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或慢性期症状无关。然而，在这方面， 神经影像学提供了亚震荡冲击波后白色物质损伤的初步证据。与mTBI一样， 亚震荡爆炸与巨大的空间和个体间异质性有关， 爆炸事件的变化亚震荡、mTBI和PTSD的显著局限性 神经影像学研究结果来自受影响个体与匹配个体的组平均数据的比较， 控制，往往掩盖个人特定的功能。幸运的是， 静息态功能磁共振成像（rs-fMRI）的采集和分析现在提供了一种前所未有的能力，可以映射个体- 主题级功能连接。长时间rs-fMRI扫描（> 25分钟）结合高级个体特异性 分块方法提供了对象间异质性的量化。4个科目的210名退伍军人 类别：（1）亚震荡（2）震荡性mTBI（3）未暴露的对照组和（4）爆炸未暴露的PTSD，将 接受（1）长时间rs-fMRI扫描、结构MRI、弥散MRI，（2）爆炸暴露、头部撞击评估， 和相关的临床症状，（3）精神症状，和（4）神经认知组合。具体目标 1，我们将比较每个学科以及不同学科之间的功能和结构网络的个体特异性图。 四个主题类别。我们假设在这些细胞中存在功能和结构连接的独特模式， 每个类别中的每个主题。在具体目标2中，我们将衡量结构和 功能网络架构。我们假设亚震荡性脑损伤和 mTBI组将起源于结构改变，但PTSD的解偶联来源将来自 功能性改变在具体目标3中，我们将把功能和结构网络连接与 爆炸暴露事件，mTBI症状，PTSD症状，PTSD症状群，抑郁症 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接性的个体特定特征的算法， 结构连接和结构-功能耦合，对应于亚震荡，mTBI，PTSD， 对照组。退伍军人的诊断和临床管理面临的巨大挑战是 将一系列复杂或重叠的暴露、病史、症状和临床体征划分为不同的 病因学定义的诊断实体。我们提出了分析方法来解开异质性， 从神经成像中获得的大脑网络连接指标。我们正朝着 发现对有效治疗和临床管理的未来发展至关重要的知识。 绘制个体特异性病因学途径和疾病机制将使我们更接近 为退伍军人的健康实施精准医疗。

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.