Elucidating the neural mechanisms of spatial disorientation in vestibular migraine

阐明前庭偏头痛空间定向障碍的神经机制

• 批准号: 10440379
• 负责人: Amir Kheradmand
• 金额: $ 44.18万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-06 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10440379
• 关键词: Address; Bayesian Modeling; Biological Markers; Brain; Brain Stem; Clinical; Control Groups; Data; Dependence; Development; Diagnosis; Disorientation; Dizziness; Environment; Exhibits; Eye; Functional disorder; General Population; Head; Link; Measures; Mediating; Methods; Migraine; Modeling; Optokinetic nystagmus; Pathologic Nystagmus; Patients; Peripheral; Positioning Attribute; Posture; Prevalence; Psychophysics; Recovery; Research; Role; Sensory; Sensory Process; Severities; Signal Transduction; Signs and Symptoms; Source; Space Perception; Sum; Symptoms; Techniques; Testing; Transcranial magnetic stimulation; Vertigo; Visual; Visual Motion; Visuospatial; Work; analog; base; body position; disabling symptom; effective therapy; indexing; insight; multisensory; neural correlate; neural network; neuromechanism; neurophysiology; novel; posture instability; sensory integration; sensory mechanism; spatial integration; treatment effect; treatment strategy; visual stimulus; visual tracking

Vestibular migraine (VM) is among the leading causes of dizziness in general population. The VM pathophysiology is unknown with a major gap being lack of understanding neural mechanisms underlying symptoms related to spatial disorientation in these patients. While VM patients do not have peripheral vestibular dysfunction, their symptoms triggered by changes in the head position or visual surroundings indicate dysfunction at the high-level cortical mech- anisms or their interactions with the lower-level vestibular functions. We have studied spatial orientation in a novel context of Bayesian spatial model (BSM), which is built on decades of insights into neurophysiology of multisensory processing and integration for spatial orientation. Within this framework, sensory components that encode head and eye positions are taken into account to quantify spatial orientation. In prior work from our group, we showed that VM patients have altered spatial orientation with changes in the head tilt position as well as heightened sensi- tivity to visual motion. These findings suggest abnormal sensory integration for spatial orientation in VM patients. Using the effects of transcranial magnetic stimulation (TMS), we have shown that the multisensory vestibular cortex within the temporoparietal junction (TPJ) is involved in sensory integration for spatial orientation. We have also developed a novel neurophysiological technique that can probe modulating effect of TPJ on vestibulo-ocular func- tion, using transcranial direct current stimulation (tDCS). Through application of these methods, the overall objective of this proposal is to delineate mechanisms and neural correlates of VM spatial disorientation with links to clinical symptoms in patients. Our central hypothesis is that VM patients exhibit altered TPJ function within the vestibulo- cortical network associated with abnormal sensory integration for spatial orientation. To test this hypothesis, we (i) uncover distinct sensory mechanisms related to VM spatial disorientation, (ii) investigate whether such mechanisms are linked to clinical signs and symptoms (validated measures of visuospatial symptoms and postural instability), and (iii) delineate TPJ contributions to VM pathophysiology considering its role in both high and low level vestibular functions, and whether TPJ can be targeted using TMS to modulate spatial disorientation in these patients. These steps are crucial towards devising effective treatment strategies for debilitating dizziness and spatial disorientation in VM patients.

前庭偏头痛（VM）是普通人口头晕的主要原因之一。 VM病理生理学 未知的主要差距是缺乏与空间相关症状的神经机制的理解 这些患者的迷失方向。虽然VM患者没有外围前庭功能障碍，但其症状 由头部位置或视觉周围环境的变化触发，表明在高级皮质机械处的功能障碍 Anisms或它们与低级前庭函数的相互作用。我们在小说中研究了空间取向 贝叶斯空间模型（BSM）的背景是建立在数十年来对多感觉神经生理学的见解的建立的 空间取向的处理和集成。在此框架内，编码头的感官组件 并考虑眼睛位置以量化空间取向。在我们小组的先前工作中，我们表明 VM患者随着头部倾斜位置的变化以及敏感性的变化而改变了空间取向 对视觉运动的影响。这些发现表明，VM患者的空间取向异常的感觉整合。 利用经颅磁刺激（TMS）的影响，我们表明了多感觉前庭皮层 在颞叶交界处（TPJ）中，参与了空间方向的感觉整合。我们也有 开发了一种新型的神经生理技术，该技术可以探测TPJ对前庭 - 眼功能的影响 使用经颅直流电流刺激（TDC）。通过应用这些方法，总体目标 该提议是为了描述VM空间迷失方向的机制和神经相关性与临床的联系 患者的症状。我们的中心假设是，VM患者在前庭中表现出改变的TPJ功能。 与异常的感觉积分相关的皮质网络，用于空间取向。为了检验这一假设，我们（i） 发现与VM空间迷失方向相关的不同感觉机制，（ii）研究这种机制是否存在 与临床体征和症状有关（验证的视觉空间症状和姿势不稳定的措施）， （iii）考虑其在高水平和低水平的前庭中的作用，划定TPJ对VM病理生理学的贡献 功能以及是否可以使用TMS来靶向TPJ来调节这些患者的空间迷失方向。这些 步骤对于制定有效的治疗策略至关重要，以使头晕和空间迷失方向衰弱 在VM患者中。