title: Neural substrates of levodopa-responsive gait disorders and freezing in advanced Parkinson's disease: a kinesthetic imagery approach.
abstract: Gait disturbances, including freezing of gait, are frequent and disabling symptoms of Parkinson's disease. They often respond poorly to dopaminergic treatments. Although recent studies have shed some light on their neural correlates, their modulation by dopaminergic treatment remains quite unknown. Specifically, the influence of levodopa on the networks involved in motor imagery (MI) of parkinsonian gait has not been directly studied, comparing the off and on medication states in the same patients. We therefore conducted an [H2 (15) 0] Positron emission tomography study in eight advanced parkinsonian patients (mean disease duration: 12.3 ± 3.8 years) presenting with levodopa-responsive gait disorders and FoG, and eight age-matched healthy subjects. All participants performed three tasks (MI of gait, visual imagery and a control task). Patients were tested off, after an overnight withdrawal of all antiparkinsonian treatment, and on medication, during consecutive mornings. The order of conditions was counterbalanced between subjects and sessions. Results showed that imagined gait elicited activations within motor and frontal associative areas, thalamus, basal ganglia and cerebellum in controls. Off medication, patients mainly activated premotor-parietal and pontomesencephalic regions. Levodopa increased activation in motor regions, putamen, thalamus, and cerebellum, and reduced premotor-parietal and brainstem involvement. Areas activated when patients are off medication may represent compensatory mechanisms. The recruitment of these accessory circuits has also been reported for upper-limb movements in Parkinson's disease, suggesting a partly overlapping pathophysiology between imagined levodopa-responsive gait disorders and appendicular signs. Our results also highlight a possible cerebellar contribution in the pathophysiology of parkinsonian gait disorders through kinesthetic imagery.
authors.affiliation: Université Joseph Fourier, Grenoble Universités, Grenoble, France; INSERM-UJF-CEA-CHU U836 Grenoble Institut des Neurosciences, Grenoble, France; Centre de Neuroscience Cognitive, UMR 5229 CNRS, Lyon, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Maillet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Thobois
authors.forename: Valérie
authors.initials: V
authors.lastname: Fraix
authors.forename: Jérôme
authors.initials: J
authors.lastname: Redouté
authors.forename: Didier
authors.initials: D
authors.lastname: Le Bars
authors.forename: Franck
authors.initials: F
authors.lastname: Lavenne
authors.forename: Philippe
authors.initials: P
authors.lastname: Derost
authors.forename: Franck
authors.initials: F
authors.lastname: Durif
authors.forename: Bastiaan R
authors.initials: BR
authors.lastname: Bloem
authors.forename: Paul
authors.initials: P
authors.lastname: Krack
authors.forename: Pierre
authors.initials: P
authors.lastname: Pollak
authors.forename: Bettina
authors.initials: B
authors.lastname: Debû
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D020233:Gait Disorders, Neurologic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007092:Imagination / Q000502:physiology; D007699:Kinesthesis / Q000502:physiology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D049268:Positron-Emission Tomography
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa
keywords: PET imaging; Parkinson's disease; freezing of gait; gait disorders; kinesthetic motor imagery; levodopa