The Neural Mechanisms of Anesthesia and Human Consciousness
Condition: Consciousness, Level Altered
MeSH terms: Consciousness Disorders
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      (not needed)
    

Intervention name(s): Dexmedetomidine; Propofol
Intervention type(s): Drug; Drug
Intervention description(s): Escalating concentrations until loss of responsiveness; Escalating concentrations until loss of responsiveness
Other intervention name(s): Dexdor; Propofol-Lipuro
Intervention MeSH terms: Dexmedetomidine; Propofol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Cerebral blood flow; Consciousness; Dexmedetomidine; EEG; Event related potentials; Functional magnetic resonance imaging; General anesthesia; Positron emission tomography; Propofol