All told, participants' movement times improved substantially relative to baseline following SDR induction (probability of direction [pd] = 100%), with little evidence of improvement in movement error (pd = 64.98%). Notably, the movement times were similar between SDR sessions and LDR sessions (pd = 65.93%) as participants showed a marked improvement in movement error between these sessions (pd = 99.03%). Additionally, the LDR + SDR sessions showed improvements in both movement time and accuracy relative to previous sessions (all pd > 98.43%).
The joystick outcome measures were highly correlated with both UPDRS-III scores and finger tapping rates. Investigators reported that UPDRS-III scores strongly predicted movement time, linearity, and efficiency (time: median = 0.012 seconds [HDI, 0.006-0.017], pd = 100%; Spearman's ρ = 0.298, P = .059; linearity: median = 0.122 [HDI, 0.018-0.226], pd = 98.94%; ρ = 0.462, P = .002; efficiency: median = 0.013 [HDI, 0.004-0.023], pd = 100%; ρ = 0.418, P = 0.006). Similarly, authors also noted that the finger tapping rates strongly predicted movement times (median = −0.005 s [HDI, −0.007 to −0.004], pd = 100%; ρ = −0.733, P = 5e−08).
“The major implication of these results are that we still don't yet fully understand how dopaminergic function relates to motivation and motor control and more theoretical and experimental work is needed. For patients, I think our work should reinforce the notion that it's not just the acute dose of dopaminergic drugs that has benefits, but rather the sustained use over longer periods of time (weeks/months) that has very large beneficial effects,” Lee told.
Participants displayed no modulation of movement time, error, or efficiency related to rewards at baseline and during the SDR sessions. Authors noted that a discrepancy in movement error emerged in the SDR session between $20 and both $10 and $5 rewards, contrary to expected scaling of movement linearity with reward. Notably, participants showed lower precision when anticipating a $20 reward compared with both $10 and $5. In the LDR session, no modulation of motor performance by reward was observed (all pd < 86%). However, a reward effect surfaced in the final SDR + LDR session, which provided strong evidence that participants were faster and more precise in their movements on high reward ($20) trials than on low reward ($5) trials (all pd > 95%).
Limitations of the study include the small sample size, because of challenges with recruitment of a large sample of de novo participants with PD. Authors note that it is unclear whether these new results will extend to alternative tasks with different motor requirements for successful performance. Additionally, the current study only examined 2 aspects of bradykinesia, slowing of movement and movement linearity, but it also encompasses progressive decrements in movement speed and amplitude with repetition.3
"We are interested in following up to examine how the LDR might contribute to improving other symptoms of PD, such as different facets of bradykinesia. We would encourage other researchers to consider that the LDR has very large effects and to acknowledge that we still have a relatively poor understanding of how DRT produces such amazing benefits,” Lee added.
REFERENCES
1. Brissenden JA, Scerbak T, Albin RL, Lee TG. Motivational Vigor in Parkinson's Disease Requires the Short and Long Duration Response to Levodopa. Mov Disord. Published online December 7, 2023. doi:10.1002/mds.29659
2. Mazzoni P, Hristova A, Krakauer JW. Why don't we move faster? Parkinson's disease, movement vigor, and implicit motivation. J Neurosci. 2007;27(27):7105-7116. doi:10.1523/JNEUROSCI.0264-07.2007
3. Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015;30(12):1591-1601. doi:10.1002/mds.26424
