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Microstructural and neurochemical plasticity mechanisms interact to enhance human perceptual decision-making.

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Ziminski, Joseph J 
Frangou, Polytimi 
Karlaftis, Vasilis M 
Emir, Uzay 


Experience and training are known to boost our skills and mold the brain's organization and function. Yet, structural plasticity and functional neurotransmission are typically studied at different scales (large-scale networks, local circuits), limiting our understanding of the adaptive interactions that support learning of complex cognitive skills in the adult brain. Here, we employ multimodal brain imaging to investigate the link between microstructural (myelination) and neurochemical (GABAergic) plasticity for decision-making. We test (in males, due to potential confounding menstrual cycle effects on GABA measurements in females) for changes in MRI-measured myelin, GABA, and functional connectivity before versus after training on a perceptual decision task that involves identifying targets in clutter. We demonstrate that training alters subcortical (pulvinar, hippocampus) myelination and its functional connectivity to visual cortex and relates to decreased visual cortex GABAergic inhibition. Modeling interactions between MRI measures of myelin, GABA, and functional connectivity indicates that pulvinar myelin plasticity interacts-through thalamocortical connectivity-with GABAergic inhibition in visual cortex to support learning. Our findings propose a dynamic interplay of adaptive microstructural and neurochemical plasticity in subcortico-cortical circuits that supports learning for optimized decision-making in the adult human brain.


Acknowledgements: We would like to thank the MR physics and radiographer teams at the Cambridge Wolfson Brain Imaging Centre, and Lilia Kukovska for their support and help with data collection. We would also like to thank Martina Callaghan, Nickolas Weiskopf, and the Wellcome Centre for Human Neuroimaging for providing the MPM sequences, and Guy Williams and Steve Sawiak for their expert assistance in MR-sequence testing. We would like to thank Thora Karadottir, Sonja Hofer, Jasper Poort, and Martina Callaghan for helpful comments and suggestions.


Adult, Male, Female, Humans, Learning, Brain, Magnetic Resonance Imaging, Brain Mapping, gamma-Aminobutyric Acid, Neuronal Plasticity

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PLoS Biol

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Public Library of Science (PLoS)
Wellcome Trust (205067/Z/16/Z)
Biotechnology and Biological Sciences Research Council (BB/P021255/1)
Wellcome Trust (223131/Z/21/Z)
Wellcome Trust (221633/Z/20/Z)
This work was supported by grants to ZK from the Wellcome Trust [grant number 205067/Z/16/Z, 221633/Z/20/Z], the Biotechnology and Biological Sciences Research Council [grant numbers H012508, BB/P021255/1].
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