Unresponsiveness induced by sevoflurane and propofol is associated with reduced basal forebrain cholinergic nuclei functional connectivity in humans, a pilot exploratory study

Abstract

Studies suggest the cholinergic system is involved in anesthesia-induced unconsciousness, hence unresponsiveness. A significant source of cholinergic innervation comes from basal forebrain cholinergic nuclei (BFCN), with bi-directional connections between anterior BFCN and the default mode network (DMN). Since DMN functional connectivity (FC) is consistently reduced during anesthesia-induced unresponsiveness in humans, we hypothesized that BFCN-FC during anesthesia-induced unresponsiveness is reduced and particularly, anterior BFCN-FC reductions might be related to DMN-FC reductions. Resting-state fMRI (rs-fMRI) signal correlations (i.e., a proxy for FC) were calculated. FC seeds were anterior and posterior BFCN and the DMN. Rs-fMRI data come from healthy male controls during wakefulness and anesthesia with sevoflurane (n = 15) (at fixed concentrations: 2 and 3 vol%) and propofol titrated to the endpoint of clinical unresponsiveness (n = 12), respectively. FC state differences were tested via paired t-tests; FC changes for anterior BFCN and DMN were associated via correlation analysis. We found reduced anterior and posterior BFCN-FC with sevoflurane and propofol compared to wakefulness. The correlation between reduced DMN-FC-and anterior BFCN-FC reductions was r = 0.57 (p = 0.01) for sevoflurane 3 vol%, r = 0.34 (p = 0.11) for sevoflurane 2 vol% and r = 0.47 (p = 0.06) for propofol. In summary, in this exploratory pilot study, we demonstrated reduced BFCN-FC and a potential correlation between reduced anterior BFCN-FC and DMN-FC during sevoflurane and propofol anesthesia. This suggests DMN changes as a potential factor of anterior BFCN-FC reductions during anesthesia-induced unresponsiveness and BFCN-FC reduction as a potential sign of such state.