Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Neuroscience

Supervisor

Dr. Penny A. MacDonald

2nd Supervisor

Jessica A. Grahn

Co-Supervisor

Co-Supervisor

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder that affects more than 1% of the population, a value that increases exponentially with age. In addition to the motor symptoms, patients with PD experience several non-motor symptoms, such as auditory deficits and anxiety. Auditory regularity processing, which is the ability to automatically extract and utilize regular patterns within a scene is suspected to be impaired in PD. Moreover, freezing of gait (FOG) is a motor symptom that affects a fairly automatic process, which is gait. We recruited healthy younger and older participants as well as patients with PD to take part in electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and gait studies to investigate aspects of regularity and freezing of gait in PD. Auditory stimuli structures were either random, regular, or a combination of both. We observed that aging and PD significantly impair regularity processing; however, PD did not have any additional detrimental effect on regularity processing. Furthermore, the dopaminergic system impaired regularity processing by reducing the EEG brain response associated with regularity processing and by reducing fMRI brain activity in areas linked to regularity processing. It is important to note that the difference found was only observed when passively listening to the auditory stimulus and not when actively attending to it. The additional impairment associated with the dopaminergic system might be attributed to the connections of the ventral tegmental area and its downstream connections, thus supporting the dopamine overdose hypothesis. We also proposed a new way to reduce FOG in PD patients using Alprazolam, a known anxiolytic. Reducing anxiety resulted in an increase in swing time and a decrease in gait variability, factors linked to a more stable and better gait. Given that Alprazolam managed to reduce anxiety and improve FOG symptoms, we can conclude that anxiety is a causal factor for FOG. More importantly, we advise a new method to target FOG, which can reduce falls and incapacitation and overall, improve the patients’ quality of life.

Summary for Lay Audience

Parkinson’s is a disease that affects approximately 1% of the population. This disease is characterized by motor (such as tremors) and non-motor symptoms such as impairments in the auditory system and anxiety. The ability to use regular patterns in the auditory stream is referred to as regularity processing. In our studies, we found that regularity processing is impaired in older participants and in patients with Parkinson’s. Moreover, administering levodopa, which is the main medication used to treat Parkinson’s disease, resulted in an alteration in brain activity associated with regularity processing, supposedly worsening regularity processing. Additionally, we investigated the effect of reducing anxiety on freezing of gait in Parkinson’s. Freezing of gait is a symptom experienced by some patients with Parkinson’s in which patients feel that their feet are glued to the floor. We advised a new way using anxiety medication to reduce anxiety and improve freezing symptoms in these patients. This reduction can be the first step in finding medications that efficiently reduce freezing and hence reduces the chances of falls and improves patients’ quality of life. In conclusion, we found that the dopaminergic system can be involved in regularity processing and levodopa can have negative effects on that process. Moreover, we observed a direct link between anxiety and freezing of gait and we also found a new way to improve that debilitating symptom.

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