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Updated: May 10, 2026
Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method
Published on: August 2, 2021
A cell type-specific mechanism driving the rapid antidepressant effects of transcranial magnetic stimulation
Michael W Gongwer1, Alex Qi2, Alexander S Enos3
1Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Neuroscience Interdepartmental Program, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Medical Scientist Training Program, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Abstract:
Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for brain disorders, but its therapeutic mechanism is poorly understood. We developed a mouse model of rTMS with superior clinical face validity and investigated the neural mechanism by which accelerated intermittent theta burst stimulation (aiTBS), the first rapid-acting rTMS antidepressant protocol, reversed chronic stress-induced behavioral deficits. Using fiber photometry, we showed that aiTBS drives distinct patterns of neural activity in intratelencephalic (IT) and pyramidal tract (PT) projection neurons in dorsomedial prefrontal cortex (dmPFC). However, only IT neurons exhibited persistently increased activity during both aiTBS and subsequent depression-related behaviors. aiTBS reversed stress-related loss of dendritic spines on IT, but not PT neurons, further demonstrating cell type-specific effects of stimulation. Chemogenetically inhibiting dmPFC IT, but not PT neurons, during rTMS blocked the antidepressant-like behavioral effects of aiTBS. Thus, we demonstrate a prefrontal mechanism linking rapid aiTBS-driven therapeutic effects to cell type-specific circuit plasticity.
