Human Connectome Project for Early Psychosis

 描述(由申请人提供)：人类连接组项目(HCP)是为了加快理解人脑组织的进展而发起的。为了实现这一目标，最初的HCP华盛顿大学-明尼苏达州和MGH/哈佛-加州大学洛杉矶分校的项目专注于获取和共享与1200对健康双胞胎及其兄弟姐妹的结构和功能连接相关的数据。主要目标是使用先进的3T成像技术来开发先进的数据采集和扫描序列，开发用于白质纤维结构和脑连接的后处理的新算法，以及开发用于脑连接的新的图形技术。新的资助机会公告PAR-14-281 for Connectomes to Human疾病(U01)的目的是通过将其扩展到人类大脑疾病的研究，在原始的HCP的基础上再接再厉，以获得与原始的HCP中相同的高质量数据，但目标是以迄今为止不可能的方式加速对大脑疾病的了解。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、更有效的方法方面，进展缓慢且令人沮丧。事实上，包括精神障碍在内的严重精神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严重的精神紊乱，而且对许多人来说，病程是渐进的，会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大脑连接的功能障碍，并将这些知识转化为治疗，这是至关重要的。拟议的“人类早期精神病连接组项目”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寿命Prisma协议在两个地点获取Prisma 3T磁体的成像数据，一个在波士顿，一个在印第安纳波利斯。这种成像方案被开发为与原始的HCP具有类似的高质量，但扫描时间减少，后者在精神病队列中很重要。我们还将使用HCP中的行为测量以及针对早期精神病的额外测量。我们将获取血液，储存在罗格斯大学细胞和DNA储存库(RUCDR)(AIM 1)，我们将使用华盛顿大学HCP后处理管道来处理成像数据(AIM 2)。此外，我们还将包括用于信号点检测的新成像工具、多张量纤维束成像、扩散磁共振成像(DMRI)模型，即自由水成像，以及用于扩散图像的新的协调协议(目标3)。作为一个有代表性的例子，我们还将进行一项研究，将情感性和非情感性精神病患者的大脑网络与对照组进行比较(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的成像、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来描述早期精神病的病理基础。

 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.