Is DOPA-Responsive Hypokinesia Responsible for Bimanual Coordination Deficits in Parkinson's Disease?

Abstract

Bradykinesia is a well-documented DOPA-responsive clinical feature of Parkinson's disease (PD). While amplitude deficits (hypokinesia) are a key component of this slowness, it is important to consider how dopamine influences both the amplitude (hypokinesia) and frequency components of bradykinesia when a bimanually coordinated movement is required. Based on the notion that the basal ganglia are associated with sensory deficits, the influence of dopaminergic replacement on sensory feedback conditions during bimanual coordination was also evaluated. Bimanual movements were examined in PD and healthy comparisons in an unconstrained three-dimensional coordination task. PD were tested "off" (overnight withdrawal of dopaminergic treatment) and "on" (peak dose of dopaminergic treatment), while the healthy group was evaluated for practice effects across two sessions. Required cycle frequency (increased within each trial from 0.75 to 2 Hz), type of visual feedback (no vision, normal vision, and augmented vision), and coordination pattern (symmetrical in-phase and non-symmetrical anti-phase) were all manipulated. Overall, coordination (mean accuracy and standard deviation of relative phase) and amplitude deficits during bimanual coordination were confirmed in PD participants. In addition, significant correlations were identified between severity of motor symptoms as well as bradykinesia to greater coordination deficits (accuracy and stability) in PD "off" group. However, even though amplitude deficits (hypokinesia) improved with dopaminergic replacement, it did not improve bimanual coordination performance (accuracy or stability) in PD patients from "off" to "on." Interestingly, while coordination performance in both groups suffered in the augmented vision condition, the amplitude of the more affected limb of PD was notably influenced. It can be concluded that DOPA-responsive hypokinesia contributes to, but is not directly responsible for bimanual coordination impairments in PD. It is likely that bimanual coordination deficits in PD are caused by the combination of dopaminergic system dysfunction as well as other neural impairments that may be DOPA-resistant or related to non-dopaminergic pathways.

Keywords: Parkinson’s disease; bimanual coordination; bradykinesia; dopamine; hypokinesia; motor control disorders.

Figure 1

Experimental set-up including Phantom Omni Devices, forearm constraints, and computer monitor with augmented feedback display. During testing, individuals forearms were held in place by the forearm constraints lined with foam padding and grasped the white and blue pen-shaped attachment in their hand with their thumbs on top.

Figure 2

Correlationanalyses revealing that higher motor severity in PD patients “off” (as measured by UPDRS-III) was associated with (A) greater coordination error (absolute error of relative phase, degrees) and (B) greater coordination variability (standard deviation of absolute error of relative phase, degrees). Red circles highlight the four least severe PD patients that were removed from all other analyses.

Figure 3

Mean absolute error of relative phase (degrees) compared between PD “off” and healthy comparison (HC) participants as a function of phase (in-phase = IP and anti-phase = AP) and cycle frequencies. Results showed that HC had more accurate coordination compared to PD “off” participants at faster cycle frequencies (1.25–2 Hz) in anti-phase (bars denote standard error). *Denotes significant differences between HC and PD “off” participants.

Figure 4

Mean amplitude (cm) of limb movements compared between PD “off” and healthy comparison (HC) participants as a function of cycle frequencies. Results showed that larger movement were produced by HC participants compared to PD “off” at all cycle frequencies.

Figure 5

The influence of dopamine replacement on mean amplitude (cm) of the more and less affected limb in PD participants across cycle frequencies. Results demonstrated that PD “on” had larger amplitude movements at the faster cycle frequency in the less affected limb. However, PD “off” had larger amplitude movements in the more and less affected limb at slower cycle frequencies (0.75–1 and 1 Hz, respectively) (bars denote standard error). *Denotes significant differences between PD “off” and PD “on.”