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Learning engages transient and sustained cellular mechanisms in the human brain.

Overview

Authors: Guillermina Griffa1, Marco Palombo2, Abraham Yeffal1,3, Hong-Hsi Lee4, Agustin Solano1,3, Susie Y. Huang4, Valeria Della-Maggiore1,3,5
ORCID iDs: Guillermina Griffa, Marco Palombo, Valeria Della-Maggiore
  1. IFIBIO Houssay, School of Medicine, Department of Physiology, University of Buenos Aires, Buenos Aires, Argentina
  2. Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology and School of Computer Science and Informatics, Cardiff University, Cardiff, United Kingdom
  3. ICIFI School of Science and Technology (ECyT), University of San Martín, Buenos Aires, Argentina
  4. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
  5. Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
Institutions: Universidad de Buenos Aires (Argentina); Cardiff University (United Kingdom); Harvard University (United States); Massachusetts General Hospital (United States); Athinoula A. Martinos Center for Biomedical Imaging (United States); McGill University (Canada)
Journal: PLoS biology, volume 24, issue 6, article e3003861
Dates: received 12 December 2025; accepted 4 June 2026; published online 18 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1371/journal.pbio.3003861 · PMID 42313886 · PMCID PMC13298990 · OpenAlex W7165191421
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: structural MRI / diffusion (modality), human (organism), cellular / molecular (subfield)
Methods: Statistics, fMRI & imaging
MeSH: Brain*, Learning*, Neuronal Plasticity*, Adult, Diffusion Magnetic Resonance Imaging, Female, Humans, Male, Motor Skills (* major topic)
Journal subjects: Biology and Life Sciences, Anatomy, Brain, Hippocampus, Medicine and Health Sciences, Neuroscience, Cognitive Science, Cognitive Psychology, Learning, Psychology, Social Sciences, Learning and Memory, Brain Mapping, Brain Morphometry, Diffusion Magnetic Resonance Imaging, Diagnostic Medicine, Diagnostic Radiology, Magnetic Resonance Imaging, Research and Analysis Methods, Imaging Techniques, Radiology and Imaging, Neuroimaging, Functional Magnetic Resonance Imaging, Diffusion Tensor Imaging, Physical Sciences, Materials Science, Materials Physics, Microstructure, Physics, Cell Biology, Cell Processes
Topic: Advanced Neuroimaging Techniques and Applications (Radiology, Nuclear Medicine and Imaging, Medicine), according to OpenAlex
Funding: Argentinian Agency for the Promotion of Science and Technology (FONCyT) (PICT 2018-1150, PICT 2019-2156); Office of The Director (OD) of the National Institutes of Health (NIH) in partnership with the National Institute of Dental & Craniofacial Research (NIDCR) (DP5 OD031854); National Institute of Aging (NIA) (R21 AG085795); National Institute of Neurological Disorders and Stroke (NINDS) (R01 NS118187); National Institute of Biomedical Imaging and Bioengineering (NIBIB) (U24 NS137077, U01 EB026996, P41 EB015896, P41 EB030006); UK Research and Innovation (UKRI) Future Leaders Fellowship (MR/T020296/2, UKRI1073); Medical Research Council (MRC) (MR/W031566/1)
Citations: cited by 1 paper (Europe PMC); 96 references in the paper

Abstract

Structural neuroplasticity supports learning, development, and shapes vulnerability to brain disorders, making it a central priority in neuroscience research. However, progress in humans has remained limited by the inability to probe cellular processes in vivo, leaving mechanistic insight largely dependent on animal models. To address this gap, here we combined the sub-voxel sensitivity of ultra–high-gradient diffusion MRI with the cell-compartment specificity of the Soma and Neurite Density Imaging (SANDI) model to probe structural plasticity directly in the living human brain. By tracking how learning modulates the temporal dynamics of cell bodies and cell processes, we aimed to distinguish plastic from nonplastic biological processes driving changes in microstructure. We found that learning a motor skill triggered two distinct temporal responses: a transient expansion of cell bodies across all brain regions engaged by the task, consistent with a short-lived homeostatic mechanism, and a sustained increase in cell-process density restricted to key motor regions, consistent with structural plasticity. Our approach provides a mechanistic window into human neuroplasticity and marks a significant step toward bridging the gap between animal and human neuroscience.

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

Code

The paper links to its data, not to its authors' code: see the Data section.

The paper's code and data availability statement is in the Data section.

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Data

Datasets cited

Data Availability

The dataset and scripts used for data processing and analysis are available on Zenodo (https://doi.org/10.5281/zenodo.20527091). A README file is included describing the contents of the repository.

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

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 9 MeSH terms, 7 funders, 90 references.

Cite

This paper

Griffa, G., Palombo, M., Yeffal, A., Lee, H.-H., Solano, A., Huang, S. Y., & Della-Maggiore, V. (2026). Learning engages transient and sustained cellular mechanisms in the human brain. PLoS biology, 24(6), e3003861. https://doi.org/10.1371/journal.pbio.3003861

BibTeX

@article{griffa2026learning,
author = {Griffa, Guillermina and Palombo, Marco and Yeffal, Abraham and Lee, Hong-Hsi and Solano, Agustin and Huang, Susie Y. and Della-Maggiore, Valeria},
title = {{Learning engages transient and sustained cellular mechanisms in the human brain}},
journal = {PLoS biology},
year = {2026},
month = jun,
volume = {24},
number = {6},
pages = {e3003861},
publisher = {PLOS},
issn = {1544-9173},
doi = {10.1371/journal.pbio.3003861},
url = {https://doi.org/10.1371/journal.pbio.3003861},
pmid = {42313886},
pmcid = {PMC13298990}
}

RIS

TY - JOUR
AU - Griffa, Guillermina
AU - Palombo, Marco
AU - Yeffal, Abraham
AU - Lee, Hong-Hsi
AU - Solano, Agustin
AU - Huang, Susie Y.
AU - Della-Maggiore, Valeria
TI - Learning engages transient and sustained cellular mechanisms in the human brain
T2 - PLoS biology
J2 - PLoS Biol
PY - 2026
DA - 2026/06/18
VL - 24
IS - 6
SP - e3003861
SN - 1544-9173
PB - PLOS
DO - 10.1371/journal.pbio.3003861
UR - https://doi.org/10.1371/journal.pbio.3003861
LA - en
ER -

CSL-JSON

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