Bachelor of Science, University of New Mexico (2009)
Master of Science, University of New Mexico (2015)
Doctor of Philosophy, University of New Mexico (2017)
BACKGROUND: Gulf War illness (GWI) is a condition that affects about 30% of veterans who served in the 1990-91 Persian Gulf War. Given its broad symptomatic manifestation, including chronic pain, fatigue, neurological, gastrointestinal, respiratory, and skin problems, it is of interest to examine whether GWI is associated with changes in the brain. Existing neuroimaging studies, however, have been limited by small sample sizes, inconsistent GWI diagnosis criteria, and potential comorbidity confounds.OBJECTIVES: Using a large cohort of US veterans with GWI, we assessed regional brain volumes for their associations with GWI, and quantified the relationships between any regional volumetric changes and GWI symptoms.METHODS: Structural magnetic resonance imaging (MRI) scans from 111 veterans with GWI (Age=49±6, 88% Male) and 59 healthy controls (age=51±9, 78% male) were collected at the California War Related Illness and Injury Study Center (WRIISC-CA) and from a multicenter study of the Parkinson's Progression Marker Initiative (PPMI), respectively. Individual MRI volumes were segmented and parcellated using FreeSurfer. Regional volumes of 19 subcortical, 68 cortical, and 3 brainstem structures were evaluated in the GWI cohort relative to healthy controls. The relationships between regional volumes and GWI symptoms were also assessed.RESULTS: We found significant subcortical atrophy, but no cortical differences, in the GWI group relative to controls, with the largest effect detected in the brainstem, followed by the ventral diencephalon and the thalamus. In a subsample of 58 veterans with GWI who completed the Chronic Fatigue Scale (CFS) inventory of Centers for Disease Control and Prevention (CDC), smaller brainstem volumes were significantly correlated with increased severities of fatigue and depressive symptoms.CONCLUSION: The findings suggest that brainstem volume may be selectively affected by GWI, and that the resulting atrophy could in turn mediate or moderate GWI-related symptoms such as fatigue and depression. Consequently, the brain stem should be carefully considered in future research focusing on GWI pathology.
View details for DOI 10.1016/j.neuro.2020.02.006
View details for PubMedID 32081703
Evaluation of brainstem pathways with diffusion tensor imaging (DTI) and tractography may provide insights into pathophysiologies associated with dysfunction of key brainstem circuits. However, identification of these tracts has been elusive, with relatively few in vivo human studies to date. In this paper we proposed an automated approach for reconstructing nine brainstem fiber trajectories of pathways that might be involved in pain modulation. We first performed native-space manual tractography of these fiber tracts in a small normative cohort of participants and confirmed the anatomical precision of the results using existing anatomical literature. Second, region-of-interest pairs were manually defined at each extracted fiber's termini and nonlinearly warped to a standard anatomical brain template to create an atlas of the region-of-interest pairs. The resulting atlas was then transformed non-linearly into the native space of 17 veteran patients' brains for automated brainstem tractography. Lastly, we assessed the relationships between the integrity levels of the obtained fiber bundles and pain severity levels. Fractional anisotropy (FA) measures derived using automated tractography reflected the respective tracts' FA levels obtained via manual tractography. A significant inverse relationship between FA and pain levels was detected within the automatically derived dorsal and medial longitudinal fasciculi of the brainstem. This study demonstrates the feasibility of DTI in exploring brainstem circuitries involved in pain processing. In this context, the described automated approach is a viable alternative to the time-consuming manual tractography. The physiological and functional relevance of the measures derived from automated tractography is evidenced by their relationships with individual pain severities.
View details for DOI 10.1371/journal.pone.0213952
View details for PubMedID 32069284
Comparisons of white matter (WM) fractional anisotropy (FA) values between mild traumatic brain injury (mTBI) patients and controls have revealed inconsistencies in the directions of the resulting FA changes. To address these discrepancies, we examined hemispheric FA symmetry levels across WM tracts in 150 mTBI patients relative to 96 military controls. Automated fiber quantification was used to extract 18 WM tracts with 100 FA values, which were used to compute correlation strengths between the 9 bilateral tract pairs. The Fisher z-transformed Pearson's r values were entered into an analysis of covariance examining the effects of group (mTBI and controls) and age on symmetry levels within each tract pair. The mTBI group displayed lower symmetry levels in the cortico-spinal tract and the inferior longitudinal fasciculus. Interactions between age and group were detected in the inferior fronto-occipital (IFOF), uncinate (UF), and superior longitudinal fasciculi (SLF). A similar pattern emerged in the IFOF and the UF, revealing age-related symmetry decreases in the mTBI patients despite stable levels of symmetry across age in controls. In contrast, while the control group's symmetry levels actually increased with age in the SLF, no age-related symmetry changes were detected across the mTBI participants. Here we proposed WM symmetry measures as a potential means of circumventing directional inconsistencies of trauma-related FA changes, as well as capturing more within-tract and within-subject variances of DTI metrics. Further, we demonstrated the method's utility in detecting mTBI-specific effects and their associated interactions with age.
View details for DOI 10.1089/neu.2019.6487
View details for PubMedID 31595833
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