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

Mica Rubinson,Elisha Moses,Jodie Naim-Feil,Itai Horowitz,Doron Gothelf,Nava Levit-Binnun,Juan Silva-Pereyra

doi:10.1371/journal.pone.0217383

Abstract

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.

Highlights

Attention-deficit/hyperactivity (ADHD) is a developmental psychiatric disorder involving problems with attention and/or hyperactivity and impulsivity
Several studies involving continuous performance task (CPT) (X version) reported mixed-gender children with attention-deficit/hyperactivity disorder (ADHD) having abnormally small P3 amplitudes compared to controls, which were normalized after administration of MPH [27,28,29,30]
Well-designed experiments are important when inconsistency is reported in the literature, as is the case of evoked response potential (ERP) measured in ADHD with relation to cognitive tasks and to the effects of MPH

Summary

Introduction

Attention-deficit/hyperactivity (ADHD) is a developmental psychiatric disorder involving problems with attention and/or hyperactivity and impulsivity. Several studies involving CPT (X version) reported mixed-gender children with ADHD having abnormally small P3 amplitudes compared to controls, which were normalized after administration of MPH [27,28,29,30]. In a double-blind placebo-controlled cross-over design, Verbaten et al, 1994 [27] and Klorman et al, 1979 [28] compared MPH versus placebo effects during a CPT task and found increased P3 amplitude following MPH Both studies administrated the treatments on separate days without a preceding treatment-free session, and could not account for between-days variability. Klorman et al, 1999 [34] examined the ERP response of ADHD subjects during an auditory oddball cognitive task after a counter-balanced treatment of 14-days and found an increase in the N1 amplitude after MPH ingestion compared to placebo. As the SART was shown to not result in learning effects [42], we did not expect any between-days variability

Participants

Results

Discussion