For decades, doctors have treated children with attention deficit/hyperactivity disorder (ADHD) with methylphenidate, a stimulant drug sold under the brand names Ritalin and Concerta, making it one of the most prescribed drugs for the central nervous system. One would expect researchers to now know how methylphenidate works in the brain, but little is known regarding the drug’s mechanism of action. A new study seeks to fill this gap and understand how methylphenidate interacts with cognitive control networks and attentional behavior.
The new study is published in Biological Psychiatry: Cognitive Neurosciences and Neuroimaging, published by Elsevier.
What researchers do know is that people with ADHD have lower dopamine signaling activity than neurotypical people in the interconnected brain networks that control attention and goal-directed behaviors. Specifically, methylphenidate is thought to improve ADHD symptoms by increasing dopamine levels in the nucleus accumbens (NAc), a dopamine signaling center.
In this new study, researchers led by Yoshifumi Mizuno, MD, PhD, Weidong Cai, PhD, and Vinod Menon, PhD, used brain imaging to explore the effects of methylphenidate on NAc and on a so-called triple network system. which plays a key role in behaviors that require adaptive attention control. The three networks include the salience, frontoparietal and default mode networks. Aberrant activity has been detected in the NAc and in several brain networks in children with ADHD, suggesting that a dysregulation of the system may underlie ADHD symptoms and that correcting this dysfunction may alleviate these symptoms. symptoms.
Our results demonstrate in two independent cohorts that methylphenidate alters spontaneous neuronal activity in reward and cognitive control systems in children with ADHD. Drug-induced changes in cognitive control networks result in more stable sustained attention. Our results reveal a new brain mechanism underlying methylphenidate treatment in ADHD and inform the development of biomarkers to assess treatment outcomes. »
Dr. Vinod Menon, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine.
The researchers used functional magnetic resonance imaging (fMRI) to measure the effects of methylphenidate on spontaneous brain activity in 27 children with ADHD and 49 typically developing controls. The children with ADHD were scanned at two different visits one to six weeks apart – once while receiving methylphenidate and once while receiving a placebo. (Typically developing children received no medication or placebo.) Besides the CT scan, children with ADHD also completed a standardized task to assess sustained attention. In addition, the researchers tested the reproducibility of the effects of methylphenidate on spontaneous brain activity in a second independent cohort.
Not surprisingly, the children performed better in attention tasks when they were on treatment. And as the researchers surmised, they also found greater spontaneous neuronal activity in the NAc and the salience and default mode networks when methylphenidate was given. Children with ADHD who showed greater changes in brain activity patterns in the default mode network with the drug performed better in attention tasks with the drug. The results were replicated in two independent cohorts, providing further evidence that methylphenidate can alleviate ADHD symptoms through its actions on the NAc and the triple-network cognitive system.
Cameron Carter, MD, editor of Biological Psychiatry: Cognitive Neurosciences and Neuroimagingsaid of the study: “The results, which used the widely available technique of functional resting-state MRI, confirm the positive effects of methylphenidate on attention in children with ADHD and reveal the likely mechanism of action, through enhancement of the coordinated activity of the brain network and a likely key role for the enhanced effects of dopamine in the NAc region of the brain”.
This work allows researchers to better understand how ADHD affects cognitive control networks in the brain and how methylphenidate interacts with these networks to modify behavior. The results might guide future work using brain imaging as a clinically useful biomarker of treatment response.
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Journal reference:
Mizuno, Y. et al. (2022) Methylphenidate improves spontaneous fluctuations in reward and cognitive control networks in children with attention-deficit/hyperactivity disorder. Biological Psychiatry: Cognitive Neurosciences and Neuroimaging. doi.org/10.1016/j.bpsc.2022.10.001.
