KUMJ | VOL. 23 | NO. 5 | ISSUE 93 | DECEMBER, 2026

The Relationship between Cortical GABA Levels and Short-Interval Intracortical Inhibition: A Meta-analysis of Magnetic Resonance Spectroscopy and Transcranial Magnetic Stimulation Studies
Sharma P, Grunberg K, Sharma P, Kunwar D

Abstract:
Cortical gamma-aminobutyric acid (GABA) is the brain’s principal inhibitory neurotransmitter and plays a key role in regulating motor cortical excitability. Short interval intracortical inhibition (SICI), measured via paired-pulse transcranial magnetic stimulation (TMS), is a widely used physiological index of GABAergic function. However, the strength and consistency of the association between GABA levels, quantified in vivo using magnetic resonance spectroscopy (MRS), and SICI remain unclear across studies. We conducted a random-effects meta-analysis of studies reporting correlations between MRS-derived cortical GABA concentrations and TMS-measured SICI in healthy human participants. Effect sizes were transformed to Fisher’s Z scores and pooled using the restricted maximum likelihood (REML) method. Heterogeneity was assessed using the I² statistic and Cochran’s Q test. Potential publication bias was evaluated via visual funnel plot inspection and Egger’s regression test. Results: A total of 23 effect sizes were included in the analysis. The pooled Fisher’s Z was –0.14 (95% CI, –0.26 to –0.02; P = .03), corresponding to a small but statistically significant negative correlation (r ≈ –0.14). This finding suggests that higher cortical GABA levels are modestly associated with stronger intracortical inhibition. Heterogeneity was low to moderate (I² = 35.5%; Q = 34.73; P = .04). Funnel plot inspection revealed mild asymmetry, but Egger’s test showed no significant smallstudy effects (β₁ = –0.46; P = .58), indicating minimal publication bias. This meta-analysis provides quantitative evidence supporting an inverse association between cortical GABA concentrations and SICI, reinforcing GABA’s role in modulating intracortical inhibition. While the effect size is modest, the findings appear robust and consistent. Future research should employ standardized acquisition and reporting protocols and explore the clinical relevance of this relationship in populations with disrupted GABAergic signaling.
Keyword : Cortical GABA levels, Magnetic resonance spectroscopy, Restricted maximum likelihood, Short interval intracortical inhibition