ForeFront PD Research Clinic, Brain and Mind Centre, School of Medical Sciences, The University of Sydney, Camperdown, New South Wales, Australia.
Centre for Complex Systems, The University of Sydney, Camperdown, New South Wales, Australia.
Mov Disord. 2022 Jul;37(7):1432-1443. doi: 10.1002/mds.28999. Epub 2022 Apr 5.
Freezing of gait is a complex paroxysmal phenomenon that is associated with a variety of sensorimotor, cognitive and affective deficits, and significantly impacts quality of life in patients with Parkinson's disease (PD). Despite a growing body of evidence that suggests anxiety may be a crucial contributor to freezing of gait, no research study to date has investigated neural underpinnings of anxiety-induced freezing of gait.
Here, we aimed to investigate how anxiety-inducing contexts might "set the stage for freezing," through the ascending arousal system, by examining an anxiety-inducing virtual reality gait paradigm inside functional magnetic resonance imaging (fMRI).
We used a virtual reality gait paradigm that has been validated to elicit anxiety by having participants navigate a virtual plank, while simultaneously collecting task-based fMRI from individuals with idiopathic PD with confirmed freezing of gait.
First, we established that the threatening condition provoked more freezing when compared to the non-threatening condition. By using a dynamic connectivity analysis, we identified patterns of increased "cross-talk" within and between motor, limbic, and cognitive networks in the threatening conditions. We established that the threatening condition was associated with heightened network integration. We confirmed the sympathetic nature of this phenomenon by demonstrating an increase in pupil dilation during the anxiety-inducing condition of the virtual reality gait paradigm in a secondary experiment.
In conclusion, our findings represent a neurobiological mechanistic pathway through which heightened sympathetic arousal related to anxiety could foster increased "cross-talk" between distributed cortical networks that ultimately manifest as paroxysmal episodes of freezing of gait. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
冻结步态是一种复杂的阵发性现象，与多种感觉运动、认知和情感缺陷有关，严重影响帕金森病（PD）患者的生活质量。尽管越来越多的证据表明焦虑可能是冻结步态的一个关键因素，但迄今为止，没有研究调查过焦虑引起的冻结步态的神经基础。
在这里，我们旨在通过检查功能性磁共振成像（fMRI）内的焦虑诱发虚拟现实步态范式，通过上升的唤醒系统来研究焦虑诱发的情境如何“为冻结步态做好准备”。
我们使用了一种虚拟现实步态范式，该范式已通过让参与者在虚拟板上导航来验证焦虑的诱发，同时从有确诊冻结步态的特发性 PD 个体中收集基于任务的 fMRI。
首先，我们发现与非威胁条件相比，威胁条件会引起更多的冻结。通过使用动态连通性分析，我们在威胁条件下识别出运动、边缘和认知网络内和之间增加的“串扰”模式。我们确定威胁条件与网络整合度增加有关。我们通过在二级实验中在虚拟现实步态范式的焦虑诱发条件下显示瞳孔扩张增加，证实了这种现象的交感性质。
总之，我们的发现代表了一种神经生物学机制途径，通过该途径，与焦虑相关的交感唤醒增加可能会促进分布式皮质网络之间的“串扰”增加，最终表现为阵发性冻结步态发作。© 2022 作者。运动障碍由 Wiley 期刊代表国际帕金森病和运动障碍协会出版。
