Intra- and Extracellular White Matter Micromorphology Predict the Antidepressant Effects of Transcranial Magnetic Stimulation in Patients With Major Depressive Disorder

Abstract

Background: Transcranial magnetic stimulation (TMS) is a widely used treatment for major depressive disorders (MDD). However, its physiological effects remain unclear, and its efficacy varies among patients. Functional connectivity (FC) within MDD-related networks has shown potential for predicting TMS efficacy. White matter (WM) micromorphology contributes to these connections and may provide new insights into the prediction of TMS effects and its antidepressant mechanism in MDD, which has not been thoroughly investigated. Therefore, this study aimed to identify potential predictors of TMS efficacy using whole-brain WM microstructural characteristics.

Methods: This retrospective study included 41 patients with MDD who completed 20-session TMS treatments. We examined intra- and extracellular WM using neurite orientation dispersion and density imaging (NODDI). We examined the correlations between pre-TMS whole-brain WM measures and the reduction in Montgomery–Åsberg Depression Rating Scale (MADRS) scores after TMS, as well as the longitudinal changes in regional WM measures correlated with MADRS reduction.

Results: The pre-TMS intracellular neurite density index (NDI) within the bilateral internal capsule (IC), right posterior corona radiata (PCR), right superior corona radiata (SCR), corpus callosum (CC), and bilateral posterior thalamic radiation (PTR) were positively associated with the reduction in MADRS scores. The pre-TMS extracellular free-water fraction (FWF) within the bilateral IC, splenium of the CC, and right SCR was significantly related to the reduction in MADRS scores. The FWF within the left posterior limb of the IC, left PCR, and left SCR decreased after TMS treatment.

Limitations: The study’s findings cannot rule out the potential effects of concurrent pharmaceutical therapies, as a control group not receiving TMS treatment was not included.

Conclusions: Regional NDI and FWF values at baseline could predict TMS efficacy in patients with MDD. Reducing the extracellular FWF in the left hemisphere may be a potential therapeutic mechanism of TMS in MDD.