Fenske Sonja J, Liu Janelle, Chen Haitao, Diniz Marcio A, Stephens Rebecca L, Cornea Emil, Gilmore John H, Gao Wei
Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, 116 N. Robertson Blvd., PACT 800.7G, Los Angeles, CA 90048, United States.
Department of Biomedical Sciences and Imaging, Cedars-Sinai Medical Center, 116 N. Robertson Blvd., PACT 800.7G, Los Angeles, CA 90048, United States.
Cereb Cortex. 2025 Jun 4;35(6). doi: 10.1093/cercor/bhaf133.
Evidence for sex differences in cognition in childhood is established, but less is known about the underlying neural mechanisms for these differences. Recent findings suggest the existence of brain-behavior relationship heterogeneities during infancy; however, it remains unclear whether sex underlies these heterogeneities during this critical period when sex-related behavioral differences arise. A sample of 316 infants was included with resting-state functional magnetic resonance imaging scans at neonate (3 weeks), 1 year and 2 years of age. We used multiple linear regression to test interactions between sex and resting-state functional connectivity on behavioral scores of working memory, inhibitory self-control, intelligence, and anxiety collected at 4 years of age. We found 6 age-specific, intra-hemispheric connections showing significant and robust sex differences in functional connectivity-behavior relationships. All connections are either with the prefrontal cortex or in regions with direct anatomical pathways to the prefrontal cortex. These sex differences in functional connectivity only emerge when associated with behavior and not in functional connectivity independently. Taken together, we capture robust and conserved brain mechanisms that are distinct to sex and are defined by their relationship to behavioral outcomes. Our results establish brain-behavior mechanisms as an important feature in the search for sex differences during development.
童年时期认知方面性别差异的证据已得到证实，但对于这些差异背后的神经机制却知之甚少。最近的研究结果表明，婴儿期存在脑与行为关系的异质性；然而，在这个与性别相关的行为差异出现的关键时期，性别是否是这些异质性的基础仍不清楚。研究纳入了316名婴儿样本，对其在新生儿期（3周）、1岁和2岁时进行静息态功能磁共振成像扫描。我们使用多元线性回归来测试性别与静息态功能连接之间的相互作用对4岁时收集的工作记忆、抑制性自我控制、智力和焦虑行为评分的影响。我们发现6种特定年龄的半球内连接在功能连接与行为关系上表现出显著且稳定的性别差异。所有连接均与前额叶皮层有关，或位于与前额叶皮层有直接解剖通路的区域。这些功能连接上的性别差异仅在与行为相关时出现，而非独立于功能连接之外。综合来看，我们发现了强大且保守的脑机制，这些机制因性别而异，并由它们与行为结果的关系所定义。我们的研究结果将脑与行为机制确立为在发育过程中寻找性别差异的一个重要特征。
