title: Heritability and reliability of automatically segmented human hippocampal formation subregions.
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 subregion measures may provide additional insight. Here, we evaluated the test-retest reliability and transplatform reliability (1.5T versus 3T) of the subregion segmentation module 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 the most 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 (h(2)) 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 3T ADNI-2 sample (intraclass correlation coefficient (ICC)=0.70-0.97) and moderate-to-high in the 4T QTIM sample (ICC=0.5-0.89). Transplatform reliability was strong for eleven of the twelve subregions (ICC=0.66-0.96); however, the hippocampal fissure was not consistently reconstructed across 1.5T and 3T 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 (h(2)=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.
authors.affiliation: Imaging Genetics Center, University of Southern California, Marina del Rey, CA, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Whelan
authors.affiliation: Imaging Genetics Center, University of Southern California, Marina del Rey, CA, USA.
authors.forename: Derrek P
authors.initials: DP
authors.lastname: Hibar
authors.affiliation: Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Laura S
authors.initials: LS
authors.lastname: van Velzen
authors.affiliation: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Zannas
authors.affiliation: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Tania
authors.initials: T
authors.lastname: Carrillo-Roa
authors.affiliation: Centre for Advanced Imaging, University of Queensland, Brisbane, Australia.
authors.forename: Katie
authors.initials: K
authors.lastname: McMahon
authors.affiliation: Imaging Genetics Center, University of Southern California, Marina del Rey, CA, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Prasad
authors.affiliation: Imaging Genetics Center, University of Southern California, Marina del Rey, CA, USA.
authors.forename: Sinéad
authors.initials: S
authors.lastname: Kelly
authors.affiliation: Imaging Genetics Center, University of Southern California, Marina del Rey, CA, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Faskowitz
authors.affiliation: Faculty of Health, Queensland University of Technology, Brisbane, Australia.
authors.forename: Greig
authors.initials: G
authors.lastname: deZubiracay
authors.affiliation: Basque Center on Cognition, Brain and Language, Donostia, Gipuzkoa, Spain.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Iglesias
authors.affiliation: Department of Psychiatry and Human Behavior, University of California, Irvine, USA.
authors.forename: Theo G M
authors.initials: TGM
authors.lastname: van Erp
authors.affiliation: Department of Psychiatry, Otto-von Guericke-University of Magdeburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Frodl
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Australia.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.affiliation: Imaging Genetics Center, University of Southern California, Marina del Rey, CA, USA.
authors.forename: Neda
authors.initials: N
authors.lastname: Jahanshad
authors.affiliation: Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Lianne
authors.initials: L
authors.lastname: Schmaal
authors.affiliation: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Philipp G
authors.initials: PG
authors.lastname: Sämann
authors.affiliation: Imaging Genetics Center, University of Southern California, Marina del Rey, CA, USA. Electronic address: pthomp@usc.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D001008:Anxiety Disorders / Q000235:genetics / Q000473:pathology; D003866:Depressive Disorder / Q000235:genetics / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods*; D010641:Phenotype; D012984:Software