A potential TMS-EEG biomarker for suicidal ideation could bring researchers closer to identifying measurable brain signals associated with suicide risk. In a large multisite analysis, investigators found that a specific electrical response in the prefrontal cortex was associated with suicidal ideation among adults with depression.
The finding does not establish a clinical diagnostic test. It does, however, strengthen evidence that suicidal thinking may be accompanied by detectable changes in the brain’s inhibitory signaling systems.
Why Current Suicide Risk Assessments Remain Limited
Clinicians typically evaluate suicidal ideation through interviews, questionnaires, behavioral observations, and patient-reported symptoms. These methods remain essential, but they can be affected by how comfortable a person feels disclosing suicidal thoughts and how symptoms fluctuate over time.
Researchers have therefore been investigating whether neurophysiological measurements could supplement clinical assessment. An objective measure would not replace patient conversations or clinical judgment, but it could eventually provide another layer of information when evaluating risk or monitoring treatment.
Combining Magnetic Stimulation With Brainwave Recording
The study examined transcranial magnetic stimulation combined with electroencephalography, known as TMS-EEG. This method delivers a magnetic pulse to a targeted brain region while EEG records the brain’s electrical response immediately afterward.
Researchers focused on the left dorsolateral prefrontal cortex, a region involved in emotional regulation, cognitive control, and goal-directed behavior. They analyzed two possible indicators: the N100 response and global mean field amplitude.
The N100 is a negative electrical peak that appears approximately 100 milliseconds after a TMS pulse. Global mean field amplitude provides a broader measurement of activity across the cortex.
A Large Multisite Dataset Strengthens The Analysis
The researchers aggregated cross-sectional data from 299 adults with major depressive disorder who had experienced at least one ineffective antidepressant trial. The data came from five academic medical centers and seven independent clinical trials.
After quality-control exclusions, 237 participants were included in the N100 analysis. Among them, 76 reported no suicidal ideation, 88 reported passive suicidal ideation, and 73 reported active suicidal ideation.
Pooling information across institutions created one of the largest TMS-EEG analyses conducted in this area. It also allowed the researchers to test whether the association remained present despite variations in equipment, targeting methods, and recording protocols.
TMS-EEG Biomarker For Suicidal Ideation Tracks A Prefrontal Signal
More negative N100 amplitudes in the left dorsolateral prefrontal cortex were associated with greater suicidal ideation. Each standard-deviation increase in the negative N100 response corresponded with a 52% higher likelihood of belonging to a more severe suicidal ideation category.
The relationship remained significant after accounting for age, sex, overall depression severity, and study site. It also persisted when researchers removed the suicidal ideation item from the broader depression score.
Among 87 participants who completed the Beck Scale for Suicidal Ideation, more negative N100 responses were again associated with higher scores.
The Signal May Distinguish Presence Better Than Severity
Additional analyses identified differences between participants with no suicidal ideation and those with either passive or active ideation. However, the N100 measurement did not significantly distinguish passive ideation from active ideation.
This creates an important qualification. The response may be more useful for detecting the presence of suicidal thinking than for precisely grading its severity. More sensitive, dedicated suicide assessment scales may be needed to clarify that distinction.
The second measurement, global mean field amplitude, was not significantly associated with suicidal ideation. This suggests that a localized prefrontal response may be more informative than a broader measure of cortical activation.
GABA Signaling Offers A Possible Mechanistic Explanation
The N100 response has been linked to inhibitory signaling mediated partly through GABA-B receptors. GABA is a major inhibitory neurotransmitter that helps regulate neural activity and prevent excessive excitation.
A stronger negative N100 response may therefore reflect altered inhibitory processing within the prefrontal cortex. Because this region supports emotional and behavioral regulation, disruption in its inhibitory circuitry could be relevant to suicidal thinking.
This interpretation remains a hypothesis. The study measured association, not causation, and the N100 signal may contain both cortical activity and sensory responses to the sound and physical sensation of TMS.
Clinical Translation Will Require Prospective Validation
Future studies will need standardized protocols, sham stimulation, comprehensive suicide assessments, and longitudinal follow-up. Researchers must also determine whether the N100 changes as suicidal ideation improves and whether it can predict treatment response.
For now, the findings support the N100 as a neurophysiological correlate rather than a standalone biomarker. With further validation, TMS-EEG could contribute to a more objective understanding of suicide risk while remaining integrated with careful clinical assessment.
Citations
Stapper N, et al. TMS-EEG Correlate of Suicidal Ideation in Individuals With Depression. Brain Stimulation. 2026.
Sun Y, et al. Indicators for Remission of Suicidal Ideation Following Magnetic Seizure Therapy in Patients With Treatment-Resistant Depression. JAMA Psychiatry. 2016;73(4):337-345.
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