Default mode network mechanisms of transcranial magnetic stimulation in depression

Liston, Conor; Chen, Ashley C.; Zebley, Benjamin D.; Drysdale, Andrew T.; Gordon, Rebecca; Leuchter, Bruce; Voss, Henning U.; Casey, B.J.; Etkin, Amit; Dubin, Marc J.

doi:10.1016/j.biopsych.2014.01.023

Cited by 763Transcranial Magnetic Stimulation StudiesFunctional Brain Connectivity StudiesTreatment of Major Depression

Default mode network mechanisms of transcranial magnetic stimulation in depression

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Liston, Conor, Chen, Ashley C., Zebley, Benjamin D., Drysdale, Andrew T., Gordon, Rebecca, Leuchter, Bruce, Voss, Henning U., Casey, B.J. +2 more·2014·Biological Psychiatry

DOI 10.1016/j.biopsych.2014.01.023PMC PMC4209727

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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.

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Inhibitory rTMS applied to the DLPFC is associated with decreased DLPFC activity and increased functional connectivity with the dACC.
“Inhibitory rTMS applied to the DLPFC, beyond its inhibiting effects on the DLPFC itself, is associated with decreased DLPFC activity and increased functional connectivity with the dACC 21,25 .”
From Stanford Hypnosis Integrated with Functional Connectivity-targeted Transcranial Stimulation (SHIFT): a preregistered randomized controlled trial (2024) · cites this paper as [21]
The Methods (TMS protocol; page unavailable) explicitly describe 10-Hz excitatory, not inhibitory, stimulation of the left DLPFC. The Methods (MRI data acquisition and analysis; page unavailable) describe decreased DLPFC activity in depression, not as an effect of TMS; the Results (TMS effects on connectivity between the CEN and DMN; page unavailable) report DLPFC–DMN changes, not increased DLPFC–dACC connectivity. (LLM, conf=0.90)
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TMS non-invasively modulates neuronal activity and functional connectivity using a high-intensity magnetic field to induce a brief, focal electric field in the cortex that can either activate or inhibit neurons depending on the pattern of stimulation.
“Transcranial magnetic stimulation (TMS) non-invasively modulates neuronal activity and functional connectivity [21][22][23] using a highintensity magnetic field to induce a brief, focal electric field in the cortex that can either activate or inhibit neurons depending on the pattern of the stimulation approach.”
From Stanford Hypnosis Integrated with Functional Connectivity-targeted Transcranial Stimulation (SHIFT): a preregistered randomized controlled trial (2024) · cites this paper as [21]
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Interactions such as mutual inhibition between the activity of the dorsal striatal-SN loop and the ventral striatal reward loop may be important for understanding psychiatric pathology and its heterogeneity.
“In addition, interactions (such as mutual inhibition) between the activity of the dorsal striatal-SN loop and the ventral striatal reward loop may be important for understanding psychiatric pathology and its heterogeneity”
From Cortico-striatal-thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment (2016) · cites this paper as Liston et al., 2014
These data provide a biological mechanism by which DLPFC stimulation might reduce craving.
“These data build upon studies in patients with depression [39,50] and provide a biological mechanism through which DLPFC may be effective at attenuating craving.”
From Transcranial magnetic stimulation, deep brain stimulation, and other forms of neuromodulation for substance use disorders: Review of modalities and implications for treatment (2020) · cites this paper as [50]

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Resting-state connectivity biomarkers define neurophysiological subtypes of depression
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GABA-modulating bacteria of the human gut microbiota
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“…understanding psychiatric pathology and its heterogeneity; such interactions between dorsal and ventral CSTC loops are an increasingly prevalent theme of study in recent work combining neuroimaging and neurostimulation in psychiatric illness (for example, Liston et al., 2014; Hanlon et al., 2016).”
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A systematic review of relations between resting-state functional-MRI and treatment response in major depressive disorder
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Changing Brain Networks Through Non-invasive Neuromodulation
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“Moreover, the aberrant switching between the DMN and CEN in depression has been suggested as a mechanism underlying the preoccupation with self-referential processes related to DMN hyperactivity, and deficits in cognitive functioning, associated with CEN hypoconnectivity (Menon, 2011; Manoliu et al., 2013; Kaiser et a…”
BackgroundMethodInfluential
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Authors: Liston, C., Chen, A. C., Zebley, B. D., Drysdale, A. T., Gordon, R., Leuchter, B., Voss, H. U., Casey, B. J., Etkin, A., & Dubin, M. J.
Affiliations: Cornell University (US)
VA Palo Alto Health Care System (US)
Columbia University Irving Medical Center (US)
Weill Cornell Medicine (US)
Corresponding author: Liston, Conor
ORCID: Liston, Conor
Drysdale, Andrew T.
Voss, Henning U.
Casey, B.J.
Etkin, Amit
Dubin, Marc J.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2014-10
Volume: 76
Issue: 7
Pages: 517-526
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2014.01.023
PMC: PMC4209727
OpenAlex: W1987464027
Cited by: 763
References: 79
Citations by year: 2026: 78 · 2025: 83 · 2024: 83 · 2023: 63 · 2022: 68 · 2021: 89 · 2020: 63 · 2019: 67 · 2018: 43 · 2017: 49 · 2016: 34 · 2015: 33 · 2014: 9
FWCI: 21.64
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (K99 MH097822, P50-MH079513))
Topics: Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords: repetitive transcranial magnetic stimulation, depression, default mode network, frontoparietal network, dorsolateral prefrontal cortex, subgenual cingulate, functional connectivity, treatment response prediction, neuroimaging biomarkers
MeSH terms: Adult, Brain, Brain Mapping, Major Depressive Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Transcranial Magnetic Stimulation

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Default mode network mechanisms of transcranial magnetic stimulation in depression

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