Category: Parkinson's Disease: Pathophysiology
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:  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.  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.  Katz, R., Meunier, S., & Pierrot-Deseilligny, E. (1988). Changes in presynaptic inhibition of Ia fibres in man while standing. Brain, 1988.  Rudomin P. & Schmidt R.F. (1999). Presynaptic inhibition in the vertebrate spinal cord revisited. Experimental brain research, 1999.  Shine J.M., et al. (2013). Exploring the cortical and subcortical functional magnetic resonance imaging changes with freezing in Parkinson´s disease. Brain, 2013.  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.  Fling B.W., et al. (2014). Functional reorganization of the locomotor network in Parkinson patients with freezing of gait. PloS one, 2014.  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.
To cite this abstract in AMA style:J. Lira, C. Ugrinowitsch, M. Nucci, D. Coelho, E. Barbosa, L. Teixeira, E. Júnior, F. Horak, M. Mancini, C. Batista. Decreased mesencephalic locomotor region activation explains loss of presynaptic inhibition during step initiation in people with Parkinson´s disease with freezing of gait [abstract]. Mov Disord. 2021; 36 (suppl 1). 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/. Accessed December 1, 2023.
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