A New Paired Associative Stimulation Protocol with High-Frequency Peripheral Component and High-Intensity 20 Hz Repetitive Transcranial Magnetic Stimulation—A Pilot Study

Sabin Sathyan, Aleksandra Tolmacheva, Sergei Tugin, Jyrki P. Mäkelä, Anastasia Shulga and Pantelis Lioumis
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Sabin Sathyan: Research Group of Computational Electromechanics, Department of Electrical Engineering and Automation, Aalto University, 02150 Espoo, Finland
Aleksandra Tolmacheva: BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, 00280 Helsinki, Finland
Sergei Tugin: BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, 00280 Helsinki, Finland
Jyrki P. Mäkelä: BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, 00280 Helsinki, Finland
Anastasia Shulga: BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, 00280 Helsinki, Finland
Pantelis Lioumis: BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, 00280 Helsinki, Finland

IJERPH, 2021, vol. 18, issue 21, 1-12

Abstract: Paired associative stimulation (PAS) is a stimulation technique combining transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) that can induce plastic changes in the human motor system. A PAS protocol consisting of a high-intensity single TMS pulse given at 100% of stimulator output (SO) and high-frequency 100-Hz PNS train, or “the high-PAS” was designed to promote corticomotoneuronal synapses. Such PAS, applied as a long-term intervention, has demonstrated therapeutic efficacy in spinal cord injury (SCI) patients. Adding a second TMS pulse, however, rendered this protocol inhibitory. The current study sought for more effective PAS parameters. Here, we added a third TMS pulse, i.e., a 20-Hz rTMS (three pulses at 96% SO) combined with high-frequency PNS (six pulses at 100 Hz). We examined the ability of the proposed stimulation paradigm to induce the potentiation of motor-evoked potentials (MEPs) in five human subjects and described the safety and tolerability of the new protocol in these subjects. In this study, rTMS alone was used as a control. In addition, we compared the efficacy of the new protocol in five subjects with two PAS protocols consisting of PNS trains of six pulses at 100 Hz combined with (a) single 100% SO TMS pulses (high-PAS) and (b) a 20-Hz rTMS at a lower intensity (three pulses at 120% RMT). The MEPs were measured immediately after, and 30 and 60 min after the stimulation. Although at 0 and 30 min there was no significant difference in the induced MEP potentiation between the new PAS protocol and the rTMS control, the MEP potentiation remained significantly higher at 60 min after the new PAS than after rTMS alone. At 60 min, the new protocol was also more effective than the two other PAS protocols. The new protocol caused strong involuntary twitches in three subjects and, therefore, its further characterization is needed before introducing it for clinical research. Additionally, its mechanism plausibly differs from PAS with high-frequency PNS that has been used in SCI patients.

Keywords: corticospinal tract; long interval cortical inhibition; neuroplasticity; paired associative stimulation; peripheral nerve stimulation; primary motor cortex; spinal cord injury; transcranial magnetic stimulation (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
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