Yuki Kimoto ¹ Naoki Tani ^1* Takuto Emura ¹ Takahiro Matsuhashi ¹ Takuto Yamamoto ¹ Yuya Fujita ¹ Satoru Oshino ¹ Koichi Hosomi ¹ Hui Ming Khoo ¹ Shimpei Miura ¹ Takahiro Fujinaga ¹ Takufumi Yanagisawa ^1,2 Haruhiko KIshima ¹

• ¹ Department of Neurosurgery, Graduate School of Medicine, Osaka University, Suita, Japan
• ² Institute for Advanced Co-Creation Studies, Osaka University, Suita, Osaka, Japan

Introduction: Despite using beta oscillations within the subthalamic nucleus as a biomarker of akinesia or rigidity in Parkinson’s disease, a specific biomarker for freezing of gait (FOG) remains unclear. Recently, scalp phase-amplitude coupling (PAC) measured through scalp electroencephalography (EEG) has emerged as a promising tool for analyzing brain function. In this study, we examined whether PAC could be a biomarker for FOG. Methods: We enrolled 11 patients with Parkinson’s disease and recorded scalp EEG in preparation for and during gait while simultaneously assessing motor function, including FOG. We investigated changes in cortical PAC during walking with and without FOG and examined its correlation with the postural instability and gait difficulty (PIGD) score. Results: Patient characteristics were as follows: mean age 59.1 ± 6.9 years, disease duration 13.9 ± 4.1 years, and seven men. Four trials were excluded from the analysis owing to artifacts. In the trials without FOG (n=18), beta-gamma PAC in the sensorimotor area decreased during gait preparation (p = 0.011; linear mixed-effects model), which was not the case in trials with FOG (n=6) (p = 0.64; linear mixed-effects model). Using a support vector machine, machine learning of PAC during preparation for walking predicted the presence of FOG with an accuracy of 71.2%. Conversely, PAC increased during walking in trials with FOG (p = 0.0042; linear mixed-effects model), and PAC 20 s after the start of walking was positively correlated with the PIGD score (correlation coefficient = 0.406, p = 0.032; Pearson’s rank correlation). Conclusions: Beta-gamma PAC in the sensorimotor area during preparation for walking differs depending on the emergence of FOG. As gait symptoms worsened, beta-gamma PAC in the sensorimotor area during walking gradually increased. Cortical PAC may be a biomarker for FOG in Parkinson's disease and may lead to the development of strategies to prevent falls in the future.