Disruption of cortical integration during midazolam-induced light sedation.

Abstract

This work examines the effect of midazolam‐induced light sedation on intrinsic functional connectivity of human brain, using a randomized, double‐blind, placebo‐controlled, cross‐over, within‐subject design. Fourteen healthy young subjects were enrolled and midazolam (0.03 mg/kg of the participant's body mass, to a maximum of 2.5 mg) or saline were administrated with an interval of one week. Resting‐state fMRI was conducted before and after administration for each subject. We focus on two types of networks: sensory related lower‐level functional networks and higher‐order functions related ones. Independent component analysis (ICA) was used to identify these resting‐state functional networks. We hypothesize that the sensory (visual, auditory, and sensorimotor) related networks will be intact under midazolam‐induced light sedation while the higher‐order (default mode, executive control, salience networks, etc.) networks will be functionally disconnected. It was found that the functional integrity of the lower‐level networks was maintained, while that of the higher‐level networks was significantly disrupted by light sedation. The within‐network connectivity of the two types of networks was differently affected in terms of direction and extent. These findings provide direct evidence that higher‐order cognitive functions including memory, attention, executive function, and language were impaired prior to lower‐level sensory responses during sedation. Our result also lends support to the information integration model of consciousness. Hum Brain Mapp 36:4247–4261, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.