Gottshall Jackie L, Adams Zoe M, Forgacs Peter B, Schiff Nicholas D
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, United States.
Department of Neurology, Weill Cornell Medicine, New York, NY, United States.
Front Neurol. 2019 Feb 4;10:20. doi: 10.3389/fneur.2019.00020. eCollection 2019.
Loss of organized sleep electrophysiology is a characteristic finding following severe brain injury. The return of structured elements of sleep architecture has been associated with positive prognosis across injury etiologies, suggesting a role for sleep dynamics as biomarkers of wakeful neuronal circuit function. In a continuing study of one minimally conscious state patient studied over the course of ~8½ years, we sought to investigate whether changes in daytime brain activation induced by central thalamic deep brain stimulation (CT-DBS) influenced sleep electrophysiology. In this patient subject, we previously reported significant improvements in sleep electrophysiology during 5½ years of CT-DBS treatment, including increased sleep spindle frequency and SWS delta power. We now present novel findings that many of these improvements in sleep electrophysiology regress following CT-DBS discontinuation; these regressions in sleep features correlate with a significant decrease in behavioral responsiveness. We also observe the re-emergence of alpha-delta sleep, which had been previously suppressed by daytime CT-DBS in this patient subject. Importantly, CT-DBS was only active during the daytime and has been proposed to mediate recovery of consciousness by driving synaptic activity across frontostriatal systems through the enhancement of thalamocortical output. Accordingly, the improvement of sleep dynamics during daytime CT-DBS and their subsequent regression following CT-DBS discontinuation implicates wakeful synaptic activity as a robust modulator of sleep electrophysiology. We interpret these findings in the context of the "synaptic homeostasis hypothesis," whereby we propose that daytime upregulation of thalamocortical output in the severely injured brain may facilitate organized frontocortical circuit activation and yield net synaptic potentiation during wakefulness, providing a homeostatic drive that reconstitutes sleep dynamics over time. Furthermore, we consider common large-scale network dynamics across several neuropsychiatric disorders in which alpha-delta sleep has been documented, allowing us to formulate a novel mechanistic framework for alpha-delta sleep generation. We conclude that the bi-directional modulation of sleep electrophysiology by daytime thalamocortical activity in the severely injured brain: (1) emphasizes the cyclical carry-over effects of state-dependent circuit activation on large-scale brain dynamics, and (2) further implicates sleep electrophysiology as a sensitive indicator of wakeful brain activation and covert functional recovery in the severely injured brain.
有组织的睡眠电生理丧失是重度脑损伤后的一个典型表现。睡眠结构要素的恢复与各种损伤病因的良好预后相关，这表明睡眠动态作为清醒神经元回路功能生物标志物的作用。在一项对一名处于最低意识状态的患者进行的持续约8.5年的研究中，我们试图探究丘脑中央深部脑刺激（CT-DBS）引起的白天脑激活变化是否会影响睡眠电生理。在该患者中，我们之前报道了在5.5年的CT-DBS治疗期间睡眠电生理有显著改善，包括睡眠纺锤波频率增加和慢波睡眠δ波功率增加。我们现在呈现新的发现，即CT-DBS停止后，睡眠电生理的许多这些改善会消退；这些睡眠特征的消退与行为反应性的显著下降相关。我们还观察到α-δ睡眠重新出现，在该患者中，α-δ睡眠此前被白天的CT-DBS抑制。重要的是，CT-DBS仅在白天激活，并且已被提出通过增强丘脑皮质输出驱动额纹状体系统的突触活动来介导意识恢复。因此，白天CT-DBS期间睡眠动态的改善及其在CT-DBS停止后的随后消退表明清醒突触活动是睡眠电生理的强大调节因子。我们在“突触稳态假说”的背景下解释这些发现，据此我们提出，重度损伤大脑中丘脑皮质输出的白天上调可能促进有组织的额叶皮质回路激活，并在清醒期间产生净突触增强，提供一种稳态驱动力，随着时间推移重新构建睡眠动态。此外，我们考虑了几种记录到α-δ睡眠的神经精神疾病中常见的大规模网络动态，这使我们能够为α-δ睡眠的产生制定一个新的机制框架。我们得出结论，重度损伤大脑中白天丘脑皮质活动对睡眠电生理的双向调节：（1）强调了状态依赖性回路激活对大规模脑动态的周期性延续效应，（2）进一步表明睡眠电生理是重度损伤大脑中清醒脑激活和隐性功能恢复的敏感指标。
