Resting-state EEG alpha-BOLD coupling spatially follows cortical cell-type and receptor gradients

The coupling between electroencephalography (EEG) and blood-oxygen-level-dependent (BOLD) signals has been investigated across numerous studies, but its neurobiological underpinnings remain poorly understood. Resting-state EEG alpha-BOLD coupling follows a characteristic spatial pattern, shifting from negative correlations in sensory regions to positive correlations in association cortices. In this study, we examined neurobiological correlates of resting-state alpha-BOLD coupling. We compared the spatial pattern of the alpha-BOLD coupling map to 82 cortical feature maps, including gene expression profiles of different cell types and receptor subunits as well as structural MRI measures. We identified three statistically significant ( q < 0.05 FDR-corrected) maps: the layer 6 VIP interneuron marker, excitatory layer-5 marker, and NMDA receptor subunit GRIN2C. The three significant gene maps, combined in a multiple linear regression model, explained R 2 = 0.312 of the spatial variance in alpha-BOLD coupling. Analysis of the spatial mismatch between cortical maps and the alpha-BOLD coupling map revealed that the early auditory cortex is the region that consistently diverges from predictions across gene expression and T1/T2 maps. The spatial correspondence between alpha-BOLD coupling and gene expression profiles of specific receptor subunits, neuronal types, and layer-specific populations identifies these as concrete candidates for future computational and experimental studies of alpha-BOLD coupling. Author Summary The brain’s electrical rhythms and metabolic activity are coupled, yet why this coupling differs across brain regions remains poorly understood. This study shows that resting-state alpha-BOLD coupling, a well-established link between EEG alpha oscillations and fMRI signals, maps onto the brain’s cellular landscape: regions enriched in specific inhibitory interneurons and NMDA receptor subunits show systematically different coupling strengths. These findings suggest that regional differences in cell-type composition and receptor expression, rather than purely anatomical features, could shape the spatial organization of alpha-BOLD coupling. By identifying candidate cortical features, this work can guide future experimental and computational studies, ultimately helping to establish alpha-BOLD coupling as a relevant biomarker for psychiatric and neurological disorders.