The amnesic effects of propofol on functional connectivity in the hippocampus determined by functional magnetic resonance imaging in volunteers

Abstract

Background One of the primary actions of general anaesthetic agents, apart from inducing a state of unconsciousness, is reversible impairment of memory formation during the period of administration. Failure to induce and maintain amnesia can result in recall of accidental intraoperative awareness and contribute to adverse psychological health outcomes. The precise mechanisms of action by which general anaesthetics achieve their amnesic effects are not fully understood. To this end, we focused on the hippocampus, a region critical for the formation of new episodic explicit long-term memories of the type normally inhibited by general anaesthetics. Methods We enrolled 25 healthy adult volunteers who underwent functional magnetic resonance neuroimaging (fMRI) whilst sedated with a plasma target-controlled infusion of the anaesthetic agent propofol. The functional connectivity (synchronised neuronal activity with other brain regions) of the hippocampus and microanatomical hippocampal subregions was assessed at baseline, under sedation, and during recovery. Serial plasma propofol concentrations and responses to an auditory stimulus semantic decision task were measured. Post-scanning memory testing was conducted, and memory performance was related to the fMRI data. Results Functional connectivity changes associated with an amnesic but subhypnotic depth of propofol sedation were predominantly characterised by a reduced connectivity signature of the hippocampus stratum radiatum, stratum lacunosum, stratum moleculare, CA1 stratum pyramidalis, and CA4/dentate gyrus subfields with the precuneus. Conclusions We provide evidence for differential actions of propofol on hippocampal subdivisions and limbic circuits related to amnesic efficacy, which suggests a more significant role of the precuneus in long-term memory consolidation than previously thought.