Decoding the brain's excitatory–inhibitory metabolite balance in relation to sensory responsivity and autistic traits

Abstract

Brain excitatory–inhibitory (E–I) balance plays a fundamental role in sensory and social processing. Alterations in E–I neurotransmitter systems—commonly indexed by the glutamate and glutamine (Glx)/GABA ratio—have been implicated in various neurodevelopmental conditions, including autism spectrum disorder (ASD). However, how individual differences in E–I balance relate to sensory responsivity and autism-spectrum-related traits in neurotypical populations remains poorly understood. In this study, we evaluated E-I balance across sensory-related brain regions in 92 neurotypical participants to explore its association with sensory responsivity and autistic traits. Our findings revealed that individuals with higher levels of self-reported autistic traits also exhibited stronger associations with sensory responsivity and higher Glx/GABA ratios. In cross-correlation analyses, the Glx/GABA ratio was significantly associated with both autistic traits and sensory responsivity, whereas Glx alone showed fewer associations. Clustering analyses further grouped autistic traits with the Glx/GABA ratio, rather than with the individual metabolite concentrations, suggesting that the ratio may be more behaviorally relevant than either metabolite alone. Moreover, the prefrontal Glx/GABA ratio demonstrated stronger associations with both autistic traits and sensory responsivity compared to other brain regions, a finding further supported by hierarchical moderation and mediation analyses. Overall, these results suggest that individual variability in regional E–I balance may be meaningfully related to sensory and social-affective traits, even within non-clinical populations. These findings may offer insights into the broader neurobiological mechanisms underlying sensory-affective processing across the general population spectrum.