The association between medial prefrontal GABA concentration and memory performance is disrupted in human with a high body mass index

TL;DR

This study finds that high BMI disrupts the link between brain GABA levels and memory performance in young and middle-aged humans.

Contribution

The study reveals that high BMI disrupts the relationship between medial prefrontal GABA and memory performance.

Findings

Memory performance is predicted by medial prefrontal GABA concentration in individuals with low/moderate BMI but not in those with high BMI.

High BMI is associated with disrupted GABAergic processes in the frontal cortex and lower memory performance.

Glutamate and precuneus GABA/glutamate levels are not linked to the BMI-memory relationship.

Abstract

While the somatic effects of obesity are increasingly well understood, growing evidence indicates that there is a cognitive effect such as a decline in episodic memory. Studies in animals revealed an association between obesity, memory impairment and neurotransmitters such as γ-aminobutyric acid (GABA) and glutamate. In the present study we aimed to assess the relation of body mass index (BMI) as indicator of overwight/obesity, memory and GABA / glutamate concentrations in the medial prefrontal cortex (mPFC) and precuneus in human subjects aged 19 to 41 years. We found that memory performance is predicted by mPFC GABA concentration in individuals with a low and a moderate BMI, but not in individuals with a high BMI (> 26) indicating overweight/obesity. MPFC glutamate and precuneus GABA/ glutamate levels appeared to be not related to the association between BMI and memory performance. Our findings suggest that clinically relevant overweight/obesity affects GABAergic processes in the frontal cortex and is related to lower memory performance in a group of young and middle-aged human subjects.

The online version contains supplementary material available at 10.1007/s11682-026-01121-1.

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