title: 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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: The University of Queensland, Queensland Cerebral Palsy and Rehabilitation Research Centre, Brisbane, Australia ; The University of Queensland, School of Medicine, Brisbane, Australia ; The Australian e-Health Research Centre, CSIRO, Brisbane, Australia.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Pannek
authors.affiliation: The University of Queensland, Queensland Cerebral Palsy and Rehabilitation Research Centre, Brisbane, Australia.
authors.forename: Roslyn N
authors.initials: RN
authors.lastname: Boyd
authors.affiliation: Stella Maris Scientific Institute, Pisa, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Fiori
authors.affiliation: Stella Maris Scientific Institute, Pisa, Italy ; Department of Clinical and Experimental Medicine, University of Pisa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Guzzetta
authors.affiliation: The Australian e-Health Research Centre, CSIRO, Brisbane, Australia.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Rose
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D002547:Cerebral Palsy / Q000473:pathology* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007969:Leukomalacia, Periventricular / Q000473:pathology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000473:pathology* / Q000503:physiopathology; D066127:White Matter / Q000473:pathology* / Q000503:physiopathology
keywords: AHA, assisting hand assessment; CDGM, cortical and deep grey matter; CP, cerebral palsy; CTD, children with typical development; Congenital hemiplegia; Connectome; DROP-R, detection and replacement of outliers prior to resampling; Diffusion MRI; FA, fractional anisotropy; FMAM, fit model to all measurements; GMFCS, gross motor function classification system; HARDI, high angular resolution diffusion imaging; HOMOR, higher order model outlier rejection; MACS, manual ability classification system; NBS, network based statistic; PWM, periventricular white matter; Tractography; Unilateral cerebral palsy