TMS-EEG Correlate of Suicidal Ideation in Individuals with Depression: A Multi-Site Synthesis

AI Summary

More negative N100 peak amplitude in left DLPFC associates with greater suicidal ideation severity (OR 1.52, p=0.002), independent of covariates.
No significant association between GMFA AUC (55 to 275 ms) and suicidal ideation.
N100 may reflect GABAergic inhibitory dysregulation and serve as a potential SI biomarker and treatment target, requiring validation with sham TMS-EEG.

TL;DR (AI Generated)

METHODS: This study aims to test the association between SI and two TMS-EEG measures: the negative peak at 100ms (N100) and the area under the curve (AUC) of the global mean field amplitude (GMFA).

In this multi-site data synthesis, cross-sectional TMS-EEG data from 299 adult participants with major depressive disorder and at least 1 ineffective antidepressant trial were aggregated across five academic medical centers.

Ordinal regression analysis revealed a significant positive association between more negative N100 peak amplitude in the left DLPFC and greater severity of SI (OR=1.52, p=0.002, 95%CI [1.17;1.98]), independent of age, sex, depression severity, and study site.

Basic summary

Brain Stimul. 2026 Sep 12:103206. doi: 10.1016/j.brs.2026.103206. Online ahead of print.

ABSTRACT

BACKGROUND: Suicidal ideation (SI) is a leading risk factor for suicide death, with a lifetime prevalence of 35-40% in psychiatric populations. However, the neurobiology of SI remains poorly understood. Preliminary work suggests an association between SI and neurophysiological measures derived from transcranial magnetic stimulation combined with electroencephalography (TMS-EEG).

METHODS: This study aims to test the association between SI and two TMS-EEG measures: the negative peak at 100ms (N100) and the area under the curve (AUC) of the global mean field amplitude (GMFA). In this multi-site data synthesis, cross-sectional TMS-EEG data from 299 adult participants with major depressive disorder and at least 1 ineffective antidepressant trial were aggregated across five academic medical centers. Single-pulse TMS was delivered to the left dorsolateral prefrontal cortex (DLPFC) with simultaneous EEG recording.

RESULTS: The N100 peak amplitude between 80 to 130ms, as well as the AUC-GMFA between 55 to 275ms, were extracted for each participant. Ordinal regression analysis revealed a significant positive association between more negative N100 peak amplitude in the left DLPFC and greater severity of SI (OR=1.52, p=0.002, 95%CI [1.17;1.98]), independent of age, sex, depression severity, and study site. There was no significant association between GMFA and SI.

CONCLUSION: N100 peak amplitude in the left DLPFC is a neurophysiological correlate of SI which may reflect a neurophysiological link between GABAergic inhibitory dysregulation and the pathophysiology of SI. Further research is needed to validate the findings using sham TMS-EEG and subsequently test the utility of N100 in the left DLPFC as a biomarker of SI and a possible treatment target.

PMID:42731592 | DOI:10.1016/j.brs.2026.103206

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