Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Neuroscience

Supervisor

Corneil, Brian D.

2nd Supervisor

MacDonald, Penny A.

Co-Supervisor

Abstract

Parkinson’s disease (PD) is associated with reduced dopaminergic (DA) input to the dorsal striatum (DS). This study investigated the role of DA in modulating automatic, stimulus-driven reactions by assessing contextual control of stimulus-locked responses (SLRs) in 10 PD patients off and on DA medication. The SLR is the rapid recruitment of limb muscles that drives the arm towards suddenly appearing stimuli. Participants reached away from (anti-reach) or towards (pro-reach) a target on a screen, depending on instruction appearing 500 or 1000ms before target appearance. Modulation of SLRs was assessed by comparing SLR magnitude on anti- and pro-reach trials using surface electrodes. We predicted patients would exhibit less control of the SLR while off medication, especially with only 500ms of instruction. Patients modulated the SLR less with 500ms of instruction, but there was no effect of medication state, suggesting modulation of the SLR is independent of DA input to the DS.

Summary for Lay Audience

Parkinson’s disease (PD) is a movement disorder best known for its motor symptoms such as bradykinesia (slowness of movement), tremor, rigidity, and freezing of gait. Paradoxically, PD impairs the ability to initiate voluntary movement, but leaves automatic movements triggered by external targets (e.g. quickly reaching towards a moving object) intact and uninhibited. PD is associated with significant death of the cells responsible for producing dopamine (DA) molecules in the brain pathway to the dorsal striatum (DS), the input region to the basal ganglia (BG). The BG are a set of nuclei in the brain that modulate movement by regulating opposing activating and inhibitory signals to various brain structures involved in movement. This study aimed to investigate the ability of PD patients to contextually control fast visuomotor responses by assessing their control of the stimulus-locked response (SLR). The SLR is the earliest wave of arm muscle activity in response to a suddenly appearing target, that always drives the arm towards the target. The contextual control of the SLR was measured by comparing the magnitude of the response when the participants were instructed to reach away from the target (anti-reach) to when they were instructed to reach towards it (pro-reach). The colour of a square on the screen indicated whether it was an anti- or pro-reach trial either 500 ms or 1000 ms before the target appeared. Participants completed one session off their DA medication, and one session on their medication. We found that the ability to modulate the SLR was improved when participants had a longer instructional cue. However, even when the task was most challenging with only 500 ms to process the instructional cue, there was no difference in the contextual control of the SLR off and on medication. Overall, this suggests that the ability to generate and control the SLR in unaffected by the DA deficit in PD, however data from a healthy control group is needed to confirm this conclusion.

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