Loss of presynaptic inhibition for step initiation in parkinsonian individuals with freezing of gait
- 1 April 2020
- journal article
- research article
- Published by Wiley
- Vol. 598 (8), 1611-1624
- https://doi.org/10.1113/JP279068
Abstract
Key points Individuals with freezing of gait (FoG) due to Parkinson's disease (PD) have small and long anticipatory postural adjustments (APAs) associated with delayed step initiation. Individuals with FoG ('freezers') may require functional reorganization of spinal mechanisms to perform APAs due to supraspinal dysfunction. As presynaptic inhibition (PSI) is centrally modulated to allow execution of supraspinal motor commands, it may be deficient in freezers during APAs. We show that freezers presented PSI in quiet stance (control task), but they presented loss of PSI (i.e. higher ratio of the conditioned H-reflex relative to the test H-reflex) during APAs before step initiation (functional task), whereas non-freezers and healthy control individuals presented PSI in both the tasks. The loss of PSI in freezers was associated with both small APA amplitudes and FoG severity. We hypothesize that loss of PSI during APAs for step initiation in freezers may be due to FoG. Freezing of gait (FoG) in Parkinson's disease involves deficient anticipatory postural adjustments (APAs), resulting in a cessation of step initiation due to supraspinal dysfunction. Individuals with FoG ('freezers') may require functional reorganization of spinal mechanisms to perform APAs. As presynaptic inhibition (PSI) is centrally modulated to allow execution of supraspinal motor commands, here we hypothesized a loss of PSI in freezers during APA for step initiation, which would be associated with FoG severity. Seventy individuals [27 freezers, 22 non-freezers, and 21 age-matched healthy controls (HC)] performed a 'GO'-commanded step initiation task on a force platform under three conditions: (1) without electrical stimulation, (2) test Hoffman reflex (H-reflex) and (3) conditioned H-reflex. They also performed a control task (quiet stance). In the step initiation task, the H-reflexes were evoked on the soleus muscle when the amplitude of the APA exceeded 10-20% of the mean baseline mediolateral force. PSI was quantified by the ratio of the conditioned H-reflex relative to the test H-reflex in both the tasks. Objective assessment of FoG severity (FoG-ratio) was performed. Freezers presented lower PSI levels during quiet stance than non-freezers and HC (P < 0.05). During step initiation, freezers presented loss of PSI and lower APA amplitudes than non-freezers and HC (P < 0.05). Significant correlations were only found for freezers between loss of PSI and FoG-ratio (r = 0.59, P = 0.0005) and loss of PSI and APA amplitude (r = -0.35, P < 0.036). Our findings suggest that loss of PSI for step initiation in freezers may be due to FoG.Keywords
Funding Information
- U.S. Department of Veterans Affairs (5I01RX001075)
- National Institutes of Health (R01AG006457)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (03085/2015‐0, 406609/2015‐2)
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2018/16909‐1, 2016/13115‐9)
This publication has 81 references indexed in Scilit:
- Freezing of gait: moving forward on a mysterious clinical phenomenonPublished by Elsevier ,2011
- The supplementary motor area contributes to the timing of the anticipatory postural adjustment during step initiation in participants with and without Parkinson's diseaseNeuroscience, 2009
- Spinal Cord Stimulation Restores Locomotion in Animal Models of Parkinson's DiseaseScience, 2009
- Knee trembling during freezing of gait represents multiple anticipatory postural adjustmentsExperimental Neurology, 2008
- Increased central facilitation of antagonist reciprocal inhibition at the onset of dorsiflexion following explosive strength trainingJournal of Applied Physiology, 2008
- Understanding and treating freezing of gait in parkinsonism, proposed working definition, and setting the stageMovement Disorders, 2008
- Independent and Convergent Signals From the Pontomedullary Reticular Formation Contribute to the Control of Posture and Movement During Reaching in the CatJournal of Neurophysiology, 2004
- Motor response to acute dopaminergic challenge with apomorphine and levodopa in Parkinson's disease: implications for the pathogenesis of the on-off phenomenon.Journal of Neurology, Neurosurgery & Psychiatry, 1996
- Presynaptic inhibition of soleus Ia afferent terminals in Parkinson's disease.Journal of Neurology, Neurosurgery & Psychiatry, 1994
- H reflex studies in patients with Parkinson's diseaseJournal of Neurology, Neurosurgery & Psychiatry, 1972