White matter diffusion magnetic resonance imaging of brain white matter tracts relevant to working memory in three age groups of individuals at genetic-high risk for schizophrenia

Brynn Vessey, BS

Brigham and Women’s Hospital
White matter diffusion magnetic resonance imaging of brain white matter tracts relevant to working memory in three age groups of individuals at genetic-high risk for schizophrenia

Scientific Abstract

Background: The relationship between cognitive pathologies of schizophrenia (SZ) and structural abnormalities in white matter (WM) is poorly understood. Microstructural abnormalities in WM are linked to deficits in working memory both in SZ patients, as well as those at high-risk for SZ. One such population is the genetic-high risk (GHR) population, composed of asymptomatic family members of SZ patients. The GHR population provides a way to study developmental changes in WM that may be associated with risk for SZ without the confounds of the disease. The current study aims to understand better changes in WM development in GHR subjects that may lead to impairments in working memory. To do so, three extant diffusion magnetic resonance datasets of GHR individuals over the developmental trajectory were analyzed, with a focus on 2 WM tracts implicated in working memory: the cingulum bundle (CB) and the superior longitudinal fasciculus-ii (SLF-ii).

Methods: Two datasets of 3T diffusion-weighted images of children ages 7 to 12 (24 HC and 16 GHR) and young adults ages 19 to 29 (26 HC and 43 GHR) were collected at the Massachusetts Institute of Technology. A third dataset of 3T images of toddlers aged 2 (35 HC and 18 GHR) was collected at the University of North Carolina Chapel Hill. Whole brain two-tensor tractography was performed on the WM tracts of interest. Tracts were extracted utilizing an atlas-guided fiber clustering algorithm. Fractional anisotropy of the tissue (FAt) between GHR and HCs for each WM tract were calculated.

Results: Results are still being generated. We expect to demonstrate that GHR individuals have abnormal maturation of the CB and SLF-ii tracts in comparison to HC. Group differences in the CB or SLF-ii in the toddler dataset are not expected.

Conclusion: We hope to demonstrate that the CB and SLF-ii show alterations in the GHR populations beginning as early as childhood and extending through young adulthood when compared to HC. This would provide evidence that abnormal maturation of WM may be a risk factor for SZ. Future analyses will include an exploration between working memory performance and WM tract measures in each cohort.

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research Areas

Authors

BE Vessey, BS, N Somes, BS, F Zhang, PhD, J Robertson, MS, LJ O’Donnell, PhD, ME Shenton, PhD, Y Rathi, PhD, O Pasternak, PhD, R Mesholam-Gately, PhD J Wojcik, PhD, B Brent, MD, H Thermenos, PhD, S Whitfield-Gabrieli, PhD, J Gabrieli, PhD MS Keshavan, MD, L DeLisi, MD, JH Gilmore, MD, LJ Seidman, PhD, M Kubicki, MD, PhD, AE Lyall, PhD

Principal Investigator

Amanda Lyall, PhD