Altered Structural Brain Connectivity in Healthy Carriers of the Autism Risk Gene, CNTNAP2
Altered Structural Brain Connectivity in Healthy Carriers of the Autism Risk Gene, CNTNAP2
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DOI：
10.1089/brain.2011.0030
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发表时间：
2011-12-01
影响因子：
3.4
通讯作者：
Thompson, Paul M.
中科院分区：
文献类型：
--
作者：
Dennis, Emily L.;Jahanshad, Neda;Thompson, Paul M.
对静息状态功能连接的研究揭示了大脑中内在连接的网络，这些网络在一般人群中基本上是一致的。然而，这些网络中存在尚未阐明的个体差异。在这里，我们测量了自然发生的情绪对功能连接的影响。特别是，我们研究了自我报告的焦虑水平和默认模式网络（DMN）中的连接之间的关联。健康青年（n = 43;年龄10-18）和成年参与者（n = 24，年龄19-59）完成了6分钟的静息状态功能磁共振成像扫描，然后立即完成调查问卷，评估他们在扫描期间的情绪和想法。分别对青年和成人样本进行的回归分析显示，在每组中，连接性增加的大脑区域与更高的焦虑程度有差异。在一个区域，即左岛叶皮层，两组都显示出与DMN的连接性增加（青年：-30，26，14;成人：-33，12，14），焦虑增加。在扫描过程中评估的状态焦虑与特质焦虑无关，因此我们的结果可能反映了焦虑的状态水平。据我们所知，这是第一个将自然发生的情绪与静息状态连接联系起来的研究。最近，使用功能性MRI发现，自闭症风险基因CNTNAP 2的常见变体的携带者改变了功能性大脑连接。在这里，我们用高场（4特斯拉）扩散成像扫描了328名年轻人，以验证这种基因变异的携带者会改变大脑结构连接的假设。所有参与者（209名女性，119名男性，年龄：23.4 +/- 2.17 SD岁）在4特斯拉下使用105梯度高角分辨率扩散成像（HARDI）进行扫描。在使用扩散扫描的全角分辨率执行全脑纤维束成像之后，从每个个体的共同配准的解剖数据创建70个基于皮层表面的感兴趣区域，以计算所有对皮层区域的图形度量。在图论分析中，风险等位基因（CC）纯合子的受试者具有较低的特征路径长度，在全脑分析中具有更大的小世界性和全局效率，在区域分析中，70个节点中有60个节点具有较低的偏心率（最大路径长度）。这些结果不能归结为更常见的研究性状，如纤维密度或分数各向异性的差异。这是第一项将大脑结构连接的图论指标与自闭症相关的常见遗传变异联系起来的研究，并将帮助我们了解与自闭症风险有关的电路的神经生物学。
Research on resting-state functional connectivity reveals intrinsically connected networks in the brain that are largely consistent across the general population. However, there are individual differences in these networks that have not been elucidated. Here, we measured the influence of naturally occurring mood on functional connectivity. In particular, we examined the association between self-reported levels of anxiety and connectivity in the default mode network (DMN). Healthy youth (n = 43; ages 10-18) and adult participants (n = 24, ages 19-59) completed a 6-min resting-state functional magnetic resonance imaging scan, then immediately completed questionnaires assessing their mood and thoughts during the scan. Regression analyses conducted separately for the youth and adult samples revealed brain regions in which increases in connectivity differentially corresponded to higher anxiety in each group. In one area, the left insular cortex, both groups showed similar increased connectivity to the DMN (youth: -30, 26, 14; adults: -33, 12, 14) with increased anxiety. State anxiety assessed during scanning was not correlated with trait anxiety, so our results likely reflect state levels of anxiety. To our knowledge, this is the first study to relate naturally occurring mood to resting state connectivity.Recently, carriers of a common variant in the autism risk gene, CNTNAP2, were found to have altered functional brain connectivity using functional MRI. Here, we scanned 328 young adults with high-field (4-Tesla) diffusion imaging, to test the hypothesis that carriers of this gene variant would have altered structural brain connectivity. All participants (209 women, 119 men, age: 23.4 +/- 2.17 SD years) were scanned with 105-gradient high-angular-resolution diffusion imaging (HARDI) at 4 Tesla. After performing a whole-brain fiber tractography using the full angular resolution of the diffusion scans, 70 cortical surface-based regions of interest were created from each individual's co-registered anatomical data to compute graph metrics for all pairs of cortical regions. In graph theory analyses, subjects homozygous for the risk allele (CC) had lower characteristic path length, greater small-worldness and global efficiency in whole-brain analyses, and lower eccentricity (maximum path length) in 60 of the 70 nodes in regional analyses. These results were not reducible to differences in more commonly studied traits such as fiber density or fractional anisotropy. This is the first study that links graph theory metrics of brain structural connectivity to a common genetic variant linked with autism and will help us understand the neurobiology of the circuits implicated in the risk for autism.