Improved knowledge about the particular brain regions that degenerate in frontotemporal lobardegeneration (FTLD) has led to specific predictions about what kinds of cognitive and emotional tasks wouldbe most sensitive for detecting and following changes in function resulting from this disease. Experimentalstudies in animals and healthy human participants have led to the development of tasks tapping cognitiveand emotional functions in the frontal and temporal lobes, but the value of these paradigms for trackingfunction in specific brain regions in neurodegenerative disease is unknown. The overarching goal of thisproject is to link performance on specific cognitive and behavioral tasks to regional pathology in FTLDmeasured with magnetic resonance imaging (MRI). Neuroimaging will be performed at high field-strength (4Tesla) and will include perfusion and diffusion tensor imaging, analyzed using hand-traced regions ofinterest. Performance on these novel tasks will be correlatedwith regional cortical volumes, regionalperfusion values and fractional anisotropy (FA) in specific white matter tracts. Correlations between thesemeasures and real world performance, as rated by informants, will also be examined. The project willaddress three specific aims: 1) To define the relationship between changes in the dorsal frontal regionsand specific aspects of cognitive control and regulation of emotion, 2) To define the relationship betweenchanges in the ventral and medial prefrontal regions and activation of the emotional systems formonitoring of behavior, and 3) To define the relationship between changes in the anterior temporal lobeand comprehension of verbal and non-verbal stimuli. Linkage of these functions to specific regions in thebrain could lead to their use in clinical diagnosis, monitoring the course of disease progression, andevaluating the effectiveness of present and future treatments. Furthermore, these studies will facilitate abetter understanding of brain-behavior relationships in regions with still poorly understood functions.
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