Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI) can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1–4 Hz) that can be measured and localized by resting-state magnetoencephalography (MEG). In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1–4 Hz) from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes), our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes), blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI.

[1]  Valerian Kagan,et al.  Blast exposure in rats with body shielding is characterized primarily by diffuse axonal injury. , 2011, Journal of neurotrauma.

[2]  Anders M. Dale,et al.  Vector-based spatial–temporal minimum L1-norm solution for MEG , 2006, NeuroImage.

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

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

[5]  N. Carlson Physiology of behavior , 1977 .

[6]  S Taulu,et al.  MEG recordings of DC fields using the signal space separation method (SSS). , 2004, Neurology & clinical neurophysiology : NCN.

[7]  Thomas T. Liu,et al.  MEG source imaging method using fast L1 minimum-norm and its applications to signals with brain noise and human resting-state source amplitude images , 2014, NeuroImage.

[8]  Li Cui,et al.  Evaluation of signal space separation via simulation , 2007, Medical & Biological Engineering & Computing.

[9]  W. Drongelen,et al.  Localization of brain electrical activity via linearly constrained minimum variance spatial filtering , 1997, IEEE Transactions on Biomedical Engineering.

[10]  P Gloor,et al.  Brain lesions that produce delta waves in the EEG , 1977, Neurology.

[11]  Raul Coimbra,et al.  Integrated imaging approach with MEG and DTI to detect mild traumatic brain injury in military and civilian patients. , 2009, Journal of neurotrauma.

[12]  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.

[13]  C. Rosenberg,et al.  Electroencephalography: Basic Principles, Clinical Applications, and Related Fields, 3rd Ed. , 1994 .

[14]  N. Kanwisher,et al.  A Cortical Area Selective for Visual Processing of the Human Body , 2001, Science.

[15]  Gregory A. Miller,et al.  A parietal–frontal network studied by somatosensory oddball MEG responses, and its cross-modal consistency , 2005, NeuroImage.

[16]  M Huang,et al.  Multi-start downhill simplex method for spatio-temporal source localization in magnetoencephalography. , 1998, Electroencephalography and clinical neurophysiology.

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

[18]  L. Binder,et al.  A review of mild head trauma. Part II: Clinical implications. , 1997, Journal of clinical and experimental neuropsychology.

[19]  W. Youden,et al.  Index for rating diagnostic tests , 1950, Cancer.

[20]  Seppo P. Ahlfors,et al.  New Six-Layer Magnetically-Shielded Room for MEG , 2002 .

[21]  B. Giordani,et al.  Disability caused by minor head injury. , 1981, Neurosurgery.

[22]  S. Ahlers,et al.  Blast-induced mild traumatic brain injury. , 2010, The Psychiatric clinics of North America.

[23]  Qian Luo,et al.  Complexity analysis of resting state magnetoencephalography activity in traumatic brain injury patients. , 2013, Journal of neurotrauma.

[24]  P. Basser Inferring microstructural features and the physiological state of tissues from diffusion‐weighted images , 1995, NMR in biomedicine.

[25]  S. Schultz Principles of Neural Science, 4th ed. , 2001 .

[26]  Jeffrey L. Elman,et al.  A novel integrated MEG and EEG analysis method for dipolar sources , 2007, NeuroImage.

[27]  N. Bohnen,et al.  Neuropsychological deficits in patients with persistent symptoms six months after mild head injury. , 1992, Neurosurgery.

[28]  J. Gotman,et al.  The electromicrophysiology of delta waves induced by systemic atropine , 1978, Brain Research.

[29]  Thomas T. Liu,et al.  An automatic MEG low-frequency source imaging approach for detecting injuries in mild and moderate TBI patients with blast and non-blast causes , 2012, NeuroImage.

[30]  J. Lewine,et al.  Objective Documentation of Traumatic Brain Injury Subsequent to Mild Head Trauma: Multimodal Brain Imaging With MEG, SPECT, and MRI , 2007, The Journal of head trauma rehabilitation.

[31]  Kelvin O. Lim,et al.  Diffuse and spatially variable white matter disruptions are associated with blast-related mild traumatic brain injury , 2012, NeuroImage.

[32]  Pratik Mukherjee,et al.  Structural dissociation of attentional control and memory in adults with and without mild traumatic brain injury. , 2008, Brain : a journal of neurology.

[33]  Kalanit Grill-Spector,et al.  Sparsely-distributed organization of face and limb activations in human ventral temporal cortex , 2010, NeuroImage.

[34]  P Gloor,et al.  The cortical electromicrophysiology of pathological delta waves in the electroencephalogram of cats. , 1977, Electroencephalography and clinical neurophysiology.

[35]  Evandro T. Martins,et al.  Psychiatric disorders and traumatic brain injury , 2008, Neuropsychiatric disease and treatment.

[36]  J. Talbott The Psychiatric Sequelae of Traumatic Injury , 2011 .

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

[38]  B. Rockstroh,et al.  Abnormal oscillatory brain dynamics in schizophrenia: a sign of deviant communication in neural network? , 2007, BMC psychiatry.

[39]  P. Dash,et al.  Biomarkers for the diagnosis and prognosis of mild traumatic brain injury/concussion. , 2013, Journal of neurotrauma.

[40]  M. Mesulam,et al.  Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. , 1998, Brain : a journal of neurology.

[41]  Alain Ptito,et al.  New Frontiers in Diagnostic Imaging in Concussive Head Injury , 2001, Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine.

[42]  Norbert Schuff,et al.  Advances in neuroimaging of traumatic brain injury and posttraumatic stress disorder. , 2009, Journal of rehabilitation research and development.

[43]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[44]  N. Schaul,et al.  The fundamental neural mechanisms of electroencephalography. , 1998, Electroencephalography and clinical neurophysiology.

[45]  N R Temkin,et al.  One year psychosocial outcome in head injury , 1995, Journal of the International Neuropsychological Society.

[46]  G. Larrabee,et al.  A review of mild head trauma. Part I: Meta-analytic review of neuropsychological studies. , 1997, Journal of clinical and experimental neuropsychology.

[47]  J. Lewine,et al.  Neuromagnetic assessment of pathophysiologic brain activity induced by minor head trauma. , 1999, AJNR. American journal of neuroradiology.

[48]  J. Adams,et al.  Diffuse axonal injury and traumatic coma in the primate , 1982, Annals of neurology.

[49]  L. Binder Persisting symptoms after mild head injury: a review of the postconcussive syndrome. , 1986, Journal of clinical and experimental neuropsychology.

[50]  R. Leahy,et al.  EEG and MEG: forward solutions for inverse methods , 1999, IEEE Transactions on Biomedical Engineering.

[51]  Sara C. LaHue,et al.  Resting state magnetoencephalography functional connectivity in traumatic brain injury. , 2013, Journal of neurosurgery.

[52]  Dinesh Talwar Primer of EEG with a Mini-Atlas , 2004 .

[53]  David Poeppel,et al.  Reconstructing spatio-temporal activities of neural sources using an MEG vector beamformer technique , 2001, IEEE Transactions on Biomedical Engineering.

[54]  Harvey S. Levin,et al.  Magnetic resonance imaging and computerized tomography in relation to the neurobehavioral sequelae of mild and moderate head injuries. , 1987, Journal of neurosurgery.

[55]  J. Lagopoulos,et al.  Diffuse axonal injury in severe traumatic brain injury visualized using high-resolution diffusion tensor imaging. , 2007, Journal of neurotrauma.

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

[57]  J. Sergent,et al.  Functional neuroanatomy of face and object processing. A positron emission tomography study. , 1992, Brain : a journal of neurology.

[58]  Psychosocial functioning at 1 month after head injury. , 1984, Neurosurgery.

[59]  K. Gerold,et al.  Clinicopathological heterogeneity in the classification of mild head injury. , 1996, Neurosurgery.

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

[61]  M. Tomita,et al.  Meta-analysis of facial affect recognition difficulties after traumatic brain injury. , 2011, Neuropsychology.

[62]  K A Dunn,et al.  Traumatic brain injury in the United States: A public health perspective. , 1999, The Journal of head trauma rehabilitation.

[63]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[64]  Bruce J. Fisch,et al.  Fisch and Spehlmann's Eeg Primer: Basic Principles of Digital and Analog Eeg , 1999 .

[65]  L. Noble-Haeusslein,et al.  Traumatic Brain Injury: An Overview of Pathobiology with Emphasis on Military Populations , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[66]  S. Taulu,et al.  Suppression of Interference and Artifacts by the Signal Space Separation Method , 2003, Brain Topography.

[67]  N. Kanwisher,et al.  The Fusiform Face Area: A Module in Human Extrastriate Cortex Specialized for Face Perception , 1997, The Journal of Neuroscience.

[68]  Ernst Fernando Lopes Da Silva Niedermeyer,et al.  Electroencephalography, basic principles, clinical applications, and related fields , 1982 .

[69]  Andrew J MacGregor,et al.  Injury-Specific Correlates of Combat-Related Traumatic Brain Injury in Operation Iraqi Freedom , 2011, The Journal of head trauma rehabilitation.

[70]  M. E. Spencer,et al.  A Study of Dipole Localization Accuracy for MEG and EEG using a Human Skull Phantom , 1998, NeuroImage.

[71]  K. Yeates,et al.  Pediatric Sport-Related Concussion: A Review of the Clinical Management of an Oft-Neglected Population , 2006, Pediatrics.

[72]  Se Robinson,et al.  Functional neuroimaging by Synthetic Aperture Magnetometry (SAM) , 1999 .

[73]  Christian Wienbruch,et al.  Abnormal slow wave mapping (ASWAM)—A tool for the investigation of abnormal slow wave activity in the human brain , 2007, Journal of Neuroscience Methods.