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: 10210380
• 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/10210380
• 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.

前庭性偏头痛（VM）是一般人群头晕的主要原因之一。 VM病理生理学 尚不清楚，主要差距是缺乏对与空间相关的症状背后的神经机制的了解 这些患者出现定向障碍。虽然 VM 患者没有外周前庭功能障碍，但他们的症状 由头部位置或视觉环境的变化引发的表明高级皮质机械功能障碍 有形现象或其与低级前庭功能的相互作用。我们在一本小说中研究了空间方向 贝叶斯空间模型 (BSM) 的背景，该模型建立在数十年对多感觉神经生理学的见解之上 空间定向的处理和集成。在这个框架内，编码头部的感觉成分 并考虑眼睛位置来量化空间方向。在我们小组之前的工作中，我们展示了 VM 患者随着头部倾斜位置的变化以及敏感度的提高而改变了空间定向 视觉运动的活力。这些发现表明 VM 患者的空间定向感觉统合异常。 利用经颅磁刺激（TMS）的效果，我们发现多感觉前庭皮层 颞顶交界处 (TPJ) 参与空间定向的感觉统合。我们还有 开发了一种新的神经生理学技术，可以探测 TPJ 对前庭眼功能的调节作用 化，使用经颅直流电刺激（tDCS）。通过应用这些方法，总体目标 该提案的目的是描述 VM 空间定向障碍的机制和神经相关性，并与临床联系起来 患者的症状。我们的中心假设是 VM 患者表现出前庭内 TPJ 功能的改变 与空间定向异常感觉统合相关的皮质网络。为了检验这个假设，我们 (i) 揭示与 VM 空间定向障碍相关的独特感觉机制，(ii) 研究此类机制是否 与临床体征和症状有关（视觉空间症状和姿势不稳定的有效测量）， (iii) 考虑到 TPJ 在高水平和低水平前庭中的作用，描述 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定向障碍。这些 步骤对于制定有效的治疗策略来治疗衰弱性头晕和空间定向障碍至关重要 VM 患者。