Cortical-Subcortical Network Dynamics of Anesthesia and Consciousness

麻醉和意识的皮质-皮质下网络动力学

• 批准号: 10320052
• 负责人: NADER POURATIAN
• 金额: $ 27.21万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320052
• 关键词: Absence of pain sensation; Affect; Amnesia; Anesthesia procedures; Anesthetics; Animal Model; Animals; Area; Arousal; Basal Ganglia; Basal Ganglia Diseases; Behavioral; Binding; Brain; Brain Injuries; Brain imaging; Caring; Characteristics; Clinical; Complex; Computer Models; Conscious; Consciousness Disorders; Corpus striatum structure; Deep Brain Stimulation; Dose; Drug Kinetics; EEG-based imaging; Essential Tremor; Evolution; Excessive Daytime Sleepiness; Experimental Models; Functional disorder; General Anesthesia; Globus Pallidus; Goals; Human; Hypnosis; Infusion procedures; Interdisciplinary Study; Investigation; Light; Measures; Mediating; Mediation; Modeling; Molecular; Monitor; Movement; Operative Surgical Procedures; Output; Parkinson Disease; Pathology; Patients; Persons; Pharmacodynamics; Pharmacology; Physiology; Propofol; Recovery; Reporting; Research; Research Design; Research Personnel; Research Proposals; Resolution; Role; Severity of illness; Sleep Disorders; System; Testing; Thalamic structure; Time; Unconscious State; Variant; Work; base; behavioral response; brain behavior; cohort; dynamical evolution; experience; gamma-Aminobutyric Acid; human data; human subject; implantation; injury recovery; innovation; insight; knowledgebase; nervous system disorder; neural circuit; neurophysiology; patient population; programs; response; theories

PROJECT SUMMARY/ABSTRACT General anesthesia (GA) is a pharmacologically-induced state of unresponsiveness and unconsciousness which millions of people experience every year. Despite its ubiquity, a clear and consistent picture of the brain circuits mediating consciousness and responsiveness has not emerged. Assertions from non-invasive human studies (i.e. EEG and brain imaging), modeling and animal studies implicate key cortical and subcortical brain areas (including cortex, thalamus, and basal ganglia (BG)) during anesthesia. However, studies to date are limited by the lack of direct recordings in humans from both cortical and subcortical regions with sufficient spatial, temporal, and spectral resolution during pharmacologically-induced anesthesia. Our overall hypothesis is that the mesocircuit model of consciousness, which was original proposed to characterize recovery after brain injury, can be generalized to understand mechanisms of consciousness more broadly. The current research proposal focuses on experimentally probing the mesocircuit in neurosurgical patients, taking advantage of differences in patient populations with respect to basal ganglia disease (e.g., Parkinson disease [PD] vs essential tremor [ET]), the ability to synchronously acquire high resolution BG and cortical neurophysiology, and the opportunity to modulate the circuit in a targeted fashion with deep brain stimulation (DBS) to interrogate brain-behavior relationships. We pursue three specific aims: Aim 1: To demonstrate that patients with underlying basal ganglia pathology are more sensitive to propofol than other patients. Specifically, we will use target-controlled infusion of propofol to characterize pharmacokinetic-pharmacodynamic parameters in patients with PD and ET to gain insights into the potential role of BG circuitry in regulating consciousness, bearing on our more generalized model of mesocircuit mediation of consciousness. Aim 2: To correlate temporal evolution of basal ganglia-frontoparietal cortical circuit dynamics with behavioral correlates of induction and emergence from propofol anesthesia. We will use high spatial, temporal, and spectral resolution recordings in human subjects to provide direct evidence of circuit function, temporal evolution, causal circuit flow, and brain-behavior correlates. Aim 3: To evaluate the effects of targeted mesocircuit DBS (including both globus pallidus internus and externus) on propofol induced loss and recovery of consciousness and responsiveness. The research is innovative in its use of natural variations in neurological disease and concurrent invasive recording and stimulation in humans with a mechanistic and causal study design. The proposed research is significant because it will demonstrate a complex interplay of cortical and subcortical networks with partially separable effects of anesthesia, contrary to the most common clinical approach of measuring a single, continuously scaled metric for depth of anesthesia. This program will provide important human data to shed light on the generalizability of the mesocircuit model of regulating consciousness as well as validate a human experimental model for further investigation and characterization of anesthetic effects on the human brain.

项目概要/摘要 全身麻醉 (GA) 是一种药物引起的无反应和意识不清状态， 每年有数百万人经历。尽管它无处不在，但大脑回路的清晰一致的图像 中介意识和反应能力尚未出现。非侵入性人体研究的断言 （即脑电图和脑成像）、建模和动物研究暗示了关键的皮质和皮质下大脑区域 （包括皮质、丘脑和基底神经节 (BG)）在麻醉期间。然而，迄今为止的研究仅限于 人类缺乏来自皮质和皮质下区域的直接记录，具有足够的空间、时间、 和药物诱导麻醉期间的光谱分辨率。我们的总体假设是 意识的介观电路模型最初是为了描述脑损伤后的恢复而提出的，可以 可以推广到更广泛地理解意识机制。目前的研究计划 重点是利用实验上的差异来探索神经外科患者的介观电路 基底神经节疾病患者群体（例如帕金森病 [PD] 与原发性震颤 [ET]）， 同步获取高分辨率 BG 和皮质神经生理学的能力，以及机会 通过深部脑刺激 (DBS) 以有针对性的方式调节电路以询问大脑行为 关系。我们追求三个具体目标： 目标 1：证明患有潜在基底神经节的患者 病理学比其他患者对异丙酚更敏感。具体来说，我们将使用靶控输注 丙泊酚用于表征 PD 和 ET 患者的药代动力学-药效学参数，以获得 深入了解 BG 回路在调节意识中的潜在作用，对我们更广义的模型产生影响 介导意识的介导。目标 2：关联基底神经节-额顶叶的时间演化 皮质回路动力学与异丙酚麻醉诱导和苏醒的行为相关。我们 将使用人类受试者的高空间、时间和光谱分辨率记录来提供直接证据 电路功能、时间演化、因果电路流和大脑行为相关性。目标 3：评估 靶向中间电路 DBS（包括苍白球内部和外部）对异丙酚诱导的影响 意识和反应能力的丧失和恢复。该研究的创新在于利用自然 神经系统疾病的变化以及人类同时发生的侵入性记录和刺激 机制和因果研究设计。拟议的研究意义重大，因为它将展示复杂的 皮质和皮质下网络的相互作用与麻醉的部分可分离效应相反， 测量单一、连续缩放的麻醉深度指标的常见临床方法。这 计划将提供重要的人类数据，以阐明介观电路模型的普遍性 调节意识并验证人体实验模型以进行进一步研究和 麻醉对人脑影响的表征。