Contrasting Effects of Posttraumatic Stress Disorder and Mild Traumatic Brain Injury on the Whole-Brain Resting-State Network: A Magnetoencephalography Study

The aim of this study was to evaluate alterations in whole-brain resting-state networks associated with posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI). Networks were constructed from locations of peak statistical power on an individual basis from magnetoencephalography (MEG) source series data by applying the weighted phase lag index and surrogate data thresholding procedures. Networks representing activity in the alpha bandwidth as well as wideband activity (DC-80 Hz) were created. Statistical comparisons were adjusted for age and education level. Alpha network results demonstrate reductions in network structure associated with PTSD, but no differences associated with mTBI. Wideband network results demonstrate a shift in connectivity from the alpha to theta bandwidth in both PTSD and mTBI. Also, contrasting alterations in network structure are noted, with increased randomness associated with PTSD and increased structure associated with mTBI. These results demonstrate the potential of the analysis of MEG resting-state networks to differentiate two highly comorbid conditions. The importance of the alpha bandwidth to resting-state connectivity is also highlighted, while demonstrating the necessity of considering activity in other bandwidths during network construction.

[1]  Margot J. Taylor,et al.  Detection and localization of hippocampal activity using beamformers with MEG: A detailed investigation using simulations and empirical data , 2011, Human brain mapping.

[2]  C. J. Stam,et al.  Cognition is related to resting-state small-world network topology: an magnetoencephalographic study , 2011, Neuroscience.

[3]  Yan Zhou,et al.  Early Altered Resting-State Functional Connectivity Predicts the Severity of Post-Traumatic Stress Disorder Symptoms in Acutely Traumatized Subjects , 2012, PloS one.

[4]  Tom Holroyd,et al.  Theta band activity in response to emotional expressions and its relationship with gamma band activity as revealed by MEG and advanced beamformer source imaging , 2014, Front. Hum. Neurosci..

[5]  Duncan J. Watts,et al.  Collective dynamics of ‘small-world’ networks , 1998, Nature.

[6]  Edward T. Bullmore,et al.  Network-based statistic: Identifying differences in brain networks , 2010, NeuroImage.

[7]  Gareth R. Barnes,et al.  Frequency-dependent functional connectivity within resting-state networks: An atlas-based MEG beamformer solution , 2012, NeuroImage.

[8]  David H. Salat,et al.  Brain Network Disturbance Related to Posttraumatic Stress and Traumatic Brain Injury in Veterans , 2015, Biological Psychiatry.

[9]  R. Bluhm,et al.  Alterations in default network connectivity in posttraumatic stress disorder related to early-life trauma. , 2009, Journal of psychiatry & neuroscience : JPN.

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

[11]  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.

[12]  S. Hayes,et al.  Quantitative meta-analysis of neural activity in posttraumatic stress disorder , 2012, Biology of Mood & Anxiety Disorders.

[13]  A P Georgopoulos,et al.  The synchronous neural interactions test as a functional neuromarker for post-traumatic stress disorder (PTSD): a robust classification method based on the bootstrap , 2010, Journal of neural engineering.

[14]  Jennifer R. Stapleton-Kotloski,et al.  Localization of Interictal Epileptiform Activity Using Magnetoencephalography with Synthetic Aperture Magnetometry in Patients with a Vagus Nerve Stimulator , 2014, Front. Neurol..

[15]  Natasa Kovacevic,et al.  Semantic information alters neural activation during transverse patterning performance , 2009, NeuroImage.

[16]  Alessandro Vespignani,et al.  Detecting rich-club ordering in complex networks , 2006, physics/0602134.

[17]  C. Stam,et al.  The organization of physiological brain networks , 2012, Clinical Neurophysiology.

[18]  Stephen B. Seidman,et al.  Network structure and minimum degree , 1983 .

[19]  Apostolos P Georgopoulos,et al.  Neural network modulation by trauma as a marker of resilience: differences between veterans with posttraumatic stress disorder and resilient controls. , 2013, JAMA psychiatry.

[20]  Margot J. Taylor,et al.  Development of ACC–amygdala activations in processing unattended fear , 2012, NeuroImage.

[21]  Nuria Bargallo,et al.  Resting-state functional magnetic resonance imaging activity and connectivity and cognitive outcome in traumatic brain injury. , 2013, JAMA neurology.

[22]  Raymond Fang,et al.  Disrupted modular organization of resting-state cortical functional connectivity in U.S. military personnel following concussive ‘mild’ blast-related traumatic brain injury , 2014, NeuroImage.

[23]  A. Etkin,et al.  Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. , 2007, The American journal of psychiatry.

[24]  Israel Liberzon,et al.  Does neuroimaging research examining the pathophysiology of posttraumatic stress disorder require medication-free patients? , 2010, Journal of psychiatry & neuroscience : JPN.

[25]  Jean-Loup Guillaume,et al.  Fast unfolding of communities in large networks , 2008, 0803.0476.

[26]  Lily Riggs,et al.  A complementary analytic approach to examining medial temporal lobe sources using magnetoencephalography , 2009, NeuroImage.

[27]  Margot J. Taylor,et al.  Unattended emotional faces elicit early lateralized amygdala–frontal and fusiform activations , 2010, NeuroImage.

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

[29]  R M Leahy,et al.  A sensor-weighted overlapping-sphere head model and exhaustive head model comparison for MEG. , 1999, Physics in medicine and biology.

[30]  Amit Etkin,et al.  Hippocampal Network Connectivity and Activation Differentiates Post-Traumatic Stress Disorder From Generalized Anxiety Disorder , 2013, Neuropsychopharmacology.

[31]  Elizabeth W. Pang,et al.  Event-related beamforming: A robust method for presurgical functional mapping using MEG , 2007, Clinical Neurophysiology.

[32]  N. Shah,et al.  The Default Mode Network and EEG Regional Spectral Power: A Simultaneous fMRI-EEG Study , 2014, PloS one.

[33]  Laura Astolfi,et al.  How the Statistical Validation of Functional Connectivity Patterns Can Prevent Erroneous Definition of Small-World Properties of a Brain Connectivity Network , 2012, Comput. Math. Methods Medicine.

[34]  Thomas Dierks,et al.  BOLD correlates of EEG alpha phase-locking and the fMRI default mode network , 2009, NeuroImage.

[35]  Vincent L. Gracco,et al.  Auditory evoked fields to vocalization during passive listening and active generation in adults who stutter , 2010, NeuroImage.

[36]  Helmut Laufs,et al.  Where the BOLD signal goes when alpha EEG leaves , 2006, NeuroImage.

[37]  G. Knyazev,et al.  The default mode network and EEG alpha oscillations: An independent component analysis , 2011, Brain Research.

[38]  Xin Wang,et al.  Neural Dysregulation in Posttraumatic Stress Disorder: Evidence for Disrupted Equilibrium Between Salience and Default Mode Brain Networks , 2012, Psychosomatic medicine.

[39]  M. Shenton,et al.  Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma , 2002, Nature Neuroscience.

[40]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[41]  Linda Douw,et al.  Local MEG networks: The missing link between protein expression and epilepsy in glioma patients? , 2013, NeuroImage.

[42]  O. Sporns,et al.  Complex brain networks: graph theoretical analysis of structural and functional systems , 2009, Nature Reviews Neuroscience.

[43]  Andreas Kleinschmidt,et al.  EEG-correlated fMRI of human alpha activity , 2003, NeuroImage.

[44]  G. V. van Wingen,et al.  Perceived threat predicts the neural sequelae of combat stress , 2011, Molecular Psychiatry.

[45]  R. James R. Blair,et al.  Neural dynamics for facial threat processing as revealed by gamma band synchronization using MEG , 2007, NeuroImage.

[46]  Habib Benali,et al.  Specific and Evolving Resting-State Network Alterations in Post-Concussion Syndrome Following Mild Traumatic Brain Injury , 2013, PloS one.

[47]  Qiyong Gong,et al.  Disrupted Functional Brain Connectome in Patients with Posttraumatic Stress Disorder. , 2015, Radiology.

[48]  Margot J. Taylor,et al.  Resting-state hippocampal connectivity correlates with symptom severity in post-traumatic stress disorder , 2014, NeuroImage: Clinical.

[49]  Sarah M. Rajtmajer,et al.  The Rich Get Richer: Brain Injury Elicits Hyperconnectivity in Core Subnetworks , 2014, PloS one.

[50]  Lisa M Shin,et al.  Functional neuroimaging studies of post-traumatic stress disorder , 2011, Expert review of neurotherapeutics.

[51]  Talma Hendler,et al.  Stress‐induced reduction in hippocampal volume and connectivity with the ventromedial prefrontal cortex are related to maladaptive responses to stressful military service , 2013, Human brain mapping.

[52]  R. Bluhm,et al.  Default mode network connectivity as a predictor of post‐traumatic stress disorder symptom severity in acutely traumatized subjects , 2010, Acta psychiatrica Scandinavica.

[53]  Itamar Kahn,et al.  Imbalanced neural responsivity to risk and reward indicates stress vulnerability in humans. , 2013, Cerebral cortex.

[54]  David W Wright,et al.  Position statement: definition of traumatic brain injury. , 2010, Archives of physical medicine and rehabilitation.

[55]  Richard Coppola,et al.  Evoked amygdala responses to negative faces revealed by adaptive MEG beamformers , 2008, Brain Research.

[56]  Yanling Yin,et al.  EEG default mode network in the human brain: Spectral regional field powers , 2008, NeuroImage.

[57]  S. Orr,et al.  Neurocognitive function in monozygotic twins discordant for combat exposure: relationship to posttraumatic stress disorder. , 2006, Journal of abnormal psychology.

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

[59]  Arne D. Ekstrom,et al.  Multiple interacting brain areas underlie successful spatiotemporal memory retrieval in humans , 2014, Scientific Reports.

[60]  Linda Douw,et al.  Disturbed functional brain networks and neurocognitive function in low-grade glioma patients: a graph theoretical analysis of resting-state MEG , 2009, Nonlinear biomedical physics.

[61]  Guillén Fernández,et al.  Persistent and reversible consequences of combat stress on the mesofrontal circuit and cognition , 2012, Proceedings of the National Academy of Sciences.

[62]  Talma Hendler,et al.  Human vulnerability to stress depends on amygdala's predisposition and hippocampal plasticity , 2009, Proceedings of the National Academy of Sciences.

[63]  Erik A. Wing,et al.  Hippocampal Contributions to the Large‐Scale Episodic Memory Network Predict Vivid Visual Memories , 2017, Cerebral cortex.

[64]  Christian Grillon,et al.  Distinct contributions of human hippocampal theta to spatial cognition and anxiety , 2012, Hippocampus.

[65]  A P Georgopoulos,et al.  Post-traumatic stress disorder: a right temporal lobe syndrome? , 2010, Journal of neural engineering.

[66]  Paul J. Laurienti,et al.  Comparison of characteristics between region-and voxel-based network analyses in resting-state fMRI data , 2010, NeuroImage.

[67]  M. Shenton,et al.  Clarifying the Origin of Biological Abnormalities in PTSD Through the Study of Identical Twins Discordant for Combat Exposure , 2006, Annals of the New York Academy of Sciences.

[68]  Krish D. Singh,et al.  A new approach to neuroimaging with magnetoencephalography , 2005, Human brain mapping.

[69]  Robert Oostenveld,et al.  An improved index of phase-synchronization for electrophysiological data in the presence of volume-conduction, noise and sample-size bias , 2011, NeuroImage.

[70]  Theiler,et al.  Generating surrogate data for time series with several simultaneously measured variables. , 1994, Physical review letters.

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

[72]  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.

[73]  Cornelis J Stam,et al.  Graph theoretical analysis of complex networks in the brain , 2007, Nonlinear biomedical physics.

[74]  R. N. Spreng,et al.  eview eurocircuitry models of posttraumatic stress disorder and beyond : meta-analysis of functional neuroimaging studies , 2012 .