The previous grant period developed clinical and imaging criteria for frontotemporal dementia (FTD) subgroups, and tested hypotheses about the cognitive and neural basis for semantic and grammatical aspects of language. In the current grant period, we propose to continue hypothesis-driven studies of progressive aphasia and systematically investigate the behavioral and neural basis for the social disorder in FTD.
SPECIFIC AIM 1 : We will examine clinically asymptomatic family members of patients with a tau mutation to define a prodromal form of FTD. We will also pursue longitudinal behavioral and imaging studies to characterize FTD patients with a social disorder, paralleling our work with progressive aphasia.
SPECIFIC AIM 2 : Semantic deficits in Semantic Dementia (SD) have been related to degraded object knowledge, but the pattern of lost object knowledge is inconsistent. We will test the hypothesis that the diagnostic value of object features is impaired in SD. Cognitive and fMRI data will determine the basis for this disorder, and test whether this is related to left ventral temporal disease.
SPECIFIC AIM 3 : Quantitative acoustic speech analyses and grammatical agreements, combined with fMRI, will test the hypothesis that there are 2 forms of Progressive Non-fluent Aphasia (PNFA) - impaired grammar in comprehension and expression related to left ventral inferior frontal (BA 45/47) disease, and a dysarthric articulatory disorder related to left frontal opercular and insula disease.
SPECIFIC AIM 4 : Our two-component model of social functioning includes features of social knowledge, and executive resources that mediate implementing this knowledge in a social context. We will test the hypothesis that a social disorder in FTD is due to poor inhibitory control and limited working memory that govern factors such as the rules associated with social knowledge. We will use cognitive and fMRI data to test the hypothesis that a social disorder is due to interruption of a large-scale neural network that includes right medial orbital frontal cortex and anterior prefrontal cortex.
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