Default mode network in concussed individuals in response to the YMCA physical stress test.

We hypothesize that the evolution of mild traumatic brain injury (mTBI) may be related to differential effects of a concussive blow on the functional integrity of the brain default mode network (DMN) at rest and/or in response to physical stress. Accordingly, in this resting-state functional magnetic resonance imaging (fMRI) study, we examined 14 subjects 10±2 days post-sports-related mTBI and 15 age-matched normal volunteers (NVs) to investigate the possibility that the integrity of the DMN is disrupted at the resting state and/or following the physical stress test. First, all mTBI subjects were asymptomatic based upon clinical evaluation and neuropsychological (NP) assessments prior to the MRI session. Second, the functional integrity within the DMN, a main resting-state network, remained resilient to a single concussive blow. Specifically, the major regions of interest (ROIs) constituting the DMN (e.g., the posterior cingulate cortex [PCC]/precuneus area, the medial prefrontal cortex [MPFC], and left and right lateral parietal cortices [LLP and RLP]) and the connectivity within these four ROIs was similar between NVs and mTBI subjects prior to the YMCA physical stress test. However, the YMCA physical stress test disrupted the DMN, significantly reducing the magnitude of the connection between the PCC and left lateral parietal ROI, and PCC and right lateral parietal ROI, as well as between the PCC and MPFC in mTBI subjects. Thus while the DMN remained resilient to a single mTBI without exertion at 10 days post-injury, it was altered in response to limited physical stress. This may explain some clinical features of mTBI and provide some insight into its mechanism. This important finding should be considered by clinical practitioners when making decisions regarding return-to-play and clearing mTBI athletes for sports participation.

[1]  Michael A. Kiraly,et al.  Traumatic Brain Injury and Delayed Sequelae: A Review - Traumatic Brain Injury and Mild Traumatic Brain Injury (Concussion) are Precursors to Later-Onset Brain Disorders, Including Early-Onset Dementia , 2007, TheScientificWorldJournal.

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

[3]  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.

[4]  F. Webbe,et al.  Short-term and long-term outcome of athletic closed head injuries. , 2003, Clinics in sports medicine.

[5]  R. Cantu,et al.  Consensus statement on Concussion in Sport 3rd International Conference on Concussion in Sport held in Zurich, November 2008. , 2009, Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine.

[6]  M. Just,et al.  Functional connectivity in a baseline resting-state network in autism , 2006, Neuroreport.

[7]  M. Lowe,et al.  Functional Connectivity in Single and Multislice Echoplanar Imaging Using Resting-State Fluctuations , 1998, NeuroImage.

[8]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[9]  S. Rombouts,et al.  Consistent resting-state networks across healthy subjects , 2006, Proceedings of the National Academy of Sciences.

[10]  A. Braun,et al.  Decoupling of the brain's default mode network during deep sleep , 2009, Proceedings of the National Academy of Sciences.

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

[12]  W. Singer,et al.  Dynamic predictions: Oscillations and synchrony in top–down processing , 2001, Nature Reviews Neuroscience.

[13]  Robert C. Cantu,et al.  Concussion Classification: Ongoing Controversy , 2006 .

[14]  David F Meaney,et al.  Mild traumatic brain injury and diffuse axonal injury in swine. , 2011, Journal of neurotrauma.

[15]  P. Skudlarski,et al.  Detection of functional connectivity using temporal correlations in MR images , 2002, Human brain mapping.

[16]  Abraham Z. Snyder,et al.  A default mode of brain function: A brief history of an evolving idea , 2007, NeuroImage.

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

[18]  M. Boly,et al.  Brain Connectivity in Pathological and Pharmacological Coma , 2010, Front. Syst. Neurosci..

[19]  Kelvin O. Lim,et al.  Evidence of disrupted functional connectivity in the brain after combat-related blast injury , 2011, NeuroImage.

[20]  Paul B. Johnson,et al.  Premotor and parietal cortex: corticocortical connectivity and combinatorial computations. , 1997, Annual review of neuroscience.

[21]  A. Harvey,et al.  Postconcussive symptoms and posttraumatic stress disorder after mild traumatic brain injury. , 1999, The Journal of nervous and mental disease.

[22]  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.

[23]  Samantha J. Broyd,et al.  Attention-Induced Deactivations in Very Low Frequency EEG Oscillations: Differential Localisation According to ADHD Symptom Status , 2011, PloS one.

[24]  D. Sharp,et al.  PATH57 Altered structural and functional network connectivity predicts cognitive function after traumatic brain injury , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[25]  Michael D. Greicius,et al.  Development of functional and structural connectivity within the default mode network in young children , 2010, NeuroImage.

[26]  S. Rombouts,et al.  Reduced resting-state brain activity in the "default network" in normal aging. , 2008, Cerebral cortex.

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

[28]  K. Çiftçi,et al.  Minimum Spanning Tree Reflects the Alterations of the Default Mode Network During Alzheimer’s Disease , 2011, Annals of Biomedical Engineering.

[29]  Tianzi Jiang,et al.  Altered resting-state functional connectivity patterns of anterior cingulate cortex in adolescents with attention deficit hyperactivity disorder , 2006, Neuroscience Letters.

[30]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

[31]  B. Biswal,et al.  Functional connectivity in the motor cortex of resting human brain using echo‐planar mri , 1995, Magnetic resonance in medicine.

[32]  Thomas T. Liu,et al.  A component based noise correction method (CompCor) for BOLD and perfusion based fMRI , 2007, NeuroImage.

[33]  Kevin Murphy,et al.  The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced? , 2009, NeuroImage.

[34]  M. Hallett,et al.  International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome , 1997, Journal of the Neurological Sciences.

[35]  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.

[36]  J. Provenzale Imaging of traumatic brain injury: a review of the recent medical literature. , 2010, AJR. American journal of roentgenology.

[37]  Simon B Eickhoff,et al.  Investigating the Functional Heterogeneity of the Default Mode Network Using Coordinate-Based Meta-Analytic Modeling , 2009, The Journal of Neuroscience.

[38]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[39]  S. Debener,et al.  Default-mode brain dysfunction in mental disorders: A systematic review , 2009, Neuroscience & Biobehavioral Reviews.

[40]  A. Fleisher,et al.  Altered default mode network connectivity in alzheimer's disease—A resting functional MRI and bayesian network study , 2011, Human brain mapping.

[41]  J. Kwon,et al.  Reduced prefrontal functional connectivity in the default mode network is related to greater psychopathology in subjects with high genetic loading for schizophrenia , 2011, Schizophrenia Research.

[42]  P. Fransson How default is the default mode of brain function? Further evidence from intrinsic BOLD signal fluctuations , 2006, Neuropsychologia.

[43]  D. Pennell,et al.  Functional abnormalities in normally appearing athletes following mild traumatic brain injury: a functional MRI study , 2010, Experimental Brain Research.

[44]  Mark Lovell,et al.  Return to play following sports-related concussion. , 2004, Clinics in sports medicine.

[45]  J. Bazarian,et al.  Mild traumatic brain injury in the United States, 1998–2000 , 2005, Brain injury.

[46]  S. Slobounov,et al.  Alteration of Cortical Functional Connectivity as a Result of Traumatic Brain Injury Revealed by Graph Theory, ICA, and sLORETA Analyses of EEG Signals , 2010, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[47]  M. Greicius,et al.  Resting-state functional connectivity reflects structural connectivity in the default mode network. , 2009, Cerebral cortex.

[48]  F. Hillary,et al.  Neuroimaging of working memory dysfunction and the dilemma with brain reorganization hypotheses , 2008, Journal of the International Neuropsychological Society.

[49]  M. Bulut,et al.  MR imaging in the detection of diffuse axonal injury with mild traumatic brain injury , 2008, Neurological research.

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

[51]  D. Pennell,et al.  Are functional deficits in concussed individuals consistent with white matter structural alterations: combined FMRI & DTI study , 2010, Experimental Brain Research.

[52]  P. Liddle,et al.  Task-related default mode network modulation and inhibitory control in ADHD: effects of motivation and methylphenidate. , 2011, Journal of child psychology and psychiatry, and allied disciplines.

[53]  Glenn Curtiss,et al.  Factors moderating neuropsychological outcomes following mild traumatic brain injury: A meta-analysis , 2005, Journal of the International Neuropsychological Society.

[54]  J. Bailes,et al.  When to consider retiring an athlete after sports-related concussion. , 2011, Clinics in sports medicine.

[55]  G. Lazzarino,et al.  Biochemical and neurochemical sequelae following mild traumatic brain injury: summary of experimental data and clinical implications. , 2010, Neurosurgical focus.

[56]  R. Caminiti,et al.  Cortical networks for visual reaching , 2004, Experimental Brain Research.

[57]  Christa Neuper,et al.  Individual differences in mathematical competence predict parietal brain activation during mental calculation , 2007, NeuroImage.

[58]  R. Ruff,et al.  Mild traumatic brain injury and neural recovery: rethinking the debate. , 2011, NeuroRehabilitation.

[59]  Daniel P. Kennedy,et al.  Functional abnormalities of the default network during self- and other-reflection in autism. , 2008, Social cognitive and affective neuroscience.

[60]  G. Pearlson,et al.  Decreased prefrontal cortex activity in mild traumatic brain injury during performance of an auditory oddball task , 2010, Brain Imaging and Behavior.

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

[62]  David K Menon,et al.  Traumatic brain injury , 2011, Philosophical Transactions of the Royal Society B: Biological Sciences.

[63]  Shobini L. Rao,et al.  Reduction of functional brain connectivity in mild traumatic brain injury during working memory. , 2009, Journal of neurotrauma.

[64]  Paul B. Johnson,et al.  Cortical networks for visual reaching: physiological and anatomical organization of frontal and parietal lobe arm regions. , 1996, Cerebral cortex.

[65]  B. Biswal,et al.  Network homogeneity reveals decreased integrity of default-mode network in ADHD , 2008, Journal of Neuroscience Methods.

[66]  Jonathan D. Power,et al.  A Parcellation Scheme for Human Left Lateral Parietal Cortex , 2010, Neuron.

[67]  B. Biswal,et al.  Functional connectivity of default mode network components: Correlation, anticorrelation, and causality , 2009, Human brain mapping.

[68]  V. Calhoun,et al.  Lateral differences in the default mode network in healthy controls and patients with schizophrenia , 2010, Human brain mapping.

[69]  G. Buzsáki,et al.  Neuronal Oscillations in Cortical Networks , 2004, Science.

[70]  M. Greicius,et al.  Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI , 2004, Proc. Natl. Acad. Sci. USA.

[71]  Daniel P. Kennedy,et al.  Failing to deactivate: resting functional abnormalities in autism. , 2006, Proceedings of the National Academy of Sciences of the United States of America.