Postconcussional disorder and PTSD symptoms of military‐related traumatic brain injury associated with compromised neurocircuitry

Traumatic brain injury (TBI) is a common combat injury, often through explosive blast, and produces heterogeneous brain changes due to various mechanisms of injury. It is unclear whether the vulnerability of white matter differs between blast and impact injury, and the consequences of microstructural changes on neuropsychological function are poorly understood in military TBI patients. Diffusion tensor imaging (DTI) techniques were used to assess the neurocircuitry in 37 US service members (29 mild, 7 moderate, 1 severe; 17 blast and 20 nonblast), who sustained a TBI while deployed, compared to 14 nondeployed, military controls. High‐dimensional deformable registration of MRI diffusion tensor data was followed by fiber tracking and tract‐specific analysis along with region‐of‐interest analysis. DTI results were examined in relation to post‐concussion and post‐traumatic stress disorder (PTSD) symptoms. The most prominent white matter microstructural injury for both blast and nonblast patients was in the frontal fibers within the fronto‐striatal (corona radiata, internal capsule) and fronto‐limbic circuits (fornix, cingulum), the fronto‐parieto‐occipital association fibers, in brainstem fibers, and in callosal fibers. Subcortical superior‐inferiorly oriented tracts were more vulnerable to blast injury than nonblast injury, while direct impact force had more detrimental effects on anterior‐posteriorly oriented tracts, which tended to cause heterogeneous left and right hemispheric asymmetries of white matter connectivity. The tractography using diffusion anisotropy deficits revealed the cortico‐striatal‐thalamic‐cerebellar‐cortical (CSTCC) networks, where increased post‐concussion and PTSD symptoms were associated with low fractional anisotropy in the major nodes of compromised CSTCC neurocircuitry, and the consequences on cognitive function were explored as well. Hum Brain Mapp 35:2652–2673, 2014. © 2013 Wiley Periodicals, Inc.

[1]  Hidenao Fukuyama,et al.  Activation of the precuneus is related to reduced reaction time in serial reaction time tasks , 2005, Neuroscience Research.

[2]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

[3]  Habib Benali,et al.  Diffusion tensor imaging and white matter lesions at the subacute stage in mild traumatic brain injury with persistent neurobehavioral impairment , 2011, Human brain mapping.

[4]  N. Bargalló,et al.  Diffusion tensor imaging differences relate to memory deficits in diffuse traumatic brain injury , 2011, BMC neurology.

[5]  Scott A. Huettel,et al.  Diffusion tensor imaging of adult age differences in cerebral white matter: relation to response time , 2004, NeuroImage.

[6]  D R Rutgers,et al.  White Matter Abnormalities in Mild Traumatic Brain Injury: A Diffusion Tensor Imaging Study , 2008, American Journal of Neuroradiology.

[7]  W. Young,et al.  Corticofugal axonal degeneration in rats after middle cerebral artery occlusion. , 1989, Stroke.

[8]  L. Gentry,et al.  Traumatic brain stem injury: MR imaging. , 1989, Radiology.

[9]  M. Poca,et al.  Differences in visual vs. verbal memory impairments as a result of focal temporal lobe damage in patients with traumatic brain injury , 2006, Brain injury.

[10]  Gady Agam,et al.  Development of a human brain diffusion tensor template , 2009, NeuroImage.

[11]  Michael S. Jaffee,et al.  Case report of a soldier with primary blast brain injury , 2009, NeuroImage.

[12]  Arthur W. Toga,et al.  Atlas-based whole brain white matter analysis using large deformation diffeomorphic metric mapping: Application to normal elderly and Alzheimer's disease participants , 2009, NeuroImage.

[13]  N C Andreasen,et al.  Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Jason E. Schillerstrom,et al.  Executive clock drawing correlates with performance-based functional status in people with combat-related mild traumatic brain injury and comorbid posttraumatic stress disorder. , 2010, Journal of rehabilitation research and development.

[15]  P. Basser,et al.  In vivo fiber tractography using DT‐MRI data , 2000, Magnetic resonance in medicine.

[16]  Khader M Hasan,et al.  Serial changes in the white matter diffusion tensor imaging metrics in moderate traumatic brain injury and correlation with neuro-cognitive function. , 2009, Journal of neurotrauma.

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

[18]  J. Langlois,et al.  The Epidemiology and Impact of Traumatic Brain Injury: A Brief Overview , 2006, The Journal of head trauma rehabilitation.

[19]  P. Parizel,et al.  Imaging findings in diffuse axonal injury after closed head trauma , 1998, European Radiology.

[20]  G. E. Alexander,et al.  Parallel organization of functionally segregated circuits linking basal ganglia and cortex. , 1986, Annual review of neuroscience.

[21]  Karl J. Friston,et al.  A unified statistical approach for determining significant signals in images of cerebral activation , 1996, Human brain mapping.

[22]  Paul A. Yushkevich,et al.  Deformable registration of diffusion tensor MR images with explicit orientation optimization , 2006, Medical Image Anal..

[23]  Elyssa B. Margolis,et al.  The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons? , 2006, The Journal of physiology.

[24]  Konstantinos Arfanakis,et al.  Enhanced ICBM diffusion tensor template of the human brain , 2011, NeuroImage.

[25]  T. Hortobágyi,et al.  Traumatic axonal damage in the brain can be detected using β‐APP immunohistochemistry within 35 min after head injury to human adults , 2007, Neuropathology and applied neurobiology.

[26]  A. Håberg,et al.  Reduced fractional anisotropy does not change the shape of the hemodynamic response in survivors of severe traumatic brain injury. , 2010, Journal of neurotrauma.

[27]  J. W. Papez A PROPOSED MECHANISM OF EMOTION , 1937 .

[28]  Robert L Kane,et al.  ANAM genogram: historical perspectives, description, and current endeavors. , 2007, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[29]  B. Thompson,et al.  MR imaging of head trauma: review of the distribution and radiopathologic features of traumatic lesions. , 1988, AJR. American journal of roentgenology.

[30]  G. Johnson,et al.  Short-term DTI predictors of cognitive dysfunction in mild traumatic brain injury , 2008, Brain injury.

[31]  Michael L. Lipton,et al.  Robust detection of traumatic axonal injury in individual mild traumatic brain injury patients: Intersubject variation, change over time and bidirectional changes in anisotropy , 2012, Brain Imaging and Behavior.

[32]  R. Vanderploeg,et al.  The Structure of Postconcussive Symptoms in 3 US Military Samples , 2010 .

[33]  Terrence R. Oakes,et al.  Diffusion Tensor Imaging and Its Application to Traumatic Brain Injury: Basic Principles and Recent Advances , 2012 .

[34]  Peter Gruen,et al.  Novel diffusion tensor imaging methodology to detect and quantify injured regions and affected brain pathways in traumatic brain injury. , 2010, Magnetic resonance imaging.

[35]  R. Barkley,et al.  Comprehensive evaluation of attention deficit disorder with and without hyperactivity as defined by research criteria. , 1990, Journal of consulting and clinical psychology.

[36]  Richard M. McCarron,et al.  Measurement of blast wave by a miniature fiber optic pressure transducer in the rat brain , 2007, Journal of Neuroscience Methods.

[37]  A. Tessler,et al.  Pathology of blast-related brain injury. , 2009, Journal of rehabilitation research and development.

[38]  Rjh Rudy Cloots,et al.  Multi-scale mechanics of traumatic brain injury: predicting axonal strains from head loads , 2013, Biomechanics and modeling in mechanobiology.

[39]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[40]  V. Wedeen,et al.  Diffusion MRI of Complex Neural Architecture , 2003, Neuron.

[41]  Matthew P. G. Allin,et al.  Atlasing location, asymmetry and inter-subject variability of white matter tracts in the human brain with MR diffusion tractography , 2011, NeuroImage.

[42]  Sean Connell,et al.  Novel model to investigate blast injury in the central nervous system. , 2011, Journal of neurotrauma.

[43]  C. Hoge,et al.  Combat duty in Iraq and Afghanistan, mental health problems and barriers to care. , 2004, U.S. Army Medical Department journal.

[44]  Louis M French,et al.  Symptom complaints following combat-related traumatic brain injury: Relationship to traumatic brain injury severity and posttraumatic stress disorder , 2009, Journal of the International Neuropsychological Society.

[45]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.

[46]  P. Basser,et al.  Diffusion tensor MR imaging of the human brain. , 1996, Radiology.

[47]  S. O'Bryant,et al.  Clinical Utility of Trial 1 of the Test of Memory Malingering (TOMM) , 2008, Applied neuropsychology.

[48]  H. Levin,et al.  Diffusion tensor imaging of acute mild traumatic brain injury in adolescents , 2008, Neurology.

[49]  Keith D. Cicerone,et al.  Persistent postconcussion syndrome: The structure of subjective complaints after mild traumatic brain injury , 1995 .

[50]  Louis French,et al.  Traumatic brain injury in the war zone. , 2005, The New England journal of medicine.

[51]  Jingshan Shi,et al.  Expression of c-Fos and c-Myc and deposition of beta-APP in neurons in the adult rat brain as a result of exposure to short-lasting impulse noise. , 2002, Journal of neurotrauma.

[52]  Pratik Mukherjee,et al.  Diffusion Tensor Imaging of Mild Traumatic Brain Injury , 2010, The Journal of head trauma rehabilitation.

[53]  David F Meaney,et al.  In-vitro approaches for studying blast-induced traumatic brain injury. , 2009, Journal of neurotrauma.

[54]  J. Adams,et al.  Diffuse axonal injury in head injury: Definition, diagnosis and grading , 1989, Histopathology.

[55]  V. Wedeen,et al.  Fiber crossing in human brain depicted with diffusion tensor MR imaging. , 2000, Radiology.

[56]  Roland Bammer,et al.  Cognitive processing speed and the structure of white matter pathways: Convergent evidence from normal variation and lesion studies , 2008, NeuroImage.

[57]  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.

[58]  I. Cernak The Importance of Systemic Response in the Pathobiology of Blast-Induced Neurotrauma , 2010, Front. Neur..

[59]  Michael Chopp,et al.  MRI evaluation of axonal reorganization after bone marrow stromal cell treatment of traumatic brain injury , 2011, NMR in biomedicine.

[60]  Arthur W. Toga,et al.  Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template , 2008, NeuroImage.

[61]  Papez Jw A proposed mechanism of emotion. 1937. , 1995 .

[62]  A. Mayer,et al.  A prospective diffusion tensor imaging study in mild traumatic brain injury , 2010, Neurology.

[63]  I Cernak,et al.  Ultrastructural and functional characteristics of blast injury-induced neurotrauma. , 2001, The Journal of trauma.

[64]  R. Ruff,et al.  Relationships between mild traumatic brain injury sustained in combat and post-traumatic stress disorder , 2010, F1000 medicine reports.

[65]  A. Rodríguez-Fornells,et al.  Reward Networks in the Brain as Captured by Connectivity Measures , 2009, Front. Neurosci..

[66]  J. Hardman,et al.  Pathology of head trauma. , 2002, Neuroimaging clinics of North America.

[67]  P. Parizel,et al.  New developments in the neuroradiological diagnosis of craniocerebral trauma , 2005, European Radiology.

[68]  C. Weiller,et al.  Checkerboard fields in multiple sclerosis , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[69]  Wang Zhan,et al.  Patterns of altered cortical perfusion and diminished subcortical integrity in posttraumatic stress disorder: An MRI study , 2011, NeuroImage.

[70]  Michael Brady,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

[71]  Bruce D. McCandliss,et al.  Extent of Microstructural White Matter Injury in Postconcussive Syndrome Correlates with Impaired Cognitive Reaction Time: A 3T Diffusion Tensor Imaging Study of Mild Traumatic Brain Injury , 2008, American Journal of Neuroradiology.

[72]  R. Henry,et al.  Diffusion Tensor MR Imaging and Fiber Tractography: Technical Considerations , 2008, American Journal of Neuroradiology.

[73]  Timothy Edward John Behrens,et al.  Discordant white matter N-acetylasparate and diffusion MRI measures suggest that chronic metabolic dysfunction contributes to axonal pathology in multiple sclerosis , 2007, NeuroImage.

[74]  King H. Yang,et al.  Concussion in Professional Football: Brain Responses by Finite Element Analysis: Part 9 , 2005, Neurosurgery.

[75]  M. Matsushita,et al.  Utility of diffusion tensor imaging in the acute stage of mild to moderate traumatic brain injury for detecting white matter lesions and predicting long-term cognitive function in adults. , 2011, Journal of neurosurgery.

[76]  Mary R. Newsome,et al.  Diffusion tensor imaging of mild to moderate blast-related traumatic brain injury and its sequelae. , 2010, Journal of neurotrauma.

[77]  M. Greicius,et al.  Decoding subject-driven cognitive states with whole-brain connectivity patterns. , 2012, Cerebral cortex.

[78]  E. Walker,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[79]  A. Alexander,et al.  White matter tractography using diffusion tensor deflection , 2003, Human brain mapping.

[80]  J D Pickard,et al.  Cognitive sequelae of head injury: involvement of basal forebrain and associated structures. , 2004, Brain : a journal of neurology.

[81]  M. Raichle,et al.  Detection of blast-related traumatic brain injury in U.S. military personnel. , 2011, The New England journal of medicine.

[82]  J. Hesselink,et al.  MR imaging of brain contusions: a comparative study with CT. , 1988, AJR. American journal of roentgenology.

[83]  C. Liston,et al.  Frontostriatal microstructure modulates efficient recruitment of cognitive control. , 2006, Cerebral cortex.

[84]  Stephen M. Smith,et al.  Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference , 2009, NeuroImage.

[85]  Ron Dumont,et al.  Delis‐Kaplan Executive Function System , 2008 .

[86]  P. Basser,et al.  Estimation of the effective self-diffusion tensor from the NMR spin echo. , 1994, Journal of magnetic resonance. Series B.

[87]  D. Salat,et al.  Choice reaction time performance correlates with diffusion anisotropy in white matter pathways supporting visuospatial attention. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[88]  E. Blanchard,et al.  Psychometric properties of the PTSD Checklist (PCL). , 1996, Behaviour research and therapy.

[89]  D. Hovda,et al.  The neurophysiology of concussion. , 2014, Progress in neurological surgery.

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

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

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

[93]  Taeun Chang,et al.  The pathobiology of moderate diffuse traumatic brain injury as identified using a new experimental model of injury in rats , 2004, Neurobiology of Disease.

[94]  D Yves von Cramon,et al.  Diffuse axonal injury associated with chronic traumatic brain injury: evidence from T2*-weighted gradient-echo imaging at 3 T. , 2003, AJNR. American journal of neuroradiology.

[95]  Michael S. Gazzaniga,et al.  Functional Connectivity: Integrating Behavioral, Diffusion Tensor Imaging, and Functional Magnetic Resonance Imaging Data Sets , 2005, Journal of Cognitive Neuroscience.

[96]  M. H. Parks,et al.  Disruption of frontocerebellar circuitry and function in alcoholism. , 2003, Alcoholism, clinical and experimental research.

[97]  Thomas J Balkin,et al.  Automated Neuropsychological Assessment Metrics: repeated assessment with two military samples. , 2011, Aviation, space, and environmental medicine.

[98]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[99]  Adrian Angold,et al.  Relations Between Continuous Performance Test Performance Measures and ADHD Behaviors , 2003, Journal of abnormal child psychology.

[100]  R. Kikinis,et al.  A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury , 2012, Brain Imaging and Behavior.

[101]  J. W. Papez A proposed mechanism of emotion. 1937. , 1995, The Journal of neuropsychiatry and clinical neurosciences.

[102]  Paul A. Yushkevich,et al.  Structure-specific statistical mapping of white matter tracts , 2007, NeuroImage.

[103]  A. Sorensen,et al.  Diffusion tensor imaging as potential biomarker of white matter injury in diffuse axonal injury. , 2004, AJNR. American journal of neuroradiology.

[104]  Craig A Branch,et al.  Diffusion-tensor imaging implicates prefrontal axonal injury in executive function impairment following very mild traumatic brain injury. , 2009, Radiology.

[105]  Derick R. Peterson,et al.  Diffusion tensor imaging detects clinically important axonal damage after mild traumatic brain injury: a pilot study. , 2007, Journal of neurotrauma.

[106]  K. Taber,et al.  Blast-related traumatic brain injury: what is known? , 2006, The Journal of neuropsychiatry and clinical neurosciences.

[107]  Sriram Vasudevan,et al.  Global white matter analysis of diffusion tensor images is predictive of injury severity in traumatic brain injury. , 2007, Journal of neurotrauma.

[108]  Richard J. Haier,et al.  Brain networks for working memory and factors of intelligence assessed in males and females with fMRI and DTI , 2010 .

[109]  Rocco Armonda,et al.  Explosive blast neurotrauma. , 2009, Journal of neurotrauma.

[110]  J. Frank,et al.  The contribution of gliosis to diffusion tensor anisotropy and tractography following traumatic brain injury: validation in the rat using Fourier analysis of stained tissue sections. , 2011, Brain : a journal of neurology.

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

[112]  Y. Sheline Neuroimaging studies of mood disorder effects on the brain , 2003, Biological Psychiatry.

[113]  Larry A Tupler,et al.  Cognitive sequelae of blast-related versus other mechanisms of brain trauma , 2009, Journal of the International Neuropsychological Society.

[114]  Jeffrey D. Lewis,et al.  Posttraumatic stress symptoms in OIF/OEF service members with blast-related and non-blast-related mild TBI. , 2010, NeuroRehabilitation.

[115]  Shu-Wei Sun,et al.  Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia , 2003, NeuroImage.

[116]  Derek K. Jones,et al.  Diffusion‐tensor MRI: theory, experimental design and data analysis – a technical review , 2002 .

[117]  Susumu Mori,et al.  Fiber tracking: principles and strategies – a technical review , 2002, NMR in biomedicine.

[118]  Hongtu Zhu,et al.  Structural equation modeling and principal component analysis of gray matter volumes in major depressive and bipolar disorders: Differences in latent volumetric structure , 2010, Psychiatry Research: Neuroimaging.

[119]  D. Warden,et al.  Military TBI During the Iraq and Afghanistan Wars , 2006, The Journal of head trauma rehabilitation.

[120]  I. Melle,et al.  The validity of d prime as a working memory index: Results from the “Bergen n-back task” , 2010, Journal of clinical and experimental neuropsychology.

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

[122]  Stefan Gazdzinski,et al.  Tract-based spatial statistics (TBSS) of diffusion tensor imaging data in alcohol dependence: Abnormalities of the motivational neurocircuitry , 2009, Psychiatry Research: Neuroimaging.

[123]  H. Blumberg Dimensions in the Development of Bipolar Disorder , 2007, Biological Psychiatry.

[124]  C. Nicholson Electric current flow in excitable cells J. J. B. Jack, D. Noble &R. W. Tsien Clarendon Press, Oxford (1975). 502 pp., £18.00 , 1976, Neuroscience.

[125]  Sterling C. Johnson,et al.  Longitudinal changes in patients with traumatic brain injury assessed with diffusion-tensor and volumetric imaging , 2008, NeuroImage.

[126]  Y. Bhattacharjee Shell Shock Revisited: Solving the Puzzle of Blast Trauma , 2008, Science.

[127]  Keiji Hashimoto,et al.  Voxel- and atlas-based analysis of diffusion tensor imaging may reveal focal axonal injuries in mild traumatic brain injury -- comparison with diffuse axonal injury. , 2012, Magnetic resonance imaging.

[128]  D. Stuss Traumatic brain injury: relation to executive dysfunction and the frontal lobes. , 2011, Current opinion in neurology.

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

[130]  Adrian Raine,et al.  Neural foundations to moral reasoning and antisocial behavior. , 2006, Social cognitive and affective neuroscience.

[131]  L. French,et al.  Military traumatic brain injury: an examination of important differences a , 2010, Annals of the New York Academy of Sciences.

[132]  B. Mädler,et al.  Diffusion Tensor Imaging Findings Are Not Strongly Associated With Postconcussional Disorder 2 Months Following Mild Traumatic Brain Injury , 2012, The Journal of head trauma rehabilitation.