Researchers have made great progress in understanding how the most commonly used ADHD (Attention Deficit Hyperactivity Disorder) medications function in the treatment of ADHD, such as stimulants like methylphenidate (e.g., Ritalin) and amphetamine-based pharmaceuticals (e.g., Adderall).
For decades, doctors have used methylphenidate, a stimulant drug sold as Ritalin and Concerta, to treat children with attention-deficit/hyperactivity disorder (ADHD), making it one of the most commonly prescribed treatments aimed at the central nervous system. Researchers might assume to know how methylphenidate works in the brain by now, yet nothing is known about the drug’s mechanism of action. A recent study aims to bridge this knowledge gap by investigating how methylphenidate interacts with cognitive control networks and attentional behavior.
Elsevier publishes the new study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.
What researchers do know is that persons with ADHD have lower dopamine signaling activity in the interconnected brain networks that control attention and goal-directed actions than neurotypical individuals. Methylphenidate, in particular, is thought to alleviate ADHD symptoms by raising dopamine levels in the nucleus accumbens (NAc), a center for dopamine signaling.
Our findings demonstrate in two independent cohorts that methylphenidate changes spontaneous neural activity in reward and cognitive control systems in children with ADHD. Our findings reveal a novel brain mechanism underlying methylphenidate treatment in ADHD and inform biomarker development for evaluating treatment outcomes.
Dr. Menon
Researchers led by Yoshifumi Mizuno, MD, Ph.D., Weidong Cai, PhD, and Vinod Menon, PhD, used brain imaging to investigate the effects of methylphenidate on the NAc and a system known as the triple network system, which is important in behaviors that require adaptive management of attention. The salience, frontoparietal, and default mode networks are among the three. In children with ADHD, abnormal activity was observed in the NAc and various brain networks, implying that dysregulation in the system may underpin ADHD symptoms and that addressing the malfunction may ameliorate such symptoms.
“Our findings demonstrate in two independent cohorts that methylphenidate changes spontaneous neural activity in reward and cognitive control systems in children with ADHD. Medication-induced changes in cognitive control networks result in more stable sustained attention. Our findings reveal a novel brain mechanism underlying methylphenidate treatment in ADHD and inform biomarker development for evaluating treatment outcomes,” noted Dr. Menon, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine.
The researchers examined the effects of methylphenidate on spontaneous brain activity in 27 children with ADHD and 49 normally developing controls using functional magnetic resonance imaging (fMRI). Children with ADHD were scanned twice, one to six weeks apart, once while using methylphenidate and once while taking a placebo. (Typically, neither medication nor placebo was given to developing youngsters.) Children with ADHD also completed a standardized activity to assess sustained attention outside of the scanner. The researchers also investigated the replicability of methylphenidate’s effects on spontaneous brain activity in a second independent cohort.
Unsurprisingly, when youngsters were medicated, they performed better on concentration challenges. When methylphenidate was delivered, the researchers observed increased spontaneous neuronal activity in the NAc, as well as the salience and default mode networks, as predicted. With medication, children with ADHD who showed greater alterations in brain activity patterns in the default mode network fared better on attention activities. The findings were repeated in two independent cohorts, adding to the evidence that methylphenidate may ameliorate ADHD symptoms through its activities on the NAc and the triple network cognitive system.
According to Cameron Carter, MD, the editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, “the findings, which used the widely available technique of resting-state functional MRI, confirm the positive effects of methylphenidate on attention in children with ADHD and reveal the likely mechanism of action, through improved coordinated brain network activity and a likely key role for enhanced dopamine effects in the NAc region of the brain.”
The findings help researchers better understand how ADHD affects cognitive control networks in the brain and how methylphenidate interacts with these networks to change behavior. The findings could help guide future research into brain imaging as a therapeutically meaningful biomarker of therapy response.
