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

映射特定主题的结构和功能连接性，以解析亚脑震荡爆炸、轻度 TBI 和 PTSD 的独特贡献

• 批准号: 10426070
• 负责人: RAJENDRA A MOREY
• 金额: --
• 依托单位: DURHAM VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10426070
• 关键词: Acute; Affect; Behavioral Symptoms; Brain; Brain Concussion; Brain imaging; Categories; Chronic; Chronic Phase; Clinical; Clinical Management; Cognition; Complex; Control Groups; Coupled; Coupling; Data; Development; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Etiology; Evaluation; Event; Explosion; Exposure to; Functional Magnetic Resonance Imaging; Future; Goals; Health; Heterogeneity; Image; Individual; Injury; Knowledge; Magnetic Resonance Imaging; Major Depressive Disorder; Maps; Masks; Measurable; Measures; Methodology; Methods; Mild Concussions; Neurobehavioral Manifestations; Neurocognitive; Pathologic; Pathway interactions; Pattern; Performance; Post-Traumatic Stress Disorders; Recording of previous events; Research; Rest; Source; Spatial Distribution; Stereotyping; Structure; Surface; Symptoms; Traumatic Brain Injury; Veterans; Work; advanced analytics; algorithm training; analytical method; blast exposure; brain tissue; comparison group; depressive symptoms; effective therapy; experience; functional MRI scan; head impact; indexing; individual variation; mild traumatic brain injury; military veteran; mood symptom; network architecture; neuroimaging; neuropsychiatric symptom; optimal treatments; precision medicine; psychiatric symptom; recruit; subconcussion; symptom cluster; vector; white matter

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.

抽象的 根据定义，亚语爆炸与急性或慢性期症状无关。然而， 神经影像学提供了亚语爆炸后对白质损坏的初始证据。和mtbi一样 亚语爆炸与巨大的空间和个体间异质性有关 爆炸事件的变异性。亚语，MTBI和PTSD的显着限制 神经影像学研究结果是从受影响个体的群体平均数据比较以匹配的 倾向于掩盖个人特定特征的控件。幸运的是，最近的方法论进步 现在，静止状态fMRI（RS-FMRI）的获取和分析提供了绘制个人的前所未有的能力 主题级功能连接。长RS-FMRI扫描（> 25分钟）和高级个人特异性 分析方法提供了主体间异质性的定量。来自4个主题的210名退伍军人 类别：（1）亚语（2）脑震荡MTBI（3）未暴露的对照和（4）爆炸 - 无暴露的PTSD，将 接受（1）长RS-FMRI扫描，结构MRI，扩散MRI，（2）评估爆炸暴露，头部撞击， 和相关的临床症状，（3）精神病症状，以及（4）神经认知电池。在特定目标中 1，我们将比较每个主题和之间的功能和结构网络的个体图 四个主题类别。我们假设在功能和结构连接之间的独特模式 在特定的目标2中，我们将衡量结构和结构之间的一致性 功能网络体系结构。我们假设在亚语和 MTBI组将源自结构性改变，但PTSD中的解偶联的来源将来自 功能改变。在特定的目标3中，我们将将功能和结构网络连接与 围绕爆炸暴露，MTBI症状，PTSD症状，PTSD症状簇，抑郁症的事件 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的个人特定特征的算法， 结构连通性和结构功能耦合，对应于亚语，MTBI，PTSD和 对照组。在退伍军人的诊断和临床管理中，一个压倒性的挑战是 将复杂的阵列或重叠的暴露，历史，符号和临床标志描述为不同 病因定义的诊断实体。我们提出了分析方法来阐明异质性， 索引大脑网络连通性指标来自神经影像学。我们正在大步向前 发现对未来开发有效治疗和临床管理至关重要的知识。 映射个体特异性的病因途径和疾病机制将使我们更近一步 为退伍军人的健康实施精确医学。