title: Default mode network mechanisms of transcranial magnetic stimulation in depression.
abstract: 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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences (CL, ACC, AE), Stanford University School of Medicine, Palo Alto, California; Brain and Mind Research Institute and Department of Psychiatry (CL, ATD, RG, BL, BJC, MJD), Weill Cornell Medical College. Electronic address: col2004@med.cornell.edu.
authors.forename: Conor
authors.initials: C
authors.lastname: Liston
authors.affiliation: Department of Psychiatry and Behavioral Sciences (CL, ACC, AE), Stanford University School of Medicine, Palo Alto, California; Sierra-Pacific Mental Illness Research, Education, and Clinical Center (ACC, AE), Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Chen
authors.affiliation: Department of Psychiatry (BDZ), Columbia University College of Physicians and Surgeons.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Zebley
authors.affiliation: Brain and Mind Research Institute and Department of Psychiatry (CL, ATD, RG, BL, BJC, MJD), Weill Cornell Medical College.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Drysdale
authors.affiliation: Brain and Mind Research Institute and Department of Psychiatry (CL, ATD, RG, BL, BJC, MJD), Weill Cornell Medical College.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gordon
authors.affiliation: Brain and Mind Research Institute and Department of Psychiatry (CL, ATD, RG, BL, BJC, MJD), Weill Cornell Medical College.
authors.forename: Bruce
authors.initials: B
authors.lastname: Leuchter
authors.affiliation: Department of Radiology (HUV), Weill Cornell Medical College, New York, New York.
authors.forename: Henning U
authors.initials: HU
authors.lastname: Voss
authors.affiliation: Brain and Mind Research Institute and Department of Psychiatry (CL, ATD, RG, BL, BJC, MJD), Weill Cornell Medical College.
authors.forename: B J
authors.initials: BJ
authors.lastname: Casey
authors.affiliation: Department of Psychiatry and Behavioral Sciences (CL, ACC, AE), Stanford University School of Medicine, Palo Alto, California; Sierra-Pacific Mental Illness Research, Education, and Clinical Center (ACC, AE), Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
authors.forename: Amit
authors.initials: A
authors.lastname: Etkin
authors.affiliation: Brain and Mind Research Institute and Department of Psychiatry (CL, ATD, RG, BL, BJC, MJD), Weill Cornell Medical College.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Dubin
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D003865:Major Depressive Disorder / Q000503:physiopathology* / Q000628:therapy*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D050781:Transcranial Magnetic Stimulation
keywords: Central executive network; TMS; default mode network; depression; resting state fMRI