Baclofen, a GABAB receptor agonist, impairs motor learning in healthy people and changes inhibitory dynamics in motor areas

Ioana-Florentina Grigoras; Elias Geist; Ainslie Johnstone; William T Clarke; Uzay Emir; Caroline Nettekoven; Jacob M. Levenstein; Liliana Capitao; Charlotte J Stagg

doi:10.1162/IMAG.a.979

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Baclofen, a GABAB receptor agonist, impairs motor learning in healthy people and changes inhibitory dynamics in motor areas

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Baclofen, a GABAB receptor agonist, impairs motor learning in healthy people and changes inhibitory dynamics in motor areas

Ioana-Florentina Grigoras, Elias Geist, Ainslie Johnstone, William T Clarke, Uzay Emir, Caroline Nettekoven, Jacob M. Levenstein, Liliana Capitao and Charlotte J Stagg

Imaging Neuroscience, Vol.3, pp.1-15

2025

DOI: https://doi.org/10.1162/IMAG.a.979

PMCID: PMC12580813

PMID: 41190329

Appears in Thompson Institute Research Collection

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Abstract

GABA

motor learning

MRSI

baclofen

MR spectroscopy

Other Collaborations

Thompson Institute Special Collection

Inhibition mediated by γ-aminobutyric acid (GABA) is implicated in motor plasticity and learning, with [GABA] in the motor cortex decreasing during motor learning. However, the causal relationship between [GABA] and learning has yet to be determined. Here, we conducted a within-subject, double-blind, placebo-controlled, crossover study to investigate the effect of increased GABAergic inhibition via GABAB-receptor agonist baclofen on motor learning and Magnetic Resonance Spectroscopic Imaging (MRSI) metrics. Increasing GABA-mediated inhibition with baclofen did not change response times, but significantly impaired motor sequence learning. In parallel, we demonstrated a blunting of the expected decrease in [GABA] during motor learning. These results highlight a causal role for GABAergic inhibition in motor learning and may have clinical implications: baclofen is commonly used to treat post brain-injury spasticity, but may impair motor learning during rehabilitation.

Details

Title: Baclofen, a GABAB receptor agonist, impairs motor learning in healthy people and changes inhibitory dynamics in motor areas
Authors: Ioana-Florentina Grigoras (Corresponding Author) - MRC Brain Network Dynamics Unit
Elias Geist - University of Oxford
Ainslie Johnstone - University of Oxford
William T Clarke - Oxford Health NHS Foundation Trust
Uzay Emir - University of Oxford
Caroline Nettekoven - University of Oxford
Jacob M. Levenstein - University of the Sunshine Coast, Queensland, Thompson Institute
Liliana Capitao - University of Minho
Charlotte J Stagg - MRC Brain Network Dynamics Unit
Publication details: Imaging Neuroscience, Vol.3, pp.1-15
Publisher: MIT Press
Date published: 2025
DOI: 10.1162/IMAG.a.979
ISSN: 2837-6056
PMID: 41190329; PMC12580813
Copyright note: © 2025 The Authors. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. For a full description of the license, please visit https://creativecommons.org/licenses/by/4.0/legalcode.
Data Availability: Image and data processing pipelines, as well as MRI sequence parameters, are publicly available here: https:// git.fmrib.ox.ac.uk/grigoras/baclofen_mri/. The raw MRI data are protected and not available due to data privacy laws.
Grant note: C.J.S. was supported by a Wellcome Trust Senior Research Fellowship (224430/Z/21/Z). W.T.C. was supported by a Wellcome Trust Career Development Award (225924/Z/22/Z). C.R.N. was supported by a Wellcome Trust Early Career Award (306553/Z/23/Z). The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust (203139/Z/16/Z and 203139/A/16/Z). L.C. currently works at the Psychology Research Centre (PSI/01662), School of Psychology, University of Minho, supported by the Foundation for Science and Technology (FCT) through the Portuguese State Budget (Ref.: UID/PSI/ 01662/2020). L.C. is individually funded by a Research Fellowship also from the Foundation for Science and Technology (FCT) (Ref: 2021.00415.CEECIND). This study was supported by the NIHR Oxford Health Biomedical Research Centre (OH BRC, IHR203316).
Organisation Unit: Thompson Institute
Language: English
Record Identifier: 991179281302621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Neuroimaging; Neurosciences

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