The brain-bases of responsiveness variability under moderate anaesthesia

Abstract

Anaesthesia combined with functional neuroimaging provides a powerful approach for understanding the brain mechanisms that change as consciousness fades. Although propofol is used ubiquitously in clinical interventions that reversibly suppress consciousness, its effect varies substantially between individuals, and the brain bases of this variability remain poorly understood. We asked whether three networks that are primary sites of propofol-induced sedation and key to conscious cognition — the dorsal attention (DAN), executive control (ECN), and default mode (DMN) network — underlie responsiveness variability under anaesthesia. Healthy participants (N=17) underwent propofol sedation inside the fMRI scanner at dosages of ‘moderate’ anaesthesia, and behavioural responsiveness was measured with a target detection task. To assess information processing, participants were scanned during an active engagement condition comprised of a suspenseful auditory narrative, in addition to the resting state. A behavioural investigation in a second group of non-anesthetized participants (N=25) qualified the attention demands of narrative understanding, which we then related to the brain activity of participants who underwent sedation. 30% of participants showed no delay in reaction times relative to wakefulness, whereas the others, showed significantly delayed and fragmented responses, or full omission of responses. These responsiveness differences did not relate to information processing differences. Rather, only the functional connectivity within the ECN during wakefulness differentiated the participants’ responsiveness level, with significantly stronger connectivity in the fast relative to slow responders. Consistent with this finding, fast responders had significantly higher grey matter volume in the frontal cortex aspect of the ECN. For the first time, these results show that responsiveness variability during propofol anaesthesia relates to inherent differences in brain function and structure within the executive control network, which can be predicted prior to sedation. These results shed light on the brain bases of responsiveness differences and highlight novel markers that may help to improve the accuracy of awareness monitoring during clinical anaesthesia.