Neurobiology of persistent perceptual postural dizziness (PPPD): Effects of galvanic vestibular stimulation (GVS) on behavioral, psychophysical, functional and structural brain imaging parameters

持续性持续性姿势知觉性头晕（PPPD）是一种非常常见的头晕障碍，具有巨大的心理社会负担，已于2017年被Barany Society分类。患者主诉慢性姿势和步态不平衡，但无定量感觉或小脑异常。通常，注意力分散调节姿势不平衡及其感知强度。在几个病理生理学的假设增加视觉刺激的敏感性（加剧视觉要求的环境）与感官间的感觉处理和受损的内部预测模型的更新重新加权出现可行的。然而，以前的研究都没有阐明大脑活动对前庭刺激的反应，前庭刺激引起了一种类似的感知，这种感知是PPPD的特征。这是通过前庭电刺激（GVS）的方式进行本项目提案的主要目标。我们将使用感觉和感觉间（视觉-前庭）活动模式来确定神经元（事件相关功能磁共振成像，功能连接），行为（姿势图）和感知水平（感知运动）及其相互作用的缩放机制，可能会导致PPPD的临床严重程度。临床和精神病学评分的关系将揭示改变缩放机制的临床意义。前庭刺激的预测和自我控制以及注意力分散对大脑活动的影响将在额外的认知实验中进行检查。这些是通常改变PPPD行为临床特征。最后，我们希望提供一个模型，内部期望如何主导感觉加工作为驱动力的PPPD。患者对先前形成但不准确的期望的依赖将使感知的感觉（前庭）输入不充分，不足以并入实验刺激可变性，并且可能是运动命令功能失调的更新，例如通过产生肢体僵硬导致姿势不平衡。

Persistent persistent postural-perceptual dizziness (PPPD) is a very common dizziness disorder with enormous psychosocial burden that has been classified by the Barany Society in 2017. Patients complain about chronic postural and gait imbalance in the absence of quantitative sensory or cerebellar abnormalities. Typically, attentional distraction modulates postural imbalance and its perceived intensity. Among several pathophysiological hypotheses increased sensitivity to visual stimuli (exacerbation in visually demanding environments) with intersensory re-weighting of sensory processing and impaired updating of internal prediction models appear feasible ones. None of the previous studies, however, has elucidated brain activity in response to vestibular stimuli evoking a similar perception of one’s own body sway that is characteristic for PPPD. This is a main objective of this project proposal by means of galvanic vestibular stimulation (GVS). We will use sensory and inter-sensory (visual-vestibular) activity patterns to identify scaling mechanisms on a neuronal (event-related fMRI, functional connectivity), behavioral (posturography) and a perceptual level (perceived motion) and their interactions that may account for the clinical severity of PPPD. The relation of clinical and psychiatric scores will shed light on the clinical meaning of altered scaling mechanisms. The influence of prediction and self-control of the vestibular stimuli as well as attentional distraction on the brain activity will be examined in additional cognitive experiments. These are clinical feature that typically modify behavior in PPPD. At the end we hope to provide a model how internal expectations dominate sensory processing as driving force in PPPD. The patient’s reliance on previously formed but inaccurate expectations will make the perceived sensory (vestibular) input inadequate, insufficient to incorporate experimental stimulus variability and presumably the update of motor commands dysfunctional, e.g. by producing limb stiffness leading to postural imbalance.