Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, United States of America.
Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, United States of America.
J Neural Eng. 2024 Jun 13;21(3). doi: 10.1088/1741-2552/ad5407.
. Therapeutic brain stimulation is conventionally delivered using constant-frequency stimulation pulses. Several recent clinical studies have explored how unconventional and irregular temporal stimulation patterns could enable better therapy. However, it is challenging to understand which irregular patterns are most effective for different therapeutic applications given the massively high-dimensional parameter space.. Here we applied many irregular stimulation patterns in a single neural circuit to demonstrate how they can enable new dimensions of neural control compared to conventional stimulation, to guide future exploration of novel stimulation patterns in translational settings. We optogenetically excited the septohippocampal circuit with constant-frequency, nested pulse, sinusoidal, and randomized stimulation waveforms, systematically varying their amplitude and frequency parameters.We first found equal entrainment of hippocampal oscillations: all waveforms provided similar gamma-power increase, whereas no parameters increased theta-band power above baseline (despite the mechanistic role of the medial septum in driving hippocampal theta oscillations). We then compared each of the effects of each waveform on high-dimensional multi-band activity states using dimensionality reduction methods. Strikingly, we found that conventional stimulation drove predominantly 'artificial' (different from behavioral activity) effects, whereas all irregular waveforms induced activity patterns that more closely resembled behavioral activity.. Our findings suggest that irregular stimulation patterns are not useful when the desired mechanism is to suppress or enhance a single frequency band. However, novel stimulation patterns may provide the greatest benefit for neural control applications where entraining a particular mixture of bands (e.g. if they are associated with different symptoms) or behaviorally-relevant activity is desired.
. 治疗性脑刺激通常使用恒定频率的刺激脉冲进行。最近的几项临床研究探索了非常规和不规则的时变刺激模式如何能够实现更好的治疗效果。然而，由于参数空间极高维度，理解对于不同的治疗应用哪种不规则模式最有效是具有挑战性的。. 在这里，我们在单个神经回路中应用了许多不规则的刺激模式，以证明与传统刺激相比，它们如何能够为神经控制带来新的维度，从而为在转化环境中探索新型刺激模式提供指导。我们用光遗传学刺激隔海马回路，使用恒定频率、嵌套脉冲、正弦和随机刺激波形，系统地改变它们的幅度和频率参数。. 我们首先发现海马体振荡的同步性相等：所有波形都提供了相似的伽马功率增加，而没有任何参数将 theta 波段功率增加到基线以上（尽管中隔核在驱动海马体 theta 振荡方面具有机制作用）。然后，我们使用降维方法比较了每种波形对高维多波段活动状态的影响。引人注目的是，我们发现传统刺激主要驱动“人为”（与行为活动不同）效应，而所有不规则波形诱导的活动模式更接近行为活动。. 我们的发现表明，当期望的机制是抑制或增强单个频带时，不规则刺激模式并不有用。然而，对于那些需要调制特定波段（例如，它们与不同症状相关）或与行为相关的活动的神经控制应用，新型刺激模式可能会提供最大的益处。
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