Disruption of cortical integration during midazolam-induced light sedation

Hum Brain Mapp. 2015 Nov;36(11):4247-61. doi: 10.1002/hbm.22914. Epub 2015 Aug 28.

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.

Keywords: independent component analysis (ICA); midazolam; resting-state functional MRI (rs-fMRI); sedation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cerebral Cortex / drug effects*
  • Connectome / methods*
  • Conscious Sedation
  • Double-Blind Method
  • Female
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / pharmacology*
  • Male
  • Mental Processes / drug effects*
  • Midazolam / administration & dosage
  • Midazolam / pharmacology*
  • Nerve Net / drug effects*
  • Young Adult

Substances

  • Hypnotics and Sedatives
  • Midazolam