Noradrenergic activity as a key target in modulating consciousness.

Abstract

How the brain generates conscious experiences remains profoundly mysterious. Pharmacological interventions that alter the state of consciousness have been proposed as a tool to investigate the neural mechanisms of consciousness. However, we have recently demonstrated that the sedative Propofol influences both conscious and unconscious neural processing. Altered arousal, and other pharmacological effects, therefore cannot be assumed a priori to provide information specifically on conscious neural processes. Instead, effects on both conscious and unconscious processes need to be considered. Here we investigated the role of noradrenergic activity in conscious and unconscious visuospatial processing. In Study 1 we used Dexmedetomidine, a sedative that specifically targets α2A noradrenergic receptors. In Study 2, we used sleep deprivation as a natural state of altered arousal, which exerts partially overlapping effects on noradrenaline levels. Unlike Propofol, both Dexmedetomidine and sleep deprivation selectively altered brain activity (fMRI BOLD signal change) during conscious processing. However, the two methods produced distinct effects on visuospatial bias during low arousal: while Dexmedetomidine reduced leftward bias, sleep deprivation increased leftward bias. These differential effects on spatial bias were explained by an unexpected increase in sympathetic drive, as indexed by increased activity in the central autonomic network and in heart rate, from sleep deprivation, that indicate increased rather than decreased noradrenaline levels during task performance. Together, these findings emphasize noradrenergic activity as a target for pharmacological manipulations of consciousness, which could open a window to its neurophysiological underpinnings.