Identifying neural pathophysiology in juvenile fibromyalgia

确定青少年纤维肌痛的神经病理生理学

• 批准号: 10242702
• 负责人: Robert C Coghill
• 金额: $ 39.1万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242702
• 关键词: Adolescent; Adult; Aerobic Exercise; Affect; Affective; Aftercare; Ancillary Study; Anxiety; Brain; Brain Mapping; Brain imaging; Characteristics; Child; Clinical; Cognitive Therapy; Data; Development; Dimensions; Disease; Disease Management; Early Diagnosis; Exercise; Fatigue; Female; Female Adolescents; Fibromyalgia; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Goals; Hypersensitivity; Judgment; Kentucky; Laboratory Finding; Lead; Location; Machine Learning; Measures; Mental Depression; Modeling; Motor; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Neurologic; Ohio; Output; Pain; Pain Measurement; Pain Research; Pain intensity; Painless; Parents; Parietal; Patients; Pattern; Persistent pain; Physical Function; Physiological; Prediction of Response to Therapy; Randomized Clinical Trials; Recommendation; Research; Sampling; Sensory; Site; Specific qualifier value; Stigmatization; Stimulus; Symptoms; Techniques; Testing; Time; Training; United States National Institutes of Health; base; brain abnormalities; chronic painful condition; cingulate cortex; clinical pain; clinical predictors; cohort; critical period; depressive symptoms; disability; fibromyalgia patients; hands-on learning; innovation; multisensory; neural correlate; neural patterning; neuromuscular; neurophysiology; pain symptom; parent project; physical symptom; psychologic; psychological symptom; relating to nervous system; response; treatment effect; treatment response

ABSTRACT Juvenile-onset fibromyalgia (JFM) is a debilitating, chronic pain condition affecting adolescents, primarily females, during a critical period for brain development, and that persists into adulthood for the majority of patients. Due to the lack of definite physical or laboratory findings, JFM has been questioned as a clinical entity, and sometimes regarded as merely an expression of anxiety or depression. This leads to poor understanding, stigmatization, and appropriate disease management, underscoring the need for identifying objective pathophysiology. We have previously used machine learning applied to fMRI data to yield multivariate patterns of distributed brain activity that, together, can identify test subjects as adult FM patients vs. healthy adults with high cross-validated accuracy (93%). However, extrapolating adult FM brain abnormalities to JFM is problematic, given the many factors impacting the developing adolescent brain and the clinical differences between adult and juvenile forms of the disease. The goal of this proposal is to identify brain pathophysiology characteristic of JFM during tailored symptom provocation tasks. There is currently a complete lack of research into the brain correlates of pain in children with widespread pain/JFM. This study will lay the foundation for a line of research in understanding the neurophysiologic underpinnings of JFM, discovering whether brain pathophysiology in JFM differs from adult FM, and assessing treatment effects on specific markers of brain pathophysiology. This study is an R01 ancillary study to the NIH/NIAMS-funded trial (R01 AR070474; Kashikar-Zuck), “Multi-site randomized clinical trial of Fibromyalgia Integrative Training for Juvenile Fibromyalgia (FIT Teens)”. The exceptionally well characterized cohort of JFM patients from the parent trial presents a unique opportunity to study JFM neural correlates. Our time-sensitive study will transform the scientific output of the parent project by identifying neurophysiological correlates of pain, psychological and physical symptoms in this large, representative, extensively-characterized sample of JFM patients before and after treatment. We hypothesize that machine learning applied to fMRI data during tailored symptom-provocation tasks will identify patterns of neural activity predictive of JFM status (vs. healthy), which will correlate with JFM symptom dimensions (pain, non-painful sensory hypersensitivity, fatigue, and depressive symptoms). This ancillary study will utilize the comprehensive psychological and physical functioning profiles already being captured in the parent R01 trial to identify clinically meaningful neurologic measures in JFM and explore the potential for these measures to change with treatment. This line of research has the potential for a profound impact on understanding and identifying JFM pathophysiology and providing neuro-physiologically informed treatment recommendations.

抽象的 青少年发病的纤维肌痛 (JFM) 是一种使人衰弱的慢性疼痛，主要影响青少年 女性正处于大脑发育的关键时期，并且大多数人都会持续到成年期 患者。由于缺乏明确的物理或实验室检查结果，JFM 作为临床治疗方法受到质疑。 实体，有时被视为仅仅是焦虑或抑郁的表达。这导致贫困 理解、污名化和适当的疾病管理，强调需要识别 客观的病理生理学。我们之前使用机器学习应用于功能磁共振成像数据来产生 分布式大脑活动的多变量模式，共同可以将测试对象识别为成年 FM 患者 与健康成年人相比，具有高交叉验证准确度 (93%)。然而，推断成人 FM 大脑 鉴于影响青少年大脑发育和发育的因素有很多，JFM 异常是有问题的。 该疾病的成人和青少年形式之间的临床差异。该提案的目标是确定 JFM 在定制症状激发任务期间的脑病理生理学特征。目前有一个 完全缺乏对广泛疼痛/JFM 儿童疼痛与大脑相关性的研究。这项研究将 为理解 JFM 的神经生理学基础的一系列研究奠定基础， 发现 JFM 的大脑病理生理学是否与成人 FM 不同，并评估治疗效果 脑病理生理学的特定标志物。本研究是 NIH/NIAMS 资助试验的 R01 辅助研究 （R01 AR070474；Kashikar-Zuck），“纤维肌痛综合训练的多中心随机临床试验 青少年纤维肌痛（FIT 青少年）”。来自 JFM 患者的特征非常明确的队列 家长试验提供了研究 JFM 神经相关性的独特机会。我们的时间敏感的研究将 通过识别疼痛的神经生理学相关性来改变父项目的科学成果， 这个大型、有代表性、广泛表征的 JFM 样本中的心理和身体症状 患者在治疗前和治疗后。我们假设机器学习应用于功能磁共振成像数据 症状激发任务将识别预测 JFM 状态（与健康）的神经活动模式，这 与 JFM 症状维度（疼痛、非疼痛性感觉超敏反应、疲劳和 抑郁症状）。这项辅助研究将利用综合的心理和身体 母体 R01 试验中已捕获功能概况，以确定具有临床意义的神经系统 JFM 中的措施并探索这些措施随治疗而改变的潜力。这一研究方向 有可能对理解和识别 JFM 病理生理学产生深远影响，并提供 神经生理学的治疗建议。