White matter markers and predictors for subject-specific rTMS response in major depressive disorder

• Published in: Journal of affective disorders Vol. 299; pp. 207 - 214
• Main Authors: Ning, Lipeng, Rathi, Yogesh, Barbour, Tracy, Makris, Nikos, Camprodon, Joan A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2022
• Subjects: Depression; Depressive Disorder, Major - diagnostic imaging; Depressive Disorder, Major - therapy; Diffusion MRI; Gyrus Cinguli; Humans; Neural plasticity; Predictor; Prefrontal Cortex - diagnostic imaging; Psychiatric/Mental Health; Transcranial Magnetic Stimulation; Treatment Outcome; White Matter - diagnostic imaging; Neural plasticity; Depression; Diffusion MRI; Transcranial magnetic stimulation; Predictor; diffusion MRI; predictor; transcranial magnetic stimulation; depression; neural plasticity
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2021.12.005

•rTMS-induced microstructural changes in patients with depression are examined using dMRI.•Subject-specific brain targets were used for treatment based on the functional connectivity.•rTMS has changed dMRI measures in fiber bundles connected the anterior-medial-prefrontal cortex.•Changes in dMRI measures of lateral-prefrontal fiber bundles are related with improved response.•dMRI measures of lateral-prefrontal fiber bundles at baseline can predict treatment response. Repetitive transcranial magnetic stimulation (rTMS) has established therapeutic efficacy for major depressive disorder (MDD). While translational research has focused primarily on understanding the mechanism of action of TMS on functional activation and connectivity, the effects on structural connectivity remain largely unknown especially when rTMS is applied using subject-specific brain targets. This study aims to use novel diffusion magnetic resonance imaging (dMRI) analysis to examine microstructural changes related to rTMS treatment response using a unique cohort of 21 patients with MDD treated using rTMS with subject-specific targets. White matter dMRI microstructural measures and clinical scores were captured before and after the full course of treatment. We defined disease-relevant fiber bundles connected to different subregions of the left prefrontal cortex and analyzed changes in diffusion properties as well as correlations between the changes of dMRI measures and the changes in Hamilton Depression Rating Scale (HAMD). No significant changes were observed in tracts connected to the TMS targets. rTMS significantly increased the extra-axonal free-water volume, fractional anisotropy and decreased the radial diffusivity in anterior-medial prefrontal fiber bundles but did not lead to raw changes in lateral prefrontal tracts. That said, the microstructural changes in the lateral prefrontal white matter were significantly correlated with treatment response. Moreover, pre-rTMS dMRI measures of the dorsal anterior cingulate cortex and lateral prefrontal cortex connections are correlated with changes in HAMD scores. Microstructural changes in the anterior-medial and lateral prefrontal white matter are potentially involved in treatment response to TMS, though further investigation is needed using larger datasets.