Objective: This study aimed to explore whether PD patients responsive to rhythmic auditory cues (RAC), identified by lower gait variability during cued relative to uncued gait, exhibit more preserved LTP-like plasticity in the primary motor cortex (M1) than non-responders.

Background: Gait impairments are among the most disabling features of PD, and RAC are widely used in rehabilitation despite variable effectiveness¹. At the same time, PD is characterized by impaired neural plasticity in M1, including reduced LTP-like plasticity². In this context, RAC may act not merely as an online aid, but as a trigger for compensatory motor-skill acquisition³. Accordingly, responsiveness to RAC may depend on the engagement of cortical and subcortical networks involved in movement acquisition⁴, together with relatively preserved M1 LTP-like plasticity and more efficient movement-related beta modulation during cued gait^5,6.

Method: We enrolled 20 responders (67,6 ± 7,7; H&Y: 2,1 ± 0,31) and 18 non-responders (67,6 ± 7,8; H&Y: 2,1 ± 0,40) with PD. Corticospinal excitability was assessed with an I/O curve at 80%, 100%, 120%, 140% and 160% of resting motor threshold (RMT), before and after intermittent theta burst stimulation (iTBS) over M1. Area under the I/O curve (AUC) was also computed. RAC responsiveness was assessed separately; responders showed an absolute reduction in stride time variability of ≥0.5 points during cued versus uncued gait^7,8.

Results: RAC responders exhibited increased corticospinal excitability after iTBS, with higher MEPs at 100%, 120%, 140%, and 160% of RMT (all p<0.01), as well as higher AUC (p<0.001). No significant post-iTBS changes were found in non-responders. Post-iTBS AUC was also higher in responders than non-responders (p<0.01), whereas no baseline group differences emerged.

Conclusion: These findings suggest that PD patients responsive to RAC show more preserved LTP-like plasticity in M1 than non-responders, supporting the hypothesis that cue responsiveness may rely on greater residual capacity for compensatory motor-skill acquisition. Preserved M1 plasticity may therefore contribute to the neurophysiological basis of RAC responsiveness in PD, possibly together with more efficient movement-related beta modulation during cued gait. This study is part of the broader UNITE-PD project (EU-JPND), whose final aim is to disentangle the neural underpinnings of cueing strategies in PD.

References: 1. Cosentino, C. et al. One cue does not fit all: A systematic review with meta-analysis of the effectiveness of cueing on freezing of gait in Parkinson’s disease. Neurosci. Biobehav. Rev. 150, 105189 (2023).
2. Suppa, A. et al. Lack of LTP-like plasticity in primary motor cortex in Parkinson’s disease. Exp. Neurol. 227, 296–301 (2011).
3. Rochester, L. et al. Evidence for motor learning in Parkinson’s disease: Acquisition, automaticity and retention of cued gait performance after training with external rhythmical cues. Brain Res. 1319, 103–111 (2010).
4. Doyon, J. & Benali, H. Reorganization and plasticity in the adult brain during learning of motor skills. Curr. Opin. Neurobiol. 15, 161–167 (2005).
5. Tosserams, A. et al. Cortical Correlates of Gait Compensation Strategies in Parkinson Disease. Ann. Neurol. 91, 329–341 (2022).
6. Ghilardi, M. F., Tatti, E. & Quartarone, A. Beta power and movement-related beta modulation as hallmarks of energy for plasticity induction: Implications for Parkinson’s disease. Park. Relat. Disord. 88, 136–139 (2021).
7. Albers, C. et al. Understanding Cueing Strategies for Gait Impairments in Parkinson’s Disease: study protocol of the international UNITE-PD study. European Journal of Neuroscience vol. 63 at https://doi.org/10.1111/ejn.70382 (2025).
8. Tosserams, A. et al. Evaluation of Compensation Strategies for Gait Impairment in Patients with Parkinson Disease. Neurology 99, E2253–E2263 (2022).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/preserved-neuroplasticity-in-patients-affected-by-parkinsons-disease-responders-to-external-auditory-cueing-strategies/