-Original-

Modafinil Decreased Thalamic Activation in Auditory Emotional Processing: A Randomized Controlled Functional Magnetic Resonance Imaging Study

Tomoko Hama^1-3, Michihiko Koeda¹, Yumiko Ikeda⁴, Amane Tateno¹, Tokuhiro Kawara², Hidenori Suzuki⁴ and Yoshiro Okubo¹

¹Department of Neuropsychiatry, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
²Faculty of Health Science Technology, Bunkyo Gakuin University, Tokyo, Japan
³Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences, Ehime, Japan
⁴Department of Pharmacology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan

Background: Modafinil improves wakefulness and attention, is approved in Japan for treatment of narcolepsy, and was reported to be effective for attention-deficit/hyperactivity disorder. However, it was reported to induce emotional instability, including mania, depression, and suicidal ideation. Such side effects may be related to changes in cognitive behavior caused by the effects of modafinil on emotional recognition. However, the effects of modafinil on the neural basis of emotional processing have not been fully verified. We used functional magnetic resonance imaging to investigate the effects of modafinil on the neural basis of auditory emotional processing.
Methods: This study adopted a placebo-controlled within-subject crossover design. Data from 14 participants were analyzed. The effects of modafinil on cerebral activation and task performance during an emotional judgement task were analyzed.
Results: Task accuracy decreased significantly and response time of emotional judgement was significantly delayed by modafinil, as compared with placebo. Right thalamic activation in auditory emotional processing was significantly less in the modafinil condition than in the placebo condition. In addition, reduction of right thalamic activation by modafinil was positively correlated with accuracy of emotional judgement.
Conclusions: Our findings suggest that modafinil acts on the right thalamus and changes behavior and brain function associated with auditory emotional processing. These results indicate that modafinil might change emotional recognition by reducing emotional activation related to social communication.

J Nippon Med Sch 2021; 88: 485-495

Keywords
emotion, fMRI, modafinil, psychopharmacology, thalamus

Correspondence to
Yoshiro Okubo, MD, PhD, Department of Neuropsychiatry, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
okubo-y@nms.ac.jp

Received, December 19, 2020
Accepted, December 26, 2020