Human Connectome Project for Early Psychosis

 描述（由申请人提供）：启动人类连接组计划（HCP）以加速了解人脑组织的进展。为了实现这一目标，最初的HCP华盛顿-明尼苏达大学和MGH/哈佛-加州大学洛杉矶分校项目专注于获取和共享1200名健康双胞胎及其兄弟姐妹的结构和功能连接相关数据。其主要目的是使用先进的3 T成像开发先进的数据采集和扫描序列，开发新的算法后处理的白色物质纤维结构和大脑连接，并开发新的图形技术的大脑连接。新的资助机会公告的目的，PAR-14-281人类疾病相关的连接体（U 01），是建立在原始HCP的基础上，将其扩展到人类大脑疾病的研究，以获得与原始HCP相同的高质量数据，但目标是以迄今为止不可能的方式加速大脑疾病的知识。重要的是，在将大脑知识转化为治疗严重精神障碍等人类大脑疾病的新的更有效的治疗方法方面，进展缓慢且令人沮丧。事实上，严重精神障碍，包括精神病性障碍，是一种脑部疾病，不仅具有破坏性，因为它们会导致生命早期发生的严重破坏，而且对许多人来说，疾病的过程是渐进的，导致慢性衰弱和早期死亡。因此，需要加速了解这些疾病中结构和功能性大脑连接功能障碍，并将这些知识转化为治疗，这是至关重要的。拟议的“人类连接组早期精神病项目”的主要目标是获得与原始HCP获得的数据一致的高质量数据。为此，我们将使用HCP Lifespan Prisma方案在两个研究中心（一个位于波士顿，一个位于印第安纳波利斯）采集Prisma 3 T磁体的成像数据。该成像方案被开发为具有与原始HCP相似的高质量，但具有减少的扫描时间，后者在精神病队列中很重要。我们还将使用来自HCP的行为测量以及针对早期精神病的其他测量。我们将采集血液储存在罗格斯大学细胞和DNA储存库（RUCDR）（目标1），我们将使用华盛顿大学HCP后处理管道处理成像数据（目标2）。此外，我们将包括用于信号下降检测的新成像工具，多张量纤维束成像，扩散磁共振成像（dMRI）模型，即，自由水成像，和一个新的扩散图像协调协议（目标3）。作为一个代表性的例子，我们还将进行一项研究，比较情感和非情感精神病组与对照组的大脑网络（目标4）。因此，主要目标是以与HCP一致的方式获得关于早期精神病患者的重要队列的高质量成像、行为、认知和遗传数据，这些数据将提供给研究界用于未来的研究。这些数据将提供一个独特的机会，以表征早期精神病的病理基质。

 DESCRIPTION (provided by applicant): The Human Connectome Project (HCP) was initiated to accelerate progress in understanding the organization of the human brain. To accomplish this goal, the original HCP Washington-University-Minnesota and MGH/Harvard-UCLA Projects have focused on acquiring and sharing data relevant to structural and functional connectivity in 1200 healthy twins and their siblings. The main aims have been to use advanced 3T imaging to develop advanced data acquisition and scanning sequences, to develop novel algorithms for post-processing of white matter fiber structure and brain connectivity, and to develop novel graphical techniques for brain connectomes. The purpose of the new funding opportunity announcement, PAR-14-281 for Connectomes Related to Human Diseases (U01), is to build upon the original HCP by extending it to the study of human brain diseases in order to acquire the same high quality data as in the original HCP, but with the goal of accelerating knowledge of brain diseases in a manner heretofore not possible. Importantly, progress has been slow and frustrating in translating knowledge of the brain to new and more effective treatments for human brain diseases such as severe mental disorders. In fact, severe mental disorders, which include psychotic disorders, are brain diseases that are not only devastating because they result in severe disruptions that occur early in life, but, for many, the course of illness is progressive, leading to chronic debilitation and early mortality. Thus the need to accelerate knowledge of dysfunctions in structural and functional brain connectivity in these disorders, and to translate this knowledge to treatment, is critical. The primary goal of the proposed "Human Connectome Project on Early Psychosis" is to acquire high quality data consistent with data acquired by the original HCP. To this end, we will acquire imaging data on Prisma 3T magnets at two sites, one in Boston and one in Indianapolis, using the HCP Lifespan Prisma protocol. This imaging protocol was developed to be of similar high quality to the original HCP, but with reduced scan time, the latter important in a psychosis cohort. We will also use behavioral measures from the HCP as well as additional measures specific to early psychosis. We will acquire blood to be stored at the Rutgers University Cell and DNA Repository (RUCDR)(Aim 1), and we will use the Washington University HCP post-processing pipeline to process imaging data (Aim 2). Additionally, we will include new imaging tools for signal drop detection, multi-tensor tractography, diffusion magnetic resonance imaging (dMRI) models, i.e., free-water imaging, and a new harmonization protocol for diffusion images (Aim 3). We will also perform, as a representative example, a study comparing brain networks of affective and non-affective psychosis groups with controls (Aim 4). The main goals are thus to acquire high quality imaging, behavioral, cognitive, and genetic data on an important cohort of early psychosis patients, in a manner consistent with the HCP, which will be made available to the research community for future studies. Such data will provide a unique opportunity to characterize the pathological substrates of early psychosis.