title: Callosal Function in Pediatric Traumatic Brain Injury Linked to Disrupted White Matter Integrity.
abstract: Traumatic brain injury (TBI) often results in traumatic axonal injury and white matter (WM) damage, particularly to the corpus callosum (CC). Damage to the CC can lead to impaired performance on neurocognitive tasks, but there is a high degree of heterogeneity in impairment following TBI. Here we examined the relation between CC microstructure and function in pediatric TBI. We used high angular resolution diffusion-weighted imaging (DWI) to evaluate the structural integrity of the CC in humans following brain injury in a sample of 32 children (23 males and 9 females) with moderate-to-severe TBI (msTBI) at 1-5 months postinjury, compared with well matched healthy control children. We assessed CC function through interhemispheric transfer time (IHTT) as measured using event-related potentials (ERPs), and related this to DWI measures of WM integrity. Finally, the relation between DWI and IHTT results was supported by additional results of neurocognitive performance assessed using a single composite performance scale. Half of the msTBI participants (16 participants) had significantly slower IHTTs than the control group. This slow IHTT group demonstrated lower CC integrity (lower fractional anisotropy and higher mean diffusivity) and poorer neurocognitive functioning than both the control group and the msTBI group with normal IHTTs. Lower fractional anisotropy-a common sign of impaired WM-and slower IHTTs also predicted poor neurocognitive function. This study reveals that there is a subset of pediatric msTBI patients during the post-acute phase of injury who have markedly impaired CC functioning and structural integrity that is associated with poor neurocognitive functioning.
  
  
  CONCLUSIONS
  Traumatic brain injury (TBI) is the primary cause of death and disability in children and adolescents. There is considerable heterogeneity in postinjury outcome, which is only partially explained by injury severity. Imaging biomarkers may help explain some of this variance, as diffusion weighted imaging is sensitive to the white matter disruption that is common after injury. The corpus callosum (CC) is one of the most commonly reported areas of disruption. In this multimodal study, we discovered a divergence within our pediatric moderate-to-severe TBI sample 1-5 months postinjury. A subset of the TBI sample showed significant impairment in CC function, which is supported by additional results showing deficits in CC structural integrity. This subset also had poorer neurocognitive functioning. Our research sheds light on postinjury heterogeneity.
authors.affiliation: Imaging Genetics Center, Mary and Mark Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, California 90292.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Dennis
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, California 90024, Fuller Theological Seminary School of Psychology, Pasadena, California 91101.
authors.forename: Monica U
authors.initials: MU
authors.lastname: Ellis
authors.affiliation: Fuller Theological Seminary School of Psychology, Pasadena, California 91101.
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Marion
authors.affiliation: Imaging Genetics Center, Mary and Mark Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, California 90292.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, California 90024.
authors.forename: Lisa
authors.initials: L
authors.lastname: Moran
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, California 90024, Department of Psychology, Norwegian University of Science and Technology, NO-7491 Trondheim, Norway, Department of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, NO-7030 Trondheim, Norway.
authors.forename: Alexander
authors.identifier: http://orcid.org/0000-0001-8691-3860
authors.initials: A
authors.lastname: Olsen
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, California 90024.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kernan
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, California 90024.
authors.forename: Talin
authors.identifier: http://orcid.org/0000-0002-2270-8566
authors.initials: T
authors.lastname: Babikian
authors.affiliation: Harbor-UCLA Medical Center and Los Angeles BioMedical Research Institute, Department of Pediatrics, Torrance, California 90502.
authors.forename: Richard
authors.identifier: http://orcid.org/0000-0002-7998-4713
authors.initials: R
authors.lastname: Mink
authors.affiliation: Miller Children's Hospital, Long Beach, California 90806.
authors.forename: Christopher
authors.initials: C
authors.lastname: Babbitt
authors.affiliation: LAC+USC Medical Center, Department of Pediatrics, Los Angeles, California 90033.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Johnson
authors.affiliation: UCLA Brain Injury Research Center, Department of Neurosurgery and Division of Pediatric Neurology, Mattel Children's Hospital, Los Angeles, California 90095.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Giza
authors.affiliation: Imaging Genetics Center, Mary and Mark Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, California 90292, Departments of Neurology, Pediatrics, Psychiatry, Radiology, Engineering, and Ophthalmology, University of Southern California, Los Angeles, California 90033, and pthomp@usc.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, California 90024, Department of Psychology, UCLA, Los Angeles, California 90024.
authors.forename: Robert F
authors.identifier: http://orcid.org/0000-0002-4994-9642
authors.initials: RF
authors.lastname: Asarnow
mesh_terms: D000293:Adolescent; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology*; D016022:Case-Control Studies; D002648:Child; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology*; D003337:Corpus Callosum / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D005071:Evoked Potentials; D005260:Female; D007839:Functional Laterality; D015600:Glasgow Coma Scale; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007362:Intensive Care Units; D008297:Male; D009483:Neuropsychological Tests; D010775:Photic Stimulation; D015898:Tomography Scanners, X-Ray Computed; D014163:Transfer, Psychology / Q000502:physiology*; D066127:White Matter / Q000473:pathology*
keywords: DTI; ERP; corpus callosum; interhemispheric transfer time; traumatic brain injury