Background 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. Objective 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). Methods 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. Results 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. Conclusions 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

Background: Freezing of gait (FOG) in Parkinson’s disease (PD) has been shown to be more frequent in stressful situations, implicating anxiety. Heart rate (HR) has been shown to increase prior to a FOG episode supporting the notion that elevated stress levels may trigger FOG. However, no studies to date have investigated whether elevated HR precedes all subtypes of FOG or only those episodes that are driven by anxiety. Objective: The present study sought to investigate whether 1) HR increases prior to FOG episodes in nonspecific environments (Experiment 1), and if 2) HR increases prior to FOG when provoked in high but not low threat environments using a virtual reality paradigm (Experiment 2). Methods: In Experiment 1, 10 of 19 participants with PD and FOG (PD + FOG) experienced FOG during a series of walking trials. In Experiment 2, 12 of 23 participants with PD + FOG experienced FOG while walking across an elevated and ground level narrow plank in virtual reality. HR was collected throughout the duration of both experiments, while FOG was quantified by experts using video review and tagging. Results: HR significantly increased 2–3 seconds prior to a FOG episode during Experiment 1. In Experiment 2, HR significantly increased 4–6 seconds prior to a FOG episode, specifically while navigating the elevated plank. However, there were no significant increases in HR prior to FOG episodes when participants navigated the ground plank. Conclusion: This study extends previous work further demonstrating that increases in HR prior to FOG episodes appear linked to elevated anxiety levels.

Background: Although prior research has established that freezing of gait (FOG) in Parkinson’s disease (PD) is associated with anxiety, only one study to date has directly manipulated anxiety levels to induce FOG. Objective: The current study aimed to replicate these previous findings and evaluate whether a seated version of a ‘threat’ virtual reality (VR) paradigm could induce anxiety and provoke FOG. Methods: Twenty-four PD patients with FOG were assessed across various threat conditions in both a walking VR paradigm (Experiment 1) and a seated VR paradigm (Experiment 2). Both paradigms manipulated the height (i.e., elevated vs ground) and width (wide vs narrow) of the planks participants were instructed to walk across. Results: Across both experiments, the Elevated + Narrow condition provoked significantly greater number of freezing episodes compared to all other conditions. Higher levels of self-reported anxiety were reported during the Elevated+Narrow condition compared to all other conditions in Experiment 1, and compared to the Ground condition in Experiment 2. Conclusion: These findings confirm that anxiety contributes to FOG and validates the use of a seated VR threat paradigm for provoking anxiety-related freezing. This enables future studies to combine this paradigm with functional MRI to explore the neural correlates underlying the role of anxiety in FOG.

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