We will study the effects of frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), and mild cognitive impairment (MCI) on socioemotional functioning using laboratory procedures that allow for precise assessment of a number of aspects of actual emotional functioning including: (a) emotional reactivity (the type and magnitude of responses to salient challenges and opportunities), (b) emotion regulation (the ability to adjust emotional responses to situational demands) and (c) empathy and prosocial behavior (recognizing others'emotions and responding to their distress). These laboratory-based assessments measure the major aspects of emotional responding, including: (a) subjective emotional experience, (b) emotional expressive behavior, (c) emotional language, and (d) autonomic and somatic nervous system physiology. This approach allows us to identify specific areas of lost and preserved socioemotional functioning in FTLD and AD, compared to each other and to MCI and controls. A particular focus of the proposed work is on understanding the basis of symptoms of FTLD that are very troublesome for caregivers, including a progressive loss of "warmth" and an increase in socially inappropropriate behavior. We will use our detailed analyses of emotional functioning to explore the particular deficits that contribute to these real world symptoms. Delineating specific deficits will enable us to make strong links to damage in specific brain circuits (explored via structural imaging) and particular kinds of neuropathology (explored at autopsy). In addition, we will determine the extent to which changes in particular aspects of socioemotional functioning are related to genetic risk factors for FTLD by studying unaffected family members with and without suspected genetic markers in families with a high incidence of FTLD.

Public Health Relevance

Frontotemporal lobar degeneration is a devastating neurological disease that primarily affects social and emotional functioning. Increasing our understanding of the specific nature of these effects and relating them to underlying biological factors will be useful for diagnosing this condition, for understanding the challenges and burdens presented to caregivers, and for evaluating the effectiveness of future treatments.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
San Francisco
United States
Zip Code
Sturm, Virginia E; Yokoyama, Jennifer S; Eckart, Janet A et al. (2015) Damage to left frontal regulatory circuits produces greater positive emotional reactivity in frontotemporal dementia. Cortex 64:55-67
Wagshal, Dana; Sankaranarayanan, Sethu; Guss, Valerie et al. (2015) Divergent CSF ? alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 86:244-50
Bloch, Lian; Haase, Claudia M; Levenson, Robert W (2014) Emotion regulation predicts marital satisfaction: more than a wives' tale. Emotion 14:130-44
Possin, Katherine L; LaMarre, Amanda K; Wood, Kristie A et al. (2014) Ecological validity and neuroanatomical correlates of the NIH EXAMINER executive composite score. J Int Neuropsychol Soc 20:20-8
Ranasinghe, Kamalini G; Hinkley, Leighton B; Beagle, Alexander J et al. (2014) Regional functional connectivity predicts distinct cognitive impairments in Alzheimer's disease spectrum. Neuroimage Clin 5:385-95
Sanders, David W; Kaufman, Sarah K; DeVos, Sarah L et al. (2014) Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron 82:1271-88
Lehmann, Manja; Ghosh, Pia M; Madison, Cindee et al. (2014) Greater medial temporal hypometabolism and lower cortical amyloid burden in ApoE4-positive AD patients. J Neurol Neurosurg Psychiatry 85:266-73
Sanchez-Juan, Pascual; Ghosh, Pia M; Hagen, Jayne et al. (2014) Practical utility of amyloid and FDG-PET in an academic dementia center. Neurology 82:230-8
Henry, Maya L; Wilson, Stephen M; Ogar, Jennifer M et al. (2014) Neuropsychological, behavioral, and anatomical evolution in right temporal variant frontotemporal dementia: a longitudinal and post-mortem single case analysis. Neurocase 20:100-9
Lee, Suzee E; Khazenzon, Anna M; Trujillo, Andrew J et al. (2014) Altered network connectivity in frontotemporal dementia with C9orf72 hexanucleotide repeat expansion. Brain 137:3047-60

Showing the most recent 10 out of 279 publications