Predicting Clinical Gains and Side Effects of Stimulant Medication in Pediatric Attention-Deficit/Hyperactivity Disorder by Combining Measures From qEEG and ERPs in a Cued GO/NOGO Task

Geir Ogrim, Juri D Kropotov, Geir Ogrim, Juri D Kropotov

Abstract

Objectives: The study aim was to develop 2 scales: predicting clinical gains and risk of acute side effects of stimulant medication in pediatric attention-deficit/hyperactivity disorder (ADHD), combining measures from EEG spectra, event-related potentials (ERPs), and a cued visual GO/NOGO task.

Methods: Based on 4-week systematic medication trials, 87 ADHD patients aged 8 to 17 years were classified as responders (REs, n = 62) or non-REs (n = 25), and belonging to the side effects (SEs, n = 42) or no-SEs (n = 45) groups. Before starting the trial, a 19-channel EEG was registered twice: Test 1 (T1) without medication and T2 on a single dose of stimulant medication a few days before the trial. EEG was registered T1 and T2: 3 minutes eyes-closed, 3 minutes eyes-open, and 20 minutes cued GO/NOGO. EEG spectra, ERPs, omissions, commissions, reaction time (RT), and RT variability were computed. Groups were compared at T1 and T2 on quantitative EEG (qEEG), ERPs and behavioral parameters; effect sizes ( d) were estimated. Variables with d > 0.5 were converted to quartiles, multiplied by corresponding d, and summed to obtain 2 global scales.

Results: Six variables differed significantly between REs and non-REs (T1: theta/alpha ratio, P3NOGO amplitude. Differences T2-T1: Omissions, RT variability, P3NOGO, contingent negative variation [CNV]). The global scale d was 1.86. Accuracy (receiver operating characteristic) was 0.92. SEs and no-SEs differed significantly on 4 variables. (T1: RT, T2: novelty component and alpha peak frequency, and RT changes. Global scale d = 1.08 and accuracy = 0.78.

Conclusion: Gains and side effects of stimulants in pediatric ADHD can be predicted with high accuracy by combining EEG spectra, ERPs, and behavior from baseline and single-dose tests. ClinicalTrials.gov identifier: NCT02695355.

Keywords: ADHD; ERPs; predictions; qEEG; stimulants.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Grand-average event-related potentials (ERPs) in the cued GO/NOGO task. ERPs for all subjects and T1 and T2 are averaged (n = 176). (a) Left to right: ERPs at Cz and Pz electrodes to the first stimuli: animal-Cue (black lines) and plant-No Cue (gray lines), ERPs to the second relevant stimuli: GO (black lines) and NOGO (gray lines). ERPs to second ignored stimuli: visual alone (black lines), and visual + Novel auditory stimuli (gray lines). (b) Maps for the main components: P3 Cue, contingent negative variation (CNV) Cue for Cue stimuli, P3 GO and P3 NOGO for GO and NOGO stimuli, N1 and P2 waves to visual + Novel auditory stimuli. The arrows in (a) indicate the components.
Figure 2.
Figure 2.
Grand-average event-related potentials (ERPs) for responders (REs) and non-REs. (a) Grand-average NOGO ERPs at Cz and Pz electrodes for REs and non-REs at T1 (light green = RE, red = non-RE), T2 (dark green = RE, pink = non-RE), and T2-T1 differences (light blue = RE, dark blue = non-RE). Vertical gray line = onset of stimulus presentation. Contingent negative variation (CNV) indicates prestimulus baseline. (b) Maps of ERPs for REs and non-REs taken at maximums of P3 NOGO waves indicated by arrows at (a).
Figure 3.
Figure 3.
Grand-average event-related potentials (ERPs) in the group of patients with side effects (SE) and no-side effects (no-SE). (a) Grand-average ERPs to novelty at Cz and Pz electrodes for SEs and no-SEs taken at T1 (light green, no-SE; red, SE), T2 (dark green, no-SE; pink, SE), and T2 − T1 differences (light blue, no-SE; dark blue, SE). Maps of ERPs for SEs and non-SEs taken at maximums of P3 NOGO waves indicated by arrows at (a).

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