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

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.”


  1. I am a caregiver of someone with Parkinson’s first diagnosed in 2005, and I concur with the experimental findings. Being late or missing a dose of Sinemet has motivational consequences that are often verbalized by the patient.

  2. Dr. C says:

    This is a good explanation about how dopamine and task initiation are linked together. Something I have written about in my columns, and which I think could be considered as an early sign of PD (when combined with other information). Maybe someone will do research on the additional benefits of adding brain training for minimizing PD’s task initiation effects.

  3. Recently it has been shown that PD and ALZ patients have leaky blood brain barriers via scientists at UCLA. This is likely the linkage to old age from both diseases. Since PD patients are prescribed carbidopa and levodopa this creates a deadly situation. Carbidopa would be effective if an d only if it does not pass the blood-brain barrier. But if the blood-brain barrier were leaky carbidopa would penetrate the BBB. If that happened what would be the outcome? Carbidopa is an amino acid decarboxylase inhibitor and if it got into the brain of older people it would prevent the levodopa from producing dopamine. The consequence of that is death. Further more the combination of levodopa/carbidopa produces a dwindling respone or tachyphylaxsis over time. Why would that occur? As the levo dopa was being converted less and less to dopamine -this action would produce a dwindling response over time which is exactly what happens.
    When l- dopa was originally given alone from 1960-1975 the death rate went down. From 1975-to present day the death rate has climbed 400% or four fold. Why did this occur? It is because the drug companies and the federal government have ignored the data. In addition credit should be given to Dr Hinz from Florida who found that carbidopa reacts with vitamin B6 forming an inactive complex. The body has 9 essential amino acids bout needs a total of 20 amino acids. Therefore, it makes the other 12 amino acids from the original 9 using vitamin B6 the transamination vitamin. When the vitamin B6 is complexed with carbidopa by Schiff base formation it depletes the vitamin B6 and the person taking carbidopa/levodopa becomes malnourished. Likely the malnourishment and the leakage of the blood-brain barrier combines to create an early death for patients taking the combined therapy.

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