BACKGROUND Approaches to predictably control neural oscillations are needed to understand their causal role in brain function in healthy or diseased states and to advance the development of neuromodulation therapies. In this study, we present a closed-loop neural control and optimization framework to actively suppress or amplify low-frequency neural oscillations observed in local field potentials in real-time by using electrical stimulation. OBJECTIVE /Hypothesis: The rationale behind this control approach and our working hypothesis is that neural oscillatory activity evoked by electrical pulses can suppress or amplify spontaneous oscillations via destructive or constructive interference when stimulation pulses are continuously delivered with appropriate amplitudes and at precise phases of these oscillations in a closed-loop scheme. METHODS We tested our hypothesis in two nonhuman primates that exhibited a robust increase in low-frequency (8-30 Hz) oscillatory power in the subthalamic nucleus (STN) following administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To test our neural control approach, we targeted 8-17 Hz oscillations and used electrode arrays and electrical stimulation waveforms similar to those used in humans chronically implanted with brain stimulation systems. Stimulation parameters that maximize the suppression or amplification of neural oscillations were predicted using mathematical models of the stimulation evoked oscillations. RESULTS Our neural control and optimization approach was capable of actively and robustly suppressing or amplifying oscillations in the targeted frequency band (8-17 Hz) in real-time in the studied subjects. CONCLUSIONS The results from this study support our hypothesis and suggest that the proposed neural control framework allows one to characterize in controlled experiments the functional role of frequency-specific neural oscillations by using electrodes and stimulation waveforms currently being employed in humans.

中文翻译：

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使用刺激诱发振荡实时抑制和放大频率特异性神经活动

背景技术需要可预测地控制神经振荡的方法，以了解它们在健康或患病状态下的脑功能中的因果作用，并推进神经调节疗法的发展。在这项研究中，我们提出了一种闭环神经控制和优化框架，通过使用电刺激来主动抑制或放大在局部场电位中实时观察到的低频神经振荡。目标/假设：这种控制方法背后的基本原理和我们的工作假设是，当刺激脉冲以适当的幅度和精确的振荡相位连续传递时，由电脉冲引起的神经振荡活动可以通过破坏性或建设性干扰来抑制或放大自发振荡在闭环方案中。方法 我们在两种非人类灵长类动物身上检验了我们的假设，在给予神经毒素 1-甲基-4-苯基-1,2 后，它们的丘脑底核 (STN) 低频 (8-30 Hz) 振荡功率显着增加， 3,6-四氢吡啶（MPTP）。为了测试我们的神经控制方法，我们以 8-17 Hz 振荡为目标，并使用与长期植入脑刺激系统的人类所使用的电极阵列和电刺激波形类似的波形。使用刺激诱发振荡的数学模型来预测最大化抑制或放大神经振荡的刺激参数。结果我们的神经控制和优化方法能够主动、稳健地抑制或放大研究对象实时目标频段（8-17 Hz）的振荡。结论 这项研究的结果支持我们的假设，并表明所提出的神经控制框架允许人们通过使用目前在人类中使用的电极和刺激波形在受控实验中表征频率特异性神经振荡的功能作用。