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Heritability and reliability of automatically segmented human hippocampal formation subregions

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Date
2016
Author
Whelan, Christopher D.
Hibar, Derrek P.
van Velzen, Laura S.
Zannas, Anthony S.
Carrillo-Roa, Tania
McMahon, Katie
Prasad, Gautam
Kelly, Sinéad
Faskowitz, Joshua
deZubiracay, Greig
Iglesias, Juan E.
van Erp, Theo G.M.
Frodl, Thomas
Martin, Nicholas G.
Wright, Margaret J.
Jahanshad, Neda
Schmaal, Lianne
Sämann, Philipp G.
Thompson, Paul M.
for the Alzheimer's Disease Neuroimaging Initiative
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Christopher D. Whelan, Derrek P. Hibar, Laura S. van Velzen, Anthony S. Zannas, Tania Carrillo-Roa, Katie McMahon, Gautam Prasad, Sinéad Kelly, Joshua Faskowitz, Greig deZubiracay, Juan E. Iglesias, Theo G.M. van Erp, Thomas Frodl, Nicholas G. Martin, Margaret J. Wright, Neda Jahanshad, Lianne Schmaal, Philipp G. Sämann, Paul M. Thompson, Heritability and reliability of automatically segmented human hippocampal formation subregions, In NeuroImage, Volume 128, 2016, Pages 125-137, ISSN 1053-8119, https://doi.org/10.1016/j.neuroimage.2015.12.039.
URI
http://hdl.handle.net/10810/22694
Abstract
The human hippocampal formation can be divided into a set of cytoarchitecturally and functionally distinct subregions, involved in different aspects of memory formation. Neuroanatomical disruptions within these subregions are associated with several debilitating brain disorders including Alzheimer's disease, major depression, schizophrenia, and bipolar disorder. Multi-center brain imaging consortia, such as the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, are interested in studying disease effects on these subregions, and in the genetic factors that affect them. For large-scale studies, automated extraction and subsequent genomic association studies of these hippocampal subregionmeasuresmay provide additional insight. Here, we evaluated the test–retest reliability and transplatform reliability (1.5 T versus 3 T) of the subregion segmentationmodule in the FreeSurfer software package using three independent cohorts of healthy adults, one young (Queensland Twins Imaging Study, N= 39), another elderly (Alzheimer's Disease Neuroimaging Initiative, ADNI-2, N =163) and another mixed cohort of healthy and depressed participants (Max Planck Institute, MPIP,N=598).We also investigated agreement between themost recent version of this algorithm (v6.0) and an older version (v5.3), again using the ADNI-2 and MPIP cohorts in addition to a sample from the Netherlands Study for Depression and Anxiety (NESDA) (N=221). Finally, we estimated the heritability (h2) of the segmented subregion volumes using the full sample of young, healthy QTIM twins (N=728). Test–retest reliability was high for all twelve subregions in the 3 T ADNI-2 sample (intraclass correlation coefficient (ICC)=0.70–0.97) andmoderate-to-high in the 4 TQTIM sample (ICC=0.5–0.89). Transplatform reliabilitywas strong for eleven of the twelve subregions (ICC=0.66–0.96); however, the hippocampal fissure was not consistently reconstructed across 1.5 T and 3 T field strengths (ICC = 0.47–0.57). Between-version agreement was moderate for the hippocampal tail, subiculum and presubiculum (ICC = 0.78–0.84; Dice Similarity Coefficient (DSC)=0.55–0.70), and poor for all other subregions (ICC=0.34–0.81; DSC=0.28–0.51). All hippocampal subregion volumes were highly heritable (h2=0.67–0.91). Our findings indicate that eleven of the twelve human hippocampal subregions segmented using FreeSurfer version 6.0 may serve as reliable and informative quantitative phenotypes for future multi-site imaging genetics initiatives such as those of the ENIGMA consortium.
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