Noradrenergic activity as a key target in modulating consciousness.

Noradrenergic activity plays a key role in conscious visuospatial processing, distinct from general arousal effects. Two experiments—one using the sedative Dexmedetomidine (which targets α2A noradrenergic receptors) and another using sleep deprivation—both selectively altered brain activity (fMRI BOLD signal) during conscious processing, unlike the sedative Propofol, which affects both conscious and unconscious processing. However, the two methods produced opposite effects on visuospatial bias: Dexmedetomidine reduced leftward bias, while sleep deprivation increased leftward bias. The sleep deprivation effect was linked to an unexpected increase in sympathetic drive, indicated by heightened central autonomic network activity and heart rate, suggesting increased noradrenaline levels during task performance. These findings highlight noradrenergic activity as a target for studying consciousness.

Study at a glance

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.