Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
From the Neuroimaging Research Unit (F.A., E.G.S., S.B., C.C., F.F., C.P., E.C., V.C., M.F.), Division of Neuroscience, and Neurology Unit (F.A., E.G.S., G.M., F.C., M.F.), IRCCS San Raffaele Scientific Institute; Vita-Salute San Raffaele University (F.A., F.F., C.P., M.F.); Neurorehabilitation Unit (N.R., M.F.), IRCCS San Raffaele Scientific Institute; Experimental Neuropathology Unit (N.R.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute; Unit of Neurology 5-Neuropathology (P.C., S.P., C.V.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Neurology Unit (L.T., I.A.), "San Gerardo" Hospital and University of Milano-Bicocca, Monza; Department of Neurology and Laboratory of Neuroscience (V.S.), IRCCS Istituto Auxologico Italiano, Milan; "Dino Ferrari" Center (V.S.), Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Italy; Department of Neurology (K.A.J.), and Department of Radiology (J.W.), Mayo Clinic, Rochester, MN; and Neurophysiology Service (M.F.), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Published: May 2023
AI Article Synopsis
Article Abstract
Background And Objectives: MRI connectomics is an ideal tool to test a network-based model of pathologic propagation from a disease epicenter in neurodegenerative disorders. In this study, we used a novel graph theory-based MRI paradigm to explore functional connectivity reorganization, discerning between direct and indirect connections from disease epicenters, and its relationship with neurodegeneration across clinical presentations of the frontotemporal dementia (FTD) spectrum, including behavioral variant of FTD (bvFTD), nonfluent variant of primary progressive aphasia (nfvPPA), and semantic variant of primary progressive aphasia (svPPA).
Methods: In this observational cross-sectional study, disease epicenters were defined as the peaks of atrophy of a cohort of patients with high confidence of frontotemporal lobar degeneration pathology (Mayo Clinic). These were used as seed regions for stepwise functional connectivity (SFC) analyses in an independent (Milan) set of patients with FTD to assess connectivity in regions directly and indirectly connected to the epicenters. Correlations between SFC architecture in healthy conditions and atrophy patterns in patients with FTD were also tested.
Results: As defined by comparing the 42 Mayo Clinic patients with 15 controls, disease epicenters were the left anterior insula for bvFTD, left supplementary motor area for nfvPPA, and left inferior temporal gyrus (ITG) for svPPA. Compared with 94 age-matched controls, patients with bvFTD (n = 64) and nfvPPA (n = 34) of the Milan cohort showed widespread decreased SFC in bilateral cortical regions with direct/indirect connections with epicenters and increased SFC either in directly connected regions, physically close to the respective seed region, or in more distant cortical/cerebellar areas with indirect connections. Across all link steps, svPPA (n = 36) showed SFC decrease mostly within the temporal lobes, with co-occurrent SFC increase in cerebellar regions at indirect link steps. The average stepwise topological distance from the left ITG in a reference group of 50 young healthy controls correlated with regional gray matter volume in svPPA, consistent with network-based degeneration.
Discussion: Our findings demonstrate that each FTD syndrome is associated with a characteristic interplay of decreased and increased functional connectivity with the disease epicenter, affecting both direct and indirect connections. SFC revealed novel insights regarding the topology of functional disconnection across FTD syndromes, holding the promise to be used to model disease progression in future longitudinal studies.
