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.
Highlights
Paired Associative Stimulation (PAS), first introduced by Stefan et al [1], is a noninvasive neuromodulation paradigm
An otherwise similar protocol but without the third pulse led to a strong motor-evoked potentials (MEPs) depression [33]. Since this two-pulse inhibitory protocol overrode the excitatory action of the high-PAS protocol, and here the excitatory three-pulse protocol led to MEP potentiation, we suggest that the cortical effect of the transcranial magnetic stimulation (TMS)
The main objective of this study was to investigate whether the PAS paradigm used in spinal cord injury (SCI) rehabilitation consisting of a 100-Hz peripheral nerve stimulation (PNS) and single TMS pulses given at 100%
Summary
The main objective of this study was to investigate whether the PAS paradigm used in SCI rehabilitation consisting of a 100-Hz PNS and single TMS pulses given at 100%
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