24.2%。记忆力下降2例,情绪改变7例,睁眼困难1例,肢体异动15例;无明显的致残性永久并发症和副作用。结论双侧丘脑底核DBS手术的安全性较高,可明显改善PD病人的运动功能。     

Improvement of sleep quality in patients with advanced Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus.

Most Parkinson's patients complain about sleep problems. The subjective effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on nocturnal disabilities and sleep quality was elucidated by the recently established Parkinson's disease sleep scale (PDSS). The DBS-treated group obtained significant improvement of motor function assessed by the Unified Parkinson's Disease Rating Scale. The mean total PDSS improved significantly after surgery whereas no change was found for the control group. Significant improvements of individual questions were obtained for overall sleep quality and motor symptoms whereas nocturia and daytime sleepiness did not change despite significant reduction of parkinsonian medication.     

帕金森病患者丘脑底核电极植入术中位置判断和调整

目的探讨帕金森病患者脑深部刺激术（DBS）中丘脑底核（STN）电极植入位置准确性判断和调整。方法对137例帕金森病（PD）患者进行了丘脑底核DBS治疗,其中单侧68例,双侧69例。采用磁共振扫描,图像直接定位和坐标值定位相结合的方法计算靶点坐标,微电极记录细胞外放电。术中采用微毁损效应,观察刺激效果和副作用,X线透视和带立体定向头架MRI复查。结果绝大部分患者都能观察到电极植入的微毁损效应、电刺激效果和刺激副作用,术中X线透视和带立体定向头架MRI复查能观察到电极实际位置,并进行必要的调整。结论通过微毁损效应、电刺激效果和刺激副作用观察以及术中影像学检查能及时纠正电极位置偏差,减少二次手术,从而提高PD患者的DBS疗效。     

Cortical network organization reflects clinical response to subthalamic nucleus deep brain stimulation in Parkinson's disease

The degree of response to subthalamic nucleus deep brain stimulation (STN‐DBS) is individual and hardly predictable. We hypothesized that DBS‐related changes in cortical network organization are related to the clinical effect. Network analysis based on graph theory was used to evaluate the high‐density electroencephalography (HDEEG) recorded during a visual three‐stimuli paradigm in 32 Parkinson''s disease (PD) patients treated by STN‐DBS in stimulation “off” and “on” states. Preprocessed scalp data were reconstructed into the source space and correlated to the behavioral parameters. In the majority of patients (n = 26), STN‐DBS did not lead to changes in global network organization in large‐scale brain networks. In a subgroup of suboptimal responders (n = 6), identified according to reaction times (RT) and clinical parameters (lower Unified Parkinson''s Disease Rating Scale [UPDRS] score improvement after DBS and worse performance in memory tests), decreased global connectivity in the 1–8 Hz frequency range and regional node strength in frontal areas were detected. The important role of the supplementary motor area for the optimal DBS response was demonstrated by the increased node strength and eigenvector centrality in good responders. This response was missing in the suboptimal responders. Cortical topologic architecture is modified by the response to STN‐DBS leading to a dysfunction of the large‐scale networks in suboptimal responders.     

Deep brain stimulation of the subthalamic nucleus transiently enhances loss-chasing behaviour in patients with Parkinson's disease

Dopaminergic treatments are associated with impulse control disorders such as pathological gambling in a subset of patients with Parkinson's Disease. While deep brain stimulation of the subthalamic nucleus has been reported to reduce symptoms of impulse control disorders in some Parkinson's Disease patients, little is known about its specific effects on gambling behaviour. In this experiment, we investigated the effects of deep brain stimulation of the subthalamic nucleus on one of the central features of pathological gambling: the tendency to chase losses. Loss-chasing is associated with impaired control over gambling behaviour and it is one of the most salient features of pathological gambling as it presents in the clinic. Twenty two patients with advanced idiopathic Parkinson's Disease and chronically implanted subthalamic nucleus electrodes for deep brain stimulation completed a simple laboratory model of loss-chasing behaviour twice: once with and once without stimulation. Exploratory analysis indicated that deep brain stimulation of the subthalamic nucleus increased the value of losses chased by patients with Parkinson's Disease when shifting from off- to on-stimulation. These effects were not attributable to changes in state affect or to the motor impairments produced by the withdrawal of deep brain stimulation of the subthalamic nucleus. The effects of the stimulation on the value of losses chased were more pronounced in female than in male patients and reduced in patients taking dopamine receptor agonists. Collectively, these results suggest that deep brain stimulation of the subthalamic nucleus can transiently alter the evaluation of accumulated losses during gambling episodes in idiopathic Parkinson's Disease.     

The effects of levodopa and ongoing deep brain stimulation on subthalamic beta oscillations in Parkinson's disease

Local field potentials (LFPs) recorded through electrodes implanted in the subthalamic nucleus (STN) for deep brain stimulation (DBS) in patients with Parkinson's disease (PD) show that oscillations in the beta frequency range (8-20 Hz) decrease after levodopa intake. Whether and how DBS influences the beta oscillations and whether levodopa- and DBS-induced changes interact remains unclear. We examined the combined effect of levodopa and DBS on subthalamic beta LFP oscillations, recorded in nine patients with PD under four experimental conditions: without levodopa with DBS turned off; without levodopa with DBS turned on; with levodopa with DBS turned on; and with levodopa with DBS turned off. The analysis of STN-LFP oscillations showed that whereas levodopa abolished beta STN oscillations in all the patients (p = 0.026), DBS significantly decreased the beta oscillation only in five of the nine patients studied (p = 0.043). Another difference was that whereas levodopa completely suppressed beta oscillations, DBS merely decreased them. When we combined levodopa and DBS, the levodopa-induced beta disruption prevailed and combining levodopa and DBS induced no significant additive effect (p = 0.500). Our observations suggest that levodopa and DBS both modulate LFP beta oscillations.     

Functional imaging of subthalamic nucleus deep brain stimulation in Parkinson's disease

Deep brain stimulation of the subthalamic nucleus is an accepted treatment for the motor complications of Parkinson's disease. The therapeutic mechanism of action remains incompletely understood. Although the results of deep brain stimulation are similar to the results that can be obtained by lesional surgery, accumulating evidence from functional imaging and clinical neurophysiology suggests that the effects of subthalamic nucleus‐deep brain stimulation are not simply the result of inhibition of subthalamic nucleus activity. Positron emission tomography/single‐photon emission computed tomography has consistently demonstrated changes in cortical activation in response to subthalamic nucleus‐deep brain stimulation. However, the technique has limited spatial and temporal resolution, and therefore the changes in activity of subcortical projection sites of the subthalamic nucleus (such as the globus pallidus, substantia nigra, and thalamus) are not as clear. Clarifying whether clinically relevant effects from subthalamic nucleus‐deep brain stimulation in humans are mediated through inhibition or excitation of orthodromic or antidromic pathways (or both) would contribute to our understanding of the precise mechanism of action of deep brain stimulation and may allow improvements in safety and efficacy of the technique. In this review we discuss the published evidence from functional imaging studies of patients with subthalamic nucleus‐deep brain stimulation to date, together with how these data inform the mechanism of action of deep brain stimulation. © 2011 Movement Disorder Society     

Mechanisms of action underlying the efficacy of deep brain stimulation of the subthalamic nucleus in Parkinson's disease: central role of disease severity

Despite consensus on some neurophysiological hallmarks of the Parkinsonian state (such as beta) band increase) a single mechanism is unlikely to explain the efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN). Most experimental evidence to date correlates with an extreme degree of nigral neurodegeneration and not with different stages of PD progression. It seems inappropriate to combine substantially different patients – newly diagnosed, early fluctuators or advanced dyskinetic individuals – within the same group. An efficacious STN‐DBS imposes a new activity pattern within brain circuits, favouring alpha‐ and gamma‐like neuronal discharge, and restores the thalamo‐cortical transmission pathway through axonal activation. In addition, stimulation via the dorsal contacts of the macro‐electrode may affect cortical activation antidromically. However, basal ganglia (BG) modulation remains cardinal for ‘OFF’‐’ON’ transition (as revealed by cGMP increase occurring during STN‐DBS in the substantia nigra pars reticulata and internal globus pallidus). New research promises to clarify to what extent STN‐DBS restores striato‐centric bidirectional plasticity, and whether non‐neuronal cellular actions (microglia, neurovascular) play a part. Future studies will assess whether extremely anticipated DBS or lesioning in selected patients are capable of providing neuroprotection to the synuclein‐mediated alterations of synaptic efficiency. This review addresses these open issues through the specific mechanisms prevailing in a given disease stage. In patients undergoing early protocol, alteration in endogenous transmitters and recovery of plasticity are concurrent players. In advanced stages, re‐modulation of endogenous band frequencies, disruption of pathological pattern and/or antidromic cortical activation are, likely, the prominent modes.     

Evolution of Parkinson's disease during 4 years of bilateral deep brain stimulation of the subthalamic nucleus.

Patients with advanced Parkinson's disease (PD) and motor complications can obtain significant symptom improvement by deep brain stimulation (DBS) of the subthalamic nucleus (STN). Very little is published, however, about long-term effect and disease evolution during DBS. We performed a 4-year prospective study of the first 22 consecutive patients treated with STN DBS. The patients were evaluated with Unified Parkinson's Disease Rating Scale Part II to VI and a patient diary concerning on-off periods and dyskinesia. Patients were scored before surgery on medication and off medication for 10 to 12 hours and in four conditions 1 and 4 years after surgery: off medication+/-stimulation and on medication+/-stimulation. In advanced PD, a significant reduction of dyskinesia and off periods was present 4 years (90%/67%) after the operation. Total motor function on stimulation alone improved 55% at 4 years, compared with baseline and activities of daily living (42%). On stimulation, significant worsening of axial symptoms and speech was present from 1 to 4 years. To evaluate disease evolution, motor symptoms were assessed off stimulation and medication for 12 hours and were found not to worsen compared with baseline, which is remarkable in an otherwise progressive disorder. Five patients developed dementia. Severe adverse events were not observed.