Modafinil enhances alerting-related brain activity in attention networks

Psychopharmacology (Berl). 2017 Jul;234(14):2077-2089. doi: 10.1007/s00213-017-4614-9. Epub 2017 Apr 3.


Rationale: Modafinil is a wake-promoting agent and has been reported to be effective in improving attention in patients with attentional disturbance. However, neural substrates underlying the modafinil effects on attention are not fully understood.

Objectives: We employed a functional magnetic resonance imaging (fMRI) study with the attention network test (ANT) task in healthy adults and examined which networks of attention are mainly affected by modafinil and which neural substrates are responsible for the drug effects.

Methods: We used a randomized placebo-controlled within-subjects cross-over design. Twenty-three healthy adults participated in two series of an fMRI study, taking either a placebo or modafinil. The participants performed the ANT task, which is designed to measure three distinct attentional networks, alerting, orienting, and executive control, during the fMRI scanning. The effects of modafinil on behavioral performance and regional brain activity were analyzed.

Results: We found that modafinil enhanced alerting performance and showed greater alerting network activity in the left middle and inferior occipital gyri as compared with the placebo. The brain activations in the occipital regions were positively correlated with alerting performance.

Conclusions: Modafinil enhanced alerting performance and increased activation in the occipital lobe in the alerting network possibly relevant to noradrenergic activity during the ANT task. The present study may provide a rationale for the treatment of patients with distinct symptoms of impaired attention.

Keywords: Alerting; Attention network test; Modafinil; fMRI.

MeSH terms

  • Adult
  • Attention / drug effects*
  • Benzhydryl Compounds / pharmacology*
  • Brain / physiopathology*
  • Cross-Over Studies
  • Executive Function / physiology*
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Modafinil
  • Orientation
  • Wakefulness-Promoting Agents / pharmacology*


  • Benzhydryl Compounds
  • Wakefulness-Promoting Agents
  • Modafinil