Background:Sensory processing difficulties are common across neurodevelopmental disorders. Thus, reliable measures are needed to understand the biological underpinnings of these differences. This study aimed to define a scoring methodology specific to auditory (AOR) and tactile (TOR) over-responsivity. Second, in a pilot cohort using MRI Diffusion Tensor Imaging, we performed a proof of concept study of whether children with AOR showed measurable differences in their white matter integrity. Methods:This study included children with AOR and TOR from a mixed neurodevelopmental disorder cohort including autism and sensory processing dysfunction (n = 176) as well as neurotypical children (n = 128). We established cohorts based on sensory over-responsivity using parent report (Short Sensory Profile (SSP)) and direct assessment (Sensory Processing-Three Dimensions: Assessment (SP-3D:A)) measures. With a subset of the children (n = 39), group comparisons, based on AOR phenotype, were conducted comparing the white matter fractional anisotropy in 23 regions of interest. Results:Using direct assessment, 31% of the children with neurodevelopmental disorders had AOR and 27% had TOR. The inter-test agreement between SSP and SP-3D:A for AOR was 65% and TOR was 50%. Children with AOR had three white matter tracts showing decreased fractional anisotropy relative to children without AOR. Conclusions:This study identified cut-off scores for AOR and TOR using the SSP parent report and SP-3D:A observation. A combination of questionnaire and direct observation measures should be used in clinical and research settings. The SSP parent report and SP-3D:A direct observation ratings overlapped moderately for sensory related behaviors. Based on these preliminary structural neuroimaging results, we suggest a putative neural network may contribute to AOR.