Importance: Pediatric concussion has a rising incidence and can lead to long-term symptoms in nearly 30% of children. Resting state functional magnetic resonance imaging (rs-fMRI) disturbances are a common pathological feature of concussion, though no studies have examined sex-differences with respect to this outcome. Despite known sex-differences in how pediatric concussion presents, females have remained understudied in rs-fMRI studies, precluding a sex-specific understanding of the functional neuropathology of pediatric concussion. Objective: To provide the first insights into sex-specific rs-fMRI differences in pediatric concussion. Design, setting, and participants: Secondary data analysis of rs-fMRI data collected on children with concussion recruited from in a pediatric hospital setting, with control data accessed from the open-source ABIDE-II database. In total, 27 children with concussion (14 females) approximately one-month post-injury and 1:1 age- and sex-matched healthy controls comprised our sample. Exposure: Patients received a physician diagnosis of concussion. ABIDE-II healthy controls were typically developing. Main outcomes & measures: Seed-based (which permitted an examination of whole-brain connectivity, fitting with the exploratory nature of the present study) and region of interest (ROI) analyses were used to examine sex-based rs-fMRI differences. Threshold-free cluster enhancement (TFCE) and a family-wise error (FWE) corrected p-values were used to identify significantly different clusters. Results: In comparing females with concussion to healthy females, seed-based analyses (in order of largest effect) showed hypo-connectivity between the anterior cingulate cortex of the salience network and the precuneus (TFCE=1173.6, p=FWE=0.002) and cingulate gyrus (TFCE=1039.7, p-FWE=0.008), and the posterior cingulate cortex (PCC) of the default mode network and the paracingulate gyrus (TFCE=870.1, p-FWE=0.015) and sub-callosal cortex (TFCE=795.4, p-FWE=0.037); hyper-connectivity was observed between the lateral pre-frontal cortex and inferior frontal gyrus (TFCE=1215.4, p-FWE=0.002) and lateral occipital cortex (TFCE=854.9, p-FWE=0.020) and between the PCC and cerebellum (TFCE=791.0, p-FWE=0.038). ROI analyses showed primarily patterns of hyper-connectivity in females. No differences were observed between males with concussion and healthy males on seed-based or ROI analyses. Conclusions and relevance: There are alterations in rs-fMRI in females with concussion at one-month post-injury that are not present in males, which provides further evidence that recovery timelines in pediatric concussion may differ by sex.

中文翻译：

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小儿脑震荡静息状态功能性大脑活动的性别差异。

重要性：小儿脑震荡的发病率不断上升，可导致近 30% 的儿童出现长期症状。静息状态功能性磁共振成像 (rs-fMRI) 障碍是脑震荡的常见病理特征，尽管没有研究检查过与此结果相关的性别差异。尽管在小儿脑震荡的表现方面存在已知的性别差异，但在 rs-fMRI 研究中对女性的研究仍然不足，从而排除了对小儿脑震荡的功能性神经病理学的性别特异性理解。目的：提供对小儿脑震荡中性别特异性 rs-fMRI 差异的初步见解。设计、设置和参与者：对从儿科医院招募的脑震荡儿童收集的 rs-fMRI 数据进行二级数据分析，控制数据从开源 ABIDE-II 数据库访问。总共有 27 名脑震荡儿童（14 名女性）在受伤后大约 1 个月和 1:1 年龄和性别匹配的健康对照构成我们的样本。暴露：患者接受了医生的脑震荡诊断。ABIDE-II 健康对照通常正在发育。主要结果和措施：基于种子（允许检查全脑连通性，符合本研究的探索性）和感兴趣区域 (ROI) 分析用于检查基于性别的 rs-fMRI 差异。无阈值聚类增强 (TFCE) 和家庭错误 (FWE) 校正的 p 值用于识别显着不同的聚类。结果：在比较患有脑震荡的女性与健康女性时，基于种子的分析（按最大效果顺序）显示突出网络的前扣带回皮层与楔前叶（TFCE=1173.6，p=FWE=0.002）和扣带回（TFCE=1039.7，p-FWE= 0.008)，以及默认模式网络的后扣带回皮层 (PCC) 和副扣带回 (TFCE=870.1, p-FWE=0.015) 和胼胝体皮层 (TFCE=795.4, p-FWE=0.037)；在外侧前额叶皮层和下额叶回 (TFCE=1215.4, p-FWE=0.002) 和外侧枕叶皮层 (TFCE=854.9, p-FWE=0.020) 以及 PCC 和小脑 (TFCE) 之间观察到超连接=791.0，p-FWE=0.038）。ROI 分析主要显示女性的超连接模式。在基于种子或 ROI 的分析中，没有观察到脑震荡男性和健康男性之间的差异。结论和相关性：