One novel aspect of our model is that it provides an approach, i.e. PAC in M1, to quantitatively track dynamic changes of the motor circuit in the occurrence of FOG. Previously, abnormal PAC has been documented in the M1 area in both animal models and humans with Parkinson’s disease. It was shown that beta-gamma PAC is correlated with the severity of bradykinesia and decreases during movement.17,37,38 In our study, we also observed reduced PAC during walking as compared to standing. We hypothesize that the release of cortical broad-gamma amplitude from low oscillation phases may facilitate the motor execution.39 While by demonstrating that trials with significantly different walking velocities had similar PAC as long as freezing did not occur (Supplementary Fig. 3), we showed that PAC was not a mere reflection of movement intensity but did indicate motor impairments related to FOG. PAC as one class of cross-frequency coupling is considered a vital fundamental mechanism underlying information processing.16 In normal states, the modulation of the high-frequency amplitude by the low-frequency rhythms is highly dynamic and task-specific.17,40 In the pathological Parkinson’s disease
