DIFFUSION TENSOR IMAGING ABNORMALITIES IN THE UNCINATE FASCICULUS AND INFERIOR LONGITUDINAL FASCICULUS IN PHELAN-MCDERMID SYNDROME

Abstract Objective This cohort study utilized diffusion tensor imaging tractography to compare the uncinate fasciculus and inferior longitudinal fasciculus in children with Phelan-McDermid Syndrome to age matched controls and investigated trends between autism spectrum diagnosis symptoms and the integrity of the uncinate fasciculus and inferior longitudinal fasciculus white matter tracts. Methods This research was conducted under a longitudinal, network study that aims to map the genotype, phenotype, and natural history of Phelan-McDermid Syndrome and identify biomarkers using neuroimaging (ClinicalTrial NCT02461420). Patients were 3-21 years of age and underwent longitudinal neuropsychological assessment over 24 months. MRI processing and analyses were completed using previously validated image analysis software distributed as the Computational Radiology Kit ( http://crl.med.harvard.edu/ ). Whole brain connectivity was generated for each subject using a stochastic streamline tractography algorithm, and automatically defined regions of interest were used to map the uncinate fasciculus and inferior longitudinal fasciculus. Results There were 10 participants (50% male; mean age 11.17 years) with Phelan-McDermid Syndrome (n=8 with autism). Age-matched controls, enrolled in a separate longitudinal study (NIH R01 NS079788), underwent the same protocol. There was a statistically significant decrease in the uncinate fasciculus fractional anisotropy measure and a statistically significant increase in uncinate fasciculus mean diffusivity measure, in the patient group vs controls in both right and left tracts (p ≤ 0.024). Conclusion Because the uncinate fasciculus plays a critical role in social and emotional interaction, this tract may underlie some deficits seen in the Phelan-McDermid Syndrome population. These findings need to be replicated in a larger cohort.