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

Abstract

Key pointsr 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.r 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.r 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.r The loss of PSI in freezers was associated with both small APA amplitudes and FoG severity. r We hypothesize that loss of PSI during APAs for step initiation in freezers may be due to FoG.Abstract 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 Jumes Lira is a Master's researcher of the Exercise Neuroscience Research Group, School of Arts, Sciences and Humanities, University of São Paulo, Brazil. His work has focused on understanding the spinal inhibitory mechanisms in Parkinson's disease using neurophysiological approaches. More specifically, he is interested in identifying alterations in spinal pathways related to freezing of gait of Parkinson's disease during functional tasks, leading to the development of mechanistic-based interventions for physical therapy. others J Physiol 598.8step 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 los...

The Adapted Resistance Training with Instability Randomized Controlled Trial for Gait Automaticity

“…3,11,22 The ARTI program incorporates complex motor exercises with dual-task conditions, which require high attentional, motor control, and sensorimotor demands. These primary characteristics of ARTI are very important to restore gait automaticity in freezers because they present an inadequate integration of sensory inputs and proprioceptive deficits, 52 as external somatosensory cues can mitigate freezing events while walking 53 as well as DTC on gait speed and stride length. 54 Second, freezers present worse attentional control to perform dual-task walking than nonfreezers, as gait attentiondirected cues (visual external information) improve dual-task walking.…”

A Randomized, Controlled Trial of Exercise for Parkinsonian Individuals With Freezing of Gait

“…4,5 Individuals with FOG (freezers) show delayed step initiation associated with repetitive anticipatory postural adjustments (APAs) as if they cannot inhibit their postural preparation and release their stepping motor program. 6 In fact, FOG has been associated with small and prolonged APAs during step initiation 7 and deficits in cognitive inhibition. 5 Thus, we hypothesize that improving APAs and cognitive inhibition could contribute to decreased FOG severity.…”

“…14 No study has investigated the effects of exercise intervention on MLR activation and gait initiation (APAs) in freezers. Thus, as abnormal APAs and dysfunction in cognitive inhibition are associated with FOG 5,7 and linked to impairments in MLR, we hypothesized that exercise interventions aiming to improve these aspects could increase MLR activation and decrease FOG severity.…”

Freezing of Gait in Parkinson’s Disease: Risk Factors, Their Interactions, and Associated Nonmotor Symptoms

“…Reactive and dynamic postural control have been identified as the most affected postural control systems in FOG [ 34 , 35 ], specifically weight-shifting impairments and inadequate scaling and timing of postural responses, especially when occurring under time constraints [ 36 ]. This appears to be related to loss of presynaptic inhibition for step initiation [ 37 ]. Other than balance-gait impairment, bradykinesia was also strongly correlated with FOG in our study, most other studies similarly supporting the relationship of more severe motor disability with an increased risk of FOG [ 4 , 5 , 9 , 11 , 13 , 14 ].…”