Persistent cognitive impairment in major depressive disorder (MDD) affects both treatment outcomes and psychosocial functioning, emphasizing the critical need for effective treatment. However, there is still a lack of effective treatment at present. Our previous studies found that the impairment in cognitive flexibility (CF) persisted even in remitted patients with MDD. This impairment was correlated with hypo-connectivity between the left inferior parietal lobule (IPL) and the right dorsal prefrontal cortex (dPFC). Based on these findings, we hypothesize that the hypo-connectivity between the left IPL and the right dPFC is the neural basis of CF impairment, and targeted interventions of this connection may alleviate CF impairment and thus improve treatment outcomes as well as psychosocial functioning of patients with MDD. The present study proposes to employ cognitive training for MDD patients with CF impairment. By comparing changes in CF and brain functional connectivity via task-based fMRI before and after the intervention, we aim to clarify the effect of cognitive training on cognitive performance, treatment outcomes and psychosocial functioning, and identify the critical role of the hypo-connectivity between the left IPL and the right dPFC underlying CF impairment. Furthermore, we will conduct a randomized controlled trial to investigate the effect of individualized dual-target repetitive transcranial magnetic stimulation (rTMS) on CF by targeting the hypo connectivity between the left IPL and the right dPFC. The results will further validate the critical role of this connection in modulating CF performance and provide a reliable intervention target for reducing CF impairment.
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Change in cognitive flexibility assessed by Trail Making Test Part B minus Part A (TMT B-A)
Timeframe: Baseline to 4 weeks