Global cortical dynamics in sleep and general anesthesia

项目总结/摘要 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， 神经生物学，以解决一个根本性的跨学科问题：全球大脑状态是如何组织的？ 大脑在不同的全局状态下运作的能力，包括清醒、睡眠和全身麻醉，是至关重要的 对人类健康和医学的贡献。该项目旨在了解皮层网络如何通过毫秒- 在宏观空间维度上自组织以维持全局状态， 几分钟到几小时在人类中，脑电图和脑磁图（EEG，MEG）和颅内皮层电图， 脑电描记术（ECoG）探测神经动力学与毫秒级的分辨率，但解释是具有挑战性的，由于 其微观电流源的模糊性。该项目将使用新的，计算复杂的分析- ses和逼真的生物物理建模，结合大规模的生理记录，以提供洞察力 皮质神经活动的本质，特别是睡眠和全身麻醉的整体组织。 指导博士后阶段将建立在胡锦涛电生理研究的初步结果， 全身麻醉诱导过程中的人皮质动力学。通过使用先进的统计信号处理 高密度脑电图记录，这项研究表明，无意识的大脑在全身麻醉期间， 产生两种截然不同的节奏活动这些模式是无法区分的经典 功率谱方法，因此以前没有观察到。这些结果表明丙泊酚一般和- 感觉不是一个单一的状态，而是包含着多种整体模式。这些发现的意义将是 通过分析在每种无意识状态下听觉刺激的处理过程是如何改变的， 异丙酚全身麻醉引起的。通过计算和统计分析皮层事件相关的 潜在的，这个项目将探讨神经活动的时间过程后，控制听觉事件，以测试 麻醉诱导和麻醉苏醒是否对感觉加工有不同的调节。 在这些研究中获得的初步结果将直接导致R 00的独立研究。使用 颅内记录，从在治疗过程中植入电极阵列的患者获得， 癫痫，这项研究将提供第一张人类特定活动的精细尺度空间组织图。 与全身麻醉相关的模式。电流和磁通量通过多个 将凭经验测量人类受试者头部中的介电组织的多层。最后，知识- 从这些全身麻醉研究中获得的优势和工具将被用来研究组织， 生理睡眠中的节律活动，特别是旨在测试一个新的假设下的电路- 说谎的睡眠纺锤波总之，这些研究将提供一个经验验证的框架， 在清醒和无意识状态下整个大脑神经元活动的整体组织。

Project Summary/Abstract 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 millisec- ond-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 electrocorti- cography (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 analy- ses and realistic biophysical modeling, combined with large-scale physiological recordings, to provide insight into the nature of cortical neural activity, in particular the global organization of sleep and general anesthesia. The mentored postdoctoral phase will build on preliminary results from electrophysiological studies of hu- man 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 classical power spectral methods and hence were not observed previously. These results indicate propofol general an- esthesia 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 multi- ple layers of dielectric tissue in the head of a human subject will be measured empirically. Finally, the knowl- edge and tools resulting from these studies of general anesthesia will be leveraged to investigate the organiza- tion 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.