Gamma-hydroxybutyrate increases brain resting-state functional connectivity of the salience network and dorsal nexus in humans

Neuroimage. 2018 Jun:173:448-459. doi: 10.1016/j.neuroimage.2018.03.011. Epub 2018 Mar 7.

Abstract

According to the triple network hypothesis the brain is equipped with three core neurocognitive networks: the default mode (DMN), the salience (SN), and the central executive (CEN) network. Moreover, the so called dorsal nexus, has met growing interest as it is a hub region connecting these three networks. Assessment of resting-state functional connectivity (rsFC) of these networks enables the elucidation of drug-induced brain alterations. Gamma-hydroxybutyrate (GHB) is a GHB/GABA-B receptor agonist that induces a paradoxical state of mixed stimulation and sedation at moderate doses, which makes it a valuable tool to investigate neural signatures of subjective drug effects. Employing a placebo-controlled, double-blind, randomized, cross-over design, we assessed the effects of GHB (35 mg/kg p. o.) in 19 healthy male subjects on DMN-, SN-, CEN-, and dorsal nexus-rsFC measured by functional magnet resonance imaging and applying independent component as well as seed-based analyses, while subjective drug effects were investigated using visual analog scales (VAS). Subjectively, GHB increased VAS ratings of a general drug effect, stimulation, and sedation. Intrinsic DMN-, and CEN-rsFC remained largely unchanged under GHB, but the drug increased SN-DMN-rsFC and SN-dorsal nexus-rsFC, while dorsal nexus-rsFC was reciprocally increased to both the SN (right anterior insula) and to the CEN (right middle frontal gyrus). Increased sedation significantly predicted the observed SN-dorsal nexus-rsFC. In conclusion, GHB generates a unique stimulant/sedative subjective state that is paralleled by a complex pattern of increased functional connectivity encompassing all three core neurocognitive networks of the brain, while increased SN-dorsal nexus-rsFC was demonstrated to be a potential signature of the sedative component of the drug effect.

Keywords: Attention network; Dorsomedial prefrontal cortex; Fronto-parietal network; Intrinsic connectivity; Pharmaco-fMRI; Sodium oxybate.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Brain / drug effects*
  • Brain / physiology
  • Brain Mapping / methods
  • Double-Blind Method
  • GABA-B Receptor Agonists / pharmacology*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Nerve Net / drug effects*
  • Nerve Net / physiology
  • Sodium Oxybate / pharmacology*
  • Young Adult

Substances

  • GABA-B Receptor Agonists
  • Sodium Oxybate