Gray and white matter changes associated with tool-use learning in macaque monkeys.

We used noninvasive MRI and voxel-based morphometry (VBM) to detect changes in brain structure in three adult Japanese macaques trained to use a rake to retrieve food rewards. Monkeys, who were naive to any previous tool use, were scanned repeatedly in a 4-T scanner over 6 weeks, comprising 2 weeks of habituation followed by 2 weeks of intensive daily training and a 2-week posttraining period. VBM analysis revealed significant increases in gray matter with rake performance across the three monkeys. The effects were most significant (P < 0.05 corrected for multiple comparisons across the whole brain) in the right superior temporal sulcus, right second somatosensory area, and right intraparietal sulcus, with less significant effects (P < 0.001 uncorrected) in these same regions of the left hemisphere. Bilateral increases were also observed in the white matter of the cerebellar hemisphere in lobule 5. In two of the monkeys who exhibited rapid learning of the rake task, gray matter volume in peak voxels increased by up to 17% during the intensive training period; the earliest changes were seen after 1 week of intensive training, and they generally peaked when performance on the task plateaued. In the third monkey, who was slower to learn the task, peak voxels showed no systematic changes. Thus, VBM can detect significant brain changes in individual trained monkeys exposed to tool-use training for the first time. This approach could open up a means of investigating the underlying neurobiology of motor learning and other higher brain functions in individual animals.