| 2009 — 2013 |
Mendez, Mario F. |
R01Activity Code Description:
To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Multidisciplinary Study of Social Behavior and Emotion in Frontotemporal Dementia @ University of California Los Angeles
DESCRIPTION (provided by applicant): 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.
|
0.906 |
| 2016 |
Mendez, Mario F. |
RF1Activity Code Description:
To support a discrete, specific, circumscribed project to be performed by the named investigator(s) in an area representing specific interest and competencies based on the mission of the agency, using standard peer review criteria. This is the multi-year funded equivalent of the R01 but can be used also for multi-year funding of other research project grants such as R03, R21 as appropriate. |
Early-Onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks @ University of California Los Angeles
? DESCRIPTION (provided by applicant): Unlike the usual late-onset Alzheimer's disease (LOAD), early-onset AD (EOAD), with onset before age 65, includes a high percentage of phenotypic variants. These non-familial, variants (vEOAD) present, not with progressive memory loss, but with language, visuospatial, or other cognitive difficulties. We now understand AD as a disorder that manifests with disturbed cognition reflecting disturbed neural networks. A multivariate analysis of neuropsychological tests, the gold standard for objectively defining neurocognitive impairments, coupled with structural and functional neuroimaging analysis of connectomes, can identify the neurocognitive-neural network profiles of vEOAD patients, compared to those with typical AD. This knowledge can increase our understanding of the heterogeneity of AD and how it causes disease. Objective. This proposal aims to show that vEOAD comprises its own clinical-neurobiological disorder, or type 2 AD, evident by a specific neurocognitive profile on neuropsychological tests and by specific structural and functional neural network involvement on magnetic resonance imaging (MRI). The neurobiology of Type 2 AD, which is composed of overlapping clinical syndromes that cluster together, challenges the prevailing view of initial ?42-amyloid deposition followed by neurofibrillary tangle (NFT) formation in the entorhinal- hippocampal cortex, and suggests involvement and propagation via alternate neural networks. Methods. This study recruits 60 vEOAD patients, 30 typical amnestic EOAD patients, and 30 typical LOAD patients as well as 60 normal, age-matched controls. In Specific Aim 1, all participants undergo neuropsychological tests and neurological tasks related to potentially affected brain regions. It assesses and corroborates a proposed neuropsychological test profile for the diagnosis and one-year follow-up of Type 2 AD. In Specific Aim 2, the EOAD participants undergo MRI measures of structural and functional neural networks using connectomic analysis of diffusion tensor imaging and resting-state functional MRI. Anticipated Results. This proposal hopes to show that vEOAD constitutes a Type 2 AD. Specific Aim 1 defines the neuropsychological components of Type 2 AD. Specific Aim 2 shows that, compared to typical amnestic EOAD or LOAD, Type 2 AD initially spares entorhinal-hippocampi cortex and the default mode network in favor of alternate frontoparietal networks (e.g., central executive network). Together, these specific aims define the distinct neurocognitive-neural network profile of Type 2 AD compared to typical amnestic AD. Conclusions. By recognizing the underlying neurocognitive-neural network profile of Type 2 AD in relation to typical AD, researchers gain crucial knowledge of the variations in the pathophysiological manifestations and neural propagation of this disease. In addition to information that can help in the diagnosis and management of EOAD, this proposal can stimulate novel research into the reasons for this neurobiological heterogeneity in AD and could potentially lead to interventions based on alternate neurocognitive-neural network profiles.
|
0.906 |