Circadian and homeostatic modulation of functional connectivity and regional cerebral blood flow in humans under normal entrained conditions

J Cereb Blood Flow Metab. 2014 Sep;34(9):1493-9. doi: 10.1038/jcbfm.2014.109. Epub 2014 Jun 18.


Diurnal rhythms have been observed in human behaviors as diverse as sleep, olfaction, and learning. Despite its potential impact, time of day is rarely considered when brain responses are studied by neuroimaging techniques. To address this issue, we explicitly examined the effects of circadian and homeostatic regulation on functional connectivity (FC) and regional cerebral blood flow (rCBF) in healthy human volunteers, using whole-brain resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). In common with many circadian studies, we collected salivary cortisol to represent the normal circadian activity and functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Intriguingly, the changes in FC and rCBF we observed indicated fundamental decreases in the functional integration of the default mode network (DMN) moving from morning to afternoon. Within the anterior cingulate cortex (ACC), our results indicate that morning cortisol levels are negatively correlated with rCBF. We hypothesize that the homeostatic mechanisms of the HPA axis has a role in modulating the functional integrity of the DMN (specifically, the ACC), and for the purposes of using fMRI as a tool to measure changes in disease processes or in response to treatment, we demonstrate that time of the day is important when interpreting resting-state data.

Publication types

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

MeSH terms

  • Adult
  • Blood Flow Velocity / physiology
  • Cerebral Angiography
  • Cerebrovascular Circulation / physiology*
  • Circadian Rhythm / physiology*
  • Gyrus Cinguli* / blood supply
  • Gyrus Cinguli* / diagnostic imaging
  • Gyrus Cinguli* / physiology
  • Humans
  • Hydrocortisone / metabolism
  • Hypothalamo-Hypophyseal System* / blood supply
  • Hypothalamo-Hypophyseal System* / diagnostic imaging
  • Hypothalamo-Hypophyseal System* / physiology
  • Magnetic Resonance Angiography
  • Male
  • Pituitary-Adrenal System* / blood supply
  • Pituitary-Adrenal System* / diagnostic imaging
  • Pituitary-Adrenal System* / physiology
  • Saliva / metabolism


  • Hydrocortisone