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 R2 = 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 SummaryThe brains 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 brains 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.