Sequential bilateral dorsolateral prefrontal versus right lateral orbitofrontal/left dorsolateral prefrontal TMS for major depression: A large naturalistic case series
Bibliographic record
Abstract
Major depressive disorder (MDD) remains one of the most debilitating conditions worldwide, with ~30 % of patients developing treatment-resistant depression (TRD) after failing 2 pharmacotherapy trials [1].Repetitive transcranial magnetic stimulation (TMS) has shown promise as a treatment for MDD (including TRD), achieving remission rates of 19-37 % with high-frequency (HF; >5Hz) TMS to the left-dorsolateral prefrontal cortex (L-DLPFC) [2].Comparable outcomes have been noted between sequential bilateral (SBL)-DLPFC-TMS and HF-L-DLPFC-TMS [3].For DLPFC-TMS non-responders, emerging evidence suggests the right lateral orbitofrontal cortex (R-LOFC) -implicated in 'non-reward' processing, rumination, and MDD pathophysiology [4] -as an alternative TMS target, alone or as an add-on DLPFC-TMS) [5][6][7][8].A key question is whether integrating R-LOFC-TMS with L-DLPFC-TMS from the outset enhances outcomes.Here, we compared clinical outcomes for SBL-DLPFC-TMS (1Hz-R-DLPFC-TMS + 20Hz-L-DLPFC-TMS; F4-F3) versus R-LOFC/L-DLPFC-TMS (1Hz-R-LOFC-TMS + 20Hz-L-DLPFC-TMS; F8-F3) in TMS-naive MDD patients.Depression and anxiety scores, symptom subitems (anhedonia, suicidality, sleep, rumination proxy), and demographics were assessed, and explored as predictors of remission/non-remission for each protocol.This retrospective, naturalistic study included 3562 consenting TMSnaive patients with non-psychotic MDD treated between April 2019 and December 2023, following exclusions detailed in Fig. S1.This intent-totreat (ITT) sample comprised 2773 patients who received the F4-F3 protocol, and 789 patients who received the F8-F3 protocol.A Completer sample (N = 3202) was further defined, from which patients were excluded if they ended TMS after fewer than 30 sessions of treatment without meeting response criteria, leaving 2486 in the F4-F3 group and 716 in the F8-F3 group.The SBL-DLPFC protocol consisted of 360 pulses of 1Hz to R-DLPFC (F4 target, 60s on 30s off, 6 trains, 8.5min) followed by 1200 pulses of 20Hz to L-DLPFC (F3 target, 2s on 4s off, 30 trains, 3min).The R-LOFC/ L-DLPFC protocol shifted the right-sided target from F4 to F8 (R-LOFC), with all other parameters unchanged.F3 and F4 were localized using the BeamF3 scalp heuristic, and F8 was localized at 15 % of head
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.002 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".