Motor Sequence Learning and Consolidation in Unilateral De Novo Patients with Parkinson's Disease

Abstract

Previous research investigating motor sequence learning (MSL) and consolidation in patients with Parkinson's disease (PD) has predominantly included heterogeneous participant samples with early and advanced disease stages; thus, little is known about the onset of potential behavioral impairments. We employed a multisession MSL paradigm to investigate whether behavioral deficits in learning and consolidation appear immediately after or prior to the detection of clinical symptoms in the tested (left) hand. Specifically, our patient sample was limited to recently diagnosed patients with pure unilateral PD. The left hand symptomatic (LH-S) patients provided an assessment of performance following the onset of clinical symptoms in the tested hand. Conversely, right hand affected (left hand asymptomatic, LH-A) patients served to investigate whether MSL impairments appear before symptoms in the tested hand. LH-S patients demonstrated impaired learning during the initial training session and both LH-S and LH-A patients demonstrated decreased performance compared to controls during the next-day retest. Critically, the impairments in later learning stages in the LH-A patients were evident even before the appearance of traditional clinical symptoms in the tested hand. Results may be explained by the progression of disease-related alterations in relevant corticostriatal networks.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Experimental Design.

See text for details of each phase. W/U = warm-up.

Fig 2. Block Duration in Session 1 (A) and Session 2 (B).

Data points represent group means for each block and error bars depict standard errors. Black squares = healthy controls; blue circles = left hand asymptomatic (LH-A) patients with PD; red crosses = left hand symptomatic patients (LH-S) with PD. Thick solid lines represent group-averaged trajectories based on a single exponential fit.

Fig 3. The number of correct sequences in Session 1 (A) and Session 2 (B).

Data points represent group means for each block and error bars depict standard errors. Black squares = healthy controls; blue circles = left hand asymptomatic (LH-A) patients with PD; red crosses = left hand symptomatic patients (LH-S) with PD.

Fig 4. Performance Index (PI) in Session 1 (A) and Session 2 (B).

Data points represent group means for each block and error bars depict standard errors. Black squares = healthy controls; blue circles = left hand asymptomatic (LH-A) patients with PD; red crosses = left hand symptomatic patients (LH-S) with PD. Thick solid lines represent group-averaged trajectories based on a single exponential fit.

Fig 5. Schematic of how performance on the MSL task may reflect disease progression.

All participants completed the MSL task with their non-dominant left hand. X’s denote the affected side and the size of the X represents the relative magnitude of the impairment. Squares indicate that the right (contralateral) striatum is more critical for the execution of the MSL task since the left hand was used. In the left hand symptomatic (LH-S) group, the MSL task targeted the more affected right striatum. In contrast, in the left hand asymptomatic (LH-A) group, motor deficits were limited to the right side; thus, the MSL task targeted the less affected right striatum. In the control group, the MSL task targeted the intact right striatum. Comparison of the experimental groups may represent progression of PD. Please note that this schematic is intended to depict the laterality aspect of the research approach and does not address changes within striatal subregions as a function of MSL training. These details are discussed in the main text.