Elucidating the neural mechanisms of spatial disorientation in vestibular migraine

前庭性偏头痛（VM）是普通人群头晕的主要原因之一。VM病理生理学 是未知的，主要差距是缺乏对空间相关症状的神经机制的理解。 这些病人的精神错乱。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， 或它们与低级前庭功能的相互作用。我们研究了小说中的空间取向 贝叶斯空间模型（BSM）的背景下，这是建立在几十年的洞察神经生理学的多感觉 空间定位的处理和整合。在这个框架内，编码头部的感觉成分 并且考虑眼睛位置来量化空间取向。在我们小组之前的工作中，我们展示了 VM患者的空间定向随着头部倾斜位置的变化而改变，并且感觉增强， 视觉运动的能力。这些发现表明VM患者空间定向的感觉整合异常。 使用经颅磁刺激（TMS）的效果，我们已经表明，多感觉前庭皮层 颞顶交界区（TPJ）内的神经元参与空间定向的感觉整合。我们还 开发了一种新的神经生理技术，可以探测TPJ对前庭-眼功能的调节作用， 采用经颅直流电刺激（tDCS）。通过这些方法的应用， 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， 患者的症状。我们的中心假设是VM患者在前庭内表现出TPJ功能的改变， 与空间定向的异常感觉整合相关的皮质网络。为了验证这个假设，我们（i） 揭示与VM空间定向障碍相关的不同感觉机制，（ii）调查这些机制是否 与临床体征和症状相关（视觉空间症状和姿势不稳定的有效测量）， 和（iii）描述TPJ对VM病理生理学的贡献，考虑其在高水平和低水平前庭中的作用。 功能，以及是否可以使用TMS靶向TPJ来调节这些患者的空间定向障碍。这些 制定有效的治疗策略来治疗使人虚弱的头晕和空间定向障碍是至关重要的 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.