Journal article
Global connectivity and local excitability changes underlie antidepressant effects of repetitive transcranial magnetic stimulation
Neuropsychopharmacology (New York, N.Y.), Vol.45(6), pp.1018-1025
05/01/2020
DOI: 10.1038/s41386-020-0633-z
PMCID: PMC7162876
PMID: 32053828
Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a commonly- used treatment for major depressive disorder (MDD). However, our understanding of the mechanism by which TMS exerts its antidepressant effect is minimal. Furthermore, we lack brain signals that can be used to predict and track clinical outcome. Such signals would allow for treatment stratification and optimization. Here, we performed a randomized, sham-controlled clinical trial and measured electrophysiological, neuroimaging, and clinical changes before and after rTMS. Patients (N = 36) were randomized to receive either active or sham rTMS to the left dorsolateral prefrontal cortex (dlPFC) for 20 consecutive weekdays. To capture the rTMS-driven changes in connectivity and causal excitability, resting fMRI and TMS/EEG were performed before and after the treatment. Baseline causal connectivity differences between depressed patients and healthy controls were also evaluated with concurrent TMS/fMRI. We found that active, but not sham rTMS elicited (1) an increase in dlPFC global connectivity, (2) induction of negative dlPFC-amygdala connectivity, and (3) local and distributed changes in TMS/EEG potentials. Global connectivity changes predicted clinical outcome, while both global connectivity and TMS/EEG changes tracked clinical outcome. In patients but not healthy participants, we observed a perturbed inhibitory effect of the dlPFC on the amygdala. Taken together, rTMS induced lasting connectivity and excitability changes from the site of stimulation, such that after active treatment, the dlPFC appeared better able to engage in top-down control of the amygdala. These measures of network functioning both predicted and tracked clinical outcome, potentially opening the door to treatment optimization.
Details
- Title: Subtitle
- Global connectivity and local excitability changes underlie antidepressant effects of repetitive transcranial magnetic stimulation
- Creators
- Neir Eshel - Stanford UniversityCorey J. Keller - Stanford UniversityWei Wu - Stanford UniversityJing Jiang - Stanford UniversityColleen Mills-Finnerty - Stanford UniversityJulia Huemer - Medical University of ViennaRachael Wright - Stanford UniversityGregory A. Fonzo - Stanford UniversityNaho Ichikawa - Hiroshima UniversityDavid Carreon - Stanford UniversityMelinda Wong - Stanford UniversityAndrew Yee - Stanford UniversityEmmanuel Shpigel - Stanford UniversityYi Guo - ShenZhen People’s HospitalLisa McTeague - Medical University of South CarolinaAdi Maron-Katz - Stanford UniversityAmit Etkin - Stanford University
- Resource Type
- Journal article
- Publication Details
- Neuropsychopharmacology (New York, N.Y.), Vol.45(6), pp.1018-1025
- Publisher
- Springer Nature
- DOI
- 10.1038/s41386-020-0633-z
- PMID
- 32053828
- PMCID
- PMC7162876
- ISSN
- 0893-133X
- eISSN
- 1740-634X
- Number of pages
- 8
- Grant note
- DP1 MH116506; T32 MH019908; K23 MH104849; K23 MH118466; R01 MH126639; T32 MH019938 / NIMH NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) DP5 OD028128 / NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 05/01/2020
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984360004002771
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