Dopaminergic Therapy Improves Cognitive Motivation in Parkinson’s Patients, Study Reports

Dopaminergic treatment normalizes cognitive motivation in patients with Parkinson’s disease, making them more likely to choose a higher reward option in a computer-based task, a study reports.

The study, “Dopamine restores cognitive motivation in Parkinson’s disease,” was published in the journal Brain.

Approximately 40 percent of Parkinson’s patients experience a decrease in motivation, including cognitive apathy, which may manifest as needing assistance to start a mental activity or speech.

Dopamine plays a key role in motivating individuals to invest physical effort in return for a reward. Although lower levels of dopamine associated with Parkinson’s disease are believed to play a key role in cognitive apathy, scientists still need conclusive evidence.

The two current explanations for the link between dopamine and cognitive motivation include promoting cognitive effort and boosting working memory, a form of short-term memory important for reasoning and decision-making.

Recent studies of human motivation have used neuroeconomic approaches, which require participants to decide how much effort they are willing to make in exchange for a given reward. This strategy is valuable in the context of Parkinson’s, as the subjective value a person places on something is represented in the striatum — an area of the brain with reduced dopamine levels in Parkinson’s patients — and may be an objective marker of individual apathy.

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Now, a team of Australian researchers have evaluated whether dopamine is key to decision-making based on cognitive effort. The investigators used a new task, in which 20 participants with idiopathic (of unknown cause) Parkinson’s (mean age of 67.1 years, 12 men) had to choose between a low-effort/low-reward option and a high-effort/high-reward offer in each trial. Of the participants, 12 were determined to be apathetic based on the Dimensional Apathy Scale (DAS).

To account for the effects of the disease and treatment, patients were tested on levodopa and/or dopamine agonists and off (following overnight withdrawal) dopaminergic treatment, and choices were compared with those of 20 healthy individuals used as controls.

Each session had two phases. In the initial reinforcement phase, participants were taught to perform each level of cognitive effort to a ceiling performance, “to ensure that they could be positively reinforced on every trial at every effort level,” according to the researchers.

Cognitive effort was assessed as the number of rapid serial visual streams (one to six) that participants had to monitor for a target stimulus (the letter “T”) over 10 seconds. Each trial, for a total of 60 trials, consisted of 24 stimuli. Stimuli were presented on a laptop monitor, positioned about 60 cm from the participants.

The participants had to press a button to indicate the appearance of the target letter. At the end of each trial, the participants were awarded one point if they were able to complete the trial above a threshold level, or zero if not.

The initial reinforcement phase was followed by the choice phase, where participants had to indicate their preference between a baseline low-effort/low-reward and a variable high-effort/high-reward offer (10-point maximum). They were told their decisions were hypothetical and did not affect their compensation.

Results revealed that patients off medication were significantly less motivated, perceived the task to be more mentally demanding, and chose the more valuable offer less frequently than controls. This was particularly evident at high levels of effort and intermediate levels of reward.

Dopaminergic treatment lessened the perception of mental demand and made patients more willing to accept the more valuable offer independent of the likelihood of success, revealing no differences from controls.

Computational models then showed that dopamine reduced the variability in choice behavior. The data further showed that choices correlated with the executive subscale of the DAS, which specifically assesses cognitive motivation. According to the scientists, this suggests a close relationship between their measure of cognitive effort and subjective reports of day-to-day cognitive apathy.

“Here, we present the first evidence that dopamine causally modulates cognitive motivation,” the researchers wrote. “From a clinical perspective, these data emphasize the importance of optimizing dopaminergic therapy, not only to improve the motor symptoms and physical motivation in patients with Parkinson’s, but also to improve their willingness to engage in cognitively demanding behaviour.”