Phase-dependent suppression of beta oscillations in Parkinson's disease patients
Phase-dependent suppression of beta oscillations in Parkinson's disease patients
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帕金森病患者β振荡的相位依赖性抑制
DOI：
10.1101/372599
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Holt A
中科院分区：
文献类型：
--
作者：
Holt A
大脑区域内部和之间的同步振荡有助于正常处理，但在疾病中往往会被放大。一个突出的例子是从帕金森病患者的皮层和丘脑底核记录到的异常持续的β频率（120 Hz）振荡。计算模型表明，这种振荡的幅度可以通过在特定相位施加刺激来调制。这种策略将允许选择性地瞄准振荡，对其他活动参数的影响相对较小。在这里，活动记录从10个清醒的，帕金森病患者（6名男性，4名女性人类受试者）进行功能性神经外科手术。我们证明，在连续的周期中，到达特定患者特定的β振荡阶段的刺激可以抑制高达40%的这种病理生理活动的振幅，而放大效应相对较弱。抑制效应伴随着丘脑底核（ESTA）神经元的节律输出和与内侧皮质同步的减少。虽然刺激可以改变海马神经元的尖峰模式，但对放电率没有净效应，这表明β同步性降低是尖峰活动相对时间改变的结果，而不是兴奋性的整体变化。总之，这些结果确定了皮质基底神经节同步性的一种新的内在特性，这表明正在进行的神经振荡的相位可能是治疗帕金森病的可行且有效的控制信号。这项工作具有潜在的影响，为其他脑部疾病夸张的神经元同步和探测功能的节奏活动在健康brain.Significance声明在帕金森氏病（PD），运动障碍与夸张的β频率振荡在大脑皮层和丘脑底核（PD）。在接受神经外科手术的PD患者中使用一种新的刺激方法，我们证明了当连续的电脉冲到达振荡的特定相位时，β-振荡可以被抑制。这种效应可能是因为中断了神经元活动的时间，而不是兴奋性，因为刺激改变了神经元尖峰的放电模式，而没有改变整体频率。这些发现显示了振荡相位作为“闭环”刺激的输入的潜力，这可以为治疗脑疾病和阐明神经元振荡在健康脑中的作用提供有价值的神经调节策略。
Synchronized oscillations within and between brain areas facilitate normal processing, but are often amplified in disease. A prominent example is the abnormally sustained beta-frequency (∼20 Hz) oscillations recorded from the cortex and subthalamic nucleus of Parkinson's disease patients. Computational modeling suggests that the amplitude of such oscillations could be modulated by applying stimulation at a specific phase. Such a strategy would allow selective targeting of the oscillation, with relatively little effect on other activity parameters. Here, activity was recorded from 10 awake, parkinsonian patients (6 male, 4 female human subjects) undergoing functional neurosurgery. We demonstrate that stimulation arriving on a particular patient-specific phase of the beta oscillation over consecutive cycles could suppress the amplitude of this pathophysiological activity by up to 40%, while amplification effects were relatively weak. Suppressive effects were accompanied by a reduction in the rhythmic output of subthalamic nucleus (STN) neurons and synchronization with the mesial cortex. While stimulation could alter the spiking pattern of STN neurons, there was no net effect on firing rate, suggesting that reduced beta synchrony was a result of alterations to the relative timing of spiking activity, rather than an overall change in excitability. Together, these results identify a novel intrinsic property of cortico-basal ganglia synchrony that suggests the phase of ongoing neural oscillations could be a viable and effective control signal for the treatment of Parkinson's disease. This work has potential implications for other brain diseases with exaggerated neuronal synchronization and for probing the function of rhythmic activity in the healthy brain.SIGNIFICANCE STATEMENTIn Parkinson's disease (PD), movement impairment is correlated with exaggerated beta frequency oscillations in the cerebral cortex and subthalamic nucleus (STN). Using a novel method of stimulation in PD patients undergoing neurosurgery, we demonstrate that STN beta oscillations can be suppressed when consecutive electrical pulses arrive at a specific phase of the oscillation. This effect is likely because of interrupting the timing of neuronal activity rather than excitability, as stimulation altered the firing pattern of STN spiking without changing overall rate. These findings show the potential of oscillation phase as an input for “closed-loop” stimulation, which could provide a valuable neuromodulation strategy for the treatment of brain disorders and for elucidating the role of neuronal oscillations in the healthy brain.