The Cognitive and Neural Basis of Apathy in Frontotemporal Degeneration

这个国家研究服务奖（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研究者，专注于神经退行性疾病（ND）患者冷漠等神经行为改变的生物学机制。除了学术课程和研究技能的获得之外，我建议将NRSA的重点放在目标导向行为的障碍上，这在ND中很常见，但研究不足。冷漠综合征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影响。冷漠是与额纹状体系统破坏相关的主要神经精神综合征之一，但其行为和生物学机制尚不清楚。冷漠在行为变异性额颞叶变性（bvFTD）中尤为普遍，据报道在轻度患者中高达90.5%我假设冷漠有三种亚型，它们会损害目标导向行为的不同组成部分，并且每一种亚型的冷漠都与特定的神经解剖学底物有关。我将使用一种新的计算机反应时间测试和神经成像来研究这些经验。我有超过5年的高级执业护士和研究护士协调员的经验，在全国排名的实验室研究ND行为的神经基础，并可以直接访问神经心理学和神经影像学数据的大型数据库。我的研究培训将由两位国际知名科学家指导，一位是知名老年护理专家和领导者Lois Evans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Murray Grossman博士。这项研究培训的长期影响将对ND患者、他们的护理人员和家庭产生深远的影响。由于我们对这种情况的潜在机制了解不足，目前对冷漠的治疗受到阻碍。对冷漠的精确描述将使我们能够对病人实施最合适的治疗。与国家护理研究所（NINR）的优先事项一致，这项工作将有助于更好地理解这些行为发生的原因，并根据这些知识，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.