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Systematic Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.00895

A systematic review of paired associative stimulation (PAS) to modulate lower limb corticomotor excitability: Implications for stimulation parameter selection and experimental design.

  • 1Health and Rehabilitation Research Institute, Auckland University of Technology, New Zealand

Non-invasive neuromodulatory interventions have the potential to influence neural plasticity and augment motor rehabilitation in people with stroke. Paired associative stimulation (PAS) involves the repeated pairing of single pulses of electrical stimulation to a peripheral nerve and single pulses of transcranial magnetic stimulation over the contralateral primary motor cortex. The efficacy of PAS in the lower limb of healthy and stroke populations has not been systematically appraised, and optimal protocols, including stimulation parameter settings, have yet to be determined. This systematic review evaluates: a) the efficacy of PAS on lower limb corticomotor excitability in healthy and stroke populations, and b) the stimulation parameters employed. Five databases were searched for randomised, non-randomised, and pre-post experimental studies, that investigated the efficacy of lower limb PAS in healthy and stroke populations. Two independent reviewers identified eligible studies and assessed methodological quality using the modified Downs and Blacks Tool and the TMS Checklist. PAS stimulation parameters and TMS measurement methods were also extracted and compared. Twelve articles, comprising 24 experiments, met the inclusion criteria. Four articles evaluated PAS in people with stroke. Following a single session of PAS, 21 experiments reported modulation of corticomotor excitability, lasting up to 60 minutes; however, the research lacked methodological rigour. Intervention stimulation parameters were highly variable across experiments, and whilst these appeared to influence efficacy, variations in the intervention and outcome assessment methods hindered the ability to draw conclusions about optimal parameters. Lower limb PAS requires further investigation before considering its translation into clinical practice. Eight key recommendations are offered as a guide for enhancing future research in the field.

Keywords: Paired associative stimulation, Transcrania magnetic stimulation, cortical excitability, Neuronal plasticity (MeSH), STDP, primary motor cortex, Rehabilitation (MeSH), Stroke (MeSH), Systematic review

Received: 21 May 2019; Accepted: 09 Aug 2019.

Copyright: © 2019 Alder, Signal, Olsen and Taylor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mrs. Gemma Alder, Auckland University of Technology, Health and Rehabilitation Research Institute, Auckland, New Zealand,