Gait-related brain activity in people with Parkinson disease with freezing of gait

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.

Figure 1. Gait imagery task.

After reading the cue, the participant closes his eyes, pushes a button, and begins imagining. At the completion of gait imagery, he again presses the button and opens his eyes.

Figure 2. Regions of interest.

Regions were identified for each individual separately based on standard definitions (see Methods). Shown are examples of regions defined for four subjects: supplementary motor area (a), putamen and globus pallidus (b), cerebellar locomotor region (c), and mesencephalic locomotor region (d). A-Anterior; P-Posterior; R-Right; L-Left.

Figure 3. Gait imagery times in FoG− and FoG+ during short and long gait imagery tasks.

“Long” gait imagery tasks took significantly longer than “short” gait imagery tasks (denoted by *, F_1,16 = 34.6; p<0.001, repeated measures ANOVA). Differences between FoG+ and FoG− did not reach significance.

Figure 4. Correlation between actual and imagined walking times for freezers and non-freezers.

Correlation statistics represent all participants.

Figure 5. Mean Beta weights (with respect to rest) for FoG- and FoG+ during imagined walking in the right GP.

A group effect, corrected for MDS-UPDRS and gait imagery speed, was noted such that FoG+ exhibited smaller BOLD signal than FoG- (p = 0.01). Error bars represent standard error of the mean.

Figure 6. Mean beta weights (with respect to rest) for FoG− and FoG+ during imagined walking in the right SMA, right GP, and right MLR.

Error bars represent standard error of the mean. *ANCOVA group differences after correcting for MDS-UPDRS and gait imagery speed.