Abstract
ObjectiveFreezing of gait is detrimental to patients with idiopathic Parkinson’s disease (PD). Its pathophysiology represents a multilevel failure of motor processing in the cortical, subcortical, and brainstem circuits, ultimately resulting in ineffective motor output of the spinal pattern generator. Electrophysiological studies pointed to abnormalities of oscillatory activity in freezers that covered a broad frequency range including the theta, alpha, and beta bands. We explored muscular frequency domain activity with respect to freezing, and used deep brain stimulation to modulate these rhythms thereby evaluating the supraspinal contributions to spinal motor neuron activity.MethodsWe analyzed 9 PD freezers and 16 healthy controls (HC). We studied the patients after overnight withdrawal of dopaminergic medication with stimulation off, stimulation of the subthalamic nucleus (STN-DBSonly) or the substantia nigra pars reticulate (SNr-DBSonly), respectively. Patients performed a walking paradigm passing a narrow obstacle. We analyzed the frequency-domain spectra of the tibialis anterior (TA) and gastrocnemius (GA) muscles in ‘regular gait’ and during the ‘freezing’ episodes.ResultsIn stimulation off, PD freezers showed increased muscle activity of the alpha and low-beta band compared to HC in both TA and GA. This activity increase was present during straight walking and during the freezes to similar extent. STN- but not SNr-DBS decreased this activity and paralleled the clinical improvement of freezing.ConclusionWe found increased muscle activation of the alpha and lower beta band in PD freezers compared to HC, and this was attenuated with STN-DBS. Future studies may use combined recordings of local field potentials, electroencephalography (EEG), and electromyography (EMG) to interrogate the supraspinal circuit mechanisms of the pathological activation pattern of the spinal pattern generator.
Highlights
Freezing of gait (FoG) in Parkinson’s disease (PD) represents the defective spinal motor output depending on the supraspinal cortical, subcortical, and brainstem contributions (Lewis and Shine, 2016; Snijders et al, 2016; Weiss et al, 2020)
Healthy Controls vs. Parkinson’s Disease in ‘Stimulation Off’ Parkinson’s disease patients in ‘stimulation off (StimOff) ’ showed higher power of both the tibialis anterior (TA) and the GA compared to healthy controls (HC) in the cluster-based statistical comparison from 1 to 45 Hz during ‘regular gait.’
Statistical analysis revealed similar results: PD patients in ‘StimOff ’ showed higher power of both the TA and the GA compared to HC in the cluster-based statistical comparison from 1 to 45 Hz during ‘regular gait.’
Summary
Freezing of gait (FoG) in Parkinson’s disease (PD) represents the defective spinal motor output depending on the supraspinal cortical, subcortical, and brainstem contributions (Lewis and Shine, 2016; Snijders et al, 2016; Weiss et al, 2020). In human PD, nigral stimulation modulated clinical and kinematic gait measures (Scholten et al, 2017; Heilbronn et al, 2019) and FoG It has to be kept in mind that these conclusions stem from piloting observations and have to be confirmed in larger clinical trials (Snijders et al, 2016; Garcia-Rill et al, 2019; Weiss et al, 2020)
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