The Neural Mechanisms of Anesthesia and Human Consciousness (LOC-2013)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Regional cerebral blood flow
研究概览
简要总结
The explanation of consciousness poses one of the greatest challenges to science and philosophy in the 21st century. It remains unclear what consciousness is and how it emerges from brain activity. By studying anesthesia and sleep, the investigators aim to reveal what happens in the brain when consciousness is lost and when it returns. During the study, a series of Positron Emission Tomography (PET), Magnetic Resonance Imaging (MRI) and electroencephalography (EEG) studies will be carried out on healthy male subjects to reveal the neural correlates of consciousness. Consciousness of the subjects will be manipulated with normal sleep and anesthetic agents dexmedetomidine and propofol.
First, various neurophysiological tools to separate consciousness, connectedness and responsiveness during normal sleep will be tested. The most suitable methods and subjects will be selected and then tested during anesthetic-induced sedation and loss of responsiveness (LOR). The anesthetics (dexmedetomidine or propofol) will be administered as target-controlled infusions (TCI) with step-wise concentration-increments until LOR is detected. Then, TCIs are repeated in the same subjects but adjusted according to the individual drug target concentrations sufficient for LOR, and a series of PET perfusion imaging measurements will be performed to obtain the brain activity information in various states of consciousness. The same subjects will then be imaged with PET for brain activity after sleep deprivation (awake), during various sleep stages and immediately after awakening. Finally, ten dexmedetomidine subjects will be given the drug once more, and functional MRI (fMRI) data will be collected at various states of consciousness before and during verbal and nonverbal vocalizations. EEG will be continuously collected in all sessions. The depth of anesthesia will be measured using quantitative EEG and bispectral index (BIS) monitoring.
The results may lead to the discovery of new and better objective indicators of the depth of anesthesia and consciousness, and new insights into the understanding of neural mechanisms behind drug-induced loss of consciousness and ultimately the mechanisms of action of (general) anesthetics as well as consciousness itself.
详细描述
(not needed)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 30 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age 20-30 years
- •Good general health i.e. American Society of Anesthesiologists (ASA) physical status I
- •Fluent in Finnish language
- •Right handedness
- •Written informed consent
- •Good sleep quality
排除标准
- •Chronic medication
- •History of alcohol and/or drug abuse
- •Strong susceptibility for allergic reactions
- •Serious nausea in connection with previous anesthesia
- •Strong susceptibility for nausea
- •Any use of drugs or alcohol during the 48 hours preceding anesthesia
- •Use of caffeine products 10-12 hours prior the study, 24 hours before sleep studies
- •Clinically significant previous cardiac arrhythmia / cardiac conduction impairment
- •Clinically significant abnormality in prestudy laboratory tests
- •Positive result in the drug screening test
- •Blood donation within 90 days prior to the study
- •Participation in any medical study with an experimental drug or device during the preceding 60 days
- •The study subject has undergone a prior PET or SPECT study
- •Any contraindication to magnetic resonance imaging (MRI)
- •Hearing impairment
- •Detected unsuitability based on initial electrophysiological measurements
- •Detected unsuitability based on MRI scanning results
- •Sleep disorder or severe sleep problem
研究组 & 干预措施
Dexmedetomidine
Intravenous dexmedetomidine using target controlled infusion
干预措施: Dexmedetomidine (Drug)
Propofol
Intravenous propofol using target controlled infusion
干预措施: Propofol (Drug)
结局指标
主要结局
Regional cerebral blood flow
时间窗: Several measurements during two separate days within 2 months
Altogether 14 PET scans during two separate study days. Cerebral blood flow changes will be used as surrogates for changes in regional brain activity.
次要结局
- EEG(Continuous data collection during five separate days within 2 months)
- Functional magnetic resonance imaging (fMRI)(Several measurements during one day)
- Event related potentials(Several time points during five separate days within 2 months)
研究者
Harry Scheinin
Adjunct Professor
University of Turku