Network Biomarkers

项目6题为“网络生物标志物”，将开发新的网络连接分析，用于检测和监测临床前FTD和早期临床bvFTD。总体目标是超越普遍存在的障碍，将内在连接网络（ICN）映射作为神经退行性疾病的生物标志物。最近的研究表明，每种神经退行性综合征都针对一个特定的、大规模的分布式网络，可以使用ICN方法在健康大脑中识别出这些网络。作为一种非侵入性、可重复、动态的功能成像方式，ICN标测有可能在FTD药物发现中发挥重要作用。ICN如何在症状前FTD基因突变携带者和早期 然而，bvFTD仍然未知。此外，没有关于FTD的ICN纵向变化或ICN完整性与临床缺陷的关系的数据。解决这些问题和开发ICN生物标志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，我们将努力克服这些问题，并解决有关早期网站的关键问题， 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受试者和健康对照受试者（通过核心A（临床）招募，通过核心D（遗传学）进行基因分型，通过核心E（成像）进行成像，并在项目3（情绪）中根据情绪处理进行表征），确定ICN变化的纵向进展和与年龄的相关性。我们将继续努力 具体目标：（1）确定首次评价时检测临床前FTD和早期临床bvFTD的最可靠和灵敏的ICN分析策略，（2）确定6个月和12个月间隔内临床前FTD和早期临床bvFTD的纵向网络连接变化，（3）将临床前FTD、早期bvFTD和svPPA的特定ICN变化与情感功能丧失联系起来（与项目3）。拟议研究的成功完成可能有助于为该领域提供早期FTD和相关神经退行性疾病的非侵入性诊断和疾病监测神经影像学生物标志物。

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.