Methylphenidate is currently used to treat attention-deficit hyperactivity disorder (ADHD). The drug can be effective, but scientists are unsure exactly how the drug works. New research conducted at the Okinawa Institute of Science and Technology Graduate University (OIST) has shed light on how the drug affects the brain. The research could help with the development of more targeted medications to treat ADHD.
ADHD is characterized by poor concentration, hyperactivity, and impulsivity and individuals with the disorder can have difficulty regulating emotions. While the disorder is common and has been well studied, the cause not well understood.
Researchers at OIST have suggested ADHD may be caused by irregularities in dopamine release by neurons in the brain. Dopamine is involved in reward-motivated behavior. The researchers suggest in patients with ADHD, their neurons release less dopamine when a reward is expected and too much when a reward is given. That makes it hard for sufferers to engage in behavior that does not produce an immediate reward and they can be easily distracted by stimuli that do produce immediate rewards.
Methylphenidate is a stimulant that scientists believe has an effect on dopamine levels in the brain. It can help to improve concentration, reduce hyperactivity, and controls other symptoms in ADHD patients. However, the actions of the drug are not well understood.
The OIST researchers investigated the action of the drug on an area of the brain known to be involved in the reward system and where dopamine is mostly released – the ventral striatum. The researchers used a functional magnetic resonance imaging (fMRI) scanner to measure brain activity while research participants – young adults – played a computer game that simulated a slot machine.
The game showed a specific symbol when the participants won money and a different symbol when they didn’t. The participants quickly learned that the symbols corresponded to winning or not winning money and served as reward-predicting and non-reward-predicting cues.
Scans were taken of the ventral striatum on two occasions, one where the participants were given a placebo and a second time when they were given Methylphenidate. Participants with ADHD had similar neuronal activity in the ventral striatum when both symbols were displayed, but activity increased when the reward-predicting cue was displayed after taking Methylphenidate. After taking the drug, neuronal activity remained the same when the non-reward-predicting cue was displayed.
In participants with ADHD who had taken the placebo, increased neuronal activity in the ventral striatum correlated with increased activity in the prefrontal cortex when the reward was given. The prefrontal cortex is the region of the brain involved in decision making. The correlation was low when Methylphenidate was taken, and also in participants who did not have ADHD.
The research suggests that there is increased interaction between both areas of the brain in patients with ADHD, and Methylphenidate increases levels of the neurotransmitter norepinephrine, which regulates dopamine in the ventral striatum when rewards are given.
“Methylphenidate is effective but has some side effects, so some people are hesitant to take the medication or give it to their children,” said Dr. Emi Furukawa, first author of the study. “If we can understand what part of the mechanism results in therapeutic effects, we could potentially develop drugs that are more targeted.”
You can read more about the study in the paper – Methylphenidate modifies reward cue responses in adults with ADHD: An fMRI study – which was recently published in the journal Neuropharmacology. DOI: 10.1016/j.neuropharm.2019.107833