Propofol Anesthesia Increases Long-range Frontoparietal Corticocortical Interaction in the Oculomotor Circuit in Macaque Monkeys

Background: Frontoparietal functional connectivity decreases with multiple anesthetics using electrophysiology and functional imaging. This decrease has been proposed as a final common functional pathway to produce anesthesia. Two alternative measures of long-range cortical interaction are coherence and phase-amplitude coupling. Although phase-amplitude coupling within frontal cortex changes with propofol administration, the effects of propofol on phase-amplitude coupling between different cortical areas have not previously been reported. Based on phase-amplitude coupling observed within frontal lobe during the anesthetized period, it was hypothesized that between-lead phase-amplitude coupling analysis should decrease between frontal and parietal leads during propofol anesthesia. Methods: A published monkey electrocorticography data set (N = 2 animals) was used to test for interactions in the cortical oculomotor circuit, which is robustly interconnected in primates, and in the visual system during propofol anesthesia using coherence and interarea phase-amplitude coupling. Results: Propofol induces coherent slow oscillations in visual and oculomotor networks made up of cortical areas with strong anatomic projections. Frontal eye field within-area phase-amplitude coupling increases with a time course consistent with a bolus response to intravenous propofol (modulation index increase of 12.6-fold). Contrary to the hypothesis, interareal phase-amplitude coupling also increases with propofol, with the largest increase in phase-amplitude coupling in frontal eye field low-frequency phase modulating lateral intraparietal area β-power (27-fold increase) and visual area 2 low-frequency phase altering visual area 1 β-power (19-fold increase). Conclusions: Propofol anesthesia induces coherent oscillations and increases certain frontoparietal interactions in oculomotor cortices. Frontal eye field and lateral intraparietal area show increased coherence and phase-amplitude coupling. Visual areas 2 and 1, which have similar anatomic projection patterns, show similar increases in phase-amplitude coupling, suggesting higher order feedback increases in influence during propofol anesthesia relative to wakefulness. This suggests that functional connectivity between frontal and parietal areas is not uniformly decreased by anesthetics.