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Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions.

ABSTRACT: BACKGROUND: Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. AIM: The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. METHODS: Data of 50 children with unilateral CP caused by periventricular white matter lesions (5-17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7-16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm(2)) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment-AHA) was assessed in connections that showed significant differences in FA compared to CTD. RESULTS: FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r(2) = 0.16-0.44; p < 0.05). CONCLUSION: This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention.

SUBMITTER: Pannek K

PROVIDER: S-EPMC4081979 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The white matter (WM) represents approximately half the cerebrum volume and is profoundly affected in Alzheimer's disease (AD). However, both the WM responses to AD as well as potential influences of this compartment to dementia pathogenesis remain comparatively neglected. Neuroimaging studies have revealed WM alterations are commonly associated with AD and renewed interest in examining the pathologic basis and importance of these changes. In AD subjects, immunohistochemistry and electron microscopy revealed changes in astrocyte morphology and myelin loss as well as up to 30% axonal loss in areas of WM rarefaction when measured against non-demented control (NDC) tissue. Comparative proteomic analyses were performed on pooled samples of periventricular WM (PVWM) obtained from AD (n=4) and NDC (n=5) subjects with both groups having a mean age of death of 86 years. All subjects had an apolipoprotein E ε3/3 genotype with the exception of one NDC subject who was ε2/3. Urea-detergent homogenates were analyzed using two different separation techniques: 2-dimensional isoelectric focusing/reverse-phase chromatography and 2-dimensional difference gel electrophoresis (2D-DIGE). Proteins with different expression levels between the 2 diagnostic groups were identified using MALDI-Tof/Tof mass spectrometry. In addition, Western blots were used to quantify proteins of interest in individual AD and NDC cases. Our proteomic studies revealed that when WM protein pools were loaded at equal amounts of total protein for comparative analyses, there were quantitative differences between the 2 groups. Molecules related to cytoskeleton maintenance, calcium metabolism and cellular survival such as glial fibrillary acidic protein, vimentin, tropomyosin, collapsin response mediator protein-2, calmodulin, S100-P, annexin A1, α-internexin, α- and β-synuclein, α-B-crystalline, fascin-1, ubiquitin carboxyl-terminal esterase and thymosine were altered between AD and NDC pools. Our experiments suggest that WM activities become globally impaired during the course of AD with significant morphological, biochemical and functional consequential implications for gray matter function and cognitive deficits. These observations may endorse the hypothesis that WM dysfunction is not only a consequence of AD pathology, but that it may precipitate and/or potentiate AD dementia.

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Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions.

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