Long Madison, Kar Preeti, Forkert Nils D, Landman Bennett A, Giesbrecht Gerald F, Dewey Deborah, Gibbard W Ben, Tortorelli Christina, McMorris Carly A, Huo Yuankai, Lebel Catherine
Department of Radiology, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Department of Electrical and Computer Engineering, Vanderbilt University, USA; Department of Computer Science, Vanderbilt University, USA.
Dev Cogn Neurosci. 2025 Aug 23;75:101608. doi: 10.1016/j.dcn.2025.101608.
Sex differences in brain volume are well established across ages however, limited research has investigated if sex differences in brain structure associate with early cognitive outcomes. Moreover, associations among sex, brain structure, and cognition in individuals with prenatal alcohol exposure (PAE), the most common known cause of developmental delay in North America, are unclear. Here, we investigated associations between executive function (measured by the BRIEF or BRIEF-P Global Executive Composite (GEC) and the Statue subtest of the NEPSY-II) and volumes of 36 gray matter regions in a longitudinal MRI sample of 169 young children (N=37; 534 total scans) aged 2-8 years. We found significant three-way interactions between sex, alcohol exposure, and executive function in 22 regions for GEC and 6 regions for Statue. Unexposed males showed negative executive function-volume associations, whereas males with PAE showed opposite associations. Unexposed females showed strong positive executive function-volume associations whereas females with PAE showed weak positive associations. We also evaluated reduced models in regions without significant 3-way interactions and found significant two-way interactions of sex and executive function for the GEC in three regions, and for the Statue in 22 regions. Males showed a negative executive function-volume relationship whereas females showed a positive relationship, regardless of exposure status. Our results suggest that males with PAE and unexposed females show relatively more mature volume-executive function relationships than females with PAE and unexposed males. This study highlights the importance of considering sex in investigations of brain and cognition, especially in populations with PAE.
脑容量的性别差异在各个年龄段都已得到充分证实。然而，关于脑结构的性别差异是否与早期认知结果相关的研究却很有限。此外，产前酒精暴露（PAE）是北美已知最常见的发育迟缓原因，关于PAE个体的性别、脑结构和认知之间的关联尚不清楚。在此，我们在一个包含169名2至8岁幼儿（N = 37；共534次扫描）的纵向MRI样本中，研究了执行功能（通过BRIEF或BRIEF - P全球执行综合量表（GEC）以及NEPSY - II的雕像子测试来衡量）与36个灰质区域体积之间的关联。我们发现，在GEC的22个区域和雕像子测试的6个区域中，性别、酒精暴露和执行功能之间存在显著的三向交互作用。未暴露的男性表现出执行功能与体积的负相关，而有PAE的男性则表现出相反的关联。未暴露的女性表现出执行功能与体积的强正相关，而有PAE的女性则表现出弱正相关。我们还在没有显著三向交互作用的区域评估了简化模型，发现对于GEC，在三个区域存在性别和执行功能的显著双向交互作用，对于雕像子测试，在22个区域存在这种交互作用。无论暴露状态如何，男性表现出执行功能与体积的负相关关系，而女性表现出正相关关系。我们的结果表明，与有PAE的女性和未暴露的男性相比，有PAE的男性和未暴露的女性表现出相对更成熟的体积 - 执行功能关系。这项研究强调了在脑与认知研究中考虑性别的重要性，尤其是在有PAE的人群中。
