Global cortical dynamics in sleep and general anesthesia

描述(申请人提供)：这项拟议的研究结合了生物物理学、统计信号处理、计算数据分析和神经生物学，以解决一个根本的跨学科问题：全球大脑状态是如何组织的？大脑在不同的全球状态下工作的能力，包括清醒、睡眠和全身麻醉，对人类健康和医学至关重要。这个项目旨在了解大脑皮层网络如何通过毫秒级的电信号相互作用，在宏观空间维度上自组织，以维持几分钟到几小时的全球状态。在人类中，脑电和脑磁图(EEG，MEG)和脑皮层脑电图仪(ECoG)可以探测毫秒级分辨率的神经动力学，但由于其微观电流来源的模糊性，解释具有挑战性。这个项目将使用新的，计算复杂的分析和现实的生物物理模型，结合大规模的生理记录，提供对皮质神经活动的本质的洞察，特别是睡眠和全身麻醉的全球组织。指导博士后阶段将建立在全麻诱导期间人类皮质动力学的电生理学研究的初步结果基础上。通过使用高密度脑电记录的高级统计信号处理，这项研究表明，在全身麻醉期间，无意识的大脑产生两种截然不同的节奏活动。这些模式无法用经典的功率谱方法区分，因此以前没有观察到。这些结果表明异丙酚全麻不是一种单一状态，而是由多个整体模式组成的。这些发现的意义将通过分析异丙酚全身麻醉引起的每种无意识状态下听觉刺激处理的变化来进行。通过对皮层事件相关电位的计算和统计分析，本项目将探索 受控听觉事件后神经活动的时间进程，以测试麻醉诱导和苏醒是否对感觉加工进行不同的调节。在这些研究中获得的初步结果将直接导致R00的独立研究。利用在癫痫治疗过程中植入电极阵列的患者的颅内记录，这项研究将提供人类第一个精细尺度的MAP 与全身麻醉相关的特定活动模式的空间组织。电流和磁通量通过人体头部多层介电组织的传播将被经验地测量。最后，从这些关于全身麻醉的研究中获得的知识和工具将被用来研究生理睡眠中节律性活动的组织，特别是旨在测试一种新的假说，即潜在睡眠纺锤体的回路。总之，这些研究将为理解清醒和无意识状态下整个大脑神经元活动的全球组织提供一个经验性验证的框架。

DESCRIPTION (provided by applicant): The proposed research combines biophysics, statistical signal processing, computational data analysis, and neurobiology, to address a fundamentally interdisciplinary problem: How are global brain states organized? The brain's ability to operate in distinct global states, including waking, sleep, and general anesthesia, is critical for human health and medicine. This project aims to understand how cortical networks, interacting via millisecond -scale electrical signals, self-organize over macroscopic spatial dimensions to sustain global states for minutes to hours. In humans, electro- and magnetoencephalography (EEG, MEG) and intracranial electrocorticography (ECoG) probe neural dynamics with ms-scale resolution, but interpretation is challenging due to the ambiguity of their microscopic current sources. This project will use new, computationally sophisticated analyses and realistic biophysical modeling, combined with large-scale physiological recordings, to provide insight into the nature of cortical neural activity, in particular the global organizatin of sleep and general anesthesia. The mentored postdoctoral phase will build on preliminary results from electrophysiological studies of human cortical dynamics during induction of general anesthesia. By using advanced statistical signal processing of high-density EEG recordings, this research showed that the unconscious brain during general anesthesia generates two categorically distinct types of rhythmic activity. These patterns are indistinguishable by classica power spectral methods and hence were not observed previously. These results indicate propofol general anesthesia is not a unitary state, but comprises multiple global mode. The implications of these findings will be pursued by analyzing how auditory stimulus processing is altered during each state of unconsciousness evoked by propofol general anesthesia. Through computational and statistical analysis of cortical event-related potentials this project will probe the time course of neural activity following controlled auditory events to test whether the induction and emergence from anesthesia modulate sensory processing differentially. The preliminary results obtained in these studies will lead directly to the R00 independent research. Using intracranial recordings, obtained from patients implanted with arrays of electrodes in the course of treatment for epilepsy, this study will provide the first map in humans of the fine-scale spatial organization of specific activity patterns associated with general anesthesia. The propagation of currents and magnetic flux through the multiple layers of dielectric tissue in the head of a human subject will be measured empirically. Finally, the knowledge and tools resulting from these studies of general anesthesia will be leveraged to investigate the organization of rhythmic activity in physiological sleep, specifically aiming to test a new hypothesis for the circuit under- lying sleep spindles. Together, these studies will provide an empirically validated framework for understanding the global organization of neuronal activity throughout the brain within waking and unconscious states.