E. Sarasso1,2,3, F. Agosta1,3, N. Piramide1,3, E. Canu1,3, M.A. Volontè4, M. Filippi1,4,5,3
1IRCCS San Raffaele Scientific Institute, Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Milan, Italy, 2IRCCS San Raffaele Scientific Institute, Laboratory of Movement Analysis, Milan, Italy, 3Vita-Salute San Raffaele University, Milan, Italy, 4IRCCS San Raffaele Scientific Institute, Neurology Unit, Milan, Italy, 5IRCCS San Raffaele Scientific Institute, Neurophysiology Unit, Milan, Italy

Background: The functional neural correlates underpinning the pathophysiology of freezing of gait (FoG) in Parkinson’s disease (PD) patients have been explored using functional magnetic resonance imaging (fMRI). Recent evidence suggested a problematic interplay between motor, cognitive, and emotional circuits in the underlying mechanisms of FoG. However, the majority of MRI studies have investigated the activity of brain circuits involved in FoG manifestation using motor tasks and no study has investigated the activity of the whole emotional circuit using specific task-based approaches in PD-FoG patients.

Purpose: The aim of this study was to assess the fMRI activity of the emotional brain circuit during a “FoG-observation-task” in PD-FoG patients relative to a sample of healthy controls.

Methods: Twenty-four PD-FoG patients and 18 age- and sex-matched healthy controls performed clinical and neuropsychological evaluations, and fMRI experiments including:
i) “FoG-observation-task” consisting of watching a patient experiencing FoG during a walking task (usually evoking FoG);
ii) “gait-observation-task” consisting of watching a healthy subject performing similar walking tasks without experiencing FoG.

Results: During both tasks, PD-FoG patients showed reduced activity of the fronto-parietal mirror neuron system (MNS) relative to healthy controls. In the “FoG-observation-task” relative to the “gait-observation-task”, PD-FoG patients revealed increased recruitment of the anterior medial prefrontal cortex and decreased activity of the parietal MNS, while healthy controls showed increased recruitment of the dorsomedial prefrontal cortex, supplementary motor area and hippocampus and decreased activity of the fronto-parietal MNS.

Conclusion(s): During the observation of a subject experiencing FoG, healthy controls recruited brain regions associated with cognitive empathy, while PD-FoG patients recruited areas related to the elaboration of self-related emotions such as the ventromedial prefrontal cortex likely linked to the evoked FoG experience.

Implications: The emotional brain circuit is involved in the mechanisms underlying FoG. Future studies should assess if rehabilitative treatments targeted both to the improvement of motor skills and to the management of emotions could further improve FoG. Task-based fMRI should be considered as a useful complementary outcome measure to monitor specific rehabilitative training effects in PD-FoG patients.

Funding, acknowledgements: This study was partially supported by the Jacques and Gloria Gossweiler Foundation.

Keywords: Parkinson’s disease, freezing of gait, fMRI

Topic: Neurology: Parkinson's disease

Did this work require ethics approval? Yes
Institution: IRCCS San Raffaele Scientific Institute; Milan, Italy
Committee: Human Research Ethics Committee of San Raffaele Scientific Institute, Milan, Italy
Ethics number: AOT in PD FOG-JGGF

All authors, affiliations and abstracts have been published as submitted.

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