Concurrent multimodal imaging demonstrates that EEG-based excitation/inhibition balance reflects glutamate and GABA balance

Magnetic Resonance Spectroscopy (MRS)-derived excitation/inhibition (E/I) ratio is recognized as a valuable index of attentional modulation, the plasticity and stability of learning states, and disordered functioning. Inferring the E/I ratio from electroencephalography (EEG), however, offers greater accessibility and superior temporal resolution, and therefore holds strong potential for advancing research on dynamic neural processes. Yet, the underlying neurochemical mechanisms contributing to changes in EEG-based E/I ratio remain unclear. In this study we used concurrent EEG and magnetic resonance spectroscopy (MRS) to examine how the EEG-based E/I ratio correlates with the MRS-based E/I ratio in sleeping humans of both sexes (n = 15). The MRS-based E/I ratio was calculated as the ratio of Glx (glutamate + glutamine) to GABA+ (GABA + co-edited macromolecules) concentrations in early visual areas. We estimated 10 candidate EEG-based E/I indices using four algorithms across multiple spontaneous frequency bands from the occipital region. Uniquely, we quantified the associations between EEG- and MRS-based E/I ratios by separately analyzing between-subject and within-subject variations. We found that each EEG-based E/I algorithm showed reliable and positive associations with MRS-based E/I, particularly in the alpha band, which is known to play a key role in attentional modulation and in the plasticity and stability of learning states. These results highlight the potential of EEG-based E/I measures to serve as practical indices of neurochemical dynamics in early visual cortex.<b>Significance Statement</b> Although a balance between cortical excitation and inhibition is important for many functions, measurement of this balance has remained a challenge. Candidate methods to efficiently measure excitation/inhibition balance via electroencephalography (EEG) have been proposed, but validation of these methods using concurrent measurement of neurochemistry (i.e., using magnetic resonance spectroscopy) has been lacking. The results reported here show that several candidate EEG-based measures of excitation/inhibition balance are reliably and positively associated with the ratio of excitatory to inhibitory neurotransmitters. Such results provide a necessary foundation for advancing methods, basic research, and applied research using efficient EEG measures of excitation/inhibition balance to understand brain states.