The Cognitive and Neural Basis of Apathy in Frontotemporal Degeneration

这一个人国家研究服务奖(NRSA)的目的是为神经科学护士提供研究培训，使其成为一名独立的调查员，专注于导致神经退行性疾病(ND)患者冷漠等神经行为变化的生物机制。除了学术课程和研究技能的获得，我建议把这次NRSA的重点放在目标导向行为的障碍上，这些行为在ND中非常常见，但没有得到足够的研究。冷漠综合症被定义为自我产生或自愿行为的减少，1对患者的发病率和死亡率以及家庭照顾者的负担具有深远的后果。冷漠是与额叶-纹状体系统破坏相关的主要神经精神综合征之一，但冷漠背后的行为和生物学机制尚不清楚。冷漠在行为变异型额颞部退行性变(BvFTD)中尤其普遍，据报道，高达90.5%的轻度患者有这种情况。2我假设有三种不同的冷漠亚型，它们损害了目标导向行为的不同组成部分，并且每种亚型的冷漠都与特定的神经解剖基础有关。我将使用一种新型的计算机化反应时间测试和神经成像来对这些进行实证研究。我有5年以上在国家一级实验室担任高级实践护士和研究护士协调员的经验，该实验室研究ND行为的神经基础，并可以直接访问神经心理学和神经成像数据的大型数据库。我的研究培训将由两位国际知名科学家指导，一位是著名的老年学护理专家和领导者露易丝·埃文斯博士，另一位是备受赞誉的认知神经学家和经验丰富的科学家穆雷·格罗斯曼博士。这项研究培训的长期影响将对ND患者、他们的照顾者和家人产生深远的影响。目前对冷漠的治疗一直受到阻碍，因为我们对这种情况背后的机制缺乏了解。对冷漠的准确描述将使我们能够为患者实施最合适的治疗。与国家护理研究所(NINR)的优先事项一致，这项工作将导致更好地理解为什么会发生这些行为，有了这些知识，专业和非专业护理人员可以实施量身定制的干预措施。

The purpose of this individual National Research Service Award (NRSA) is to provide research training for a neuroscience nurse to become an independent investigator focusing on the biological mechanisms that contribute to neurobehavioral changes such as apathy in patients with neurodegenerative disease (ND). In addition to scholarly coursework and the acquisition of research skills, I propose to focus this NRSA on impairments of goal-directed behavior that are very common but understudied in ND. The syndrome of apathy, defined as a reduction in self-generated or voluntary behavior,1 has profound consequences for morbidity and mortality in the patient and for family caregiver burden. Apathy is one of the primary neuropsychiatric syndromes associated with the disruption of the frontal-striatal system, but the behavioral and biological mechanisms underlying apathy are not well understood. Apathy is especially prevalent in behavioral variant Frontotemporal Degeneration (bvFTD), where it is reported in up to 90.5% of mild stage patients.2 I hypothesize three subtypes of apathy that compromise distinct components of goal-directed behavior, and that each of these subtypes of apathy are associated with a specific neuroanatomic substrate. I will investigate these empirically using a novel computerized reaction time test and neuroimaging. I have had more than 5 years experience as an Advanced Practice Nurse and Research Nurse Coordinator in a nationally ranked laboratory that studies the neural basis for behavior in ND and have direct access to a large database of neuropsychological and neuroimaging data. My research training will be guided by two internationally known scientists, Dr. Lois Evans, a well-known gerontological nurse expert and leader, and Dr. Murray Grossman, a highly acclaimed cognitive neurologist and experienced scientist. The long-term impact of this research training will be profound for patients with ND, their caregivers, and families. Current treatment of apathy has been hindered because of our poor understanding of the mechanisms underlying this condition. The precise characterization of apathy will allow us to implement the most appropriate therapy for a patient. Consistent with the National Institute of Nursing Research (NINR) priorities, this work will lead to a better understanding of why these behaviors occur and with this knowledge, tailored interventions can be implemented by professional and lay caregivers.