Primary progressive aphasia (PPA) is a clinical syndrome in which degeneration of language regions in thedominant hemisphere is associated with progressive deficits in speech and/or language function. The overallgoals of this project are to use functional magnetic resonance imaging (fMRI) to investigate neural changesunderlying linguistic deficits in PPA, and to use this information to better discriminate patients with variants ofPPA 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 differentlikelihoods 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, andacquire fMRI data along with structural MRI, linguistic and cognitive measures. The fMRI paradigm consists ofa syntactic processing task with seven conditions parametrically varying in syntactic complexity. The researchwill address two specific aims. The first is to identify the relationships between volume loss, changes infunctional MRI activation, and linguistic deficits, in the different PPA variants.
The second aim i s to improvedifferential diagnosis of PPA variants using machine learning algorithms incorporating both structural andfunctional 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 #
5R03DC010878-03
Application #
8207220
Study Section
Special Emphasis Panel (ZDC1-SRB-Y (51))
Program Officer
Cooper, Judith
Project Start
2010-07-07
Project End
2013-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
3
Fiscal Year
2011
Total Cost
$121,967
Indirect Cost
Name
University of Arizona
Department
Otolaryngology
Type
Schools of Arts and Sciences
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
DeMarco, Andrew T; Wilson, Stephen M; Rising, Kindle et al. (2017) Neural substrates of sublexical processing for spelling. Brain Lang 164:118-128
Wilson, Stephen M; DeMarco, Andrew T; Henry, Maya L et al. (2016) Variable disruption of a syntactic processing network in primary progressive aphasia. Brain 139:2994-3006
Wilson, Stephen M; Lam, Daniel; Babiak, Miranda C et al. (2015) Transient aphasias after left hemisphere resective surgery. J Neurosurg 123:581-93
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
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; Brandt, Temre H; Henry, Maya L et al. (2014) Inflectional morphology in primary progressive aphasia: an elicited production study. Brain Lang 136:58-68
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
Deleon, Jessica; Gesierich, Benno; Besbris, Max et al. (2012) Elicitation of specific syntactic structures in primary progressive aphasia. Brain Lang 123:183-90

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