Dysfunctional Limbic Circuitry Underlying Freezing of Gait in Parkinson's Disease

Moran Gilat, Kaylena A. Ehgoetz Martens, Oscar Miranda-Domínguez, Ishu Arpan, James M. Shine, Martina Mancini, Damien A. Fair, Simon J.G. Lewis, Fay B. Horak

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Freezing of gait (FOG) is a poorly understood symptom affecting many patients with Parkinson's disease (PD). Despite growing evidence of a behavioral link between anxiety, attention and FOG in PD, no research to date has investigated the neural mechanisms that might explain this relationship. The present study therefore examined resting-state MRI functional connectivity between the amygdala, striatum and frontoparietal attentional control network in PD patients with (freezers: n = 19) and without FOG (non-freezers: n = 21) in the dopaminergic ‘off’ state. Functional connectivity was subsequently correlated with an objective measure of FOG severity and a subjective scale of affective disorder within each group. Connectivity between the right amygdala and right putamen was significantly increased in freezers compared to non-freezers (p < 0.01). Furthermore, freezers showed increased anti-coupling between the frontoparietal network and left amygdala (p = 0.011), but reduced anti-coupling between this network and the right putamen (p = 0.027) as compared to non-freezers. Key functional connections between the amygdala, putamen and frontoparietal network were significantly associated with FOG severity and a fear of falling. This study provides the first evidence that dysfunctional fronto-striato-limbic processes may underpin the link between anxiety and FOG in PD. It is proposed that freezers have heightened striato-limbic load and reduced top-down attentional control at rest, which when further challenged by the parallel processing demands of walking may precipitate FOG.

Original languageEnglish (US)
Pages (from-to)119-132
Number of pages14
JournalNeuroscience
Volume374
DOIs
StatePublished - Mar 15 2018

Keywords

  • Parkinson's disease
  • amygdala
  • anxiety
  • functional MRI
  • gait disorders
  • putamen

ASJC Scopus subject areas

  • Neuroscience(all)

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    Gilat, M., Ehgoetz Martens, K. A., Miranda-Domínguez, O., Arpan, I., Shine, J. M., Mancini, M., Fair, D. A., Lewis, S. J. G., & Horak, F. B. (2018). Dysfunctional Limbic Circuitry Underlying Freezing of Gait in Parkinson's Disease. Neuroscience, 374, 119-132. https://doi.org/10.1016/j.neuroscience.2018.01.044