Differences in Neurovascular Coupling in Patients with Major Depressive Disorder: Evidence from Simultaneous Resting-State EEG-fNIRS

Neurovascular coupling (NVC), the relationship between neural activity and cerebral hemodynamic responses, remains poorly understood in major depressive disorder (MDD). To investigate alterations in NVC associated with depressive symptom severity, we simultaneously recorded resting-state electroencephalography (rsEEG) and functional near-infrared spectroscopy (fNIRS) in 206 participants, including 134 patients with MDD and 72 healthy controls stratified by age to disentangle disease-related alterations from age-associated effects. NVC in the prefrontal cortex (PFC) was characterized by the consistency and temporal lag between spontaneous electrophysiological peaks and corresponding hemodynamic responses. We found that age significantly enhances the NVC consistency (p < 0.05), whereas this relationship was altered in patients with MDD during both the oxygen-consumption phase and the subsequent hemodynamic compensation phase. Furthermore, among patients with MDD, the strength of this consistency decreased more significantly with greater illness severity (partial r = -0.336, p = 0.0601). These findings suggest that changes in neurovascular coupling effects are strongly associated with the severity of depression. By leveraging wearable neuroimaging techniques, this study provides multimodal evidence for altered neurovascular coupling in depression and highlights its potential as a biomarker for disease monitoring and recovery trajectories.