Functional Mechanism of Neural Control in Post-Concussion Convergence Insufficiency

项目概要/摘要：在过去的6年里，我们的研究小组研究了 典型性会聚功能不全（TYP-CI）是儿童中最常见的双眼视觉障碍 和年轻人（3.4%至12.7%5-11），导致20篇出版物12 -31，另有4篇在审查中，6篇在准备中。 我们进行了唯一的随机临床试验（RCT）整合客观眼球运动和功能磁共振成像结果 措施，实现100%的计划入学率和保留100名年轻成人。 与对照相比，眼蚓部（OVM）内TYP-CI的功能活性降低， 楔叶OVM和楔叶的功能活动与会聚峰速度显著相关 提供了对这些缺陷的第一次机械识别，这些缺陷给那些受影响的人造成了重大负担。23 我们的纵向研究结果发现，基于办公室的聚散刺激的神经机制的变化， /抑制疗法（OBVAT）是增加额眼场（FEF）和丘脑功能活动。 FEF和丘脑的功能活动增加与会聚峰显著相关 速度23,32,33 结果导致个性化的护理点治疗， TYP-CI患者的症状。而我们的研究和其他RCT的结果表明，OBVAT是最 有效的治疗，以补救症状和改善视力功能的TYP-CI儿童34-36和 37，38这些参与者中没有一个有头部损伤的历史，这是一种与CI有关的病理学。我们 研究小组已经证明，CI的患病率在儿童中较高（38%至49%）39，40， 与非脑震荡人群相比，持续性脑震荡后症状（PPCS-CI）的成年人41，42。 目前，PPCS-CI尚无有效的治疗方法。这种患病率、发病方式 （长期与突然发作），和严重的条件已导致辩论是否 对于PPCS-CI，应采用对TYP-CI有效的诊断和管理程序， 表明，需要新的研究来优化PPCS-CI管理。我们有独特的优势， 通过建立我们的工作，为这些问题提供答案， TYP-CI和OBVAT给予TYP-CI。这种研究是非常重要的，因为PPCS-CI是 与影响返回学校/运动、43-47工作、48-51或驾驶的衰弱性视觉症状相关。52 我们已经确定了治疗PPCS-CI的三个重要差距，必须解决这些差距，以确定其治疗效果。 最有效的管理。首先，鉴于病因上的明显差异，是否存在显著差异 TYP-CI和PPCS-CI之间的差异与客观眼球运动测量（峰值速度，最终幅度， 和重复性）由于潜在的神经机制差异？第二，什么是潜在的神经 与TYP-CI相比，PPCS-CI的OBVAT机制？第三，OBVAT对PPCS-CI的有效性如何， 与TYP-CI不同的给药剂量？这次更新解决了临床科学中的这些空白。

Project Summary/Abstract: During the past 6 years, our study team investigated the neural mechanism of typically-occurring convergence insufficiency (TYP-CI), the most common binocular vision disorder in children and young adults (3.4% to 12.7%5–11) leading to 20 publications12–31 with 4 more in review and 6 in preparation. We conducted the only randomized clinical trial (RCT) integrating objective eye movement and fMRI outcome measures, achieving 100% planned enrollment and retention of 100 young adults.28 Our results localized the reduction in functional activity for TYP-CI compared to controls within the oculomotor vermis (OVM) and the cuneus. Functional activity in the OVM and cuneus was significantly correlated to convergence peak velocity providing the first mechanistic identification of these deficits that create significant burden to those afflicted. 23 Our longitudinal results discovered that the neural mechanistic change stimulated by office-based vergence /accommodative therapy (OBVAT) is an increase in the frontal eye field (FEF) and thalamus functional activity. Increased functional activity from the FEF and thalamus significantly correlates to convergence peak velocity. 23,32,33 Results are leading to personalized point-of-care therapies remediating the debilitating symptoms for TYP-CI patients. While our research and results of other RCTs show that OBVAT is the most effective treatment for remediating symptoms and improving vision function in both TYP-CI children 34–36 and adults, 37,38 none of these participants had a history of head injury, a pathology that has been linked to CI. Our research team has demonstrated that the prevalence of CI is higher (38% to 49%) in children 39,40 and adults 41,42 with persistent post-concussive symptoms (PPCS-CI), than in the non-concussed population. Currently, there is no validated treatment for PPCS-CI. This difference in prevalence, mode of onset (longstanding versus sudden onset), and severity of the condition has led to a debate about whether the diagnostic and management procedures effective for TYP-CI should be utilized for PPCS-CI, and strongly suggests that new research is needed to optimize PPCS-CI management. We are uniquely positioned to provide answers to these questions by building on our work establishing the neurofunctional mechanism of TYP-CI and OBVAT administered to TYP-CI. Such research is of great importance because PPCS-CI is associated with debilitating visual symptoms impacting the return to school/sports, 43–47 work, 48–51 or driving. 52 We have identified three significant gaps for the treatment of PPCS-CI that must be addressed to determine its most effective management. First, given the obvious differences in etiology, are there significant differences between TYP-CI and PPCS-CI related to objective eye movement measures (peak velocity, final amplitude, and repeatability) due to underlying neural mechanistic differences? Second, what is the underlying neural mechanism of OBVAT for PPCS-CI compared to TYP-CI? Third, how effective is OBVAT for PPCS-CI and is the dosage of administration different than TYP-CI? This renewal addresses these gaps in clinical science.