Published August 21, 2018 | Version v1
Journal article Open

Propofol-induced unresponsiveness is associated with impaired feedforward connectivity in cortical hierarchy

Creators

  • 1. 1Department of Anesthesiology, University of Wisconsin, Madison, WI, USA
  • 2. Faculty of Engineering, University of Bristol, Bristol, UK,
  • 3. Department of Anaesthesia, Waikato Hospital, Hamilton, New Zealand
  • 4. Coma Science Group, GIGA-consciousness, University of Liège, Liège, Belgium
  • 5. Anesthesia and Intensive Care Laboratory, GIGA-Consciousness, University of Liège, Liège, Belgium; Department of Anestheisa and ICM, CHU Liège, Liège, Belgium; University Department of Anesthesia and ICM, CHR Citadelle, Liège, Belgium
  • 6. Department of Anestheisa and ICM, CHU Liège, Liège, Belgium
  • 7. Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
  • 8. Department of Anesthesiology, University of Wisconsin, Madison, WI, USA; Rambam Healthcare Campus, Haifa, Israel
  • 9. Department of Psychiatry, University of Wisconsin, Madison, WI, USA
  • 10. Coma Science Group, GIGA-consciousness, University of Liège, Liège, Belgium; Department of Neurology, CHU Liège, Liège, Belgium,
  • 11. Department of Psychiatry, University of Wisconsin, Madison, WI, USA; Department of Neurology, University of Wisconsin, Madison, WI, USA

Description

Background: Impaired consciousness has been associated with impaired cortical signal propagation after transcranial
magnetic stimulation (TMS). We hypothesised that the reduced current propagation under propofol-induced unresponsiveness
is associated with changes in both feedforward and feedback connectivity across the cortical hierarchy.
Methods: Eight subjects underwent left occipital TMS coupled with high-density EEG recordings during wakefulness and
propofol-induced unconsciousness. Spectral analysis was applied to responses recorded from sensors overlying six hierarchical
cortical sources involved in visual processing. Dynamic causal modelling (DCM) of induced timeefrequency
responses and evoked response potentials were used to investigate propofol’s effects on connectivity between regions.
Results: Sensor space analysis demonstrated that propofol reduced both induced and evoked power after TMS in occipital,
parietal, and frontal electrodes. Bayesian model selection supported a DCM with hierarchical feedforward and
feedback connections. DCM of induced EEG responses revealed that the primary effect of propofol was impaired feedforward
responses in cross-frequency theta/alphaegamma coupling and within frequency theta coupling (F contrast,
family-wise error corrected P<0.05). An exploratory analysis (thresholded at uncorrected P<0.001) also suggested that
propofol impaired feedforward and feedback beta band coupling. Post hoc analyses showed impairments in all feedforward
connections and one feedback connection from parietal to occipital cortex. DCM of the evoked response potential
showed impaired feedforward connectivity between left-sided occipital and parietal cortex (T contrast P=0.004, Bonferroni
corrected).

Files

Sanders et al. - 2018 - Propofol-induced unresponsiveness is associated wi.pdf

Files (1.5 MB)

Additional details

Funding

LUMINOUS – Studying, Measuring and Altering Consciousness through information theory in the electrical brain 686764
European Commission