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Relationship between GABA levels and task-dependent cortical excitability in children with attention-deficit/hyperactivity disorder.

Authors :
Harris AD
Gilbert DL
Horn PS
Crocetti D
Cecil KM
Edden RAE
Huddleston DA
Mostofsky SH
Puts NAJ
Source :
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology [Clin Neurophysiol] 2021 May; Vol. 132 (5), pp. 1163-1172. Date of Electronic Publication: 2021 Mar 10.
Publication Year :
2021

Abstract

Objective: Compared to typically developing (TD) peers, children with attention deficit hyperactivity disorder (ADHD) manifest reduced short interval cortical inhibition (SICI) in the dominant motor cortex measured with transcranial magnetic stimulation (TMS). This multimodal study investigates the inhibitory neurophysiology and neurochemistry by evaluating the relationship between SICI and γ-amino butyric acid (GABA+) levels, measured with magnetic resonance spectroscopy (MRS).<br />Methods: Across two sites, 37 children with ADHD and 45 TD children, ages 8-12 years, participated. Single and paired pulse TMS to left motor cortex quantified SICI during REST and at times of action selection (GO) and inhibition (STOP) during a modified Slater-Hammel stop signal reaction task. MRS quantified GABA+ levels in the left sensorimotor cortex. Relationships between SICI and GABA+, as well as stopping efficiency and clinical symptoms, were analyzed with correlations and repeated-measure, mixed-models.<br />Results: In both groups, higher GABA+ levels correlated with less SICI. In TD children only, higher GABA+ levels correlated with larger TMS motor evoked potentials (MEPs) at REST. In GO and STOP trials, higher GABA+ was associated with smaller MEP amplitudes, for both groups. Overall, GABA+ levels did not differ between groups or correlate with ADHD clinical symptoms.<br />Conclusions: In children with higher motor cortex GABA+, motor cortex is less responsive to inhibitory TMS (SICI). Comparing the relationships between MRS-GABA+ levels and responses to TMS at REST vs. GO/STOP trials suggests differences in inhibitory neurophysiology and neurotransmitters in children with ADHD. These differences are more prominent at rest than during response inhibition task engagement.<br />Significance: Evaluating relationships between GABA+ and SICI may provide a biomarker useful for understanding behavioral diagnoses.<br />Competing Interests: Declaration of Competing Interest Dr. Gilbert has received honoraria and/or travel support from the Tourette Association of America/ Centers for Disease Control and Prevention, the American Academy of Pediatrics, the Child Neurology Society, the Texas Neurological Society, and the American Academy of Neurology. He has received compensation for expert testimony for the U.S. National Vaccine Injury Compensation Program, through the Department of Health and Human Services, and for the US Armed Services/US Attorney’s Office of VA. Dr. Gilbert has received research support from the NIH (NIMH, NINDS). He has received funding for work as a clinical trial site investigator fromEcopipam Pharmaceuticals (clinical trial, Tourette Syndrome) and EryDel (clinical trial, Ataxia Telangiectasia). He has received book royalties from Elsevier and Wolters Kluwer. Dr. Edden has received grants from Siemens.<br /> (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1872-8952
Volume :
132
Issue :
5
Database :
MEDLINE
Journal :
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
Publication Type :
Academic Journal
Accession number :
33780723
Full Text :
https://doi.org/10.1016/j.clinph.2021.01.023