Loss of presynaptic inhibition for step initiation in parkinsonian individuals with freezing of gait

Author(s)

Lira, Jumes Leopoldino Oliveira ^[1] ; Ugrinowitsch, Carlos ^[2] ; Coelho, Daniel Boari ^{[3, 4]} ; Teixeira, Luis Augusto ^[4] ; de Lima-Pardini, Andrea Cristina ^[5] ; Magalhaes, Fernando Henrique ^[1] ; Barbosa, Egberto Reis ^[6] ; Horak, Fay B. ^[7] ; Silva-Batista, Carla ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Arts Sci & Humanities, Exercise Neurosci Res Grp, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Sch Phys Educ & Sport, Lab Strength Training, Sao Paulo, SP - Brazil

^[3] Fed Univ ABC, Biomed Engn, Sao Bernardo Do Campo, SP - Brazil

^[4] Univ Sao Paulo, Sch Phys Educ & Sport, Human Motor Syst Lab, Sao Paulo, SP - Brazil

^[5] Queens Univ, Ctr Neurosci Studies, Kingston, ON - Canada

^[6] Univ Sao Paulo, Dept Neurol, Movement Disorders Clin, Sch Med, Sao Paulo, SP - Brazil

^[7] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 - USA

• Document type: Journal article
• Source: JOURNAL OF PHYSIOLOGY-LONDON; v. 598, n. 8, p. 1611-1624, APR 2020.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 18/16909-1 - Effects of resistance training with instability on clinical outcomes, spinal mechanisms, and brain metrics in individuals with freezing of gait in Parkinson's disease
• Grantee: Carla da Silva Batista
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 15/13096-1 - Neuromuscular adaptations associated with sports practice: effect of muscle fatigue on electromyographic parameters and on postural control
• Grantee: Fernando Henrique Magalhães
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/13115-9 - Effects of resistance training with instability on clinical outcomes, spinal mechanisms, and brain metrics in individuals with freezing of gait in Parkinson's disease
• Grantee: Carla da Silva Batista
• Support Opportunities: Scholarships in Brazil - Post-Doctoral