Investigating the Working Mechanism of Transcranial Direct Current Stimulation

Emma Lescrauwaet; Mathieu Sprengers; Evelien Carrette; Chloé Algoet; Ann Mertens; Debby Klooster; Steven Beumer; Rob Mestrom; Robrecht Raedt; Paul Boon; Kristl Vonck

Investigating the Working Mechanism of Transcranial Direct Current Stimulation

Emma Lescrauwaet (Corresponding author), Mathieu Sprengers, Evelien Carrette, Chloé Algoet, Ann Mertens, Debby Klooster, Steven Beumer, Rob Mestrom, Robrecht Raedt, Paul Boon, Kristl Vonck

Onderzoeksoutput: Bijdrage aan tijdschrift › Tijdschriftartikel › Academic › peer review

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BACKGROUND: Transcranial direct current stimulation (tDCS) is used to modulate neuronal activity, but the exact mechanism of action (MOA) is unclear. This study investigates tDCS-induced modulation of the corticospinal excitability and the underlying MOA. By anesthetizing the scalp before applying tDCS and by stimulating the cheeks, we investigated whether stimulation of peripheral and/or cranial nerves contributes to the effects of tDCS on corticospinal excitability.

MATERIALS AND METHODS: In a randomized cross-over study, four experimental conditions with anodal direct current stimulation were compared in 19 healthy volunteers: 1) tDCS over the motor cortex (tDCS-MI), 2) tDCS over the motor cortex with a locally applied topical anesthetic (TA) on the scalp (tDCS-MI + TA), 3) DCS over the cheek region (DCS-C), and 4) sham tDCS over the motor cortex(sham). tDCS was applied for 20 minutes at 1 mA. Motor evoked potentials (MEPs) were measured before tDCS and immediately, 15, 30, 45, and 60 minutes after tDCS. A questionnaire was used to assess the tolerability of tDCS.

RESULTS: A significant MEP amplitude increase compared with baseline was found 30 minutes after tDCS-MI, an effect still observed 60 minutes later; no time∗condition interaction effect was detected. In the other three conditions (tDCS-MI + TA, DCS-C, sham), no significant MEP modulation was found. The questionnaire indicated that side effects are significantly lower when the local anesthetic was applied before stimulation than in the other three conditions.

CONCLUSIONS: The significant MEP amplitude increase observed from 30 minutes on after tDCS-MI supports the modulatory effect of tDCS on corticospinal neurotransmission. This effect lasted one hour after stimulation. The absence of a significant modulation when a local anesthetic was applied suggests that effects of tDCS are not solely established through direct cortical stimulation but that stimulation of peripheral and/or cranial nerves also might contribute to tDCS-induced modulation.

Originele taal-2	Engels
Tijdschrift	Neuromodulation
Volume	XX
Nummer van het tijdschrift	X
Vroegere onlinedatum	14 jun. 2024
Status	E-publicatie vóór gedrukte publicatie - 14 jun. 2024

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Financiering

Source(s) of financial support: Evelien Carrette is supported by a research grant from the Geneeskundige Stichting Koningin Elisabeth. Robrecht Raedt is supported by grants of the FWO (Fonds Wetenschappelijk Onderzoek) Flanders and Bijzonder Onderzoeks Fonds (BOF)\u2013UGent special research fund. Kristl Vonck has been funded by the BOF-UGent special research fund. Paul Boon is supported by grants of the FWO Flanders, BOF-UGent, Ghent University Hospital, and E-Epilepsy (European Union). The study was part of a collaboration project entitled \u201CPerStim,\u201D which is cofunded by the Dutch PPP Allowance made available by Health Holland, Top Sector Life Sciences & Health to EpilepsieNL to stimulate public-private partnerships.Emma Lescrauwaet, Ann Mertens, Chlo\u00E9 Algoet, Evelien Carrette, and Robrecht Raedt reported no conflict of interest. Debby Klooster was supported by a FWO junior postdoctoral grant (1259121N). Mathieu Sprengers, Steven Beumer, and Rob Mestrom were partially funded by the Dutch PPP Allowance made available by Health Holland, Top Sector Life Sciences & Health, to EpilepsieNL. Kristl Vonck obtained a Bijzonder Onderzoeks Fonds (BOF) grant of Ghent University for the purchase of transcranial magnetic stimulation (TMS) equipment, obtained consultancy fees from LivaNova, Synergia Medical, All Man Foundation, Precisis, and Angelini Pharma and participates in the advisory board of LivaNova, Synergia Medical, Precisis, and Angelini Pharma. Paul Boon obtained a BOF grant of Ghent University for the purchase of TMS equipment, obtained consultancy fees from LivaNova, Medtronic, and Angelini Pharma and participates in the advisory board of LivaNova, Synergia Medical, and Medtronic.

Financiers	Financiernummer
Angelini Pharma
Fonds Wetenschappelijk Onderzoek
European Commission
Ghent University Hospital
Medtronic, Inc.
Health~Holland	1259121N

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title = "Investigating the Working Mechanism of Transcranial Direct Current Stimulation",

abstract = "BACKGROUND: Transcranial direct current stimulation (tDCS) is used to modulate neuronal activity, but the exact mechanism of action (MOA) is unclear. This study investigates tDCS-induced modulation of the corticospinal excitability and the underlying MOA. By anesthetizing the scalp before applying tDCS and by stimulating the cheeks, we investigated whether stimulation of peripheral and/or cranial nerves contributes to the effects of tDCS on corticospinal excitability.MATERIALS AND METHODS: In a randomized cross-over study, four experimental conditions with anodal direct current stimulation were compared in 19 healthy volunteers: 1) tDCS over the motor cortex (tDCS-MI), 2) tDCS over the motor cortex with a locally applied topical anesthetic (TA) on the scalp (tDCS-MI + TA), 3) DCS over the cheek region (DCS-C), and 4) sham tDCS over the motor cortex(sham). tDCS was applied for 20 minutes at 1 mA. Motor evoked potentials (MEPs) were measured before tDCS and immediately, 15, 30, 45, and 60 minutes after tDCS. A questionnaire was used to assess the tolerability of tDCS.RESULTS: A significant MEP amplitude increase compared with baseline was found 30 minutes after tDCS-MI, an effect still observed 60 minutes later; no time∗condition interaction effect was detected. In the other three conditions (tDCS-MI + TA, DCS-C, sham), no significant MEP modulation was found. The questionnaire indicated that side effects are significantly lower when the local anesthetic was applied before stimulation than in the other three conditions.CONCLUSIONS: The significant MEP amplitude increase observed from 30 minutes on after tDCS-MI supports the modulatory effect of tDCS on corticospinal neurotransmission. This effect lasted one hour after stimulation. The absence of a significant modulation when a local anesthetic was applied suggests that effects of tDCS are not solely established through direct cortical stimulation but that stimulation of peripheral and/or cranial nerves also might contribute to tDCS-induced modulation.",

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author = "Emma Lescrauwaet and Mathieu Sprengers and Evelien Carrette and Chlo{\'e} Algoet and Ann Mertens and Debby Klooster and Steven Beumer and Rob Mestrom and Robrecht Raedt and Paul Boon and Kristl Vonck",

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T1 - Investigating the Working Mechanism of Transcranial Direct Current Stimulation

AU - Lescrauwaet, Emma

AU - Sprengers, Mathieu

AU - Carrette, Evelien

AU - Algoet, Chloé

AU - Mertens, Ann

AU - Klooster, Debby

AU - Beumer, Steven

AU - Mestrom, Rob

AU - Raedt, Robrecht

AU - Boon, Paul

AU - Vonck, Kristl

PY - 2024/6/14

Y1 - 2024/6/14

N2 - BACKGROUND: Transcranial direct current stimulation (tDCS) is used to modulate neuronal activity, but the exact mechanism of action (MOA) is unclear. This study investigates tDCS-induced modulation of the corticospinal excitability and the underlying MOA. By anesthetizing the scalp before applying tDCS and by stimulating the cheeks, we investigated whether stimulation of peripheral and/or cranial nerves contributes to the effects of tDCS on corticospinal excitability.MATERIALS AND METHODS: In a randomized cross-over study, four experimental conditions with anodal direct current stimulation were compared in 19 healthy volunteers: 1) tDCS over the motor cortex (tDCS-MI), 2) tDCS over the motor cortex with a locally applied topical anesthetic (TA) on the scalp (tDCS-MI + TA), 3) DCS over the cheek region (DCS-C), and 4) sham tDCS over the motor cortex(sham). tDCS was applied for 20 minutes at 1 mA. Motor evoked potentials (MEPs) were measured before tDCS and immediately, 15, 30, 45, and 60 minutes after tDCS. A questionnaire was used to assess the tolerability of tDCS.RESULTS: A significant MEP amplitude increase compared with baseline was found 30 minutes after tDCS-MI, an effect still observed 60 minutes later; no time∗condition interaction effect was detected. In the other three conditions (tDCS-MI + TA, DCS-C, sham), no significant MEP modulation was found. The questionnaire indicated that side effects are significantly lower when the local anesthetic was applied before stimulation than in the other three conditions.CONCLUSIONS: The significant MEP amplitude increase observed from 30 minutes on after tDCS-MI supports the modulatory effect of tDCS on corticospinal neurotransmission. This effect lasted one hour after stimulation. The absence of a significant modulation when a local anesthetic was applied suggests that effects of tDCS are not solely established through direct cortical stimulation but that stimulation of peripheral and/or cranial nerves also might contribute to tDCS-induced modulation.

AB - BACKGROUND: Transcranial direct current stimulation (tDCS) is used to modulate neuronal activity, but the exact mechanism of action (MOA) is unclear. This study investigates tDCS-induced modulation of the corticospinal excitability and the underlying MOA. By anesthetizing the scalp before applying tDCS and by stimulating the cheeks, we investigated whether stimulation of peripheral and/or cranial nerves contributes to the effects of tDCS on corticospinal excitability.MATERIALS AND METHODS: In a randomized cross-over study, four experimental conditions with anodal direct current stimulation were compared in 19 healthy volunteers: 1) tDCS over the motor cortex (tDCS-MI), 2) tDCS over the motor cortex with a locally applied topical anesthetic (TA) on the scalp (tDCS-MI + TA), 3) DCS over the cheek region (DCS-C), and 4) sham tDCS over the motor cortex(sham). tDCS was applied for 20 minutes at 1 mA. Motor evoked potentials (MEPs) were measured before tDCS and immediately, 15, 30, 45, and 60 minutes after tDCS. A questionnaire was used to assess the tolerability of tDCS.RESULTS: A significant MEP amplitude increase compared with baseline was found 30 minutes after tDCS-MI, an effect still observed 60 minutes later; no time∗condition interaction effect was detected. In the other three conditions (tDCS-MI + TA, DCS-C, sham), no significant MEP modulation was found. The questionnaire indicated that side effects are significantly lower when the local anesthetic was applied before stimulation than in the other three conditions.CONCLUSIONS: The significant MEP amplitude increase observed from 30 minutes on after tDCS-MI supports the modulatory effect of tDCS on corticospinal neurotransmission. This effect lasted one hour after stimulation. The absence of a significant modulation when a local anesthetic was applied suggests that effects of tDCS are not solely established through direct cortical stimulation but that stimulation of peripheral and/or cranial nerves also might contribute to tDCS-induced modulation.

KW - Mechanism of action

KW - motor evoked potentials

KW - neuromodulation

KW - transcranial direct current stimulation

KW - transcranial magnetic stimulation

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SN - 1094-7159

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JO - Neuromodulation

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Investigating the Working Mechanism of Transcranial Direct Current Stimulation

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