Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Canada.
Krembil Research Institute, University of Toronto, Ontario, Canada; Department of Physiology, Toronto Western Hospital and University of Toronto, Ontario, Canada.
Brain Stimul. 2021 May-Jun;14(3):513-530. doi: 10.1016/j.brs.2021.03.008. Epub 2021 Mar 20.
Electrical stimulation in the kilohertz-frequency range has gained interest in the field of neuroscience. The mechanisms underlying stimulation in this frequency range, however, are poorly characterized to date.
OBJECTIVE/HYPOTHESIS: To summarize the manifold biological effects elicited by kilohertz-frequency stimulation in the context of the currently existing literature and provide a mechanistic framework for the neural responses observed in this frequency range.
A comprehensive search of the peer-reviewed literature was conducted across electronic databases. Relevant computational, clinical, and mechanistic studies were selected for review.
The effects of kilohertz-frequency stimulation on neural tissue are diverse and yield effects that are distinct from conventional stimulation. Broadly, these can be divided into 1) subthreshold, 2) suprathreshold, 3) synaptic and 4) thermal effects. While facilitation is the dominating mechanism at the subthreshold level, desynchronization, spike-rate adaptation, conduction block, and non-monotonic activation can be observed during suprathreshold kilohertz-frequency stimulation. At the synaptic level, kilohertz-frequency stimulation has been associated with the transient depletion of the available neurotransmitter pool - also known as synaptic fatigue. Finally, thermal effects associated with extrinsic (environmental) and intrinsic (associated with kilohertz-frequency stimulation) temperature changes have been suggested to alter the neural response to stimulation paradigms.
The diverse spectrum of neural responses to stimulation in the kilohertz-frequency range is distinct from that associated with conventional stimulation. This offers the potential for new therapeutic avenues across stimulation modalities. However, stimulation in the kilohertz-frequency range is associated with distinct challenges and caveats that need to be considered in experimental paradigms.
在神经科学领域，千赫兹频率范围内的电刺激引起了人们的兴趣。然而，迄今为止，这种频率范围内刺激的机制还没有得到很好的描述。
目的/假设：总结目前文献中千赫兹频率刺激引起的多种生物学效应，并为该频率范围内观察到的神经反应提供一个机制框架。
对电子数据库进行了全面的同行评议文献检索。选择了相关的计算、临床和机制研究进行综述。
千赫兹频率刺激对神经组织的影响是多种多样的，产生的效果与传统刺激明显不同。广义上，这些可以分为 1）亚阈，2）阈上，3）突触和 4）热效应。虽然在亚阈水平上促进作用是主要机制，但在阈上千赫兹频率刺激时，可以观察到去同步化、尖峰率适应、传导阻滞和非单调激活。在突触水平上，千赫兹频率刺激与可利用神经递质池的短暂耗竭有关，也称为突触疲劳。最后，与环境（外部）和内在（与千赫兹频率刺激相关）温度变化相关的热效应被认为会改变对刺激模式的神经反应。
千赫兹频率范围内刺激引起的神经反应的多样性与传统刺激相关的反应明显不同。这为跨刺激模式的新治疗途径提供了潜力。然而，千赫兹频率范围内的刺激与独特的挑战和注意事项相关，这些在实验范式中需要考虑。
