BackgroundThis study explored a novel multimodal neuroimaging approach to assess neurovascular coupling (NVC) in humans using electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS), and transcranial Doppler ultrasound (TCD). MethodsFifteen participants (nine females; age 19–32) completed concurrent EEG-fNIRS-TCD imaging during motor (finger tapping) and visual (“Where's Waldo?”) tasks, with synchronized monitoring of blood pressure, capnography, and heart rate. fNIRS assessed microvascular oxygenation within the frontal, motor, parietal, and occipital cortices, while the middle and posterior cerebral arteries (MCA/PCA) were insonated using TCD. A 16-channel EEG set-up was placed according to the 10–20 system. Wilcoxon signed-rank tests were used to compare physiological responses between the active and resting phases of the tasks, while cross-correlations with zero legs compared cerebral and systemic hemodynamic responses across both tasks. ResultsTime-frequency analysis demonstrated a reduction in alpha and low beta band power in electrodes C3/C4 during finger tapping (p<0.045) and all electrodes during the Waldo task (all p<0.001). During Waldo, cross-correlation analysis demonstrated the change in oxygenated hemoglobin and cerebral blood velocity had a moderate-to-strong negative correlation with systemic physiological influences, highlighting the measured change resulted from neuronal input. Deoxygenated hemoglobin displayed the greatest negative cross-correlation with the MCA/PCA within the motor cortices and visual during the motor and visual tasks, respectively (range:0.54, -0.82). ConclusionsThis investigation demonstrated the feasibility of the proposed EEG-fNIRS-TCD response to comprehensively assess the NVC response within human, specifically quantifying the real-time temporal synchrony between neuronal activation (EEG), microvascular oxygenation changes (fNIRS), and conduit artery velocity alterations (TCD).