Reduced Hippocampal Volumes Partially Mediate Effects of Prenatal Alcohol Exposure on Spatial Navigation on a Virtual Water Maze Task in Children
Reduced Hippocampal Volumes Partially Mediate Effects of Prenatal Alcohol Exposure on Spatial Navigation on a Virtual Water Maze Task in Children
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DOI：
10.1111/acer.14310
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发表时间：
2020-03-20
影响因子：
3.2
通讯作者：
Jacobson, Sandra W.
中科院分区：
文献类型：
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作者：
Dodge, Neil C.;Thomas, Kevin G. F.;Jacobson, Sandra W.
背景 产前酒精暴露 (PAE) 与莫里斯水迷宫 (MWM) 表现较差有关，这是一项依赖于海马功能的啮齿动物空间导航测试。我们最近在 MWM 的人体模拟装置——虚拟水迷宫 (VWM) 上证实了 PAE 儿童的这些发现。先前的研究表明，海马体对 PAE 特别敏感。我们的目的是确定海马体积是否介导 PAE 和虚拟导航之间的关系。方法 VWM 和 MRI 海马数据是从南非开普敦的一个严重暴露的样本中收集的 50 名惯用右手的 10 岁儿童的海马数据。 PAE 数据是从她们怀孕期间的母亲那里收集的，孩子们接受了胎儿酒精谱系障碍 (FASD) 畸形专家的检查。在 VWM 中，参与者仅使用远端房间线索，尝试通过一系列学习试验来了解虚拟水池中隐藏平台的位置。海马体积是使用 FreeSurfer 从完成 VWM 任务 1 周内进行的 MRI 扫描得出的。结果 胎儿酒精综合症 (FAS)/部分 FAS 和非综合症重度暴露 (HE) 组的海马体积均小于对照组。即使在控制颅内容积 (ICV) 后，PAE 仍与右侧海马体积减少相关。海马体积也与 VWM 表现呈正相关。 PAE 和 VWM 表现之间的关系部分是由右海马体积介导的，而不是由总 ICV 介导的。结论这些数据证实了之前的报告，将 PAE 与 VWM 上较差的空间导航联系起来，并且是第一个提供直接证据的证据，表明该区域的体积减少部分介导了 FASD 诊断与地点学习的关系，表明 PAE 特别损害了在导航任务中成功定位隐藏平台所需的空间信息的编码能力。
Background Prenatal alcohol exposure (PAE) has been linked to poorer performance on the Morris water maze (MWM), a test of spatial navigation in rodents that is dependent on hippocampal functioning. We recently confirmed these findings in children with PAE on a human analog of the MWM, the virtual water maze (VWM). Previous studies have shown that the hippocampus is particularly sensitive to PAE. Our aim was to determine whether hippocampal volume mediates the relation between PAE and virtual navigation.Methods VWM and MRI hippocampal data were collected from 50 right-handed 10-year-old children in a heavily exposed Cape Town, South African sample. PAE data had been collected from their mothers during pregnancy, and the children were examined by expert fetal alcohol spectrum disorder (FASD) dysmorphologists. In the VWM, the participant attempts to learn the location of a hidden platform in a virtual pool of water across a series of learning trials using only distal room cues. Hippocampal volumes were derived using FreeSurfer from MRI scans administered within 1 week of completing the VWM task.Results Both the fetal alcohol syndrome (FAS)/partial FAS and nonsyndromal heavy-exposed (HE) groups had smaller hippocampal volumes than controls. PAE was associated with reduced right hippocampal volumes even after control for total intracranial volume (ICV). Hippocampal volume was also positively associated with VWM performance. The relation between PAE and VWM performance was partially mediated by right hippocampal volume but not by total ICV.Conclusions These data confirm previous reports linking PAE to poorer spatial navigation on the VWM and are the first to provide direct evidence that volume reductions in this region partially mediate the relation of FASD diagnosis to place learning, suggesting that PAE specifically impairs the ability to encode the spatial information necessary for successful location of the hidden platform on a navigation task.