The prevailing model of amnesia holds that it depends on damage to a group of loosely related structures, collectively called the medial temporal lobe (MTL). One influential theory holds that these areas work together as a single functional unit. According to this theory, the structures in the MTL store the memory of specific objects, facts and events. We have developed a competing hypothesis, which holds that different structures within the MTL have specialized functions, and that their collective functions extend beyond those assigned to the MTL by the prevailing model. The ability to learn novel skills throughout our lifetime is known to be mediated by structural changes in the brain. However, the nature of the structural changes and the spatiotemporal dynamics of such changes during the course of learning are unclear. Here, we trained nave subjects in two tasks differing in complexity. The subjects were first trained to criterion in the one-place task, a visuomotor task which required the subject to reach and touch an object on a computer screen to earn a reward. Next, the subjects were trained in the scenes task, in which they learned to touch a target foreground object placed in an artificial scene composed of multiple geometric elements to earn a reward. The subjects learned several unique scenes concurrently; the identity and location of the target object differed across scenes but was fixed within scenes. We acquired diffusion magnetic resonance images (dMRI) from the subjects across two timepoints using a Bruker 4.7T MRI system. The pre-training scans were acquired before any formal training and the post-training scans were acquired when the subjects reached criterion in the second (scenes) task or failed to reach criterion despite extensive training. Behaviorally, the subjects showed wide individual variability in their ability to acquire the different tasks, with 2 of the 8 subjects failing to learn the one-place task. Interestingly, subjects that required fewer trials to criterion in the one-place task learned faster in the scenes task (rho = - 0.77 p < 0.04). Examination of the spatial topography of changes in dMRI measures based on a median split analysis with group (good/bad learners) and timepoint (Pre/Post) as factors in a linear mixed effects model revealed a significant main effect of group, with the good learners showing higher Fractional Anisotropy (FA) of the right internal capsule, anterior commissure and crus of the fornix. Finally, correlation analysis between the learning profile and changes in dMRI measures revealed: (a) a trend towards a positive correlation between faster learning in the scenes task and global increase in white matter volume; (b) more trials to criterion in the one-place task correlated positively with an increase in FA and a decrease in Radial Diffusivity in the dorsal parieto-occipital white matter. This region is considered part of the fronto-occipito fasciculus, which has been associated with reaching and grasping arm movements. Overall, the pattern of changes in the dMRI measures suggest that prolonged experience in performing the training tasks evokes changes in tissue microstructure consistent with changes in myelination. Additional subjects are required to draw firm conclusions regarding the relationship between changes in white matter and learning.
