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Updated: Mar 9, 2026
08:29
Standardized Induction and Assessment of Long-term Potentiation-like Cortical Plasticity Using Transcranial Magnetic Stimulation
Published on: November 7, 2025
491
Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex
Martin V Sale1, Abbey S Nydam2, Jason B Mattingley3
1Queensland Brain Institute, The University of Queensland, QLD, Australia; School of Health and Rehabilitation Sciences, The University of Queensland, QLD, Australia.
Summary
Introducing stimulus uncertainty into paired associative stimulation (PAS) enhanced cortical plasticity. This modified PAS approach, using transcranial magnetic stimulation (TMS), shows promise for boosting neuroplasticity in the human motor cortex.
Area of Science:
- Neuroscience
- Motor Cortex Plasticity
- Human Cortical Excitability
Background:
- Paired associative stimulation (PAS) is used to induce plasticity in the human cortex.
- Conventional PAS, which pairs peripheral stimuli with transcranial magnetic stimulation (TMS), often yields inconsistent results.
- The predictable nature of standard PAS may limit its effectiveness in promoting plasticity.
Purpose of the Study:
- To investigate if introducing stimulus uncertainty into the PAS paradigm can enhance cortical plasticity.
- To explore the impact of prediction error on neuroplasticity induction.
- To determine if uncertainty boosts the effectiveness of PAS in the motor cortex.
Main Methods:
- A modified PAS paradigm was developed with a random mix of paired and unpaired (TMS-only) stimuli.
- Participants received auditory cues predicting or not predicting the upcoming stimulus type (uncertainty manipulation).
- Cortical excitability was measured using motor evoked potentials (MEPs) from the abductor pollicis brevis (APB) muscle before and after PAS.
Main Results:
- MEP amplitude significantly increased 15 minutes after PAS under the maximum uncertainty condition.
- No significant change in MEP amplitude was observed in the no uncertainty condition.
- There was no significant difference in post-PAS MEP amplitudes between the two conditions.
Conclusions:
- Stimulus uncertainty may enhance plasticity induction in the human motor cortex via the PAS paradigm.
- Prediction error, driven by stimulus uncertainty, could be a key factor in boosting neuroplasticity.
- Future research should examine the time course and specific aspects of stimulus uncertainty that enhance plasticity.
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