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Background  Endogenous paired associative stimulation (ePAS) is a neuromodulatory intervention that has potential to aid stroke recovery. ePAS involves pairing endogenous electroencephalography (EEG) signals known as movement-related cortical potentials (MRCPs), with peripheral electrical stimulation. Previous studies have used transcranial magnetic stimulation (TMS) to demonstrate changes in corticomotor excitability following ePAS. However, the use of TMS as a measure in stroke research is limited by safety precautions, intolerance, and difficulty generating a measurable response in more severely affected individuals. We were interested in evaluating the effect of ePAS using more feasible measures in people with stroke. This study asks whether ePAS produces immediate improvements in the primary outcomes of maximal voluntary isometric contraction (MVIC) and total neuromuscular fatigue of the dorsiflexor muscles, and in the secondary outcomes of muscle power, voluntary activation (VA), central fatigue, peripheral fatigue, and electromyography activity.    Method  In this repeated-measures cross-over study, 15 participants with chronic stroke completed two interventions, ePAS and sham, in a randomized order. During ePAS, 50 repetitions of visually cued dorsiflexion were completed, while single pulses of electrical stimulation were delivered to the deep branch of the common peroneal nerve. Each somatosensory volley was timed to arrive in the primary motor cortex at the peak negativity of the MRCP. Univariate and multivariate linear mixed models were used to analyze the primary and secondary data, respectively.    Results  There was a statistically significant increase in dorsiflexor MVIC immediately following the ePAS intervention (mean increase 7 N), compared to the sham intervention (mean change 0 N) (univariate between-condition analysis  p  = 0.047). The multivariate analysis revealed a statistically significant effect of ePAS on VA of the tibialis anterior muscle, such that ePAS increased VA by 7 percentage units (95% confidence interval 1.3–12.7%). There was no statistically significant effect on total neuromuscular fatigue, muscle power, or other secondary measures.    Conclusion  A single session of ePAS can significantly increase isometric muscle strength and VA in people with chronic stroke. The findings confirm that ePAS has a central neuromodulatory mechanism and support further exploration of its potential as an adjunct to stroke rehabilitation. In addition, the findings offer alternative, feasible outcome measures for future research.    Clinical trial registration  Australia New Zealand Clinical Trials Registry ACTRN12617000838314 (www.anzctr.org.au), Universal Trial Number U953714.

frontiers in human neuroscience

Peripheral Electrical Stimulation Paired With Movement-Related Cortical Potentials Improves Isometric Muscle Strength and Voluntary Activation Following Stroke