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

University of Turku

Status and phase

Completed

Phase 4

Conditions

Consciousness, Level Altered

Treatments

Drug: Propofol

Drug: Dexmedetomidine

Study type

Interventional

Funder types

Other

Identifiers

NCT01889004

KLnro 72/2013 (Registry Identifier)

266467 (Other Grant/Funding Number)

LOC-2013

2013-001496-21 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

(not needed)

Enrollment

47 patients

Sex

Male

Ages

20 to 30 years old

Volunteers

Accepts Healthy Volunteers

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