Browsing by Author "Koerte, Inga K."

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    Adverse Outcome Following Mild Traumatic Brain Injury Is Associated with Microstructure Alterations at the Gray and White Matter Boundary
    (MDPI, 2023-08-21) Pankatz, Lara; Rojczyk, Philine; Seitz-Holland, Johanna; Bouix, Sylvain; Jung, Leonard B.; Wiegand, Tim L. T.; Bonke, Elena M.; Sollmann, Nico; Kaufmann, Elisabeth; Carrington, Holly; Puri, Twishi; Rathi, Yogesh; Coleman, Michael J.; Pasternak, Ofer; George, Mark S.; McAllister, Thomas W.; Zafonte, Ross; Stein, Murray B.; Marx, Christine E.; Shenton, Martha E.; Koerte, Inga K.; Psychiatry, School of Medicine
    The gray matter/white matter (GM/WM) boundary of the brain is vulnerable to shear strain associated with mild traumatic brain injury (mTBI). It is, however, unknown whether GM/WM microstructure is associated with long-term outcomes following mTBI. The diffusion and structural MRI data of 278 participants between 18 and 65 years of age with and without military background from the Department of Defense INTRuST study were analyzed. Fractional anisotropy (FA) was extracted at the GM/WM boundary across the brain and for each lobe. Additionally, two conventional analytic approaches were used: whole-brain deep WM FA (TBSS) and whole-brain cortical thickness (FreeSurfer). ANCOVAs were applied to assess differences between the mTBI cohort (n = 147) and the comparison cohort (n = 131). Associations between imaging features and post-concussive symptom severity, and functional and cognitive impairment were investigated using partial correlations while controlling for mental health comorbidities that are particularly common among military cohorts and were present in both the mTBI and comparison group. Findings revealed significantly lower whole-brain and lobe-specific GM/WM boundary FA (p < 0.011), and deep WM FA (p = 0.001) in the mTBI cohort. Whole-brain and lobe-specific GM/WM boundary FA was significantly negatively correlated with post-concussive symptoms (p < 0.039), functional (p < 0.016), and cognitive impairment (p < 0.049). Deep WM FA was associated with functional impairment (p = 0.002). Finally, no significant difference was observed in cortical thickness, nor between cortical thickness and outcome (p > 0.05). Findings from this study suggest that microstructural alterations at the GM/WM boundary may be sensitive markers of adverse long-term outcomes following mTBI.
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    Age‐dependent white matter disruptions after military traumatic brain injury: Multivariate analysis results from ENIGMA brain injury
    (Wiley, 2022) Bouchard, Heather C.; Sun, Delin; Dennis, Emily L.; Newsome, Mary R.; Disner, Seth G.; Elman, Jeremy; Silva, Annelise; Velez, Carmen; Irimia, Andrei; Davenport, Nicholas D.; Sponheim, Scott R.; Franz, Carol E.; Kremen, William S.; Coleman, Michael J.; Williams, M. Wright; Geuze, Elbert; Koerte, Inga K.; Shenton, Martha E.; Adamson, Maheen M.; Coimbra, Raul; Grant, Gerald; Shutter, Lori; George, Mark S.; Zafonte, Ross D.; McAllister, Thomas W.; Stein, Murray B.; Thompson, Paul M.; Wilde, Elisabeth A.; Tate, David F.; Sotiras, Aristeidis; Morey, Rajendra A.; Psychiatry, School of Medicine
    Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age‐related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non‐negative matrix factorization (NMF) is a data‐driven approach that detects covarying patterns (components) within high‐dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self‐reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta‐Analysis) Military Brain Injury working group. Regressions were used to examine TBI‐ and mTBI‐related associations in NMF‐derived components while adjusting for age, sex, post‐traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age‐dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q < 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age‐dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans.
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    White Matter Microstructure Is Associated with Serum Neuroactive Steroids and Psychological Functioning
    (Mary Ann Liebert, 2023) Umminger, Lisa F.; Rojczyk, Philine; Seitz-Holland, Johanna; Sollmann, Nico; Kaufmann, Elisabeth; Kinzel, Philipp; Zhang, Fan; Kochsiek, Janna; Langhein, Mina; Kim, Cara L.; Wiegand, Tim L. T.; Kilts, Jason D.; Naylor, Jennifer C.; Grant, Gerald A.; Rathi, Yogesh; Coleman, Michael J.; Bouix, Sylvain; Tripodis, Yorghos; Pasternak, Ofer; George, Mark S.; McAllister, Thomas W.; Zafonte, Ross; Stein, Murray B.; O'Donnell, Lauren J.; Marx, Christine E.; Shenton, Martha E.; Koerte, Inga K.; Psychiatry, School of Medicine
    Military service members are at increased risk for mental health issues, and comorbidity with mild traumatic brain injury (mTBI) is common. Largely overlapping symptoms between conditions suggest a shared pathophysiology. The present work investigates the associations among white matter microstructure, psychological functioning, and serum neuroactive steroids that are part of the stress-response system. Diffusion-weighted brain imaging was acquired from 163 participants (with and without military affiliation) and free-water-corrected fractional anisotropy (FAT) was extracted. Associations between serum neurosteroid levels of allopregnanolone (ALLO) and pregnenolone (PREGNE), psychological functioning, and whole-brain white matter microstructure were assessed using regression models. Moderation models tested the effect of mTBI and comorbid post-traumatic stress disorder (PTSD) and mTBI on these associations. ALLO is associated with whole-brain white matter FAT (β = 0.24, t = 3.05, p = 0.006). This association is significantly modulated by PTSD+mTBI comorbidity (β = 0.00, t = 2.50, p = 0.027), although an mTBI diagnosis alone did not significantly impact this association (p = 0.088). There was no significant association between PREGNE and FAT (p = 0.380). Importantly, lower FAT is associated with poor psychological functioning (β = -0.19, t = -2.35, p = 0.020). This study provides novel insight into a potential common pathophysiological mechanism of neurosteroid dysregulation underlying the high risk for mental health issues in military service members. Further, comorbidity of PTSD and mTBI may bring the compensatory effects of the brain's stress response to their limit. Future research is needed to investigate whether neurosteroid regulation may be a promising tool for restoring brain health and improving psychological functioning.