Functional near‐infrared spectroscopy as a biomarker of TMS efficacy in treatment‐resistant depression

Background Reliable biomarkers for predicting treatment response and suicide risk in treatment‐resistant depression (TRD) are limited. Functional near‐infrared spectroscopy (fNIRS) offers a noninvasive means to assess prefrontal cortical activation linked to therapeutic outcomes. Methods In a double‐blind, randomized, sham‐controlled trial, 100 inpatients with TRD received either active or sham prolonged intermittent theta‐burst stimulation (aiTBS) over the left dorsolateral prefrontal cortex (DLPFC) across 2 weeks. fNIRS measured oxyhemoglobin (oxy‐Hb) levels at rest and during a verbal fluency task (VFT) and two‐back working memory task, both before and after aiTBS. Clinical outcomes included Montgomery‐Åsberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale item 3 (HAMD‐3), and Beck Scale for Suicide Ideation (BSS). Results Baseline BSS, HAMD‐3, and MADRS scores did not differ between groups (all P > 0.05). Post‐treatment, the active group showed significant improvements in BSS, HAMD‐3, and MADRS (all P < 0.05). Active aiTBS increased oxy‐Hb in the left DLPFC and right orbitofrontal cortex (OFC) during the two‐back task, and in the left DLPFC, OFC, and frontopolar cortex (FPC) during the VFT. Greater left DLPFC activation during the VFT correlated with MADRS improvement, and baseline OFC activation predicted antidepressant response. No fNIRS measures predicted changes in suicidality. Conclusions Task‐evoked prefrontal activation—especially in the left DLPFC and OFC—may serve as a biomarker for antidepressant efficacy in TRD, though fNIRS did not predict suicide risk reduction.