Default mode network mechanisms of transcranial magnetic stimulation in depression.

TitleDefault mode network mechanisms of transcranial magnetic stimulation in depression.
Publication TypeJournal Article
Year of Publication2014
AuthorsListon C, Chen AC, Zebley BD, Drysdale AT, Gordon R, Leuchter B, Voss HU, Casey BJ, Etkin A, Dubin MJ
JournalBiol Psychiatry
Date Published2014 Oct 01
KeywordsAdult, Brain, Brain Mapping, Depressive Disorder, Major, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Transcranial Magnetic Stimulation

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for depression, but its underlying mechanism of action remains unknown. Abnormalities in two large-scale neuronal networks-the frontoparietal central executive network (CEN) and the medial prefrontal-medial parietal default mode network (DMN)-are consistent findings in depression and potential therapeutic targets for TMS. Here, we assessed the impact of TMS on activity in these networks and their relation to treatment response.

METHODS: We used resting state functional magnetic resonance imaging to measure functional connectivity within and between the DMN and CEN in 17 depressed patients, before and after a 5-week course of TMS. Motivated by prior reports, we focused on connectivity seeded from the DLPFC and the subgenual cingulate, a key region closely aligned with the DMN in depression. Connectivity was also compared with a cohort of 35 healthy control subjects.

RESULTS: Before treatment, functional connectivity in depressed patients was abnormally elevated within the DMN and diminished within the CEN, and connectivity between these two networks was altered. Transcranial magnetic stimulation normalized depression-related subgenual hyperconnectivity in the DMN but did not alter connectivity in the CEN. Transcranial magnetic stimulation also induced anticorrelated connectivity between the DLPFC and medial prefrontal DMN nodes. Baseline subgenual connectivity predicted subsequent clinical improvement.

CONCLUSIONS: Transcranial magnetic stimulation selectively modulates functional connectivity both within and between the CEN and DMN, and modulation of subgenual cingulate connectivity may play an important mechanistic role in alleviating depression. The results also highlight potential neuroimaging biomarkers for predicting treatment response.

Alternate JournalBiol. Psychiatry
PubMed ID24629537
PubMed Central IDPMC4209727
Grant ListP50-MH079513 / MH / NIMH NIH HHS / United States
P50 MH079513 / MH / NIMH NIH HHS / United States
R00 MH097822 / MH / NIMH NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States
K99 MH097822 / MH / NIMH NIH HHS / United States