Abstract

Altered connectivity within and between the resting-state networks (RSNs) brought about by anesthetics that induce altered consciousness remains incompletely understood. It is known that the dorsal attention network (DAN) and its anticorrelations with other RSNs have been implicated in consciousness. However, the role of DAN-related functional patterns in drug-induced sedative effects is less clear. In the current study, we investigated altered functional connectivity of the DAN during midazolam-induced light sedation. In a placebo-controlled and within-subjects experimental study, fourteen healthy volunteers received midazolam or saline with a 1-week interval. Resting-state fMRI data were acquired before and after intravenous drug administration. A multiple region of interest-driven analysis was employed to investigate connectivity within and between RSNs. It was found that functional connectivity was significantly decreased by midazolam injection in two regions located in the left inferior parietal lobule and the left middle temporal area within the DAN as compared with the saline condition. We also identified three clusters in anticorrelation between the DAN and other RSNs for the interaction effect, which included the left medial prefrontal cortex, the right superior temporal gyrus, and the right superior frontal gyrus. Connectivity between all regions and DAN was significantly decreased by midazolam injection. The sensorimotor network was minimally affected. Midazolam decreased functional connectivity of the dorsal attention network. These findings advance the understanding of the neural mechanism of sedation, and such functional patterns might have clinical implications in other medical conditions related to patients with cognitive impairment.

Highlights

  • Conscious sedation represents an initial stage of anesthesia accompanying alteration of consciousness [1]

  • Considering neuroimaging evidence, awareness may depend on two main resting-state networks (RSNs): a dorsal attention network (DAN) routinely mediating external processing and attention-demanding cognitive function and a default mode network (DMN), which is engaged during self-related processes [21,22]

  • As compared with the saline condition, functional connectivity within the DAN was significantly decreased by midazolam injection located in the left IPL and the left motion complex (MT) (Figure 4 and Supplementary Table S1)

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Summary

Introduction

Conscious sedation represents an initial stage of anesthesia accompanying alteration of consciousness [1]. Anesthesia alters brain activity and regional cerebral metabolism in a dose-dependent manner, and different anesthetic agents may produce a variety of functional connectivity patterns [8,14]. Functional connectivity changes during anesthetic-induced light sedation are still unclear, and RSNs that may be sensitive to alterations in states of consciousness still require further investigation. In our previous study, which was restricted to the functional connectivity within different resting-state networks, we did not identify significant connectivity changes within the DMN during midazolam-induced light sedation [26]. Changes in functional connectivity within the DAN are still poorly investigated, hampering our understanding of the neural basis of the effects of midazolam-induced light sedation on external awareness

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