This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. There is great individual variation in the structure and function of the brain. Discovering the determinants of this variation will not only advance our knowledge of normal brain development, but further our understanding of developmental disorders and diseases that affect the brain. The long-term objective of this application is to characterize the differential roles of genes and environment in shaping brain structure and function, to map and identify the genes involved, and to characterize the impact of brain relevant genetic polymorphisms. We shall collect structural images on a genetically informative sample of 700 Australian twins and their non-twin singleton siblings (aged 20-26 yrs) from whom we have previously obtained measures of cognitive functioning, and for whom we have extensive genotyping already available. Using state-of-the-art brain mapping techniques we will establish the genetic architecture and show the trajectory of genetic effects on brain morphometry (Specific Aim 1). In addition to structural MRI, twins and their siblings will participate in diffusion tensor (DTI) (Specific Aim 2) and functional (fMRI) imaging (Specific Aim 3). Our brain mapping techniques will be extended, for the first time, to model genetic and non-genetic influences on white matter micro-structure, and to reveal the genetic topography. The functional imaging study will apply the widely used 'N-back'working memory task, since this is the process most directly linked to individual differences in cognitive ability. We shall assess the extent of genetic mediation and generate the first detailed heritability maps of neuronal activity during working memory. Multivariate genetic modeling of twin/sibling covariance will be used to estimate the relative contributions of genetic factors to co-variance between regional brain structures, areas of working memory-related brain activation, and cognitive ability (Specific Aim 4). Genome-wide linkage and association scans (funded elsewhere) will be used to identify genetic loci that contribute to heritability of brain morphometry and functioning (Specific Aim 5). We will also screen three brain relevant genetic polymorphisms for affects on selected neural phenotypes using sib-pair allelic association analysis (Specific Aim 6). No other imaging study in twins has been designed specifically to use such a QTL-mapping strategy, and this will be at marked cost savings due to the employment of an existing well-genotyped sample.
A final aim i s to provide a unique and valuable resource base for future investigation (Specific Aim 7). The results of this study will provide fundamental information on genetic mechanisms influencing variation in brain structure and function. This will provide new insights into the origin of individual differences in cognitive functioning and vulnerability to brain disorders.
|Green, Shulamite A; Hernandez, Leanna; Bookheimer, Susan Y et al. (2016) Salience Network Connectivity in Autism Is Related to Brain and Behavioral Markers of Sensory Overresponsivity. J Am Acad Child Adolesc Psychiatry 55:618-626.e1|
|Kodumuri, Nishanth; Sebastian, Rajani; Davis, Cameron et al. (2016) The association of insular stroke with lesion volume. Neuroimage Clin 11:41-5|
|Levine, Andrew J; Soontornniyomkij, Virawudh; Achim, Cristian L et al. (2016) Multilevel analysis of neuropathogenesis of neurocognitive impairment in HIV. J Neurovirol 22:431-41|
|OrdÃ³Ã±ez, Anna E; Loeb, Frances F; Zhou, Xueping et al. (2016) Lack of Gender-Related Differences in Childhood-Onset Schizophrenia. J Am Acad Child Adolesc Psychiatry 55:792-9|
|Agis, Daniel; Goggins, Maria B; Oishi, Kumiko et al. (2016) Picturing the Size and Site of Stroke With an Expanded National Institutes of Health Stroke Scale. Stroke 47:1459-65|
|Joshi, Shantanu H; Vizueta, Nathalie; Foland-Ross, Lara et al. (2016) Relationships Between Altered Functional Magnetic Resonance Imaging Activation and Cortical Thickness in Patients With Euthymic Bipolar I Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging 1:507-517|
|Becker, James T; Kingsley, Lawrence A; Molsberry, Samantha et al. (2015) Cohort Profile: Recruitment cohorts in the neuropsychological substudy of the Multicenter AIDS Cohort Study. Int J Epidemiol 44:1506-16|
|Ajilore, Olusola; Vizueta, Nathalie; Walshaw, Patricia et al. (2015) Connectome signatures of neurocognitive abnormalities in euthymic bipolar I disorder. J Psychiatr Res 68:37-44|
|Chung, Yoonho; Jacobson, Aron; He, George et al. (2015) Prodromal Symptom Severity Predicts Accelerated Gray Matter Reduction and Third Ventricle Expansion Among Clinically High Risk Youth Developing Psychotic Disorders. Mol Neuropsychiatry 1:13-22|
|Masters, Michael; Bruner, Emiliano; Queer, Sarah et al. (2015) Analysis of the volumetric relationship among human ocular, orbital and fronto-occipital cortical morphology. J Anat 227:460-73|
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