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J Neurosci. 2013 Dec 11;33(50):19499-503. doi: 10.1523/JNEUROSCI.3048-13.2013.

Motor skill learning induces changes in white matter microstructure and myelination.

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  • 1Oxford Centre for Functional MRI of the Brain and Neuropathology, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Department of Experimental Psychology, and Cancer Research-UK/Medical Research Council Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Oxford OX1 2JD, United Kingdom, School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287, and Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario M5T 3H7, Canada.

Abstract

Learning a novel motor skill is associated with well characterized structural and functional plasticity in the rodent motor cortex. Furthermore, neuroimaging studies of visuomotor learning in humans have suggested that structural plasticity can occur in white matter (WM), but the biological basis for such changes is unclear. We assessed the influence of motor skill learning on WM structure within sensorimotor cortex using both diffusion MRI fractional anisotropy (FA) and quantitative immunohistochemistry. Seventy-two adult (male) rats were randomly assigned to one of three conditions (skilled reaching, unskilled reaching, and caged control). After 11 d of training, postmortem diffusion MRI revealed significantly higher FA in the skilled reaching group compared with the control groups, specifically in the WM subjacent to the sensorimotor cortex contralateral to the trained limb. In addition, within the skilled reaching group, FA across widespread regions of WM in the contralateral hemisphere correlated significantly with learning rate. Immunohistological analysis conducted on a subset of 24 animals (eight per group) revealed significantly increased myelin staining in the WM underlying motor cortex in the hemisphere contralateral (but not ipsilateral) to the trained limb for the skilled learning group versus the control groups. Within the trained hemisphere (but not the untrained hemisphere), myelin staining density correlated significantly with learning rate. Our results suggest that learning a novel motor skill induces structural change in task-relevant WM pathways and that these changes may in part reflect learning-related increases in myelination.

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