AUTHOR=Song Wenjing , Zhang Zixuan , Lv Bingchen , Li Jinyu , Chen Hao , Zhang Shenyang , Zu Jie , Dong Liguo , Xu Chuanying , Zhou Manli , Zhang Tao , Xu Ran , Zhu Jienan , Shen Tong , Zhou Su , Cui Chenchen , Huang Shuming , Wang Xi , Nie Yujing , Aftab Kainat , Xiao Qihua , Zhang Xueling , Cui Guiyun , Zhang Wei TITLE=High-frequency rTMS over bilateral primary motor cortex improves freezing of gait and emotion regulation in patients with Parkinson’s disease: a randomized controlled trial JOURNAL=Frontiers in Aging Neuroscience VOLUME=16 YEAR=2024 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1354455 DOI=10.3389/fnagi.2024.1354455 ISSN=1663-4365 ABSTRACT=Background

Freezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson’s disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD.

Methods

This study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes.

Results

Two patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1.

Conclusion

High-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD.