Neuromuscular Dynamic Range in Parkinson's Disease: Cortico-Muscular Signatures of Freezing Across a Graded Gait Demand Continuum

Freezing of gait (FOG) is one of the most disabling symptoms of Parkinson's disease, and neither why some patients freeze nor what precedes an episode is understood. An episode presents as an attempt to step that no effective step follows, so the motor command fails to reach the leg muscles as an effective output at some level of the descending pathway. The signal that carries that command along this path is the corticospinal drive, and it can be measured while a patient walks as the coupling between cortical and muscular activity. Scalp EEG and lower-limb EMG were recorded in people with Parkinson's disease with and without freezing of gait, on medication, during walking conditions of increasing demand and during voluntary and requested stops. Corticomuscular and intermuscular coherence were estimated by wavelet coherence and analysed both as the rate of coherence bursts and as the mean coherence in fixed windows; EEG band power was analysed alongside, and video-annotated freezing episodes were compared with the stops of the same subjects. During gait, freezers carried a larger share of theta than non-freezers in every walking condition. With increasing demand, corticomuscular coherence in the high beta and gamma bands rose in both groups and intermuscular coherence at the ankle rose in non-freezers, while muscle activity fell. The rise was smaller in freezers in almost every band and condition and absent in high beta during obstacle navigation, the one cell on which both analyses and both metrics converged. The smaller modulation did not come from a lower level of coupling: during ordinary walking freezers produced more corticomuscular bursts than non-freezers, and no difference in intermuscular level held under both threshold rules. A freezing episode shared with a stop only the rise of intermuscular coherence at its onset: muscle activity did not collapse, the gamma rise of corticomuscular coherence was absent, and low beta corticomuscular coherence fell in the second before the onset, in every subject and in no stop. Freezing of gait is thus marked by a reduced range over which corticomuscular and intermuscular coupling are modulated by demand, and the episode is preceded by a loss of corticomuscular coupling rather than by a fall of muscle activity. Both measures are therefore worth developing further, as candidate biomarkers of freezing of gait and as a tool for studying its pathophysiology.