Shi J.,Arizona State University |
Lepore N.,Childrens Hospital Los Angeles |
Gutman B.A.,University of Southern California |
Thompson P.M.,Imaging Genetics Center |
And 3 more authors.
Human Brain Mapping | Year: 2014
The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer's disease (AD). Hippocampal volumes are generally smaller in AD patients carrying the e4 allele compared to e4 noncarriers. Here we examined the effect of APOE e4 on hippocampal morphometry in a large imaging database-the Alzheimer's Disease Neuroimaging Initiative (ADNI). We automatically segmented and constructed hippocampal surfaces from the baseline MR images of 725 subjects with known APOE genotype information including 167 with AD, 354 with mild cognitive impairment (MCI), and 204 normal controls. High-order correspondences between hippocampal surfaces were enforced across subjects with a novel inverse consistent surface fluid registration method. Multivariate statistics consisting of multivariate tensor-based morphometry (mTBM) and radial distance were computed for surface deformation analysis. Using Hotelling's T2 test, we found significant morphological deformation in APOE e4 carriers relative to noncarriers in the entire cohort as well as in the nondemented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes. Our findings are consistent with previous studies that showed e4 carriers exhibit accelerated hippocampal atrophy; we extend these findings to a novel measure of hippocampal morphometry. Hippocampal morphometry has significant potential as an imaging biomarker of early stage AD. © 2014 Wiley Periodicals, Inc.
Xiang S.,Arizona State University |
Yuan L.,Arizona State University |
Fan W.,Huawei |
Wang Y.,Arizona State University |
And 2 more authors.
NeuroImage | Year: 2014
Bio-imaging technologies allow scientists to collect large amounts of high-dimensional data from multiple heterogeneous sources for many biomedical applications. In the study of Alzheimer's Disease (AD), neuroimaging data, gene/protein expression data, etc., are often analyzed together to improve predictive power. Joint learning from multiple complementary data sources is advantageous, but feature-pruning and data source selection are critical to learn interpretable models from high-dimensional data. Often, the data collected has block-wise missing entries. In the Alzheimer's Disease Neuroimaging Initiative (ADNI), most subjects have MRI and genetic information, but only half have cerebrospinal fluid (CSF) measures, a different half has FDG-PET; only some have proteomic data. Here we propose how to effectively integrate information from multiple heterogeneous data sources when data is block-wise missing. We present a unified "bi-level" learning model for complete multi-source data, and extend it to incomplete data. Our major contributions are: (1) our proposed models unify feature-level and source-level analysis, including several existing feature learning approaches as special cases; (2) the model for incomplete data avoids imputing missing data and offers superior performance; it generalizes to other applications with block-wise missing data sources; (3) we present efficient optimization algorithms for modeling complete and incomplete data. We comprehensively evaluate the proposed models including all ADNI subjects with at least one of four data types at baseline: MRI, FDG-PET, CSF and proteomics. Our proposed models compare favorably with existing approaches. © 2013 Elsevier Inc.
Peng D.X.,Stanford University |
Kelley R.G.,Stanford University |
Quintin E.-M.,Stanford University |
Raman M.,Stanford University |
And 2 more authors.
Human Brain Mapping | Year: 2014
Individuals with fragile X syndrome (FXS) exhibit frontal lobe-associated cognitive and behavioral deficits, including impaired general cognitive abilities, perseverative behaviors, and social difficulties. Neural signals related to these functions are communicated through frontostriatal circuits, which connect with distinct regions of the caudate nucleus (CN). Enlargement of the CN is the most robust and reproduced neuroanatomical abnormality in FXS, but very little is known on how this affects behavioral/cognitive outcomes in this condition. Here, we investigated topography within focal regions of the CN associated with prefrontal circuitry and its link with aberrant behavior and intellect in FXS. Imaging data were acquired from 48 individuals with FXS, 28 IQ-matched controls without FXS (IQ-CTL), and 36 typically developing controls (TD-CTL). Of the total participant count, cognitive and behavioral assessment data were obtained from 44 individuals with FXS and 27 participants in the IQ-CTL group. CN volume and topography were compared between groups. Correlations were performed between CN topography and cognitive as well as behavioral measures within FXS and IQ-CTL groups. As expected, the FXS group had larger CN compared with both IQ-CTL and TD-CTL groups. Correlations between focal CN topography and frontal lobe-associated cognitive and behavioral deficits in the FXS group supported the hypothesis that CN enlargement is related to abnormal orbitofrontal-caudate and dorsolateral-caudate circuitry in FXS. These findings deepen our understanding of neuroanatomical mechanisms underlying cognitive-behavioral problems in FXS and hold promise for informing future behavioral and psychopharmacological interventions targeting specific neural pathways. © 2013 Wiley Periodicals, Inc.
Renteria M.E.,QIMR Berghofer Medical Research Institute |
Renteria M.E.,University of Queensland |
Hansell N.K.,QIMR Berghofer Medical Research Institute |
Strike L.T.,QIMR Berghofer Medical Research Institute |
And 9 more authors.
Genes, Brain and Behavior | Year: 2014
Understanding the aetiology of patterns of variation within and covariation across brain regions is key to advancing our understanding of the functional, anatomical and developmental networks of the brain. Here we applied multivariate twin modelling and principal component analysis (PCA) to investigate the genetic architecture of the size of seven subcortical regions (caudate nucleus, thalamus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens) in a genetically informative sample of adolescents and young adults (N=1038; mean age=21.6±3.2years; including 148 monozygotic and 202 dizygotic twin pairs) from the Queensland Twin IMaging (QTIM) study. Our multivariate twin modelling identified a common genetic factor that accounts for all the heritability of intracranial volume (0.88) and a substantial proportion of the heritability of all subcortical structures, particularly those of the thalamus (0.71 out of 0.88), pallidum (0.52 out of 0.75) and putamen (0.43 out of 0.89). In addition, we also found substantial region-specific genetic contributions to the heritability of the hippocampus (0.39 out of 0.79), caudate nucleus (0.46 out of 0.78), amygdala (0.25 out of 0.45) and nucleus accumbens (0.28 out of 0.52). This provides further insight into the extent and organization of subcortical genetic architecture, which includes developmental and general growth pathways, as well as the functional specialization and maturation trajectories that influence each subcortical region. This multivariate twin study identifies a common genetic factor that accounts for all the heritability of intracranial volume (0.88) and a substantial proportion of the heritability of all subcortical structures, particularly those of the thalamus (0.71 out of 0.88), pallidum (0.52 out of 0.75) and putamen (0.43 out of 0.89). In parallel, it also describes substantial region-specific genetic contributions to the heritability of the hippocampus (0.39 out of 0.79), caudate nucleus (0.46 out of 0.78), amygdala (0.25 out of 0.45) and nucleus accumbens (0.28 out of 0.52). © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
Couvy-Duchesne B.,QIMR Berghofer Medical Research Institute |
Couvy-Duchesne B.,University of Queensland |
Blokland G.A.M.,QIMR Berghofer Medical Research Institute |
Blokland G.A.M.,University of Queensland |
And 6 more authors.
NeuroImage | Year: 2014
Head motion (HM) is a critical confounding factor in functional MRI. Here we investigate whether HM during resting state functional MRI (RS-fMRI) is influenced by genetic factors in a sample of 462 twins (65% fema≤ 101 MZ (monozygotic) and 130 DZ (dizygotic) twin pairs; mean age: 21 (SD=3.16), range 16-29). Heritability estimates for three HM components-mean translation (MT), maximum translation (MAXT) and mean rotation (MR)-ranged from 37 to 51%. We detected a significant common genetic influence on HM variability, with about two-thirds (genetic correlations range 0.76-1.00) of the variance shared between MR, MT and MAXT. A composite metric (HM-PC1), which aggregated these three, was also moderately heritable (h2=42%). Using a sub-sample (N=35) of the twins we confirmed that mean and maximum translational and rotational motions were consistent "traits" over repeated scans (r=0.53-0.59); reliability was even higher for the composite metric (r=0.66). In addition, phenotypic and cross-trait cross-twin correlations between HM and resting state functional connectivities (RS-FCs) with Brodmann areas (BA) 44 and 45, in which RS-FCs were found to be moderately heritable (BA44: h2-=0.23 (sd=0.041), BA45: h2-=0.26 (sd=0.061)), indicated that HM might not represent a major bias in genetic studies using FCs. Even so, the HM effect on FC was not completely eliminated after regression. HM may be a valuable endophenotype whose relationship with brain disorders remains to be elucidated. © 2014 Elsevier Inc.