Associations of mTBI and post-traumatic stress to amygdala structure and functional connectivity in military Service Members

Introduction Traumatic brain injury (TBI) is one of the highest public health priorities, especially among military personnel where comorbidity with post-traumatic stress symptoms and resulting consequences is high. Brain injury and post-traumatic stress symptoms are both characterized by dysfunctional brain networks, with the amygdala specifically implicated as a region with both structural and functional abnormalities. Methods This study examined the structural volumetrics and resting state functional connectivity of 68 Active Duty Service Members with or without chronic mild TBI (mTBI) and comorbid symptoms of Post-Traumatic Stress (PTS). Results and discussion Structural analysis of the amygdala revealed no significant differences in volume between mTBI and healthy comparison participants with and without post-traumatic stress symptoms. Resting state functional connectivity with bilateral amygdala revealed decreased anterior network connectivity and increased posterior network connectivity in the mTBI group compared to the healthy comparison group. Within the mTBI group, there were significant regions of correlation with amygdala that were modulated by PTS severity, including networks implicated in emotional processing and executive functioning. An examination of a priori regions of amygdala connectivity in the default mode network, task positive network, and subcortical structures showed interacting influences of TBI and PTS, only between right amygdala and right putamen. These results suggest that mTBI and PTS are associated with hypo-frontal and hyper-posterior amygdala connectivity. Additionally, comorbidity of these conditions appears to compound these neural activity patterns. PTS in mTBI may change neural resource recruitment for information processing between the amygdala and other brain regions and networks, not only during emotional processing, but also at rest.

[1]  Danielle C. Mathersul,et al.  Emotion dysregulation and heart rate variability improve in US veterans undergoing treatment for posttraumatic stress disorder: Secondary exploratory analyses from a randomised controlled trial , 2022, BMC Psychiatry.

[2]  R. Raghupathi,et al.  A Role for the Amygdala in Impairments of Affective Behaviors Following Mild Traumatic Brain Injury , 2021, Frontiers in Behavioral Neuroscience.

[3]  E. Bigler Volumetric MRI Findings in Mild Traumatic Brain Injury (mTBI) and Neuropsychological Outcome , 2021, Neuropsychology Review.

[4]  Xiao Chen,et al.  Aberrant Correlation Between the Default Mode and Salience Networks in Mild Traumatic Brain Injury , 2020, Frontiers in Computational Neuroscience.

[5]  C. Cullum,et al.  Sex Differences and Reporting of SCAT-5 Concussion Symptoms in Adolescent Athletes , 2020, Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine.

[6]  Roland R. Lee,et al.  Brain Amygdala Volume Increases in Veterans and Active-Duty Military Personnel With Combat-Related Posttraumatic Stress Disorder and Mild Traumatic Brain Injury , 2020, The Journal of head trauma rehabilitation.

[7]  J. Kelly,et al.  White Matter and Cognition in Traumatic Brain Injury. , 2018, Journal of Alzheimer's disease : JAD.

[8]  Timothy J. McDermott,et al.  Veterans with PTSD demonstrate amygdala hyperactivity while viewing threatening faces: A MEG study , 2018, Biological Psychology.

[9]  D. Rueckert,et al.  Regional brain morphometry in patients with traumatic brain injury based on acute- and chronic-phase magnetic resonance imaging , 2017, PloS one.

[10]  E. Elbogen,et al.  Traumatic Brain Injury in Iraq and Afghanistan Veterans: New Results From a National Random Sample Study. , 2017, The Journal of neuropsychiatry and clinical neurosciences.

[11]  Terence M Keane,et al.  Psychometric properties of the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (PCL-5) in veterans. , 2016, Psychological assessment.

[12]  R. Lanius,et al.  Unique insula subregion resting-state functional connectivity with amygdala complexes in posttraumatic stress disorder and its dissociative subtype , 2016, Psychiatry Research: Neuroimaging.

[13]  E. Liemburg,et al.  Brain network dysregulation, emotion, and complaints after mild traumatic brain injury , 2016, Human brain mapping.

[14]  Miranda Olff,et al.  Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder , 2016, Neuropsychopharmacology.

[15]  K. Russell,et al.  Psychiatric outcomes after pediatric sports-related concussion. , 2015, Journal of neurosurgery. Pediatrics.

[16]  Rao P. Gullapalli,et al.  Disruptions in Resting State Functional Connectivity and Cerebral Blood Flow in Mild Traumatic Brain Injury Patients , 2015, PloS one.

[17]  J. Harp,et al.  Exploring the Relationship Between Mild Traumatic Brain Injury Exposure and the Presence and Severity of Postconcussive Symptoms Among Veterans Deployed to Iraq and Afghanistan , 2015, PM & R : the journal of injury, function, and rehabilitation.

[18]  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.

[19]  Kristine Yaffe,et al.  Epidemiology of mild traumatic brain injury and neurodegenerative disease , 2015, Molecular and Cellular Neuroscience.

[20]  Wei Liu,et al.  Exploring Variations in Functional Connectivity of the Resting State Default Mode Network in Mild Traumatic Brain Injury , 2015, Brain Connect..

[21]  D. Salat,et al.  Close‐range blast exposure is associated with altered functional connectivity in Veterans independent of concussion symptoms at time of exposure , 2014, Human brain mapping.

[22]  William P. Milberg,et al.  Deployment-related psychiatric and behavioral conditions and their association with functional disability in OEF/OIF/OND veterans. , 2015, Journal of traumatic stress.

[23]  W. Milberg,et al.  Correspondence of the Boston Assessment of Traumatic Brain Injury-Lifetime (BAT-L) Clinical Interview and the VA TBI Screen , 2015, The Journal of head trauma rehabilitation.

[24]  S. Cappa,et al.  Brain connectivity in neurodegenerative diseases—from phenotype to proteinopathy , 2014, Nature Reviews Neurology.

[25]  Rebecca J. Theilmann,et al.  Voxel-wise resting-state MEG source magnitude imaging study reveals neurocircuitry abnormality in active-duty service members and veterans with PTSD , 2014, NeuroImage: Clinical.

[26]  Min Yang,et al.  Validation of the Headache Impact Test (HIT-6) in patients with chronic migraine , 2014, Health and Quality of Life Outcomes.

[27]  R. Wennberg,et al.  Is there evidence for neurodegenerative change following traumatic brain injury in children and youth? A scoping review , 2014, Front. Hum. Neurosci..

[28]  M. Banich,et al.  Reduced Amygdala Volume Is Associated with Deficits in Inhibitory Control: A Voxel- and Surface-Based Morphometric Analysis of Comorbid PTSD/Mild TBI , 2014, BioMed research international.

[29]  D. Tate,et al.  Preliminary findings of cortical thickness abnormalities in blast injured service members and their relationship to clinical findings , 2014, Brain Imaging and Behavior.

[30]  Oz Malkesman,et al.  Traumatic Brain Injury – Modeling Neuropsychiatric Symptoms in Rodents , 2013, Front. Neurol..

[31]  E. Bigler Traumatic brain injury and cognitive reserve , 2013 .

[32]  E. Bigler Traumatic brain injury, neuroimaging, and neurodegeneration , 2012, Front. Hum. Neurosci..

[33]  Janice R. Kuo,et al.  Amygdala volume in combat-exposed veterans with and without posttraumatic stress disorder: a cross-sectional study. , 2012, Archives of general psychiatry.

[34]  Bruce Fischl,et al.  Within-subject template estimation for unbiased longitudinal image analysis , 2012, NeuroImage.

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

[36]  M. Stevens,et al.  Multiple resting state network functional connectivity abnormalities in mild traumatic brain injury , 2012, Brain Imaging and Behavior.

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

[38]  Timothy E. Ham,et al.  Investigating white matter injury after mild traumatic brain injury. , 2011, Current opinion in neurology.

[39]  I. Liberzon,et al.  The Neurocircuitry of Fear, Stress, and Anxiety Disorders , 2011, Neuropsychopharmacology.

[40]  Min Yang,et al.  Validation of the Headache Impact Test (HIT-6™) across episodic and chronic migraine , 2011, Cephalalgia : an international journal of headache.

[41]  Bruce Fischl,et al.  Highly accurate inverse consistent registration: A robust approach , 2010, NeuroImage.

[42]  Murray B Stein,et al.  Exploring the convergence of posttraumatic stress disorder and mild traumatic brain injury. , 2009, The American journal of psychiatry.

[43]  J. Corrigan,et al.  Reliability and Predictive Validity of the Ohio State University TBI Identification Method With Prisoners , 2009, The Journal of head trauma rehabilitation.

[44]  Daniel S. Margulies,et al.  Functional connectivity of the human amygdala using resting state fMRI , 2009, NeuroImage.

[45]  D. Warden,et al.  Traumatic Brain Injury Screening: Preliminary Findings in a US Army Brigade Combat Team , 2009, The Journal of head trauma rehabilitation.

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

[47]  J. Corrigan,et al.  Initial Reliability and Validity of the Ohio State University TBI Identification Method , 2007, The journal of head trauma rehabilitation.

[48]  Bruce Fischl,et al.  Geometrically Accurate Topology-Correction of Cortical Surfaces Using Nonseparating Loops , 2007, IEEE Transactions on Medical Imaging.

[49]  Jocelyne Bachevalier,et al.  Hippocampus, amygdala, and basal ganglia morphometrics in children after moderate‐to‐severe traumatic brain injury , 2007, Developmental medicine and child neurology.

[50]  Charles Marmar,et al.  Bringing the war back home: mental health disorders among 103,788 US veterans returning from Iraq and Afghanistan seen at Department of Veterans Affairs facilities. , 2007, Archives of internal medicine.

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

[52]  L. Heimer,et al.  The limbic lobe and its output channels: Implications for emotional functions and adaptive behavior , 2006, Neuroscience & Biobehavioral Reviews.

[53]  D. Charney,et al.  Neurobiology of anxiety disorders and implications for treatment. , 2006, The Mount Sinai journal of medicine, New York.

[54]  Anders M. Dale,et al.  Reliability of MRI-derived measurements of human cerebral cortical thickness: The effects of field strength, scanner upgrade and manufacturer , 2006, NeuroImage.

[55]  S. Rauch,et al.  Amygdala, Medial Prefrontal Cortex, and Hippocampal Function in PTSD , 2006, Annals of the New York Academy of Sciences.

[56]  Anders M. Dale,et al.  Reliability in multi-site structural MRI studies: Effects of gradient non-linearity correction on phantom and human data , 2006, NeuroImage.

[57]  D. Yang,et al.  Alterations in cerebral perfusion in posttraumatic stress disorder patients without re-exposure to accident-related stimuli , 2006, Clinical Neurophysiology.

[58]  Matthew J. Barton,et al.  Neural Networks of Information Processing in Posttraumatic Stress Disorder: A Functional Magnetic Resonance Imaging Study , 2005, Biological Psychiatry.

[59]  Anders M. Dale,et al.  Sequence-independent segmentation of magnetic resonance images , 2004, NeuroImage.

[60]  A. M. Dale,et al.  A hybrid approach to the skull stripping problem in MRI , 2004, NeuroImage.

[61]  Darin D Dougherty,et al.  Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. , 2004, Archives of general psychiatry.

[62]  A. Dowson,et al.  A six-item short-form survey for measuring headache impact: The HIT-6™ , 2003, Quality of Life Research.

[63]  Ravi S. Menon,et al.  Brain activation during script-driven imagery induced dissociative responses in PTSD: a functional magnetic resonance imaging investigation , 2002, Biological Psychiatry.

[64]  A. Dale,et al.  Whole Brain Segmentation Automated Labeling of Neuroanatomical Structures in the Human Brain , 2002, Neuron.

[65]  Stephen M. Smith,et al.  Temporal Autocorrelation in Univariate Linear Modeling of FMRI Data , 2001, NeuroImage.

[66]  A M Dale,et al.  Measuring the thickness of the human cerebral cortex from magnetic resonance images. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[67]  R. F. Muzic,et al.  Higher Brain Blood Flow at Amygdala and Lower Frontal Cortex Blood Flow in PTSD Patients with Comorbid Cocaine and Alcohol Abuse Compared with Normals , 2000, Psychiatry.

[68]  A. Dale,et al.  Cortical Surface-Based Analysis II: Inflation, Flattening, and a Surface-Based Coordinate System , 1999, NeuroImage.

[69]  Anders M. Dale,et al.  Cortical Surface-Based Analysis I. Segmentation and Surface Reconstruction , 1999, NeuroImage.

[70]  Alan C. Evans,et al.  A nonparametric method for automatic correction of intensity nonuniformity in MRI data , 1998, IEEE Transactions on Medical Imaging.

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

[72]  A. Dale,et al.  Improved Localizadon of Cortical Activity by Combining EEG and MEG with MRI Cortical Surface Reconstruction: A Linear Approach , 1993, Journal of Cognitive Neuroscience.

[73]  B. Levander,et al.  Computer Tomography of the Brain and Spectrophotometry of the CSF in Cerebral Concussion and Contusion , 1978, Acta radiologica: diagnosis.

[74]  M. Lipton,et al.  Neuroimaging in Blast-Related Mild Traumatic Brain Injury , 2017, The Journal of head trauma rehabilitation.

[75]  Wei Liu,et al.  Assessing the Impact of Post-Traumatic Stress Symptoms on the Resting-State Default Mode Network in a Military Chronic Mild Traumatic Brain Injury Sample , 2017, Brain Connect..

[76]  Gregory McCarthy,et al.  Altered Resting-State Functional Connectivity of Basolateral and Centromedial Amygdala Complexes in Posttraumatic Stress Disorder , 2014, Neuropsychopharmacology.

[77]  C. Sripada,et al.  The functional neuroanatomy of PTSD: a critical review. , 2008, Progress in brain research.

[78]  M. Jenkinson Non-linear registration aka Spatial normalisation , 2007 .

[79]  Nikos Makris,et al.  Automatically parcellating the human cerebral cortex. , 2004, Cerebral cortex.

[80]  Benedicto Crespo-Facorro,et al.  Major depression following traumatic brain injury. , 2004, Archives of general psychiatry.

[81]  Anders M. Dale,et al.  Automated manifold surgery: constructing geometrically accurate and topologically correct models of the human cerebral cortex , 2001, IEEE Transactions on Medical Imaging.

[82]  A. Dale,et al.  High‐resolution intersubject averaging and a coordinate system for the cortical surface , 1999, Human brain mapping.