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Modafinil enhances alerting-related brain activity in attention networks



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.


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.


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.


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.


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.

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The authors are entirely responsible for the scientific content of this paper. We are thankful to the Clinical Imaging Center for Healthcare, Nippon Medical School, for their support. In particular, we thank Koji Nagaya, Megumi Hongo, Koji Kanaya, Masaya Suda, and Minoru Sakurai for their technical assistance with the MRI examinations and Michiyo Tamura for research assistance. We also thank Chieko Kishi and Yumiko Fukano for help as clinical research coordinators and Arndt Gerz for his English editing of the manuscript. This work was partially supported by a Grant-in-Aid for Scientific Research (B) (24791237 to Y.I.) from the Japan Society for the Promotion of Science, Japan, and a Ministry of Education, Culture, Sports, Science and Technology-Supported Program for the Strategic Research Foundation at Private Universities, 2008–2012, Japan (S0801035 to H.S.).

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Correspondence to Hidenori Suzuki.

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Ikeda, Y., Funayama, T., Tateno, A. et al. Modafinil enhances alerting-related brain activity in attention networks. Psychopharmacology 234, 2077–2089 (2017).

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