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.

The role of prefrontal cortex during postural control in Parkinsonian syndromes a functional near-infrared spectroscopy study

“…gait) in aging have demonstrated the role of the prefrontal cortex using different neuroimaging methods (Holtzer et al, 2014a) like functional MRI (Allali et al, 2014b; Blumen et al, 2014) or PET-Scan (la Fougere et al, 2010). However, few studies address this issue in older adults with PS using direct online assessments of prefrontal brain regions (Maillet et al, 2014; Thevathasan et al, 2012). In the PS population, extracortical regions, like the pedunculopontine nucleus (Thevathasan et al, 2012) or cerebellar regions (Maillet et al, 2014) appear to play a key role in the cerebral networks involved in the control of gait.…”

“…However, few studies address this issue in older adults with PS using direct online assessments of prefrontal brain regions (Maillet et al, 2014; Thevathasan et al, 2012). In the PS population, extracortical regions, like the pedunculopontine nucleus (Thevathasan et al, 2012) or cerebellar regions (Maillet et al, 2014) appear to play a key role in the cerebral networks involved in the control of gait. In terms of postural control, previous studies (Goble et al, 2011; Karim et al, 2013b) showed that older adults recruit cerebral networks involving temporal and prefrontal regions, as well as the subcortical areas.…”

Brain activation underlying turning in Parkinson’s disease patients with and without freezing of gait: a virtual reality fMRI study

“…We hypothesized that PD patients with FOG would be slower and more variable in their step times during the navigation of a turn in the VR 18,19 and that turning would elicit altered activation patterns in the STN 7 and its hyperdirect frontal cortex connections. 9–11 In addition, we expected to find differences across the cortical, striatal and other subcortical regions that have previously been identified in PD patients with FOG during structural MRI, 11,20 fMRI resting state, 21 PET gait imagery tasks 22 and during fMRI with a gait imagery tasks, 23,24 upper limb motor task, 25 and VR performance. 13,16,17 …”

Brain metabolic abnormalities during gait with freezing in Parkinson’s disease

“…when the person in the vertical position, rather than in the horizontal position required for concomitant MRI acquisition) ( Bartels and Leenders, 2008;Maillet et al, 2012;Herman et al, 2013;Shine et al, 2013d). Recently, researchers have found new ways of studying FoG by using mental imagery of gait (Snijders et al, 2011;Crémers et al, 2012;Maillet et al, 2015;Peterson et al, 2014aPeterson et al, , 2014b and virtual reality tasks (Shine et al, 2013a(Shine et al, , 2013b(Shine et al, , 2013cShine et al, 2011b). Other functional MRI approaches are based on creating the equivalent of FoG for the upper limbs (Vercruysse et al, 2014a) or performing alternating foot movements in the supine position (Shine et al, 2013a(Shine et al, , 2013b(Shine et al, , 2013cShine et al, 2011b) in order to individualize motor blocks that could be time-locked with changes in brain perfusion.…”