Neuroimaging Biomarkers of Symptom Severity, Adverse Life Events and Prognosis in Motor Functional Neurological Disorders

运动功能性神经疾病症状严重程度、不良生活事件和预后的神经影像生物标志物

• 批准号: 10218015
• 负责人: David Lewis Perez
• 金额: $ 19.74万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-14 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10218015
• 关键词: Amygdaloid structure; Anterior; Applications Grants; Atrophic; Awareness; Behavior; Behavioral; Biologic Development; Biological; Biological Markers; Brain; Caring; Characteristics; Child Abuse; Clinic; Clinical; Clinical Research; Complement; Conversion disorder; Data; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Dorsal; Electroencephalography; Emotions; Evaluation; Event; Exhibits; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Growth; Healthcare Systems; Imaging Techniques; Individual; Insula of Reil; Laboratories; Laboratory Study; Life; Limb structure; Link; Magnetic Resonance Imaging; Measures; Mediating; Medical; Modeling; Moods; Morbidity - disease rate; Motor; Movement Disorders; Network-based; Neurobiology; Neurology; Neurosciences; Outpatients; Patient Self-Report; Patients; Population; Population Research; Prevalence; Prognosis; Psychiatry; Psychometrics; Publishing; Quality of life; Regulation; Research; Research Training; Rest; Risk Factors; Scientist; Seizures; Sensory; Severities; Somatoform Disorders; Structure; Symptoms; Techniques; Testing; Thick; Training; Traumatic Brain Injury; Vision; Work; base; cingulate cortex; clinical phenotype; cohort; cost; disorder risk; disorder subtype; experience; gray matter; health related quality of life; imaging modality; imaging study; improved; interest; magnetic resonance imaging biomarker; midbrain central gray substance; morphometry; multimodality; nervous system disorder; neuroimaging; neuroimaging marker; neuropsychiatric disorder; neuropsychiatry; neuroregulation; novel; preservation; prognostic; relating to nervous system; research study; response biomarker; tool development; tractography; treatment research; treatment response; white matter

PROJECT SUMMARY/ABSTRACT Functional Neurological Disorder (FND/ Conversion Disorder) is a highly prevalent and disabling neuropsychiatric condition. Motor FND symptoms include Nonepileptic Seizures, Functional Movement Disorders and Functional Weakness. Clinical research across these motor FND subtypes, including research studies from the candidate's laboratory, suggest that these populations share many clinical and phenotypic similarities that warrant increased research integration (Perez et al. Cogn Behav Neurol 2016; Matin & Perez et al. J Neuropsychiatry Clin Neurosci 2017). Furthermore, despite the prevalence of motor FND, little is known about the underlying neuropathophysiology of this condition, which is a prerequisite for the development of biologically informed prognostic and treatment response biomarkers. Across 3 published neurobiologically focused articles, the candidate proposed a framework through which to conceptualize motor FND (Perez et al. J Neuropsychiatry Clin Neurosci 2012, 2015, Clin EEG Neurosci 2015). It is suggested that motor FND develops in the context of structural and functional alterations in neurocircuits mediating emotion awareness/expression, bodily awareness, viscerosomatic processing and behavioral regulation. A particular focus of this grant application is the specific hypothesis that FND symptoms relate to structural and functional alterations within the salience network, which includes the anterior insula, anterior cingulate cortex, dorsal amygdala and periaqueductal gray. The overall goal of this proposal is to comprehensively investigate structural and functional MRI biomarkers of symptom severity, adverse life event burden (a FND risk factor) and prognosis across motor FND. Across aims 1-3 of this proposal, multimodal structural and functional magnetic resonance imaging (MRI) techniques (including voxel-based morphometry, cortical thickness, resting-state functional connectivity and diffusion tensor imaging tractography) are used to systemically probe brain-symptom severity, brain-trauma burden and brain-prognosis relationships. Novel aspects of this proposal include the study of the full spectrum of motor FND, consistent with a trans-diagnostic approach and Dr. Perez's training in the full complement of structural and resting state functional MRI techniques. This project leverages the candidate's past fMRI experience probing brain-symptom relationships in other neuropsychiatric disorders (Perez et al. Psychiatry Res 2015; Psychiatry Clin Neurosci 2016), as well as Dr. Perez's recently published MRI study probing gray matter volume associations with self-report measures of symptom severity and childhood abuse burden in patients with motor FND (Perez et al. J Neurol Neurosurg Psychiatry 2017). Pilot data for all 3 aims is presented in this proposal. These studies in motor FND will identify trans-diagnostic neural biomarkers linked to symptom severity, adverse life events and prognosis. The results of this project will catalyze future comprehensive prognostic and treatment research including the potential future study of targeted neuromodulation and treatment response biomarkers based on baseline neuroimaging profiles.

项目摘要/摘要 功能性神经系统障碍（FND/转化障碍）是一种高度普遍且残疾的 神经精神疾病。运动FND症状包括非癫痫发作，功能运动 疾病和功能弱点。这些电动机FND亚型的临床研究，包括研究 候选人实验室的研究表明，这些人群具有许多临床和表型 需要增加研究融合的相似性（Perez等人，Cogn Behav Neurol 2016； Matin＆Perez et al。 J Neuropsychiry Clin Neurosci 2017）。此外，尽管电动机流行率很高，但知之甚少 关于这种疾病的潜在神经病理生理学，这是发展的先决条件 生物学知情的预后和治疗反应生物标志物。在3个发表的神经生物学上 候选人的重点文章提出了一个框架，通过该框架将运动fnd概念化（Perez等。 J神经精神病学临床Neurosci 2012，2015，Clin EEG Neurosci 2015）。建议电动机FND 在介导情绪的神经回路中的结构和功能变化的背景下发展 意识/表达，身体意识，内脏处理和行为调节。一个特殊的 该赠款应用的重点是特定的假设，即FND症状与结构和功能有关 显着网络内的变化，包括前岛，前扣带回皮质，背侧 杏仁核和周围灰色。该提案的总体目标是全面调查 症状严重程度，不良生活事件负担（FND风险因素）的结构和功能性MRI生物标志物 和整个电动机FND的预后。跨该提案的目标1-3，多模式结构和功能 磁共振成像（MRI）技术（包括基于体素的形态计量学，皮质厚度， 静止状态功能连接性和扩散张量成像拖拉术）用于系统探测 大脑症的严重程度，脑部 - 创伤负担和脑pro症关系。该提议的新颖方面 包括对整个运动FND的研究，与跨诊断方法一致和博士一致。 佩雷斯（Perez）在结构和静止状态功能性MRI技术的完整补充中进行了培训。这个项目 利用候选人过去的fMRI经验，探索其他神经精神病学中的脑震荡关系 疾病（Perez等，Psychiatry Res 2015; Psychiatry Clin Neurosci 2016）以及Perez博士最近的 已发表的MRI研究探测具有自我报告症状严重程度的灰质体积关联 运动FND患者的儿童虐待负担（Perez等人JNeurol Neurosurg Psychiatry 2017）。 本提案中介绍了所有3个目标的试点数据。这些在电动机FND中的研究将识别跨诊断 神经生物标志物与症状严重程度，不良生活事件和预后有关。这个项目的结果将 催化未来的综合预后和治疗研究，包括对未来的潜在研究 基于基线神经成像谱的靶向神经调节和治疗反应生物标志物。

项目成果

Individual differences in social network size linked to nucleus accumbens and hippocampal volumes in functional neurological disorder: A pilot study.

功能性神经系统疾病中与伏隔核和海马体积相关的社交网络大小的个体差异：一项试点研究。

• DOI: 10.1016/j.jad.2019.07.061
• 发表时间: 2019
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Ospina,JuanPablo;Larson,AnnaG;Jalilianhasanpour,Rozita;Williams,Benjamin;Diez,Ibai;Dhand,Amar;Dickerson,BradfordC;Perez,DavidL
• 通讯作者: Perez,DavidL

Autonomic, Endocrine, and Inflammation Profiles in Functional Neurological Disorder: A Systematic Review and Meta-Analysis.

• DOI: 10.1176/appi.neuropsych.21010025
• 发表时间: 2022
• 期刊: The Journal of neuropsychiatry and clinical neurosciences
• 作者: Paredes-Echeverri S;Maggio J;Bègue I;Pick S;Nicholson TR;Perez DL
• 通讯作者: Perez DL

Individual differences in interoceptive accuracy and prediction error in motor functional neurological disorders: A DTI study.

• DOI: 10.1002/hbm.25304
• 发表时间: 2021-04-01
• 期刊: Human brain mapping
• 影响因子: 4.8
• 作者: Sojka P;Diez I;Bareš M;Perez DL
• 通讯作者: Perez DL

Additional occupational therapy considerations for functional neurological disorders: a potential role for sensory processing.

功能性神经系统疾病的其他职业治疗注意事项：感觉处理的潜在作用。

• DOI: 10.1017/s1092852918000950
• 发表时间: 2018
• 期刊: CNS spectrums
• 影响因子: 3.3
• 作者: Ranford,Jessica;Perez,DavidL;MacLean,Julie
• 通讯作者: MacLean,Julie

The role of the anterior and midcingulate cortex in the neurobiology of functional neurologic disorder.

前扣带皮层和中扣带皮层在功能性神经系统疾病的神经生物学中的作用。

• DOI: 10.1016/b978-0-444-64196-0.00014-5
• 发表时间: 2019
• 期刊: Handbook of clinical neurology
• 作者: Ospina,JuanPablo;Jalilianhasanpour,Rozita;Perez,DavidL
• 通讯作者: Perez,DavidL