Effects of a single‐dose methylphenidate challenge on resting‐state functional connectivity in stimulant‐treatment naive children and adults with ADHD

Abstract

Prior studies suggest that methylphenidate, the primary pharmacological treatment for attention‐deficit/hyperactivity disorder (ADHD), alters functional brain connectivity. As the neurotransmitter systems targeted by methylphenidate undergo significant alterations throughout development, the effects of methylphenidate on functional connectivity may also be modulated by age. Therefore, we assessed the effects of a single methylphenidate challenge on brain network connectivity in stimulant‐treatment naïve children and adults with ADHD. We obtained resting‐state functional MRI from 50 boys (10–12 years of age) and 49 men (23–40 years of age) with ADHD (DSM IV, all subtypes), before and after an oral challenge with 0.5 mg/kg methylphenidate; and from 11 boys and 12 men as typically developing controls. Connectivity strength (CS), eigenvector centrality (EC), and betweenness centrality (BC) were calculated for the striatum, thalamus, dorsal anterior cingulate cortex (dACC), and prefrontal cortex (PFC). In line with our hypotheses, we found that methylphenidate decreased measures of connectivity and centrality in the striatum and thalamus in children with ADHD, but increased the same metrics in adults with ADHD. Surprisingly, we found no major effects of methylphenidate in the dACC and PFC in either children or adults. Interestingly, pre‐methylphenidate, participants with ADHD showed aberrant connectivity and centrality compared to controls predominantly in frontal regions. Our findings demonstrate that methylphenidate's effects on connectivity of subcortical regions are age‐dependent in stimulant‐treatment naïve participants with ADHD, likely due to ongoing maturation of dopamine and noradrenaline systems. These findings highlight the importance for future studies to take a developmental perspective when studying the effects of methylphenidate treatment.

Functional Near-Infrared Spectroscopy of English-Speaking Adults With Attention-Deficit/Hyperactivity Disorder During a Verbal Fluency Task

“…This may be because medicated patients were receiving various classes of psychotropic drugs and refrained from methylphenidate on the day of participation. Interestingly, our results are in line with a recent fMRI study that also found no major effects of a single methylphenidate challenge on the prefrontal cortex activity of adults with ADHD (Kaiser et al, 2022). These negative findings may be explained by the association between SNAP-25 polymorphisms and methylphenidate-induced hemodynamic changes (J.…”

Methylphenidate is more effective to improve inhibitory control and working memory compared to tDCS in children and adolescents with attention deficit/hyperactivity disorder: a proof-of-concept study

“…Third, a single stimulation of the anodal tDCS may not have been sufficient to give an effect. Although a single dose of MPH has been shown to affect brain network connectivity and cognitive symptoms (Epstein et al, 2007;Rubia et al, 2009Rubia et al, , 2011Kaiser et al, 2022), evidence converges that non-invasive brain stimulation techniques achieve their maximum effectiveness when the stimulation sessions are repeated (Fecteau et al, 2014;Meron et al, 2015;Lefaucheur et al, 2017). Multiple sessions of tDCS induce cumulative neurobiological effects over time, generating more robust neuroplasticity processes (Nitsche and Paulus, 2000;Boggio et al, 2009;Monte-Silva et al, 2013) that have greater efficacy on behavioral symptoms and neurocognitive measures.…”

Multi-omics approach reveals dysregulated genes during hESCs neuronal differentiation exposure to paracetamol

“…Considering that this is an in vitro system, the findings are compelling since structural cortical changes and catecholaminergic transmission have been the target of various epidemiological studies and drug clinical trials, both in children and adults with ADHD. 87 , 88 , 89 , 90 It is biologically plausible that medications that cross the placenta and the blood-brain barrier, may interfere with normal fetal brain neurodevelopment, previously shown for valproic acid, and more recently for topiramate. 91 This is especially relevant for substances that cross the blood-brain barrier, which is considered functional by the 8th week of gestation.…”