TY - JOUR
T1 - Motor cortex inhibition and modulation in children with ADHD
AU - Gilbert, Donald L.
AU - Huddleston, David A.
AU - Wu, Steve W.
AU - Pedapati, Ernest V.
AU - Horn, Paul S.
AU - Hirabayashi, Kathryn
AU - Crocetti, Deanna
AU - Wassermann, Eric M.
AU - Mostofsky, Stewart H.
N1 - Funding Information:
This research was funded by R01 MH095014 and R01 MH085328.
Publisher Copyright:
© American Academy of Neurology.
PY - 2019/8/6
Y1 - 2019/8/6
N2 - 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.
AB - 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.
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U2 - 10.1212/WNL.0000000000007899
DO - 10.1212/WNL.0000000000007899
M3 - Article
C2 - 31315973
AN - SCOPUS:85071069777
SN - 0028-3878
VL - 93
SP - E599-E610
JO - Neurology
JF - Neurology
IS - 6
ER -