Motor skill learning induces changes in white matter microstructure and myelination

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.

Figure 1.

Behavioral results. A, Average accuracy scores for SR animals for all training days (black) and UR rats for the day 11 test (gray) (n = 24). B, Average number of reaches per day for SR (black) and UR (gray) (n = 24 animals per group). Error bars represent SEM.

Figure 2.

A, TBSS between-group analysis revealed that SR animals have significantly higher FA than UR and CC animals in WM areas comprising the external capsule and cingulum colocalized with somatomotor GM areas in the contralateral hemisphere to the trained paw. Right, Mean FA from within the significant cluster is plotted for each group to visualize the range of values. B, TBSS within-group correlation analysis showed that, within the SR group, animals with steeper learning rates have higher FA in widespread WM areas. Right, Scatter plot of mean FA within the significant cluster versus learning rate for individual animals is displayed for visualization of the range of values. All clusters shown at p < 0.05, corrected for multiple comparisons.

Figure 3.

A, Representative anti-MBP-stained sections. Scale bar, 200 μm. B, SR animals have significantly higher MBP stain intensity than UR animals. C, Animals with higher MBP stain intensity in WM subjacent M1 contralateral to the trained paw learn the reaching task faster (n = 7). D, No correlation with performance was found for the WM underlying M1 on the ipsilateral side (n = 8). Low luminance values reflect higher stain intensity. Vertical scales have been inverted for intuitive reading. Error bars represent SEM. *p < 0.05.