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Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury
Published on: November 19, 2012
Longitudinal Gray Matter Trajectories in Pediatric Mild Traumatic Brain Injury
Ashley L Ware1, Catherine Lebel2, Adrian Onicas2
1From the Department of Psychology (A.L.W.), Georgia State University, Atlanta; Department of Neurology (A.L.W.), University of Utah, Salt Lake City; Departments of Psychology (A.L.W., A.O., K.O.Y.) and Radiology (C.L., B.G.G.), Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute, University of Calgary, Alberta, Canada; Computer Vision Group (A.O.), Sano Centre for Computational Medicine, Kraków 30-054, Poland; Department of Radiology (N.A.), University of Ottawa, Children's Hospital of Eastern Ontario Research Institute; Department of Psychology (M.H.B.), University of Montreal & CHU Sainte-Justine Hospital Research Center, Québec; Department of Biomedical Engineering (C.B.), University of Alberta, Edmonton; Division of Neurology (B.H.B.), Department of Pediatrics, University of British Columbia and BC Children's Hospital Research Institute, Vancouver; University of Alberta and Stollery Children's Hospital (W.C.), Edmonton; Department of Radiology (M.D.), Radio-oncology and Nuclear Medicine, Institute of Biomedical Engineering, University of Montreal; CHU Sainte-Justine Research Center, Québec; Department of Pediatrics (Q.D.), University of British Columbia, BC Children's Hospital Research Institute, Vancouver; CHU Sainte-Justine Research Center (S.D.), Department of Radiology, Radio-oncology and Nuclear Medicine, University of Montreal, Québec; Departments of Pediatrics and Emergency Medicine (S.B.F.), Cumming School of Medicine, University of Calgary, Alberta; Department of Pediatric Emergency Medicine (J.G.); CHU Sainte-Justine, Department of Pediatrics, University of Montréal, Québec; Children's Hospital of Eastern Ontario Research Institute (A.-A.L., R.Z.); Department of Cellular and Molecular Medicine (A.-A.L.) and Pediatrics and Emergency Medicine (R.Z.), University of Ottawa; and Department of Pediatrics and Emergency Medicine (R.Z.), University of Ottawa, Children's Hospital of Eastern Ontario Research Institute, Canada. alware@gsu.edu.
Background And Objectives:
This prospective, longitudinal cohort study examined trajectories of brain gray matter macrostructure after pediatric mild traumatic brain injury (mTBI).
Methods:
Children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) were recruited from 5 pediatric emergency departments. Reliable change between preinjury and 1 month postinjury symptom ratings was used to classify mTBI with or without persistent symptoms. Children completed postacute (2-33 days) and/or chronic (3 or 6 months) postinjury T1-weighted MRI, from which macrostructural metrics were derived using automated segmentation. Linear mixed-effects models were used, with multiple comparisons correction.
Results:
Groups (N = 623; 407 mTBI/216 OI; 59% male; age mean = 12.03, SD = 2.38 years) did not differ in total brain, white, or gray matter volumes or regional subcortical gray matter volumes. However, time postinjury, age at injury, and biological sex-moderated differences among symptom groups in cortical thickness of the angular gyrus, basal forebrain, calcarine cortex, gyrus rectus, medial and posterior orbital gyrus, and the subcallosal area all corrected p < 0.05. Gray matter macrostructural metrics did not differ between groups postacutely. However, cortical thinning emerged chronically after mTBI relative to OI in the angular gyrus in older children (d [95% confidence interval] = -0.61 [-1.15 to -0.08]); and in the basal forebrain (-0.47 [-0.94 to -0.01]), subcallosal area (-0.55 [-1.01 to -0.08]), and the posterior orbital gyrus (-0.55 [-1.02 to -0.08]) in females. Cortical thinning was demonstrated for frontal and occipital regions 3 months postinjury in males with mTBI with persistent symptoms vs without persistent symptoms (-0.80 [-1.55 to -0.05] to -0.83 [-1.56 to -0.10]) and 6 months postinjury in females and younger children with mTBI with persistent symptoms relative to mTBI without persistent symptoms and OI (-1.42 [-2.29 to -0.45] to -0.91 [-1.81 to -0.01]).
Discussion:
These findings signal little diagnostic and prognostic utility of postacute gray matter macrostructure in pediatric mTBI. However, mTBI altered the typical course of cortical gray matter thinning up to 6 months postinjury, even after symptoms typically abate in most children. Collapsing across symptom status obscured the neurobiological heterogeneity of discrete clinical outcomes after pediatric mTBI. The results illustrate the need to examine neurobiology in relation to clinical outcomes and within a neurodevelopmental framework.
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