Network Biomarkers

题为“网络生物标记物”的项目6将开发新的网络连通性分析，用于检测和监测临床前FTD和早期临床bvFTD。首要目标是跨越障碍，实现作为神经退行性疾病生物标记物的内在连接网络(ICN)映射。最近的研究表明，每个神经退行性综合征的目标是一个特定的、大规模的分布式网络，可以使用ICN方法在健康的大脑中识别该网络。ICN标测作为一种无创、可重复、动态的功能成像手段，有可能在FTD药物开发中发挥重要作用。症状前FTD基因突变携带者和早期患者中ICN的分解 然而，bvFTD仍然未知。此外，还没有关于FTD中ICN的纵向变化或ICN完整性如何与临床缺陷相关的数据。解决这些问题和开发ICN生物标记物的现有障碍包括缺乏患者的可靠性数据，以及需要建立方法学共识。在项目6中，我们将设法克服这些问题，并解决有关早期站点的关键问题， 通过研究临床前FTD(无症状FTD基因突变携带者)、早期临床bvFTD、早期svPPA的受试者和通过Core A(临床)招募的、通过Core D(遗传学)进行基因分型、通过Core E(成像)进行成像并在项目3(情绪)中以情绪处理为特征的健康对照组，来研究ICN的纵向进展和症状相关性变化。我们将致力于以下工作 具体目标：(1)在第一次评估时确定检测临床前FTD和早期临床bvFTD的最可靠和最灵敏的ICN分析策略；(2)确定6个月和12个月期间临床前FTD和早期临床bvFTD的纵向网络连通性变化；以及(3)将特定的ICN变化与临床前FTD、早期bvFTD和svPPA的情绪功能丧失联系起来(项目3)。拟议研究的成功完成可能有助于为该领域提供一种非侵入性诊断和疾病监测的神经成像生物标记物，用于早期FTD，并有可能用于相关的神经退行性疾病。

Project 6, entitled "Network biomarkers" will develop novel network connectivity analyses for detecting and monitoring preclinical FTD and early clinical bvFTD. The overarching goal is to move beyond prevaling barriers to implementing intrinsic connectivity network (ICN) mapping as a neurodegenerative disease biomarker. Recent research suggests that each neurodegenerative syndrome targets a specific, large-scale distributed network that can be identified in the healthy brain using ICN methods. As a non-invasive, repeatable, dynamic functional imaging modality, ICN mapping has the potential to play a vital role in FTD drug discovery. How ICNs break down in presymptomatic FTD gene mutation carriers and patients with early bvFTD, however, remains unknown. Furthermore, no data are available regarding longitudinal ICN changes in FTD or how ICN integrity relates to clinical deficits. Existing barriers to addressing these questions and developing ICN biomarkers include lack of reliability data in patients and the need to build methodological consensus. In Project 6, we will seek to overcome these issues and address key questions about early sites, longitudinal progression, and symptom-relevance of ICN changes by studying subjects with preclinical FTD (asymptomatic FTD gene mutation carriers), early clinical bvFTD, early svPPA, and healthy controls recruited through Core A (Clinical), genotyped through Core D (Genetics), imaged through Core E (Imaging) and characterized in terms of emotion processing in Project 3 (Emotions). We will pursue the following specific aims: (1) To determine the most reliable and sensitive ICN analysis strategy for detecting preclinical FTD and early clinical bvFTD at first evaluation, (2) To identify longitudinal network connectivity changes in preclinical FTD and early clinical bvFTD over 6- and 12-month intervals, and (3) To link specific ICN changes to loss of emotional functioning in preclinical FTD, early bvFTD and svPPA (with Project 3). Successful completion of the proposed studies could help provide the field with a non-invasive diagnostic and disease monitoring neuroimaging biomarker for early FTD and, potentially, for related neurodegenerative diseases.