This is an application for a K23 award for Dr. David Perry, a behavioral neurology fellow at the University of California, San Francisco Memory and Aging Center (MAC). Dr. Perry is establishing himself as a young investigator in patient-oriented clinical research of reward processing in neurodegenerative disease. This K23 award will provide Dr. Perry with the support necessary to accomplish the following goals: 1) to gain expertise in neurodegenerative disease and neuropsychiatric symptom management;2) to develop proficiency in the use and analysis of structural and functional neuroimaging;3) to gain experience in the use of psychophysiological measures;4) to advance his knowledge of biostatistics [and clinical trials];and 5) to develop an independent clinical research career. To achieve these goals, Dr. Perry has assembled a mentoring team comprised of two primary mentors: Dr. Howard Rosen (a neurologist with expertise in neurodegenerative disease, psychophysiology, and neuroimaging analysis) and Dr. Joel Kramer (a neuropsychologist with expertise in cognitive and behavioral systems);one co-mentor, Dr. Bruce Miller (neurologist with expertise in behavioral neurology, neurodegenerative disease, and clinical research);and five consultants: [Dr. Craig Nelson (a geriatric psychiatrist), Dr. Chiadi Onyike (a geriatric psychiatrist and specialist in behavioral variant frontotemporal dementia (bvFTD)), Dr. Adam Boxer (a neurologist with expertise in clinical trials in bvFTD),] Dr. John Neuhaus (a biostatistician) and Dr. Mark D'Esposito (a professor of neuroscience with expertise in functional neuroimaging and reward processing). The proposed research will examine reward processing in bvFTD. Reward processing involves a determination of what an individual will pursue or work for, such as food, money, or social approval. Dr. Perry will administer laboratory tasks of reward processing to patients with bvFTD, Alzheimer's disease, and healthy control subjects to determine the aspect of valuation of reward that is altered in bvFTD (Aim 1). Dr. Perry will correlate the findings from these laboratory tasks with structural and functional imaging to determine the anatomic correlates of these behaviors (Aim 2) and with real-life functional measures to determine the effect reward processing changes have in patients'lives (Aim 3). Data collection will take place at the MAC. The results of this research will improve understanding of the behavioral symptoms in bvFTD, will direct future studies into symptomatic treatment in the illness, will provide objective tests to distinguish neurodegenerative diseases, and will offer reward-based measures as an additional tool for use in animal models of bvFTD. This K23 training will enable Dr. Perry to apply concepts of reward processing to the understanding of other neurodegenerative diseases.
Though behavioral variant frontotemporal dementia and reward processing involve overlapping brain regions, and symptoms in the disease suggest abnormal valuation of reward, there has been little formal study of the relationship between the illness and this process. Clarification of the reward deficit, its impact on daily function, and it anatomy will further efforts to find symptomatic treatments, provide tests to distinguish this illness from other neurodegenerative diseases, and be applicable to drug testing in animal models of disease.
|Hua, Alice Y; Sible, Isabel J; Perry, David C et al. (2018) Enhanced Positive Emotional Reactivity Undermines Empathy in Behavioral Variant Frontotemporal Dementia. Front Neurol 9:402|
|Sturm, Virginia E; Brown, Jesse A; Hua, Alice Y et al. (2018) Network Architecture Underlying Basal Autonomic Outflow: Evidence from Frontotemporal Dementia. J Neurosci 38:8943-8955|
|Seo, Sang Won; Thibodeau, Marie-Pierre; Perry, David C et al. (2018) Early vs late age at onset frontotemporal dementia and frontotemporal lobar degeneration. Neurology 90:e1047-e1056|
|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|
|Fernández-Fournier, Mireya; Perry, David C; Tartaglia, Maria Carmela et al. (2017) Precipitous Deterioration of Motor Function, Cognition, and Behavior. JAMA Neurol 74:591-596|
|Perry, David C; Brown, Jesse A; Possin, Katherine L et al. (2017) Clinicopathological correlations in behavioural variant frontotemporal dementia. Brain 140:3329-3345|
|Krabbe, Grietje; Minami, S Sakura; Etchegaray, Jon I et al. (2017) Microglial NF?B-TNF? hyperactivation induces obsessive-compulsive behavior in mouse models of progranulin-deficient frontotemporal dementia. Proc Natl Acad Sci U S A 114:5029-5034|
|Spina, Salvatore; Schonhaut, Daniel R; Boeve, Bradley F et al. (2017) Frontotemporal dementia with the V337M MAPT mutation: Tau-PET and pathology correlations. Neurology 88:758-766|
|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|
|Perry, David C; Sturm, Virginia E; Peterson, Matthew J et al. (2016) Association of traumatic brain injury with subsequent neurological and psychiatric disease: a meta-analysis. J Neurosurg 124:511-26|
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