Heritability of working memory brain activation.
Heritability of working memory brain activation.
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DOI：
10.1523/jneurosci.5334-10.2011
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发表时间：
2011-07-27
期刊：
影响因子：
--
通讯作者：
Wright MJ
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文献类型：
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作者：
Blokland GA;McMahon KL;Thompson PM;Martin NG;de Zubicaray GI;Wright MJ
虽然这是理解任务相关大脑激活中个体差异的关键，但遗传对这些个体差异的贡献在很大程度上仍然未知。在这里，我们报告了319例健康、年轻成人、人类同卵和异卵双胞胎（平均年龄23.6±1.8 S.D.）的大样本中逐体素遗传模型拟合。他们在高磁场（4特斯拉）下进行功能性磁共振成像（fMRI）期间执行n-back工作记忆任务。任务相关的脑反应模式（BOLD信号差为2-back减去0-back）具有显著的遗传性，在额下回、额中回和额上级上回、左侧辅助运动区、中央前回和中央后回、中扣带回皮质、内侧上级回、角回、上级顶叶小叶（包括楔前叶）和上级枕上回的估计值最高（40 - 65%）。此外，40对双胞胎的子样本的高重测信度表明，在功能磁共振成像大脑反应的非遗传变异主要是由于独特的环境影响，而不是测量误差。因此，工作记忆网络激活的个体差异受到遗传因素的显著影响。通过在大样本中建立认知脑功能的遗传性，提供良好的统计能力，并使用逐体素分析，这项研究提供了必要的证据，任务相关的脑激活被认为是精神或神经系统疾病的内表型，并代表了神经影像遗传学领域的重大新贡献。这些遗传脑图谱应该有助于通过全基因组关联研究发现影响认知脑功能的基因变异，从而可能开辟治疗脑疾病的新途径。
Although key to understanding individual variation in task-related brain activation, the genetic contribution to these individual differences remains largely unknown. Here we report voxel-by-voxel genetic model fitting in a large sample of 319 healthy, young adult, human identical and fraternal twins (mean age 23.6±1.8 S.D.) who performed an n-back working memory task during functional magnetic resonance imaging (fMRI) at high magnetic field (4 Tesla). 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, pre- and postcentral gyri, middle cingulate cortex, superior medial gyrus, angular gyrus, superior parietal lobule, including precuneus, and superior occipital gyri. Furthermore, high test-retest reliability for a subsample of 40 twins indicates that non-genetic variance in the fMRI brain response is largely due to unique environmental influences rather than measurement error. Individual variations in activation of the working memory network are therefore significantly influenced by genetic factors. 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. 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.