Levodopa-induced Modulation of Gait Kinematics and Muscle Synergies in Parkinson's Disease

Rukiye Aydin, Hiroyuki Hamada, Ken Kikuchi, Shingo Shimoda, Yoshihiro Kameyama, Kazunori Sato, Daiki Kamiyama, Eriko Kitahara, Atsushi Yamashita,  Tomokazu Shimazu, Genko Oyama, Toshiyuki Fujiwara and Qi An

Gait impairments in Parkinson’s disease (PD) are impacted by disrupted neuromuscular coordination and are known to improve after dopaminergic medication. While behavioral differences between OFF (prior to medication) and ON (post medication) states have been well established, the underlying neuromuscular mechanisms such as how joint kinematics and muscle coordination are reorganized after medication remain poorly characterized. This study investigates how levodopa modulates lower-limb joint angles and muscle synergies during gait in patients with PD, assessments conducted approximately 40 - 45 minutes apart in OFF and ON states (before and after levodopa, respectively). Lower-limb joint angles and surface EMG data were collected from 13 PD patients (mean age: 63.2 ± 6.8 years; 9 males; UPRDS Part III: OFF mean = 39.2 ± 12.3; ON mean = 11.6 ± 4.1) during overground walking in both OFF and ON states. Hip, knee, and ankle joint angles were analyzed across gait cycles to extract kinematic metrics, including extension peak angle, time to peak and range of motion (ROM). Four muscle synergies (Synergy 1 to Synergy 4) were extracted using a non-negative matrix factorization and temporal components were evaluated for peak activation, time to peak, and activation duration. Results revealed that during ON state gait, both ROM hip extension (OFF = 26.03º ± 6.7, ON = 36.33º ± 4, p =0.0002) and peak hip extension (OFF = 19.7º ± 8.5, ON = 9.5º ± 9.45, p=0.0012) significantly improved, showing greater range and deeper extension during stance, potentially contributing to enhanced propulsion. Temporal muscle synergy analysis revealed significant differences between medication states, especially in Synergy 2, which temporally aligns with hip extension during mid to end stance phase of the gait cycle. In ON state, Synergy 2 showed a shorter activation time (OFF = 49 ± 11% of gait cycle, ON= 33 ± 11% of gait cycle, p=0.01) and a higher peak activation (OFF = 0.5 ± 0.2, ON =0.7 ± 0.2, p= 0.01). Hence, ON state revealed a more robust and refined activation with higher amplitude but shorter time. These results suggest enhanced and temporally more localized synergy activation in ON compared to OFF state. Notably, improvements in hip extension during ON state were mirrored by changes in Synergy 2, indicating increased activation strength and efficient recruitment timing during mid to late stance phase of gait cycle. Together, findings highlight that dopaminergic medication enhances both joint-level movement and neuromuscular coordination, particularly around the mid to end stance phase. Muscle synergy analysis offers insights into interpreting kinematic changes during ON-to-OFF transition.