Increasing the frequency of peripheral component in paired associative stimulation strengthens its efficacy

Aleksandra Tolmacheva,Anastasia Shulga,Jyrki P. Mäkelä

doi:10.1038/s41598-019-40474-0

Aleksandra Tolmacheva, Anastasia Shulga + Show 1 more

Open Access

https://doi.org/10.1038/s41598-019-40474-0

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Abstract

Paired associative stimulation (PAS), a combination of transcranial magnetic stimulation (TMS) with peripheral nerve stimulation (PNS), is emerging as a promising tool for alleviation of motor deficits in neurological disorders. The effectiveness and feasibility of PAS protocols are essential for their use in clinical practice. Plasticity induction by conventional PAS can be variable and unstable. Protocols effective in challenging clinical conditions are needed. We have shown previously that PAS employing 50 Hz PNS enhances motor performance in chronic spinal cord injury patients and induces robust motor-evoked potential (MEP) potentiation in healthy subjects. Here we investigated whether the effectiveness of PAS can be further enhanced. Potentiation of MEPs up to 60 minutes after PAS with PNS frequencies of 25, 50, and 100 Hz was tested in healthy subjects. PAS with 100 Hz PNS was more effective than 50 (P = 0.009) and 25 Hz (P = 0.016) protocols. Moreover, when administered for 3 days, PAS with 100 Hz led to significant MEP potentiation on the 3rd day (P = 0.043) even when the TMS target was selected suboptimally (modelling cases where finding an optimal site for TMS is problematic due to a neurological disease). PAS with 100 Hz PNS is thus effective and feasible for clinical applications.

Highlights

Paired associative stimulation (PAS) is a noninvasive technique that combines peripheral electrical nerve stimulation (PNS) of the limbs and transcranial magnetic stimulation (TMS) of the motor cortex[1,2]
Consistent with the present data, we have previously shown that peripheral nerve stimulation (PNS) (50 Hz) alone has no effect on motor-evoked potential (MEP); TMS alone does not lead to MEP potentiation[13]
We have previously shown that PAS protocol with high-frequency PNS does not require motor imagery to induce MEP potentiation in healthy subjects[13]

Summary

Introduction

Paired associative stimulation (PAS) is a noninvasive technique that combines peripheral electrical nerve stimulation (PNS) of the limbs and transcranial magnetic stimulation (TMS) of the motor cortex[1,2]. Optimizing PAS can be challenging even in healthy subjects This is even more so in neurological patients, as the central nervous system (CNS) pathology may modify the signal conduction in the targeted neural pathways. It is challenging to detect MEPs (usually with an abnormal latency and shape) from spasticity-contaminated EMG11 To overcome these issues, we previously employed a PAS protocol consisting of a high-frequency PNS train and high-intensity TMS. We previously employed a PAS protocol consisting of a high-frequency PNS train and high-intensity TMS This modification provided a wider range of ISIs for effective PAS11–13 and is beneficial in chronic SCI patients when applied as a long-term treatment. We tested our most effective protocol in the condition mimicking the situation in patients whose optimal TMS target in the cortex cannot be precisely identified

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