How Tremor Affects Learning Abilities in Patients With Parkinson Disease

Patients with Parkinson disease (PD) who do not experience tremor were found to show improvements in reward learning after taking dopaminergic medication, while those with PD and tremor exhibited no benefit in reinforcement learning, according to study findings published in the journal Brain.

As the researchers note, severity of motor signs is highly variable among patients with PD, particularly the presence or absence of tremor. “This variability in tremor relates to variation in cognitive/motivational impairment, as well as the spatial distribution of neurodegeneration in the midbrain and dopamine depletion in the striatum,” explain the study authors.

They sought to examine whether this variability in tremor presence, of which 1 in 4 patients do not experience these symptoms, may help in explaining another notable variability in PD: the effects of dopaminergic medication on reinforcement learning. Characterized by the loss of dopamine, those affected by PD become less sensitive to learning through rewards as the disease progresses, which can be further exacerbated by the presence of tremor as those with and without this symptom exhibit different dopaminergic phenotypes.

In the study, the researchers recruited 43 tremor-dominant and 20 nontremor patients with PD who were tested both OFF, defined as abstinence from medication for more than 3 times the drug half-life, and ON dopaminergic medication (200/50-mg levodopa-benserazide), while 22 age-matched control subjects were also recruited to be tested twice OFF medication. Participants completed a reinforcement learning task designed to dissociate effects on learning rate from effects on motivational choice, in which their tendency to go or not go in the face of reward or threat of punishment was analyzed.

Among nontremor patients, dopaminergic medication was found to improve reward-based choice, in contrast with tremor-dominant patients who improved from punishment.

"We observed that, with medication, patients without tremor got better at a task in which they had to learn to push a button in order to receive a reward (points). This result fully agrees with prior research. However, remarkably enough, patients with tremor would exhibit an opposite effect,” said  Hanneke den Ouden, PhD, brain researcher at Radboud University, in a statement.

Speaking further on the implications of these findings, study author Rick Helmich, MD, PhD, neurologist at Radboud university medical center, additionally highlighted in the statement the need to improve our understanding of how tremor plays a role in the dopamine systems of patients with PD and its subsequent impact on motor isses and cognition.

"Whether someone experiences tremor or not might therefore potentially have a significant predictive value regarding the effectiveness of medication in the cognitive domain. However, more and larger studies are needed before this can be confirmed," said Helmich.

Reference

van Nuland AJ, Helmich RC, Dirkx MF, et al. Effects of dopamine on reinforcement learning in Parkinson’s disease depend on motor phenotype. Brain. Published online November 4, 2020. doi:10.1093/brain/awaa335