Research Article: Effects of methylphenidate on the ERP amplitude in youth with ADHD: A double-blind placebo-controlled cross-over EEG study

Date Published: May 31, 2019

Publisher: Public Library of Science

Author(s): Mica Rubinson, Itai Horowitz, Jodie Naim-Feil, Doron Gothelf, Nava Levit-Binnun, Elisha Moses, Juan Silva-Pereyra.


Methylphenidate (MPH) is a first line drug for attention-deficit/hyperactivity disorder (ADHD), yet the neuronal mechanisms underlying the condition and the treatment are still not fully understood. Previous EEG studies on the effect of MPH in ADHD found changes in evoked response potential (ERP) components that were inconsistent between studies. These inconsistencies highlight the need for a well-designed study which includes multiple baseline sessions and controls for possible fatigue, learning effects and between-days variability. To this end, we employ a double-blind placebo-controlled cross-over study and explore the effect of MPH on the ERP response of subjects with ADHD during a Go/No-Go cognitive task. Our ERP analysis revealed significant differences in ADHD subjects between the placebo and MPH conditions in the frontal-parietal region at 250ms-400ms post stimulus (P3). Additionally, a decrease in the late 650ms-800ms ERP component (LC) is observed in frontal electrodes of ADHD subjects compared to controls. The standard deviation of response time of ADHD subjects was significantly smaller in the MPH condition compared to placebo and correlated with the increased P3 ERP response in the frontoparietal electrodes. We suggest that mental fatigue plays a role in the decrease of the P3 response in the placebo condition compared to pre-placebo, a phenomenon that is significant in ADHD subjects but not in controls, and which is interestingly rectified by MPH.

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Attention-deficit/hyperactivity (ADHD) is a developmental psychiatric disorder involving problems with attention and/or hyperactivity and impulsivity. ADHD is often associated with anxiety, depression, difficulties with social interactions, learning disabilities and behavior disorders [1,2]. While the prevalence of ADHD is estimated to be higher than 10% among children [3], the neuronal causes of the disorder are still not fully understood. The standard of care medication in most cases is methylphenidate (MPH), which acts as a stimulant that intervenes in dopamine uptake. However, its role in curbing the disorder is also not fully elucidated yet.

Well-designed experiments are particularly important when inconsistency is reported in the literature, as is the case of ERP measured in ADHD with relation to cognitive tasks and to the effects of MPH. Less than a handful of studies have used placebo-controlled cross-over designs [27,28,32,34] which account for within-subject variability and placebo effects. Furthermore, none have accounted for between-days variability by performing a cognitive baseline session across all test days.




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