Electroencephalographic coherence and cortical acetylcholine during ketamine-induced unconsciousness

Abstract

There is limited understanding of cortical neurochemistry and cortical connectivity during ketamine anaesthesia. We conducted a systematic study to investigate the effects of ketamine on cortical acetylcholine (ACh) and electroencephalographic coherence. Male Sprague-Dawley rats (n=11) were implanted with electrodes to record electroencephalogram (EEG) from frontal, parietal, and occipital cortices, and with a microdialysis guide cannula for simultaneous measurement of ACh concentrations in prefrontal cortex before, during, and after ketamine anaesthesia. Coherence and power spectral density computed from the EEG, and ACh concentrations, were compared between conscious and unconscious states. Loss of righting reflex was used as a surrogate for unconsciousness. Ketamine-induced unconsciousness was associated with a global reduction of power (P=0.02) in higher gamma bandwidths (>65 Hz), a global reduction of coherence (P≤0.01) across a broad frequency range (0.5-250 Hz), and a significant increase in ACh concentrations (P=0.01) in the prefrontal cortex. Compared with the unconscious state, recovery of righting reflex was marked by a further increase in ACh concentrations (P=0.0007), global increases in power in theta (4-10 Hz; P=0.03) and low gamma frequencies (25-55 Hz; P=0.0001), and increase in power (P≤0.01) and coherence (P≤0.002) in higher gamma frequencies (65-250 Hz). Acetylcholine concentrations, coherence, and spectral properties returned to baseline levels after a prolonged recovery period. Ketamine-induced unconsciousness is characterized by suppression of high-frequency gamma activity and a breakdown of cortical coherence, despite increased cholinergic tone in the cortex.