Wang Zhaoxiang, Feng Zhouyan, Wei Xuefeng
Key Lab of Biomedical Engineering for Education Ministry, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China.
Department of Biomedical Engineering, The College of New Jersey, Ewing, NJ, United States.
Front Neurosci. 2018 Oct 24;12:783. doi: 10.3389/fnins.2018.00783. eCollection 2018.
Deep brain stimulation (DBS) has been used for treating many brain disorders. Clinical applications of DBS commonly require high-frequency stimulations (HFS, ∼100 Hz) of electrical pulses to obtain therapeutic efficacy. It is not clear whether the electrical energy of HFS functions other than generating firing of action potentials in neuronal elements. To address the question, we investigated the reactions of downstream neurons to pulse sequences with a frequency in the range 50-200 Hz at afferent axon fibers in the hippocampal CA1 region of anesthetized rats. The results show that the mean rates of neuronal firing induced by axonal HFS were similar even for an up to fourfold difference (200:50) in the number and thereby in the energy of electrical pulses delivered. However, HFS with a higher pulse frequency (100 or 200 Hz) generated more randomness in the firing pattern of neurons than a lower pulse frequency (50 Hz), which were quantitatively evaluated by the significant changes of two indexes, namely, the peak coefficients and the duty ratios of excitatory phase of neuronal firing, induced by different frequencies (50-200 Hz). The findings indicate that a large portion of the HFS energy might function to generate a desynchronization effect through a possible mechanism of intermittent depolarization block of neuronal membranes. The present study addresses the demand of high frequency for generating HFS-induced desynchronization in neuronal activity, which may play important roles in DBS therapy.
深部脑刺激（DBS）已被用于治疗多种脑部疾病。DBS的临床应用通常需要对电脉冲进行高频刺激（HFS，约100Hz）以获得治疗效果。目前尚不清楚HFS的电能除了在神经元元件中引发动作电位发放外是否还有其他作用。为了解决这个问题，我们在麻醉大鼠海马CA1区的传入轴突纤维上，研究了下游神经元对频率在50-200Hz范围内的脉冲序列的反应。结果表明，即使电脉冲数量相差高达四倍（200:50），从而电能也相差四倍，轴突HFS诱导的神经元发放平均速率仍相似。然而，较高脉冲频率（100或200Hz）的HFS比低脉冲频率（50Hz）在神经元发放模式上产生了更多的随机性，这通过两个指标的显著变化进行了定量评估，即由不同频率（50-200Hz）诱导的神经元发放的峰值系数和兴奋期占空比。这些发现表明，HFS的大部分能量可能通过神经元膜间歇性去极化阻滞的可能机制发挥作用，以产生去同步化效应。本研究满足了在神经元活动中产生HFS诱导的去同步化所需的高频要求，这可能在DBS治疗中发挥重要作用。
