Objective: Test if symptoms of Parkinson’s disease (PD) develop through aberrant plasticity.

Background: Recent results in 6-hydroxydopamine-lesioned mice show that repeated performance of simple motor tasks following dopamine depletion paradoxically causes progressive worsening of performance [1]. This worsening performance (“aberrant learning”) is task specific, compounds across days, and can be reversed by practicing the same tasks after administration of levodopa. If patients with PD also exhibit aberrant learning, this could explain the long-duration response (LDR) to levodopa [2-4] and suggest strategies for pairing motor activity with dopaminergic medications for optimal efficacy [5].

Method: Patients with PD presenting to clinic after overnight medication withdrawal were asked to perform a simple finger tapping task (rapidly opening and tapping the dominant thumb and index finger for 10 seconds) during 10 trials separated by 1 minute. Movements were filmed and thumb and index finger locations were tracked using DeepLabCut [6]. Distance between thumb and index finger tips was plotted over time and local peaks were extracted to measure the amplitude of each movement. Sequence effect (SE), decrementing amplitude of repeated movements characteristic of bradykinesia in PD [7], was quantified by fitting an exponential decay model to amplitudes within each trial.

Results: We have so far completed data analysis for one participant. DeepLabCut allowed highly accurate tracking of fingertip positions each each frame [figure 1A]. We observed a pronounced SE within each trial [figure 1B]. Mean movement amplitude became smaller and SE became more negative across trials [figure 1C].

Conclusion: These preliminary results are consistent with our prediction that repeated motor performance off dopaminergic medications drives worsening of bradykinesia. If this effect replicates in a larger cohort of patients, it would support our hypothesis that Parkinsonian motor symptoms result from aberrant plasticity. Future directions will include examining how SE and aberrant learning are impacted by levodopa and deep brain stimulation of the subthalamic nucleus.

Figure 1

References: 1. Cheung, T.H.C., et al., Learning critically drives parkinsonian motor deficits through imbalanced striatal pathway recruitment. Proc Natl Acad Sci U S A, 2023. 120(12): p. e2213093120.
2. Cotzias, G.C., P.S. Papavasiliou, and R. Gellene, Modification of Parkinsonism—chronic treatment with L-dopa. New England Journal of Medicine, 1969. 280(7): p. 337-345.
3. Nutt, J., Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, 1994: PHARMACODYNAMICS OF LEVODOPA IN PARKINSON’S DISEASE. Clinical and experimental pharmacology and physiology, 1995. 22(11): p. 837-840.
4. Beeler, J.A., et al., Dopamine‐dependent motor learning: insight into levodopa’s long‐duration response. Annals of neurology, 2010. 67(5): p. 639-647.
5. Beeler, J.A., et al., A role for dopamine-mediated learning in the pathophysiology and treatment of Parkinson’s disease. Cell Rep, 2012. 2(6): p. 1747-61.
6. Nath, T., et al., Using DeepLabCut for 3D markerless pose estimation across species and behaviors. Nat Protoc, 2019. 14(7): p. 2152-2176.
7. Kang, S.Y., et al., Characteristics of the sequence effect in Parkinson’s disease. Mov Disord, 2010. 25(13): p. 2148-55.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/computer-vision-quantification-of-repeated-finger-tapping-demonstrates-aberrant-plasticity-in-parkinsons-disease/