Motor cortex inhibition and modulation in children with ADHD

Donald L. Gilbert, David A. Huddleston, Steve W. Wu, Ernest V. Pedapati, Paul S. Horn, Kathryn Hirabayashi, Deanna Crocetti, Eric M. Wassermann, Stewart H Mostofsky

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e599-e610
JournalNeurology
Volume93
Issue number6
DOIs
StatePublished - Aug 6 2019

Fingerprint

Motor Cortex
Attention Deficit Disorder with Hyperactivity
Motor Evoked Potentials
Transcranial Magnetic Stimulation
Neurobehavioral Manifestations
Motor Skills
Inhibition (Psychology)
Reaction Time
Cues
Case-Control Studies

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Gilbert, D. L., Huddleston, D. A., Wu, S. W., Pedapati, E. V., Horn, P. S., Hirabayashi, K., ... Mostofsky, S. H. (2019). Motor cortex inhibition and modulation in children with ADHD. Neurology, 93(6), e599-e610. https://doi.org/10.1212/WNL.0000000000007899

Motor cortex inhibition and modulation in children with ADHD. / Gilbert, Donald L.; Huddleston, David A.; Wu, Steve W.; Pedapati, Ernest V.; Horn, Paul S.; Hirabayashi, Kathryn; Crocetti, Deanna; Wassermann, Eric M.; Mostofsky, Stewart H.

In: Neurology, Vol. 93, No. 6, 06.08.2019, p. e599-e610.

Research output: Contribution to journalArticle

Gilbert, DL, Huddleston, DA, Wu, SW, Pedapati, EV, Horn, PS, Hirabayashi, K, Crocetti, D, Wassermann, EM & Mostofsky, SH 2019, 'Motor cortex inhibition and modulation in children with ADHD', Neurology, vol. 93, no. 6, pp. e599-e610. https://doi.org/10.1212/WNL.0000000000007899
Gilbert DL, Huddleston DA, Wu SW, Pedapati EV, Horn PS, Hirabayashi K et al. Motor cortex inhibition and modulation in children with ADHD. Neurology. 2019 Aug 6;93(6):e599-e610. https://doi.org/10.1212/WNL.0000000000007899
Gilbert, Donald L. ; Huddleston, David A. ; Wu, Steve W. ; Pedapati, Ernest V. ; Horn, Paul S. ; Hirabayashi, Kathryn ; Crocetti, Deanna ; Wassermann, Eric M. ; Mostofsky, Stewart H. / Motor cortex inhibition and modulation in children with ADHD. In: Neurology. 2019 ; Vol. 93, No. 6. pp. e599-e610.
@article{00c92e1ff6ce4637aff9f61fb50c3ff0,
title = "Motor cortex inhibition and modulation in children with ADHD",
abstract = "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.",
author = "Gilbert, {Donald L.} and Huddleston, {David A.} and Wu, {Steve W.} and Pedapati, {Ernest V.} and Horn, {Paul S.} and Kathryn Hirabayashi and Deanna Crocetti and Wassermann, {Eric M.} and Mostofsky, {Stewart H}",
year = "2019",
month = "8",
day = "6",
doi = "10.1212/WNL.0000000000007899",
language = "English (US)",
volume = "93",
pages = "e599--e610",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

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

PY - 2019/8/6

Y1 - 2019/8/6

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85071069777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071069777&partnerID=8YFLogxK

U2 - 10.1212/WNL.0000000000007899

DO - 10.1212/WNL.0000000000007899

M3 - Article

VL - 93

SP - e599-e610

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 6

ER -