Summary: Study reveals how methylphenidate interacts with cognitive control networks and attentional behaviors. Methylphenidate alters spontaneous neuronal activity in reward and cognitive control systems in children with ADHD. The changes result in more stable sustained attention.
For decades, doctors have treated children with Attention Deficit/Hyperactivity Disorder (ADHD) with methylphenidate, a stimulant drug sold as Ritalin and Concerta, making it one of the most more widely prescribed for the central nervous system. One would expect researchers to now know how methylphenidate works in the brain, but little is known about the drug’s mechanism of action.
Now, a new study seeks to fill that gap and understand how methylphenidate interacts with cognitive control networks and attentional behavior.
The new study appears in Biological psychiatry: cognitive neurosciences and neuroimaging.
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 hub of dopamine signaling.
In the new study, researchers led by Yoshifumi Mizuno, MD, Ph.D., Weidong Cai, Ph.D., and Vinod Menon, Ph.D., used brain imaging to explore the effects of methylphenidate on the NAc and so-called triple network system that plays a key role in behaviors that require adaptive control of attention.
The three networks include the salience, frontoparietal, and default mode networks. Aberrant activity was detected in the NAc and in several brain networks in children with ADHD, suggesting that dysregulation of the system may underlie ADHD symptoms and that correcting the dysfunction could alleviate these symptoms.
“Our results demonstrate in two independent cohorts that methylphenidate alters spontaneous neural activity in reward and cognitive control systems in children with ADHD. Drug-induced changes in cognitive control networks result in increased sustained attention steady.
“Our findings reveal a new brain mechanism underlying methylphenidate treatment in ADHD and inform the development of biomarkers to assess treatment outcomes,” noted Dr. Menon, Department of Psychiatry and Behavioral Sciences, Faculty of Medicine from Stanford University.
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.)
Apart from the CT scan, children with ADHD also performed a standardized task to assess sustained attention. Additionally, the researchers tested the replicability of the effects of methylphenidate on spontaneous brain activity in a second independent cohort.
Unsurprisingly, children performed better on attention tasks when taking medication. 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 displayed increased changes in brain activity patterns in the default-mode network with medication performed better on attention tasks with medication.
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 resting-state functional MRI, confirm the positive effects of methylphenidate on attention in children with ADHD and reveal the likely mechanism of action, through enhanced coordinated activity of the brain network and a likely key role for the enhanced effects of dopamine in the NAc region of the brain.
The work gives researchers a better understanding of how ADHD affects cognitive control networks in the brain and how methylphenidate interacts with these networks to modify behavior. The results could guide future work using brain imaging as a clinically useful biomarker of treatment response.
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“Methylphenidate improves spontaneous fluctuations in reward and cognitive control networks in children with attention deficit/hyperactivity disorder” by Yoshifumi Mizuno et al. Biological psychiatry: cognitive neurosciences and neuroimaging
Methylphenidate improves spontaneous fluctuations in reward and cognitive control networks in children with attention-deficit/hyperactivity disorder
Methylphenidate, a first-line treatment for attention-deficit/hyperactivity disorder (ADHD), is thought to influence dopaminergic neurotransmission in the nucleus accumbens (NAc) and its associated brain circuits, but this hypothesis has yet to be established. systematically tested.
We conducted a randomized, placebo-controlled, double-blind crossover trial in 27 children with ADHD. Children with ADHD were scanned twice with resting-state functional MRI under methylphenidate and placebo conditions, as well as an assessment of sustained attention. We examined spontaneous neural activity in the NAc and the salience, frontoparietal, and default mode networks, and their links to behavioral changes. The replicability of the effects of methylphenidate on spontaneous neural activity was examined in a second independent cohort.
Methylphenidate increased spontaneous neuronal activity in the NAc and the salience and default mode networks. Methylphenidate-induced changes in spontaneous activity patterns in the default mode network were associated with improvements in intra-individual response variability during a sustained attention task. Critically, despite the differences in clinical trial protocols and data acquisition parameters, the NAc and the salience and default mode networks showed reproducible patterns of methylphenidate-induced changes in l spontaneous activity in two independent cohorts.
We provide reproducible evidence demonstrating that methylphenidate enhances spontaneous neural activity in NAc and cognitive control networks in children with ADHD, resulting in more stable sustained attention. The results identify a new neural mechanism underlying methylphenidate treatment in ADHD and inform the development of clinically useful biomarkers to assess treatment outcomes.
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