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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG022983-07
Application #
8236913
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Silverberg, Nina B
Project Start
2003-12-01
Project End
2016-02-29
Budget Start
2012-03-15
Budget End
2013-02-28
Support Year
7
Fiscal Year
2012
Total Cost
$282,037
Indirect Cost
$53,661
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Sturm, Virginia E; Perry, David C; Wood, Kristie et al. (2017) Prosocial deficits in behavioral variant frontotemporal dementia relate to reward network atrophy. Brain Behav 7:e00807
Perry, David C; Brown, Jesse A; Possin, Katherine L et al. (2017) Clinicopathological correlations in behavioural variant frontotemporal dementia. Brain 140:3329-3345
Perry, David C; Datta, Samir; Sturm, Virginia E et al. (2017) Reward deficits in behavioural variant frontotemporal dementia include insensitivity to negative stimuli. Brain 140:3346-3356
Chiong, Winston; Wood, Kristie A; Beagle, Alexander J et al. (2016) Neuroeconomic dissociation of semantic dementia and behavioural variant frontotemporal dementia. Brain 139:578-87
Kalapatapu, Raj K; Delucchi, Kevin L; Wang, Sophia et al. (2016) Substance use history in behavioral-variant frontotemporal dementia versus primary progressive aphasia. J Addict Dis 35:36-41
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
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Perry, David C; Kramer, Joel H (2015) Reward processing in neurodegenerative disease. Neurocase 21:120-33
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
Perry, David C; Sturm, Virginia E; Wood, Kristie A et al. (2015) Divergent processing of monetary and social reward in behavioral variant frontotemporal dementia and Alzheimer disease. Alzheimer Dis Assoc Disord 29:161-4

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