摘要：Non-fluent/agrammatic primary progressive aphasia (naPPA), also known as progressive nonfluentaphasia, is a progressive neurodegenerative condition most prominently associated with slowed,effortful speech and frontotemporal lobar degeneration (FTLD) spectrum pathology. Grammaticalcomprehension difficulty is a necessary characteristic of naPPA, but clinical measures ofgrammatical comprehension are rare. We developed a novel measure of grammaticalcomprehension using a two-alternative forced-choice sentence-picture matching task, and examinedthis comparatively in 39 patients with variants of PPA (naPPA=12, logopenic variant PPA=15, andsemantic variant PPA=12), 27 non-aphasic patients with behavioral-variant frontotemporaldegeneration (bvFTD), and 12 healthy controls. We related the neuroanatomic basis for grammaticalcomprehension difficulty to volumetric grey matter (GM) atrophy and diffusion tensor imaging ofwhole-brain fractional anisotropy (FA) in white matter (WM) tracts. Patients with naPPA hadselective difficulty understanding cleft sentence structures, while all PPA variants and bvFTD patientswere impaired with more complex, center-embedded sentences. bvFTD patients were also impairedunderstanding sentences involving short-term memory. GM imaging showed frontal and anterior-superior temporal atrophy, most prominently in the left hemisphere. Reduced FA was seen inseveral WM tracts mediating projections from left frontal/anterior-superior temporal regions,including the arcuate fasciculus, the inferior frontal-occipital fasciculus, and the anterior corpuscallosum. Regressions related grammatical comprehension difficulty in naPPA to left anteriorsuperior temporal atrophy and reduced FA in projections from this region through the anterior corpuscallosum and inferior frontal-occipital fasciculus. We also used multimodal imaging to assess largescale neural networks underlying effortful expression in 15 naPPA patients with FTLD spectrumpathology. Grammatical expression was assessed with a digitized semi-structured speech sampleinvolving a description of wordless children’s picture story. naPPA patients had significantly slowedspeech. They used significantly simplified grammatical forms, and their speech containedsignificantly more grammatical errors than controls. Regression analyses suggested disruption ofthree large-scale GM-WM neural networks in naPPA that support grammatical expression, includingarcuate fasciculus projections from the inferior frontal lobe, inferior frontal-occipital fasciculusprojections from the anterior-superior temporal lobe, and projections in anterior corpus callosumbetween left and right inferior frontal regions. These findings emphasize the role of large-scaleneural networks in language, and suggest that distinct grammatical deficits in naPPA are associatedwith interruption of several frontal-temporal neural networks.
