The overarching goal of this project is to determine the cognitive, neuroanatomic and physiological underpinnings of the profound deficits in behavioral regulation exhibited by patients with behavioral variant frontotemporal dementia (bvFTD). Patients with bvFTD and other frontal lobe disorders often present with severe behavioral dysfunction despite relatively intact performance on standard clinical measures of attention, working memory, problem solving, and executive function. A primary question is to what degree these behaviors reflect deficits in cognition (e.g., cognitive control, awareness of errors, error correction), or whether they reflect a primary underlying deficit in the processing of reward and punishment. We propose to study 50 patients with mild bvFTD, 50 Alzheimer's disease patients matched for demographics and dementia severity, and 50 normal controls. We will study the cognitive components of behavioral regulation by assessing conflict monitoring, error detection, and error correction, and we will evaluate the motivational components by employing reward processing paradigms. Behavioral studies will be carried out in conjunction with functional MRI to study the brain systems that mediate these behaviors. Our results will hopefully shed light on why these patients fail to inhibit inappropriate actions and offer guidance toward new interventions.

Public Health Relevance

The Inability to control impulses and inhibit inappropriate behavior has a devastating impact on patients with frontal lobe disorders. The overarching goal of this project is to study patients with behavioral-variant frontotemporal dementia to better understand the cognitive and neurological underpinnings of these maladaptive behaviors. The potential contribution to public health lies in the hope that a better understanding of the neural systems that mediate behavioral dyscontrol will lead to improvements in care.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Silverberg, Nina B
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Mansoor, Yael; Jastrzab, Laura; Dutt, Shubir et al. (2015) Memory profiles in pathology or biomarker confirmed Alzheimer disease and frontotemporal dementia. Alzheimer Dis Assoc Disord 29:135-40
Scherling, Carole S; Hall, Tracey; Berisha, Flora et al. (2014) Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration. Ann Neurol 75:116-26
Kramer, Joel H; Mungas, Dan; Possin, Katherine L et al. (2014) NIH EXAMINER: conceptualization and development of an executive function battery. J Int Neuropsychol Soc 20:11-9
Perry, David C; Sturm, Virginia E; Wood, Kristie A et al. (2013) Divergent Processing of Monetary and Social Reward in Behavioral Variant Frontotemporal Dementia and Alzheimer Disease. Alzheimer Dis Assoc Disord :
Lee, Suzee E; Tartaglia, Maria C; Yener, Gorsev et al. (2013) Neurodegenerative disease phenotypes in carriers of MAPT p.A152T, a risk factor for frontotemporal dementia spectrum disorders and Alzheimer disease. Alzheimer Dis Assoc Disord 27:302-9
Possin, Katherine L; Feigenbaum, Dana; Rankin, Katherine P et al. (2013) Dissociable executive functions in behavioral variant frontotemporal and Alzheimer dementias. Neurology 80:2180-5
Bettcher, Brianne Magouirk; Wilheim, Reva; Rigby, Taylor et al. (2012) C-reactive protein is related to memory and medial temporal brain volume in older adults. Brain Behav Immun 26:103-8
Gyurak, Anett; Goodkind, Madeleine S; Kramer, Joel H et al. (2012) Executive functions and the down-regulation and up-regulation of emotion. Cogn Emot 26:103-18
Possin, Katherine L; Laluz, Victor R; Alcantar, Oscar Z et al. (2011) Distinct neuroanatomical substrates and cognitive mechanisms of figure copy performance in Alzheimer's disease and behavioral variant frontotemporal dementia. Neuropsychologia 49:43-8
Krueger, Casey E; Rosen, Howard J; Taylor, H Gerry et al. (2011) Know thyself: real-world behavioral correlates of self-appraisal accuracy. Clin Neuropsychol 25:741-56

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