# A Synergistic Examination of Excitatory‐Inhibitory Balance in First‐Episode Schizophrenia Merging 7‐Tesla Magnetic Resonance Spectroscopic Imaging and Magnetoencephalography

## TL;DR

This study links reduced GABA levels in schizophrenia patients to abnormal brain activity and worse symptoms using advanced brain imaging techniques.

## Contribution

The study is the first to merge 7T MRSI and MEG to show how GABA/Glu ratios relate to auditory gamma-band responses and clinical outcomes in first-episode schizophrenia.

## Key findings

- Lower GABA/Glu ratios in the superior temporal sulcus correlate strongly with reduced evoked gamma-band response power in first-episode schizophrenia.
- Left hemisphere GABA/Glu ratios are inversely linked to symptom severity and positively linked to social functioning scores.
- Right hemisphere gamma-band response power correlates positively with symptom severity in first-episode schizophrenia.

## Abstract

Excitatory/inhibitory (E/I) imbalance is a proposed neural disruption in schizophrenia supported by magnetic resonance spectroscopic imaging (MRSI) evidence of altered gamma‐aminobutyric acid (GABA) and glutamate (Glu) levels. However, there exists a paucity of data linking these abnormalities to impaired in vivo brain function putatively reflecting E/I imbalance. Here, associations between GABA/Glu and the evoked early auditory gamma‐band response (EAGBR) were examined in first‐episode schizophrenia (FESz).

Twelve FESz underwent resting‐state 7T‐MRSI and magnetoencephalography (MEG) recorded during an auditory oddball task. MRSI spectra and source‐localized MEG data were extracted from overlapping regions of left (LH) and right (RH) superior temporal sulcus. Associations between evoked EAGBR power and GABA/Glu, GABA/Cre, and Glu/Cre ratios were assessed. The Brief Psychiatric Rating Scale (BPRS) and Global Functioning: Role/Social (GF: Role/Social) scales were collected.

GABA/Glu ratios were inversely correlated with EAGBR power (LH: ρ = −0.87; RH: ρ = −0.85). LH GABA/Glu ratios were also inversely correlated with BPRS scores (ρ = −0.64) and positively correlated with GF: Social (ρ = 0.64) scores while RH EAGBR power was positively correlated with BPRS scores (ρ = 0.70). Stepwise linear regressions suggest these relationships were driven primarily by GABA concentrations.

Associations in FESz between GABA/Glu ratios, clinical ratings, and EAGBR power suggests this evoked gamma‐band response reflects cortical hyperexcitability within the auditory system that is closely tied to disease debility at this early illness stage. These data highlight the potential of merging high‐precision, in vivo neuro‐chemical assays via 7‐Tesla MRSI and physiological measures from MEG to validate established cellular models of disease.

A merged analysis of 7T MRSI and MEG recordings revealed an association between smaller GABA/Glutamate ratios and the evoked early auditory gamma‐band response (EAGBR), a potential marker of cortical hyperexcitability, in first‐episode schizophrenia. This relationship, and associated clinical outcomes, appear to be driven by GABA levels.