Global cortical dynamics in sleep and general anesthesia

睡眠和全身麻醉中的整体皮质动态

• 批准号: 8424933
• 负责人: ERAN A MUKAMEL
• 金额: $ 8.49万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8424933
• 关键词: Action Potentials; Address; Affect; Anesthesia procedures; Animal Model; Auditory; Auditory Evoked Potentials; Base of the Brain; Biological Markers; Biophysics; Brain; Brain Part; Brain imaging; Brain region; Clinic; Clinical Treatment; Collaborations; Communication; Conflict (Psychology); Coupling; Data; Data Analyses; Diagnosis; Dimensions; Disease; Electrocorticogram; Electrodes; Electroencephalography; Epilepsy; Esthesia; Event; Event-Related Potentials; General Anesthesia; Head; Health; Hour; Human; Implant; Individual; Intractable Epilepsy; Knowledge; Lead; Magnetic Resonance Imaging; Magnetism; Magnetoencephalography; Maps; Measures; Medicine; Mentors; Methods; Microelectrodes; Microscopic; Mining; Modeling; Modern Medicine; Monitor; Nature; Neural Network Simulation; Neurobiology; Neurologist; Neurons; Neurosciences; Neurosurgeon; Patient Monitoring; Patients; Pattern; Phase; Physiological; Physiology; Propofol; Recovery; Research; Resolution; Sensory Process; Signal Transduction; Site; Sleep; Source; Stereotyping; Structure; Techniques; Testing; Thalamic structure; Time; Tissues; Unconscious State; Validation; Work; auditory stimulus; base; computational neuroscience; computerized data processing; density; design; human subject; imaging modality; insight; millisecond; neuroimaging; neuroregulation; reconstruction; relating to nervous system; response; stimulus processing; tool

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. PUBLIC HEALTH RELEVANCE: The proposed research will investigate how brain activity changes during transitions between different states such as waking and sleep, as well as during the induction of general anesthesia. We aim to understand how the normal communication between neurons in different parts of the brain is disrupted following the loss of consciousness during sleep or general anesthesia. Such an understanding will help design better techniques for monitoring patients during induction of general anesthesia, and will be useful for diagnosing and treating disorders that affect sleep.

描述（由申请人提供）：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，对人类健康和医学至关重要。该项目旨在了解皮层网络如何通过毫秒级电信号相互作用，在宏观空间维度上自我组织，以维持几分钟到几小时的全局状态。在人类中，脑电和脑磁图（EEG， MEG）和颅内皮质电图（ECoG）以毫秒级分辨率探测神经动力学，但由于其微观电流来源的模糊性，解释具有挑战性。该项目将使用新的、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，来深入了解皮层神经活动的本质，特别是睡眠和全身麻醉的整体组织。受指导的博士后阶段将建立在全身麻醉诱导时人体皮质动力学的电生理研究的初步结果之上。通过对高密度脑电图记录进行先进的统计信号处理，本研究表明，全身麻醉时无意识的大脑产生两种截然不同的节律活动类型。这些模式是无法区分的经典功率谱方法，因此没有观察到以前。这些结果表明异丙酚全身麻醉不是一个单一的状态，而是包含多个全局模式。这些发现的意义将通过分析在异丙酚全身麻醉引起的每个无意识状态下听觉刺激处理是如何改变的来实现。通过计算和统计分析，本项目将探讨皮层事件相关电位