What are the neurophysiological correlates of paired associative stimulation (PAS) in inducing plastic changes in human motor cortex (M1)? Here, Arrigoni and colleagues (2024) will apply transcranial magnetic stimulation (TMS) to left M1 paired with electrical stimulation of the right median nerve at an ISI of 25 ms or 10 ms to induce long-term potentiation (LTP) or long-term depression (LTD), respectively. Arrigoni and colleagues (2024) will determine if these stimulation pairings effect cortical excitability using motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs). Specifically, they hypothesize PASLTP will increase the peak-to-peak amplitude of MEPs, whereas PASLTD will decrease the amplitude, replicating previous work. They will then extend these previous findings by examining TEPs. The authors anticipate modulation of the P30 and P60, which are TEPs thought to reflect local cortical excitability. They plan to account for the MEP reafference which may also mediate the P60 amplitude by stimulating at sub- and supra- motor threshold. Further, they hypothesize an increase of the N100, a marker of inhibitory processing mediated by GABA, by PASLTD. Finally, the authors will also examine the impact of cortical excitability over time to determine the duration of the PAS effects.   

 

This detailed examination of TEPs following PAS stimulation will determine which TEPs could be used as biomarkers with the induction of LTP and LTD through stimulation. The authors have built in an MEP replication for the PAS stimulation, supporting previous literature and acting as a positive control.  

 

The Stage 1 manuscript was evaluated by three expert reviewers across two rounds. Following in-depth review and responses from the authors, the recommender determined that Stage 1 criteria was met and awarded in-principle acceptance (IPA).

 

URL to the preregistered Stage 1 protocol: https://osf.io/detjc (under temporary private embargo)
 
Level of bias control achieved: Level 6. No part of the data or evidence that will be used to answer the research question yet exists and no part will be generated until after IPA. 
 
List of eligible PCI RR-friendly journals:

 

References
 
1. Arrigoni, E., Bolognini, N., Pisoni, A. & Guidali, G. (2024). Neurophysiological correlates of plasticity induced by paired associative stimulation (PAS) targeting the motor cortex: a TMS-EEG registered report. In principle acceptance of Version 3 by Peer Community in Registered Reports. https://osf.io/detjc