This competitive renewal studies the cognitive and neural basis for semantic memory deficits in Alzheimer's disease (AD). Our cognitive model includes distributed feature knowledge and categorization processes that integrate this knowledge. This maps onto a large-scale neural network where feature knowledge is biased to a particular anatomic distribution, and categorization processes are supported by prefrontal cortex (PFC) and posterior temporal-parietal heteromodal association cortex (PHAC). We found in the prior grant cycle that AD patients have impaired rule-based categorization, and fMRI work related this in part to PFC.
Specific Aim 1 examines the role of specific executive resources (selective attention/inhibitory control, working memory, and task-switching) during rule-based categorization in AD, and assess the neural substrate for this with fMRI. We expect poor rule-based categorization in AD that is due to limited and dissociable executive resources, fMRI will relate each executive resource to different portions of PFC. We also found in the prior grant cycle that AD patients have limited similarity-based categorization under specific circumstances, and fMRI related this in part to PHAC.
Specific Aim 2 assesses factors that affect the organization of features during similarity-based categorization and the comparisons of test stimuli with previously encountered exemplars and prototypes. We expect that AD patients have poor similarity-based categorization due to difficulty organizing large feature sets and comparing these with previously encountered exemplars, fMRI will relate this to PHAC and anterior prefrontal cortex. Our previous work showed reduced activation of PFC and PHAC in AD during semantic memory challenges for multiple categories of knowledge, and we will assess whether this is due to impaired categorization processes in AD with fMRI. We expect that limited rule-based categorization is related to reduced PFC activation in AD, and poor similarity-based categorization is related in part to limited PHAC activation. Work in the previous grant cycle also showed that degraded knowledge in semantic memory is not necessarily category-specific.
Specific Aim 3 will study the status of diagnostic feature knowledge and feature redundancy in semantic networks. We expect the diagnostic status of feature knowledge to be impaired in AD, and to see greater reliance on feature redundancy in AD patients' semantic comprehension, fMRI will relate feature diagnosticity to PFC across multiple categories of knowledge. ? ?
| Irwin, David J; Byrne, Matthew D; McMillan, Corey T et al. (2016) Semi-Automated Digital Image Analysis of Pick's Disease and TDP-43 Proteinopathy. J Histochem Cytochem 64:54-66 |
| Olm, Christopher A; Kandel, Benjamin M; Avants, Brian B et al. (2016) Arterial spin labeling perfusion predicts longitudinal decline in semantic variant primary progressive aphasia. J Neurol 263:1927-38 |
| Irwin, David J; Brettschneider, Johannes; McMillan, Corey T et al. (2016) Deep clinical and neuropathological phenotyping of Pick disease. Ann Neurol 79:272-87 |
| Massimo, Lauren; Zee, Jarcy; Xie, Sharon X et al. (2015) Occupational attainment influences survival in autopsy-confirmed frontotemporal degeneration. Neurology 84:2070-5 |
| Olm, Christopher A; McMillan, Corey T; Spotorno, Nicola et al. (2014) The relative contributions of frontal and parietal cortex for generalized quantifier comprehension. Front Hum Neurosci 8:610 |
| Ash, Sharon; Menaged, Anna; Olm, Christopher et al. (2014) Narrative discourse deficits in amyotrophic lateral sclerosis. Neurology 83:520-8 |
| Toledo, Jon B; Van Deerlin, Vivianna M; Lee, Edward B et al. (2014) A platform for discovery: The University of Pennsylvania Integrated Neurodegenerative Disease Biobank. Alzheimers Dement 10:477-484.e1 |
| Peelle, Jonathan E; Powers, John; Cook, Philip A et al. (2014) Frontotemporal neural systems supporting semantic processing in Alzheimer's disease. Cogn Affect Behav Neurosci 14:37-48 |
| Grossman, Murray (2014) Biomarkers in the primary progressive aphasias. Aphasiology 28:922-940 |
| Irwin, David J; McMillan, Corey T; Suh, EunRan et al. (2014) Myelin oligodendrocyte basic protein and prognosis in behavioral-variant frontotemporal dementia. Neurology 83:502-9 |
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