Although substantial heritability for certain features of brain structure has now been firmly established by twin studies, only a handful of neuroimaging studies has examined the heritability of task-related neural activity, as captured by fMRI. Furthermore, the n-back task robustly activates areas ( Owen et al., 2005) shown to be highly heritable in twin studies of brain structure ( Schmitt et al., 2007). In addition, prior studies have shown that working memory task performance measures are heritable phenotypes ( Ando et al., 2001 Luciano et al., 2001 Polderman et al., 2006). Activation during this task is affected in persons with genetically influenced neurodegenerative ( Wishart et al., 2004) and neuropsychiatric disorders ( Callicott et al., 1998 Matsuo et al., 2007), and in healthy family members at increased genetic risk for some of these disorders ( Callicott et al., 2003 Drapier et al., 2008). To tease apart these contributions to individual variability, we measured brain response to an n-back working memory (WM) task. It is of considerable interest to know how much of this variability is due to genetic differences between people, how much to their (unique) environmental experience, and how much to measurement error. However, even with a rigidly standardized stimulus or task, we know that the brain's response is highly variable between people. These genetic brain maps should facilitate discovery of gene variants influencing cognitive brain function through genome-wide association studies, potentially opening up new avenues in the treatment of brain disorders.įunctional magnetic resonance imaging (fMRI) is a powerful tool for interrogating the mechanisms of the brain's response to different environmental stimuli. By establishing the heritability of cognitive brain function in a large sample that affords good statistical power, and using voxel-by-voxel analyses, this study provides the necessary evidence for task-related brain activation to be considered as an endophenotype for psychiatric or neurological disorders, and represents a substantial new contribution to the field of neuroimaging genetics. Individual variations in activation of the working memory network are therefore significantly influenced by genetic factors. Furthermore, high test-retest reliability for a subsample of 40 twins indicates that nongenetic variance in the fMRI brain response is largely due to unique environmental influences rather than measurement error. Patterns of task-related brain response (BOLD signal difference of 2-back minus 0-back) were significantly heritable, with the highest estimates (40–65%) in the inferior, middle, and superior frontal gyri, left supplementary motor area, precentral and postcentral gyri, middle cingulate cortex, superior medial gyrus, angular gyrus, superior parietal lobule, including precuneus, and superior occipital gyri. Here we report voxel-by-voxel genetic model fitting in a large sample of 319 healthy, young adult, human identical and fraternal twins (mean ± SD age, 23.6 ± 1.8 years) who performed an n-back working memory task during functional magnetic resonance imaging (fMRI) at a high magnetic field (4 tesla). Although key to understanding individual variation in task-related brain activation, the genetic contribution to these individual differences remains largely unknown.
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