帕金森病患者丘脑腹外侧核团神经元振荡活动特点

目的 探讨帕金森病(PD)患者丘脑腹外侧核团(Vop/Vim)神经元振荡活动与PD症状的关系.方法 23例PD患者在接受立体定向丘脑毁损术时应用微电极和肌电记录技术采集细胞和肢体电活动.单细胞和峰间隔分析鉴别细胞放电频率和模式;功率谱分析神经元振荡活动与症状的关系.PD综合评分量表(UPDRS)进行疗效评估.结果 114个振荡活动神经元中78％伴有震颤节律,并与肢体震颤相关;22％伴有β节律.发现震颤节律振荡活动神经元主要分布在Vim,β节律振荡活动神经元主要分布在Vop (P ＜0.05).结论 Vim是改善震颤的最佳靶点.β节律振荡活动神经元与僵直、运动不相关,提示Vop可以改善PD僵直和迟缓.     

帕金森病患者丘脑腹外侧核团神经元的电活动特点

目的：探讨丘脑腹外侧核（VL）神经元电活动与帕金森性震颤的关系。方法：应用微电极记录和肌电记录技术。对19例帕金森性震颤患者实施立体定向Vim切开术的同时,对Vim的神经元电信号和对侧肢体肌电活动进行记录。电信号的采集和放大器用四通道微电极放大器系统及PolyView软件,采样频率为7.5kHz。电极阻抗在0.1至0.5MΩ,数据分析包括：神经元放电频率,幅度,放电间期,神经元和肌电活动的相关性。结果：在19个针道记录到189个神经元簇,其中簇辨电活动与肢体姿势性震颤一致的有78个,占41%,这78个VL神经元放电活动与肢体震颤（4-6Hz)的相关系数为R^2=0.68。单细胞分析表明78个震颤细胞群放电频率在6-16Hz,平均放电频率8Hz(n=78)。另外101VL神经元族（59%）紧张型放电在6-35Hz之间,其中19个Vim神经元（19）与运动刺激相关,而16个Vc神经元（16%）与触觉相关,结论：VL核团作为皮层-丘脑-基底节环路的重要中继站,接受来自基底节的输入,参与了原发性帕金森震颤的发生发展。     

运动障碍病的神经电生理基础

目的探讨运动障碍病的细胞学病理生理基础,提高手术治疗的有效率和安全性.方法回顾过去3年的工作,1200例运动障碍病患者接受了微电极导向的立体定向神经外科手术.包括帕金森性病(PD)、原发性震颤(ET)、扭转痉挛和痉挛性斜颈等.手术的靶点包括苍白球腹后部(PVP),丘脑底核(STN)和丘脑腹外侧核(VL).术中应用微电极和肌电(EMG)记录技术,采集GPi,STN和VL神经元和肢体肌电活动.术后应用分析软件甄别单细胞及其电活动特点,分析其与临床症状的关系,并进行相关性检验.结果PD性震颤在GPi,STN、VL获得相关神经元簇放电频率是不一致,可指导临床.原发性震颤在丘脑腹中间核(Vim)获取的放电频率,也有临床指导意义.扭转痉挛和痉挛性斜颈扭转痉挛和痉挛性斜颈患者的神经元簇放电无明显规则可寻.结论识别和确定GPi、STN和VL细胞电活动特点及其分布,对于指导立体定向手术的功能定位,提高运动障碍病手术治疗的疗效和降低手术并发症具有重要的意义.     

帕金森病患者丘脑底核的微电极定位技术

目的　研究帕金森病(PD)患者丘脑底核(STN)及其邻近结构神经元电活动的特点,指导手术靶点的准确定位。方法　30例PD患者在行STN电极埋植(8例)或毁损术(22例)时,应用微电极和EMG记录技术,采集STN及其邻近结构的细胞外电活动和肢体的EMG活动。分析其电活动的特点。结果　在31个记录针道中,共记录到388个STN神经元,其中14%呈紧张性放电,28%呈规律性簇状放电,58%呈不规则或簇状放电。放电频率20～50Hz,平均42.2±11.6Hz。确认震颤细胞,节律为3.8～6Hz,与肢体震颤密切相关(r=0.63,P<0.01)。多数(82%)震颤细胞位于STN中上部分。黑质神经元呈均匀的紧张性放电,放电频率72.5±17.9Hz。结论　STN及其邻近结构存在特征性的电活动,微电极记录技术为STN手术的精确定位提供了可靠的技术保证。     

书写痉挛患者丘脑腹外侧核团细胞电活动特点

目的 探讨书写痉挛(WC)患者丘脑腹外侧核团(VL)细胞电活动特点,为临床治疗提供可靠的依据.方法 10例WC患者在行立体定向VL毁损术的同时,应用微电极和肌电记录技术采集VL细胞和手术对侧肢体肌电活动.分析不同细胞的放电模式和平均自发放电频率(MSFR),并探讨VL细胞放电活动与肢体肌电的关系.结果 在10个针道中共甄别出85个VL神经元,61.2%的神经元呈不规则放电活动,MSFR为(20.3±14.9)Hz,变异系数(CV)为1.38±0.40;38.8%的神经元为紧张性放电活动,MSFR为(44.4±21.5)Hz,CV为0.84±0.11.功率谱相关性分析发现VL细胞放电活动的改变与WC相关(P＜0.05,n=12).结论 VL参与WC的病理生理过程.     

运用障碍病的神经电生理基础

目的：探讨运动障碍病的细胞学病理生理基础。提高手术治疗的有效率和安全性。方法：回顾过去3年的工作,1200例运动障碍病患者接受了微电极导向的立体定向神经外科手术,包括帕金森性病（PD）、原发性震颤（ET）、扭转痉挛和痉挛性斜颈等。手术的靶点包括苍白球腹后部（PVP）,丘脑底核（STN）和丘脑腹外侧核（VL）。术中应用微电极和肌电（EMG）记录技术,采集GPi,STN和VL神经元和肢体肌电活动,术后应用分析软件甄别单细胞及其电活动特点,分析其与临床症状的关系。并进行相关性检验。结果：PD性震颤：在GPi,STN、VL获得相关神经元簇放电频率是不一致,可指导临床,原发性震颤;在丘脑腹中间核（Vim)获取的放电频率,也有临床指导意义。扭转痉挛和痉挛性伤痛颈：扭转痉挛和痉挛性伤痛颈患者的神经元簇放电无明显规则可寻,结论：识别和确定GPi、STN和VL细胞电活动特点及其分布,对于指导立体定向手术的功能定位,提高运动障碍病手术治疗的疗效和降低手术并发症具有重要的意义。     

帕金森性震颤和与震颤相关的电活动

目的对PD患者行STN和GPi切开术术中应用微电极记录技术采集神经元的电活动,术后分析其与震颤的关系和特点,为手术选择最佳的毁损位置提供客观的电生理指标.方法40个PD患者,其中21例PD患者接受了立体定向GPi切开术和19例PD患者接受立体定向STN切开术.病人要求清醒合作且处于“关”状态.术中应用微电极和肌电(EMG)记录技术,采集GPi和STN神经元和手术对侧肢体震颤的生物电活动.术后应用分析软件甄别单细胞及其电活动特点,分析其与震颤症状的关系,并进行相关性检验.结果在21个针道共记录到184 GPi个神经元单位,其簇状放电的节律与肢体震颤的节律高度一致(4～6Hz),R2=0.78(P＜0.01).在20个针道共记录到161个STN神经元单位,其放电频率在42～88Hz之间.STN的簇状放电的节律与肢体震颤的节律一致(4～6Hz),R2=0.64(P＜0.01).毁损这些震颤细胞导致震颤症状的消失.结论震颤型PD患者的GPi和STN存在与肢体震颤节律一致的震颤细胞,且震颤和震颤细胞有着内在的关系.对于指导手术毁损的部位和范围提供了可靠的依据.     

内苍白球震颤细胞的电活动与帕金森性震颤

目的 探讨帕金森病（PD）特征性震颤与内苍白球（GPi）神经元电活动的关系，指导手术靶点的精确定位。方法 10例PD患者接受了立体定向苍白球腹后部毁损术，术中应用微电极和肌电（EMG）记录技术，采集GPi神经元和肢体震颤的生物电活动。术后应用分析软件甄别单细胞及其电活动特点，分析其与震颤症状的关系，并进行相关性检验。结果 在GPi共记录到了112个神经元，有57个（51％）震颤细胞，且主要分布在视束上方4－6mm，其簇状放电的节律与肢体震颤的节律高度一致（4－6Hz），R^2＝0.71（P＜0.01）。毁损震颤细胞导致震颤症状的消失。结论 震颤型PD患者的GPi存在电活动与肢体震颤节律一致的震颤细胞，该细胞的发现和定位，对于指导手术毁损的部位和范围具有重要意义。     

微电极导向立体定向手术治疗原发性震颤

目的：探讨丘脑腹外则Vim核中与震颤症状相关的神经细胞电活动的规律,总结丘脑毁损术治疗原性震颤（ET）的临床效果和安全性。方法：对42例ET患者行单侧微电极导向的丘脑毁损术。采用FAHN的临床震颤评分法对其中11例患者术前及术后进行定量评估和分析。结果：Vim核中神经细胞的簇状电活动节律与肢体震颤的节律有肯定的一致性,毁损这些与震颤症状相关的神经细胞后,所有ET患者手术对侧肢体的震颤完全消失;震颤的整体改善率52％,特殊动作和功能改善54％,功能残疾改善率77％,长期随访疗效稳定,其中40例患者的震颤症状密切相关,毁损这些细胞能完全永久性地消除震颤症状。     

帕金森病人GPi、Vim及STN的电生理特性研究

目的　探讨帕金森病 (PD)患者的苍白球内侧部 (GPi) ,丘脑腹外侧中间核 (Vim)及丘脑底核 (STN)的电生理特性。方法　用立体定向毁损术治疗 54例PD手术中 ,应用美国FHC公司生产的微电极记录系统 ,记录GPi、Vim和STN不同部位的电活动。结果　PD病人的丘脑内和基底节不同结构部位的电活动频率、幅度、放电方式和背景噪声均有显著差异 ;Vim中可记录到与震颤同步的高频放电 ,GPi、STN可记录到一致稳定的放电活动。结论　利用GPi、Vim和STN不同部位的电活动特性 ,可以为立体定向治疗PD手术中的精确定位 ,提高疗效 ,降低并发症提供参考依据     

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.     

Neuronal activity in the basal ganglia and thalamus in patients with dystonia.

OBJECTIVE: To explore the role of abnormal neuronal activity in the basal ganglia and thalamus in the generation of dystonia. METHODS: Microelectrode recording was performed in the globus pallidus internus (GPi), ventral thalamic nuclear group ventral oral posterior/ventral intermediate, Vop/Vim) and subthalamic nucleus (STN) in patients with primary dystonia (n=11) or secondary dystonia (n=9) during surgery. Electromyogram (EMG) was simultaneously recorded in selected muscle groups. Single unit analysis and cross-correlations were carried out. RESULTS: Three hundred and sixty-seven neurons were obtained from 29 trajectories (GPi: 13; Vop/Vim: 12; STN: 4), 87% exhibited altered neuronal activity including grouped discharges in GPi (n=79) and STN (n=37), long-lasting neuronal activity (n=70) and rapid neuronal discharge (n=86) in Vop/Vim. There were neurons in Vop, GPi and STN firing at the same frequency as EMG during dystonia (mean: 0.39 Hz, range 0.12-0.84 Hz). Significant correlations between neuronal activity and EMG at the frequency of dystonia were obtained (GPi: r2=0.7 (n=31), Vop/Vim: r2=0.64 (n=18) and STN: r2=0.86 (n=17)). CONCLUSIONS: Consistent with previous findings of abnormalities observed in Vop/VIM and GPi in relation to dystonia, the present data further show that the altered activity in GPi, specifically in dorsal subregions of GPi, Vop/Vim and STN is likely to be directly involved in the production of dystonic movement. Dystonia-related neuronal activity observed in motor thalamus and basal ganglia nuclei of GPi and STN indicates a critical role of their interactions affecting both indirect and direct pathways in the development of either generalized or focal dystonia. SIGNIFICANCE: These data support a central role of the basal ganglia in producing dystonic movements.     

Subcortical neuronal ensembles: an analysis of motor task association, tremor, oscillations, and synchrony in human patients

Deep brain stimulation (DBS) has expanded as an effective treatment for motor disorders, providing a valuable opportunity for intraoperative recording of the spiking activity of subcortical neurons. The properties of these neurons and their potential utility in neuroprosthetic applications are not completely understood. During DBS surgeries in 25 human patients with either essential tremor or Parkinson's disease, we acutely recorded the single-unit activity of 274 ventral intermediate/ventral oralis posterior motor thalamus (Vim/Vop) neurons and 123 subthalamic nucleus (STN) neurons. These subcortical neuronal ensembles (up to 23 neurons sampled simultaneously) were recorded while the patients performed a target-tracking motor task using a cursor controlled by a haptic glove. We observed that modulations in firing rate of a substantial number of neurons in both Vim/Vop and STN represented target onset, movement onset/direction, and hand tremor. Neurons in both areas exhibited rhythmic oscillations and pairwise synchrony. Notably, all tremor-associated neurons exhibited synchrony within the ensemble. The data further indicate that oscillatory (likely pathological) neurons and behaviorally tuned neurons are not distinct but rather form overlapping sets. Whereas previous studies have reported a linear relationship between power spectra of neuronal oscillations and hand tremor, we report a nonlinear relationship suggestive of complex encoding schemes. Even in the presence of this pathological activity, linear models were able to extract motor parameters from ensemble discharges. Based on these findings, we propose that chronic multielectrode recordings from Vim/Vop and STN could prove useful for further studying, monitoring, and even treating motor disorders.     

Role of thalamic nuclei in the hypertonia and tremor of Parkinson disease

Intraoperative recordings allowed the ventralis intermedius nucleus (Vim) to be distinguished from the ventrolateral nucleus (VL). Characteristics of the Vim include marked spontaneous activity, bursts synchronous with tremor, response of certain cells to contralateral kinesthetic and peripheral electric stimuli and paresthesia provoked by an intraoperative stimulus. Coagulation of Vim abolishes tremor while coagulation of VL abolishes hypertonus.     

Ethanol withdrawal results in aberrant membrane properties and synaptic responses in periaqueductal gray neurons associated with seizure susceptibility

The midbrain periaqueductal gray (PAG) is implicated as a component of the neuronal network for ethanol withdrawal (ETX) seizures and in other forms of audiogenic seizure (AGS) in rats. Previous in vivo experiments suggest that neurons in the ventrolateral PAG (VL PAG) are required for generation of the clonic and tonic seizure behaviors of AGS. During these seizures, PAG neuronal firing rates increase markedly, but the intracellular events, contributing to this phenomenon, have not been characterized. In the present in vitro study, intracellular current-clamp recordings were obtained from 115 control VL PAG neurons and 71 neurons during ETX. The amount of depolarizing current that needed to be injected into ETX neurons in order to generate an action potential (AP) (N=40) was significantly less than control (N=52). ETX also yielded a significant leftward shift in the frequency-current curve of VL PAG neurons. VL PAG neurons during ETX had significantly enhanced spike firing tendencies, but the firing pattern was similar in ETX and control. ETX significantly increased the incidence of spontaneous APs and the frequency of firing above those in control. A number of cellular properties [e.g. resting membrane potential (RMP), amplitude of AP, AP width at half-height, input resistance and time constant] did not differ significantly between ETX and control neurons. The current-voltage (I-V) relationships of the ETX and control VL PAG neurons were nearly linear between RMP and 80 mV more negative than RMP, whereas the I-V relation was non-linear beyond this range. Stimulation in the dorsolateral PAG in either ETX or control neurons evoked a fast excitatory postsynaptic potential (EPSP) and a slow inhibitory postsynaptic potential (IPSP). The stimulus intensities required to evoke EPSPs were significantly lower than control in neurons during ETX. Epileptiform firing was observed commonly (20%) during ETX but was never seen in control rats. Paired-pulse responses evoked paired-pulse inhibition in approximately 80% of VL PAG neurons from control rats (N=38), which was significantly above the incidence (12%) of this pattern during ETX (N=25). Paired-pulse facilitation was significantly more common (88%) in VL PAG neurons (N=25) during ETX compared to approximately 20% in controls (N=38). These aberrant membrane and synaptic properties provide direct evidence regarding the basis of the hyperexcitability observed in VL PAG neurons in vivo that contribute to propagation mechanisms of clonic and tonic convulsions, occurring during ETX.     

UNIT ACTIVITY CONNECTED WITH MOVEMENT INITIATION AND AROUSAL SITUATIONS RECORDED FROM THE VENTROLATERAL NUCLEUS OF THE HUMAN THALAMUS

A total of 21 microelectrode recordings from the human thalamus were made during stereotactic operations on patients with Parkinson's disease, intention tremor and dystonia. The electrode consisted of a 0.5 mm laquered tungsten wire having an electrolytically sharpened tip of about 5 μ. The electrode was inserted into the thalamus coaxially in a guiding probe the distal uninsulated ring of which served as the indifferent electrode. The probe was fitted to the standard Riechert stereotactic crown. All but one of the patients were fully conscious during the study. Activity of both single and multiunit type was obtained from the ventrolateral (VL) nucleus. Spontaneous irregular and spontaneous rhytmic activities with different frequencies were recorded. Of special interest were the rhythms within the same range as the Parkinsonian tremor. The results of previous investigations were largely confirmed. The earlier reported phenomena connected with the initiation of voluntary motor acts were recorded but the results did not show the previously indicated close correlation between activated thalamic units and certain muscle groups. Muscle vibration causing local tonic vibration reflexes and a potentiation of the Parkinsonian tremor had no obvious effect upon the firing patterns of units in the VL nucleus. Marked changes in the activity of the VL neurons were often observed in response to arousal stimuli of different types. Anything happening suddenly to the subject could produce either intense bursts of single and multiunit activity, or interruption of spontaneous activity or changes in regularity of firing. Responses of this sort, which were characterized by rapid habituation, were seen most frequently in patients with intention tremor and dystonia. The findings suggest that in patients of this type the midbrain reticular activating system exerts an abnormal influence on the synaptic events in the ventrolateral nucleus.     

Effects of apomorphine on globus pallidus neurons in parkinsonian patients

Current hypotheses of basal ganglia dysfunction in Parkinson's disease (PD) propose that neuronal hypoactivity in the globus pallidus externus (GPe), and hyperactivity in the output nuclei and the external and internal portions of the globus pallidus internus (GPi, e and GPi, i, respectively), result in the cardinal symptoms of PD. To test this theory, the nonselective D₁- and D₂-dopamine receptor agonist apomorphine (30–100 μg/kg SC) was administered to 14 levodoparesponsive PD patients who were off medication (“of” state) while recording neurons in GP. For 15 neurons that were continuously monitored, apomorphine was found to increase the firing rate of 3 neurons in GPe, and decrease the rate of 12 in GPi. The mean firing rates of many different neurons were determined before (n = 285) and at various intervals after (n = 184) the injection of the drug. The mean rates before apomorphine were as follows: GPe, 45 Hz (SD 15, n = 85); GPi, e, 67 Hz (SD 14, n = 125); and GPi, i, 85 Hz (SD 19, n = 75). At 25 to 35 minutes after APO, the rate of GPe neurons had increased to 72 Hz (SD 18, n = 7), the rate of GPi, e neurons had decreased to 39 Hz (SD 15, n = 15), and in GPi, i the rate decreased to 34 Hz (SD 22, n = 18). Eighty minutes after apomorphine administration, the mean firing rates returned to preadministration values. This study supports current models of basal ganglia dysfunction in PD and suggests that the thereapeutic effect of apomorphine results from a normalization of the imbalance of neuronal activity in the direct and indirect pathways.