Hemispheric brain asymmetry is a basic organizational principle of the human brain and has been implicated in various psychiatric conditions, including autism spectrum disorder. Brain asymmetry is not a uniquely human feature and is observed in other species such as the mouse. Yet, asymmetry patterns are generally nuanced, and substantial sample sizes are required to detect these patterns. In this pre-registered study, we use a mouse dataset from the Province of Ontario Neurodevelopmental Network, which comprises structural MRI data from over 2000 mice, including genetic models for autism spectrum disorder, to reveal the scope and magnitude of hemispheric asymmetry in the mouse. Our findings demonstrate the presence of robust hemispheric asymmetry in the mouse brain, such as larger right hemispheric volumes towards the anterior pole and larger left hemispheric volumes toward the posterior pole, opposite to what has been shown in humans. This suggests the existence of species-specific traits. Further clustering analysis identified distinct asymmetry patterns in autism spectrum disorder models, a phenomenon that is also seen in atypically developing participants. Our study shows potential for the use of mouse models to understand the biological bases of typical and atypical brain asymmetry but also warrants caution as asymmetry patterns seem to differ between humans and mice.

半球脑不对称是人脑的基本组织原则，与各种精神疾病有关，包括自闭症谱系障碍。大脑不对称并不是人类独有的特征，在其他物种（如小鼠）中也观察到。然而，不对称模式通常是微妙的，需要大量的样本量来检测这些模式。在这项预先注册的研究中，我们使用了来自安大略省神经发育网络的小鼠数据集，其中包括来自 2000 多只小鼠的结构 MRI 数据，包括自闭症谱系障碍的遗传模型，以揭示小鼠半球不对称的范围和幅度。我们的研究结果表明，小鼠大脑中存在强大的半球不对称性，例如朝向前极的右半球体积较大，朝向后极的左半球体积较大，这与在人类中显示的情况相反。这表明存在物种特异性状。进一步的聚类分析确定了自闭症谱系障碍模型中不同的不对称模式，这种现象也出现在非典型发育的参与者中。我们的研究表明，使用小鼠模型来了解典型和非典型大脑不对称性的生物学基础的潜力，但也需要谨慎，因为人类和小鼠之间的不对称模式似乎不同。