Brain Network Mechanism of Fast and Slow Recoveries in Pharmacologically and Pathologically Induced Unconsciousness

药理学和病理学引起的无意识快速和慢速恢复的脑网络机制

• 批准号: 10284145
• 负责人: UnCheol Lee
• 金额: $ 23.4万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10284145
• 关键词: Anesthesia procedures; Anesthetics; Arousal; Behavioral; Biological Models; Brain; Brain imaging; Cell Nucleus; Clinical; Coma; Complex; Computer Models; Conscious; Consciousness Disorders; Data; Development; Disease; Epilepsy; Failure; Foundations; General Anesthesia; Goals; Human; Intervention; Knowledge; Lead; Legal patent; Link; Mediating; Minimally Conscious States; Mission; Modeling; Monitor; National Institute of General Medical Sciences; Neurobiology; Neurons; Outcome; Pathologic; Patients; Pharmacology; Physics; Prefrontal Cortex; Process; Public Health; Rattus; Recovery; Reporting; Research; Research Proposals; Sleep; Syndrome; System; Testing; Tetrodotoxin; Time; Unconscious State; Wakefulness; Work; base; behavioral outcome; biological systems; cholinergic; clinical care; human subject; imaging study; insight; mind control; neural circuit; neuroimaging; novel strategies; predictive modeling; translational study

Project Summary/Abstract It is not understood why some patients recover from unconsciousness (anesthesia and coma) at a relatively faster rate while others show prolonged recovery times; or do not recover at all from coma. Traditionally, the approaches to fill this critical gap in our knowledge has focused on the subcortical nuclei linked to the states of arousal (sleep, wake, anesthesia), but recent neuroimaging studies suggest that consciousness, rather than being a product of a localized neural circuit, is likely to be an emergent phenomenon resulting from complex interactions between spatially and temporally distributed activity of neurons across the brain. Accumulating evidences suggest that criticality, an optimal balanced state between order and disorder, in the brain presents highly informative, integrative, and sensitive state such that it has been suggested as a necessary condition for the emergence of consciousness. We recently demonstrated that the level of consciousness during general anesthesia correlates with the degree of brain criticality, and similar findings have been reported from other groups. Therefore, we hypothesize that facilitating the brain networks towards criticality will accelerate the recovery of consciousness from anesthesia and disorders of consciousness. However, controlling criticality is a challenging problem and has not been attempted in the brain networks. Using a novel approach, we will apply explosive synchronization, a phenomenon wherein a small perturbation to a network can lead to an abrupt state transition through global network synchronization, to control brain criticality. By reconceptualizing the mechanism of explosive synchronization as a mechanism of criticality transition, we will be able to systematically study fast and slow transitions in brain criticality and the effect on state transitions. Our long-term goal is to use the principles of physics to develop neuroscientific foundations for the strategies to accelerate the recovery from anesthesia and coma. The objective of the proposed studies is to explore explosive synchronization as a mechanism for the recovery of consciousness. The rationale for the proposed research is that characterization of the relationship between criticality transition and fast/slow recovery of consciousness will provide insights into the fundamental network level mechanisms that govern fast and slow state transitions and will also help inform translational studies aimed at accelerating recovery from unconsciousness. We will pursue the following two specific aims: 1) Determine the relationship between explosive synchronization in the brain networks and the recovery of consciousness from anesthesia and coma. We will use computational modeling to identify the brain network conditions linked to fast and slow state transitions, and test the model predictions using empirical data from anesthesia (human and rat) and coma (human) studies. 2) Determine the causal effect of changes in brain network criticality on the recovery of consciousness from anesthesia in rat. We will use our recently reported rat models of fast and slow recovery of consciousness from anesthesia to investigate a causal relationship between recovery of consciousness and brain criticality.

项目总结/摘要 目前尚不清楚为什么有些患者在相对较短的时间内从无意识（麻醉和昏迷）中恢复过来。 速度更快，而其他人则显示出延长的恢复时间;或者根本没有从昏迷中恢复过来。传统上 填补我们知识中这一关键空白的方法主要集中在皮层下核团上，这些核团与神经元的状态有关。 唤醒（睡眠，清醒，麻醉），但最近的神经成像研究表明，意识，而不是 作为局部神经回路的产物，很可能是复杂的神经系统引起的一种新兴现象。 大脑中神经元活动的时空分布之间的相互作用。积累 有证据表明，大脑中存在临界状态，即有序与无序之间的最佳平衡状态 高度信息化、综合化和敏感状态，因此它被认为是 意识的出现。我们最近证明，一般情况下的意识水平 麻醉与大脑临界状态的程度相关，其他研究也报道了类似的发现。 组因此，我们假设，促进大脑网络走向临界状态将加速大脑网络的发展。 从麻醉中恢复意识和意识障碍。然而，控制关键性是一个 这是一个具有挑战性的问题，尚未在大脑网络中尝试过。我们将使用一种新颖的方法， 爆炸性同步，一种对网络的小扰动可能导致突然状态的现象 通过全球网络同步过渡，控制大脑临界状态。通过重新定义机制 爆炸同步作为一种机制的临界过渡，我们将能够系统地研究快速 以及大脑临界状态的缓慢转变和对状态转变的影响。我们的长期目标是利用 物理学的原则，以发展神经科学基础的战略，以加速恢复， 麻醉和昏迷所提出的研究的目的是探讨爆炸同步作为一种 恢复意识的机制。拟议研究的基本原理是， 临界过渡和意识的快速/缓慢恢复之间的关系将提供以下见解 管理快速和慢速状态转换的基本网络级机制，也将有助于通知 旨在加速从无意识中恢复的转化研究。我们将继续开展以下两项工作： 具体目标：1）确定大脑网络中的爆炸性同步与大脑网络中的爆炸性同步之间的关系。 从麻醉和昏迷中恢复意识。我们将使用计算机建模来识别大脑 与快速和慢速状态转换相关的网络条件，并使用经验数据测试模型预测 麻醉（人和大鼠）和昏迷（人）研究。2)确定大脑变化的因果影响 网络临界度对大鼠麻醉苏醒的影响我们将使用我们最近报告的 麻醉后快速和缓慢意识恢复模型，以研究麻醉后快速和缓慢意识恢复之间的因果关系 意识恢复和大脑临界状态。