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

Abstract

Background: Modafinil is effective for improving wakefulness and attention, is used to treat patients with narcolepsy as an approved drug in Japan, and has been reported to be effective in attention-deficit hyperactivity disorder. On the other hand, modafinil has been reported to induce emotional instability including mania, depression, and suicidal ideation. Such side effects may be related to changes in cognitive behavior by the influence of modafinil on cerebral function of emotional recognition. However, the effect of modafinil on the neural basis of emotional processing has not been fully verified. We aimed to clarify the effects of modafinil on the neural basis of auditory emotional processing by functional magnetic resonance imaging. Methods: This study adopted a placebo-controlled within-subject cross-over design. The data of 14 subjects were finally analyzed. The effect of modafinil on cerebral activation and task performance during an emotional judgement task was analyzed. Results: Accuracy of the task decreased significantly and response time of emotional judgement was significantly delayed by modafinil compared with placebo. Right thalamic activation in auditory emotional processing was significantly less in the modafinil group than the placebo group. In addition, reduction of right thalamic activation by modafinil was positively correlated with the decrease in accuracy of emotional judgement. Conclusions: Our findings suggest that modafinil could act on the right thalamus, changing the behavior and brain function associated with auditory emotional processing. These results indicate that modafinil could change emotional recognition by reducing emotional activation related to social communication.