Elucidating the neural mechanisms of spatial disorientation in vestibular migraine

前庭偏头痛是引起普通人群头晕的主要原因之一。VM的病理生理学 是未知的，主要的差距是缺乏对空间相关症状潜在的神经机制的了解 这些患者的定向障碍。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触发表明高级皮质机制功能障碍- 异常或它们与较低水平的前庭功能的相互作用。我们研究了一部小说中的空间方位 贝叶斯空间模型(BSM)的背景，该模型建立在对多感觉的神经生理学的数十年见解的基础上 空间定向的处理和集成。在这个框架内，编码头部的感觉组件 并考虑眼睛位置来量化空间方向。在我们团队之前的工作中，我们展示了 随着头部倾斜位置的改变以及感觉的增强，VM患者的空间定向发生了变化。 对视觉运动的能动性。这些发现提示VM患者在空间定向方面感觉统合异常。 利用经颅磁刺激(TMS)的效应，我们证明了前庭皮质的多感觉 在颞顶交界处(TPJ)，参与了空间定向的感觉整合。我们还有 建立了一种新的神经生理学技术，可以探索三七总皂甙对前庭-眼功能的调节作用。 经颅直流电刺激(Tdcs)。通过这些方法的应用，总体目标是 这项建议的目的是描述VM空间定向障碍的机制和神经相关性，并与临床联系起来 病人的症状。我们的中心假设是，VM患者在前庭内表现出TPJ功能的改变- 皮质网络与空间定向的异常感觉整合有关。为了检验这一假设，我们(I) 揭示与VM空间定向障碍相关的不同感觉机制，(Ii)调查这种机制是否 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)， 以及(Iii)考虑到TPJ在高水平和低水平前庭中的作用，描绘了TPJ对VM病理生理学的贡献 功能，以及是否可以使用TMS靶向TMS来调节这些患者的空间定向障碍。这些 针对虚弱的头晕和空间定向障碍，制定有效的治疗策略的步骤至关重要。 在VM患者中。

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.