The Leslie & Susan Goldschmied (Gonda) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 52900, Israel.
The Leslie & Susan Goldschmied (Gonda) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 52900, Israel; Department of Neurobiology, The George S. Wise Faculty of Life Science & Sagol School for Neuroscience, Tel Aviv University, Tel Aviv 69978, ,Israel.
Neurobiol Dis. 2016 Sep;93:28-34. doi: 10.1016/j.nbd.2016.04.003. Epub 2016 Apr 12.
Parkinson's disease (PD) is characterized by excessive beta band oscillations (BBO) in neuronal spiking activity across basal ganglia (BG) nuclei. High frequency stimulation of the subthalamic nucleus, an effective treatment for PD, suppresses these oscillations. There is still a heated debate on the origin and propagation of BBO and their association to clinical symptoms. The key prerequisite in addressing these issues is to obtain an accurate estimation of the subpopulation of oscillatory neurons and the magnitude of their oscillations. Studies have shown that neurons in different BG nuclei vary dramatically in the magnitude of their oscillations. However, the stochastic nature of neuronal activity subsamples the oscillatory neuronal rate functions, thus causing standard spectral analysis methods to be dramatically biased by biological and experimental factors such as variations in the neuronal firing rate across BG nuclei. In order to overcome these biases, and directly analyze the expression of BBO within BG nuclei, we used a novel objective method, the modulation index. This method reveals that unlike previous spectral results, individual neurons in the different nuclei display similar magnitudes of oscillations, whereas only the size of the oscillatory subpopulation varies between nuclei. During stimulation, the magnitude of the BBO does not change but the fraction of oscillatory neurons decreases in the globus pallidus internus, leading to a significant change in BG output. This non-biased oscillation quantification thus enables the reconstruction of oscillations at the single neuron and nuclei population levels, and calls for a reassessment of the role of BBO during PD.
帕金森病(PD)的特征是基底神经节(BG)核内神经元放电活动中过度的β波段振荡(BBO)。丘脑底核的高频刺激是 PD 的一种有效治疗方法,它可以抑制这些振荡。关于 BBO 的起源、传播及其与临床症状的关系,仍存在激烈的争论。解决这些问题的关键前提是准确估计振荡神经元的亚群及其振荡幅度。研究表明,不同 BG 核中的神经元在其振荡幅度上存在显著差异。然而,神经元活动的随机性质会对振荡神经元的速率函数进行抽样,从而导致标准频谱分析方法受到生物和实验因素(如 BG 核内神经元放电率的变化)的严重偏差。为了克服这些偏差,并直接分析 BG 核内 BBO 的表达,我们使用了一种新的客观方法,即调制指数。该方法表明,与之前的光谱结果不同,不同核内的单个神经元显示出相似的振荡幅度,而只有振荡子群的大小在核之间发生变化。在刺激过程中,BBO 的幅度不变,但内苍白球中的振荡神经元比例下降,导致 BG 输出的显著变化。这种无偏差的振荡量化方法使得在单个神经元和核群体水平上重建振荡成为可能,并呼吁重新评估 BBO 在 PD 期间的作用。