Increased anti-correlation between the left dorsolateral prefrontal cortex and the default mode network following Stanford Neuromodulation Therapy (SNT): analysis of a double-blinded, randomized, sham-controlled trial
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SNT is a high-dose accelerated intermittent theta-burst stimulation (iTBS) protocol coupled with functional-connectivity-guided targeting that is an efficacious and rapid-acting therapy for treatment-resistant depression (TRD). We used resting-state functional MRI (fMRI) data from a double-blinded sham-controlled randomized controlled trial 1 to reveal the neural correlates of SNT-based symptom improvement. Neurobehavioral data were acquired at baseline, post-treatment, and 1-month follow-up. Our primary analytic objective was to investigate changes in seed-based functional connectivity (FC) following SNT and hypothesized that FC changes between the treatment target and the sgACC, DMN, and CEN would ensue following active SNT but not sham. We also investigated the durability of post-treatment observed FC changes at a 1-month follow-up. Study participants included transcranial magnetic stimulation (TMS)-naive adults with a primary diagnosis of moderate-to-severe TRD. Fifty-four participants were screened, 32 were randomized, and 29 received active or sham SNT. An additional 5 participants were excluded due to imaging artifacts, resulting in 12 participants per group (Sham: 5F; SNT: 5F). Although we did not observe any significant group × time effects on the FC between the individualized stimulation target (L-DLPFC) and the CEN or sgACC, we report an increased magnitude of negative FC between the target site and the DMN post-treatment in the active as compared to sham SNT group. This change in FC was sustained at the 1-month follow-up. Further, the degree of change in FC was correlated with improvements in depressive symptoms. Our results provide initial evidence for the putative changes in the functional organization of the brain post-SNT.
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Recent studies evaluating connectivity changes after accelerated depression treatment have found increased inhibitory strength from rMFG to the entire medial DMN, rather than increased inhibitory connections from rMFG to sgACC.
“However, recent studies evaluating connectivity changes after accelerated depression treatment have not found increased inhibitory connections from rMFG to sgACC, but rather find increased inhibitory strength from rMFG to the entire medial DMN 14 .”
From Functional MRI Guided Accelerated Intermittent Theta Burst Stimulation for Chronic Post-Concussive Syndrome: A Feasibility and Efficacy Study (2025) · cites this paper as [14]
The Results (ROI and seed-based analyses; page unavailable) report stronger negative functional connectivity between the personalized L-DLPFC target and the DMN after active SNT, but no significant change between that target and the sgACC. The paper does not identify the target as rMFG or measure inhibitory strength; it reports functional connectivity, with a whole-DMN ROI result and a separate medial prefrontal cluster result. (LLM, conf=0.87)
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Cites
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Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial
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Bartholomeusz, E. J., Fong, A. K., Tervort, T. J., Gaufin, L. M., & Allen, M. D. (2025) · doi:10.1101/2025.10.08.25336734
- Authors
- Gajawelli, N., Geoly, A. D., Batail, J.-M., Xiao, X., Maron-Katz, A., Cole, E., Azeez, A., Kratter, I. H., Saggar, M., & Williams, N. R.
- Affiliations
- Stanford University (US)
- Centre Hospitalier Guillaume Régnier (FR)
- Corresponding author
- Williams, Nolan R.
- ORCID
- Venue
- npj Mental Health Research
- Published
- 2024-07-06
- Volume
- 3
- Issue
- 1
- Pages
- 35-35
- ISSN
- 2731-4251 (ISSN-L)
- PMC
- PMC11227523
- OpenAlex
- W4400387020
- Cited by
- 18
- References
- 3
- Citations by year
- 2026: 12 · 2025: 4 · 2024: 2
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Mental Health Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH Director’s New Innovator Award (MH119735)
- Brain and Behavior Research Foundation
- Charles R. Schwab
- David and Amanda Chao Fund II
- Amy Roth PhD Fund
- The Neuromodulation Research Fund
- The Lehman Family
- Still Charitable Trust
- Marshall and Dee Ann Payne Fund
- Gordie Brookstone Fund
- The Mellam Family Foundation
- The Baszucki Brain Research Fund
- 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
- treatment-resistant depression, intermittent theta burst stimulation, seed-based functional connectivity, dorsolateral prefrontal cortex, default mode network, anterior cingulate cortex, frontoparietal network, resting-state functional connectivity, treatment durability
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