Inhibition/excitation balance is associated with functional connectivity during cognitive flexibility performance.

Overview

Authors: Geraldine Rodríguez-Nieto^1,2,3, Mark Mikkelsen⁴, Stephan P Swinnen^1,2

ORCID iDs: Geraldine Rodríguez-Nieto, Mark Mikkelsen

Movement Control and Neuroplasticity Research Group, Biomedical Sciences, KU Leuven, Leuven 3001, Belgium
KU Leuven Brain Institute, KU Leuven, Leuven 3000, Belgium
Rehabilitation Research Institute (REVAL), University of Hasselt, Diepenbeek 3500, Belgium
Department of Radiology, Weill Cornell Medicine, New York, NY, USA

Journal: Brain communications, volume 8, issue 5, article fcag319

Dates: received 20 November 2025; accepted 3 August 2026; published online 28 September 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1093/braincomms/fcag319 · PMID 42802878 · PMCID PMC13616520

Status: data only

Categories: fMRI (modality), human (organism), cognitive (subfield)

Methods: Connectivity, fMRI & imaging

Keywords: GABA, glutamate, functional connectivity, cognitive flexibility, ageing

Funding: Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders); G039821N; Excellence of Science; 30446199; KU Leuven (Katholieke Universiteit Leuven); C16/15/070

Citations: not cited yet (Europe PMC); 59 references in the paper

Research resources: precuneus) from the Harvard-Oxford atlas RRID:SCR_001476

Abstract

The primary excitatory and inhibitory neurotransmitters, glutamate and GABA, regulate neural communication. In this cross-sectional study, we investigated whether the large-scale functional connectivity of two important brain hubs, the inferior frontal cortex and the inferior parietal lobe, is associated with changes in the GABA/Glx (glutamate + glutamine) balance in the in vivo human brain during a cognitive flexibility task. Furthermore, we explored age differences in this relationship, given the alterations in neurotransmitter levels and in cognitive flexibility performance in older adults. Forty young (18–35 years; 26 females) and forty older (60–85 years; 21 females) adults participated. The MRI protocol included functional MRI and baseline and task-related magnetic resonance spectroscopy. Results showed that task-induced modulation of GABA+/Glx is associated with functional connectivity from the inferior frontal cortex and inferior parietal lobe during cognitive flexibility performance. In particular, young adults showed stronger functional connectivity associated with increased inhibitory tone in the inferior frontal cortex than older adults, whereas the pattern was reversed in the inferior parietal lobe. In addition, whereas the connectivity between the left inferior parietal lobe and the bilateral putamen in young adults predicted better cognitive flexibility (left putamen: r = 0.41, P = 0.05; right putamen: r = 0.51 P = 0.01; controlling for GABA modulation), this relationship had an opposite direction in older adults (left putamen: r = −0.33, P = 0.05; right putamen: r = −0.31 P = 0.01; controlling for GABA modulation). In sum, these results show that neurometabolic dynamics and functional connectivity underlying cognitive flexibility undergo substantial changes during ageing.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

osf:t8dzn, at OSF; found in “Data availability”

Data availability

The dataset used for the present study can be found in the OSF repository: https://osf.io/t8dzn/overview?view_only=9cf0a6744ed04ca597146fa730bc37c4

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 5 keywords, 6 funders, 0 references, 1 RRID.

Cite

This paper

Rodríguez-Nieto, G., Mikkelsen, M., & Swinnen, S. P. (2026). Inhibition/excitation balance is associated with functional connectivity during cognitive flexibility performance. Brain communications, 8(5), fcag319. https://doi.org/10.1093/braincomms/fcag319

BibTeX

@article{rodrigueznieto2026inhibition, author = {Rodríguez-Nieto, Geraldine and Mikkelsen, Mark and Swinnen, Stephan P}, title = {{Inhibition/excitation balance is associated with functional connectivity during cognitive flexibility performance}}, journal = {Brain communications}, year = {2026}, month = sep, volume = {8}, number = {5}, pages = {fcag319}, publisher = {Oxford University Press}, issn = {2632-1297}, doi = {10.1093/braincomms/fcag319}, url = {https://doi.org/10.1093/braincomms/fcag319}, pmid = {42802878}, pmcid = {PMC13616520} }

RIS

TY - JOUR AU - Rodríguez-Nieto, Geraldine AU - Mikkelsen, Mark AU - Swinnen, Stephan P TI - Inhibition/excitation balance is associated with functional connectivity during cognitive flexibility performance T2 - Brain communications J2 - Brain Commun PY - 2026 DA - 2026/09/28 VL - 8 IS - 5 SP - fcag319 SN - 2632-1297 PB - Oxford University Press DO - 10.1093/braincomms/fcag319 UR - https://doi.org/10.1093/braincomms/fcag319 LA - en ER -

CSL-JSON

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