Motor cortex inhibition and modulation in children with ADHD

Abstract

ObjectiveCompared to typically developing (TD) peers, children with attention-deficit/hyperactivity disorder (ADHD) consistently demonstrate impaired transcranial magnetic stimulation (TMS)-evoked short interval cortical inhibition (SICI) of motor evoked potentials (MEPs) in resting motor cortex (M1). To determine whether perturbed M1 physiology also reflects clinically relevant behavioral dysfunction, we evaluated M1 physiology during a cognitive control task taxing motor response selection/inhibition.MethodsIn this case-control study, behavioral ratings, motor skill (assessed using standardized examination), and left M1 physiology were evaluated in 131 right-handed, 8- to 12-year-old children (66 ADHD: mean 10.5 years, 43 male; 65 TD: mean 10.6 years, 42 male). The primary outcomes were MEP amplitudes and SICI, evaluated during rest and during a modified “racecar” Slater-Hammel stop signal reaction task, with TMS pulses administered 150 ms prior to the target go action and after the dynamic stop cue.ResultsGo responses were significantly slower (p = 0.01) and more variable (p = 0.002) in ADHD. Children with ADHD showed less M1 SICI at rest (p = 0.02) and during go (p = 0.03) and stop trials (p = 0.02). Rest M1 excitability increased during response inhibition task engagement (p < 0.0001). This Task-Related Up-Modulation (TRUM) was less robust across and within groups, with diminished task upmodulation associated with significantly more severe ADHD behavioral ratings and slower stop signal reaction times.ConclusionChildren with ADHD show anomalous motor cortex physiology, with deficient SICI across behavioral states and less TRUM from rest to action selection. Associations of these physiologic measures with ADHD symptoms and cognitive control measures support further investigation into biological mechanisms.

Associations Between Task-Related Modulation of Motor-Evoked Potentials and EEG Event-Related Desynchronization in Children with ADHD

“…Within the larger sample that received TMS, we found that, compared with TD children, children with ADHD showed reduced SICI at rest and during the action-selection phase of the task (selecting to go or to stop), such that reduced SICI at rest does not resolve or normalize during engagement with this task. Additionally, we found that the amount of task-related up modulation (TRUM) of motor cortex excitability during this task was diminished in children with ADHD (Gilbert et al 2019). However, SICI and TRUM were only minimally correlated with one another (Zea Vera et al 2020), supporting the notion that these measures may be differentially sensitive to distinct mechanisms of altered physiology within ADHD.…”

“…We therefore expected SICI-alpha ERD correlations in both groups and no interaction effect. Finally, within the larger TMS sample, children with ADHD showed less TRUM (Gilbert et al 2019). Within the larger ADHD sample, they showed less alpha ERD (McAuliffe et al 2020).…”

“…The third TMS index reported was dubbed by our laboratory “TRUM”: Task-Related Up Modulation (of motor-evoked potentials) (Gilbert et al 2019; Zea Vera et al 2020). Interestingly, compared to rest, SICI diminishes during preparation to act and during actions (Garry and Thomson 2009; Hoegl et al 2012; Gilbert et al 2019) and is thus modulated by task-presence. Like the ERD, this metric is task associated.…”

“…Like the ERD, this metric is task associated. In the current set of experiments, TRUM was studied in the context of a modified, child-friendly version of the Slater Hammel Stop Signal Task (SST) (Guthrie Michael D. et al 2018; Gilbert et al 2019), which evaluates response inhibition performance. Different phases of the task are understood to represent action selection and response preparation.…”

“…The goal of the current paper is to directly explore associations between task-based and resting measures of EEG and TMS indices. As many participants participated in only one procedure or the other, prior publications from larger samples of which the one presented here is a subset have reported independently on TMS (Gilbert et al 2019) and EEG (McAuliffe et al 2020). Within the larger sample that received TMS, we found that, compared with TD children, children with ADHD showed reduced SICI at rest and during the action-selection phase of the task (selecting to go or to stop), such that reduced SICI at rest does not resolve or normalize during engagement with this task.…”