Large-scale EEG neural network changes in response to therapeutic TMS

Brain Stimul. 2022 Mar-Apr;15(2):316-325. doi: 10.1016/j.brs.2022.01.007. Epub 2022 Jan 17.


Background: Transcranial magnetic stimulation (TMS) is an effective therapy for patients with treatment-resistant depression. TMS likely induces functional connectivity changes in aberrant circuits implicated in depression. Electroencephalography (EEG) "microstates" are topographies hypothesized to represent large-scale resting networks. Canonical microstates have recently been proposed as markers for major depressive disorder (MDD), but it is not known if or how they change following TMS.

Methods: Resting EEG was obtained from 49 MDD patients at baseline and following six weeks of daily TMS. Polarity-insensitive modified k-means clustering was used to segment EEGs into constituent microstates. Microstates were localized via sLORETA. Repeated-measures mixed models tested for within-subject differences over time and t-tests compared microstate features between TMS responder and non-responder groups.

Results: Six microstates (MS-1 - MS-6) were identified from all available EEG data. Clinical response to TMS was associated with increases in features of MS-2, along with decreased metrics of MS-3. Nonresponders showed no significant changes in any microstate. Change in occurrence and coverage of both MS-2 (increased) and MS-3 (decreased) correlated with symptom change magnitude over the course of TMS treatment.

Conclusions: We identified EEG microstates associated with clinical improvement following a course of TMS therapy. Results suggest selective modulation of resting networks observable by EEG, which is inexpensive and easily acquired in the clinic setting.

Keywords: EEG; MDD; Microstates; Neuromodulation; TMS.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers
  • Brain / physiology
  • Depressive Disorder, Major* / therapy
  • Electroencephalography
  • Humans
  • Neural Networks, Computer
  • Transcranial Magnetic Stimulation*


  • Biomarkers