Arrested development and disrupted callosal microstructure following pediatric traumatic brain injury: relation to neurobehavioral outcomes

Chronic pediatric traumatic brain injury (TBI) is associated with significant and persistent neurobehavioral deficits. Using diffusion tensor imaging (DTI), we examined area, fractional anisotropy (FA), radial diffusion, and axial diffusion from six regions of the corpus callosum (CC) in 41 children and adolescents with TBI and 31 comparison children. Midsagittal cross-sectional area of the posterior body and isthmus was similar in younger children irrespective of injury status; however, increased area was evident in the older comparison children but was obviated in older children with TBI, suggesting arrested development. Similarly, age was correlated significantly with indices of tissue microstructure only for the comparison group. TBI was associated with significant reduction in FA and increased radial diffusivity in the posterior third of the CC and in the genu. The axial diffusivity did not differ by either age or group. Logistic regression analyses revealed that FA and radial diffusivity were equally sensitive to post-traumatic changes in 4 of 6 callosal regions; radial diffusivity was more sensitive for the rostral midbody and splenium. IQ, working memory, motor, and academic skills were correlated significantly with radial diffusion and/or FA from the isthmus and splenium only in the TBI group. Reduced size and microstructural changes in posterior callosal regions after TBI suggest arrested development, decreased organization, and disrupted myelination. Increased radial diffusivity was the most sensitive DTI-based surrogate marker of the extent of neuronal damage following TBI; FA was most strongly correlated with neuropsychological outcomes.

[1]  A. Barkovich.  Magnetic resonance techniques in the assessment of myelin and myelination , 2005, Journal of Inherited Metabolic Disease.

[2]  Timothy Edward John Behrens,et al.  Integrity of white matter in the corpus callosum correlates with bimanual co-ordination skills , 2007, NeuroImage.

[3]  Russell Schachar,et al.  Working memory after traumatic brain injury in children , 2002, Annals of neurology.

[4]  T. Klingberg,et al.  Maturation of White Matter is Associated with the Development of Cognitive Functions during Childhood , 2004, Journal of Cognitive Neuroscience.

[5]  J. Sweeney,et al.  White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study. , 2007, Brain : a journal of neurology.

[6]  J M Fletcher,et al.  Interhemispheric transfer of visual, auditory, tactile, and visuomotor information in children with hydrocephalus and partial agenesis of the corpus callosum. , 1999, Journal of clinical and experimental neuropsychology.

[7]  M. Just,et al.  From the SelectedWorks of Marcel Adam Just 1992 A capacity theory of comprehension : Individual differences in working memory , 2017 .

[8]  V. Haughton,et al.  Diffusion tensor MR imaging in diffuse axonal injury. , 2002, AJNR. American journal of neuroradiology.

[9]  J. Povlishock,et al.  Myelinated and unmyelinated axons of the corpus callosum differ in vulnerability and functional recovery following traumatic brain injury , 2005, Experimental Neurology.

[10]  B. Barres,et al.  Why is Wallerian degeneration in the CNS so slow? , 2007, Annual review of neuroscience.

[11]  Linda Ewing-Cobbs,et al.  Psychosocial outcome of TBI in children with unilateral frontal lesions , 2004, Journal of the International Neuropsychological Society.

[12]  T. Inder,et al.  OC6.02: Growth rate of corpus callosum in very premature infants , 2005, AJNR. American journal of neuroradiology.

[13]  Joseph K. Torgesen,et al.  Comprehensive Test of Phonological Processing , 1997 .

[14]  Larry A. Kramer,et al.  Diffusion tensor imaging-based tissue segmentation: Validation and application to the developing child and adolescent brain , 2007, NeuroImage.

[15]  N. Minshew,et al.  Development of the corpus callosum in childhood, adolescence and early adulthood. , 2002, Life sciences.

[16]  Luis Concha,et al.  Diffusion tensor imaging of time-dependent axonal and myelin degradation after corpus callosotomy in epilepsy patients , 2006, NeuroImage.

[17]  Marko Wilke,et al.  Correlation of white matter diffusivity and anisotropy with age during childhood and adolescence: a cross-sectional diffusion-tensor MR imaging study. , 2002, Radiology.

[18]  Linda Ewing-Cobbs,et al.  Predictors of secondary attention-deficit/hyperactivity disorder in children and adolescents 6 to 24 months after traumatic brain injury. , 2005, Journal of the American Academy of Child and Adolescent Psychiatry.

[19]  H S Levin,et al.  Correlation of atrophy measures on MRI with neuropsychological sequelae in children and adolescents with traumatic brain injury. , 2001, Brain injury.

[20]  Thomas A. Gennarelli,et al.  Diffuse Axonal Injury: An Important Form of Traumatic Brain Damage , 1998 .

[21]  B. Jennett,et al.  ASSESSMENT OF OUTCOME AFTER SEVERE BRAIN DAMAGE A Practical Scale , 1975, The Lancet.

[22]  Linda Ewing-Cobbs,et al.  Modeling of Longitudinal Academic Achievement Scores After Pediatric Traumatic Brain Injury , 2004, Developmental neuropsychology.

[23]  T. Klingberg,et al.  Combined analysis of DTI and fMRI data reveals a joint maturation of white and grey matter in a fronto-parietal network. , 2003, Brain research. Cognitive brain research.

[24]  K. Hasan,et al.  Diffusion tensor fractional anisotropy of the normal‐appearing seven segments of the corpus callosum in healthy adults and relapsing‐remitting multiple sclerosis patients , 2005, Journal of magnetic resonance imaging : JMRI.

[25]  L. Bérubé,et al.  [Clinical neuropsychology]. , 1982, Nursing Quebec.

[26]  P. Hüppi,et al.  Diffusion tensor imaging of normal and injured developing human brain ‐ a technical review , 2002, NMR in biomedicine.

[27]  Khader M Hasan,et al.  Retrospective measurement of the diffusion tensor eigenvalues from diffusion anisotropy and mean diffusivity in DTI , 2006, Magnetic resonance in medicine.

[28]  R. McKinstry,et al.  Diffusion tensor imaging and tractography of human brain development. , 2006, Neuroimaging clinics of North America.

[29]  Khader M Hasan,et al.  Computation of the fractional anisotropy and mean diffusivity maps without tensor decoding and diagonalization: Theoretical analysis and validation , 2003, Magnetic resonance in medicine.

[30]  Ramona O Hopkins,et al.  Traumatic brain injury and atrophy of the cingulate gyrus. , 2002, The Journal of neuropsychiatry and clinical neurosciences.

[31]  J D Pickard,et al.  Analysis of acute traumatic axonal injury using diffusion tensor imaging , 2007, British journal of neurosurgery.

[32]  Ron Dumont,et al.  Gray Oral Reading Tests–Fourth Edition , 2008 .

[33]  D. Wilson‐Costello,et al.  Corpus Callosum Size and Very Preterm Birth: Relationship to Neuropsychological Outcome , 2006 .

[34]  K. Hasan.  Diffusion tensor eigenvalues or both mean diffusivity and fractional anisotropy are required in quantitative clinical diffusion tensor MR reports: fractional anisotropy alone is not sufficient. , 2006, Radiology.

[35]  P. Boesiger,et al.  SENSE‐DTI at 3 T , 2004, Magnetic resonance in medicine.

[36]  John R. Griffiths.  NMR in biomedicine at 20 , 2008 .

[37]  Ron Dumont,et al.  Woodcock‐Johnson III Tests of Achievement , 2008 .

[38]  Khader M. Hasan,et al.  Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson’s disease , 2007, Neurobiology of Disease.

[39]  Hsiao-Fang Liang,et al.  Noninvasive detection of cuprizone induced axonal damage and demyelination in the mouse corpus callosum , 2006, Magnetic resonance in medicine.

[40]  J. Povlishock,et al.  Neurobiology of Disease Identification and Characterization of Heterogeneous Neuronal Injury and Death in Regions of Diffuse Brain Injury: Evidence for Multiple Independent , 2022 .

[41]  P J Basser,et al.  New Histological and Physiological Stains Derived from Diffusion‐Tensor MR Images , 1997, Annals of the New York Academy of Sciences.

[42]  J. Povlishock,et al.  Pathophysiology of neural injury: therapeutic opportunities and challenges. , 2000, Clinical neurosurgery.

[43]  Jagath C. Rajapakse,et al.  Regional MRI measurements of the corpus callosum: a methodological and developmental study , 1996, Brain and Development.

[44]  Jack M Fletcher,et al.  Brain Activation Profiles During the Early Stages of Reading Acquisition , 2002, Journal of child neurology.

[45]  Denis Le Bihan,et al.  Looking into the functional architecture of the brain with diffusion MRI , 2003, Nature Reviews Neuroscience.

[46]  K M Hasan,et al.  Corpus callosum diffusion anisotropy correlates with neuropsychological outcomes in twins disconcordant for traumatic brain injury. , 2006, AJNR. American journal of neuroradiology.

[47]  J. Langlois,et al.  The Incidence of Traumatic Brain Injury Among Children in the United States: Differences by Race , 2005, The Journal of head trauma rehabilitation.

[48]  P. Rakić,et al.  Axon overproduction and elimination in the corpus callosum of the developing rhesus monkey , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[49]  S. F. Witelson.  Hand and sex differences in the isthmus and genu of the human corpus callosum. A postmortem morphological study. , 1989, Brain : a journal of neurology.

[50]  Brian A Wandell,et al.  Temporal-callosal pathway diffusivity predicts phonological skills in children , 2007, Proceedings of the National Academy of Sciences.

[51]  Hao Huang,et al.  DTI tractography based parcellation of white matter: Application to the mid-sagittal morphology of corpus callosum , 2005, NeuroImage.

[52]  B. Jennett,et al.  Assessment of coma and impaired consciousness. A practical scale. , 1974, Lancet.

[53]  G J Barker,et al.  Diffusion imaging shows abnormalities after blunt head trauma when conventional magnetic resonance imaging is normal , 2001, Journal of neurology, neurosurgery, and psychiatry.

[54]  J. Mitchell.  Comprehensive Test of Phonological Processing , 2001 .

[55]  J. Fletcher,et al.  Corpus Callosum Damage and InterhemispherIc Transfer of Information following Closed Head Injury in Children , 1999, Cortex.

[56]  Linda Ewing-Cobbs,et al.  Prediction of cognitive sequelae based on abnormal computed tomography findings in children following mild traumatic brain injury. , 2008, Journal of neurosurgery. Pediatrics.

[57]  J. Griffin,et al.  Delayed Macrophage Responses and Myelin Clearance during Wallerian Degeneration in the Central Nervous System: The Dorsal Radiculotomy Model , 1994, Experimental Neurology.

[58]  Khader M Hasan,et al.  Quantitative diffusion tensor tractography of association and projection fibers in normally developing children and adolescents. , 2007, Cerebral cortex.

[59]  Khader M Hasan,et al.  Diffusion tensor quantification of the macrostructure and microstructure of human midsagittal corpus callosum across the lifespan , 2008, NMR in biomedicine.

[60]  J C Rajapakse,et al.  A quantitative MRI study of the corpus callosum in children and adolescents. , 1996, Brain research. Developmental brain research.

[61]  J. Klein,et al.  Human Motor Corpus Callosum: Topography, Somatotopy, and Link between Microstructure and Function , 2007, The Journal of Neuroscience.

[62]  Jens Frahm,et al.  Topography of the human corpus callosum revisited—Comprehensive fiber tractography using diffusion tensor magnetic resonance imaging , 2006, NeuroImage.

[63]  Christopher J. Cannistraci,et al.  Regional brain volume abnormalities and long-term cognitive outcome in preterm infants. , 2000, JAMA.

[64]  B. Thompson,et al.  Trauma to the corpus callosum: MR features. , 1988, AJNR. American journal of neuroradiology.

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

[66]  V. Menon,et al.  White matter development during childhood and adolescence: a cross-sectional diffusion tensor imaging study. , 2005, Cerebral cortex.

[67]  E. Bigler,et al.  Quantitative magnetic resonance imaging in traumatic brain injury. , 2001, The Journal of head trauma rehabilitation.

[68]  D. Holtzman,et al.  Selective Vulnerability of Late Oligodendrocyte Progenitors to Hypoxia–Ischemia , 2002, The Journal of Neuroscience.

[69]  H S Levin,et al.  Reduction of corpus callosum growth after severe traumatic brain injury in children , 2000, Neurology.

[70]  B Jennett,et al.  Assessment of outcome after severe brain damage. , 1975, Lancet.

[71]  Andrew L. Alexander,et al.  Diffusion tensor imaging of the corpus callosum in Autism , 2007, NeuroImage.

[72]  C. Beaulieu,et al.  The basis of anisotropic water diffusion in the nervous system – a technical review , 2002, NMR in biomedicine.

[73]  Babak A. Ardekani,et al.  ttention-Deficit/Hyperactivity Disorder: Preliminary Diffusion Tensor Imaging Study , 2005 .

[74]  N. Nakayama,et al.  Evidence for white matter disruption in traumatic brain injury without macroscopic lesions , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[75]  G. Johnson,et al.  Diffuse axonal injury in mild traumatic brain injury: a diffusion tensor imaging study. , 2005, Journal of neurosurgery.

[76]  Harvey S. Levin,et al.  Mild head injury classification. , 1990, Neurosurgery.

[77]  B. Sahakian,et al.  Head Circumference and Brain and Hippocampal Volume after Severe Traumatic Brain Injury in Childhood , 2005, Pediatric Research.

[78]  Harvey S. Levin,et al.  Mild head injury classification. , 1990, Neurosurgery.

[79]  Roland Bammer,et al.  Diffusion tensor imaging using single‐shot SENSE‐EPI , 2002, Magnetic resonance in medicine.

[80]  Keith Owen Yeates,et al.  A prospective study of short- and long-term outcomes after traumatic brain injury in children: behavior and achievement. , 2002, Neuropsychology.

[81]  Sterling C. Johnson,et al.  Corpus callosum morphology in normal controls and traumatic brain injury: Sex differences, mechanisms of injury, and neuropsychological correlates. , 1996 .

[82]  D. Holtzman,et al.  Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury , 2007, Experimental Neurology.

[83]  P. Skudlarski,et al.  Disruption of posterior brain systems for reading in children with developmental dyslexia , 2002, Biological Psychiatry.

[84]  A. Benton,et al.  Mild head injury , 1990 .

[85]  Harvey S. Levin,et al.  Late MRI after head injury in children: relationship to clinical features and outcome , 1992, Child's Nervous System.

[86]  P. Basser,et al.  Toward a quantitative assessment of diffusion anisotropy , 1996, Magnetic resonance in medicine.

[87]  Jagath C. Rajapakse,et al.  Development of the human corpus callosum during childhood and adolescence: A longitudinal MRI study , 1999, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[88]  Volkmar Glauche,et al.  Diffusion tensor imaging detects early Wallerian degeneration of the pyramidal tract after ischemic stroke , 2004, NeuroImage.

[89]  D. O. Hebb,et al.  The effect of early and late brain injury upon test scores, and the nature of adult intelligence. , 1942 .

[90]  P. Rakić,et al.  Development of the corpus callosum and cavum septi in man , 1968, The Journal of comparative neurology.

[91]  D. Doyle,et al.  Diffuse brain damage of immediate impact type. Its relationship to 'primary brain-stem damage' in head injury. , 1977, Brain : a journal of neurology.

[92]  Robert C. Tasker,et al.  Changes in White Matter Late after Severe Traumatic Brain Injury in Childhood , 2006, Developmental Neuroscience.

[93]  Alan C. Evans,et al.  Intellectual ability and cortical development in children and adolescents , 2006, Nature.

[94]  Linda Ewing-Cobbs,et al.  Late intellectual and academic outcomes following traumatic brain injury sustained during early childhood. , 2006, Journal of neurosurgery.

[95]  Erin D Bigler,et al.  Diffusion tensor imaging in the corpus callosum in children after moderate to severe traumatic brain injury. , 2006, Journal of neurotrauma.

[96]  Foss Mv.  MANAGEMENT OF VIRUS HEPATITIS. , 1964 .

[97]  Guy B. Williams,et al.  Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices , 2006, NeuroImage.

[98]  Barbara J. Wendling,et al.  Woodcock-Johnson III Tests of Achievement. , 2009 .

[99]  R. Todd,et al.  The importance of regressive changes in the development of the nervous system: towards a neurobiological theory of child development. , 1988, Psychiatric developments.