Ritalin works by increasing the amount of dopamine released in the striatum, a key region in the brain related to motivation, action and cognition. Dopamine is a molecule that transports signals between nerve cells, and previous studies have shown that higher levels of dopamine make both humans and rodents more motivated to perform physically demanding tasks. The question was whether this was also the case for cognitive tasks: do the stimulants increase your ability to do something, or do they make you more motivated?
From observation to test
The study was conceptualized after the team at Radboudumc, led by professor Cognitive Neuropsychiatry Roshan Cools, theme Stress-related disorders, made an intriguing observation about the efficacy of drugs that stimulate dopamine receptors (used in Parkinson’s disease for example). It turned out that the effects of those drugs vary greatly across individuals, and that these effects can be predicted from the individuals’ baseline dopamine levels. The researchers wanted to find out if this was also true for methylphenidate, the active substance in drugs like Ritalin and Concerta that are used by so many people with ADHD, but also as smart pills by healthy people to enhance cognition and performance.
Using a model developed at Brown University, suggesting that dopamine changes the way the striatum emphasizes the benefits rather than the costs of completing physical and mental actions, Cools, from the Donders Institute for Brain, Cognition and Behaviour, set out to run an experiment. She and her team studied a group of healthy adults between 18 and 43 years of age. They measured the normal dopamine levels of each participant (using a PET-scan), and then asked them if they would take part in a series of cognitively demanding tasks. Some of these tasks were easier than others, but with varying amounts of monetary rewards, those who took on the hardest tasks stood to make the most money.
The participants participated in the experiment three times: once after taking a placebo, once after taking methylphenidate and once taking sulpiride, an antipsychotic drug that is thought to elevate dopamine levels when taken in low doses (at higher doses it is used to treat schizophrenia and major depressive disorder).
Cost versus benefit
The results of the experiment matched the mathematical model. Those with lower dopamine levels made decisions that shows they were more focused on avoiding difficult cognitive work – in other words, more sensitive to the costs of completing the work. The group with high dopamine levels, on the contrary, acted more sensitive to the differences in the amount of money they could earn – in other words, more focused on the potential benefits of completing the task. It did not matter whether the elevated dopamine levels were natural, or enhanced by the drugs.
The researchers hope their study helps future researchers and medical professionals better understand cognitive mechanisms, allowing them to identify connections between dopamine levels and disorders such as anxiety, depression, ADHD and schizophrenia.