Mesencephalic Locomotor Region and Presynaptic Inhibition during Anticipatory Postural Adjustments in People with Parkinson's Disease

Carla Silva-Batista; Jumes Lira; Daniel Boari Coelho; Andrea Cristina de Lima-Pardini; Mariana Penteado Nucci; Eugenia Casella Tavares Mattos; Fernando Henrique Magalhaes; Egberto Reis Barbosa; Luis Augusto Teixeira; Edson Amaro Junior; Carlos Ugrinowitsch; Fay B Horak

doi:10.3390/brainsci14020178

Mesencephalic Locomotor Region and Presynaptic Inhibition during Anticipatory Postural Adjustments in People with Parkinson's Disease

Brain Sci. 2024 Feb 15;14(2):178. doi: 10.3390/brainsci14020178.

Authors

Affiliations

¹ Exercise Neuroscience Research Group, University of São Paulo, São Paulo 05508-070, Brazil.
² Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA.
³ School of Arts, Sciences and Humanities, University of São Paulo, São Paulo 03828-000, Brazil.
⁴ School of Physical Education and Sport, University of São Paulo, São Paulo 05508-030, Brazil.
⁵ Biomedical Engineering, Federal University of ABC, São Bernardo do Campo 09210-170, Brazil.
⁶ Centre for Neuroscience Studies, Queen's University, Kingston, ON K7L 3N6, Canada.
⁷ Department of Radiology, University of São Paulo, São Paulo 05508-090, Brazil.
⁸ Instituto de Ciencias e Tecnologia, Universidade Federal de São Paulo, São Paulo 09913-030, Brazil.
⁹ Movement Disorders Clinic, Department of Neurology, School of Medicine, University of São Paulo, São Paulo 05508-070, Brazil.

Abstract

Individuals with Parkinson's disease (PD) and freezing of gait (FOG) have a loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) for step initiation. The mesencephalic locomotor region (MLR) has connections to the reticulospinal tract that mediates inhibitory interneurons responsible for modulating PSI and APAs. Here, we hypothesized that MLR activity during step initiation would explain the loss of PSI during APAs for step initiation in FOG (freezers). Freezers (n = 34) were assessed in the ON-medication state. We assessed the beta of blood oxygenation level-dependent signal change of areas known to initiate and pace gait (e.g., MLR) during a functional magnetic resonance imaging protocol of an APA task. In addition, we assessed the PSI of the soleus muscle during APA for step initiation, and clinical (e.g., disease duration) and behavioral (e.g., FOG severity and APA amplitude for step initiation) variables. A linear multiple regression model showed that MLR activity (R² = 0.32, p = 0.0006) and APA amplitude (R² = 0.13, p = 0.0097) explained together 45% of the loss of PSI during step initiation in freezers. Decreased MLR activity during a simulated APA task is related to a higher loss of PSI during APA for step initiation. Deficits in central and spinal inhibitions during APA may be related to FOG pathophysiology.

Keywords: H-reflex; anticipatory postural adjustment; freezers; mesencephalic locomotor region; presynaptic inhibition; step initiation.

Grants and funding

Fundação de Amparo à Pesquisa do Estado de São Paulo under award numbers 2015/13096-1 for Carlos Ugrinowitsch, 2016/13115-9 and 2018/16909-1 for Carla Silva-Batista, the Conselho Nacional de Desenvolvimento Científico e Tecnológico under award numbers 406609/2015-2 for Carlos Ugrinowitsch, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior under award numbers 88887.388143/2019-00 and 03085/2015-0 for Carlos Ugrinowitsch, and Oregon Health & Science University Fellowship for Diversity in Research under award number 2022 (OFDIR-OHSU) for Carla Silva-Batista.