Objective: This study investigates the role of dopamine (DA) in modulation of automatic stimulus-driven responses. We investigated the effect of PD, DA medication, and instruction time on the modulation of express reaching responses (ERR).

Background: PD is a movement disorder associated with depleted DA in the basal ganglia, causing slowed and reduced voluntary movement [1]. However, recent evidence suggests a separate, fast visuomotor pathway is preserved [2]. A marker for examining this pathway is the ERR, the rapid, automatic recruitment of upper limb muscles towards a suddenly appearing target in reaching tasks [3]. Preliminary data reveals preserved ERRs in PD, suggesting they are generated independently of DA-dependent striatal loops. However little is known about how the contextual modulation of this pathway is affected by PD.

Method: The study will include 20 PD patients and 20 age-matched healthy controls (HC) tested at an ON session (PD patients take DA medication as prescribed; HC take single dose of levodopa) and an OFF session (PD patients refrain from DA medication; HC take placebo). ERRs are measured with surface electrodes during a reaching task consisting of assorted pro-reach (reach towards) and anti-reach (reach away) trials. Contextual modulation of ERRs is quantified by comparing the magnitude on anti-reach trials to that on pro-reach trials. The trial type (pro/anti-reach) is indicated by a cue either 500ms or 1000ms before target onset.

Results: Preliminary results (n=10 PD, 5 HC) reveal the magnitude of the ERR on pro-reach trials is not affected by PD (p=.740) indicating fast visuomotor responses are spared by the disease. Compared to HC, PD patients are unable to modulate the magnitude of ERRs according to task instruction and have a significantly lower modulation index (p<.001). This effect is most evident when PD patients have only 500ms of instruction time. While there was no effect of medication on the magnitude of ERRs (p=.783), participants had significantly higher EMG activity during the voluntary reaching movement in the ON state (p=.047), suggesting different effects of DA on different phases of muscle recruitment during a reach.

Conclusion: Fast visuomotor responses are spared and upregulated in PD, as patients are unable to suppress automatic responses in favour of voluntary actions. This suggests contrasting effects of PD on two separate descending pathways involved in different phases of movement.

References: [1] Davie, 2008
[2] Merritt et al., 2017
[3] Pruszynski et al., 2010

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dopaminergic-modulation-of-express-reaching-responses-in-parkinsons-disease/