Primary progressive aphasia (PPA) is a clinical syndrome in which degeneration of language regions in the dominant hemisphere is associated with progressive deficits in speech and/or language function. The overall goals of this project are to use functional magnetic resonance imaging (fMRI) to investigate neural changes underlying linguistic deficits in PPA, and to use this information to better discriminate patients with variants of PPA from each other and from normal aging. Recent studies have identified three clinical variants of PPA: progressive non-fluent aphasia (PNFA), semantic dementia (SD) and logopenic progressive aphasia (LPA). Each variant is associated with characteristic linguistic features, distinct patterns of brain atrophy, and different likelihoods of particular underlying pathogenic processes, making correct differential diagnosis highly relevant. We will recruit 48 patients with PPA (16 of each variant) and 24 normal controls over a three year period, and acquire fMRI data along with structural MRI, linguistic and cognitive measures. The fMRI paradigm consists of a syntactic processing task with seven conditions parametrically varying in syntactic complexity. The research will address two specific aims. The first is to identify the relationships between volume loss, changes in functional MRI activation, and linguistic deficits, in the different PPA variants.
The second aim i s to improve differential diagnosis of PPA variants using machine learning algorithms incorporating both structural and functional imaging measures.

Public Health Relevance

PPA is a devastating disorder that prevents individuals from communicating and functioning in society. The knowledge gained in this study will increase our understanding of the neural basis of language processing and its breakdown in PPA, and will contribute to earlier, more accurate differential diagnosis of PPA variants, enabling emerging therapies to be targeted to likely underlying etiologies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
5R03DC010878-04
Application #
8247172
Study Section
Special Emphasis Panel (ZDC1-SRB-Y (51))
Program Officer
Cooper, Judith
Project Start
2010-07-07
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2012
Total Cost
$121,968
Indirect Cost
$32,907
Name
University of Arizona
Department
Otolaryngology
Type
Schools of Arts and Sciences
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Wilson, Stephen M; DeMarco, Andrew T; Henry, Maya L et al. (2014) What role does the anterior temporal lobe play in sentence-level processing? Neural correlates of syntactic processing in semantic variant primary progressive aphasia. J Cogn Neurosci 26:970-85
Wilson, Stephen M; Brandt, Temre H; Henry, Maya L et al. (2014) Inflectional morphology in primary progressive aphasia: an elicited production study. Brain Lang 136:58-68
Farias, Dana; Davis, Christine Herrick; Wilson, Stephen M (2014) Treating apraxia of speech with an implicit protocol that activates speech motor areas via inner speech. Aphasiology 28:515-532
Wilson, Stephen M (2014) The impact of vascular factors on language localization in the superior temporal sulcus. Hum Brain Mapp 35:4049-63
Wilson, Stephen M; Rising, Kindle; Stib, Matthew T et al. (2013) Dysfunctional visual word form processing in progressive alexia. Brain 136:1260-73
Wilson, Stephen M; Galantucci, Sebastiano; Tartaglia, Maria Carmela et al. (2012) The neural basis of syntactic deficits in primary progressive aphasia. Brain Lang 122:190-8
Galantucci, Sebastiano; Tartaglia, Maria Carmela; Wilson, Stephen M et al. (2011) White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain 134:3011-29
Ogar, J M; Baldo, J V; Wilson, S M et al. (2011) Semantic dementia and persisting Wernicke's aphasia: linguistic and anatomical profiles. Brain Lang 117:28-33
Wilson, Stephen M; Galantucci, Sebastiano; Tartaglia, Maria Carmela et al. (2011) Syntactic processing depends on dorsal language tracts. Neuron 72:397-403
Lee, Suzee E; Rabinovici, Gil D; Mayo, Mary Catherine et al. (2011) Clinicopathological correlations in corticobasal degeneration. Ann Neurol 70:327-40

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