Aperiodic slope reflects glutamatergic tone in the human brain

Sheldon, A. A.; Moser, H. R.; Abdullahi, K. S.; Allison, K. D.; Mulder, C. B.; Montoya, S. A.; Sponheim, S. R.; Marjanska, M.; Schallmo, M.-P.

doi:10.1101/2025.05.15.654118

bioRxiv · 10.1101/2025.05.15.654118

Aperiodic slope reflects glutamatergic tone in the human brain

Sheldon, A. A.·Moser, H. R.·Abdullahi, K. S.·Allison, K. D.·Mulder, C. B.·Montoya, S. A.·Sponheim, S. R.·Marjanska, M.·Schallmo, M.-P.

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Abstract

Excitatory and inhibitory neural processes are essential for every aspect of brain function, but current non-invasive neuroimaging methods to study these in the human brain are limited. Recent studies which separate oscillatory and aperiodic components of electrophysiological power spectra have highlighted a relationship between aperiodic activity and functional brain states. Studies in both animal models and humans suggest that the aperiodic slope of electrophysiological power spectra reflects the local balance of excitatory:inhibitory (E:I) synaptic transmission. Aperiodic slope varies across individuals, brain states, and clinical populations, which may reflect important differences in E:I balance. However, there is currently a lack of evidence linking aperiodic slope to other measures of excitation and inhibition in the human brain. Here, we show that flatter (less steep) aperiodic slopes from human electroencephalography (EEG) are associated with higher concentrations of the excitatory neurotransmitter glutamate measured with 7 tesla magnetic resonance spectroscopy (MRS) in the occipital lobe at rest. This suggests that individual differences in aperiodic neural activity reflect cortical glutamate concentrations, providing important insight for understanding changes in neural excitation across brain states and neuropsychiatric populations (e.g., schizophrenia) where glutamatergic function may differ. Our results support the use of aperiodic slope as a non-invasive marker for excitatory tone in the human brain.

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Sheldon, A. A., Moser, H. R., Abdullahi, K. S., Allison, K. D., Mulder, C. B., Montoya, S. A., Sponheim, S. R., Marjanska, M., Schallmo, M.-P.. 2025-05-20. Aperiodic slope reflects glutamatergic tone in the human brain. https://doi.org/10.1101/2025.05.15.654118

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