We aim at 1) investigating spared and altered intrinsic functional connectivity networks (speech production vs. semantic networks) in semantic variant primary progressive aphasia (svPPA) and their association with underlying grey matter (GM) volume; 2) identifying behavioral correlates of functional connectivity changes in svPPA.

svPPA is a clinical syndrome characterized by a dissociation between impaired semantic processing and preserved speech production. Substantial literature reveals the selective vulnerability of a specific brain network in the neurodegeneration processes in svPPA (i.e. semantic network), but less is known about the mechanisms underlying possible adaptive changes involving preserved language functions and associated neural networks (i.e. speech production network).

Using whole-brain, seed-based connectivity on task-free Magnetic Resonance Imaging (MRI) data, we compared the functional connectivity of two networks involved in semantic and speech production processes between 32 svPPA patients and 46 healthy controls. Using measures of semantics (mean noun lexical frequency, mean noun familiarity, single word-comprehension) and speech production (articulation rate, speech rate, verbal agility), we investigated brain-behavior correlations.

svPPA patients showed decreased functional connectivity in the semantic network between left anterior middle temporal (aMTG) and left angular and cingulate regions, dependent on the underlying GM atrophy. Conversely, they also presented increased connectivity in the speech production network between left inferior frontal and left supramarginal regions independent of underlying GM atrophy. Impaired lexico-semantic measures in svPPA did not correlate with any regions of decreased functional connectivity but did with the GM volume in the aMTG. Increased speech production measures in svPPA correlated instead with increased connectivity between left inferior frontal and supramarginal regions.

These results highlight the interplay between spared and altered language networks in svPPA. Our findings provide a compelling model for studying compensatory mechanisms in response to disease in svPPA that might inform the design of rehabilitation strategies.