Creativity is the ability to produce work that is novel, high in quality, and appropriate to an audience. One domain of creativity comes from musical improvisation, in which individuals spontaneously create novel auditory-motor sequences that are aesthetically rewarding. Here we test the hypothesis that individual differences in creative behavior are subserved by mesial and lateral differences in white matter connectivity. We compare jazz improvising musicians against classical (non-improvising) musicians and non-musician control subjects in musical performance and diffusion tensor imaging. Subjects improvised on short musical motifs and underwent DTI. Statistical measures of fluency and entropy for musical performances predicted expert ratings of creativity for each performance. Tract-Based Spatial Statistics (TBSS) showed higher Fractional Anisotropy (FA) in the cingulate cortex and corpus callosum in jazz musicians. FA in the cingulate also correlated with entropy. Probabilistic tractography from these mesial regions to lateral seed regions of the arcuate fasciculus, a pathway known to be involved in sound perception and production, showed mesial-to-lateral connectivity that correlated with improvisation training. Results suggest that white matter connectivity between lateral and mesial structures may integrate domain-general and domain-specific components of creativity.