TY - JOUR
T1 - Motor cortex excitability and inhibitory imbalance in autism spectrum disorder assessed with transcranial magnetic stimulation
T2 - a systematic review
AU - Masuda, Fumi
AU - Nakajima, Shinichiro
AU - Miyazaki, Takahiro
AU - Yoshida, Kazunari
AU - Tsugawa, Sakiko
AU - Wada, Masataka
AU - Ogyu, Kamiyu
AU - Croarkin, Paul E.
AU - Blumberger, Daniel M.
AU - Daskalakis, Zafiris J.
AU - Mimura, Masaru
AU - Noda, Yoshihiro
N1 - Funding Information:
F.M. reports no biomedical interests. S.N. has received fellowship grants from Canadian Institute of Health Research (CIHR), research support from Japan Society for the Promotion of Science (Grant-in-Aid for Young Scientists A, Grants-in-Aid for Scientific Research B, and Grants-in-Aid for Scientific Research C), Japan Society for the Promotion of Science, Japan Agency for Medical Research and development (AMED), Japan Research Foundation for Clinical Pharmacology, Naito Foundation, Uehara Memorial Foundation, Takeda Science Foundation, Daiichi Sankyo Research Program, and Novartis Research Program and manuscript fees or speaker’s honoraria from Dainippon-Sumitomo Pharma and Yoshitomi-Yakuhin within the past 3 years. T.M. reports no biomedical interests. K.Y. has received manuscript fees from Sumitomo Dainippon Pharma, fellowship grants from the Japan Research Foundation for Clinical Pharmacology, and consultant fees from Bracket within the past 3 years. S.T., M.W., R.T., and K.O. report no biomedical interests. P.E.C. has received research grant support from Pfizer, Inc., NIMH, the Brain and Behavior Research Foundation, and the Mayo Clinic Foundation. He has served as a site subprincipal or principal investigator (without additional compensation) for Eli Lilly and Co., Forest Laboratories, Inc., Merck & Co., Inc., and Pfizer, Inc.; has received equipment support from Neuronetics, Inc.; and receives supplies and genotyping services from Assurex Health, Inc. for an investigator-initiated study. He is the primary investigator for a multicenter study funded by Neuronetics, Inc. He is a site investigator for a study funded by NeoSync, Inc. D. M.B. receives research support from the Canadian Institutes of Health Research (CIHR), National Institutes of Health—US (NIH), Weston Brain Institute, Brain Canada, and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd., and he is the site principal investigator for three sponsor-initiated studies for Brainsway Ltd. He received in-kind equipment support from Magventure for this investigator-initiated study. He received medication supplies for an investigator-initiated trial from Indivior. He has served on an advisory board for Janssen. Z.J.D. has received within the last 3 years both research and equipment in-kind support for an investigator-initiated study through Brainsway Ltd. and Magventure. M.M. has received grants or speaker’s honoraria from Asahi Kasei Pharma, Astellas Pharmaceutical, Daiichi Sankyo, Dainippon-Sumitomo Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Meiji-Seika Pharma, Mochida Pharmaceutical, MSD, Novartis Pharma, Otsuka Pharmaceutical, Pfizer, Shionogi, Takeda, Tanabe Mitsubishi Pharma, and Yoshitomi-Yakuhin within 3 years. Y.N. receives a Grant-in-Aid for Young Scientists (KAKENHI), a research grant from Japan Agency for Medical Research and development (AMED). Y.N. receives an investigator-initiated clinical study grant from TEIJIN PHARMA LIMITED. He also receives research grants from Japan Health Foundation, Meiji Yasuda Mental Health Foundation, Mitsui Life Social Welfare Foundation, Takeda Science Foundation, SENSHIN Medical Research Foundation, Health Science Center Foundation, and Daiichi Sankyo Scholarship Donation Program. He has received research supports from Otsuka Pharmaceutical Co., Ltd, Shionogi & Co., Ltd., and Meiji-Seika Pharma Co., Ltd. He receives equipment-in-kind support for an investigator-initiated study from Magventure Inc.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Cortical excitation/inhibition (E/I) imbalances contribute to various clinical symptoms observed in autism spectrum disorder (ASD). However, the detailed pathophysiologic underpinning of E/I imbalance remains uncertain. Transcranial magnetic stimulation (TMS) motor-evoked potentials (MEP) are a non-invasive tool for examining cortical inhibition in ASD. Here, we conducted a systematic review on TMS neurophysiology in motor cortex (M1) such as MEPs and short-interval intracortical inhibition (SICI) between individuals with ASD and controls. Out of 538 initial records, we identified six articles. Five studies measured MEP, where four studies measured SICI. There were no differences in MEP amplitudes between the two groups, whereas SICI was likely to be reduced in individuals with ASD compared with controls. Notably, SICI largely reflects GABA(A) receptor-mediated function. Conversely, other magnetic resonance spectroscopy and postmortem methodologies assess GABA levels. The present review demonstrated that there may be neurophysiological deficits in GABA receptor-mediated function in ASD. In conclusion, reduced GABAergic function in the neural circuits could underlie the E/I imbalance in ASD, which may be related to the pathophysiology of clinical symptoms of ASD. Therefore, a novel treatment that targets the neural circuits related to GABA(A) receptor-mediated function in regions involved in the pathophysiology of ASD may be promising.
AB - Cortical excitation/inhibition (E/I) imbalances contribute to various clinical symptoms observed in autism spectrum disorder (ASD). However, the detailed pathophysiologic underpinning of E/I imbalance remains uncertain. Transcranial magnetic stimulation (TMS) motor-evoked potentials (MEP) are a non-invasive tool for examining cortical inhibition in ASD. Here, we conducted a systematic review on TMS neurophysiology in motor cortex (M1) such as MEPs and short-interval intracortical inhibition (SICI) between individuals with ASD and controls. Out of 538 initial records, we identified six articles. Five studies measured MEP, where four studies measured SICI. There were no differences in MEP amplitudes between the two groups, whereas SICI was likely to be reduced in individuals with ASD compared with controls. Notably, SICI largely reflects GABA(A) receptor-mediated function. Conversely, other magnetic resonance spectroscopy and postmortem methodologies assess GABA levels. The present review demonstrated that there may be neurophysiological deficits in GABA receptor-mediated function in ASD. In conclusion, reduced GABAergic function in the neural circuits could underlie the E/I imbalance in ASD, which may be related to the pathophysiology of clinical symptoms of ASD. Therefore, a novel treatment that targets the neural circuits related to GABA(A) receptor-mediated function in regions involved in the pathophysiology of ASD may be promising.
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U2 - 10.1038/s41398-019-0444-3
DO - 10.1038/s41398-019-0444-3
M3 - Review article
C2 - 30846682
AN - SCOPUS:85062583629
SN - 2158-3188
VL - 9
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 110
ER -