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。     

帕金森病患者苍白球神经元电生理活动的特点

目的探讨原发性帕金森病的症状与苍白球内侧部神经元电活动的关系.方法22例实施立体定向苍白球切开术治疗原发性PD患者,术中应用微电极记录和肌电记录技术,对内苍白球神经元细胞外电信号和对侧肢体肌电活动进行记录.数据分析包括放电频率,幅度,间期及时程;t检验用来比较GPie和GPii神经元电活动特点.结果在22个针道记录到的428个苍白球神经元簇中,有149个(34%)GPie神经元簇,288个(66%)GPie神经元簇.GPie神经元紧张型自发放电的平均频率是36±16.3Hz;而GPii神经元紧张型自发放电的平均频率是101±34Hz,两组神经元紧张性放电频率的比较显示明显的差异(t检验,P＜0.005).另外,苍白球边界细胞放电频率平均为11±3.7Hz.结论苍白球内侧部(GPii)神经元紧张性活动的过度活跃,与原发性PD症状的发生和病理生理过程相关.     

帕金森病患者丘脑腹外侧核的微电极定位技术

目的研究帕金森病患者丘脑腹外侧核(VL)神经元电活动的特点,指导手术靶点的精确定位。方法25例患者在接受立体定向丘脑手术时,应用微电极记录技术采集细胞的电活动资料,分析单细胞的电活动。结果共记录并甄别出258个神经元,44%的神经元簇状放电的节律与肢体震颤的节律高度相关(R=0.78),确认为震颤细胞,且多数位于Vim(n=75);11%的神经元放电对肢体运动有反应,确认为运动相关细胞。结论VL中的细胞电活动有明确的特点,特别是Vim存在着大量的震颤细胞,为手术靶点的定位提供了重要指征。     

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。     

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.     

帕金森病患者僵直迟缓症状神经元电活动特点研究

目的探讨帕金森病(PD)患者僵直迟缓症状的神经元电活动特点。方法 25例僵直迟缓为主征的PD患者接受立体定向丘脑底核(STN)脑深部电极植入术(DBS)。术中通过微电极记录技术采集神经元电活动。应用单细胞分析方法,峰间隔分析方法分析神经元放电的频率和形式,应用功率谱分析方法分析神经元放电周期节律。结果分析了180个信号稳定的神经元,平均放电频率为(40.6±22.3)Hz;有35.6%(n=64)神经元有周期节律性放电,放电周期节律在β节律内。结论β节律的神经元周期节律性电活动可能和PD僵直迟缓症状的病理生理改变有关。     

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.     

帕金森病猴苍白球神经元的电生理特性

目的 探讨帕金森病(Parkimon disease,PD)猴模型苍白球(globus pallidus,GP)神经元的电生理特性,为研究帕金森病的病理生理过程提供动物实验依据.方法 应用颈内动脉注射1-甲基4-苯基-1,2,3,6-四氧吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyri-dine,MPTP)建立PD猴模型.在立体定向仪引导下记录造模前后猴病理及正常生理状态下GP神经元的放电活动,并对其放电模式进行分析.结果 电生理记录显示外侧苍白球神经元(29个)放电频率在生理状态下为(4.39±2.10)Hz,在病理状态下(34个)为(9.69±4.99)Hz(P<0.05);内侧苍白球神经元放电频率在生理状态下(25个)为(2.69±1.57)Hz,在病理状态下(31个)为(17.50±4.94)Hz(P<0.01);在记录到内侧苍白球神经元单一放电时,进行长时间观察并给予APO(0.2 mg/kg)肌注,可见神经元放电频率和振幅明显减低.结论 PD猴模型GP神经元较生理状态下放电频率明显增加,其放电模式也有明显变化,簇状放电模式比例增大.     

帕金森病猴丘脑底核神经元的电生理特性

目的探讨帕金森病(PD)猴模型丘脑底核(STN)神经元的电生理特性,为研究帕金森病的病理生理过程提供动物实验依据。方法应用颈内动脉注射MPTP建立PD猴模型。在立体定向仪引导下应用细胞外记录的方法记录"造模"前后猴病理及正常生理状态下STN神经元的放电活动,并对其放电模式进行分析。结果电生理记录显示STN神经元放电频率在生理状态下为2.03±1.12Hz;在病理状态下为9.58±0.85 Hz(P<0.01)。在生理状态下有20个(20/35,57.14%)神经元呈现簇发放电,有15个(15/35,42.86%)神经元呈现连续放电;在PD病理状态下有10个(10/12,85.71%)神经元呈现簇发放电,有2个(2/12,14.29%)神经元呈现连续放电(P<0.05)。生理状态下STN神经元的ISI序列散在分布于30～980ms之间;在PD病理状态下当STN神经元呈连续放电时,ISI分布于50～360ms之间,在150ms以下有一个分布密集条带,当STN神经元呈簇发放电时,ISI分布于30～470ms之间,在40ms以下有一个分布密集条带。结论PD猴模型STN神经元较生理状态下放电频率明显增加,其放电模式也有明显变化,簇状放电模式比例增大,ISI序列发生明显变化。     

Functional changes in thalamic relay neurons after focal cerebral infarct: a study of unit recordings from VPL neurons after MCA occlusion in rats.

We evaluated neuronal and histological changes of thalamic neurons 1, 4, 7, and 14 days after middle cerebral artery (MCA) occlusion in rats. After the somatosensory evoked potentials (SEPs) were measured from the cerebral cortex, the thalamic relay neuronal activities were recorded with a glass microelectrode following repetitive electrical stimulation of the contralateral forepaw at frequencies ranging from 1 to 50 Hz. In approximately 95% of the occluded rats, the ipsilateral somatosensory cortex and/or the subcortical somatosensory pathway developed infarct, resulting in SEP loss. We evaluated unit data from rats with abolished SEPs. The average firing rate of the nucleus ventralis posterolateralis (VPL) neurons in response to 25 stimulations at 30 Hz was significantly reduced to 0.1 spike/stimulus 1 day after MCA occlusion. In sham-operated rats, the same stimulation produced 0.7 spike/stimulus. The firing rate recovered to 0.4 spike/stimulus at 30-Hz stimulation 4 and 7 days after occlusion. This was followed by resuppression (0.1 spike/stimulus) 14 days after occlusion. Histological study revealed some abnormal neurons in the ipsilateral thalamus 7 days after occlusion. We were unable to find normal-shaped neurons in the VPL 14 days after occlusion. The present study demonstrates that cortical infarct produces functional and morphologic changes that gradually and progressively affect the ipsilateral thalamus, although incomplete transient recovery of somatosensory transmission may occur.     

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.     

Effect of deep brain stimulation of GPI on neuronal activity of the thalamic nucleus ventralis oralis in a dystonic patient.

OBJECTIVE: To record the possible effect of acute deep brain stimulation (DBS) of the globus pallidus internus (GPI) on the neuronal activity of the ventralis oralis anterior (VOA) nucleus of the thalamus. METHODS: Under general propofol anaesthesia, extracelullar single unit recordings were performed in VOA of a post-anoxic dystonic patient previously implanted with GPI located electrodes for chronic DBS. RESULTS: Neurons recorded in the VOA could be classified in two cell subpopulations: a high firing rate (16.5 Hz) and low burst index (BI; 15.6) type and a low firing rate (5.5 Hz) and high BI (35.6) type. GPI electrical stimulation reduced the frequency and increased the BI of the high firing rate cells while leaving the other cell type unchanged. CONCLUSION: These results demonstrate that pallidal DBS is able to inhibit a subpopulation of motor thalamic cells and question the pathophysiological model of dystonia based on a low firing rate of GPI cells.     

Tremor-related activity of neurons in the 'motor' thalamus: changes in firing rate and pattern in the MPTP vervet model of parkinsonism

The pathophysiology of parkinsonian tremor remains a matter of debate with two opposing hypotheses proposing a peripheral and a central origin, respectively. A central origin of tremor could arise either from a rhythmic activity of the internal segment of the globus pallidus (GPi) or from a structure such as the thalamus, outside the basal ganglia. In this study, single-unit recordings were performed in three 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys within the GPi and within three territories of the motor thalamus (delimited by their afferent inputs from the GPi, the substantia nigra and the cerebellum, respectively). For each recorded neuron, we compared the variations in firing rate and pattern in tremor and no tremor periods. Tremor either occurred spontaneously or was induced by external stimulation. When the animals entered into a tremor period we observed: (i) an increase in the mean firing rate in about half of the recorded neurons of the motor thalamus; and (ii), a change from an irregular to a rhythmic discharge within the range of tremor frequency (5-7 Hz) in about 10% of the recorded neurons of the motor thalamus (pallidal and cerebellar territories) and the GPi. Most of the thalamic neurons that exhibited a rhythmic discharge during tremor were found to be sensitive to external stimulation. Because the changes in firing rate occurred predominantly in the motor thalamus and not in the GPi, and because a fast rhythmic discharge of 10-15 Hz was frequently observed in the GPi and not in the motor thalamus, we conclude that thalamic activity is not a simple reproduction of basal ganglia output. Moreover, we suggest that thalamic processing of basal ganglia outputs could participate in the genesis of tremor, and that this thalamic processing could be influenced by sensory inputs and/or changes in attentional level elicited by external stimulation.     

The spontaneous firing patterns of forebrain neurons. IV. Effects of bilateral and unilateral frontal cortical ablations on firing of caudate, globus pallidus and thalamic neurons

To assess the effects of partial deafferentation of the neostriatum on spontaneous neuronal activity in the basal ganglia and related thalamic nuclei, ablations of frontal cortex were carried out in adult cats. Postoperative measures of interspike intervals of single neurons in the caudate nucleus, globus pallidus and ventral anterior-ventral lateral complex of the thalamus revealed a slowing of neuronal firing in these structures as compared with non-lesioned controls. The fact that deafferentation by cortical damage produces changes in neuronal firing in target neurons of the striatum (globus pallidus) and in thalamic neurons at least two synapses removed from the striatum is noteworthy. The possible extent to which these results might have been influenced by reduction of cortical inputs to or denervation of the thalamus is discussed.     

Receptive fields of thalamic neurons projecting to the motor cortex in the cat

The locations and receptive fields of thalamic neurons projecting to the motor cortex were examined and the following results were obtained. (1) Neurons located at the border area between nucleus ventralis lateralis (VL) and nucleus ventralis posterolateralis (VPL) could be activated antidromically from the motor cortex. (2) These neurons received topographically organized somesthetic inputs arising from skin and deep receptors. (3) The receptive fields of neurons in the small area of the motor cortex where these thalamic neurons projected could be examined in 8 instances. In 6 instances, the cortical neurons and the thalamic projection neurons were activated by exactly the same stimuli in the periphery. (4) Removal of the sensory cortex did not significantly change the characteristics of afferent inputs from the periphery to the motor cortex. (5) It is concluded that the motor cortex receives somesthetic inputs directly from the thalamus. The functional role of these inputs was discussed in relation to the known cortical reflexes.     

Effect of substantia nigra stimulation on identified neurons in the VL-VA thalamic complex: Comparison between intact and chronically decorticated cats

The effects of substantia nigra (SN) stimulation on the activity of the nucleus ventralis lateralis of the thalamus (VL) have been studied. The VL cells were identified as relay or non-relay cells among the cerebellothalamocortical pathway on the basis of orthodromical activation from the cerebellum and antidromical activation from the cortex. Certain experiments were performed after wide pericruciate decortication in order to eliminate the response due to unavoidable activation of corticofugal fibers. These results show that nigrothalamic neurons exert an inhibitory effect on VL cells. This inhibition was observed on the relay as well as on non-relay cells and was strong enought to suppress the cerebellar monosynaptic excitatory input. Thus the SN can modulate the information running along the cerebellothalamocortical pathway. The topographic localization of inhibited cells suggests that the SN controls the activity of the thalamic neurons which interfere with axial and proximal musculature.     

Different cellular types in mesopontine cholinergic nuclei related to ponto-geniculo-occipital waves

The only mesopontine neurons previously described as involved in the transfer of ponto-geniculo-occipital (PGO) waves from the brain stem to the thalamus were termed PGO-on bursting cells. We have studied, in chronically implanted cats, neuronal activities in brain-stem peribrachial (PB) and laterodorsal tegmental (LDT) cholinergic nuclei in relation to PGO waves recorded from the lateral geniculate (LG) thalamic nucleus during rapid-eye-movement (REM) sleep. We constructed peri-PGO histograms of PB/LDT cells' discharges and analyzed the interspike interval distribution during the period of increased neuronal activity related to PGO waves. Six categories of PGO-related PB/LDT neurons with identified thalamic projections were found: 4 classes of PGO-on cells: PGO-off but REM-on cells: and post-PGO cells. The physiological characteristics of a given cell class were stable even during prolonged recordings. One of these cell classes (1) represents the previously described PGO-on bursting neurons, while the other five (2-6) are newly discovered neuronal types. (1) Some neurons (16% of PGO-related cells) discharged stereotyped low-frequency (120-180 Hz) spike bursts preceding the negative peak of the LG-PGO waves by 20-40 msec. These neurons had low firing rates (0.5-3.5 Hz) during all states. (2) A distinct cell class (22% of PGO-related neurons) fired high-frequency spike bursts (greater than 500 Hz) about 20-40 msec prior to the thalamic PGO wave. These bursts were preceded by a period (150-200 msec) of discharge acceleration on a background of tonically increased activity during REM sleep. (3) PGO-on tonic neurons (20% of PGO-related neurons) discharged trains of repetitive single spikes preceding the thalamic PGO waves by 100-150 msec, but never fired high-frequency spike bursts. (4) Other PGO-on neurons (10% of PGO-related neurons) discharged single spikes preceding thalamic PGO waves by 15-30 msec. On the basis of parallel intracellular recordings in acutely prepared, reserpine-treated animals, we concluded that the PGO-on single spikes arise from conventional excitatory postsynaptic potentials and do not reflect tiny postinhibitory rebounds. (5) A peculiar cellular class, termed PGO-off elements (8% of PGO-related neurons), consisted of neurons with tonic, high discharge rates (greater than 30 Hz) during REM sleep. These neurons stopped firing 100-200 msec before and during the thalamic PGO waves. (6) Finally, other neurons discharged spike bursts or tonic spike trains 100-300 msec after the initially negative peak of the thalamic PGO field potential (post-PGO elements, 23% of PGO-related neurons).(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of ramped-frequency thalamic deep brain stimulation on tremor and activity of modeled neurons

ObjectiveWe conducted intraoperative measurements of tremor to quantify the effects of temporally patterned ramped-frequency DBS trains on tremor.MethodsSeven patterns of stimulation were tested in nine subjects with thalamic DBS for essential tremor: stimulation ‘off’, three ramped-frequency stimulation (RFS) trains from 130 → 50 Hz, 130 → 60 Hz, and 235 → 90 Hz, and three constant frequency stimulation (CFS) trains at 72, 82, and 130 Hz. The same patterns were applied to a computational model of the thalamic neural network.ResultsTemporally patterned 130 → 60 Hz ramped-frequency trains suppressed tremor relative to stimulation ‘off,’ but 130 → 50 Hz, 130 → 60 Hz, and 235 → 90 Hz ramped-frequency trains were no more effective than constant frequency stimulation with the same mean interpulse interval (IPI). Computational modeling revealed that rhythmic burst-driver inputs to thalamus were masked during DBS, but long IPIs, concurrent with pauses in afferent cerebellar and cortical firing, allowed propagation of bursting activity. The mean firing rate of bursting-type model neurons as well as the firing pattern entropy of model neurons were both strongly correlated with tremor power across stimulation conditions.ConclusionFrequency-ramped DBS produced equivalent tremor suppression as constant frequency thalamic DBS. Tremor-related thalamic burst activity may result from burst-driver input, rather than by an intrinsic rebound mechanism.SignificanceRamping stimulation frequency may exacerbate thalamic burst firing by introducing consecutive pauses of increasing duration to the stimulation pattern.