A Different Brain: Anomalies of Functional and Structural Connections in Williams Syndrome

Chiara Gagliardi,Alberto De Luca,Denis Peruzzo,Andrea Nordio,Renato Borgatti,Filippo Arrigoni,Alexander Leemans,Alice Decio

doi:10.3389/fneur.2018.00721

Chiara Gagliardi, Alberto De Luca + Show 6 more

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https://doi.org/10.3389/fneur.2018.00721

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Abstract

We describe the results of a functional and structural brain connectivity analysis comparing a homogeneous group of 10 young adults with Williams Syndrome (WS; 3 females, age 20. 7 ± 3.7 years, age range 17.4–28.7 years) to a group of 18 controls of similar age (3 females, age 23.9 ± 4.4 years, age range 16.8–30.2), with the aim to increase knowledge of the structure – function relationship in WS. Subjects underwent a 3T brain MRI exam including anatomical, functional (resting state) and structural (diffusion MRI) sequences. We found convergent anomalies in structural and functional connectivity in the WS group. Altered Fractional Anisotropy (FA) values in parieto-occipital regions were associated with increased connectivity in the antero-posterior pathways linking parieto-occipital with frontal regions. The analysis of resting state data showed altered functional connectivity in the WS group in main brain networks (default mode, executive control and dorsal attention, sensori-motor, fronto—parietal, ventral stream). The combined analysis of functional and structural connectivity displayed a different pattern in the two groups: in controls the highest agreement was found in frontal and visual areas, whereas in WS patients in posterior regions (parieto-occipital and temporal areas). These preliminary findings may reflect an altered “wiring” of the brain in WS, which can be driven by hyper-connectivity of the posterior regions as opposed to disrupted connectivity in the anterior areas, supporting the hypothesis that a different brain (organization) could be associated with a different (organization of) behavior in Williams Syndrome.

Highlights

William Syndrome (WS) is a neurodevelopmental disorder caused by a hemizygous deletion in 7q11.23 [1]
Voxel-wise analysis showed clusters of lower Fractional Anisotropy (FA) in middle and superior cerebellar peduncles, posterior limbs of internal capsules, and in the splenium of corpus callosum for WS patients compared to healthy controls (HC)
A small cluster of higher FA was present in the adjacent parieto-occipital white matter of the left hemisphere, in WS patients compared to HCs (Figure 1)

Summary

Introduction

William Syndrome (WS) is a neurodevelopmental disorder caused by a hemizygous deletion in 7q11.23 [1]. Other rare atypical deletions have been reported, Abbreviations: dMRI, Diffusion MRI; DMN, Default Mode Network; DTI, Diffusion Tensor Imaging; FA, Fractional anisotropy; FC, Functional connectivity; fMRI, Functional MRI; GM, Gray matter; HC, Healthy controls; ICA, Independent component analysis; WM, White matter; WS, Williams syndrome; WSCR, WS critical region. WS has a prevalence of 1:7.500 to 20.000 live births [6, 7] and is characterized by mild-to-severe intellectual disability and an uneven social and cognitive profile [8]. The neurocognitive profile of WS is characterized by a peculiar impairment in visuospatial construction with a relative preservation of concrete language skills, and an overall mildto- severe intellectual disability [8, 9]. Individuals with WS usually display high sociability, excessive empathy, impulsivity, inattention, sadness, and depression as well as generalized anxiety disorder and hyperactivity disorder (ADHD) [10]

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