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

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.

Enhancing neural markers of attention in children with ADHD using a digital therapeutic

“…Examining each time window separately, MFT changes were most evident immediately following stimulus presentation ('early') and in preparation for the upcoming task trial ('late'), although it should be noted that we did not observe a formal statistical interaction between session and time window for these analyses. Early processing (approximately 100 ms post-stimulus presentation) is thought to reflect initial orienting of attentional resources [41][42][43], while late processing (approximately 650-800 ms post-stimulus presentation) may reflect post-response processes, such as suppressing the previous stimulus and updating in preparation for the upcoming trial [26]. With respect to the present study, children with ADHD have shown impaired neural oscillations for both early and late stimulus processing [26].…”

“…Here, we focused on post-stimulus ERSP changes in peak MFT, as in our previous work [18]. In addition to peak MFT, other work has pointed to the relevance of early and late EEG-based components in populations with cognitive control and attentional difficulties, such as ADHD [26][27][28][29]. To examine potential timing differences across the 0-880 ms time course, we created 120 ms composite bins at 3 timepoints during the trials: (1) the first three windows ('early': 0-120 ms), (2) the three windows around the MFT peak ('peak': 160-280 ms, as the peak time bin was found to be 200-240 ms, see Results), and (3) the last three windows ('late': 760-880 ms).…”

Caudate and cerebellar involvement in altered P2 and P3 components of GO/NoGO evoked potentials in children with attention‐deficit/hyperactivity disorder

“…Regarding specifically visual inhibition tasks, atypical N2 and P3 have been widely described in children and adolescents (Doehnert et al., 2010; Groom et al., 2008, 2010; Johnstone & Clarke, 2009; Rubinson et al., 2019). Although debate persists, N2 is considered to be related to early inhibition control (Falkenstein et al., 1999; Sur & Sinha, 2009) and more specifically to conflict monitoring (Albares et al., 2015; Donkers & van Box tel, 2004; Enriquez‐Geppert et al., 2010; Huster et al., 2013).…”

“…Most robust ERP alterations have been reported in early orienting, memory encoding, inhibitory control, and error‐processing components in children with ADHD compared with typically developing children (TDC; Barry et al., 2003; Johnstone et al., 2013; Kaiser et al., 2020; Lenartowicz et al., 2014, 2019). Because inhibition control has been considered as the primary deficit in ADHD (Barkley, 1997), measures of inhibition processes like GO/NoGO tasks were extensively used to investigate EEG features of ADHD (Baijot et al., 2016, 2017; Buchmann et al., 2011; Groom et al., 2010; Johnstone & Clarke, 2009; Rubinson et al., 2019; Wiersema et al., 2006).…”

The Influence of Filters on EEG-ERP Testing: Analysis of Motor Cortex in Healthy Subjects

“…One of the more popular environments used for preprocessing is MATLAB software together with open packages, i.e., EEGLAB, ERPLAB [20], SPM or Fieldtrip, or commercial ones, i.e., Curry or BESA. The aforementioned filters have been widely described in scientific papers both in technical terms, FIR [21,22], IIR [23,24], FFT [25,26], NOTCH, and in clinical applications or in typical research, FIR [27], NOTCH [28], FFT [29].…”