Left cortical activation and combined diagnostic utility during three verbal fluency tasks in major depressive...

Recent functional near-infrared spectroscopy (fNIRS) studies have shown reduced left cortical hemodynamic responses in major depressive disorder (MDD), suggesting a promising neuroimaging biomarker for diagnosis. However, given MDD's pronounced clinical heterogeneity and widespread cognitive impairments, reliance on a single task-based activation index may be insufficiently sensitive. Therefore, this study aims to combine three Chinese verbal fluency tasks (VFTs) with distinct cognitive demands to delineate MDD-related aberrant neural response patterns and to derive more comprehensive, robust fNIRS biomarkers for objective diagnostic classification.

This study recruited 60 patients with MDD and 60 demographically matched healthy controls (HCs). Hemodynamic changes in the left cortex were measured using a 48-channel fNIRS during the three VFTs. Demographics information, clinical characteristics and VFT performance were also collected.

Each Chinese VFT variant elicited a different pattern of left cortical activation. Relative to HCs, patients with MDD exhibited significantly reduced activation in both the left dorsolateral and medial prefrontal cortices. Moreover, integrating neural activation indices across all three VFTs substantially enhanced the discrimination between MDD patients and HCs compared with any single task.

In light of the heterogeneous nature of depression and its broad impact on multiple cognitive domains, combining multiple cognitive paradigms may develop richer and more reliable fNIRS-based biomarkers for the identification of MDD.