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Genetic contributions to changes of fiber tracts of ventral visual stream in 22q11.2 deletion syndrome

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Abstract

Patients with 22q11.2 deletion syndrome (22q11.2DS) represent a population at high risk for developing schizophrenia, as well as learning disabilities. Deficits in visuo-spatial memory are thought to underlie some of the cognitive disabilities. Neuronal substrates of visuo-spatial memory include the inferior fronto-occipital fasciculus (IFOF) and the inferior longitudinal fasciculus (ILF), two tracts that comprise the ventral visual stream. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) is an established method to evaluate white matter (WM) connections in vivo. DT-MRI scans of nine 22q11.2DS young adults and nine matched healthy subjects were acquired. Tractography of the IFOF and the ILF was performed. DT-MRI indices, including Fractional anisotropy (FA, measure of WM changes), axial diffusivity (AD, measure of axonal changes) and radial diffusivity (RD, measure of myelin changes) of each of the tracts and each group were measured and compared. The 22q11.2DS group showed statistically significant reductions of FA in IFOF in the left hemisphere. Additionally, reductions of AD were found in the IFOF and the ILF in both hemispheres. These findings might be the consequence of axonal changes, which is possibly due to fewer, thinner, or less organized fibers. No changes in RD were detected in any of the tracts delineated, which is in contrast to findings in schizophrenia patients where increases in RD are believed to be indicative of demyelination. We conclude that reduced axonal changes may be key to understanding the underlying pathology of WM leading to the visuo-spatial phenotype in 22q11.2DS.

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Acknowledgments

We thank Dr. F. Jolesz for funding the scans, Andrew Hyatt for drawing ROIs for the purpose of reliability measurements for the tractography method and the BWH Center for Clinical Investigation for statistical consultation.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This work was supported by a Brain and Behavior Research Foundation (formerly called NARSAD) (Young Investigator Award to ZK); by the US Department of Veterans Affairs (Merit Awards to MES), (Schizophrenia Center to MES); and by National Institute of Health (Career Reentry Supplement to ZK on MH 50740 to MES), (MH 070047 to MES), (MH 080272 to MES and to MK), (RO1 MH082918 to SB)(U54 EB005149 to RK, to MK, to MES); (NAC P41 RR 13218 to RK).

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Authors and Affiliations

  1. Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, 1249 Boylston Street, Boston, MA, 02115, USA

    Zora Kikinis, Nikos Makris, Sylvain Bouix, Diandra Lucia, Michael J. Coleman, Martha E. Shenton & Marek Kubicki

  2. Psychiatry and Neurology Departments, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Nikos Makris

  3. Department of Psychiatry, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA

    Christine T. Finn

  4. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Erica Tworog-Dube

  5. Surgical Planning Laboratory, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Ron Kikinis & Martha E. Shenton

  6. Department of Genetics, Harvard Medical School, Boston, MA, USA

    Raju Kucherlapati

  7. Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System, Harvard Medical School, Brockton, MA, USA

    Martha E. Shenton & Marek Kubicki

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  1. Zora Kikinis
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Correspondence to Zora Kikinis.

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Kikinis, Z., Makris, N., Finn, C.T. et al. Genetic contributions to changes of fiber tracts of ventral visual stream in 22q11.2 deletion syndrome. Brain Imaging and Behavior 7, 316–325 (2013). https://doi.org/10.1007/s11682-013-9232-5

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