Multimodal Functional Imaging of Auditory Perception Under General Anesthesia

描述(申请人提供)：神经科学和医学中的一个基本问题是了解全身麻醉的机制。这项名为“全麻下听觉感知的多模式功能成像”的提案是为了响应NINDS计划宣布的导师量化研究职业发展奖(K25)而提交的。应聘者寻求接受神经生物学和麻醉临床药理学方面的培训，以便将多模式功能成像方法应用于全身麻醉机制的研究。临床上通过观察对外界刺激的反应丧失来衡量全身麻醉下的意识丧失。然而，临床昏迷的患者可能会有听觉感知和记忆，这可能会导致手术后回忆起麻醉过程中的事件。术后回忆的后果包括睡眠障碍、做梦、噩梦、闪回和焦虑，以及创伤后应激障碍。临床麻醉脑监测器是基于固定的麻醉相关脑电(EEG)模式和患者意识的临床评估之间的经验关系，但不能测量麻醉下负责听觉感知的功能性脑区的活动。该项目的目标是同时使用脑电和功能磁共振成像来表征麻醉引起的听觉系统功能的变化。将在不同程度的异丙酚麻醉下测量fMRI对感知声音时间包络的反应，范围从轻度镇静到深度麻醉，同时进行脑电检查。用fMRI测量的听觉知觉处理的变化将与临床意识水平、异丙酚药物水平和麻醉相关的脑电模式有关。这些研究将提供一种方法来量化麻醉诱导的意识丧失后发生的知觉处理量，以及与知觉处理丧失相关的脑电模式。通过这个研究项目，以及教学课程和教程，候选人将接受麻醉的神经生物学和临床药理学方面的培训。该奖项提供的培训将帮助候选人实现长期的职业目标，即领导一个独立的生物医学研究计划，研究麻醉的系统神经科学。全麻每天为5万多名患者进行内科和外科手术，但其基本的大脑机制尚不清楚。尽管安全性有所提高，但麻醉会导致严重的副作用，如心肺抑制或手术后回忆。通过这些研究，我们希望开始发展必要的基础神经科学知识，以改善麻醉药物和监测，并有朝一日解决麻醉相关的发病率问题。

DESCRIPTION (provided by applicant): A fundamental problem in neuroscience and medicine is to understand the mechanisms of general anesthesia. This proposal, "Multimodal Functional Imaging of Auditory Perception Under General Anesthesia", is submitted in response to the NINDS program announcement for Mentored Quantitative Research Career Development Awards (K25). The candidate seeks to gain training in the neurobiology and clinical pharmacology of anesthesia in order to apply multimodal functional imaging methods to the study of the mechanisms of general anesthesia. Loss of consciousness under general anesthesia is measured clinically by observing the loss of response to external stimuli. However, auditory perception and memory are possible in patients who are clinically unconscious, which may result in post-operative recall of events during anesthesia. Consequences of post-operative recall include sleep disturbances, dreams, nightmares, flashbacks and anxiety, as well as post-traumatic stress disorder. Clinical anesthetic brain monitors are based on empirical relationships between stereotyped anesthesia-related electroencephalographic (EEG) patterns and clinical assessments of patient awareness, but cannot measure activity within functional brain regions responsible for auditory perception under anesthesia. The goal of this project is to characterize anesthesia-induced changes of function in the auditory system using simultaneous EEG and fMRI. FMRI responses to perception of sound temporal envelope will be measured at varying levels of propofol anesthesia, ranging from light sedation to deep anesthesia, with simultaneous EEG. Changes in auditory perceptual processing measured with fMRI will be related to clinical level of consciousness, propofol drug levels, and anesthesia-related EEG patterns. These studies will provide a means to quantify the amount of perceptual processing that occurs after anesthesia-induced loss of consciousness, as well as the EEG patterns that correlate with loss of perceptual processing. Through this research project, as well as didactic courses and tutorials, the candidate will be trained in the neurobiology and clinical pharmacology of anesthesia. The training provided by this Award will help the candidate achieve the long-term career goal of leading an independent biomedical research program to study the systems neuroscience of anesthesia. General anesthesia is administered to over 50,000 patients daily for medical and surgical procedures, but its basic brain mechanisms are not known. Despite safety improvements, anesthesia results in serious side effects such as cardio-respiratory depression or post-operative recall. Through these studies, we hope to begin developing the fundamental neuroscience knowledge necessary to improve anesthetic drugs and monitoring, and to one day solve the problem of anesthesia-related morbidity.