Modulation of Auditory Novelty Processing by Dexmedetomidine and Natural Sleep: A Human Intracranial Electrophysiology Study

Identifying neural signatures of loss of consciousness is a major goal of neuroscience. The local/global auditory novelty paradigm has been useful in characterizing sensory processing across arousal states. Propofol suppresses responses to long-term novelty (global deviance, GD) at subhypnotic doses; suppression of responses to short-term novelty (local deviance, LD) outside auditory cortex may represent a biomarker of loss of consciousness. Dexmedetomidine is an alpha-2 adrenergic agonist that induces sleep-like sedation. This study examined whether the changes in auditory novelty processing observed with propofol, a GABA-ergic agent, also occur with dexmedetomidine and during sleep. Intracranial recordings were obtained in neurosurgical patients undergoing monitoring for refractory epilepsy. Stimuli were vowel sequences incorporating LD and GD. Neural activity was recorded during wakefulness, administration of dexmedetomidine, and sleep and was examined as the averaged evoked potential (AEP) and high gamma (70–150 Hz) power. AEP responses were more broadly distributed than high gamma activity. Results previously observed with propofol were replicated with dexmedetomidine. Subhypnotic doses led to decreased LD effects and a precipitous decline in GD effects. Loss of responsiveness was associated with loss of LD effects outside the auditory cortex. Likewise, daytime sleep was associated with cessation of GD effects and confinement of LD effects to the auditory cortex. Results support the generalizability of changes in auditory novelty processing to dexmedetomidine and sleep. Preservation of LD effects in the auditory cortex indicates that the auditory cortex continues to monitor the environment following loss of responsiveness.