Kang Qi, Talesh Amir Roshani, Lang Eric J, Sahin Mesut
Biomedical Engineering Department, New Jersey Institute of Technology, Newark, NJ, United States of America.
Department of Neuroscience and Physiology, and Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, United States of America.
J Neural Eng. 2024 Dec 13;21(6):066028. doi: 10.1088/1741-2552/ad9ad1.
Transcranial alternating current stimulation (tACS) and its variants are being tested in clinical trials for treatment of neurological disorders, and cerebellar tACS (ctACS) in particular has garnered much interest because of the involvement of the cerebellum in these disorders. The main objective of this study was to investigate the frequency tuning curves for the entrainment of the Purkinje cells (PCs) and the cerebellar nuclear (CN) cells by their axonal projections. In addition, we aimed to investigate the temporal and steady-state characteristics of the PC-CN transsynaptic modulation under clinically relevant stimulation waveforms.Experiments were conducted in anesthetized rats with the electrical stimulations applied to the cerebellar cortex while the spiking activity of PC and CN cells were recorded extracellularly. The PC-CN modulation was tested in a wide range of AC frequencies (1-1000 Hz). Furthermore, high-frequency AC stimulation (40-400 Hz) repeated at 4 Hz, that we termed, was tested for its transient and steady-state responses.. The CN cell firing patterns suggest that the population of projecting PCs that is entrained by the surface stimulation consists of the cells that are entrained in 180° opposite phases to each other. The CN cell spiking activity in general follows the entrainment pattern of the projecting PCs in the transient response. The CN entrainment during the steady-state turns into suppression at high frequencies of the stimulation. The PC responses could be explained with a simple statistical model that suggested that low-frequency (as well as DC) and high-frequency AC modulation may be operating through different neural mechanisms.High-frequency AC stimulation with a low-frequency envelope can be leveraged to induce CN modulation at theta frequencies. These results may explain some of the clinical findings and provide insight for future clinical trials of ctACS.
经颅交流电刺激(tACS)及其变体正在临床试验中用于治疗神经系统疾病,尤其是小脑经颅交流电刺激(ctACS),由于小脑参与这些疾病,它已引起了广泛关注。本研究的主要目的是研究通过轴突投射对浦肯野细胞(PCs)和小脑核(CN)细胞进行夹带的频率调谐曲线。此外,我们旨在研究在临床相关刺激波形下PC-CN突触调制的时间和稳态特征。在麻醉大鼠中进行实验,将电刺激施加于小脑皮质,同时在细胞外记录PC和CN细胞的放电活动。在广泛的交流频率(1 - 1000 Hz)范围内测试PC-CN调制。此外,还测试了以4 Hz重复的高频交流电刺激(40 - 400 Hz)的瞬态和稳态反应,我们将其称为……CN细胞的放电模式表明,被表面刺激夹带的投射PC群体由彼此相位相差180°的细胞组成。在瞬态反应中,CN细胞的放电活动通常遵循投射PC的夹带模式。在稳态期间,高频刺激时CN夹带会转变为抑制。PC反应可以用一个简单的统计模型来解释,该模型表明低频(以及直流)和高频交流调制可能通过不同的神经机制起作用。可以利用具有低频包络的高频交流电刺激来诱导θ频率下的CN调制。这些结果可能解释一些临床发现,并为未来ctACS的临床试验提供见解。