Structural connectivity of the anterior cingulate in children with unilateral cerebral palsy due to white matter lesions

In this work we investigate the structural connectivity of the anterior cingulate cortex (ACC) and its link with impaired executive function in children with unilateral cerebral palsy (UCP) due to periventricular white matter lesions. Fifty two children with UCP and 17 children with typical development participated in the study, and underwent diffusion and structural MRI. Five brain regions were identified for their high connectivity with the ACC using diffusion MRI fibre tractography: the superior frontal gyrus, medial orbitofrontal cortex, rostral middle frontal gyrus, precuneus and isthmus cingulate. Structural connectivity was assessed in pathways connecting these regions to the ACC using three diffusion MRI derived measures: fractional anisotropy (FA), mean diffusivity (MD) and apparent fibre density (AFD), and compared between participant groups. Furthermore we investigated correlations of these measures with executive function as assessed by the Flanker task. The ACC–precuneus tract had significantly different MD (p < 0.0001) and AFD (p = 0.0072) between groups, with post-hoc analysis showing significantly increased MD in the right hemisphere of children with left hemiparesis compared with controls. The ACC–superior frontal gyrus tract had significantly different FA (p = 0.0049) and MD (p = 0.0031) between groups. AFD in this tract (contralateral to side of hemiparesis; right hemisphere in controls) showed a significant relationship with Flanker task performance (p = 0.0045, β = −0.5856), suggesting that reduced connectivity correlates with executive dysfunction. Reduced structural integrity of ACC tracts appears to be important in UCP, in particular the connection to the superior frontal gyrus. Although damage to this area is heterogeneous it may be important in early identification of children with impaired executive function.

[1]  Revital Nossin-Manor,et al.  Preterm neonatal diffusion processing using detection and replacement of outliers prior to resampling , 2011, Magnetic resonance in medicine.

[2]  C. Eriksen,et al.  Effects of noise letters upon the identification of a target letter in a nonsearch task , 1974 .

[3]  Alan Connelly,et al.  Connectivity-based fixel enhancement: Whole-brain statistical analysis of diffusion MRI measures in the presence of crossing fibres , 2015, NeuroImage.

[4]  Derek K. Jones,et al.  Investigating the prevalence of complex fiber configurations in white matter tissue with diffusion magnetic resonance imaging , 2013, Human brain mapping.

[5]  Giovanni Cioni,et al.  Is hemiplegic cerebral palsy equivalent to amblyopia of the corticospinal system? , 2007, Annals of neurology.

[6]  S. Caillies,et al.  Theory of mind and irony comprehension in children with cerebral palsy. , 2012, Research in developmental disabilities.

[7]  Sachio Takashima,et al.  Qualitative Brain MRI at Term and Cognitive Outcomes at 9 Years After Very Preterm Birth , 2012, Pediatrics.

[8]  Alan Connelly,et al.  3940 Decreased Apparent Fibre Density in Dravet Syndrome , 2013 .

[9]  B. Dubois,et al.  Functions of the left superior frontal gyrus in humans: a lesion study. , 2006, Brain : a journal of neurology.

[10]  P. Basser,et al.  Water Diffusion Changes in Wallerian Degeneration and Their Dependence on White Matter Architecture , 2000 .

[11]  Kerstin Pannek,et al.  Quantitative comparison of cortical and deep grey matter in pathological subtypes of unilateral cerebral palsy , 2014, Developmental medicine and child neurology.

[12]  B. Vogt,et al.  Contributions of anterior cingulate cortex to behaviour. , 1995, Brain : a journal of neurology.

[13]  Jessica M Sun,et al.  Brain structural connectivity increases concurrent with functional improvement: Evidence from diffusion tensor MRI in children with cerebral palsy during therapy , 2015, NeuroImage: Clinical.

[14]  Alan Connelly,et al.  Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution , 2004, NeuroImage.

[15]  A. Cavanna,et al.  The precuneus: a review of its functional anatomy and behavioural correlates. , 2006, Brain : a journal of neurology.

[16]  M. Hysing,et al.  Psychiatric disorders among children with cerebral palsy at school starting age. , 2012, Research in developmental disabilities.

[17]  A. Eliasson,et al.  The Manual Ability Classification System (MACS) for children with cerebral palsy: scale development and evidence of validity and reliability. , 2006, Developmental medicine and child neurology.

[18]  C. Dunnett A Multiple Comparison Procedure for Comparing Several Treatments with a Control , 1955 .

[19]  K. Hustad,et al.  Intelligibility of 4-year-old children with and without cerebral palsy. , 2012, Journal of speech, language, and hearing research : JSLHR.

[20]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

[21]  Mara Cercignani,et al.  Twenty‐five pitfalls in the analysis of diffusion MRI data , 2010, NMR in biomedicine.

[22]  R. Boyd,et al.  Executive function in children and adolescents with unilateral cerebral palsy , 2013, Developmental medicine and child neurology.

[23]  Stephen E. Rose,et al.  HOMOR: Higher Order Model Outlier Rejection for high b-value MR diffusion data , 2012, NeuroImage.

[24]  T. Paus Primate anterior cingulate cortex: Where motor control, drive and cognition interface , 2001, Nature Reviews Neuroscience.

[25]  Alan Connelly,et al.  Anatomically-constrained tractography: Improved diffusion MRI streamlines tractography through effective use of anatomical information , 2012, NeuroImage.

[26]  E. Stejskal Use of Spin Echoes in a Pulsed Magnetic‐Field Gradient to Study Anisotropic, Restricted Diffusion and Flow , 1965 .

[27]  D. Cadman,et al.  THE GROSS MOTOR FUNCTION MEASURE: A MEANS TO EVALUATE THE EFFECTS OF PHYSICAL THERAPY , 1989, Developmental medicine and child neurology.

[28]  Rakesh K. Gupta,et al.  DTI correlates of cognition in term children with spastic diplegic cerebral palsy. , 2013, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[29]  Joshua W. Brown,et al.  Conflict effects without conflict in anterior cingulate cortex: Multiple response effects and context specific representations , 2009, NeuroImage.

[30]  A. Guzzetta,et al.  Relationship between brain structure on magnetic resonance imaging and motor outcomes in children with cerebral palsy: a systematic review. , 2013, Research in developmental disabilities.

[31]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. , 1996, Journal of magnetic resonance. Series B.

[32]  Hae-Jeong Park,et al.  Distortion correction of high b-valued and high angular resolution diffusion images using iterative simulated images , 2011, NeuroImage.

[33]  Mark Jenkinson,et al.  Fast, automated, N‐dimensional phase‐unwrapping algorithm , 2003, Magnetic resonance in medicine.

[34]  M. Kumar,et al.  Treatment-induced plasticity in cerebral palsy: a diffusion tensor imaging study. , 2008, Pediatric neurology.

[35]  S. Rose,et al.  Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions , 2014, NeuroImage: Clinical.

[36]  Joseph V. Hajnal,et al.  High b-value HARDI analysis in neonates scanned at term-equivalent age reveals correlation between apparent white matter fibre density and immaturity at birth , 2012 .

[37]  C. Rowe,et al.  Tractographic Threshold-Free Cluster Enhancement : Whole-Brain Statistical Analysis of Diffusion MRI Measures in the Presence of Crossing Fibres , 2012 .

[38]  M. Rushworth,et al.  Behavioral / Systems / Cognitive Connectivity-Based Parcellation of Human Cingulate Cortex and Its Relation to Functional Specialization , 2008 .

[39]  Joshua W. Brown Con fl ict effects without con fl ict in anterior cingulate cortex : Multiple response effects and context speci fi c representations , 2009 .

[40]  Stuart Crozier,et al.  Voxel-based analysis of Alzheimer's Disease using apparent fibre density , 2012 .

[41]  Alan Connelly,et al.  SIFT: Spherical-deconvolution informed filtering of tractograms , 2013, NeuroImage.

[42]  Greg Brown,et al.  An automated strategy for the delineation and parcellation of commissural pathways suitable for clinical populations utilising high angular resolution diffusion imaging tractography , 2010, NeuroImage.

[43]  Y. Kim,et al.  Changes in diffusion tensor tractographic findings associated with constraint-induced movement therapy in young children with cerebral palsy , 2014, Clinical Neurophysiology.

[44]  Iona Novak,et al.  Clinical Prognostic Messages From a Systematic Review on Cerebral Palsy , 2012, Pediatrics.

[45]  R. Boyd,et al.  Everyday psychological functioning in children with unilateral cerebral palsy: does executive functioning play a role? , 2014, Developmental medicine and child neurology.

[46]  E. Ringelstein,et al.  Handedness and hemispheric language dominance in healthy humans. , 2000, Brain : a journal of neurology.

[47]  I. Krägeloh-Mann,et al.  The role of magnetic resonance imaging in elucidating the pathogenesis of cerebral palsy: a systematic review , 2007, Developmental medicine and child neurology.

[48]  P. V. van Zijl,et al.  Three‐dimensional tracking of axonal projections in the brain by magnetic resonance imaging , 1999, Annals of neurology.

[49]  R. Boyd,et al.  Brain structure and executive functions in children with cerebral palsy: a systematic review. , 2013, Research in developmental disabilities.

[50]  Alan Connelly,et al.  Robust determination of the fibre orientation distribution in diffusion MRI: Non-negativity constrained super-resolved spherical deconvolution , 2007, NeuroImage.

[51]  Derek K. Jones Challenges and limitations of quantifying brain connectivity in vivo with diffusion MRI , 2010 .

[52]  Roslyn N Boyd,et al.  New insights into the pathology of white matter tracts in cerebral palsy from diffusion magnetic resonance imaging: a systematic review , 2012, Developmental medicine and child neurology.

[53]  Ingeborg Krägeloh-Mann,et al.  Cerebral palsy update , 2009, Brain and Development.

[54]  Stuart Crozier,et al.  Apparent Fibre Density: A novel measure for the analysis of diffusion-weighted magnetic resonance images , 2012, NeuroImage.

[55]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[56]  Stephen M. Smith,et al.  DTI measures in crossing-fibre areas: Increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease , 2011, NeuroImage.

[57]  P. Basser,et al.  MR diffusion tensor spectroscopy and imaging. , 1994, Biophysical journal.

[58]  A. Gordon,et al.  Capturing neuroplastic changes after bimanual intensive rehabilitation in children with unilateral spastic cerebral palsy: A combined DTI, TMS and fMRI pilot study , 2015, Research in developmental disabilities.

[59]  Jonathan D. Cohen,et al.  Conflict monitoring versus selection-for-action in anterior cingulate cortex , 1999, Nature.

[60]  Yu Bai,et al.  Model-based registration to correct for motion between acquisitions in diffusion MR imaging , 2008, 2008 5th IEEE International Symposium on Biomedical Imaging: From Nano to Macro.