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 proposal, 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 proposal 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 proposal will further evaluate the specificity of these behaviors with psychophysiologic measures. For these two Specific Aims, this proposal predicts greater and more specific disturbances in sociomoral emotional behaviors among patients bvFTD, in comparison to controls.
In Specific Aim 3, this proposal will correlate the assessments of SME with regional abnormalities and three-dimensional cortical mapping on magnetic resonance imaging (MRI). This proposal 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 proposal 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 proposal 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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZAG1-ZIJ-1 (M1))
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Silverberg, Nina B
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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Mendez, Mario F (2018) Non-Neurogenic Language Disorders: A Preliminary Classification. Psychosomatics 59:28-35
Mendez, Mario F; Fong, Sylvia S; Ashla, Mark M et al. (2018) Skin Conduction Levels Differentiate Frontotemporal Dementia From Alzheimer's Disease. J Neuropsychiatry Clin Neurosci 30:208-213
Mendez, Mario F (2018) Methylphenidate Treatment for Patients With Posterior Cortical Atrophy. J Neuropsychiatry Clin Neurosci :appineuropsych17120356
Mendez, Mario F (2018) Manic behavior and asymmetric right frontotemporal dementia from a novel progranulin mutation. Neuropsychiatr Dis Treat 14:657-662
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
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
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
Panchal, Hemali; Paholpak, Pongsatorn; Lee, Grace et al. (2016) Neuropsychological and Neuroanatomical Correlates of the Social Norms Questionnaire in Frontotemporal Dementia Versus Alzheimer's Disease. Am J Alzheimers Dis Other Demen 31:326-32

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