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 OFF state, perpetually elevated M1 PAC may reflect a restricted cortical activation state in which M1 neurons are not able to respond dynamically to communication across other cortical and subcortical circuits. Given that M1 is a crucial node in human gait physiology,10 a pathological hypersynchrony in M1, through entrainment and phase locking of the broad-gamma activity to the beta carrier rhythm, could underpin the pathological basis for FOG in Parkinson’s disease. Alternatively, elevated PAC may reflect changes in the sharpness and asymmetry of cortical beta band waves, representing the excessive neural synchrony in the basal ganglia-thalamocortical loop.41,42 Here, our data reveal moderate correlations of PAC and beta waveform shape and sharpness asymmetry measures (Supplementary Fig. 6). This suggests, neither mechanism alone can explain PAC in our study and that either one demonstrates a form of excessive synchrony in M1 and could be relevant to the pathology of FOG.
