Altered Central Multisensory Processing in Post-concussion Vestibular Dysfunction

项目摘要/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 以视觉和运动刺激引起前庭症状为特征。我们假设病人可能 从前庭处理的多感官，特别是视觉输入的权重改变中受益匪浅 用于补偿中枢或外周前庭损害的网络，尽管这种情况可能会持续并成为 适应不良，导致持续的前庭症状。然而，多感官加工的变化 潜在的PCVD在很大程度上是理论上的，代表着我们理解中的一个重大知识鸿沟。 在最近的一项初步研究中，我们发现初级前庭皮质和前庭的选择性激活增加。 亚急性PCVD患者在一种新的基于任务的fMRI视觉-成像过程中的多感觉加工区域 前庭范式以及视觉和前庭处理之间改变的静息状态fMRI连通性 中心，这与症状严重程度相关。我们的中心假设是持续性PCVD是由于 多感觉前庭处理，视觉和动眼运动输入的激活/连接增加 前庭网络。 以前根据临床症状对脑震荡进行分类的努力有限，因为这是预先存在的 症状可能类似于脑震荡后的症状。我们假设定义PCVD的内表型 结合使用临床和神经影像指标的患者将更好地细分这一群体，并将 与前庭康复治疗(VRT)的反应相关。 为了评估这些假设，我们提出了以下三个具体目标：(1)定义区域脑 使用一种新的视觉-识别技术将PCVD患者与脑震荡恢复组和对照组区分开来 基于前庭任务的fMRI范式及其与主客观前庭测试的相关性；(2)确定 PCVD组与恢复组和对照组比较的功能网络和动态变化 静息组及其与主客观前庭测试的相关性；以及(3)对PCVD受试者进行分层 使用临床和神经成像指标转化为内表型，并确定这些指标的预测能力 预测VRT反应的内表型。我们建议进行三组纵向研究：(1)亚急性 PCVD患者，(2)有症状脑震荡但后来康复的患者，以及(3)健康 控制。所有受试者都将接受全面的前庭测试和脑核磁共振检查。PCVD受试者将重复 VRT完成后的临床检查。我们预计还将确认和扩展我们的初步数据发现 随着内表型的发展，这将成为VRT反应的预测模型。拟议的研究将填补目前 知识差距，推动新疗法的开发，识别神经成像/临床模式，预测 治疗反应，并导致开发量身定做的、以患者为中心的治疗方案。

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.