Primary progressive aphasia: Perspectives from functional and structural neuroimaging.

摘要

Primary progressive aphasia (PPA) is a debilitating neurodegenerative syndrome that principally impairs the cognitive domain of language. Patients demonstrate deficits in a variety of language faculties including object naming (anomia), word finding, single word and sentence reading, speech comprehension, repetition, syntactic processing, and paraphasia. PPA has been associated with selective atrophy within the left hemisphere in the vicinity of the Sylvian fissure, the known location of neural systems supporting language function. This dissertation is a compilation of work examining the neural correlates of dysfunction within the language network in non-fluent PPA, using functional and structural magnetic resonance imaging (fMRI) in conjunction with single word processing tasks. This dissertation also employs dynamic causal modeling (DCM) for the investigation of inter-regional influences within the PPA language network, and voxel-based morphometry (VBM) to quantitatively characterize grey matter atrophy in PPA. The studies in this dissertation reveal behavioral dysfunction and altered functional neuroanatomy for phonological and lexico-semantic single word processing associated with significant left temporoparietal atrophy, and altered network interactions within the language network, specifically from posterior superior temporal lobe (Wernicke's area) to inferior frontal gyrus (Broca's area) in PPA. These disruptions impact both incidental and explicit lexico-semantic processing, and may underlie the myriad clinical language deficits observed in PPA.