Mapping Subject-Specific Structural and Functional Connectivity to Parse the Unique Contributions of Subconcussive Blast, Mild TBI, and PTSD

摘要 根据定义，亚震荡冲击波与急性期或慢性期症状无关。然而， 神经成像提供了亚震荡冲击波对脑白质造成损害的初步证据。与mTBI一样， 亚震荡冲击波与巨大的空间和个体间的异质性有关，这种异质性由 围绕爆炸的事件的可变性。亚震荡、mTBI和创伤后应激障碍的显著局限性 神经影像研究结果来自于将受影响个体的群体平均数据与匹配的数据进行比较 倾向于屏蔽特定于个人的功能的控件。幸运的是，最近在方法学上的进展 静态功能磁共振成像(RS-fMRI)的获取和分析现在提供了前所未有的能力来描绘个体- 主题级功能连接。长RS-fMRI扫描(&gt；25分钟)与先进的个人特定扫描相结合 分类方法提供了学科间异质性的量化。来自4个主题的210名退伍军人 分类：(1)亚震荡(2)脑震荡(3)未暴露的对照组和(4)未暴露的创伤后应激障碍 进行(1)长RS-fMRI扫描、结构MRI、弥散磁共振成像、(2)爆炸暴露评估、头部撞击、 和相关的临床症状，(3)精神症状，和(4)神经认知电池。以特定的目标 1，我们将比较每个受试者的功能和结构网络的个体地图 4个学科类别。我们假设功能和结构之间存在独特的连接模式 每个类别都有单独的主题。在具体目标2中，我们将测量结构和结构之间的一致性 功能强大的网络架构。我们假设亚冲击波和亚冲击波中的结构-功能解耦 MTBI组将起源于结构改变，但PTSD的解偶联来源将来自 功能改变。在具体目标3中，我们将把功能和结构网络连接与 与冲击波暴露有关的事件、mTBI症状、创伤后应激障碍症状、创伤后应激障碍症状群、抑郁 症状、其他神经精神症状和神经认知表现。支持向量回归 方法将训练能够识别功能连通性的个体特定特征的算法， 结构连通性和结构-功能耦合对应于亚震荡、mTBI、PTSD和 对照组。退伍军人的诊断和临床管理中的一个压倒性挑战是 将一个复杂的阵列或重叠的暴露、病史、症状和临床体征描绘成不同的 病因学定义的诊断实体。我们提出了解开异质性的分析方法，该方法 从神经成像中得出的大脑网络连通性指标索引。我们正在朝着以下目标迈出重要一步 发现对未来有效治疗和临床管理的发展至关重要的知识。 绘制特定个体的疾病致病途径和机制图将使我们更接近 实施精准医疗保障退役军人健康。

ABSTRACT Subconcussive blast is, by definition, not associated with acute or chronic phase symptoms. However, neuroimaging offers initial evidence of damage to white matter following subconcussive blast. As with mTBI, subconcussive blast is associated with tremendous spatial and inter-individual heterogeneity resulting from variability in the events surrounding blast. A significant limitation of subconcussive, mTBI, and PTSD neuroimaging research results from the comparison of group-averaged data of affected individuals to matched controls that tends to mask individual-specific features. Fortunately, recent methodological advances in the acquisition and analysis of resting-state fMRI (rs-fMRI) now offer an unprecedented ability to map individual- subject-level functional connectivity. Long rs-fMRI scans (> 25 min) coupled with advanced individual-specific parcellation methods provides quantification of inter-subject heterogeneity. 210 veterans from 4 subject categories: (1) subconcussive (2) concussive mTBI (3) unexposed controls and (4) blast-unexposed PTSD, will undergo (1) long rs-fMRI scans, structural MRI, diffusion MRI, (2) assessment of blast exposure, head impact, and associated clinical symptoms, (3) psychiatric symptoms, and (4) a neurocognitive battery. In Specific Aim 1, we will compare individual-specific maps of functional and structural networks in every subject and between the 4 subject categories. We hypothesize unique patterns of functional and structural connectivity among individual subjects in each category. In Specific Aim 2, we will measure the congruence between structural and functional network architectures. We hypothesize that the structure-function uncoupling in subconcussive and mTBI groups will originate from structural alterations but the source of uncoupling in PTSD will be from functional alterations. In Specific Aim 3, we will relate functional and structural network connectivity to the events surrounding blast exposure, mTBI symptoms, PTSD symptoms, PTSD symptom clusters, depression symptoms, other neuropsychiatric symptoms, and neurocognitive performance. Support vector regression methods will train algorithms capable of recognizing individual-specific features of functional connectivity, structural connectivity, and structure-function coupling that correspond to the subconcussive, mTBI, PTSD, and control groups. An overwhelming challenge in the diagnosis and clinical management of veterans, is delineating a complex array or overlapping exposures, histories, symptoms, and clinical signs into distinct etiologically defined diagnostic entities. We propose analytic methods for unraveling heterogeneity, which index brain network connectivity metrics derived from neuroimaging. We are taking important strides toward discovering knowledge that is essential to future development of effective treatments and clinical management. Mapping individual-specific etiologic pathways and mechanisms of disease will move us one step closer to implementing precision medicine for Veterans’ health.