Deep learning models reveal replicable, generalizable, and behaviorally relevant sex differences in human functional brain organization.
Deep learning models reveal replicable, generalizable, and behaviorally relevant sex differences in human functional brain organization.
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深度学习模型揭示了人类大脑功能组织中可复制、可推广和行为相关的性别差异。
DOI：
10.1073/pnas.2310012121
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发表时间：
2024-02
影响因子：
11.1
通讯作者：
S. Ryali;Yuan Zhang;C. de los Angeles;Kaustubh Supekar;Vinod Menon
中科院分区：
文献类型：
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作者：
S. Ryali;Yuan Zhang;C. de los Angeles;Kaustubh Supekar;Vinod Menon
性在人类大脑发育、衰老以及精神和神经疾病的表现中起着至关重要的作用。然而，我们对人类大脑功能组织的性别差异及其行为后果的理解一直受到不一致的发现和缺乏复制的阻碍。在这里，我们使用时空深度神经网络（stDNN）模型来解决这些挑战，以揭示区分男性和女性大脑的潜在功能性大脑动力学。我们的stDNN模型准确地区分了男性和女性的大脑，在来自相同个体和三个独立队列（N ~ 1，500名20至35岁的年轻人）的多期数据中表现出一贯的高交叉验证准确率（>90%），可复制性和可推广性。可解释人工智能（XAI）分析显示，与默认模式网络、纹状体和边缘系统网络相关的大脑特征在各个阶段和独立队列中始终表现出显著的性别差异（效应量> 1.5）。此外，XAI衍生的大脑特征准确地预测了性别特异性认知特征，这一发现也被独立复制。我们的研究结果表明，功能性脑动力学的性别差异不仅具有高度可复制性和普遍性，而且与行为相关，挑战了男女大脑组织连续体的概念。我们的研究结果强调了性别作为人类大脑组织中的生物决定因素的关键作用，对开发精神和神经系统疾病的个性化性别特异性生物标志物具有重要意义，并为未来的研究提供了创新的基于人工智能的计算工具。
Sex plays a crucial role in human brain development, aging, and the manifestation of psychiatric and neurological disorders. However, our understanding of sex differences in human functional brain organization and their behavioral consequences has been hindered by inconsistent findings and a lack of replication. Here, we address these challenges using a spatiotemporal deep neural network (stDNN) model to uncover latent functional brain dynamics that distinguish male and female brains. Our stDNN model accurately differentiated male and female brains, demonstrating consistently high cross-validation accuracy (>90%), replicability, and generalizability across multisession data from the same individuals and three independent cohorts (N ~ 1,500 young adults aged 20 to 35). Explainable AI (XAI) analysis revealed that brain features associated with the default mode network, striatum, and limbic network consistently exhibited significant sex differences (effect sizes > 1.5) across sessions and independent cohorts. Furthermore, XAI-derived brain features accurately predicted sex-specific cognitive profiles, a finding that was also independently replicated. Our results demonstrate that sex differences in functional brain dynamics are not only highly replicable and generalizable but also behaviorally relevant, challenging the notion of a continuum in male-female brain organization. Our findings underscore the crucial role of sex as a biological determinant in human brain organization, have significant implications for developing personalized sex-specific biomarkers in psychiatric and neurological disorders, and provide innovative AI-based computational tools for future research.