Abstract

Advances in our understanding of neural plasticity have prompted the emergence of neuromodulatory interventions, which modulate corticomotor excitability (CME) and hold potential for accelerating stroke recovery. Endogenous paired associative stimulation (ePAS) involves the repeated pairing of a single pulse of peripheral electrical stimulation (PES) with endogenous movement-related cortical potentials (MRCPs), which are derived from electroencephalography. However, little is known about the optimal parameters for its delivery. A factorial design with repeated measures delivered four different versions of ePAS, in which PES intensities and movement type were manipulated. Linear mixed models were employed to assess interaction effects between PES intensity (suprathreshold (Hi) and motor threshold (Lo)) and movement type (Voluntary and Imagined) on CME. ePAS interventions significantly increased CME compared to control interventions, except in the case of Lo-Voluntary ePAS. There was an overall main effect for the Hi-Voluntary ePAS intervention immediately post-intervention (p = 0.002), with a sub-additive interaction effect at 30 min’ post-intervention (p = 0.042). Hi-Imagined and Lo-Imagined ePAS significantly increased CME for 30 min post-intervention (p = 0.038 and p = 0.043 respectively). The effects of the two PES intensities were not significantly different. CME was significantly greater after performing imagined movements, compared to voluntary movements, with motor threshold PES (Lo) 15 min post-intervention (p = 0.012). This study supports previous research investigating Lo-Imagined ePAS and extends those findings by illustrating that ePAS interventions that deliver suprathreshold intensities during voluntary or imagined movements (Hi-Voluntary and Hi-Imagined) also increase CME. Importantly, our findings indicate that stimulation intensity and movement type interact in ePAS interventions. Factorial designs are an efficient way to explore the effects of manipulating the parameters of neuromodulatory interventions. Further research is required to ensure that these parameters are appropriately refined to maximise intervention efficacy for people with stroke and to support translation into clinical practice.

Highlights

  • Advances in our understanding of neural plasticity have prompted the emergence of non-invasive neuromodulatory interventions [1]

  • Factorial designs are an efficient way to explore the effects of manipulating the parameters of neuromodulatory interventions

  • The primary aim of this study was to investigate whether Endogenous paired associative stimulation (ePAS) delivered using single pulses of suprathreshold peripheral electrical stimulation (PES), paired with movement-related cortical potentials (MRCPs) produced during voluntary ankle dorsiflexion movements, would yield a super-additive increase in corticomotor excitability (CME) in healthy adults, and whether this effect would be maintained for 45 min post-intervention

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Summary

Introduction

Advances in our understanding of neural plasticity have prompted the emergence of non-invasive neuromodulatory interventions [1]. These interventions have the potential to facilitate adaptive neural plasticity in partially disrupted neural networks and promote motor recovery following neurological injury such as stroke [2]. Paired associative stimulation (PAS) is an example of a non-invasive neuromodulatory intervention that is based on the principles of Hebbian-associative plasticity [3,4]. PAS involves the repeated temporal pairing of two stimuli, usually a single pulse of electrical stimulation to a peripheral nerve with a single pulse of transcranial magnetic stimulation (TMS) over the contralateral primary motor cortex (M1) [5].

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