Short-term learning induces white matter plasticity in the fornix

Abstract

Magnetic resonance imaging (MRI) has greatly extended the exploration of neuroplasticity in behaving animals and humans. Imaging studies recently uncovered structural changes that occur in gray and white matter, mainly after long-term training. A recent diffusion tensor imaging (DTI) study showed that training in a car racing game for 2 h induces changes in the hippocampus and parahippocampal gyri. However, the effect of short-term training on the white matter microstructure is unknown. Here we investigated the influence of short learning tasks on structural plasticity in the white matter, and specifically in the fornix, in humans and rats. Human subjects performed a 2 h spatial learning task, and rats underwent training for 1 d in a Morris water maze. Between tasks, subjects were scanned with DTI, a diffusion MRI framework sensitive to tissue microstructure. Using tract-based spatial statistics, we found changes in diffusivity indices in both humans and rats. In both species, changes in diffusion in the fornix were correlated with diffusion changes in the hippocampus, as well as with behavioral measures of improvement in the learning tasks. These results, which provide the first indication of short-term white matter plasticity in the human brain, suggest that the adult brain white matter preserves dynamic characteristics and can be modified by short-term learning experiences. The extent of change in white matter was correlated with their extent in gray matter, suggesting that all components of the neural network are capable of rapid remodeling in response to cognitive experiences.

Figures

Figure 1.

A, Improvement in the car racing game. Normalized lap times (mean ± SEM) show significant reduction in time required to complete the track in the LG group (n = 33) but not in the AC group (n = 13). B, Improvement in the water-maze task shown by the reduction in the time required to reach the hidden platform (mean ± SEM) (n = 19). This figure is based on data presented by Sagi et al. (2012), excluding subjects that were not part of the analyses in the current study.

Figure 2.

Changes in diffusion indices after short-term learning tasks. Statistical images were threshold at p < 0.05 for display purposes. A, Reduction in MD in the two learning subgroups as identified by TBSS. Statistical images are overlaid on the mean FA image of all subjects and the fornix skeleton mask (green). Red clusters show reduction in MD in LG group. Blue clusters display reduction in MD in the second subgroup, LG2. B, Reduction in λ1 (blues voxels) is presented, overlaid on the fornix skeleton mask (green) and the men FA image. C, Mean values of the percentage of change in MD revealed by the group × time interaction analysis between the learning group and the two control groups (p < 0.01 clusters ≥ 5). D, Reduction in MD in the two rat subgroups after 1 d training in the Morris water maze. Red clusters present regions in which reduction in MD in the L group was found, and blue clusters display the reduction in L2. Results are superimposed on the fornix skeleton (green) and the mean FA rat image. E, Reduction in L1 in the L group, overlaid on the fornix skeleton (green) and the mean FA map. F, Mean values of the percentage of change in MD in the analysis across groups (p < 0.01).

Figure 3.

Correlation between changes in gray matter (hippocampus) and the difference in diffusion in the fornix. A, Statistical maps showing correlation of MD (red) and λ1 (blue) with the percentage of change in the hippocampus are thresholded at p < 0.005 and overlaid on the fornix mask (green) and the mean FA map. B, Correlation analysis of the difference in MD values with the percentage of change in the hippocampus (p < 0.05, corrected; r = 0.62). C, Colocalization of regions in which decrease in MD was found (red; p < 0.05 for display purposes) and correlation analysis of the difference in λ1 with changes in MD the hippocampus (blue; p < 0.005), overlaid on the fornix skeleton mask (green) and mean FA image. D, Correlation analysis of the difference in λ1 values with the percentage of change in MD in the hippocampus (p < 0.05, corrected; r = 0.87).

Figure 4.

Correlation analysis between changes in MD in the hippocampus of rats undergoing 1 d of water-maze training with the change in diffusion indices in the fornix. A, Regions in which positive correlation between changes in MD in the fornix and the percentage of change in MD in the hippocampus (red; p < 0.005) are superimposed on the fornix skeleton mask (green) and mean FA image. B, Correlation analysis of the difference in MD in the fornix and the percentage of change in MD in the hippocampus (p < 0.05, corrected; r = 0.9). C, A positive correlation was also found between the difference in RD and the percentage of change in MD in the hippocampus (blue; p < 0.005), overlaid on the fornix skeleton mask (green) and mean FA image. D, Correlation analysis between the difference in RD and the percentage of change in MD in the hippocampus (p < 0.05, corrected; r = 0.87).

Figure 5.

Correlation analysis between changes in diffusion indices in the fornix and behavioral measurements. A, Regions in which changes in FA were found to correlate with improvement in the car racing game (red; p < 0.005), overlaid on the fornix mask (green) and mean FA image. B, Correlation analysis of change in FA in the fornix and improvement in lap time (p < 0.005; r = −0.74). C, Regions in which a correlation between averaged picture score and changes in MD were found (p < 0.005), colocalized with clusters showing MD decrease (p < 0.05), overlaid on the fornix mask (green) and mean FA image. D, Correlation analysis between changes in MD in the fornix and averaged picture score (p < 0.005; r = 0.52). E, Blue clusters present regions in which correlation between changes in RD in the fornix and improvement in the Morris water maze (p < 0.05 for display purposes) was found, overlaid on the fornix skeleton mask (green) and mean FA image. F, Correlation analysis between changes in RD and improvement in Morris water maze (p < 0.005; r = 0.78).