Altered Central Multisensory Processing in Post-concussion Vestibular Dysfunction

项目总结/摘要 持续性脑震荡后前庭功能障碍（PCVD）患者表现出视觉运动敏感性 以视觉和运动刺激诱发前庭症状为特征。我们假设患者可能 从多感觉，特别是视觉输入到前庭处理的权重改变中获益 网络，以弥补中枢或外周前庭损伤，虽然这可能会持续下去，并成为 适应不良导致持续的前庭症状然而，多感觉处理的变化， PCVD的基本原理在很大程度上是理论性的，代表了我们理解中的一个重大知识缺口。 在最近的一项初步研究中，我们发现初级前庭皮质和前庭皮质的选择性激活增加， 在一项新的基于任务的功能磁共振成像视觉- 前庭范例以及视觉和前庭处理之间静息状态fMRI连接的改变 中心，这与症状严重程度相关。我们的中心假设是持续性MVD是由于改变 多感觉前庭处理，视觉和眼神经输入的激活/连接增加， 前庭神经网络 先前根据临床症状对脑震荡进行分类的努力受到限制， 症状可能与脑震荡后的症状相似我们假设定义PCVD的内表型 使用临床和神经影像学指标组合的患者将更好地细分该人群， 与前庭康复治疗（VRT）的反应相关。 为了验证这些假说，我们提出了以下三个具体目标：（1）定义区域脑 激活，区分PCVD患者与脑震荡恢复和对照组使用一种新的视觉- 前庭功能磁共振成像模式与主观和客观前庭测试的相关性;（2）识别 与恢复和对照组相比，PCVD组的功能网络和动态状态发生改变 组在休息和相关性与主观和客观前庭测试;和（3）分层PCVD受试者 使用临床和神经影像学指标， 内表型预测VRT反应。我们提出了一个纵向研究，分为三组：（1）亚急性 PCVD患者，（2）既往有症状性脑震荡但已恢复的患者，和（3）健康 对照所有受试者将接受全面的前庭测试和脑部MRI。PCVD受试者将重复 完成VRT后进行临床试验。我们希望确认和扩大我们的初步数据发现以及 作为VRT反应的预测模型。拟议的研究将填补目前的 知识的差距，推动新疗法的发展，确定预测神经影像学/临床模式， 治疗反应，并导致定制的，以患者为中心的治疗方案的发展。

Project Summary/Abstract Patients with persistent post-concussion vestibular dysfunction (PCVD) demonstrate visual motion sensitivity characterized by visual and motion stimuli inducing vestibular symptoms. We hypothesize that patients may acutely benefit from altered weighting of multisensory, particularly visual, input into vestibular processing networks to compensate for central or peripheral vestibular impairment, although this may persist and become maladaptive, leading to persistent vestibular symptoms. However, the changes in multisensory processing that underlie PCVD are largely theoretical and represent a significant knowledge gap in our understanding. In a recent pilot study, we found selective increased activation in the primary vestibular cortex and vestibular multisensory processing regions in patients with subacute PCVD during a novel task-based fMRI visual- vestibular paradigm as well as altered resting-state fMRI connectivity between visual and vestibular processing centers, which correlates with symptom severity. Our central hypothesis is that persistent PCVD is due to altered multisensory vestibular processing, with increased activation/connectivity of visual and oculomotor inputs into the vestibular network. Prior efforts to classify concussion based upon clinical symptoms have been limited as pre-existing symptoms may mimic post-concussion symptoms. We hypothesize that defining endophenotypes for PCVD patients using a combination of clinical and neuroimaging metrics will better subdivide this population and will correlate with response to vestibular rehabilitation therapy (VRT). To assess these hypotheses, we propose the following three Specific Aims: (1) define regional brain activation that distinguishes PCVD patients from concussion recovered and control groups using a novel visual- vestibular task-based fMRI paradigm and correlations with subjective and objective vestibular testing; (2) identify alterations in functional networks and dynamic states in the PCVD group compared to recovered and control groups at rest and correlations with subjective and objective vestibular testing; and (3) stratify PCVD subjects into endophenotypes using clinical and neuroimaging metrics and determine the predictive power of these endophenotypes to predict VRT response. We propose a longitudinal study with three groups: (1) subacute PCVD patients, (2) patients with prior symptomatic concussion but who have since recovered, and (3) healthy controls. All subjects will undergo comprehensive vestibular testing and brain MRI. PCVD subjects will repeat clinical testing after completion of VRT. We expect to confirm and expand our preliminary data findings as well as develop endophenotypes that will be predictive model of VRT response. The proposed study will fill in current gaps in knowledge, drive the development of novel therapies, identify neuroimaging/clinical patterns that predict therapy response, and lead to the development of tailored, patient-centric therapy programs.