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，亚震荡冲击波与急性期或慢性期症状无关。 与 mTBI 一样，神经影像学提供了脑震荡后脑白质损伤的初步证据。 亚震荡爆炸与巨大的空间和个体间的异质性有关，这是由于 爆炸周围事件的变异性是亚震荡、mTBI 和 PTSD 的显着限制。 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 幸运的是，最近在方法论上取得了进展。 静息态功能磁共振成像 (rs-fMRI) 的采集和分析现在提供了前所未有的能力来绘制个体图谱 受试者级功能连接性长 rs-fMRI 扫描（> 25 分钟）与先进的个体特异性相结合。 分区方法提供了来自 4 个受试者的 210 名退伍军人的受试者间异质性的量化。 类别：(1) 亚震荡性 (2) 震荡性 mTBI (3) 未暴露对照和 (4) 爆炸未暴露 PTSD，将 接受 (1) 长时间 rs-fMRI 扫描、结构 MRI、扩散 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，以及（4）特定目标的神经认知能力。 1，我们将比较每个主题和之间的功能和结构网络的个体特定图 我们的 4 个学科类别之间具有独特的功能和结构连接模式。 在具体目标 2 中，我们将衡量每个类别中的各个主题之间的一致性。 我们勇敢地面对次震荡和功能网络结构的解耦。 mTBI 群体将起源于结构改变，但 PTSD 中解耦的来源将来自 在具体目标 3 中，我们将把功能和结构网络连接与 围绕爆炸暴露的事件、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。 方法将训练能够识别功能连接的个体特定特征的算法， 对应于亚震荡、mTBI、PTSD 和 对照组是退伍军人诊断和临床管理中的一个巨大挑战。 将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 我们提出了阐明异质性的分析方法，其中 索引源自神经影像的大脑网络连接指标我们正在朝着这一方向迈出重要的一步。 发现对于未来开发有效治疗和临床管理至关重要的知识。 绘制个体特异性病因途径和疾病机制将使我们更进一步 为退伍军人的健康实施精准医疗。