Escitalopram Decreases Cross-Regional Functional Connectivity within the Default-Mode Network

PLoS One. 2013 Jun 27;8(6):e68355. doi: 10.1371/journal.pone.0068355. Print 2013.

Abstract

The default-mode network (DMN), which comprises medial frontal, temporal and parietal regions, is part of the brain's intrinsic organization. The serotonergic (5-HT) neurotransmitter system projects to DMN regions from midbrain efferents, and manipulation of this system could thus reveal insights into the neurobiological mechanisms of DMN functioning. Here, we investigate intrinsic functional connectivity of the DMN as a function of activity of the serotonergic system, through the administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram. We quantified DMN functional connectivity using an approach based on dual-regression. Specifically, we decomposed group data of a subset of the functional time series using spatial independent component analysis, and projected the group spatial modes to the same and an independent resting state time series of individual participants. We found no effects of escitalopram on global functional connectivity of the DMN at the map-level; that is, escitalopram did not alter the global functional architecture of the DMN. However, we found that escitalopram decreased DMN regional pairwise connectivity, which included anterior and posterior cingulate cortex, hippocampal complex and lateral parietal regions. Further, regional DMN connectivity covaried with alertness ratings across participants. Our findings show that escitalopram altered intrinsic regional DMN connectivity, which suggests that the serotonergic system plays an important role in DMN connectivity and its contribution to cognition. Pharmacological challenge designs may be a useful addition to resting-state functional MRI to investigate intrinsic brain functional organization.

Publication types

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

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / physiology*
  • Brain Mapping
  • Citalopram / pharmacology*
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Rest
  • Serotonin / metabolism
  • Serotonin Uptake Inhibitors / pharmacology*

Substances

  • Serotonin Uptake Inhibitors
  • Citalopram
  • Serotonin

Grant support

This study was in part financially supported by grants from pharmaceutical industries (Organon, Pierre Fabre, FAES pharma, GSK) and the European Committee to JR, and by grants from the Netherlands Organisation for Scientific Research (NWO) to VV, JR and EF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.