Network Biomarkers

项目6名为“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，实现内在连接网络（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。作为一种非侵入性、可重复、动态的功能成像方式，ICN制图在FTD药物发现中发挥着至关重要的作用。症状前FTD基因突变携带者和早期FTD患者中icn是如何分解的

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.