Possible additive effects of combining rTMS with cognitive control training on mood and cognition in healthy subjects

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Major depressive disorder (MDD) is a highly prevalent mental disorder and a leading cause of disability worldwide. Current treatments are not always effective, especially for treatment resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) on the dorsolateral prefrontal cortex (DLPFC) is an effective treatment for TRD by normalising depression related activity, but the effectiveness can be further improved. The mechanism of action is believed to be the modulation of cognitive control and HF-rTMS on the DLPFC improves cognitive control. Cognitive control training (CCT) is another effective treatment for depression by improving cognitive control which also targets the DLPFC. This randomised study investigates whether the combination of rTMS and CCT could have possible additive augmentation effects on mood and cognitive control in a healthy population. In a randomised order 17 participants received a single session of neuronavigated high-frequency rTMS with CCT, and a single session of neuronavigated high-frequency rTMS with a control task. After each intervention a negative mood was induced. We found no additive augmentation effects of the combination of rTMS and CCT on mood and cognitive control. Effects of the negative mood induction on mood and cognitive control were established, but no effects of rTMS and CCT were found to negate these induced negative mood affects. Overall, our results demonstrate that no additive augmentation effects were found by combining rTMS and CCT in a healthy population, even with the methodological improvement of the use of resting state-fMRI based neuronavigation with individualised targets. Combining rTMS with CCT as cognitive task has not shown any indication of augmentation effects for potential application in clinical practice to improve treatment efficacy. However, the personalisation of rTMS with personalised targets and resting state-fMRI based neuronavigation could be valuable for clinical implementation. keywords mood induction, rTMS, cognitive control training, resting state-fMRI based neuronavigation, augmentation
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