The trajectory of cortical GABA across the lifespan, an individual participant data meta-analysis of edited MRS studies

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Abstract

GABA is the principal inhibitory neurotransmitter in the human brain and can be measured with Magnetic Resonance Spectroscopy (MRS). Conflicting accounts report decreases and increases in cortical GABA levels across the lifespan. This incompatibility may be an artifact of the size and age-range of the samples utilized in these studies. No single study to date has included the entire lifespan. In this study, 8 suitable datasets were integrated to generate a model of the trajectory of frontal GABA estimates (as reported through edited MRS; both expressed as ratios and in institutional units). across the lifespan. Data were fit using both a log-normal curve and a nonparametric spline as regression models using a multi-level Bayesian model utilizing the Stan language. Integrated data show the lifespan trajectory of frontal GABA measures involves an early period of increase, followed by a period of stability during early adulthood, with a gradual decrease during adulthood and aging that is described well by both spline and log-normal models. The information gained will provide a general framework to inform expectations of future studies based on the age of the population being studied.

Data availability

All data and code used in this manuscript can be found here https://osf.io/rmhwc/

The following data sets were generated

(2020) The trajectory of cortical GABA levels across the lifespan
Open Science Framework, rmhwc.

https://osf.io/rmhwc/

The following previously published data sets were used

1. Mikkelsen M et al
(2017) Big GABA: Edited MR spectroscopy at 24 research sites.
doi: 10.1016/j.neuroimage.2017.07.021.

https://www.nitrc.org/projects/biggaba/

Article and author information

Author details

Eric C Porges

Clinical and Health Psychology, University of Florida, Gainesville, United States

For correspondence
eporges@phhp.ufl.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3885-5859
Greg Jensen

Columbia University, New York, United States

Competing interests
The authors declare that no competing interests exist.
Brent Foster

Clinical and Health Psychology, University of Florida, Gainesville, United States

Competing interests
The authors declare that no competing interests exist.
Richard AE Edden PhD

Johns Hopkins University School of Medicine, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Nicolaas AJ Puts

King's College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.

Funding

National Institutes of Health (KO1AA025306)

Eric C Porges

Evelyn F. McKnight Brain Research Foundation

Eric C Porges

Center for Cognitive Aging and Memory at the University of Florida

Eric C Porges

National Institutes of Health (R00MH107719)

Nicolaas AJ Puts

National Institutes of Health (R01EB016089)

Richard AE Edden PhD

National Institutes of Health (R01MH106564)

Richard AE Edden PhD

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.