Postural instability and gait disability: related but separable manifestations of Parkinson’s disease

Background of the study: Postural instability and gait disturbances are among the most incapacitating features of Parkinson’s disease (PD), both for patients and their caregivers. Better pathophysiological insights are needed to provide a rational basis for improved treatment strategies. It is widely assumed that the neural substrate is identical for gait and balance problems. We propose a new pathophysiological scenario, suggesting that although gait impairment and postural instability may temporally coincide in PD, they have distinct neural substrates.
Objective of the study: The primary objective of this study is to compare the brain activity of PD patients with prominent balance or gait impairments while they mentally imagine swaying or walking respectively. A secondary objective of this study is to compare the brain activity of PD patients with balance impairments and a group of healthy subjects while they mentally imagine swaying.
Study design: We will test the hypothesis according to which gait and balance have distinct neural substrates using functional magnetic resonance imaging (fMRI) to document brain activity during task performance.
Study population: We will include 30 PD patients and 20 matched healthy volunteers. We only include patients with dopa-resistant gait and balance problems, because this represents the greatest treatment challenge in clinical practice, and because the pathophysiology underlying dopa-resistant symptoms remains unknown.

This research aims at better understanding the pathophysiology of gait and balance disorders in Parkinson's disease. Specifically, we propose a radically new and contrasting viewpoint, namely that even though gait impairment and postural instability may temporally coincide in Parkinson's disease, they actually have distinct neural substrates. Proving this concept and identifying the respective neural substrates could
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potentially have great clinical and therapeutic implications. If proven to be correct, this would imply that gait and balance difficulties would require different therapeutic approaches. Having a better understanding of the underlying cerebral substrates will also help to better understand why certain therapies have adverse effects on just gait or balance, and better inform clinicians how to avoid this.

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We will test the hypothesis according to which gait and balance have distinct neural substrates using functional magnetic resonance imaging (fMRI) to document brain activity during task performance.
To avoid confounding influences of actual movements, subjects are instructed to mentally simulate the act of swaying and walking, but without actually performing it (‘motor imagery’). To characterize the neural circuit underlying gait control in PD, we use a validated motor imagery protocol. To characterize the neural circuit underlying postural control, we extend this approach and apply a newly developed protocol for motor imagery of balance that closely matches the protocol used for gait. Specifically, we will use a dynamic balance task (imagining to sway on a balance board), because this is clinically more relevant than static balance. By asking subjects to alternately imagine walking or sway, we can directly contrast and isolate the neural substrates of gait and postural control. Finding differences in neural substrate between gait and balance would have great fundamental and clinical implications. First, this would imply that gait impairment and postural instability result from different pathologies in the brain. Second, this would help to create a model for designing specific therapeutic approaches that are required to combat each of these symptoms.