Brain structural and functional abnormalities in Parkinson’s disease patients with freezing of gait (P6.072)

Objectives: To assess brain functional and structural network alterations in Parkinson’s disease with freezing of gait (PD-FoG). Background: FoG is not associated with PD cardinal features, but is correlated with postural instability and cognitive impairment. Few studies so far have investigated the neural correlates of FoG in PD, suggesting altered locomotor and frontoparietal connectivities in these patients. Methods: T1-weighted, diffusion tensor (DT) MRI and resting state (RS) fMRI were obtained from 23 PD-FoG patients and 36 controls. Subjects underwent clinical, motor functional, and neuropsychological evaluations. Gray matter (GM) volumes were assessed using Voxel-based Morphometry. White matter (WM) damage was assessed using Tract-Based Spatial Statistics. RS fMRI data were analyzed using a model free (MELODIC) approach investigating sensorimotor, visual and cognitive brain networks. Results: Patients presented mild FoG and executive, visuospatial and verbal learning deficits. No GM atrophy was found in patients relative to controls. Compared with controls, patients showed WM damage of the locomotor pathways (including the peduncolopontine tract), corpus callosum, cingulum, and WM underneath the frontal, parietal and occipital cortices, bilaterally. RS fMRI analysis showed that PD-FoG was associated with a decreased functional connectivity relative to controls in the sensorimotor, associative-visual, default-mode, ventral-attentive, and left frontoparietal networks. More severe FoG was associated with lower functional connectivity within the associative-visual network. Greater motor disability and worse cognitive performances were associated with more severe WM damage and reduced functional connectivity in the sensorimotor, default-mode, and ventral-attentive networks. Conclusions: PD-FoG patients showed a disrupted structural and functional connectivity of the locomotor, associative visual, attentive and memory-related brain networks, which was related to FoG and disease severity, and executive and visuospatial deficits. These findings support the theory of FoG as the result of a poor integration between motor programming, visuospatial and attentional abilities. Study Supported by: Jacques and Gloria Gossweiler Foundation.