Zirh T A, Lenz F A, Reich S G, Dougherty P M
Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD 21287-7713, USA.
Neuroscience. 1998 Mar;83(1):107-21. doi: 10.1016/s0306-4522(97)00295-9.
It has been proposed that parkinsonian tremor is produced either by the activity of an intrinsic thalamic pacemaker or by the oscillation of an unstable long loop reflex arc. The former (central) hypothesis proposes that overactivity of neurons in the internal segment of the globus pallidus inhibits or hyperpolarizes thalamic neurons. When hyperpolarized, thalamic cells oscillate with bursting of the type associated with low threshold calcium spikes (low threshold spike-bursts). Low threshold spike-bursts can be identified by particular patterns of interspike intervals within the burst. The alternative (peripheral) hypothesis proposes that tremor results from oscillation of a reflex arc transmitting activity from muscle stretch receptors to thalamus, motor cortex, and back to the stretched muscle. When the gain of this reflex is increased, the arc may become unstable and oscillate. Oscillations produced by peripheral inputs may produce an acceleration-deceleration pattern within the burst which results in sinusoidal modulation of a spike train if bursting is periodic. We have assessed these two hypotheses by studying the pattern of interspike intervals occurring within bursts recorded in patients with parkinsonian tremor. The spike trains were analysed for 118 cells located in the ventral nuclear group including ventralis intermedius (thalamic cerebellar relay nucleus, n=48) and ventralis oralis posterior (thalamic pallidal relay nucleus, n=39) of patients with parkinsonian tremor. Two cells recorded in ventralis intermedius of a sleeping patient with chronic pain showed bursting activity similar to the low threshold spike-bursts recorded in sleeping animals, suggesting a common mechanism for low threshold spike-bursts across species. Forty-two cells recorded in patients with parkinsonian tremor (ventralis intermedius, n=19; ventralis oralis posterior, n=12) were classified as tremor-related cells because their activity was characterized by both a concentration of power at tremor frequency and significant correlation with tremor. Eleven tremor-related cells, 10 located in ventralis intermedius or ventralis oralis posterior and most responding to sensory inputs, had an acceleration-deceleration pattern of intraburst firing. Only one cell, a tremor-related cell in ventralis intermedius, showed the pattern expected of presumed low threshold spike-bursts. Therefore, intraburst interspike interval patterns consistent with either the central or the peripheral hypothesis were recorded in the thalamus of patients with parkinsonian tremor. Twenty-one tremor-related cells (15 cells in ventralis intermedius or ventralis oralis posterior) had bursts with intraburst interspike intervals which were independent of position of the interspike interval within the burst. Therefore, the activity of the majority of cells was not consistent with either hypothesis, suggesting that another oscillatory process may contribute to parkinsonian tremor.
有人提出，帕金森震颤要么是由丘脑内在起搏器的活动产生的，要么是由不稳定的长环反射弧的振荡产生的。前一种（中枢）假说认为，苍白球内侧段神经元的过度活动会抑制丘脑神经元或使其超极化。当丘脑神经元超极化时，它们会以与低阈值钙峰（低阈值峰-爆发）相关的爆发形式振荡。低阈值峰-爆发可以通过爆发内峰间间隔的特定模式来识别。另一种（外周）假说认为，震颤是由一个反射弧的振荡引起的，该反射弧将活动从肌肉牵张感受器传递到丘脑、运动皮层，然后再回到被拉伸的肌肉。当这个反射的增益增加时，这个弧可能会变得不稳定并振荡。外周输入产生的振荡可能会在爆发内产生加速-减速模式，如果爆发是周期性的，这会导致尖峰序列的正弦调制。我们通过研究帕金森震颤患者记录的爆发内峰间间隔模式来评估这两种假说。对位于腹侧核群的118个细胞的尖峰序列进行了分析，这些细胞来自帕金森震颤患者的腹中间核（丘脑小脑中继核，n = 48）和腹后外侧核（丘脑苍白球中继核，n = 39）。在一名患有慢性疼痛的睡眠患者的腹中间核中记录的两个细胞显示出与睡眠动物中记录的低阈值峰-爆发相似的爆发活动，这表明跨物种的低阈值峰-爆发存在共同机制。在帕金森震颤患者中记录的42个细胞（腹中间核，n = 19；腹后外侧核，n = 12）被归类为震颤相关细胞，因为它们的活动特征是在震颤频率处功率集中且与震颤有显著相关性。11个震颤相关细胞，其中10个位于腹中间核或腹后外侧核，并且大多数对感觉输入有反应，具有爆发内放电的加速-减速模式。只有一个细胞，即腹中间核中的一个震颤相关细胞，显示出假定的低阈值峰-爆发预期的模式。因此，在帕金森震颤患者的丘脑中记录到了与中枢或外周假说一致的爆发内峰间间隔模式。21个震颤相关细胞（腹中间核或腹后外侧核中有15个细胞）的爆发具有爆发内峰间间隔，这些间隔与爆发内峰间间隔的位置无关。因此，大多数细胞的活动与这两种假说都不一致，这表明另一种振荡过程可能导致帕金森震颤。
