Neurophysiological signatures of Stanford Neuromodulation Therapy in treatment resistant depression
In brief
Stanford brain stimulation cut target-site excitability by 28% by day three
In a sham-controlled trial of 24 people with treatment-resistant depression, active Stanford Neuromodulation Therapy progressively reduced cortical excitability at the treated brain site, with no change at a control site. Activity in an estimated depression-related brain source also fell and remained lower at one month; a link between baseline activity and improvement in just 12 treated participants needs larger studies.
- Journal
- Molecular psychiatry (Q1)
- Published
- 2 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Davide Momi, Derrick M Buchanan, Masataka Wada, Andrew D Geoly, Noriah J Johnson, Eleanor J Cole, et al.
- PMID
- 42686996
- DOI
- 10.1038/s41380-026-03837-4
Why clinicians should know about it
- Picked for Psychiatry and Mental Health (top studies of the week, 18 October 2026): Sham‑controlled RCT of high‑dose theta‑burst TMS in TRD
Abstract
Treatment-resistant depression (TRD) affects approximately 30% of patients with major depressive disorder. Stanford Neuromodulation Therapy (SNT), a high-dose intermittent theta-burst transcranial magnetic stimulation protocol, produces rapid antidepressant effects, but its neurophysiological mechanisms remain unclear. Here, we used longitudinal TMS-EEG to characterize the progressive neurophysiological changes induced by SNT, assess their site-specificity, and explore whether baseline neural markers are associated with clinical response. We conducted a double-blind, randomized, sham-controlled trial at Stanford University (2017-2018; analysis August 2024-October 2025) in 24 TMS-naïve participants with TRD (Montgomery-Åsberg Depression Rating Scale ≥20; ≥1 failed antidepressant trial). Participants were randomized to active (n = 12) or sham (n = 12) SNT, consisting of 10 sessions per day over 5 consecutive days targeting the left dorsolateral prefrontal cortex (90,000 pulses). TMS-EEG was acquired at two baseline sessions, before and after each treatment session, and at 1-month follow-up (14 TMS-EEG sessions in total). Active SNT progressively reduced cortical excitability at the treatment site, with significant decreases by day 3 in the early window component (-27.9%; P < 0.01), while no changes were observed at the vertex control site. Site-specific comparisons confirmed early window reductions only at the left dorsolateral prefrontal cortex (t₂₂ = -3.82; P < 0.001). SNT also selectively decreased estimated medial prefrontal source activity consistent with the subgenual anterior cingulate cortex (sgACC) across sessions (F₁₃,₂₂₂ = 4.93; P < 0.001), with effects persisting at 1-month follow-up. In an exploratory analysis in the active group (n = 12), higher baseline estimated sgACC source activity was associated with greater clinical improvement (r = -0.67; P = 0.023); although promising, the latter preliminary finding requires replication in larger, adequately powered samples before predictive utility can be established. These findings indicate that SNT induces progressive, site-specific cortical modulation and selective downstream effects on estimated sgACC source activity. Early cortical excitability changes represent candidate neurophysiological markers of SNT response, while the observed association between baseline sgACC activity and clinical outcome, while preliminary, motivates prospective investigation of subcortical source activity as a potential predictor of treatment response in larger trials. ClinicalTrials.gov Identifier: NCT03068715.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.