Neural mechanisms underlying the after-effects of repetitive paired-pulse TMS with β tACS on the human primary motor cortex

Abstract We previously reported that repetitive paired-pulse transcranial magnetic stimulation (TMS; rPPS) synchronized to the peak phase of transcranial alternating current stimulation (tACS) at the β frequency induced long-lasting after-effects on primary motor cortex (M1) with less inter-individu...

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Main Authors: Hisato Nakazono, Katsuya Ogata, Tsubasa Mitsutake, Akinori Takeda, Emi Yamada, Shozo Tobimatsu
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-92444-4
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author Hisato Nakazono
Katsuya Ogata
Tsubasa Mitsutake
Akinori Takeda
Emi Yamada
Shozo Tobimatsu
author_facet Hisato Nakazono
Katsuya Ogata
Tsubasa Mitsutake
Akinori Takeda
Emi Yamada
Shozo Tobimatsu
author_sort Hisato Nakazono
collection DOAJ
description Abstract We previously reported that repetitive paired-pulse transcranial magnetic stimulation (TMS; rPPS) synchronized to the peak phase of transcranial alternating current stimulation (tACS) at the β frequency induced long-lasting after-effects on primary motor cortex (M1) with less inter-individual variability compared with rPPS alone. Here, we investigated the plasticity mechanisms underlying combined stimulation effects using paired-pulse TMS paradigms. rPPS was applied to the peak phase of β tACS (rPPS-tACS-peak) or sham tACS (rPPS alone), or tACS was delivered without rPPS (tACS alone). Resting motor threshold (RMT) and motor evoked potentials (MEPs) elicited by single-pulse TMS, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), and short-interval intracortical facilitation (SICF) were measured before and after intervention. rPPS-tACS-peak stimulation significantly increased MEPs compared with other conditions after intervention. Although I-wave interaction was expected to be produced by the facilitation effect of rPPS, rPPS-tACS-peak did not change SICF. In contrast, SAI was decreased in rPPS-tACS-peak compared with baseline. In the control experiment, rPPS-tACS-trough did not change MEPs, SAI, and SICF. Therefore, the after-effects of rPPS-tACS-peak on M1 may be caused by a partial reduction in the inhibitory circuit mediated by cholinergic interneurons, rather than an enhancement of the facilitatory effects of rPPS.
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spelling doaj-art-28fd3762a1cf4c338a83bad1842c80382025-08-20T03:41:40ZengNature PortfolioScientific Reports2045-23222025-03-0115111110.1038/s41598-025-92444-4Neural mechanisms underlying the after-effects of repetitive paired-pulse TMS with β tACS on the human primary motor cortexHisato Nakazono0Katsuya Ogata1Tsubasa Mitsutake2Akinori Takeda3Emi Yamada4Shozo Tobimatsu5Department of Occupational Therapy, Faculty of Medical Science, Fukuoka International University of Health and WelfareDepartment of Pharmaceutical Sciences, School of Pharmacy at Fukuoka, International University of Health and WelfareClinical Research Center, Saga University HospitalResearch Center for Brain Communication, Research Institute, Kochi University of TechnologyDepartment of Linguistics, Faculty of Humanities, Kyushu UniversityDepartment of Orthoptics, Faculty of Medical Science, Fukuoka International University of Health and WelfareAbstract We previously reported that repetitive paired-pulse transcranial magnetic stimulation (TMS; rPPS) synchronized to the peak phase of transcranial alternating current stimulation (tACS) at the β frequency induced long-lasting after-effects on primary motor cortex (M1) with less inter-individual variability compared with rPPS alone. Here, we investigated the plasticity mechanisms underlying combined stimulation effects using paired-pulse TMS paradigms. rPPS was applied to the peak phase of β tACS (rPPS-tACS-peak) or sham tACS (rPPS alone), or tACS was delivered without rPPS (tACS alone). Resting motor threshold (RMT) and motor evoked potentials (MEPs) elicited by single-pulse TMS, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), and short-interval intracortical facilitation (SICF) were measured before and after intervention. rPPS-tACS-peak stimulation significantly increased MEPs compared with other conditions after intervention. Although I-wave interaction was expected to be produced by the facilitation effect of rPPS, rPPS-tACS-peak did not change SICF. In contrast, SAI was decreased in rPPS-tACS-peak compared with baseline. In the control experiment, rPPS-tACS-trough did not change MEPs, SAI, and SICF. Therefore, the after-effects of rPPS-tACS-peak on M1 may be caused by a partial reduction in the inhibitory circuit mediated by cholinergic interneurons, rather than an enhancement of the facilitatory effects of rPPS.https://doi.org/10.1038/s41598-025-92444-4Transcranial alternating current stimulationRepetitive paired-pulse transcranial magnetic stimulationCombined stimulationPaired-pulse paradigmPhase dependencePrimary motor cortex
spellingShingle Hisato Nakazono
Katsuya Ogata
Tsubasa Mitsutake
Akinori Takeda
Emi Yamada
Shozo Tobimatsu
Neural mechanisms underlying the after-effects of repetitive paired-pulse TMS with β tACS on the human primary motor cortex
Scientific Reports
Transcranial alternating current stimulation
Repetitive paired-pulse transcranial magnetic stimulation
Combined stimulation
Paired-pulse paradigm
Phase dependence
Primary motor cortex
title Neural mechanisms underlying the after-effects of repetitive paired-pulse TMS with β tACS on the human primary motor cortex
title_full Neural mechanisms underlying the after-effects of repetitive paired-pulse TMS with β tACS on the human primary motor cortex
title_fullStr Neural mechanisms underlying the after-effects of repetitive paired-pulse TMS with β tACS on the human primary motor cortex
title_full_unstemmed Neural mechanisms underlying the after-effects of repetitive paired-pulse TMS with β tACS on the human primary motor cortex
title_short Neural mechanisms underlying the after-effects of repetitive paired-pulse TMS with β tACS on the human primary motor cortex
title_sort neural mechanisms underlying the after effects of repetitive paired pulse tms with β tacs on the human primary motor cortex
topic Transcranial alternating current stimulation
Repetitive paired-pulse transcranial magnetic stimulation
Combined stimulation
Paired-pulse paradigm
Phase dependence
Primary motor cortex
url https://doi.org/10.1038/s41598-025-92444-4
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