Abstract

We seek converging evidence from cognitive studies of non-demented patients with Parkinson's disease (PD), electrocortical event-related potentials (CEPs), and functional magnetic resonance imaging (fMRI) to test our interactive neurocognitive model of core cognitive processes and executive resources in comprehension.
Specific Aim 1 manipulates executive resources (working memory, strategic planning, inhibitory control) in ambiguous sentences. PD patients' impaired sentence comprehension will be related to limitations in specific executive resources. Resource-related slowing of CEPs will be seen in PD for the same material. fMRI in young subjects with this material will recruit interactive neural networks for sentence processing: left ventral inferior frontal cortex (vIFC) and left posterolateral temporal cortex (PLTC) for core language processes, and specific cognitive resources in left dorsal IFC (dIFC), prefrontal cortex, striatum, and right PLTC. To compensate for age- and disease-related resource limitations, healthy seniors and PD patients will up-regulate resource-related networks, but we expect no change in the core sentence processing network.
Specific Aim 2 tests a material-neutral deficit for rules that depends on implicit memory. We examine regular and irregular morphology in verbs and nouns, and assess non-linguistic concept acquisition mediated by implicit- or rule-based learning. PD patients will show a material-specific deficit for rules in verbs. fMRI in young subjects will recruit left vIFC only for regular verb morphology, and dIFC for decision-making resources. d]FC will be up-regulated in aging and PD.
Specific Aim 3 assesses the generalizeability of our model to prosody comprehension. PD patients judge acoustically simple and complex prosody stimuli at baseline and during a secondary task. Restricted resources will limit PD patients' comprehension of complex prosody. fMRI in young subjects will recruit orbital frontal and dIFC only for complex prosody, and dIFC will be up-regulated in aging and PD. Our data support a componential neurocognitive architecture consisting of dynamically interactive networks modified to process sentences depending on available resources and relative demand.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS035867-06
Application #
6623609
Study Section
Special Emphasis Panel (ZRG1-BBBP-4 (01))
Program Officer
Wagster, Molly V
Project Start
1997-07-01
Project End
2007-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
6
Fiscal Year
2003
Total Cost
$376,438
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Neurology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Grossman, Murray; Powers, John; Ash, Sherry et al. (2013) Disruption of large-scale neural networks in non-fluent/agrammatic variant primary progressive aphasia associated with frontotemporal degeneration pathology. Brain Lang 127:106-20
Grossman, Murray (2012) The non-fluent/agrammatic variant of primary progressive aphasia. Lancet Neurol 11:545-55
Grossman, Murray; Bleck, Thomas P (2011) Where's the fire? Long-term neurologic outcome following cardiac arrest. Neurology 77:1418-9
Pantelyat, Alexander; Dreyfuss, Michael; Moore, Peachie et al. (2011) Acalculia in autopsy-proven corticobasal degeneration. Neurology 76:S61-3
Ash, Sharon; McMillan, Corey; Gross, Rachel G et al. (2011) The organization of narrative discourse in Lewy body spectrum disorder. Brain Lang 119:30-41
Troiani, Vanessa; Clark, Robin; Grossman, Murray (2011) Impaired verbal comprehension of quantifiers in corticobasal syndrome. Neuropsychology 25:159-65
Bonner, Michael F; Ash, Sharon; Grossman, Murray (2010) The new classification of primary progressive aphasia into semantic, logopenic, or nonfluent/agrammatic variants. Curr Neurol Neurosci Rep 10:484-90
Farag, Christine; Troiani, Vanessa; Bonner, Michael et al. (2010) Hierarchical organization of scripts: converging evidence from FMRI and frontotemporal degeneration. Cereb Cortex 20:2453-63
Gunawardena, D; Ash, S; McMillan, C et al. (2010) Why are patients with progressive nonfluent aphasia nonfluent? Neurology 75:588-94
Peelle, Jonathan E; Troiani, Vanessa; Wingfield, Arthur et al. (2010) Neural processing during older adults' comprehension of spoken sentences: age differences in resource allocation and connectivity. Cereb Cortex 20:773-82

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