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Default Mode Network Mechanisms of Transcranial Magnetic Stimulation in Depression

  • Conor Liston
    Correspondence
    Address correspondence to Conor Liston, M.D., Ph.D., Weill Cornell Medical College; Brain and Mind Research Institute and Department of Psychiatry, Belfer Research Building, 413 East 69th Street, Box 240, New York, NY 10021
    Affiliations
    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
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  • Ashley C. Chen
    Affiliations
    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
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  • Benjamin D. Zebley
    Affiliations
    Department of Psychiatry (BDZ), Columbia University College of Physicians and Surgeons
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  • Andrew T. Drysdale
    Affiliations
    Brain and Mind Research Institute and Department of Psychiatry (CL, ATD, RG, BL, BJC, MJD), Weill Cornell Medical College
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  • Rebecca Gordon
    Affiliations
    Brain and Mind Research Institute and Department of Psychiatry (CL, ATD, RG, BL, BJC, MJD), Weill Cornell Medical College
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  • Bruce Leuchter
    Affiliations
    Brain and Mind Research Institute and Department of Psychiatry (CL, ATD, RG, BL, BJC, MJD), Weill Cornell Medical College
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  • Henning U. Voss
    Affiliations
    Department of Radiology (HUV), Weill Cornell Medical College, New York, New York
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  • B.J. Casey
    Affiliations
    Brain and Mind Research Institute and Department of Psychiatry (CL, ATD, RG, BL, BJC, MJD), Weill Cornell Medical College
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  • Amit Etkin
    Affiliations
    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
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  • Marc J. Dubin
    Affiliations
    Brain and Mind Research Institute and Department of Psychiatry (CL, ATD, RG, BL, BJC, MJD), Weill Cornell Medical College
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Published:February 07, 2014DOI:https://doi.org/10.1016/j.biopsych.2014.01.023

      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.

      Key Words

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