Relationship between aberrant brain connectivity and clinical features in Angelman Syndrome: a new method using tract based spatial statistics of DTI color-coded orientation maps

Abstract

Aim: In order to relate brain structural abnormalities to clinical features of Angelman Syndrome (AS), we determined the locations of abnormal regional white matter architecture in AS children using a sensitive and objective whole brain approach to analyze diffusion tensor imaging (DTI) color-coded orientation maps.

Methods: Using tract based spatial statistics (TBSS) of DTI color-coded orientation maps, the fraction of fibers oriented in the anteroposterior (AP), mediolateral (ML) and superioinferior (SI) directions were determined in whole brain white matter of 7 children with AS (mean age: 70±25.78 months, 5 males) and 7 children with typical development (TD, mean age: 79.8±17.25 months, 4 males). TBSS of FA map was also performed for comparison.

Results: Children with AS had a significantly lower AP component than the TD group in 9 clusters (3 bilateral and 3 unilateral). Bilateral clusters were located in inferior fronto-occipital fasciculus, anterior thalamic radiation and arcuate fasciculus regions. Unilateral clusters involved left brainstem, left cingulum and right uncinate regions. Similarly, children with AS had significantly lower ML component than the TD group in 4 clusters (2 in corpus callosum and 2 unilateral clusters). Unilateral clusters were located in the left cingulum and left anterior thalamic radiation regions. SI component was lower in children with AS in two clusters compared to TD (corticospinal tract and corpus callosum). FA map clusters mostly corresponded with component clusters.

Interpretation: Children with AS have a global impairment of white matter integrity including AP, ML and SI components in whole brain suggesting a potential underlying error with axon guidance mechanisms during brain development possibly due to loss of UBE3A gene expression. Some of this aberrant connectivity can be related to the clinical features of AS.

Copyright © 2011 Elsevier Inc. All rights reserved.

Figures

Clusters with significantly lower FA, AP, ML and SI components in AS group compared to TD group obtained after TBSS analysis. A, B and C denote the representative images of coronal, axial and saggital sections. AP component clusters (shown as green) are mainly located in arcuate fasciculus (AF), anterior thalamic radiation (ATR), cingulum, Inferior fronto-occipital fasciculus (IFO) and brainstem. ML component clusters (shown as red) are located mainly in corpus callosum, cingulum and ATR. SI components clusters (shown in blue) are located in corpus callosum and corticospinal tract. FA component clusters (shown in yellow) mostly correspond to the same locations as depicted by AP, ML and SI components.