Dione Quek

Graduated from Bachelors of Psychological Sciences(Hons) in the University of Queensland in 2016. I am currently working on projects that investigates the role of anxiety in freezing of gait.

Forefront Group: Parkinson’s disease research clinic

Supervisors:

Prof. Simon Lewis

Expertise:

  • Neuroimaging
  • Freezing of gait
  • Anxiety

Neurodegeneration of interest:

PD, FOG

Project - Exploring the Relationship between Anxiety and Freezing of Gait

Research Project Abstract

The main aim of my study would be to gain a deeper understanding of the specific relationship and between FOG and anxiety. This would be completed through measuring brain activations (e.g. in the limbic system) through neuroimaging techniques, and gait measurements (i.e. number of freezing of gait, percentage of trial spent frozen) in PD patients with freezing of gait.

Specific steps to achieving this aim would begin with validating the utility of a Virtual reality (VR) seated threat paradigm, developed based on the previously validated VR walking threat paradigm. In these experiments the VR paradigm had a ‘plank’ component incorporated, where patients navigated with foot pedals, across an elevated section of walkway of variable width to modulate anxiety. Upon the validation of the seated paradigm, FMRI analysis will be conducted to examine the neural correlates underlying anxiety and freezing through the VR plank paradigm used in an MRI scanner. In addition, in order to investigate if an impaired limbic network is a factor crucial in FOG, the limbic system will also be examined during the resting state in patients who are in both their ON and OFF dopaminergic medication states.

Project tag with a disease

PD

Research Project Description

Freezing of gait (FOG) is a symptom of Parkinson’s disease (PD) that is poorly understood. It significantly impacts one’s quality of life and is not fully ameliorate by dopaminergic treatment. Physiological markers of anxiety (i.e. increased heart rate and elevated skin conductance) have been reported prior to and during episodes of FOG (Maidan et al., 2010; Mazilu et al., 2015). Furthermore, direct manipulation of threat through a walking virtual reality plank paradigm, found more anxiety, elevated skin conductance and more frequent and severe freezing of gait episodes (Ehgoetz Martens et al., 2014). These findings postulate that anxiety may be a causal factor in the freezing of gait phenomenon. As such, a series of three studies were conducted in the Parkinson’s Disease Research Clinic, to investigate neural networks underlying freezing of gait in participants with Parkinson's disease (PD).

Validate a Virtual Reality Seated VR plank paradigm

The first study aims to ascertain the causal role of anxiety in freezing of gait by replicating the results of a previous study that directly manipulated threat through a walking VR plank paradigm (Ehgoetz Martens et al., 2014). It also aims to validate a seated variation of the walking VR plank paradigm, where participants navigated across various threat conditions in VR using foot pedals. PD patients with FOG were assessed across various threat conditions in both walking and seated VR paradigms, which manipulated the height (i.e. elevated vs ground) and width (wide vs narrow) of the planks which participants navigated across. The width and height of planks in a VR plank paradigm were adjusted to elicit different levels of threat. Patients were evaluated on freezing of gait measures (i.e., severity of freezing) and A self-reported anxiety measure. Results from this study would enable future studies to combine this seated VR paradigm with functional MRI to explore the underlying neural correlates behind anxiety and freezing of gait.

Examine the Influence of Anxiety on Alterations of Brain Network Topology

The second study aims to elucidate the influence of anxiety on alterations of brain network topology in PD freezers during a virtual reality walking task-based fMRI paradigm. Parkinson’s patients with FOG completed the VR paradigm in an MRI scanner, where the task involved navigating down a corridor, with three threat conditions: (i) normal walking, (ii) wide plank (iii) narrow plank . By calculating the dynamic functional connectivity using the multiplicative temporal derivative approach on the task-based fMRI data, a set of general linear models will be used to determine whether network topology differs across the three different modalities of threat. This study is significant in determining potential alterations to the functional connectome during heightened anxiety, in which a shift into a specific dynamic connectivity state could establish a dysfunctional or compensatory dynamic network connectivity occurring in PD patient with freezing of gait.

Evaluating the influence of dopamine on limbic network connectivity at rest in Parkinson’s patients with freezing of gait

The third study aims to replicate and extend previous work which showed that Freezers had dysfunctional fronto-striato-limbic processes, specifically heightened striato-limbic load (i.e. increased connectivity between the right amygdala and putamen) in conjunction with reduced top-down attentional control (Gilat et al., 2018). The objective of the study would be to investigate the effect of dopamine on the fronto-striato-limbic circuitry in PD patients with and without FOG by conducting a seed based functional connectivity between the selected regions of interests using resting state bold data.

These studies have future implications in the advancement of FOG treatment, as by understanding precise associations between FOG and anxiety; treatment can focus on reducing anxiety to significantly reduce debilitating freezing episodes.