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bioRxiv · 10.64898/2025.12.03.691778

Examining excitation-inhibition modulation during social processing using functional Magnetic Resonance Spectroscopy

Ford, T. C.·Pasanta, D.·Parrella, N.-F.·Enticott, P. G.·White, D. J.·Puts, N. A.
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Abstract

An imbalance of brain excitation-inhibition has been implicated in social communication function across neurodevelopmental and psychiatric conditions. Recent advances in functional magnetic resonance spectroscopy (fMRS) allow non-invasive measurement of dynamic changes in excitation-inhibition neurometabolites (glutamate and GABA), revealing potential links with cognitive processes. This study used functional MRS (fMRS) to investigate whether socially-laden stimuli modulate excitatory or inhibitory neurometabolites, and whether modulation relates to social function. Forty neurotypical adults (18-40 years; 20 male) underwent 3T MRI, with fMRS data acquired using a J-difference edited MRS sequence. GABA+macromolecules (GABA+) and glutamate+glutamine (Glx) were quantified in a right social brain region (superior temporal/temporoparietal junction [STG/TPJ]) and a control region (occipital cortex). Participants viewed a fixation cross (traditional resting state MRS; 5 min), silent video clips of social interaction, and a flashing checkerboard as control stimulus (5 min each; counterbalanced). The Social Responsiveness Scale (SRS-2) assessed social function. Block analysis showed no significant differences between resting and functional (social or checkerboard) GABA+ or Glx levels (ps<.05), although Bayesian analyses showed evidence for decreased STG/TPJ GABA+ and increased occipital cortex Glx for checkerboard compared to rest. Higher SRS-2 scores were associated with higher resting STG/TPJ Glx but not GABA+, and functional metabolite levels were not associated with SRS-2 scores (ps>.1). Sliding time- window analyses showed significantly reduced Glx in social brain during social stimulation. Despite sound data collection and analysis techniques, shifts in Glx and GABA+ following social stimuli were minimal. Future research could utilise more challenging social stimuli and examine alternate social brain regions.

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Ford, T. C., Pasanta, D., Parrella, N.-F., Enticott, P. G., White, D. J., Puts, N. A.. 2025-12-08. Examining excitation-inhibition modulation during social processing using functional Magnetic Resonance Spectroscopy. https://doi.org/10.64898/2025.12.03.691778

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