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

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG019724-10
Application #
8318114
Study Section
Special Emphasis Panel (ZAG1)
Project Start
Project End
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
10
Fiscal Year
2011
Total Cost
$112,473
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Theofilas, Panos; Ehrenberg, Alexander J; Nguy, Austin et al. (2018) Probing the correlation of neuronal loss, neurofibrillary tangles, and cell death markers across the Alzheimer's disease Braak stages: a quantitative study in humans. Neurobiol Aging 61:1-12
Eser, Rana A; Ehrenberg, Alexander J; Petersen, Cathrine et al. (2018) Selective Vulnerability of Brainstem Nuclei in Distinct Tauopathies: A Postmortem Study. J Neuropathol Exp Neurol 77:149-161
Burette, Alain C; Judson, Matthew C; Li, Alissa N et al. (2018) Subcellular organization of UBE3A in human cerebral cortex. Mol Autism 9:54
Deleon, Jessica; Miller, Bruce L (2018) Frontotemporal dementia. Handb Clin Neurol 148:409-430
Zakrzewski, Jessica J; Datta, Samir; Scherling, Carole et al. (2018) Deficits in physiological and self-conscious emotional response to errors in hoarding disorder. Psychiatry Res 268:157-164
Rojas, Julio C; Bang, Jee; Lobach, Iryna V et al. (2018) CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP. Neurology 90:e273-e281
Hua, Alice Y; Sible, Isabel J; Perry, David C et al. (2018) Enhanced Positive Emotional Reactivity Undermines Empathy in Behavioral Variant Frontotemporal Dementia. Front Neurol 9:402
Miller, Zachary A; Rosenberg, Lynne; Santos-Santos, Miguel A et al. (2018) Prevalence of Mathematical and Visuospatial Learning Disabilities in Patients With Posterior Cortical Atrophy. JAMA Neurol 75:728-737
Rojas, Julio C; Stephens, Melanie L; Rabinovici, Gil D et al. (2018) Multiproteinopathy, neurodegeneration and old age: a case study. Neurocase 24:1-6
Dijkstra, Anke A; Lin, Li-Chun; Nana, Alissa L et al. (2018) Von Economo Neurons and Fork Cells: A Neurochemical Signature Linked to Monoaminergic Function. Cereb Cortex 28:131-144

Showing the most recent 10 out of 607 publications