General Anesthetics and Cerebral Cortical Sensory Integration

全身麻醉与大脑皮层感觉统合

• 批准号: 10206336
• 负责人: Anthony George Hudetz
• 金额: $ 42.46万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10206336
• 关键词: Affect; Anatomy; Anesthesia procedures; Anesthetics; Animals; Basic Science; Behavioral; Behavioral Assay; Biological Assay; Biological Models; Brain; Cerebral cortex; Cerebrum; Chronic; Code; Complex; Conscious; Consciousness Disorders; Development; Dexmedetomidine; Dose; Electrophysiology (science); Event; General Anesthesia; General anesthetic drugs; Goals; Human; Hybrids; Implant; Interneurons; Investigation; Ketamine; Knowledge; Lead; Maps; Methods; Microelectrodes; Modification; Monitor; Neurobiology; Neurons; Neurophysiology - biologic function; Parietal; Patients; Pattern; Pharmaceutical Preparations; Pharmacology; Photic Stimulation; Population; Process; Propofol; Psyche structure; Rattus; Recurrence; Reproducibility; Research Project Grants; Rodent; Running; Sensory; Specificity; Stimulus; System; Task Performances; Testing; Time; Unconscious State; Visual; Visual Cortex; Work; association cortex; desflurane; disability; electrical microstimulation; experience; flexibility; improved; in vivo; indexing; information processing; mental state; microstimulation; network models; neuronal circuitry; neuronal patterning; novel; novel strategies; sensory integration; sensory stimulus; spatiotemporal; tool; transmission process; treadmill; virtual; virtual environment; virtual reality; virtual reality environment; visual stimulus

The overall goal of this project is to apply novel approaches to probe local neuronal activity in cerebral cortex associated with complex, natural sensory experience and to determine how general anesthetics may alter sensory-specific contents of consciousness. Our general hypothesis is that anesthetic modulation of consciousness is closely tied to the modification of specific spatiotemporal patterns of neuronal activity in local cortical circuits. We will test our hypothesis in the rat visual and association cortex as a model system in vivo. We propose three specific aims. In the first aim, we will use multineuronal recording with chronically implanted microelectrode arrays to determine stereotypic neuronal firing sequences that conform to moving visual stimuli presented by virtual reality projection while the subject is allowed run on a spherical treadmill along a virtual path. We will examine how anesthetics at incremental doses may influence both spontaneous and visual stimulus-related firing sequences, comparing behaviorally defined conscious and unconscious states. We hypothesize that navigating virtual reality will induce reproducible spatiotemporal sequences of neuron ensembles and that sensory specificity of these sequences would be reduced by anesthetics particularly at a dose they produce observable signs of unconsciousness. In the second aim, we will apply electrical microstimulation to elicit reproducible local network activity patterns and map the effective connectivity of neuronal networks. We hypothesize that input-specific multineuronal firing sequences will be stabilized by repeated stimulation, will be spontaneously replayed in the absence of stimulation as a result of network plasticity and that anesthesia will degrade but not necessarily abolish all stimulus-selective sequences. In the third aim, multichannel recording and microstimulation will be combined with an adaptive artificial neuronal network model to create a closed-loop hybrid brain-to-brain assay of visual stimulus-specific information transfer between two virtual reality-embedded subjects. This will be a novel attempt to read out meaningful sensory neuronal information from a subject's brain and transfer it to another subject as a task performance agent to use it for an assessment of the first subject's state of consciousness. In all aims, we will use four drugs representing four canonical pharmacological classes of anesthetics: desflurane, propofol, dexmedetomidine, and ketamine to find a common, agent-invariant neuronal correlate of unconsciousness. The proposed project builds upon our two decades-long integrative investigations into the neuronal mechanisms of anesthesia at systems level. The work should advance our understanding of the neurobiological basis of consciousness and anesthesia. The anticipated results should augment our basic science knowledge that may lead, on the long term, to the development of improved bedside-applicable monitoring of the state of consciousness during general anesthesia and in patients with disorders of consciousness. They may also inspire new approaches to ameliorate deficits and replace or restore neural functions in patients with physical or mental disabilities.

本项目的总体目标是应用新的方法来探测大脑皮层局部神经元活动 与复杂的，自然的感觉体验相关，并确定全身麻醉剂如何改变 意识的特定感官内容。我们的一般假设是， 意识与局部神经元活动的特定时空模式的改变密切相关。 皮层回路我们将测试我们的假设在大鼠的视觉和联想皮层作为一个模型系统在体内。 我们提出三个具体目标。在第一个目标中，我们将使用多神经元记录， 植入微电极阵列以确定符合运动的刻板神经元放电序列 当受试者被允许在球形跑步机上跑步时，由虚拟现实投影呈现的视觉刺激 沿着一条虚拟的路径。我们将研究如何麻醉剂在增量剂量可能会影响自发 和视觉刺激相关的放电序列，比较行为定义的有意识和无意识 states.我们假设，虚拟现实导航将诱导可再现的时空序列， 这些序列的感觉特异性会被麻醉剂特别是 在一定剂量下，它们会产生明显的无意识迹象。在第二个目标中，我们将应用电 微刺激，以引起可再现的局部网络活动模式，并绘制有效的连接， 神经网络我们假设，输入特异性多神经元放电序列将被稳定， 重复的刺激，将在没有刺激的情况下自发重放，作为网络的结果。 可塑性和麻醉会降低，但不一定取消所有的刺激选择性序列。在 第三个目标，多通道记录和微刺激将与自适应人工神经元相结合 网络模型，以创建视觉刺激特定信息的闭环混合脑对脑分析 在两个虚拟现实嵌入主题之间转移。这将是一个有意义的小说尝试读出 感觉神经元信息从受试者的大脑，并将其转移到另一个受试者作为一个任务的性能 代理使用它来评估第一个主体的意识状态。在所有目标中，我们将使用四种药物 代表四种典型的麻醉剂药理学类别：地氟烷、异丙酚、右美托咪定， 和克他命来寻找一个共同的，代理不变的神经元相关的无意识。拟建项目 建立在我们对麻醉的神经机制长达二十年的综合研究基础上， 系统级。这项工作应该会促进我们对意识的神经生物学基础的理解， 麻醉预期的结果应该增加我们的基础科学知识，从长远来看， 长期以来，以改善床边适用的监测意识状态的发展， 全身麻醉和意识障碍患者。它们还可能激发新的方法， 改善身体或精神残疾患者的缺陷并取代或恢复神经功能。