Lateralized Connectivity between Globus Pallidus and Motor Cortex is Associated with Freezing of Gait in Parkinson's Disease

Óscar Miranda-Domínguez, Anjanibhargavi Ragothaman, Robert Hermosillo, Eric Feczko, Rosie Morris, Patricia Carlson-Kuhta, John G. Nutt, Martina Mancini, Damien Fair, Fay B. Horak

Research output: Contribution to journalArticlepeer-review

Abstract

Freezing of gait (FoG) is a brief, episodic absence or marked reduction of forward progression of the feet, despite the intention to walk, that is common in people with Parkinson's disease (PD). We hypothesized that not only motor, but higher level cognitive and attention areas may be impaired in freezers. In this study, we aimed to characterize differences in cortical and subcortical functional connectivity specific to FoG. We examined resting state neuroimaging and objective measures of FoG severity and gait from 103 individuals (28 PD + FoG, 36 PD − FoG and 39 healthy controls). Inertial sensors were used to quantify freezing severity and gait. Groups with and without FoG were matched on age, disease severity, cognitive status, and levodopa medication. MRI data was processed using surface-based registration. High-quality imaging data were used to characterize differences in connectivity specific to FoG using a pre-defined set of Regions of Interest (ROIs) and validated using whole-brain connectivity analysis. Associations between functional connectivity and objective measures of FoG were determined via predictive modeling using hold-out cross validation. We found that connectivity between the left globus pallidus (GP) and left somatosensory cortex and between two brain areas in the default and insular/vestibular networks exhibited significant differences specific to FoG and were also strong and significant predictors of FoG severity. Our findings suggest that the interplay among motor, default and vestibular areas of the left cortex are critical in the pathology of FoG.

Original languageEnglish (US)
Pages (from-to)44-58
Number of pages15
JournalNeuroscience
Volume443
DOIs
StatePublished - Sep 1 2020
Externally publishedYes

Bibliographical note

Funding Information:
Funding: This Research was supported by the Tartar Trust Fellowship (Miranda-Dominguez), OHSU Parkinson Center Pilot Grant Program (Miranda-Dominguez), NLM: the National Library of Medicine: T15LM007088 (Feczko), National Institute on Aging (NIA) grant 5R01 AG006457 PI (Horak), US Department of Veterans Affairs VA grant: I01 RX001075 PI (Horak), National Institutes of Health National Institute of Mental Health (NIMH) grants R01MH115357 (Fair) and a Supplement to Promote Diversity R01MH115357-02S1 (Hermosillo).

Publisher Copyright:
© 2020 IBRO

Keywords

  • attention systems
  • freezing of gait
  • functional connectivity
  • globus pallidus
  • Parkinson's disease

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

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