Transcranial magnetic stimulation (TMS) has been widely used in human cognitive neuroscience to examine the causal role of distinct cortical areas in perceptual, cognitive and motor functions. However, it is widely acknowledged that the effects of focal cortical stimulation can vary substantially between participants and even from trial to trial within individuals. Recent work from resting state functional magnetic resonance imaging (fMRI) studies has suggested that spontaneous fluctuations in alertness over a testing session can modulate the neural dynamics of cortical processing, even when participants remain awake and responsive to the task at hand. Here we investigated the extent to which spontaneous fluctuations in alertness during wake-to-sleep transition can account for the variability in neurophysiological responses to TMS. We combined single-pulse TMS with neural recording via electroencephalography (EEG) to quantify changes in motor and cortical reactivity with fluctuating levels of alertness defined objectively on the basis of ongoing brain activity. We observed rapid, non-linear changes in TMS-evoked responses with decreasing levels of alertness, even while participants remained responsive in the behavioural task. Specifically, we found that the amplitude of motor evoked potentials peaked during periods of EEG flattening, whereas TMS-evoked potentials increased and remained stable during EEG flattening and the subsequent occurrence of theta ripples that indicate the onset of NREM stage 1 sleep. Our findings suggest a rapid and complex reorganization of active neural networks in response to spontaneous fluctuations of alertness over relatively short periods of behavioural testing during wake-to-sleep transition.

中文翻译：

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执行任务时的警觉性波动调节皮层对经颅磁刺激的诱发反应

经颅磁刺激 (TMS) 已广泛用于人类认知神经科学，以检查不同皮质区域在感知、认知和运动功能中的因果作用。然而，人们普遍承认，局灶性皮层刺激的效果在参与者之间可能会有很大差异，甚至在个人内部的不同试验之间也可能存在差异。最近静息状态功能磁共振成像 (fMRI) 研究的工作表明，即使参与者保持清醒并对手头的任务做出反应，测试期间警觉性的自发波动可以调节皮质处理的神经动力学。在这里，我们调查了从清醒到睡眠过渡期间警觉性的自发波动在多大程度上可以解释对 TMS 的神经生理反应的变异性。我们将单脉冲 TMS 与通过脑电图 (EEG) 的神经记录相结合，以根据持续的大脑活动客观定义的波动的警觉水平来量化运动和皮质反应性的变化。我们观察到 TMS 诱发反应的快速、非线性变化随着警觉水平的降低，即使参与者在行为任务中保持响应。具体而言，我们发现运动诱发电位的幅度在 EEG 平坦化期间达到峰值，而 TMS 诱发电位在 EEG 平坦化期间增加并保持稳定，随后出现表明 NREM 第 1 阶段睡眠开始的 theta 波纹。