Abstract
Studying changes in cortical oscillations can help elucidate the mechanistic link between receptor physiology and the clinical effects of anaesthetic drugs. Propofol, a GABA-ergic drug produces divergent effects on visual cortical activity: increasing induced gamma-band responses (GBR) while decreasing evoked responses. Dexmedetomidine, an α2- adrenergic agonist, differs from GABA-ergic sedatives both mechanistically and clinically as it allows easy arousability from deep sedation with less cognitive side-effects. Here we use magnetoencephalography (MEG) to characterize and compare the effects of GABA-ergic (propofol) and non-GABA-ergic (dexmedetomidine) sedation, on visual and motor cortical oscillations. Sixteen male participants received target-controlled infusions of propofol and dexmedetomidine, producing mild-sedation, in a placebo-controlled, cross-over study. MEG data was collected during a combined visuomotor task. The key findings were that propofol significantly enhanced visual stimulus induced GBR (44% increase in amplitude) while dexmedetomidine decreased it (40%). Propofol also decreased the amplitudes of the Mv100 (visual M100) (27%) and Mv150 (52%) visual evoked fields (VEF), whilst dexmedetomidine had no effect on these. During the motor task, neither drug had any significant effect on movement related gamma synchrony (MRGS), movement related beta de-synchronisation (MRBD) or Mm100 (movement-related M100) movement-related evoked fields (MEF), although dexmedetomidine slowed the Mm300. Dexmedetomidine increased (92%) post-movement beta synchronisation/rebound (PMBR) power while propofol reduced it (70%, statistically non- significant). Overall, dexmedetomidine and propofol, at equi-sedative doses, produce contrasting effects on visual induced GBR, VEF, PMBR and MEF. These findings provide a mechanistic link between the known receptor physiology of these sedative drugs with their known clinical effects and may be used to explore mechanisms of other anaesthetic drugs on human consciousness.
Highlights
Our understanding of the mechanisms of anaesthesia and the neural correlates of anaesthesia-induced unconsciousness is incomplete
We have previously demonstrated that sedation with propofol results in increased gamma band response/power (GBR), increased alpha power suppression, and a decrease in the amplitude of the stimulus- onset evoked (both transient gamma band and visual evoked fields (VEF)) response (Saxena et al, 2013)
This study reports the findings from a combined visuomotor MEG paradigm recorded during a placebo-controlled, crossover, single-blind study of the sedative effects of propofol (GABA-ergic drug) and dexmedetomidine, on human cortical oscillations
Summary
Our understanding of the mechanisms of anaesthesia and the neural correlates of anaesthesia-induced unconsciousness is incomplete. We have previously demonstrated that sedation with propofol (as a representative drug with primarily GABA-ergic action) results in increased gamma band response/power (GBR), increased alpha power suppression, and a decrease in the amplitude of the stimulus- onset evoked (both transient gamma band and visual evoked fields (VEF)) response (Saxena et al, 2013). This provided an insight into the possible separation of the neural generators of visual gamma oscillations (CasteloBranco et al, 1998) and the differential effects of propofol on those generating mechanisms. This mechanistic discovery provides a potential biomarker to study and refine different pharmacological compounds that have similar clinical actions
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