Stepwise functional brain architecture from disease epicenter correlates with atrophy in progressive supranuclear palsy (P11-6.001)

Abstract

<h3>Objective:</h3> This study applied SFC to test the hypothesis that topological stepwise architecture propagating from the disease epicenter would shape patterns of grey matter (GM) atrophy in a cohort of patients with progressive supranuclear palsy (PSP). <h3>Background:</h3> MRI connectomics is an ideal tool to test the model of network-based spread of pathological protein aggregates in neurodegenerative disorders. Stepwise functional connectivity (SFC) is a graph-theory-based neuroimaging method, which detects whole-brain functional couplings of a selected region of interest, at increasing link-step topological distances. <h3>Design/Methods:</h3> Twenty-eight patients with PSP and 50 healthy controls underwent brain magnetic resonance imaging (MRI) on a 3T scanner, including 3D-T1 weighted and resting-state functional MRI sequences. GM was parcellated into 90 regions using the Automated Anatomical Labeling (AAL) atlas. Correlations between SFC architecture in controls and atrophy patterns in PSP patients were tested. The disease epicenter was identified as the peak of atrophy observed in an independent cohort of 13 cases with <i>post mortem</i> confirmation of PSP pathology, and used as seed region for SFC analysis. <h3>Results:</h3> The disease epicenter was identified in the left midbrain tegmental region. Compared with controls, PSP patients showed prevalent atrophy in the subcortical GM (mostly, in the thalami and caudate nuclei), but also in frontal, parietal and cerebellar cortical regions. For each region of the AAL atlas, a strong correlation was found between average link-step distance from the left midbrain in controls and mean normalized GM volume in PSP patients (r=0.37, p&lt;0.001). <h3>Conclusions:</h3> Our findings demonstrate that the brain architectural topology, as described by SFC propagating from the disease epicenter, shapes the pattern of atrophic changes in PSP, supporting the view of a network-based pathology propagation in this disease and holding the promise to be used to model disease progression in future longitudinal studies. <b>Disclosure:</b> Dr. Spinelli has nothing to disclose. Miss Ghirelli has nothing to disclose. Miss Bottale has nothing to disclose. Silvia Basaia has nothing to disclose. Ms. Cividini has nothing to disclose. Dr. Volonte has nothing to disclose. Mr. Galantucci has nothing to disclose. Giuseppe Magnani has nothing to disclose. Dr. Caso has nothing to disclose. The institution of Elisa Canu has received research support from Italian Ministry of Health . Dr. Castelnovo has nothing to disclose. Paola Caroppo has nothing to disclose. Sara Prioni has nothing to disclose. Miss Villa has nothing to disclose. Dr. Josephs has nothing to disclose. Dr. Whitwell has nothing to disclose. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Philips. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier INC. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).