The Neural Mechanisms of Anesthesia and Human Consciousness

Study Overview
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Brief Summary
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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.

Detailed Description
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(not needed)

Official Title
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The Neural Mechanisms of Anesthesia and Human Consciousness (LOC-2013)

Conditions
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Consciousness, Level Altered

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male 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 Exclusion Criteria: 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 Smoking 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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexmedetomidine<br>Intravenous dexmedetomidine using target controlled infusion | Drug: Dexmedetomidine<br>* Escalating concentrations until loss of responsiveness<br>* Other names: Dexdor;|
| Experimental: Propofol<br>Intravenous propofol using target controlled infusion | Drug: Propofol<br>* Escalating concentrations until loss of responsiveness<br>* Other names: Propofol-Lipuro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regional cerebral blood flow | Altogether 14 PET scans during two separate study days. Cerebral blood flow changes will be used as surrogates for changes in regional brain activity. | Several measurements during two separate days within 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebral blood flow, Consciousness, Dexmedetomidine, EEG, Event related potentials, Functional magnetic resonance imaging, General anesthesia, Positron emission tomography, Propofol