Sustained attention and serotonin: a pharmaco-fMRI study

Hum Psychopharmacol. 2008 Apr;23(3):221-30. doi: 10.1002/hup.923.


Objective: Evidence suggests that stimulation of serotonergic function in healthy humans causes an impairment of sustained attention. The present study assessed the influence of increased serotonin levels on brain areas involved in sustained attention.

Methods: Ten healthy volunteers (5 females, 5 males) received the selective serotonin reuptake inhibitor (SSRI) escitalopram (20 mg) and placebo in a balanced, double blind, two-way crossover design. Participants performed the Mackworth Clock Test to measure sustained attention during functional MRI measurements at 3 Tesla. Subjective measurements after pharmacological manipulation were conducted with the Bond and Lader Questionnaire.

Results: Independent of treatment, brain areas associated with task performance on a sustained attention task were activated, including right prefrontal and parietal areas. After escitalopram administration, less activation was shown in the caudate nucleus, thalamus, and frontal areas. No effect of escitalopram was shown on behavioral data although subjective measurements showed decreased alertness after escitalopram.

Conclusions: The results of the current pharmaco-functional magnetic resonance imaging (fMRI) study give a first indication of involvement of serotonin in sustained attention through modulating activation of selective brain areas including the thalamus and caudate nucleus. Possibly, these areas are involved in a subcortical network for sustained attention, but further research is necessary.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Attention / physiology*
  • Behavior / drug effects
  • Brain / anatomy & histology
  • Brain / metabolism*
  • Citalopram / pharmacology*
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Reaction Time
  • Serotonin / physiology*
  • Serotonin Uptake Inhibitors / pharmacology*


  • Serotonin Uptake Inhibitors
  • Citalopram
  • Serotonin