title: Disruption of large-scale neural networks in non-fluent/agrammatic variant primary progressive aphasia associated with frontotemporal degeneration pathology.
abstract: Non-fluent/agrammatic primary progressive aphasia (naPPA) is a progressive neurodegenerative condition most prominently associated with slowed, effortful speech. A clinical imaging marker of naPPA is disease centered in the left inferior frontal lobe. We used multimodal imaging to assess large-scale neural networks underlying effortful expression in 15 patients with sporadic naPPA due to frontotemporal lobar degeneration (FTLD) spectrum pathology. Effortful speech in these patients is related in part to impaired grammatical processing, and to phonologic speech errors. Gray matter (GM) imaging shows frontal and anterior-superior temporal atrophy, most prominently in the left hemisphere. Diffusion tensor imaging reveals reduced fractional anisotropy in several white matter (WM) tracts mediating projections between left frontal and other GM regions. Regression analyses suggest disruption of three large-scale GM-WM neural networks in naPPA that support fluent, grammatical expression. These findings emphasize the role of large-scale neural networks in language, and demonstrate associated language deficits in naPPA.
authors.affiliation: Department of Neurology, University of Pennsylvania, United States. Electronic address: mgrossma@mail.med.upenn.edu.
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
authors.forename: John
authors.initials: J
authors.lastname: Powers
authors.forename: Sherry
authors.initials: S
authors.lastname: Ash
authors.forename: Corey
authors.initials: C
authors.lastname: McMillan
authors.forename: Lisa
authors.initials: L
authors.lastname: Burkholder
authors.forename: David
authors.initials: D
authors.lastname: Irwin
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000368:Aged; D056324:Diffusion Tensor Imaging; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D064847:Multimodal Imaging; D009434:Neural Pathways / Q000473:pathology* / Q000503:physiopathology; D057178:Primary Progressive Nonfluent Aphasia / Q000473:pathology* / Q000503:physiopathology