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Background: Dysfunctional neuroplasticity may be one of the pathophysiological mechanisms underlying major depression. We have previously established methods to assess neuroplasticity from the dorsolateral prefrontal cortex (DLPFC) using a paired associative stimulation (PAS) paradigm, which pairs a preceding peripheral nerve stimulation with subsequent transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG). We aimed to investigate neuroplasticity through the PAS paradigm in the DLPFC in patients with depression compared to healthy subjects.Methods: Twenty-nine patients with depression and 28 healthy controls participated in this study. There were no significant age or sex differences between the two groups. All participants received PAS paradigm in the DLPFC. We analyzed PAS induced potentiation from the DLPFC in both groups calculating the power of TMS-evoked potentials (TEP). A two-way ANOVA with PAS effect as a within-subject factor and diagnostic group as a between-subject factor was performed to examine the group differences in the PAS paradigm.Results: DLPFC-PAS induced a significant potentiation at the stimulation site in both patients and healthy subjects (mean ± SD: 1.24 ± 0.33 [μV] vs. 1.48 ± 0.28 [μV]). However, when we compared PAS potentiation between patients and healthy subjects, there were significant main effects of PAS (F1,53  = 68.63, p < 0.0001) and PAS-by-diagnostic group interaction (F1,53  = 25.05, p < 0.0001). Post hoc analysis demonstrated that patients had a significantly lower PAS potentiation compared to healthy subjects (t55  = 3.128, p = 0.003).Conclustions: Our findings provide evidence for impaired neuroplasticity in DLPFC in patients with depression compared to healthy subjects. Such findings may ultimately help us understand the pathophysiology of MDD and mechanisms involved in its treatment. [ABSTRACT FROM AUTHOR]