Disrupted fornix integrity in children with chromosome 22q11.2 deletion syndrome

Abstract

The fornix is the primary subcortical output fiber system of the hippocampal formation. In children with 22q11.2 deletion syndrome (22q11.2DS), hippocampal volume reduction has been commonly reported, but few studies as yet have evaluated the integrity of the fornix. Therefore, we investigated the fornix of 45 school-aged children with 22q11.2DS and 38 matched typically developing (TD) children. Probabilistic diffusion tensor imaging (DTI) tractography was used to reconstruct the body of the fornix in each child׳s brain native space. Compared with children, significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) was observed bilaterally in the body of the fornix in children with 22q11.2DS. Irregularities were especially prominent in the posterior aspect of the fornix where it emerges from the hippocampus. Smaller volumes of the hippocampal formations were also found in the 22q11.2DS group. The reduced hippocampal volumes were correlated with lower fornix FA and higher fornix RD in the right hemisphere. Our findings provide neuroanatomical evidence of disrupted hippocampal connectivity in children with 22q11.2DS, which may help to further understand the biological basis of spatial impairments, affective regulation, and other factors related to the ultra-high risk for schizophrenia in this population.

Keywords: Chromosome 22q11.2 deletion; Connectivity; Hippocampal formation; Tractography; Velo-cardio-facial Syndrome.

Fig. 1

The method used for identifying the fornix-body tracts in a single participant is illustrated. Estimated tracts on the left side of the brain are shown on the co-registered T1. After manually defining ROIs of anterior (A) and posterior (B) seeds, a set of 100,000 potential pathways connecting two seed points were generated using ConTrack (C). The 1% top scored pathways were selected (D) as a valid subset of pathways.

Fig. 2

FA and RD values vary along the trajectory and significantly differ between groups especially at the posterior area. Each single line represents segments of diffusion properties along the body of fornix from anterior to posterior in each individual brain in both TD group (blue) and the 22q11.2DS group (pink). The two bold lines represent the group means at each segment. Segments with a significant group difference after FDR correction are highlighted in grey.

Fig. 3

Scatter plot of the fornix fractional anisotropy (FA) value and the volume of hippocampal formation in the right hemisphere in the 22q11.2DS group (pink) and the TD group (blue).