Dopaminergic pathways and resting-state functional connectivity in Parkinson’s disease with freezing of gait

Abstract

Graphical abstract

Longitudinal trimodal imaging of midbrain-associated network degeneration in Parkinson’s disease

“…Pasquini et al 35 described gait disturbances predicted by early caudatal dysfunction, which goes beyond the scope of this study which did not specifically address gait. However, our results also support an involvement in gait difficulties since significant changes in FOG-Q were observed between both visits and were moderately associated with dopamine depletion in the right caudate and its connectivity to the SPCl 45 .…”

Imaging the neural underpinnings of freezing of gait in Parkinson’s disease

“…Dysfunctional network connectivity between subcortical and cortical areas extended beyond cognitive and sensorimotor areas, also affecting visuospatial networks. In PD patients with FoG, abnormal FC was observed between the visual cortex, mainly of the right hemisphere, and left caudate ( Steidel et al, 2021 ), right PPN ( Wang et al, 2016 ), bilateral thalamus and GPe ( Potvin-Desrochers et al, 2019 ), when compared to PD patients without FoG. Moreover, two studies found distinct FC alterations between cerebellar and parieto-occipital regions.…”

“… Functional connectivity (FC) Whole brain and ROI seed-based analyses Cross-sectional Correlational (indirect with behavioral measures of gait) Higher FC between left GP and primary somatosensory cortex (C/T FoG-) correlate positively with behavioral measures of FoG. Lower FC between the left vestibular cortex and regions of the DMN (C/T FoG-) Interference AND/OR Perceptual Dysfunction Pietracupa et al (2018) 21 FoG+ 16 FoG- 19 HC OFF H&Y, LEDD, MMSE, UPDRS-III, FAB, HAM-D, FoG-Q and TUG Structural DTI Cross-sectional Correlational (indirect with FoG-Q and neuropsycho-logical test scores) Widespread WM disruption [predominantly in the right hemisphere between motor, cognitive & limbic structures (C/T HC)] correlates positively with cognitive scores (FAB) Interference Potvin-Desrochers et al (2019) 14 FoG+ 13 FoG- ON H&Y, UPDRS-III, HADS, MoCA, and new FOG-Q Functional connectivity (FC) Subcortical structures seed- to-voxel analysis Cross-sectional Higher FC of bilateral thalamus and bilateral GPe with visual areas (C/T FoG-) Perceptual Dysfunction Steidel et al (2021) 27 FoG+ 32 FoG- OFF H&Y, LEDD, MMSE, PANDA, PDQ39, UPDRS-III, BDI-II, tests for attention, memory, language, executive & visuospatial functions, and FoG-Q Functional connectivity (FC), seed-based analysis (left caudate cluster or ventral tegmental area, VTA) Cross-sectional Correlational (indirect with FoG-Q scores and dopaminergic degeneration) Higher FC between bilateral VTA & DMN regions and higher FC between left caudate & right visual cortex (C/T FoG-) correlate negatively with dopamine levels. In all PD: positive correlation of FoG-Q and FC of VTA with DMN regions.…”

“…Other rs-fMRI studies found abnormal connectivity patterns of cortical areas with subcortical structures in PD patients with FoG. In comparison to PD patients without FoG, PD patients with FoG showed an increase in the FC between mesencephalic locomotor regions and cortical sensorimotor areas ( Fling et al, 2014 , Lench et al, 2020 ), putamen and precuneus ( Vervoort et al, 2016 ), GP and primary somatosensory cortex ( Miranda-Domínguez et al, 2020 ), thalamus and right inferior parietal lobule ( Wang et al, 2021 ), as well as between the ventral tegmental area and areas of the default mode network ( Steidel et al, 2021 ). Notably, all these abnormalities in functional connectivity between cortical and subcortical structures were shown to be positively correlated to behavioral or subjective measures of FoG.…”

Structural Brain Network Abnormalities in Parkinson’s Disease With Freezing of Gait

“…Compared with PD FOG-patients, PD FOG+ patients showed decreased BC in the right CAU. A resting-state functional MRI (rs-fMRI) study suggested that altered functional connectivity in the CAU may cause damage to the executive function of PD FOG+ patients (Steidel et al, 2021). Thus, the decreased BC in the right CAU may be an important aspect leading to FOG, which is also an important distinction between PD FOG+ and PD FOG-.…”