Objective: The study aimed to determine whether high-definition gamma-tACS (hd-γtACS) delivered over the posterior parietal cortex (PPC)-primary motor cortex (M1) and cerebellum (CB)-M1 pathways during treadmill training with rhythmic auditory cueing (RAC) could engage these pathways and modulate M1 excitability and whether pathway efficiency differed between patients, responders, and non-responders to RAC.

Background: Gait impairments are prevalent in PD. Compensation strategies, like 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 movement and have been shown to exert, respectively, a facilitatory⁵ and an inhibitory⁶ activity on M1. TACS at gamma (i.e, 70 Hz) frequency has shown the ability to improve motor performance⁷ and restore plasticity in M1 in PD patients⁸.

Method: 18 RAC responders (R; Age: 67.4 ± 7.7 years; H&Y: 2.1 ± 0.32) and 16 non-responders (NR; Age: 66.5 ± 8.7 years; H&Y: 2.1 ± 0.33) with PD were assessed. RAC responsiveness was evaluated using inertial sensors during cued and uncued gait¹. Responders were patients having a 0.5-point absolute reduction in stride time variability compared to uncued gait. M1 excitability was assessed before and after multisite hd-γtACS over the CB-M1 and PPC-M1 pathways using an M1 input/output curve. The area under the curve (AUC) was calculated as an index of M1 excitability. A sham session served as control.

Results: Both responders and non-responders showed a significant decrease in M1 excitability (i.e., reduced AUC) after CB-M1 hd-γtACS (R: p < 0.01; NR: p < 0.01) and a significantly increased M1 excitability (i.e., increased AUC) following the PPC-M1 hd-γtACS protocol (R: p < 0.001; NR: p < 0.01). No significant differences were found in the sham condition in both groups.

Conclusion: These findings suggest that both the CB-M1 and the PPC-M1 networks’ efficiency can be enhanced following a multisite hd-γtACS protocol combined with RAC gait, with no differences between PD patients responding or not responding to cueing strategies. Moreover, they highlight the role of those pathways in cued gait, offering insights for non-invasive brain stimulation protocols for gait rehabilitation.

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. Koch, G. et al. Focal stimulation of the posterior parietal cortex increases the excitability of the ipsilateral motor cortex. J. Neurosci. 27, 6815–6822 (2007).
6. Ugawa, Y., Uesaka, Y., Terao, Y., Hanajima, R. & Kanazawa, I. Magnetic stimulation over the cerebellum in humans. Ann. Neurol. 37, 703–713 (1995).
7. 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).
8. 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/multisite-high-definition-gamma-tacs-combined-with-rhythmic-auditory-cued-gait-enhances-network-efficiency-in-patients-with-parkinsons-disease/