Little is known about the high-order interactions among brain regions measured by the similarity of higher-order features (other than the raw blood-oxygen-level-dependent signals) which can characterize higher-level brain functional connectivity (FC). Previously, we proposed FC topographical profile-based high-order FC (HOFC) and found that this metric could provide supplementary information to traditional FC for early Alzheimer’s disease (AD) detection. However, whether such findings apply to network-level brain functional integration is unknown. In this paper, we propose an extended HOFC method, termed inter-network high-order FC (IN-HOFC), as a useful complement to the traditional inter-network FC methods, for characterizing more complex organizations among the large-scale brain networks. In the IN-HOFC, both network definition and inter-network FC are defined in a high-order manner. To test whether IN-HOFC is more sensitive to cognition decline due to brain diseases than traditional inter-network FC, 77 mild cognitive impairments (MCIs) and 89 controls are compared among the conventional methods and our IN-HOFC. The result shows that IN-HOFCs among three temporal lobe-related high-order networks are dampened in MCIs. The impairment of IN-HOFC is especially found between the anterior and posterior medial temporal lobe and could be a potential MCI biomarker at the network level. The competing network-level low-order FC methods, however, either revealing less or failing to detect any group difference. This work demonstrates the biological meaning and potential diagnostic value of the IN-HOFC in clinical neuroscience studies.

中文翻译：

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轻度认知障碍患者的网络间高级功能连接（IN-HOFC）及其改变。

关于大脑区域之间通过高级特征（除了原始血氧水平相关信号以外）的相似性来衡量的高阶交互作用了解甚少，这些特征可以表征更高级别的大脑功能连接性（FC）。以前，我们提出了基于FC地形轮廓的高阶FC（HOFC），并发现该指标可以为传统FC提供早期阿尔茨海默氏病（AD）检测的补充信息。但是，这些发现是否适用于网络级大脑功能整合尚不清楚。在本文中，我们提出了一种扩展的HOFC方法，称为网络间高阶FC（IN-HOFC），作为对传统网络间FC方法的有用补充，用于表征大规模脑网络中更复杂的组织。在IN-HOFC中，两者网络定义和网络间FC以高阶方式定义。为了测试IN-HOFC是否比传统的网络间FC对由脑疾病引起的认知下降更敏感，我们比较了传统方法和我们的IN-HOFC中的77个轻度认知障碍（MCI）和89个对照。结果表明，三个时空相关的高阶网络中的IN-HOFCs在MCI中被抑制。IN-HOFC的减值尤其是发现之间前和后内侧颞叶，并且可以是在网络级的电位MCI标志物。竞争网络级低阶FC方法，但是，无论是揭示更少或无法检测到任何组差异。这项工作证明了IN-HOFC在临床神经科学研究中的生物学意义和潜在的诊断价值。