RT Journal Article
SR Electronic
T1 Motor cortex inhibition and modulation in children with ADHD
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP e599
OP e610
DO 10.1212/WNL.0000000000007899
VO 93
IS 6
A1 Gilbert, Donald L.
A1 Huddleston, David A.
A1 Wu, Steve W.
A1 Pedapati, Ernest V.
A1 Horn, Paul S.
A1 Hirabayashi, Kathryn
A1 Crocetti, Deanna
A1 Wassermann, Eric M.
A1 Mostofsky, Stewart H.
YR 2019
UL http://n.neurology.org/content/93/6/e599.abstract
AB Objective Compared 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.Methods In 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.Results Go 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.Conclusion Children 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.ADHD=attention-deficit/hyperactivity disorder; AMT=active motor threshold; CSP=cortical silent periods; FDI=first dorsal interosseous; FSIQ=full-scale IQ; GABA=γ-aminobutyric acid; ICF=intracortical facilitation; K-SADS=Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children; M1=dominant resting motor cortex; MEP=motor evoked potential; PANESS=Physical and Neurological Examination for Subtle Signs; RMT=resting motor threshold; SICF=short interval facilitation; SICI=short interval cortical inhibition; SSRT=stop-signal reaction time; TD=typically developing; TMS=transcranial magnetic stimulation; TRUM=Task-Related Up-Modulation; WISC=Wechsler Intelligence Scale for Children