Abstract

Approximately 50% of people with Parkinson disease experience freezing of gait, described as a transient inability to produce effective stepping. Complex gait tasks such as turning typically elicit freezing more commonly than simple gait tasks, such as forward walking. Despite the frequency of this debilitating and dangerous symptom, the brain mechanisms underlying freezing remain unclear. Gait imagery during functional magnetic resonance imaging permits investigation of brain activity associated with locomotion. We used this approach to better understand neural function during gait-like tasks in people with Parkinson disease who experience freezing- “FoG+” and people who do not experience freezing- ”FoG−“. Nine FoG+ and nine FoG− imagined complex gait tasks (turning, backward walking), simple gait tasks (forward walking), and quiet standing during measurements of blood oxygen level dependent (BOLD) signal. Changes in BOLD signal (i.e. beta weights) during imagined walking and imagined standing were analyzed across FoG+ and FoG− groups in locomotor brain regions including supplementary motor area, globus pallidus, putamen, mesencephalic locomotor region, and cerebellar locomotor region. Beta weights in locomotor regions did not differ for complex tasks compared to simple tasks in either group. Across imagined gait tasks, FoG+ demonstrated significantly lower beta weights in the right globus pallidus with respect to FoG−. FoG+ also showed trends toward lower beta weights in other right-hemisphere locomotor regions (supplementary motor area, mesencephalic locomotor region). Finally, during imagined stand, FoG+ exhibited lower beta weights in the cerebellar locomotor region with respect to FoG−. These data support previous results suggesting FoG+ exhibit dysfunction in a number of cortical and subcortical regions, possibly with asymmetric dysfunction towards the right hemisphere.

Highlights

  • Gait dysfunction is common in Parkinson disease (PD), and includes short steps [1], increased step time variability [2], and poor step-to-step coordination [3]

  • Two recent reports used functional magnetic resonance imaging to investigate brain activity in Freezing of Gait (FoG)+ during gait-like tasks [14,15]. These reports showed FoG+ to exhibit altered activity in the mesencephalic locomotor region (MLR) compared to people who do not freeze (FoG2) during gait imagery [14], and during lower limb motor blocks [15]. These results support the notion that altered activity in brainstem regions may relate to freezing of gait

  • 1 Participants functional magnetic resonance imaging (fMRI) data were collected from 26 participants with PD

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Summary

Introduction

Gait dysfunction is common in Parkinson disease (PD), and includes short steps [1], increased step time variability [2], and poor step-to-step coordination [3]. Two recent reports used functional magnetic resonance imaging (fMRI) to investigate brain activity in FoG+ during gait-like tasks [14,15] These reports showed FoG+ to exhibit altered activity in the mesencephalic locomotor region (MLR) compared to people who do not freeze (FoG2) during gait imagery [14], and during lower limb motor blocks [15]. Shine and colleagues showed reduced activity in the globus pallidus, putamen, and several cortical areas during motor arrests in FoG+ These studies, along with many others [14,16,17,18,19,20,21,22,23,24], have shown the efficacy of using gait-like tasks, including gait imagery, to assess locomotor dysfunction. This approach has provided important insight into brain activation during locomotion in humans [16,17,30]

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