Browsing by Author "Bouix, Sylvain"

Now showing 1 - 6 of 6
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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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    Cell type-specific manifestations of cortical thickness heterogeneity in schizophrenia
    (Springer Nature, 2022) Di Biase, Maria A.; Geaghan, Michael P.; Reay, William R.; Seidlitz, Jakob; Weickert, Cynthia Shannon; Pébay, Alice; Green, Melissa J.; Quidé, Yann; Atkins, Joshua R.; Coleman, Michael J.; Bouix, Sylvain; Knyazhanskaya, Evdokiya E.; Lyall, Amanda E.; Pasternak, Ofer; Kubicki, Marek; Rathi, Yogesh; Visco, Andrew; Gaunnac, Megan; Lv, Jinglei; Mesholam-Gately, Raquelle I.; Lewandowski, Kathryn E.; Holt, Daphne J.; Keshavan, Matcheri S.; Pantelis, Christos; Öngür, Dost; Breier, Alan; Cairns, Murray J.; Shenton, Martha E.; Zalesky, Andrew; Psychiatry, School of Medicine
    Brain morphology differs markedly between individuals with schizophrenia, but the cellular and genetic basis of this heterogeneity is poorly understood. Here, we sought to determine whether cortical thickness (CTh) heterogeneity in schizophrenia relates to interregional variation in distinct neural cell types, as inferred from established gene expression data and person-specific genomic variation. This study comprised 1849 participants in total, including a discovery (140 cases and 1267 controls) and a validation cohort (335 cases and 185 controls). To characterize CTh heterogeneity, normative ranges were established for 34 cortical regions and the extent of deviation from these ranges was measured for each individual with schizophrenia. CTh deviations were explained by interregional gene expression levels of five out of seven neural cell types examined: (1) astrocytes; (2) endothelial cells; (3) oligodendrocyte progenitor cells (OPCs); (4) excitatory neurons; and (5) inhibitory neurons. Regional alignment between CTh alterations with cell type transcriptional maps distinguished broad patient subtypes, which were validated against genomic data drawn from the same individuals. In a predominantly neuronal/endothelial subtype (22% of patients), CTh deviations covaried with polygenic risk for schizophrenia (sczPRS) calculated specifically from genes marking neuronal and endothelial cells (r = -0.40, p = 0.010). Whereas, in a predominantly glia/OPC subtype (43% of patients), CTh deviations covaried with sczPRS calculated from glia and OPC-linked genes (r = -0.30, p = 0.028). This multi-scale analysis of genomic, transcriptomic, and brain phenotypic data may indicate that CTh heterogeneity in schizophrenia relates to inter-individual variation in cell-type specific functions. Decomposing heterogeneity in relation to cortical cell types enables prioritization of schizophrenia subsets for future disease modeling efforts.
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    Evaluating Acquisition Time of rfMRI in the Human Connectome Project for Early Psychosis. How Much Is Enough?
    (Springer, 2017-09) Bouix, Sylvain; Swago, Sophia; West, John D.; Pasternak, Ofer; Breier, Alan; Shenton, Martha E.; Radiology and Imaging Sciences, School of Medicine
    Resting-state functional MRI (rfMRI) correlates activity across brain regions to identify functional connectivity networks. The Human Connectome Project (HCP) for Early Psychosis has adopted the protocol of the HCP Lifespan Project, which collects 20 min of rfMRI data. However, because it is difficult for psychotic patients to remain in the scanner for long durations, we investigate here the reliability of collecting less than 20 min of rfMRI data. Varying durations of data were taken from the full datasets of 11 subjects. Correlation matrices derived from varying amounts of data were compared using the Bhattacharyya distance, and the reliability of functional network ranks was assessed using the Friedman test. We found that correlation matrix reliability improves steeply with longer windows of data up to 11–12 min, and ≥14 min of data produces correlation matrices within the variability of those produced by 18 min of data. The reliability of network connectivity rank increases with increasing durations of data, and qualitatively similar connectivity ranks for ≥10 min of data indicates that 10 min of data can still capture robust information about network connectivities.
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    Neurocognitive markers of childhood abuse in individuals with PTSD: Findings from the INTRuST Clinical Consortium
    (Elsevier, 2020-02-01) Bomyea, Jessica; Simmons, Alan N.; Shenton, Martha E.; Coleman, Michael J.; Bouix, Sylvain; Rathi, Yogesh; Pasternak, Ofer; Coimbra, Raul; Shutter, Lori; George, Mark S.; Grant, Gerald; Zafonte, Ross D.; McAllister, Thomas W.; Stein, Murray B.; Psychiatry, School of Medicine
    To date, few studies have evaluated the contribution of early life experiences to neurocognitive abnormalities observed in posttraumatic stress disorder (PTSD). Childhood maltreatment is common among individuals with PTSD and is thought to catalyze stress-related biobehavioral changes that might impact both brain structure and function in adulthood. The current study examined differences in brain morphology (brain volume, cortical thickness) and neuropsychological performance in individuals with PTSD characterized by low or high self-reported childhood maltreatment, compared with healthy comparison participants. Data were drawn from the INjury and TRaUmatic STress (INTRuST) Clinical Consortium imaging repository, which contains MRI and self-report data for individuals classified as PTSD positive (with and without a history of mild traumatic brain injury [mTBI]), individuals with mTBI only, and healthy comparison participants. The final sample included 36 individuals with PTSD without childhood maltreatment exposure (PTSD, n = 30 with mTBI), 31 individuals with PTSD and childhood maltreatment exposure (PTSD + M, n = 26 with mTBI), and 114 healthy comparison participants without history of childhood maltreatment exposure (HC). The PTSD + M and PTSD groups demonstrated cortical thinning in prefrontal and occipital regions, and poorer verbal memory and processing speed compared to the HC group. PTSD + M participants demonstrated cortical thinning in frontal and cingulate regions, and poorer executive functioning relative to the PTSD and HC groups. Thus, neurocognitive features varied between individuals with PTSD who did versus did not have exposure to childhood maltreatment, highlighting the need to assess developmental history of maltreatment when examining biomarkers in PTSD.
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    Robust Brain Correlates of Cognitive Performance in Psychosis and Its Prodrome
    (Elsevier, 2025) Ward, Heather Burrell; Beermann, Adam; Xie, Jing; Yildiz, Gulcan; Felix, Karlos Manzanarez; Addington, Jean; Bearden, Carrie E.; Cadenhead, Kristin; Cannon, Tyrone D.; Cornblatt, Barbara; Keshavan, Matcheri; Mathalon, Daniel; Perkins, Diana O.; Seidman, Larry; Stone, William S.; Tsuang, Ming T.; Walker, Elaine F.; Woods, Scott; Coleman, Michael J.; Bouix, Sylvain; Holt, Daphne J.; Öngür, Dost; Breier, Alan; Shenton, Martha E.; Heckers, Stephan; Halko, Mark A.; Lewandowski, Kathryn E.; Brady, Roscoe O., Jr.; Psychiatry, School of Medicine
    Background: Neurocognitive impairment is a well-known phenomenon in schizophrenia that begins prior to psychosis onset. Connectome-wide association studies have inconsistently linked cognitive performance to resting-state functional magnetic resonance imaging. We hypothesized that a carefully selected cognitive instrument and refined population would allow identification of reliable brain-behavior associations with connectome-wide association studies. To test this hypothesis, we first identified brain-cognition correlations via a connectome-wide association study in early psychosis. We then asked, in an independent dataset, if these brain-cognition relationships would generalize to individuals who develop psychosis in the future. Methods: The Seidman Auditory Continuous Performance Task (ACPT) effectively differentiates healthy participants from those with psychosis. Our connectome-wide association study used the HCP-EP (Human Connectome Project for Early Psychosis) (n = 183) to identify links between connectivity and ACPT performance. We then analyzed data from the NAPLS2 (North American Prodrome Longitudinal Study 2) (n = 345), a multisite prospective study of individuals at risk for psychosis. We tested the connectome-wide association study-identified cognition-connectivity relationship in both individuals at risk for psychosis and control participants. Results: Our connectome-wide association study in early-course psychosis identified robust associations between better ACPT performance and higher prefrontal-somatomotor connectivity (p < .005). Prefrontal-somatomotor connectivity was also related to ACPT performance in at-risk individuals who would develop psychosis (n = 17). This finding was not observed in nonconverters (n = 196) or control participants (n = 132). Conclusions: This connectome-wide association study identified reproducible links between connectivity and cognition in separate samples of individuals with psychosis and at-risk individuals who would later develop psychosis. A carefully selected task and population improves the ability of connectome-wide association studies to identify reliable brain-phenotype relationships.
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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.