Cerebral Metabolic Changes Related to Freezing of Gait in Parkinson Disease

Abstract

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.

Neuroimaging advances in Parkinson's disease with freezing of gait: A systematic review

“…In contrast, other studies showed hyper rather than hypometabolism in specific frontal areas (e.g. paracentral lobule) (Mitchell et al., 2019; Tard et al., 2015). Studies investigating subcortical brain regions with PET also described functional abnormalities in subcortical structures such as the basal ganglia (Bartels et al., 2006; Tard et al., 2015) and MLR (Tard et al., 2015.…”

“…(2016)40 PD patients (69±8; 11 PD-nFOG) 11 HS (64±7)6- 18 [F]-FMTAADC activityReduced FMT uptake in putamen, caudate and LC in PD patients than HSSeverity of FOG negatively correlated with FMT uptake in LCGallardo et al. (2018)9 PD-FOG (NA) 8 PD-nFOG (NA) 18 [F]-FDGGlucose metabolismFrontal and predominantly right-sided hypometabolismNot performedMitchell et al. (2019)9 PD-FOG (68±6) 9 PD-nFOG (65±5) 18 [F]-FDGGlucose metabolism during steering of gait compared to straight walkingChanges in cortico-thalamic circuit and hyperdirect pathway (reduced activation of parietal regions; reduced deactivation of prefrontal regions and thalamus; increased activation of supplementary motor area) during staring of gaitActivity in right dorsolateral prefrontal cortex negatively correlated with stride length during steering of gaitBohnen et al.…”

“…Other PET studies compared cerebral glucose metabolism in PD-FOG and PD-nFOG (Bartels et al., 2006; Gallardo et al., 2018; Mitchell et al., 2019; Tard et al., 2015). Most of the studies demonstrated hypometabolism in frontal (Gallardo et al., 2018; Tard et al., 2015) and parietal brain regions in PD-FOG (Bartels et al., 2006; Mitchell et al., 2019) primarily involving the right hemisphere (Bartels et al., 2006; Gallardo et al., 2018). In contrast, other studies showed hyper rather than hypometabolism in specific frontal areas (e.g.…”

“…More recently, Mitchell et al. (2018) examined cerebral glucose metabolic changes during steering and straight walking and discovered cerebral glucose metabolic changes in various brain regions involving the cognitive corticothalamic circuit (Mitchell et al., 2019). Lastly, Bohnen et al.…”

New Onset On-Medication Freezing of Gait After STN-DBS in Parkinson's Disease

“…Another study revealed that patients with “on” FoG had less activation of the posterior parietal cortex and less deactivation of the dorsolateral PFC and thalamus, and increase activation in the supplementary motor area (28). The supplementary motor area has direct projections to the STN responsible for strong inhibition of a planned action (29, 30) and is strongly activated during real FoG episodes (31).…”