title: Brain structural and functional connectivity in Parkinson's disease with freezing of gait.
abstract: OBJECTIVE
  To use a multimodal approach to assess brain structural pathways and resting state (RS) functional connectivity abnormalities in patients with Parkinson's disease and freezing of gait (PD-FoG).
  
  
  METHODS
  T1-weighted, diffusion tensor (DT) MRI and RS functional MRI (fMRI) were obtained from 22 PD-FoG patients and 35 controls on a 3.0 T MR scanner. Patients underwent clinical, motor, and neuropsychological evaluations. Gray matter (GM) volumes and white matter (WM) damage were assessed using voxel based morphometry and tract-based spatial statistics, respectively. The pedunculopontine tract (PPT) was studied using tractography. RS fMRI data were analyzed using a model free approach investigating the main sensorimotor and cognitive brain networks. Multiple regression models were performed to assess the relationships between structural, functional, and clinical/cognitive variables. Analysis of GM and WM structural abnormalities was replicated in an independent sample including 28 PD-FoG patients, 25 PD patients without FoG, and 30 healthy controls who performed MRI scans on a 1.5 T scanner.
  
  
  RESULTS
  Compared with controls, no GM atrophy was found in PD-FoG cases. PD-FoG patients showed WM damage of the PPT, corpus callosum, corticospinal tract, cingulum, superior longitudinal fasciculus, and WM underneath the primary motor, premotor, prefrontal, orbitofrontal, and inferior parietal cortices, bilaterally. In PD-FoG, right PTT damage was associated with a greater disease severity. Analysis on the independent PD sample showed similar findings in PD-FoG patients relative to controls as well as WM damage of the genu and body of the corpus callosum and right parietal WM in PD-FoG relative to PD no-FoG patients. RS fMRI analysis showed that PD-FoG is associated with a decreased functional connectivity of the primary motor cortex and supplementary motor area bilaterally in the sensorimotor network, frontoparietal regions in the default mode network, and occipital cortex in the visual associative network.
  
  
  CONCLUSIONS
  This study suggests that FoG in PD can be the result of a poor structural and functional integration between motor and extramotor (cognitive) neural systems.
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Canu
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Agosta
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Laboratory of Movement Analysis, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Sarasso
authors.affiliation: Department of Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Volontè
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Basaia
authors.affiliation: Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Stojkovic
authors.affiliation: Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Elka
authors.initials: E
authors.lastname: Stefanova
authors.affiliation: Department of Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Department of Neuroradiology and CERMAC, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.affiliation: Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Kostic
authors.affiliation: Laboratory of Movement Analysis, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gatti
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000704:Analysis of Variance; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000098:blood supply* / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D020233:Gait Disorders, Neurologic / Q000150:complications / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000098:blood supply / Q000502:physiology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010300:Parkinson Disease / Q000150:complications / Q000473:pathology*; D012720:Severity of Illness Index; D013223:Statistics as Topic
chemical_list: D010100:Oxygen
keywords: Parkinson's disease; brain connectivity; diffusion tensor MRI; freezing of gait; resting state functional MRI