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Previous research using functional MRI identified brain regions associated with sensory processing sensitivity (SPS), a proposed normal phenotype trait. To further validate SPS, to characterize it anatomically, and to test the usefulness in psychology of methodologies that assess axonal properties, the present study correlated SPS proxy questionnaire scores (adjusted for neuroticism) with diffusion tensor imaging (DTI) measures. Participants (n = 408) from the Human Connectome Project were studied. Voxelwise analysis showed that mean- and radial diffusivity correlated positively with SPS scores in the right and left subcallosal and anterior–ventral cingulum bundle, and the right forceps minor of the corpus callosum, all frontal cortex areas generally underlying emotion, motivation, and cognition. Further analyses showed correlations throughout medial frontal cortical regions in the right and left ventromedial …