Connectome-based fingerprinting of clinical and functional outcomes in veterans

基于连接组的退伍军人临床和功能结果指纹识别

• 批准号: 10174847
• 负责人: Michael Esterman
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10174847
• 关键词: Address; Atlases; Brain; Brain Injuries; Brain imaging; Center for Translational Science Activities; Childhood; Classification; Clinical; Collaborations; Complex; Data; Development; Diagnosis; Diagnostic; Disease; Fingerprint; Foundations; Freedom; Functional Magnetic Resonance Imaging; Future; Goals; Individual; Intervention; Investigation; Machine Learning; Magnetic Resonance Imaging; Measures; Mental Depression; Methodology; Methods; Modeling; Neurobiology; Outcome; Pathology; Pattern; Performance; Phenotype; Population; Population Study; Post-Traumatic Stress Disorders; Procedures; Publications; Quality of life; Recovery; Reproducibility; Research; Rest; Sampling; Seminal; Structure; Techniques; Translating; Translational Research; Trauma; Treatment outcome; Veterans; Work; base; clinical diagnostics; clinical phenotype; clinical predictors; comorbidity; connectome; diagnostic accuracy; disability; dual diagnosis; effective therapy; exhaustion; functional disability; functional outcomes; improved; individual patient; individual variation; innovation; mild traumatic brain injury; neuroimaging; novel; operation; precision medicine; psychologic; relating to nervous system; service member; stress disorder; symptom cluster; trauma exposure; treatment planning; treatment response

It is increasingly recognized that returning Veterans and Service Members of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) suffer from co-occurring psychological and physical conditions that impede reintegration and make efficient and effective treatment planning difficult, if not impossible. Though it is clear that several diagnoses, particularly mTBI, PTSD, and depression are prevalent in trauma-exposed veterans, we have recently shown that specific patterns of co- occurrence of these disorders are key to understanding their functional consequences. The proposed research will investigate whether these patterns of clinical co-occurrence hold the key to discovering their neurobiological consequences. Specifically, this proposal will develop an innovative set of neuroimaging methods to determine whether these co-occurring disorders have specific neural fingerprints. Identifying such fingerprints would allow us to make diagnostic inferences about individual Veterans, and could help predict treatment outcomes and develop neurobiologically-informed interventions. To do this, the proposed studies will take advantage of existing data and will develop cutting-edge machine learning techniques and analytic procedures. Once developed, the proposed studies will poise the PI for multiple competitive Merit applications to apply these novel neural fingerprinting techniques in translational research. DESIGN AND METHODS: The proposed studies use a general set of techniques at the forefront of an exciting new era for brain imaging- MRI-based “fingerprinting”, or measuring and modeling the reproducible and yet substantial individual variation in the fMRI-based connectome (functional connectivity). This approach has the potential to translate population-based studies to investigations of the individual patient and precision medicine approaches. In Veterans, a recent study by Georgopoulos (co-I) and colleagues was able to successfully diagnose PTSD in a small, homogenous sample without comorbidities, using fMRI-based neural fingerprinting. The goal of the proposed studies is to replicate and optimize this work, as well as determine the feasibility of extracting unique and reliable neural fingerprints for veterans with complex co-occurring conditions (comorbid PTSD, mTBI, and depression). OBJECTIVES. Aim 1: Determine the feasibility of resting fMRI connectivity to predict PTSD in a polymorbid sample. Hypothesis: MRI-based fingerprinting will successfully diagnose PTSD above chance demonstrating the feasibility and validity of this fingerprinting analysis. However, diagnostic accuracy will be substantially reduced in this polymorbid sample thus demonstrating the need for future work to more finely characterize neural fingerprints associated with deployment trauma. Aim 2: Optimize this neural fingerprinting of PTSD across six different brain parcellation methods for defining the fMRI connectome. Aim 3: Determine the preliminary ability for resting fMRI connectivity to predict the functionally-relevant deployment trauma phenotype (DTP; comorbid mTBI, PTSD & depression). These Aims will motivate one or more Merit proposals to use neural fingerprinting to characterize a range of deployment- related pathologies, predict future functional outcomes, as well as guide the development of novel interventions.

人们越来越认识到，返回的退伍军人和持久行动的服役人员 自由/伊拉克自由/新黎明行动(OEF/OIF/OND)同时发生 妨碍重新融入社会和进行有效治疗的心理和身体状况 计划很困难，如果不是不可能的话。尽管很明显，有几种诊断，特别是mTBI、PTSD和 抑郁症在创伤暴露的退伍军人中很普遍，我们最近表明，特定的共同抑郁模式- 这些疾病的发生是理解其功能后果的关键。拟议的研究 将调查这些临床共同发生的模式是否掌握了发现它们的关键 神经生物学后果。具体地说，这项提议将制定一套创新的 神经成像方法确定这些共生疾病是否具有特定的神经功能 指纹。识别这样的指纹将使我们能够对个体做出诊断推断 可以帮助预测治疗结果和开发神经生物学知情的干预措施。 要做到这一点，拟议的研究将利用现有数据并开发尖端机器 学习技巧和分析程序。一旦开发完成，拟议的研究将使PI保持平衡 多个竞争性应用程序将这些新的神经指纹技术应用于翻译 研究。 设计和方法：拟议的研究使用了一套通用的技术 令人振奋的脑成像新纪元--基于磁共振成像的“指纹”，即测量和模拟可重现的 然而，基于功能磁共振成像的连接体(功能连接性)存在显著的个体差异。这 这种方法有可能将基于人群的研究转化为对个别患者的调查，并 精准医学即将到来。在退伍军人中，Georgopoulos(co-I)和他的同事最近的一项研究能够 使用基于功能磁共振成像的神经技术，在无并发症的小样本中成功诊断创伤后应激障碍 指纹识别。拟议研究的目标是复制和优化这项工作，并确定 复杂共现退伍军人唯一可靠神经指纹提取的可行性 条件(共患创伤后应激障碍、精神创伤和抑郁)。 目标。目的1：确定静息fMRI连接性预测创伤后应激障碍的可行性。 多病态样本。假设：基于MRI的指纹识别将成功诊断创伤后应激障碍 论证了该指纹分析的可行性和有效性。然而，诊断的准确性将是 大大减少了这种多病样本，从而表明了未来工作的必要性，以更精细地 描述与部署创伤相关的神经指纹。 目标2：优化创伤后应激障碍的六种不同脑分割方法的神经指纹图谱 定义功能磁共振连接体。 目的3：确定静息fMRI连接性的初步能力，以预测与功能相关的 部署创伤表型(DTP；合并mTBI、创伤后应激障碍和抑郁)。这些目标将激励一个人 或者更有价值的建议，使用神经指纹来表征一系列部署- 相关的病理学，预测未来的功能结果，以及指导 新颖的干预措施。

项目成果

Impaired executive function exacerbates neural markers of posttraumatic stress disorder.

• DOI: 10.1017/s0033291721000842
• 发表时间: 2021-04-21
• 期刊: PSYCHOLOGICAL MEDICINE
• 影响因子: 6.9
• 作者: Jagger-Rickels, Audreyana;Stumps, Anna;Rothlein, David;Park, Hannah;Fortenbaugh, Francesca;Zuberer, Agnieszka;Fonda, Jennifer R.;Fortier, Catherine B.;DeGutis, Joseph;Milberg, William;McGlinchey, Regina;Esterman, Michael
• 通讯作者: Esterman, Michael

Connectome-based functional connectivity markers of suicide attempt.

• DOI: 10.1016/j.jad.2020.11.061
• 发表时间: 2020-11
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Anna Stumps;Audreyana Jagger-Rickels;David Rothlein;M. Amick;Hannah Park;T. Evans;Francesca C. Fortenbaugh;C. Fortier;J. Fonda;Daniel Lee;W. Milberg;R. McGlinchey;J. DeGutis;M. Esterman