Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom.
MRC Brain Network Dynamics Unit, University of Oxford, Oxford, United Kingdom.
J Neural Eng. 2023 Mar 7;20(2). doi: 10.1088/1741-2552/acbc4a.
While brain stimulation therapies such as deep brain stimulation for Parkinson's disease (PD) can be effective, they have yet to reach their full potential across neurological disorders. Entraining neuronal rhythms using rhythmic brain stimulation has been suggested as a new therapeutic mechanism to restore neurotypical behaviour in conditions such as chronic pain, depression, and Alzheimer's disease. However, theoretical and experimental evidence indicate that brain stimulation can also entrain neuronal rhythms at sub- and super-harmonics, far from the stimulation frequency. Crucially, these counterintuitive effects could be harmful to patients, for example by triggering debilitating involuntary movements in PD. We therefore seek a principled approach to selectively promote rhythms close to the stimulation frequency, while avoiding potential harmful effects by preventing entrainment at sub- and super-harmonics.Our open-loop approach to selective entrainment, dithered stimulation, consists in adding white noise to the stimulation period.We theoretically establish the ability of dithered stimulation to selectively entrain a given brain rhythm, and verify its efficacy in simulations of uncoupled neural oscillators, and networks of coupled neural oscillators. Furthermore, we show that dithered stimulation can be implemented in neurostimulators with limited capabilities by toggling within a finite set of stimulation frequencies.Likely implementable across a variety of existing brain stimulation devices, dithering-based selective entrainment has potential to enable new brain stimulation therapies, as well as new neuroscientific research exploiting its ability to modulate higher-order entrainment.
虽然脑刺激疗法，如深部脑刺激治疗帕金森病（PD），可以有效，但它们尚未在神经障碍中充分发挥作用。使用节律性脑刺激来调整神经元节律被认为是一种新的治疗机制，可以恢复慢性疼痛、抑郁和阿尔茨海默病等疾病的神经典型行为。然而，理论和实验证据表明，脑刺激也可以在亚谐波和超谐波上调整神经元节律，远离刺激频率。至关重要的是，这些违反直觉的效应可能对患者有害，例如在 PD 中引发使人衰弱的不自主运动。因此，我们寻求一种有原则的方法来选择性地促进接近刺激频率的节律，同时通过防止在亚谐波和超谐波上的调整来避免潜在的有害影响。我们的开环选择性调整方法，抖动刺激，包括在刺激期间添加白噪声。我们从理论上确立了抖动刺激选择性调整给定脑节律的能力，并在未耦合神经振荡器和耦合神经振荡器网络的模拟中验证了其功效。此外，我们表明，抖动刺激可以通过在有限的刺激频率集合内切换来在具有有限能力的神经刺激器中实现。可能适用于各种现有的脑刺激设备，基于抖动的选择性调整有可能实现新的脑刺激疗法，以及利用其调整更高阶调整能力的新神经科学研究。
