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.

项目摘要/摘要 全身麻醉（GA）是药理学引起的无反应性和无意识状态， 每年有数百万的人体验。尽管无处不在，但清晰且一致的脑电路图片 介导意识和反应性尚未出现。非侵入性人类研究的主张 （即脑电图和脑成像），建模和动物研究牵涉到关键皮质和皮层脑区域 （包括麻醉期间皮质，丘脑和基底神经节（BG））。但是，迄今为止的研究受到限制 来自皮质和皮层下区域的人类缺乏直接记录，其空间，时间，时间， 在药理诱导的麻醉期间的光谱分辨率。我们的总体假设是 意识的介体模型是原始的，该模型是为表征脑损伤后恢复的原始模型，可以 被概括以更广泛地理解意识机制。当前的研究建议 专注于通过实验探测神经外科患者的介体，利用差异 患者人群关于基底神经节病（例如帕金森病[PD]与必需震颤（ET]）， 同步获得高分辨率BG和皮质神经生理学的能力，以及有机会 以深度脑刺激（DBS）的目标方式调节电路，以询问脑行为 关系。我们追求三个具体目标：目标1：证明基础基础神经节的患者 与其他患者相比，病理对丙泊酚更敏感。具体而言，我们将使用目标控制的输液 丙泊酚的表征PD患者的药代动力学 - 药物动力学参数以获得 洞悉BG电路在调节意识中的潜在作用，这与我们更广泛的模型有关 意识中介导的介导。目的2：相关的基底神经神经节的时间演变 皮质回路动力学具有诱导和丙泊性麻醉出现的行为相关性。我们 将在人类受试者中使用高空间，时间和光谱分辨率记录来提供直接证据 电路功能，时间进化，因果电路流量和脑行为相关。目标3：评估 靶向的中环DB（包括Globus pallidus internus and externus）对丙泊酚诱导的影响 意识和反应能力的丧失和恢复。该研究对自然的使用具有创新性 神经疾病的变化以及同时侵入性记录和刺激的变化 机械和因果研究设计。拟议的研究很重要，因为它将证明一个复杂的 皮质和皮质下网络与麻醉的部分可分离作用的相互作用，与最大的相反 测量单个，连续缩放度量的通用临床方法以进行麻醉深度。这 计划将提供重要的人类数据，以阐明介环模型的普遍性 调节意识以及验证人类实验模型以进行进一步研究和 麻醉对人脑的表征。