AUTHOR=Droby Amgad , Pelosin Elisa , Putzolu Martina , Bommarito Giulia , Marchese Roberta , Mazzella Luca , Avanzino Laura , Inglese Matilde 

TITLE=A Multimodal Imaging Approach Demonstrates Reduced Midbrain Functional Network Connectivity Is Associated With Freezing of Gait in Parkinson's Disease

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.583593

DOI=10.3389/fneur.2021.583593

ISSN=1664-2295

ABSTRACT=Background: The pathophysiological mechanisms underlying freezing of gait (FOG) are poorly defined. MRI studies in FOG showed a distinct pattern of cortical atrophy and decreased functional connectivity (FC) within motor and cognitive networks. Furthermore, reduced rs-FC within midbrain and frontal and temporal areas has been also described. This study investigated the patterns of whole-brain FC alterations within midbrain inter-connected regions in PD-FOG patients, and whether these patterns are linked to midbrain structural damage using a multi-modal imaging approach, combing structural and functional imaging techniques. 
Methods: 33 PD patients (16 PD-FOG, 17 PD-no FOG), and 21 sex- and age-matched healthy controls (HCs) were prospectively enrolled. All subjects underwent MRI scan at 1.5T, whereas only PD patients underwent clinical and cognitive assessment. GM integrity was measured using voxel-based morphometry (VBM). VBM findings served as basis to localize midbrain damage, and further used as a seed region for investigating whole-brain FC alterations using rs-fMRI.
Results: In rs-fMRI, patients with PD and FOG demonstrated significant decrease of midbrain-cortical FC levels in the R PCG, right postcentral, and supramarginal gyri compared to controls and the middle cingulate compared to no-FOG group. Based on regression analysis, MOCA, UPDRS-III total score, and FOG severity scores were associated with FC levels in several frontal, parietal and temporal regions.
Discussion: The present results suggest that midbrain structural damage as well as decreased FC within the brainstem functional network might contribute to FOG occurrence in PD patients.