Disruptions in Resting State Functional Connectivity and Cerebral Blood Flow in Mild Traumatic Brain Injury Patients

Mild traumatic brain injury (mTBI) is often occult to conventional imaging techniques. However, there is growing evidence that mTBI patients who lack evidence of structural intracranial injury may develop post-concussive syndrome (PCS). We investigated longitudinal alterations in resting state functional connectivity (rs-FC) in brain networks in a population of 28 patients compared to 28 matched control participants. Rs-FC and cerebral blood flow (CBF) within the nodes of the Default Mode Network (DMN) and Task Positive Network (TPN) were assessed at three time points including acute, sub-acute, and chronic stages following mTBI. Participants received the Automated Neuropsychological Assessment Metrics (ANAM) to assess cognitive performance. Main findings indicate that despite normalized cognitive performance, chronic mTBI patients demonstrate increased rs-FC between the DMN and regions associated with the salience network (SN) and TPN compared to the control populations, as well as reduced strength of rs-FC within the DMN at the acute stage of injury. In addition, chronic mTBI patients demonstrate an imbalance in the ratio of CBF between nodes of the DMN and TPN. Furthermore, preliminary exploratory analysis suggests that compared to those without chronic PCS, patients with chronic PCS reveal an imbalance in the ratio of CBF between the DMN nodes and TPN nodes across multiple stages of recovery. Findings suggest that the altered network perfusion with the associated changes in rs-FC may be a possible predictor of which mTBI patients will develop chronic PCS.

[1]  W. Weiner,et al.  Validation of the ANAM Test Battery in Parkinson's Disease , 2005 .

[2]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[3]  J. Detre,et al.  Pediatric perfusion imaging using pulsed arterial spin labeling , 2003, Journal of magnetic resonance imaging : JMRI.

[4]  Vince D. Calhoun,et al.  Impact of Analysis Methods on the Reproducibility and Reliability of Resting-State Networks , 2013, Brain Connect..

[5]  Asla Pitkänen,et al.  Association of chronic vascular changes with functional outcome after traumatic brain injury in rats. , 2010, Journal of neurotrauma.

[6]  C. Nepomuceno,et al.  Reliability and validity of the Disability Rating Scale and the Levels of Cognitive Functioning Scale in monitoring recovery from severe head injury. , 1987, Archives of physical medicine and rehabilitation.

[7]  Thomas Dierks,et al.  Static and dynamic characteristics of cerebral blood flow during the resting state in schizophrenia. , 2015, Schizophrenia bulletin.

[8]  Jonathan Z. Simon,et al.  Diffusion kurtosis as an in vivo imaging marker for reactive astrogliosis in traumatic brain injury , 2012, NeuroImage.

[9]  V. Menon,et al.  A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks , 2008, Proceedings of the National Academy of Sciences.

[10]  G. Shulman,et al.  Medial prefrontal cortex and self-referential mental activity: Relation to a default mode of brain function , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[11]  H. Muranaka,et al.  Compensatory cortical activation during performance of an attention task by patients with diffuse axonal injury: a functional magnetic resonance imaging study , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[12]  Elena A. Allen,et al.  Static and Dynamic Intrinsic Connectivity following Mild Traumatic Brain Injury. , 2015, Journal of neurotrauma.

[13]  Robert Leech,et al.  Salience network integrity predicts default mode network function after traumatic brain injury , 2012, Proceedings of the National Academy of Sciences.

[14]  D C Good,et al.  Changes in resting connectivity during recovery from severe traumatic brain injury. , 2011, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[15]  Arthur F. Kramer,et al.  Behavioural Brain Research Age-related Differences in Cortical Recruitment and Suppression: Implications for Cognitive Performance , 2022 .

[16]  A. Mayer,et al.  A functional MRI study of multimodal selective attention following mild traumatic brain injury , 2012, Brain Imaging and Behavior.

[17]  J. Langlois,et al.  Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths , 2006 .

[18]  B. Lerer,et al.  Cerebral blood flow in chronic symptomatic mild traumatic brain injury , 2003, Psychiatry Research: Neuroimaging.

[19]  Mark Hallett,et al.  Alteration of brain functional network at rest and in response to YMCA physical stress test in concussed athletes: RsFMRI study , 2011, NeuroImage.

[20]  S. Heckers,et al.  Functional resting-state networks are differentially affected in schizophrenia , 2011, Schizophrenia Research.

[21]  W. Poon,et al.  Changes of cognitive functioning following mild traumatic brain injury over a 3-month period , 2008, Brain injury.

[22]  Dennis L Reeves,et al.  Reference values for performance on the Automated Neuropsychological Assessment Metrics V3.0 in an active duty military sample. , 2006, Military medicine.

[23]  R. Larsen,et al.  The Satisfaction with Life Scale , 1985, Journal of personality assessment.

[24]  J. Ponsford,et al.  The Relationship between age, injury severity, and MRI findings after traumatic brain injury. , 2009, Journal of neurotrauma.

[25]  Kristina M. Visscher,et al.  The neural bases of momentary lapses in attention , 2006, Nature Neuroscience.

[26]  Amitabh Varshney,et al.  Investigation of Multiple Frequency Ranges Using Discrete Wavelet Decomposition of Resting-State Functional Connectivity in Mild Traumatic Brain Injury Patients , 2015, Brain Connect..

[27]  W. Poon,et al.  Antibiotics-impregnated ventricular catheter versus systemic antibiotics for prevention of nosocomial CSF and non-CSF infections: a prospective randomised clinical trial , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[28]  Thomas Dierks,et al.  Quantification of Network Perfusion in ASL Cerebral Blood Flow Data with Seed Based and ICA Approaches , 2013, Brain Topography.

[29]  F. Castellanos,et al.  Spontaneous attentional fluctuations in impaired states and pathological conditions: A neurobiological hypothesis , 2007, Neuroscience & Biobehavioral Reviews.

[30]  R. Benson,et al.  Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses. , 2015, Journal of neurotrauma.

[31]  Robert Leech,et al.  Default mode network functional and structural connectivity after traumatic brain injury. , 2011, Brain : a journal of neurology.

[32]  Robert L Kane,et al.  Identifying and monitoring cognitive deficits in clinical populations using Automated Neuropsychological Assessment Metrics (ANAM) tests. , 2007, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[33]  Rachel D. Wolfowitz,et al.  Perfusion deficits in patients with mild traumatic brain injury characterized by dynamic susceptibility contrast MRI , 2013, NMR in biomedicine.

[34]  Vinod Menon,et al.  Functional connectivity in the resting brain: A network analysis of the default mode hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[35]  J. Ponsford Factors contributing to outcome following traumatic brain injury. , 2013, NeuroRehabilitation.

[36]  M. Lovell,et al.  Prevalence of abnormal CT-scans following mild head injury. , 2000, Brain injury.

[37]  Thomas T. Liu,et al.  Neurovascular factors in resting-state functional MRI , 2013, NeuroImage.

[38]  Michael W. L. Chee,et al.  Sleep deprivation reduces default mode network connectivity and anti-correlation during rest and task performance , 2012, NeuroImage.

[39]  V. Menon,et al.  Saliency, switching, attention and control: a network model of insula function , 2010, Brain Structure and Function.

[40]  J D Pickard,et al.  Altered functional connectivity in the motor network after traumatic brain injury , 2010, Neurology.

[41]  Martin Lepage,et al.  Medial prefrontal cortex activity during memory encoding of pictures and its relation to symptomatic improvement after citalopram treatment in patients with major depression. , 2010, Journal of psychiatry & neuroscience : JPN.

[42]  B Jennett,et al.  Analyzing outcome of treatment of severe head injury: a review and update on advancing the use of the Glasgow Outcome Scale. , 1998, Journal of neurotrauma.

[43]  Karl J. Friston,et al.  Functional Connectivity: The Principal-Component Analysis of Large (PET) Data Sets , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[44]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Brian Avants,et al.  Resting cerebral blood flow alterations in chronic traumatic brain injury: an arterial spin labeling perfusion FMRI study. , 2010, Journal of neurotrauma.

[46]  Mark D'Esposito,et al.  From cognitive to neural models of working memory , 2007, Philosophical Transactions of the Royal Society B: Biological Sciences.

[47]  Marnie E. Shaw,et al.  Switching between executive and default mode networks in posttraumatic stress disorder: alterations in functional connectivity. , 2010, Journal of psychiatry & neuroscience : JPN.

[48]  J. Callicott,et al.  Age-related alterations in default mode network: Impact on working memory performance , 2010, Neurobiology of Aging.

[49]  Josef Ling,et al.  Functional connectivity in mild traumatic brain injury , 2011, Human brain mapping.

[50]  G. Manley,et al.  Focal lesions in acute mild traumatic brain injury and neurocognitive outcome: CT versus 3T MRI. , 2008, Journal of neurotrauma.

[51]  D. Norris,et al.  Abnormal whole-brain functional networks in homogeneous acute mild traumatic brain injury , 2012, Neurology.

[52]  Timothy E. Ham,et al.  Default Mode Network Connectivity Predicts Sustained Attention Deficits after Traumatic Brain Injury , 2011, The Journal of Neuroscience.

[53]  Jeffrey S. Spence,et al.  Deficits in functional connectivity of hippocampal and frontal lobe circuits after traumatic axonal injury. , 2011, Archives of neurology.

[54]  R. Kane,et al.  Performance on the Automated Neuropsychological Assessment Metrics in a Nonclinical Sample of Soldiers Screened for Mild TBI After Returning From Iraq and Afghanistan: A Descriptive Analysis , 2009, The Journal of head trauma rehabilitation.

[55]  Daniel K Sodickson,et al.  Default-mode network disruption in mild traumatic brain injury. , 2012, Radiology.

[56]  Rao P. Gullapalli,et al.  Default mode network interference in mild traumatic brain injury – A pilot resting state study , 2013, Brain Research.

[57]  D. Wade,et al.  The Rivermead Post Concussion Symptoms Questionnaire: a measure of symptoms commonly experienced after head injury and its reliability , 1995, Journal of Neurology.

[58]  John Olver,et al.  Longitudinal follow-up of patients with traumatic brain injury: outcome at two, five, and ten years post-injury. , 2014, Journal of neurotrauma.

[59]  J. Badaut,et al.  A Neurovascular Perspective for Long-Term Changes After Brain Trauma , 2011, Translational Stroke Research.

[60]  Mark Hallett,et al.  Alteration of brain default network in subacute phase of injury in concussed individuals: Resting-state fMRI study , 2012, NeuroImage.

[61]  Peter Fransson,et al.  Can resting‐state functional MRI serve as a complement to task‐based mapping of sensorimotor function? A test–retest reliability study in healthy volunteers , 2011, Journal of magnetic resonance imaging : JMRI.

[62]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[63]  John A. Detre,et al.  Relations between BOLD fMRI-Derived Resting Brain Activity and Cerebral Blood Flow , 2012, PloS one.

[64]  M. Wald,et al.  Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths, 2002-2006 , 2010 .

[65]  B. Biswal,et al.  Cingulate-Precuneus Interactions: A New Locus of Dysfunction in Adult Attention-Deficit/Hyperactivity Disorder , 2008, Biological Psychiatry.