Frontotemporal dementia (FTD) is an age-related neurodegenerative disorder characterized by disturbances in social and moral behavior. FTD is a singularly unique window to deciphering the neurobiological basis of social behavior in older age. The earliest symptoms of FTD reflect declines in self-referential social behavior (e.g., embarrassment), in emotional awareness of others (e.g., empathy), and in moral emotional experiences (e.g., fairness). These behavioral variant FTD patients are also disinhibited and unable to regulate their social behavior. The common, underlying mechanism for these disturbances may be impairment in the emotions that drive social and moral behavior (Fiske, 2002;Olsson and Ochsner, 2008). Our work has shown that social context alters autonomic emotional responses (Gehricke and Shapiro, 2001) and that the right hemisphere is responsible for both these responses (Spence et al, 1996) and the predominant regional brain atrophy in bvFTD (McMurtray et al, 2006;Mendez et al, 2008a). Together, these studies suggest that specific right frontotemporal regions mediate in specific in sociomoral emotions (SME). For this application, a multidisciplinary team of social scientists and neuroscientists have come together to study SME in bvFTD. This team takes observations of sociomoral behavior in a naturalistic setting, where it is most evident, constructs an """"""""Ethogram"""""""" or behavioral dictionary for bvFTD, tests it with behavioral and psychophysiologic measures, and investigates the brain regions involved with cortical mapping techniques. This application will define the SME and their disturbances in patients with bvFTD, compared to patients with Alzheimer's disease (AD) and normal controls. It will recruit 33 patients with early bvFTD and compare them to33 patients with AD and 33 normal controls on three Specific Aims.
Specific Aim 1 will evaluate the predicted Ethogram, generated by pilot data.
This Specific Aim will apply ethnographic methods for participant observation of patient interactions in their homes, conversational analysis to understand their verbal interactions, and supplemental behavior experiments and scales.
In Specific Aim 2, the application will further evaluate the specificity of these behaviors with psychophysiologic measures. For these two Specific Aims, this application predicts greater and more specific disturbances in sociomoral emotional behaviors among patients bvFTD, in comparison to controls.
In Specific Aim 3, this application will correlate the assessments of SME with regional abnormalities and three-dimensional cortical mapping on magnetic resonance imaging (MRI). This application predicts that most SME disturbances will correlate with atrophy in the right ventromedial frontal regions, whereas disinhibition and dysregulation corresponds to right orbitofrontal-anterior temporal regions. Other specific brain-behavior localizations may be revealed by this innovate neuroimaging. Ultimately, this application can elucidate how neurodegenerative diseases of aging impact social and moral behavior and can greatly accelerate our understanding of the neuroscience of social behavior.

Public Health Relevance

Many mental or brain disorders have disturbances in social behavior or interpersonal interactions. This application combines many specialists to study disturbed social behavior in frontotemporal dementia. The results of the project can clarify how social behavior is altered by mental disorders or brain diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG034499-03
Application #
8113303
Study Section
Special Emphasis Panel (ZAG1-ZIJ-1 (M1))
Program Officer
Silverberg, Nina B
Project Start
2009-07-15
Project End
2014-06-30
Budget Start
2011-08-01
Budget End
2012-06-30
Support Year
3
Fiscal Year
2011
Total Cost
$382,439
Indirect Cost
Name
University of California Los Angeles
Department
Neurology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Fong, Sylvia S; Navarrete, Carlos David; Perfecto, Sean E et al. (2017) Behavioral and autonomic reactivity to moral dilemmas in frontotemporal dementia versus Alzheimer's disease. Soc Neurosci 12:409-418
Mendez, Mario F (2017) Early-Onset Alzheimer Disease. Neurol Clin 35:263-281
Fong, Sylvia S; Paholpak, Pongsatorn; Daianu, Madelaine et al. (2017) The attribution of animacy and agency in frontotemporal dementia versus Alzheimer's disease. Cortex 92:81-94
Daianu, Madelaine; Mezher, Adam; Mendez, Mario F et al. (2016) Disrupted rich club network in behavioral variant frontotemporal dementia and early-onset Alzheimer's disease. Hum Brain Mapp 37:868-83
Deutsch, Mariel B; Liang, Li-Jung; Jimenez, Elvira E et al. (2016) Are we comparing frontotemporal dementia and Alzheimer disease patients with the right measures? Int Psychogeriatr 28:1481-5
Daianu, Madelaine; Mendez, Mario F; Baboyan, Vatche G et al. (2016) An advanced white matter tract analysis in frontotemporal dementia and early-onset Alzheimer's disease. Brain Imaging Behav 10:1038-1053
Granadillo, Elias D; Mendez, Mario F (2016) Pathological Joking or Witzelsucht Revisited. J Neuropsychiatry Clin Neurosci 28:162-7
Deutsch, Mariel B; Mendez, Mario F; Teng, Edmond (2015) Interactions between traumatic brain injury and frontotemporal degeneration. Dement Geriatr Cogn Disord 39:143-53
Deutsch, Mariel B; Mendez, Mario F (2015) Neurocognitive features distinguishing primary central nervous system lymphoma from other possible causes of rapidly progressive dementia. Cogn Behav Neurol 28:1-10
Mendez, Mario F; Sabodash, Valeriy (2015) Clinical amyloid imaging in logopenic progressive aphasia. Alzheimer Dis Assoc Disord 29:94-6

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