Assessing whole-cortex excitability from electromagnetic brain signals

Abstract

Cortical excitability, the propensity of neural circuits to respond to internal or external perturbations, is a fundamental property of brain functioning, shaped by local microcircuitry, large-scale networks, and neurochemical architecture. In humans, excitability is inferred from multiple indirect metrics derived from spontaneous and stimulus-driven electromagnetic activity, yet it remains unclear whether these measures reflect a common underlying construct or distinct physiological processes. Here, we systematically compared ten previously validated excitability metrics using whole-head magnetoencephalography (MEG) recorded at rest and during 40 Hz auditory stimulation in a large sample of healthy adults. The measures spanned stimulus-driven synchronization, spectral power, 1/f activity (hereafter defined as aperiodic), signal complexity, long-range temporal correlations, and phase-gamma synchronization. Hierarchical clustering revealed six separable excitability dimensions with limited redundancy, demonstrating that cortical excitability is inherently multidimensional. Aperiodic and alpha-band measures showed the strongest mutual coupling and the furthest spatial correspondence to stimulus-related responses, whereas temporal, complexity, and synchronization-based metrics were largely independent. The similarity between measures varied across cortical regions and functional networks, with maximal cluster separability in integrative and internally driven regions. These regions included orbitofrontal, temporal, anterior cingulate, and default mode areas, as well as visual and somatomotor networks. Finally, excitability dimensions showed distinct relationships with cortical morphology and neurotransmitter receptor density, implicating heterogeneous neurobiological substrates. Together, these findings provide a unified framework for interpreting excitability metrics and highlight the need for multimodal approaches when probing cortical excitability in health and disease.