Department of Biomedical Engineering, University of Minnesota, Minneapolis.
Institute for Translational Neuroscience, University of Minnesota, Minneapolis.
J Neurophysiol. 2020 Nov 1;124(5):1518-1529. doi: 10.1152/jn.00198.2020. Epub 2020 Sep 23.
The cerebellar-receiving area of the motor thalamus is the primary anatomical target for treating essential tremor with deep brain stimulation (DBS). Although neuroimaging studies have shown that higher stimulation frequencies in this target correlate with increased cortical metabolic activity, less is known about the cellular-level functional changes that occur in the primary motor cortex (M1) with thalamic stimulation and how these changes depend on the frequency of DBS. In this study, we used a preclinical animal model of DBS to collect single-unit spike recordings in M1 before, during, and after DBS targeting the cerebellar-receiving area of the motor thalamus (VPLo, nucleus ventralis posterior lateralis pars oralis). The effects of VPLo-DBS on M1 spike rates, interspike interval entropy, and peristimulus phase-locking were compared across stimulus pulse train frequencies ranging from 10 to 130 Hz. Although VPLo-DBS modulated the spike rates of 20-50% of individual M1 cells in a frequency-dependent manner, the population-level average spike rate only weakly depended on stimulation frequency. In contrast, the population-level entropy measure showed a pronounced decrease with high-frequency stimulation, caused by a subpopulation of cells that exhibited strong phase-locking and general spike-pattern regularization. Contrarily, low-frequency stimulation induced an entropy increase (spike-pattern disordering) in a relatively large portion of the recorded population, which diminished with higher stimulation frequencies. These results also suggest that changes in phase-locking and spike-pattern entropy are not necessarily equivalent pattern phenomena, but rather that they should both be weighed when quantifying stimulation-induced spike-pattern changes. The network mechanisms of thalamic deep brain stimulation (DBS) are not well understood at the cellular level. This study investigated the neuronal firing rate and pattern changes in the motor cortex resulting from stimulation of the cerebellar-receiving area of the motor thalamus. We showed that there is a nonintuitive relationship between general entropy-based spike-pattern measures and phase-locked regularization to DBS.
小脑接受区的运动丘脑是深部脑刺激（DBS）治疗原发性震颤的主要解剖靶点。尽管神经影像学研究表明，该靶点的刺激频率越高与皮质代谢活性的增加相关，但对于丘脑刺激时初级运动皮层（M1）中发生的细胞水平功能变化以及这些变化如何依赖于 DBS 的频率知之甚少。在这项研究中，我们使用了 DBS 的临床前动物模型，在刺激运动丘脑的小脑接受区（VPLo，腹后外侧核腹侧后外侧核 pars oralis）之前、期间和之后，在 M1 中收集单个单元尖峰记录。比较了 VPLo-DBS 对刺激脉冲串频率范围为 10 至 130 Hz 时 M1 尖峰率、尖峰间隔间隔熵和刺激相位锁定的影响。尽管 VPLo-DBS 以频率依赖性方式调制了 20-50％的个体 M1 细胞的尖峰率，但群体水平平均尖峰率仅与刺激频率弱相关。相比之下，群体水平熵测量值显示出随着高频刺激而明显降低，这是由表现出强烈的相位锁定和一般尖峰模式规则化的细胞亚群引起的。相反，低频刺激在记录的大部分群体中诱导了熵的增加（尖峰模式混乱），随着刺激频率的增加而减小。这些结果还表明，锁相和尖峰模式熵的变化不一定是等效的模式现象，而是在量化刺激诱导的尖峰模式变化时都应加以权衡。丘脑深部脑刺激（DBS）的网络机制在细胞水平上尚不清楚。本研究调查了刺激运动丘脑的小脑接受区引起的运动皮层神经元放电率和模式变化。我们表明，基于一般熵的尖峰模式测量值与 DBS 的锁相正则化之间存在非直观的关系。
