基于rs-fMRI探究中枢性性早熟女童海马全脑功能连接的异常改变

Abnormal Whole-Brain Functional Connectivity of the Hippocampus in Girls with Central Precocious Puberty: A rs-fMRI Study

摘要: 目的：探究中枢性性早熟(central precocious puberty, CPP)女童两侧海马的全脑功能连接(functional connectivity, FC)。材料与方法：收集2023年9月至2025年2月扬州大学附属医院儿科确诊的59例CPP女童的静息态功能磁共振(resting-state functional magnetic resonance imaging, rs-fMRI)数据与临床资料，并以中国彩巢计划(the Chinese Color Nest Project, CCNP)数据库中获取的54例正常发育(typically developing, TD)女童的rs-fMRI数据作为对照，经ComBat协调方法消除站点差异后，采用基于种子点的rs-fMRI FC算法，以两侧海马作为种子点，计算其与全脑的FC，使用双样本t检验分析两组数据的差异，采用Spearman相关性分析研究差异脑区的FC与性激素的关系。结果：与TD组相比，CPP女童两侧海马与多个脑区的FC值均表现为增高。具体表现为：(1) 以左侧海马为种子点，CPP组FC显著增加的脑区包括右顶上回、左中央后回、左内侧和旁扣带回(P_FDR < 0.05)；(2) 以右侧海马为种子点，CPP组FC显著增加的脑区包括左内侧额上回、双侧枕中回、右距状裂周围皮层、左背外侧额上回、右颞下回、左顶上回(P_FDR < 0.05)；此外，右侧海马与左侧枕中回、右侧距状裂周围皮层的FC与FSH基线呈正相关，与右内侧额上回之间的FC与FSH峰值呈正相关。结论：CPP女童双侧海马全脑功能连接显著异常，且与临床表现及FSH水平正相关。情感记忆系统与多个功能网络普遍连接增强，可能反映过早性激素暴露对脑发育的加速效应，符合皮质–边缘发育不协调理论。这为理解CPP女童情绪与认知特征提供了神经影像学依据及干预新视角。

Abstract: Objective: To explore the whole-brain functional connectivity (FC) of the bilateral hippocampi in girls with central precocious puberty (CPP). Materials and Methods: This study collected rs-fMRI data and clinical data from 59 girls with CPP in the Department of Pediatrics, Affiliated Hospital of Yangzhou University, from September 2023 to February 2025. The rs-fMRI data of 54 TD girls retrieved from the Chinese Color Nest Project (CCNP) database were used as controls. After using the ComBat harmonization method to eliminate the site differences, a seed-based rs-fMRI FC algorithm was employed, using the bilateral hippocampi as seeds to calculate their FC with the whole brain. Two-sample t-test was performed to analyse the differences between the two groups. Spearman correlation analysis was used to investigate the relationships between FC values and sex hormone levels. Results: Compared with the TD group, CPP girls showed increased FC between the bilateral hippocampi and multiple brain regions. Specifically: (1) Left hippocampus seed: increased FC in SPG.R, PoCG.L and DCG.L (P_FDR < 0.05). (2) Right hippocampus seed: increased FC in SFGmed.L, bilateral MOG, CAL.R, SFGdor.L, ITG.R and SPG.L (P_FDR < 0.05). Furthermore, the FC between the right hippocampus and MOG.L, CAL.R was positively correlated with baseline FSH levels. The FC between the right hippocampus and SFGmed.L was positively correlated with peak FSH levels. Conclusions: Girls with CPP exhibit significant abnormalities in the whole-brain functional connectivity of the bilateral hippocampi, which are positively correlated with FSH levels. The widespread enhanced connectivity between the affective memory system and multiple functional networks may reflect an accelerating effect of premature sex hormone exposure on brain development, consistent with the theory of corticolimbic developmental incoordination. This provides a neuroimaging basis for understanding the emotional and cognitive characteristics of girls with CPP and offers new perspectives for intervention.