A Systems Neuroscience Approach for the Study of General Anesthesia

用于研究全身麻醉的系统神经科学方法

基本信息

批准号：
7906893
负责人：
EMERY N BROWN
金额：
$ 87.5万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7906893
关键词：
Absence of pain sensation Adrenal Glands Adrenergic Receptor Adverse effects Affect Algorithms American Amnesia Amygdaloid structure Anatomy Anesthesia procedures Anesthesiology Anesthetics Animals Anterior Apnea Area Arousal Auditory Autonomic nervous system Award Bees Behavioral Behavioral Paradigm Binding Biological Assay Biological Models Blood Blood Pressure Blood specimen Boston Brain Brain Part Brain Stem Brain region Breathing Cardiovascular system Characteristics Clinical Clinical Medicine Clinical Nursing Research Clinical Services Clonidine Collaborations Coma Communities Complex Conscious Conscious Sedation Corpus striatum structure Coupling Critical Care Cytoskeleton Data Dentistry Development Device Designs Discipline Discipline of obstetrics Dose Drug Combinations Drug Delivery Systems Drug Kinetics Drug effect disorder Electroencephalogram Engineering Environmental air flow Esthesia Europe Failure Fright Functional Imaging Functional Magnetic Resonance Imaging Funding Mechanisms Future Gastroenterology General Anesthesia General Population General anesthetic drugs Goals Guidelines Hand Health Hearing Heart Rate Hibernation Hippocampus (Brain)Human Human Volunteers Hypnosis Hypotension Hypothalamic structure Image Infusion procedures Insula of Reil Interdisciplinary Study International Intervention Intravenous Intubation Isoflurane Knowledge Lead Learning Link Lipid A Macaca Maintenance Malpractice Measurement Measures Medial Mediating Medical Medicine Meditation Memory Methods Microdialysis Microinjections Microtubules Modality Modeling Modern Medicine Molecular Molecular Biology Monitor Monkeys Morbidity - disease rate Motor Cortex Movement Myocardial dysfunction N-Methyl-D-Aspartate Receptors Nature Nausea and Vomiting Neuroanatomy Neurology Neuromuscular Junction Neurons Neurosciences Neurosciences Research Neurosecretory Systems Neurotransmitters Nucleus Accumbens Operative Surgical Procedures Pain Pain Research Parietal Pathway interactions Patients Pattern Pediatrics Perception Peripheral Nerves Pharmaceutical Preparations Pharmacodynamics Physiologic Monitoring Physiological Play Positioning Attribute Postoperative Period Prefrontal Cortex Primates Procedures Process Property Propofol Protein Binding Protocols documentation Psychiatry Psychology Pupil Qualifying Radiology Specialty Rattus Recruitment Activity Reflex action Regulation Reporting Research Research Design Research Ethics Committees Research Personnel Resources Risk Role Safety Saimiri Site Sleep Societies Somatosensory Cortex Source Specialist Spinal Cord Spinal nerve structure Stimulus Students Study Subject Study models System Tactile Techniques Technology Testing Thalamic structure Time Tracheostomy Tube Tracheostomy procedure Training Translating Unconscious State United States United States National Institutes of Health Universities Vegetative States Ventilatory Depression Work World War II abstracting alpha-adrenergic receptor auditory pathway awake basal forebrain base biological adaptation to stress clinical practice computational neuroscience computerized data processing design drug development frontal lobe gamma-Aminobutyric Acid gray matter hemodynamics high risk human subject hypnotic improved innovation insight interest locus ceruleus structure loved ones medical schools meetings monitoring device mortality motor control nanoparticle neural circuit neuroimaging neuromechanism neurophysiology neurosurgery novel novel strategies programs quantum raphe nuclei receptor relating to nervous system research study response somatosensory spinal tract success theories volunteer

项目摘要

General anesthesia is a drug-induced, reversible condition comprised of five behavioral states: hypnosis (loss of consciousness), amnesia (loss of memory), analgesia (loss of pain sensation), akinesia (immobility), and hemodynamic stability with control of the stress response. The mechanisms by which anesthetic drugs induce the state of general anesthesia remain one of the biggest mysteries of modern medicine. Study of the neural circuitry responsible for each of the five behavioral states of general anesthesia is a fundamental question being investigated in systems neuroscience but not for the purpose of understanding anesthesia. I propose to use systems neuroscience paradigms to establish an interdisciplinary program to solve the mystery of general anesthesia. The program will consist of a set of coordinated studies in humans, monkeys and rats using the same anesthetic agents, in addition to use of dynamical systems modeling studies of anesthetic effects on neural circuits and the development of new signal processing algorithms to track in real-time the dynamics of brain states under general anesthesia. The animal studies will use established behavioral paradigms, fMRI, and multielectrode methods to track brain activity, and microinjection and novel nanoparticle methods for site- specific delivery of anesthetic drugs. The human studies will track brain states under anesthesia using fMRI and simultaneously recorded EEG. The investigators will collaborate to integrate this information across the different systems and scales. This project will lead to a more precise, neurophysiologically-based understanding of general anesthesia, safer protocols for anesthetic drug-development, site-specific methods for anesthetic drug delivery and the design of better, neurophysiologically-based methods for measuring depth of anesthesia. Therefore, this research will improve human health by reducing the risk of anesthesia-related morbidity for patients whose surgical or medical therapies require general anesthesia. This research will also have broad impact on the training of anesthesiologists by placing greater emphasis on systems neuroscience.

全身麻醉是一种药物诱导的可逆疾病，由五种行为状态组成：催眠（丢失）意识），健忘症（记忆力丧失），镇痛（失去疼痛感），阿肯西亚（Akinesia）（不动）和血液动力学稳定性，控制应力反应。麻醉药诱导的机制全身麻醉状态仍然是现代医学最大的奥秘之一。神经研究负责全身麻醉的五个行为状态的电路是一个基本问题在系统神经科学中进行调查，但不是为了理解麻醉的目的。我建议使用系统神经科学范式来建立跨学科计划来解决一般的奥秘麻醉。该程序将包括一组在人类，猴子和大鼠的协调研究同样的麻醉剂除了使用动态系统建模研究对麻醉作用的研究研究神经回路和新信号处理算法的开发，以实时跟踪大脑状态在全身麻醉下。动物研究将使用已建立的行为范例，fMRI，以及跟踪大脑活动的多电极方法，以及用于位点的显微注射和新型纳米颗粒方法麻醉药物的特定递送。人类研究将使用fMRI在麻醉下跟踪大脑状态并同时记录了脑电图。调查人员将协作以整合这些信息不同的系统和尺度。该项目将导致更精确的，基于神经生理的项目了解全身麻醉，麻醉药物开发的更安全方案，特定地点方法用于麻醉药物的递送和基于神经生理学的更好的测量深度的方法麻醉。因此，这项研究将通过降低与麻醉相关的风险来改善人类健康对于手术或医疗疗法需要全身麻醉的患者的发病率。这项研究也将通过更加重视系统神经科学来对麻醉师的培训产生广泛的影响。