Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental syndrome that has been studied intensively in order to understand relationships between the genetic microdeletion, brain development, cognitive function, and the emergence of psychiatric symptoms. White matter microstructural abnormalities identified using diffusion tensor imaging methods have been reported to affect a variety of neuroanatomical tracts in 22q11.2DS. In the present study, we sought to combine two discovery-based approaches: (1) white matter query language was used to parcellate the brain's white matter into tracts connecting pairs of 34, bilateral cortical regions and (2) the diffusion imaging characteristics of the resulting tracts were analyzed using a machine-learning method called support vector machine in order to optimize the selection of a set of imaging features that maximally discriminated 22q11.2DS and comparison subjects. With this unique approach, we both confirmed previously-recognized 22q11.2DS-related abnormalities in the inferior longitudinal fasciculus (ILF), and identified, for the first time, 22q11.2DS-related anomalies in the middle longitudinal fascicle and the extreme capsule, which may have been overlooked in previous, hypothesis-guided studies. We further observed that, in participants with 22q11.2DS, ILF metrics were significantly associated with positive prodromal symptoms of psychosis.
Keywords: (-fp), fronto-parietal aspect; (-to), temporo-occipital aspect; (-tp), temporo-parietal aspect; (22q11.2DS), 22q11.2 deletion syndrome; (AD), axial diffusivity; (DTI), diffusion tensor imaging; (DWI), diffusion weighted image; (EmC), extreme capsule; (FA), fractional anisotropy; (FOV), field of view; (GDS), Gordon Diagnostic Systems; (ILF), inferior longitudinal fasciculus; (MdLF), middle longitudinal fascicle; (RD), radial diffusivity; (ROI), region of interest; (SIPS), Structured Interview for Prodromal Syndromes; (SRS), Social Responsiveness Scale; (STG), superior temporal gyrus; (SVM), support vector machine; (UKF), Unscented Kalman Filter; (WAIS-III), Wechsler Adult Intelligence Scale – 3rd edition; (WMQL), white matter query language; (dTP), dorsal temporal pole; 22q11.2 deletion syndrome; Callosal asymmetry; Diffusion tensor imaging; Extreme capsule; Inferior longitudinal fasciculus; Machine-learning; Middle longitudinal fascicle; Support vector machine; Velocardiofacial syndrome; White matter query language.