The effects of propofol anaesthesia on molecular-enriched networks during resting-state and naturalistic listening

Placing a patient in a state of anaesthesia is crucial for modern surgical practice. However, the mechanisms by which anaesthetic drugs, such as propofol, impart their effects on consciousness remain poorly understood. Propo-fol potentiates GABAergic transmission, which purportedly has direct actions on cortex as well as indirect actions via ascending neuromodulatory systems. Functional imaging studies to date have been limited in their ability to unravel how these effects on neurotransmission impact the system-level dynamics of the brain. Here, we leveraged advances in multi-modal imaging, Receptor-Enriched Analysis of functional Connectivity by Targets (REACT), to investigate how different levels of propofol-induced sedation alter neurotransmission-related functional connec-tivity (FC), both at rest and when individuals are exposed to naturalistic auditory stimulation. Propofol increased GABA-A-and noradrenaline transporter-enriched FC within occipital and somatosensory regions respectively. Additionally, during auditory stimulation, the network related to the dopamine transporter showed reduced FC within bilateral regions of temporal and mid/posterior cingulate cortices, with the right temporal cluster showing an interaction between auditory stimulation and level of consciousness. In bringing together these micro-and macro-scale systems, we provide support for both direct GABAergic and indirect noradrenergic and dopaminergic-related network changes under propofol sedation. Further, we delineate a cognition-related reconfiguration of the dopaminergic network, highlighting the utility of REACT to explore the molecular substrates of consciousness and cognition.