On the relationship between GABA+ and glutamate across the brain

Reuben Rideaux, Shane E. Ehrhardt, Yohan Wards, Hannah L. Filmer, Jin Jin, Dinesh K. Deelchand, Małgorzata Marjańska, Jason B. Mattingley, Paul E. Dux

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Equilibrium between excitation and inhibition (E/I balance) is key to healthy brain function. Conversely, disruption of normal E/I balance has been implicated in a range of central neurological pathologies. Magnetic resonance spectroscopy (MRS) provides a non-invasive means of quantifying in vivo concentrations of excitatory and inhibitory neurotransmitters, which could be used as diagnostic biomarkers. Using the ratio of excitatory and inhibitory neurotransmitters as an index of E/I balance is common practice in MRS work, but recent studies have shown inconsistent evidence for the validity of this proxy. This is underscored by the fact that different measures are often used in calculating E/I balance such as glutamate and Glx (glutamate and glutamine). Here we used a large MRS dataset obtained at ultra-high field (7 T) measured from 193 healthy young adults and focused on two brain regions - prefrontal and occipital cortex - to resolve this inconsistency. We find evidence that there is an inter-individual common ratio between GABA+ (γ-aminobutyric acid and macromolecules) and Glx in the occipital, but not prefrontal cortex. We further replicate the prefrontal result in a legacy dataset (n = 78) measured at high-field (3 T) strength. By contrast, with ultra-high field MRS data, we find extreme evidence that there is a common ratio between GABA+ and glutamate in both prefrontal and occipital cortices, which cannot be explained by participant demographics, signal quality, fractional tissue volume, or other metabolite concentrations. These results are consistent with previous electrophysiological and theoretical work supporting E/I balance. Our findings indicate that MRS-detected GABA+ and glutamate (but not Glx), are a reliable measure of E/I balance.

Original languageEnglish (US)
Article number119273
StatePublished - Aug 15 2022

Bibliographical note

Funding Information:
This work was supported by grants from the Australian Research Council to PED and JBM ( DP180101885 ), RR ( DE210100790 ) and HLF ( DE190100299 ) and from the Australian Department of Defence (Human Performance Research (HPR) Network Partnership) to PED, HLF, and JBM. JBM was supported by a National Health and Medical Research Council (Australia) Leadership (L3) Investigator Grant ( GNT2010141) . SE & YW acknowledge support through an Australian Government Research Training Program Scholarship. DKD and MM acknowledge the support of the National Institutes of Health grants BTRC P41 EB027061 and P30 NS076408 . We thank Dr Muhammad Salah, Dr Steve C.N Hui, Dr Helge J. Zöllner and Dr Tonima Ali for helping to set up the protocol. We thank research radiographers, Nicole Atcheson and Aiman Al-Najjar, and Zoie Nott and Kali Chidley for assisting in data collection.

Publisher Copyright:
© 2022


  • 7T
  • E/I balance
  • GABA
  • Glutamate
  • MRS
  • Ultra-high field

Center for Magnetic Resonance Research (CMRR) tags

  • SMCT

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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