Objective: To investigate if decreased mesencephalic locomotor activation (MRL) activation during step initiation in an-event related fMRI protocol would explain the loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) in people with Parkinson’s disease with freezing of gait (freezers).

Background: Our group recently observed that freezers have loss of PSI during APAs.¹ PSI is centrally modulated to allow execution of supraspinal motor commands at the spinal level for postural preparation.^2,3,4 Decreased blood oxygenation level dependent (BOLD) signal within the MRL during a fMRI protocol that simulates walking is correlated with freezing of gait (FOG) severity.⁵ MLR has neurons related to APAs preceding step initiation.⁶ Thus, we hypothesized that small MLR neuronal activity would explain the loss of PSI during APAs in freezers.

Method: Clinical variables (e.g., UPDRS-III, FoG-ratio during turning test, Stroop test, and disease duration), behavioral variables during step initiation on a force platform (IPS by control and conditioned H-reflexes, APA amplitude, soleus muscle activation, tibial anterior muscle activation, and co-contraction), and beta of BOLD signal change during step initiation in an event-related fMRI protocol of areas known to initiate and pace gait (i.e., MLR, supplementary motor area, and cerebellar locomotor area [see coordinates in Table 1) were assessed on different days in 34 freezers in the ON-medication state (Table 2).

Results: Beta of BOLD signal change of the right MLR, APA amplitude, FOG-ratio, and disease duration entered the linear multiple regression model using the PROC REG of SAS (Table 3). Only decreased BOLD signal change of the right MLR (R²=0.32, P=0.0006) and decreased APA amplitude (R²=0.13, P=0.0097) explained 45% of the loss of PSI during step initiation in freezers (Table 3). See a graphical representation of these results in Figure 2.

Conclusion: Our results suggest that freezers have less central (MLR) inhibition when standing to allow for step initiation. This is reflected in loss of spinal inhibition (PSI) during postural preparation for a step. Deficit in central and spinal inhibitions during step initiation may be related to FOG pathophysiology.

References: [1] Lira, J.L.O., et al. (2020). Loss of presynaptic inhibition for step initiation in parkinsonian individuals with freezing of gait. The Journal of physiology, 2020. [2] Hultborn H., Meunier S., Morin C & Pierrot-Deseilligny (1987). Assessing changes in presynaptic inhibition of Ia fibres: a study in man and the cat. The Journal of physiology, 1987. [3] Katz, R., Meunier, S., & Pierrot-Deseilligny, E. (1988). Changes in presynaptic inhibition of Ia fibres in man while standing. Brain, 1988. [4] Rudomin P. & Schmidt R.F. (1999). Presynaptic inhibition in the vertebrate spinal cord revisited. Experimental brain research, 1999. [5] Shine J.M., et al. (2013). Exploring the cortical and subcortical functional magnetic resonance imaging changes with freezing in Parkinson´s disease. Brain, 2013. [6] Sinnamon H.M., Jassen A.K., Vita L.A. (2000). Brainsteim regions with neuronal activity patterns correlated with priming of locomotor stepping in the anesthetized rat. Neuroscience, 2000. [7] Fling B.W., et al. (2014). Functional reorganization of the locomotor network in Parkinson patients with freezing of gait. PloS one, 2014. [8] Shine J.M., et al. (2013). Freezing of gait in Parkinson’s disease is associated with functional decoupling between the cognitive control network and the basal ganglia. Brain, 2013.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/decreased-mesencephalic-locomotor-region-activation-explains-loss-of-presynaptic-inhibition-during-step-initiation-in-people-with-parkinsons-disease-with-freezing-of-gait/