Sleep-anticipating effects of melatonin in the human brain

Neuroimage. 2006 May 15;31(1):410-8. doi: 10.1016/j.neuroimage.2005.11.024. Epub 2006 Jan 20.


Melatonin, the hormone produced nocturnally by the pineal gland, is an endogenous regulator of the sleep-wake cycle. The effects of melatonin on brain activities and their relation to induction of sleepiness were studied in a randomized, double-blind, placebo controlled functional magnetic resonance imaging (fMRI) study. Melatonin, but not placebo, reduced task-related activity in the rostro-medial aspect of the occipital cortex during a visual-search task and in the auditory cortex during a music task. These effects correlated with subjective measurements of fatigue. In addition, melatonin enhanced the activation in the left parahippocampus in an autobiographic memory task. Results demonstrate that melatonin modulates brain activity in a manner resembling actual sleep although subjects are fully awake. Furthermore, the fatigue inducing effect of melatonin on brain activity is essentially different from that of sleep deprivation thus revealing differences between fatigues related to the circadian sleep regulation as opposed to increased homeostatic sleep need. Our findings highlight the role of melatonin in priming sleep-associated brain activation patterns in anticipation of sleep.

Publication types

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

MeSH terms

  • Adult
  • Arousal / drug effects
  • Auditory Perception / drug effects
  • Brain / drug effects*
  • Brain Mapping
  • Dominance, Cerebral / drug effects
  • Double-Blind Method
  • Fatigue / physiopathology*
  • Female
  • Humans
  • Image Processing, Computer-Assisted*
  • Magnetic Resonance Imaging*
  • Male
  • Melatonin / pharmacology*
  • Mental Recall / drug effects
  • Oxygen / blood
  • Psychomotor Performance / drug effects
  • Sleep / drug effects*
  • Visual Perception / drug effects
  • Wakefulness / drug effects


  • Melatonin
  • Oxygen