One of the most common forms of attention-deficit hyperactivity disorder (ADHD) medication is a stimulant drug called methylphenidate which is used to treat symptoms such as impulsiveness, bouts of hyperactivity, and the inability to focus. And while the drug does seem to work quite well, scientists don’t fully understand why. In order to try and gain a better understanding, researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) conducted a study to determine how certain areas of the brain respond to the drug which could lead to the potential development of more targeted medicine. 

No two ADHD patients will ever have the exact same responses when waiting for or receiving a reward. And neither will that of an ADHD patient and an individual without the disorder. The researchers proposed that those individuals with ADHD, released less dopamine in the brain when waiting for a reward and more when actually receiving it. “In practice, what this means is that children, or even young adults, with ADHD may have difficulty in engaging in behavior that doesn’t result in an immediate positive outcome.

For example, children may struggle to focus on schoolwork, as it may not be rewarding at the time, even though it could ultimately lead to better grades,” explained researcher and first author of the study, Dr Emi Furukawa. “Instead they get distracted by external stimuli that are novel and interesting, such as a classmate or traffic noises. 

The fMRI machine located in the IDOR imaging suite. fMRI is used to indirectly detect increased neuronal activity in an area of the brain by measuring higher levels of oxygenated to deoxygenated blood. CREDIT Andressa Dias Lemos, IDOR

Methylphenidate is thought to help those with ADHD focus by way of enhancing dopamine availability within the brain. Therefore, the team-centered their study on how the drug affects the ventral striatum, a part of the brain involved in the reward process and the release of dopamine. Using the D’Or Institute for Research and Education (IDOR)’s functional magnetic resonance imaging facility (fMRI), the researchers were able to measure the brain activity in various young adults )some with ADHD and some without) while they were playing a video game that simulated a slot machine. The ADHD individuals were scanned twice during the trial –  once when they had taken the drug and again when they had taken a placebo pill. 

Whenever the slot machine reels spun, either one of two cues were shown on the screen also. When one of the symbols was shown the individual often won money, but when the other appeared they won nothing. Therefore, the participants soon learned to associate the first symbol with that of winning money, and the second with being a non-rewarding cue. Results from the study showed that when those with ADHD took the placebo pill, neuronal activity in the ventral striatum was much the same as the response they exhibited with both the reward and non-rewarding cues. However, when methylphenidate was taken, only the reward cue increased activity in the ventral striatum, proving the individuals were capable of distinguishing between the two cues. 

Another area explored by the researchers was how neuronal activity in the medial prefrontal cortex correlated to activity within the striatum. The medial prefrontal cortex is a part of the brain that’s involved in decision-making. It receives data externally and communicates with various areas of the brain, including the striatum. When the placebo pill was taken instead of methylphenidate, there was a strong correlation between the neuronal activity in the striatum and that of the prefrontal cortex at the exact time the reward was delivered. So, the conclusion was that people with ADHD had more active communication between that of the striatum and the prefrontal cortex. This could explain the heightened sensitivity that those with ADHD experience when presented with a reward. Those who took methylphenidate and those without ADHD both had a very low activity level. 

Results from the study also indicated that a second neurotransmitter, norepinephrine, is released in the prefrontal cortex by a set of common neurons. The team has speculated that methylphenidate may boost these levels, helping to regulate dopamine levels in the striatum as rewards are delivered. “It’s becoming clear to us that the mechanism by which methylphenidate modulates the reward response is very complex,” commented Furukawa.

However, despite its complexity, the team is hopeful that further research into pinning down methylphenidate’s mechanisms of actions will benefit a lot of people worldwide. Currently there are some side effects to taking the drug which is making some people reluctant to give it to their children. If scientists can better understand the ins and outs of the drug, they may be able to better tailor it to help people without so many side effects.