Freezing of Gait in Parkinson’s disease: Utilising Virtual Reality, functional MRI and Local Field Potentials to identify the neural correlates of cueing

• Applicant: Dr. Eileen Gülke
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 522710045

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world and characterized by its typical motor impairments bradykinesia, rigidity and tremor. Besides, gait disturbances are one of the most disabling axial symptoms in PD. In the more advanced stages of the disease, up to 80% of PD patients experience freezing of gait (FOG). FOG is defined by sudden unpredictable stops in gait initiation and continuation and a major risk factor of falls. Common triggers of FOG are turning, narrow spaces but also additional cognitive load, which negatively interfere with gait. Apart from the optimization of anti-parkinsonian medication and physiotherapy, one possible strategy that has been used to overcome FOG is known as ‘cueing’. Thereby, external visual, auditory and sensory cues can improve gait parameters and reduce FOG severity by attentional strategies. Whilst the clinical benefit of cueing in PD is well appreciated, the neural correlates underpinning this effect have yet to be fully investigated. Recently, methodological advances have provided new insights from neuroimaging and neurophysiology about the pathophysiology underlying gait impairments in PD. Thereby, Virtual Reality (VR), functional magnetic resonance imaging (fMRI) and local field potential (LFP) recordings are extremely powerful tools to further study gait in PD. However, to the best of our knowledge, no studies to date have combined these methods to interrogate the phenomenon of cueing in PD. The first experiment in the proposed study seeks to investigate the relationship between visual feedback and gait through visual cueing in a seated VR gait paradigm. It explores the role of dual tasking and cue efficacy. The second experiment of this study aims to combine the VR gait paradigm with neuroimaging to identify the neural underpinnings of visually cued walking in PD. The third component of this study investigates the electrophysiological changes of local field potentials (LFP) in relation to visual cueing and dual tasking in a seated VR paradigm but also during free walking in PD patients who have previously undergone deep brain surgery of the subthalamic nucleus (STN DBS) and have a LFP sensing device in place. It is hypothesized that visual cues will improve gait parameters, even in the presence of dual tasking in a seated VR experiment, activating compensatory networks to bypass the defective basal ganglia loops and modulate oscillations in LFPs. These new insights into cueing in PD will set the stage for new research and therapeutic approaches to better understand and treat FOG in PD.

• DFG Programme: WBP Fellowship
• International Connection: Australia
• Host: Professor Dr. Simon Lewis