Objective: This study aims to test the contribution of Posterior Parietal Cortex – primary motor cortex and cerebellum – M1 pathways in decreasing gait variability during external cueing, both in responders and non-responders to cueing. To this aim, high-definition γtACS (hd-γtACS) will be used.

Background: Gait impairments are prevalent in PD. Compensation strategies, like rhythmic auditory cueing (RAC), are evidence-based approaches for gait rehabilitation in PD¹. While cueing can significantly improve mobility, its effectiveness varies among patients². PPC³ and the CB⁴ are involved in externally cued movements. γtACS has shown the ability to improve motor performance⁵ and restore plasticity in M1 in PD⁶.

Method: Eighteen RAC responders (Age: 67.4 ± 6.4 years; H&Y: 2.1 ± 0.33) and 16 RAC non-responders (Age: 66.5 ± 8.8 years; H&Y: 2.1 ± 0.33) with PD were assessed. Gait was assessed during two 2-minute continuous walking trials: an uncued trial at a self-selected comfortable speed and an externally cued trial with rhythmic auditory cueing (RAC). During RAC, participants synchronized their steps to a digital metronome. Spatiotemporal gait parameters were recorded using IMUs (APDM Opals).RAC responsiveness was assessed in a separate session using inertial sensors during cued and uncued gait, following Tosserams et al.¹. Participants were classified as responders if cued gait reduced stride time variability by at least 0.5 points versus uncued gait. Stride time variability was measured during cued and uncued gait before and after multisite hd-γtACS targeting the PPC-M1 and CB-M1 pathways, with an additional sham session.

Results: In non-responders to RAC, hd-γtACS over both CB-M1 (p = 0.02) and PPC-M1 (p = 0.01) significantly reduced stride time variability during cued gait. After stimulation, 50% (8/16) converted to responders in the CB-M1 condition and 75% (12/16) in the PPC-M1 condition. No significant changes emerged after sham, nor in responders after active stimulation.

Conclusion: Conclusions: These findings suggest that hd-γtACS on CB-M1 and PPC-M1 pathways can restore auditory cue responsiveness in patients with no initial improvement during RAC gait, highlighting CB and PPC roles in cued gait and offering insights for non-invasive brain stimulation in gait rehabilitation protocols.

References: References
1. Tosserams, A. et al. Evaluation of Compensation Strategies for Gait Impairment in Patients with Parkinson Disease. Neurology 99, E2253–E2263 (2022).
2. 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).
3. Tosserams, A. et al. Cortical Correlates of Gait Compensation Strategies in Parkinson Disease. Ann. Neurol. 91, 329–341 (2022).
4. Cerasa, A. et al. Functional changes in the activity of cerebellum and frontostriatal regions during externally and internally timed movement in Parkinson’s disease. Brain Res. Bull. 71, 259–269 (2006).
5. Santarnecchi, E. et al. High-gamma oscillations in the motor cortex during visuo-motor coordination: A tACS interferential study. Brain Res. Bull. 131, 47–54 (2017).
6. Guerra, A. et al. Enhancing Gamma Oscillations Restores Primary Motor Cortex Plasticity in Parkinson’s Disease. J. Neurosci. 40, 4788–4796 (2020).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/boosting-cerebellum-m1-and-ppc-m1-communication-via-tacs-to-improve-cued-gait-in-parkinsons-disease-patients-unresponsive-to-auditory-cueing-strategies/