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

Area of Science:

• Neuroscience
• Computational Neuroscience
• Systems Neuroscience

Background:

• The relationship between electroencephalography (EEG) and blood-oxygen-level-dependent (BOLD) signals, known as alpha-BOLD coupling, is well-documented but its neurobiological basis is unclear.
• Resting-state alpha-BOLD coupling exhibits a distinct spatial distribution, with negative correlations in sensory areas and positive correlations in association cortices.
• Understanding the cellular and molecular mechanisms driving regional variations in alpha-BOLD coupling is crucial for interpreting brain activity.

Purpose of the Study:

• To investigate the neurobiological correlates of resting-state alpha-BOLD coupling.
• To identify specific cortical features, such as gene expression profiles and structural MRI measures, that explain the spatial pattern of alpha-BOLD coupling.
• To provide a foundation for future computational and experimental research into the functional significance of alpha-BOLD coupling.

Main Methods:

• Compared the spatial pattern of resting-state alpha-BOLD coupling with 82 cortical feature maps, including gene expression data for cell types and receptor subunits, and structural MRI metrics.
• Utilized multiple linear regression to model the contribution of significant gene expression maps to the variance in alpha-BOLD coupling.
• Analyzed spatial discrepancies between cortical maps and the alpha-BOLD coupling map to pinpoint regions with divergent patterns.

Main Results:

• Identified three statistically significant gene expression maps associated with alpha-BOLD coupling: markers for layer 6 VIP interneurons, excitatory layer-5 neurons, and the NMDA receptor subunit GRIN2C.
• These three gene maps collectively explained 31.2% (R^2 = 0.312) of the spatial variance in alpha-BOLD coupling.
• The early auditory cortex showed consistent divergence from predicted patterns across gene expression and T1/T2 structural maps.

Conclusions:

• Regional differences in cell-type composition and receptor expression, particularly inhibitory interneurons and NMDA receptors, significantly shape the spatial organization of alpha-BOLD coupling.
• The findings suggest that cellular landscape features, rather than solely anatomical properties, underlie the observed regional variations in brain signal coupling.
• This study identifies specific neuronal populations and receptor subunits as key candidates for future investigations into the neurobiological basis of alpha-BOLD coupling and its potential as a biomarker.