Neurodevelopmental Trajectories Towards Neurodegenerative Disease

神经退行性疾病的神经发育轨迹

基本信息

批准号：
9127057
负责人：
ZACHARY A MILLER
金额：
$ 16.24万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-15 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9127057
关键词：
Age of Onset Aging Agrammatism Anatomy Anomia Anterior Applications Grants Articulation Disorders Atrophic Behavior Behavioral Biological Preservation Biology Biomedical Engineering Biometry Brain C9ORF72 California Characteristics Clinical Clinical Research Cognition Cognitive Control Groups DNA Sequence Alteration Data Degenerative Disorder Dementia Development Diagnosis Diagnostic Disease Disease Progression Functional Imaging Functional disorder Funding Future Gene Mutation Genes Genetic Goals Hand Handedness Health Heterogeneity Image Individual Inferior Knowledge Language Language Development Language Disorders Learning Disabilities Left Life Linguistics Magnetic Resonance Imaging Magnetoencephalography Measures Memory Mentored Patient-Oriented Research Career Development Award Mentors Multivariate Analysis Mutation Nerve Degeneration Neurodegenerative Disorders Neurodevelopmental Disorder Neurologist Neurons Parietal Patients Pattern Phase Phenotype Prevalence Prevention strategy Primary Progressive Aphasia Process Psychiatrist Questionnaires Recording of previous events Research Research Personnel San Francisco Semantics Shapes Speech Structure Syndrome Techniques Temporal Lobe Time Training Universities Variant With laterality Work aphasic base career cognitive neuroscience cognitive testing cohort design disability experience language processing multidisciplinary neurodevelopment neuroimaging neuropathology novel patient oriented phonology pre-clinical preference skills tool treatment strategy

项目摘要

DESCRIPTION (provided by applicant): This is a K23 award application for Dr. Zachary A. Miller, a behavioral neurologist at the University of California, San Francisco Memory and Aging Center (MAC) who is establishing himself as a young investigator in patient-oriented clinical research focusing on language processing in neurodegenerative disease. This K23 award will provide Dr. Miller with the necessary support to accomplish the following: (1) gain expertise in neurodegenerative disease and the cognitive neuroscience of language processing; (2) develop proficiency in the use and analysis of structural and functional neuroimaging; (3) gain experience in evaluating neurodevelopmental and genetic factors in neurodegenerative patients; (4) advance his knowledge of biostatistics; (5) gain exposure and training in the neuropathology of language disorders; and (6) develop an independent clinical research career. To achieve these goals, he assembled a multidisciplinary mentoring team with two primary mentors: Dr. Maria Luisa Gorno-Tempini (a neurologist with expertise in language disorders and advanced neuroimaging techniques) and Dr. Bruce Miller (a neurologist with expertise in behavior, neurodegenerative disease, and clinical research); a co-mentor: Dr. Srikantan Nagarajan (a bioengineer with expertise in magnetoencephalography); and three advisors: Dr. Matt State (a psychiatrist with expertise in neurodevelopmental disorders and genetics), Dr. William Seeley (a neurologist with expertise in neuropathology and functional imaging), and Dr. John Neuhaus (a biostatistician with expertise in multivariate analyses). The proposed research investigates the effect of pre-morbid, individual characteristics related to language disabilities and clinical presentation in neurodegenerative diseases. The central hypothesis is that neurodevelopmental factors are associated with increased vulnerability of the language networks to disease, leading to specific language presentations, imaging changes, and disease progression. We will study PPA and FTD gene carriers to examine the consequences of language learning disability and hand preference on clinical, cognitive, and neuroimaging phenotype. We will collect a standardized neurodevelopmental history, detailed cognitive assessment, and imaging data to determine phenotypic differences between PPA patients with and without a history of language-learning disabilities at presentation (Aim 1). We will establish hand preference and language lateralization patterns using magnetoencephalography in PPA and healthy control subjects and correlate them with measures of structural brain symmetry (Aim 2). We will collect longitudinal cognitive and neuroimaging data on PPA and FTD gene carriers and compare patterns of progression in subjects with and without language learning disabilities (Aim 3). This research will increase understanding of pre-morbid factors on clinical heterogeneity in PPA, direct future studies into early diagnostic and treatment strategies, and offer novel neurodevelopmental and imaging measures as new tools for PPA characterization and diagnosis. This K23 training will enable Dr. Miller to apply concepts of selective neurodevelopmental vulnerability to the understanding of other neurodegenerative diseases.]

描述（由应用程序提供）：这是加州大学旧金山大学记忆和老化中心（MAC）的行为神经科医生Zachary A. Miller博士的奖项申请，他正在以患者为导向的临床研究中建立自己的年轻研究者，该研究重点是神经性疾病中的语言处理。该K23奖将为米勒博士提供必要的支持，以完成以下方面：（1）获得神经退行性疾病和语言处理的认知神经科学的专业知识；（2）在结构和功能神经影像学的使用和分析方面提高熟练程度；（3）在评估神经退行性患者的神经发育和遗传因素方面获得经验；（4）提高他对生物统计学的了解；（5）在语言障碍神经病理学中获得暴露和培训；（6）发展独立的临床研究职业。实现这些目标，他与两个主要导师组成了一个多学科的心理团队：Maria Luisa Gorno-Tempini博士（具有语言障碍和高级神经影像学技术专业知识的神经科学家）和Bruce Miller博士（具有行为，神经变性疾病和临床研究的神经科学家）；副主管：Srikantan Nagarajan博士（具有磁性专业知识的生物工程师）；和三位顾问：Matt State博士（具有神经发育障碍和遗传学专业知识的精神病医生），William Seeley博士（具有神经病理学和功能成像专业知识的神经科学家）和John Neuhaus博士（具有多差异分析方面的生物统计学家）。拟议的研究调查了与语言疾病和神经退行性疾病中临床表现有关的术前，个人特征的影响。中心假设是神经发育因素与语言网络对疾病的脆弱性增加有关，导致特定的语言表现，成像变化和疾病的发展。我们将研究PPA和FTD基因携带者，以检查语言学习障碍的后果以及对临床，认知和神经成像表型的偏好。我们将收集标准化的神经发育史，详细的认知评估和成像数据，以确定在介绍时有和没有语言学习障碍病史的PPA患者之间的表型差异（AIM 1）。我们将使用PPA和健康对照受试者中的磁脑图建立手部偏好和语言横向模式，并将它们与结构性脑对称性的测量相关联（AIM 2）。我们将收集有关PPA和FTD基因载体的纵向认知和神经影像学数据，并比较患有和没有语言学习障碍的受试者的进展模式（AIM 3）。这项研究将提高对PPA临床异质性的临床异质性，将未来研究直接研究到早期诊断和治疗策略中的理解，并提供新颖的神经发育和成像措施，作为PPA表征和诊断的新工具。这种K23培训将使米勒博士能够将选择性神经发育脆弱性的概念应用于对其他神经退行性疾病的理解。]