EFFECTS ON THE THALAMUS AND INSULAR CORTEX DURING VOCAL EMOTION PROCESSING BY MODAFINIL AND BUPROPION: A PHARMACOLOGICAL MRI STUDY

Abstract Background It is known that Modafinil is the medicine to treat Narcolepsy and Attention Deficit Hyperactivity Disorder (ADHD), whereas as a side effect, modafinil is known to react emotional instability and suicidal ideation (Vorspan 2005). Bupropion is used as antidepressant to improve the recognition of negative feelings. These two medicines could affect to cerebral activation of emotional processing. Recent our studies have demonstrated that compared with placebo, modafinil decreased right thalamus activation in the recognition of vocal affective processing, and bupropion increased cerebral activation in the insular and superior temporal gyrus (Hama et.al 2021a, 2021b). However, to our knowledge, no study has not been directly examined these pharamacological effects to emotional brain circuit among the placebo, modafinil and bupropion. Purpose In the present study, we aimed to investigate the effect of modafinil and bupropion on thalamus-insular activation while the subjects were recognizing vocal affective processing, compared with placebo by using a functional MRI. Methods: Sixteen healthy volunteers (male 8) participated in this study. Before the experiments, all participants agreed with the protocol approved by ethics committee. Three series of fMRI scans, using either placebo, modafinil (200mg), or bupropion (150 mg), were examined. Each subject took a medicine before 2 hours of fMRI scanning. An auditory emotional valence judgement task was performed during fMRI scanning. The acute effects of modafinil and bupropion on cerebral activation in the emotional circuit and behavioral performance during emotional processing were analyzed by using SPM analysis, 3×4 full factorial design. Three drugs (placebo, modafinil, and bupropion) effects and 4 emotions (neutral happy, sad, anger) effects were investigated. Results Main effect of drug was significantly observed at the left insular and the right thalamus (FWE p<0.05). In the left insular, compared with placebo, cerebral activation by bupropion was significantly greater, whereas that by modafinil was slightly greater. In the right thalamus, compared with placebo, cerebral activation by modafinil was significantly less, that by bupropion was slightly less. Further, interaction effect between drug and emotion was significantly observed at the posterior cingulate (FWE p<0.05). Discussion and Conclusions From these findings, we confirmed that both modafinil and bupropion affect function of the insular and thalamus in the recognition of the emotion. Especially, modafinil significantly decrease cerebral activation at the right thalamus, bupropion significantly increase cerebral activation at the left insular.