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Patients’ Brains May Adapt to ADHD Medication

May 30, 2023 | ADHD, Medication

The neurological condition Attention Deficit Hyperactivity Disorder (ADHD) is defined by an impulsive, hyperactive, and inattentive set of symptoms.  Methylphenidate, a stimulant medicine, is frequently recommended to patients with the illness to relieve these symptoms. Scientists do not fully comprehend the drug’s mechanism of action, though.

The Okinawa Institute of Science and Technology Graduate University’s (OIST) researchers have now pinpointed specific brain regions that react to methylphenidate. The findings may enable scientists to pinpoint the drug’s exact mechanism of action and thus create more precise treatments for the ailment.

According to earlier studies, persons with ADHD behave differently in their brains when expecting and getting rewards compared to people without the disorder. Dopamine is a ‘feel-good’ neurotransmitter involved in behavior motivated by rewards. According to research from OIST, people with ADHD release less dopamine when a reward is anticipated, and more dopamine when a reward is actually provided.

“In practice, what this means is that children, or even young adults, with ADHD, may have difficulty 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. Instead, they get distracted by external stimuli that are novel and interesting, such as a classmate talking or traffic noises,” states Dr. Emi Furukawa, a researcher at OIST’s Human Developmental Neurobiology Unit under the direction of Professor Gail Tripp, and the study’s first author.

According to researchers, methylphenidate improves dopamine availability in the brain, which helps persons with ADHD retain attention. The ventral striatum, a crucial part of the reward system and the location where dopamine is mostly released, is the target of Dr. Furukawa and her team’s investigation into the drug’s effects.  The goal of the study was to examine the effects of methylphenidate on the ventral striatum’s responses to reward cues and delivery,” Furukawa.

The study, which was released in the journal Neuropharmacology, was co-authored by researchers at Rio de Janeiro, Brazil’s D’Or Institute for Research and Education (IDOR). The partnership gave the researchers access to IDOR’s functional magnetic resonance imaging (fMRI) facilities and allowed them to pool their skills from several fields.

When young adults with and without ADHD played a computer game that resembled a slot machine, the researchers used fMRI to evaluate brain activity in both groups of participants. Two times, once after taking methylphenidate and once after taking a placebo, the researchers conducted scans on the ADHD group of participants. The computer also displayed one of two signals, either the Japanese character み (mi) or そ (so), every time the slot machine’s reels spun. The players rapidly realized as they were more experienced with the game prior to being scanned that they frequently won money when the slot machine displayed み, but lost it when it displayed そ. The sign thus served as a cue that predicted rewards, as opposed to one that did not.

When people with ADHD received the placebo, the researchers discovered that neuronal activity in the ventral striatum responded similarly to both the reward-predicting and non-reward-predicting cues. They were able to distinguish between the two cues more clearly after taking methylphenidate because activity in the ventral striatum increased exclusively in response to the reward cue.

In addition, the researchers looked at the relationship between neuronal activity in the striatum and medial prefrontal cortex, an area of the brain involved in decision-making that receives information from the outside world and interacts with other regions of the brain, including the striatum.

Neuronal activity in the striatum was highly linked with activity in the prefrontal cortex at the precise moment the reward was delivered and the participants got money from the slot machine game when the ADHD patients took a placebo instead of methylphenidate. The researchers conclude that the striatum and the prefrontal cortex interact more actively in persons with ADHD, which may explain why these individuals are more sensitive to rewarding outside stimuli. This link was not as strong in methylphenidate-taking participants as it was in non-ADHD individuals.

The results implicate a second neurotransmitter, norepinephrine, in the therapeutic effects of methylphenidate. Norepinephrine is released by a subset of neurons common in the prefrontal cortex. Researchers speculate that methylphenidate might boost levels of norepinephrine in the prefrontal cortex, which in turn regulates dopamine firing in the striatum when rewards are delivered.

According to Furukawa, the way in which methylphenidate modulates the reward response is fairly complex.  Despite this, he believes that figuring out how methylphenidate works could benefit researchers in creating more effective treatments for ADHD. “Methylphenidate is effective but has some side effects, so some people are hesitant to take the medication or give it to their children,” she explained. “If we can understand what part of the mechanism results in therapeutic effects, we could potentially develop drugs that are more targeted.”

Furukawa aspires to improve behavioral therapies by comprehending how methylphenidate affects the brain. For instance, parents and instructors could assist children with ADHD to stay focused by giving them regular praise and minimizing the quantity of distracting stimuli in the surroundings while keeping in mind the difference in brain responses when they anticipate and receive rewards.

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