<p>Differences in behavioral performance between experts and novices have been reported to be closely associated with variations in brain structure. However, results and conclusions from comparisons between experts and novices remain inconsistent. One possible explanation for this inconsistency is the lack of sufficiently sensitive statistical approaches to detecting subtle structural differences in the brain. This study employed a novel voxel-based regional analysis to enhance statistical power, examining structural differences in the brain between mental abacus experts and controls without any abacus experience. After multiple-comparison correction, significant differences in grey matter volume were still observed throughout the brain, including larger volumes in key regions of the situational network consisting of the right hippocampus and fusiform gyrus, and smaller volumes in the sensorimotor network consisting of the bilateral dorsal caudate nucleus, left precentral gyrus, and right cerebellum for experts. The differences were closely associated with the duration of abacus training. The widely distributed structural differences are discussed in line with previous similar studies within and beyond the abacus domain.</p>