Semenov Iurii, Kim Vitalii, Silkuniene Giedre, Pakhomov Andrei G
Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA.
Present address: Department of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, CA 92697, USA.
Cell Rep Phys Sci. 2025 Jul 16;6(7). doi: 10.1016/j.xcrp.2025.102660. Epub 2025 Jun 16.
The capacity of temporal interference (TI) stimulation to target deep brain regions without affecting nearby surface electrodes remains uncertain. Using artifact-free optical recording, we compare excitation patterns and thresholds in hippocampal neurons stimulated by "pure" and amplitude-modulated sine waves, representing TI waveforms near electrodes and at the target, respectively. We show that pure 2- and 20-kHz sine waves induce repetitive firing at rates that increase up to 60-90 Hz with stronger electric fields. Beyond this limit, action potentials merge into sustained depolarization, resulting in an excitation block. Modulating the sine waves at 20 Hz aligns firing with amplitude "beats" and prevents the excitation block but does not lower excitation thresholds. Thus, off-target TI effects appear unavoidable, though the patterns of neuronal excitation and downstream effects may differ from those at the target. We further analyze membrane charging and relaxation kinetics at nanoscale resolution and confirm an excitation mechanism independent of envelope extraction.
时间干扰(TI)刺激在不影响附近表面电极的情况下靶向深部脑区的能力仍不确定。我们使用无伪迹光学记录,比较了分别由“纯”正弦波和调幅正弦波刺激的海马神经元的兴奋模式和阈值,这两种正弦波分别代表电极附近和靶点处的TI波形。我们发现,纯2 kHz和20 kHz正弦波以随着电场增强而增加至60 - 90 Hz的频率诱导重复放电。超过此极限,动作电位合并为持续去极化,导致兴奋阻滞。以20 Hz调制正弦波可使放电与幅度“拍频”同步并防止兴奋阻滞,但不会降低兴奋阈值。因此,尽管神经元兴奋模式和下游效应可能与靶点处不同,但脱靶TI效应似乎不可避免。我们进一步在纳米尺度分辨率下分析膜充电和弛豫动力学,并确认了一种独立于包络提取的兴奋机制。
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