Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex

Abstract

Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus (maximum uncertainty condition). Motor evoked potentials (MEPs) evoked from abductor pollicis brevis muscle quantified cortical excitability before and after PAS. MEP amplitude increased significantly 15 minutes following PAS in the maximum uncertainty condition. There was no reliable change in MEP amplitude in the no uncertainty condition, nor between post-PAS MEP amplitudes across the two conditions. These results suggest that stimulus uncertainty boost may provide a novel means to enhance plasticity induction with the PAS paradigm in human motor cortex. To provide further support to the notion that stimulus uncertainty and prediction error promote plasticity, future studies should further explore the time course of these changes, and investigate what aspects of stimulus uncertainty are critical in boosting plasticity. Highlights• Plasticity can be induced in human cortex by repeated pairing of stimuli.• This form of induced plasticity mimics behavioral associative learning. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 2• We manipulated stimulus uncertainty, which influences learning and plasticity.• When stimulus uncertainty was high, plasticity was enhanced in human motor cortex.

The effects of transcranial direct current stimulation on corticospinal and cortico-cortical excitability and response variability: Conventional versus high-definition montages

“…The CV (SD/meanx100) represents the range, or percentage variance that one SD of the data lies about the mean (Atkinson & Nevill, 1998). Its simplicity has led to use in NIBS and TMS literature (eg: (Biabani et al, 2018;Klein-Flugge et al, 2013;Sadnicka et al, 2013;Martin V. Sale et al, 2017;Temesi et al, 2017;Vassiliadis et al, 2018)).…”

The effects of transcranial direct current stimulation on corticospinal and cortico-cortical excitability and response variability: conventional versus high-definition montages

“…The CV (SD/meanx100) represents the range, or percentage variance that one SD of the data lies about the mean (Atkinson & Nevill, 1998). Its simplicity has led to use in NIBS and TMS literature (eg: (Biabani et al, 2018;Klein-Flugge et al, 2013;Sadnicka et al, 2013;Martin V. Sale et al, 2017;Temesi et al, 2017;Vassiliadis et al, 2018)).…”