The Neural Mechanisms of Anesthesia and Human Consciousness (Part 6)

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. Positron Emission Tomography (PET), Magnetic Resonance Imaging (MRI) and electroencephalography (EEG) studies will be carried out to reveal the neural correlates of consciousness. Consciousness of the subjects will be manipulated with anesthetic agents dexmedetomidine acting through α2-agonism, with propofol and sevoflurane both mainly acting through the enhancement of gamma-aminobutyric acid (GABA) system, and with S-ketamine acting through N-methyl-D-aspartate (NMDA) receptor antagonism. One-hundred-and-sixty (160) healthy male subjects will be recruited to receive EC50 concentration of either dexmedetomidine, propofol, S-ketamine or sevoflurane, or placebo while being imaged for cerebral metabolic rate of glucose (CMRglu). 40 subjects will receive dexmedetomidine, 40 subjects propofol, 20 subjects S-ketamine, 40 subjects sevoflurane and 20 subjects will receive placebo. Also genetic, immunological and metabolomics samples will be taken and analysed to find possible genetic factors explaining the variability in drug response and to find possible immunological and chemical fingerprints of acute drug effect.

Inclusion criteria

• Male
• Age 18-30 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
• 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 MRI scanning results if available before the PET scanning
• Sleep disorder or severe sleep problem