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

Tard, Céline; Delval, Arnaud; Devos, David; Lopes, Renaud; Lenfant, P.; Dujardin, K.; Hossein-Foucher, Claude; Semah, Franck; Duhamel, Alain; Defebvre, Luc; Jeune, Florence Le; Moreau, Caroline

doi:10.1016/j.neuroscience.2015.08.063

Cited by 55 publications

(49 citation statements)

References 127 publications

(189 reference statements)

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“…As described previously, cortical but not thalamic cholinergic deficits predict reduced executive, attention, and verbal learning scores in PD patients without dementia (Bohnen et al, 2012, 2015), as well as freezing-of-gait symptoms associated with increased demand on and failure of cognitive control and reduced function of cognitive control-associated cortical networks (Bartels & Leenders; 2008; Bohnen et al 2014; Giladi & Hausdorff, 2006; Shine et al, 2013; Tard et al, 2015a,b). In contrast, thalamic cholinergic denervation has been linked to falls, with Bohnen et al noting that compared to other patients, those with a history of falls had an approximately 12% reduction in thalamic AChE activity.…”

Section: 1 Discussionsupporting

confidence: 53%

Thalamic cholinergic innervation makes a specific bottom-up contribution to signal detection: Evidence from Parkinson’s disease patients with defined cholinergic losses

et al. 2017

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Successful behavior depends on the ability to detect and respond to relevant cues, especially under challenging conditions. This essential component of attention has been hypothesized to be mediated by multiple neuromodulator systems, but the contributions of individual systems (e.g., cholinergic, dopaminergic) have remained unclear. The present study addresses this issue by leveraging individual variation in regionally-specific cholinergic denervation in Parkinson's disease (PD) patients, while controlling for variation in dopaminergic denervation. Patients whose dopaminergic and cholinergic nerve terminal integrity had been previously assessed using Positron Emission Tomography (Bohnen et al., 2012) and controls were tested in a signal detection task that manipulates attentional-perceptual challenge and has been used extensively in both rodents and humans to investigate the cholinergic system's role in responding to such challenges (Demeter et al., 2008; McGaughy and Sarter, 1995; see Hasselmo & Sarter 2011 for review). In simple correlation analyses, measures of midbrain dopaminergic, cortical and thalamic cholinergic innervation all predicted preserved signal detection under challenge. However, regression analyses also controlling for age, disease severity, and other variables showed that the only significant independent neurotransmitter-related predictor over and above the other variables in the model was thalamic cholinergic integrity. Furthermore, thalamic cholinergic innervation exclusively predicted hits, not correct rejections, indicating a specific contribution to bottom-up salience processing. These results help define regionally-specific contributions of cholinergic function to different aspects of attention and behavior.

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Section: 1 Discussionsupporting

confidence: 53%

Thalamic cholinergic innervation makes a specific bottom-up contribution to signal detection: Evidence from Parkinson’s disease patients with defined cholinergic losses

et al. 2017

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“…In contrast to our findings, a previous study in PD with and without FOG showed increased metabolic activity of parietal regions and subcortical nuclei, as well as reduced activity of frontal regions during an upright complex gait task (i.e., combined dual-tasking, passing through a narrow space, and 360°turning) compared with supine rest (36). Notably, participants spent approximately 40% of the time in motor arrest.…”

Section: Discussioncontrasting

confidence: 99%

Cerebral Metabolic Changes Related to Freezing of Gait in Parkinson Disease

et al. 2018

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Freezing of gait (FOG) in Parkinson disease (PD) often occurs during steering of gait (i.e., complex gait), which is thought to arise from executive dysfunction. Our aim was to test whether cognitive corticobasal ganglia-thalamocortical circuitry is impaired and whether alternate neural circuits are used for complex gait in PD with FOG. Methods: Eighteen individuals with idiopathic PD in the off-medication state, 9 with FOG (aged 68 ± 6 y) and 9 without FOG (aged 65 ± 5 y), were included. PET was used to measure cerebral glucose metabolism during 2 gait tasks, steering and straight walking, performed during the radiotracer uptake period. Results: During steering, there was a reduced change in cerebral glucose metabolism within the cognitive corticothalamic circuit. More specifically, those with FOG had less activation of the posterior parietal cortex, less deactivation of the dorsolateral prefrontal cortex and thalamus, and increased activation in the supplementary motor area. Interestingly, activity in the dorsolateral prefrontal cortex correlated with gait impairment (i.e., reduced stride length) in the FOG group. Conclusion: These results demonstrate decreased parietal control and an alternate control mechanism mediated by prefrontal and supplementary motor areas in PD with FOG.

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“…In PD this includes degeneration of cholinergic (Rinne et al, 2008; Karachi et al, 2010; Pienaar et al, 2013), GABAergic and glycinergic cells (Pienaar et al, 2013). Neuroimaging indicates that locomotor deficits in PD patients are associated with additional MLR abnormalities (notably in the PPN), including altered connectivity between the MLR, thalamus, and motor cortical regions (Fling et al, 2013, 2014), abnormal microstructure (Vercruysse et al, 2015; Youn et al, 2015; Wang et al, 2016), atrophy of the MLR gray matter (Snijders et al, 2011; Fioravanti et al, 2015) and abnormal metabolic activity following a walking task (Tard et al, 2015). Additionally, anatomopathological studies revealed the presence in the MLR of alpha-synuclein immuno-reactive Lewy Bodies (e.g., Seidel et al, 2015), and mitochondrial abnormalities (Pienaar et al, 2013) in PD.…”

Section: Possible Role Of the Descending Dopaminergic Pathway In Pdmentioning

confidence: 99%

Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human

2017

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In vertebrates, dopamine neurons are classically known to modulate locomotion via their ascending projections to the basal ganglia that project to brainstem locomotor networks. An increased dopaminergic tone is associated with increase in locomotor activity. In pathological conditions where dopamine cells are lost, such as in Parkinson's disease, locomotor deficits are traditionally associated with the reduced ascending dopaminergic input to the basal ganglia. However, a descending dopaminergic pathway originating from the substantia nigra pars compacta was recently discovered. It innervates the mesencephalic locomotor region (MLR) from basal vertebrates to mammals. This pathway was shown to increase locomotor output in lampreys, and could very well play an important role in mammals. Here, we provide a detailed account on the newly found dopaminergic pathway in lamprey, salamander, rat, monkey, and human. In lampreys and salamanders, dopamine release in the MLR is associated with the activation of reticulospinal neurons that carry the locomotor command to the spinal cord. Dopamine release in the MLR potentiates locomotor movements through a D1-receptor mechanism in lampreys. In rats, stimulation of the substantia nigra pars compacta elicited dopamine release in the pedunculopontine nucleus, a known part of the MLR. In a monkey model of Parkinson's disease, a reduced dopaminergic innervation of the brainstem locomotor networks was reported. Dopaminergic fibers are also present in human pedunculopontine nucleus. We discuss the conserved locomotor role of this pathway from lamprey to mammals, and the hypothesis that this pathway could play a role in the locomotor deficits reported in Parkinson's disease.

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

Cited by 55 publications

References 127 publications

Thalamic cholinergic innervation makes a specific bottom-up contribution to signal detection: Evidence from Parkinson’s disease patients with defined cholinergic losses

Thalamic cholinergic innervation makes a specific bottom-up contribution to signal detection: Evidence from Parkinson’s disease patients with defined cholinergic losses

Cerebral Metabolic Changes Related to Freezing of Gait in Parkinson Disease

Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human

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