Altered resting-state prefrontal activity and network topology in adolescents with depression: an fNIRS study

Adolescent depression is associated by substantial cognitive impairment and poor treatment response, yet its neurobiological underpinnings remain insufficiently understood. Resting-state functional near-infrared spectroscopy (fNIRS) offers a portable and developmentally sensitive tool to examine intrinsic prefrontal activity and network properties.

Seventy-nine adolescents with depressive disorder (DD) and age-matched healthy controls (HC) underwent 6-min resting-state fNIRS recording over the prefrontal cortex. We extracted fractional amplitude of low-frequency fluctuations (fALFF) and resting-state functional connectivity were computed, and graph-theoretical metrics, including clustering coefficient, local/global efficiency, path length, and small-worldness were derived. Depressive and anxiety symptoms was assessed using the 17 - item Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA), and cognitive performance was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS).

Compared with HC, the DD group exhibited elevated prefrontal fALFF in multiple channels (e.g., ch11, ch26, ch31), reduced average functional connectivity within and between bilateral frontal regions (including FPA and Broca's area), and lower clustering coefficient, local efficiency, and global efficiency relative to healthy controls, whereas path length and small-worldness were preserved. Region-specific associations with cognition were observed: fALFF in ch11 positively correlated with verbal fluency, whereas fALFF in ch31 negatively correlated with executive functioning, these associations remained significant after controlling for depressive and anxiety symptom severity. Conclusions: Adolescents with depression show elevated prefrontal fALFF and reduced network efficiency, with region-specific associations with cognitive performance. These findings suggest that resting-state fNIRS is a developmentally suitable method for probing prefrontal neurocognitive alterations in youth depression.