Alteration of Temporal Organization of EEG Microstate Sequences During Propofol-induced Loss of Consciousness
Condition: Loss of Consciousness
MeSH terms: Unconsciousness
Study type: Interventional

Summary: 
      Temporal dynamics of the EEG microstates show scale-free monofractal properties. This means
      that information is encoded in the same way at different scales. It may be postulated that
      these monofractal properties of the EEG microstate sequences constitute a necessary
      prerequisite of consciousness. We postulate that clinical variations of consciousness may
      also be linked to alterations of fractal properties of EEG microstates.
    

Detailed description: 
      -  Aim of the study: Assess the alteration of temporal organization of EEG microstate
           sequences during propofol-induced loss of consciousness

        -  Methods: Prospective clinical trial. 20 right-handed adult patients, aged between 18 and
           40 years, scheduled for elective surgery under general anaesthesia, will be included.

      Patients will not receive any preoperative oral anxiolysis. After arrival in the operation
      theatre and a resting period of 10 minutes, the baseline EEG will be recorded (5 minutes
      duration). Then, after a three minutes proxygenation period with 100% oxygen, patients will
      receive an intravenous induction with propofol using the pharmacokinetic model by Schnider et
      al. The initial cerebral concentration will be 0.5 µg ml-1, which will be increased stepwise
      by 1.0 µg ml-1 until 2.5 µg ml-1, and then by 0.5 µg ml-1 until loss of consciousness. During
      the induction procedure, the patient's lungs will be gently ventilated using 100% oxygen
      through a face mask.

      Five minutes after reaching each equilibration of the blood-brain propofol concentration,
      clinical sedation (using the validated six points Observer Assessment of Alertness/Sedation
      [OAA/S] scale) will be annotated. Raw EEG, used later for fractal analysis, will be
      continuously recorded during the procedure. Corresponding OOA/S scores will be recorded on
      raw EEG. The study ends 10 minutes after the patient has lost consciousness (absence of
      response to "mild prodding or shaking" corresponding to OAA/S <2).

      The fractal analysis of EEG will be performed with a delay after anaesthesia by
      neuroscientists

        -  Hypothesis: We hypothesise that the fractal properties of EEG microstates will be
           modified in parallel with the propofol-induced loss of consciousness.

        -  EEG and DATA analysis Microstate analysis First, we will determine the maxima of the
           global field power (GFP). Because topography remains stable around peaks of the GFP,
           they are the best representatives of the momentary map topography in terms of
           signal-to-noise ratio.18 All maps marked as GFP peaks (i.e., the voltage values at all
           electrodes at that time point) will be extracted and submitted to a modified spatial
           cluster analysis using the atomize-agglomerate hierarchical clustering (AAHC) method19
           to identify the most dominant map topographies. The optimal number of template maps will
           be determined by means of a cross-validation criterion.20 We will then submit the
           template maps identified in every single subject into a second AAHC cluster analysis to
           identify the dominant clusters across all subjects. Finally, we will compute a spatial
           correlation between the templates identified at the group level and those identified for
           each subject in every run. We will so label each individual map with the group template
           it best corresponds to, to use the same labels for the subsequent group analysis.

      Then, we will compute the spatial correlation between the four template maps and the
      instantaneous EEG21 using a temporal constraint criterion of 32 ms. We will then use these
      spatial correlation time courses to select the dominant microstate m(k)∈{} at each time
      instant k and submit those time series to the fractal analysis.

        -  Fractal analysis We will split the microstate sequence into bipartitions and perform a
           random walk (on those bipartitions). After having integrated this random walk, we will
           analyse the integrated random walk by means of the wavelet transform and extract the
           fractal parameters: Hurst exponent and higher order cumulants.

        -  Fractal hypothesis One can either expect a decrease of the long-range dependency of the
           microstate sequences, i.e. one would expect lower Hurst exponents with deeper
           anaesthesia and hence loss of consciousness. Alternatively, we could also expect a
           transition from mono- to multifractality, i.e. the scaling of the temporal dynamics of
           the microstate sequences can be described at the expense of using multiple parameters,
           i.e. the Hurst exponent and higher-order cumulants that deviate from zero.
    

Intervention name(s): Target Controlled Infusion system (Orchestra Base Primea, Fresenius, France)
Intervention type(s): Device
Intervention description(s): Intravenous induction with propofol using the pharmacokinetic model by Schnider et al. The initial cerebral concentration will be 0.5 µg ml-1, which will be increased stepwise by 1.0 µg ml-1 until 2.5 µg ml-1, and then by 0.5 µg ml-1 until loss of consciousness
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: consciousness, anesthesia, electroencephalogram, microstate, long-range dependency