Borgheai Seyyed Bahram, McLinden John, Mankodiya Kunal, Shahriari Yalda
Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, RI, United States.
Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, United States.
Front Neurosci. 2020 Dec 23;14:613990. doi: 10.3389/fnins.2020.613990. eCollection 2020.
Recent evidence increasingly associates network disruption in brain organization with multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), a rare terminal disease. However, the comparability of brain network characteristics across different studies remains a challenge for conventional graph theoretical methods. One suggested method to address this issue is minimum spanning tree (MST) analysis, which provides a less biased comparison. Here, we assessed the novel application of MST network analysis to hemodynamic responses recorded by functional near-infrared spectroscopy (fNIRS) neuroimaging modality, during an activity-based paradigm to investigate hypothetical disruptions in frontal functional brain network topology as a marker of the executive dysfunction, one of the most prevalent cognitive deficit reported across ALS studies. We analyzed data recorded from nine participants with ALS and ten age-matched healthy controls by first estimating functional connectivity, using phase-locking value (PLV) analysis, and then constructing the corresponding individual and group MSTs. Our results showed significant between-group differences in several MST topological properties, including leaf fraction, maximum degree, diameter, eccentricity, and degree divergence. We further observed a global shift toward more centralized frontal network organizations in the ALS group, interpreted as a more random or dysregulated network in this cohort. Moreover, the similarity analysis demonstrated marginally significantly increased overlap in the individual MSTs from the control group, implying a reference network with lower topological variation in the healthy cohort. Our nodal analysis characterized the main local hubs in healthy controls as distributed more evenly over the frontal cortex, with slightly higher occurrence in the left prefrontal cortex (PFC), while in the ALS group, the most frequent hubs were asymmetrical, observed primarily in the right prefrontal cortex. Furthermore, it was demonstrated that the global PLV (gPLV) synchronization metric is associated with disease progression, and a few topological properties, including leaf fraction and tree hierarchy, are linked to disease duration. These results suggest that dysregulation, centralization, and asymmetry of the hemodynamic-based frontal functional network during activity are potential neuro-topological markers of ALS pathogenesis. Our findings can possibly support new bedside assessments of the functional status of ALS' brain network and could hypothetically extend to applications in other neurodegenerative diseases.
最近的证据越来越多地将脑组织中的网络破坏与多种神经退行性疾病联系起来，包括肌萎缩侧索硬化症（ALS），一种罕见的绝症。然而，对于传统的图论方法而言，不同研究之间脑网络特征的可比性仍然是一个挑战。一种解决此问题的建议方法是最小生成树（MST）分析，它提供了偏差较小的比较。在此，我们评估了MST网络分析在功能性近红外光谱（fNIRS）神经成像模态记录的血流动力学反应中的新应用，该模态用于基于活动的范式，以研究额叶功能性脑网络拓扑结构中的假设性破坏，作为执行功能障碍的标志，执行功能障碍是ALS研究中报道的最普遍的认知缺陷之一。我们分析了来自9名ALS患者和10名年龄匹配的健康对照者的数据，首先使用锁相值（PLV）分析估计功能连接性，然后构建相应的个体和组MST。我们的结果显示，在几个MST拓扑属性上存在显著的组间差异，包括叶分数、最大度、直径、偏心率和度差异。我们进一步观察到ALS组中额叶网络组织向更集中化的整体转变，这在该队列中被解释为更随机或失调的网络。此外，相似性分析表明，对照组个体MST的重叠略有显著增加，这意味着健康队列中的参考网络具有较低的拓扑变化。我们的节点分析表明，健康对照中的主要局部枢纽在额叶皮质上分布更均匀，在左前额叶皮质（PFC）中出现频率略高，而在ALS组中，最常见的枢纽是不对称的，主要出现在右前额叶皮质。此外，研究表明全局PLV（gPLV）同步指标与疾病进展相关，一些拓扑属性，包括叶分数和树层次结构，与疾病持续时间相关。这些结果表明，活动期间基于血流动力学的额叶功能网络的失调、集中化和不对称是ALS发病机制的潜在神经拓扑标志物。我们的发现可能支持对ALS脑网络功能状态进行新的床边评估，并可能推广到其他神经退行性疾病的应用中。
