The brain-bases of responsiveness variability under moderate anaesthesia

Anaesthesia combined with functional neuroimaging provides a powerful approach for understanding the brain mechanisms of consciousness. Although propofol is used ubiquitously in clinical interventions that reversibly suppress consciousness, it shows large inter-individual variability, and the brain bases of this variability remain poorly understood. We asked whether three networks key to conscious cognition -- the dorsal attention (DAN), executive control (ECN), and default mode (DMN) -- underlie responsiveness variability under anaesthesia. Healthy participants (N=17) were moderately anaesthetized during narrative understanding and resting state conditions inside the Magnetic Resonance Imaging scanner. A target detection task measured behavioural responsiveness. An independent behavioural study (N=25) qualified the attention demands of narrative understanding. 30% of participants were unaffected in their response times, thus thwarting a key aim of anaesthesia -- the suppression of behavioural responsiveness. Individuals with stronger functional connectivity within the DAN and ECN, between them, and to the DMN, and with larger grey matter volume in frontal regions were more resilient to anaesthesia. For the first time, we show that responsiveness variability during propofol anaesthesia relates to inherent differences in brain structure and function of the fronto-parietal networks, which can be predicted prior to sedation. Results highlight novel markers for improving awareness monitoring during clinical anaesthesia. Key pointsO_LIModerate propofol anaesthesia showed highly variable effects across individuals C_LIO_LI30% of healthy participants response times were unaffected by anaesthesia and 70% had significantly delayed, fragmented, or fully omitted responses C_LIO_LIGrey matter volume in frontal cortex and functional connectivity of the fronto-parietal networks predicted resilience to anaesthesia C_LI