Diffusion Tensor Imaging Abnormalities in the Uncinate Fasciculus and Inferior Longitudinal Fasciculus in Phelan-McDermid Syndrome

Abstract

Background: This cohort study utilized diffusion tensor imaging tractography to compare the uncinate fasciculus and inferior longitudinal fasciculus in children with Phelan-McDermid syndrome with age-matched controls and investigated trends between autism spectrum diagnosis and the integrity of the uncinate fasciculus and inferior longitudinal fasciculus white matter tracts.

Methods: This research was conducted under a longitudinal study that aims to map the genotype, phenotype, and natural history of Phelan-McDermid syndrome and identify biomarkers using neuroimaging (ClinicalTrial NCT02461420). Patients were aged three to 21 years and underwent longitudinal neuropsychologic 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 neuroimaging 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 versus 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.

Keywords: 22q13.3 deletion; Autism; DTI; SHANK3.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

FIGURE 1.

Example images of the ILF (A and B) and UF (C–E) overlaid on a fractional anisotropy map in two different patients with PMS. (A) Left midsagittal slice showing a representative ILF in a patient with PMS and the two ROIs (Catani et al.) used to capture the ILF: (1) dark pink: anterior temporal lobe label and (2) purple: posterior occipital lobe label. (B) A left midsagittal slice showing the sagittal ROE. Note: The axial brainstem ROE slice was applied to generate the ILF indicated, but is not shown. (C) A left side midsagittal slice showing a representative UF in a patient with PMS. (D) Left side cutaway view showing all three planes (axial, sagittal, and coronal) with orange labels showing the whole-brain sagittal ROE slice and the hemisphere coronal ROE slice. (E) Left side cutaway view showing the two ROIs (Catani et al.) used to capture the UF: (1) dark pink anterior temporal lobe label (2) light pink external capsule label. Note: The sagittal extreme capsule ROE slice was applied to generate the UF indicated, but is not shown. ILF, inferior longitudinal fasciculus; PMS, Phelan-McDermid syndrome; ROE, region of exclusion; ROI, region of inclusion; UF, uncinate fasciculus.

FIGURE 2.

Mean UF DTI metric versus age of patients and controls. Plot of mean DTI metric versus age of patients and controls for (A) FA UF left (B) FA UF right (C) MD UF left, and (D) MD UF right. DTI, diffusion tensor imaging; FA, fractional anisotropy; MD, mean diffusivity; UF, uncinate fasciculus.

FIGURE 3.

Mean ILF DTI metric versus age of patients and controls. Plot of mean DTI metric versus age of patients and controls for (A) FA ILF left, (B) FA ILF right, (C) MD ILF left, and (D) MD ILF right. DTI, diffusion tensor imaging; FA, fractional anisotropy; ILF, inferior longitudinal fasciculus; MD, mean diffusivity.