Neuromuscular correlates of subthalamic stimulation and upper limb freezing in Parkinson's disease

Objective: The pathophysiology of deep brain stimulation mechanisms and resistant freezing phenomena in idiopathic Parkinson's disease (iPD) remains incompletely understood. Further studies on the neuromuscular substrates are needed. Methods: We analyzed 16 patients with advanced iPD and bilateral subthalamic nucleus stimulation, and 13 age-and gender-matched healthy controls. Patients were tested after overnight withdrawal of medication with 'stimulation off' (StimOff) and 'stimulation on' (StimOn). Subjects performed continuous tapping of the right index finger with simultaneous recordings of biomechanical registration, EMG of finger flexors and extensors, and EEG. First, we analyzed EEG and EMG spectral measures comparing StimOff with healthy controls and StimOff with StimOn (irrespective of freezing). Second, we contrasted 'regular (unimpaired) tapping' and 'freezing' resistant to subthalamic neurostimulation as obtained in StimOn. Results: iPD showed increased intermuscular coherence around 8 Hz in StimOff that was reduced in StimOn. This 8 Hz muscular activity was not coherent to cortical activity. 'Freezing' episodes showed increased muscle activity of finger flexors and extensors at 6-9 Hz, and increased cortical activity at 7-11 Hz. During transition from regular tapping to 'freezing' the cortical activity first increased over the left sensorimotor area followed by a spread to the left frontal and right parietal areas. Conclusions: We identified neuromuscular motor network features of subthalamic neurostimulation therapy and resistant upper limb freezing that point to increased low-frequency muscular and cortical activity. Significance: Together, our findings demonstrate several motor network abnormalities associated with upper limb freezing that may translate into future research on freezing of gait in iPD.