The Neural Mechanisms of Anesthesia and Human Consciousness

Summary

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.

Conditions

• Consciousness, Level Altered

Interventions

DRUG

Dexmedetomidine

Escalating concentrations until loss of responsiveness

DRUG

Propofol

Escalating concentrations until loss of responsiveness

Sponsors & Collaborators

• Academy of Finland

  collaborator OTHER

• Hospital District of Southwestern Finland

  collaborator OTHER

• University of Turku

  lead OTHER

Principal Investigators

• Harry Scheinin, MD · University of Turku

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

30 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-02-28

Primary Completion

2016-01-31

Completion

2016-01-31

Countries

• Finland

Study Locations