Neurophysiological Assessments of Network Dysfunction in Alzheimer's Disease

阿尔茨海默病网络功能障碍的神经生理学评估

• 批准号: 10623150
• 负责人: Kamalini Gayathree Ranasinghe
• 金额: $ 17.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10623150
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease patient; Amyloid beta-Protein; Anatomy; Animal Model; Architecture; Behavioral; Biological Markers; Biometry; Brain; Brain imaging; California; Clinical; Clinical Research; Clinical Trials; Cognition; Cognitive; Cognitive aging; Cognitive deficits; Data; Dementia; Deposition; Development; Disease; Disease Progression; Environment; Evaluation; Frequencies; Functional disorder; Future; Goals; Grant; Human; Impaired cognition; Impairment; Investigation; K-Series Research Career Programs; Knowledge; Link; Magnetoencephalography; Measures; Medial; Memory; Mentors; Molecular; Nerve Degeneration; Neurobiology; Neurodegenerative Disorders; Neurologist; Neurons; Neurosciences; Pathologic; Patients; Pattern; Physicians; Play; Positioning Attribute; Positron-Emission Tomography; Process; Proteins; Research; Research Ethics; Research Institute; Research Personnel; Research Project Grants; Rest; San Francisco; Scientist; Spatial Distribution; Synapses; Synaptic plasticity; Syndrome; Techniques; Temporal Lobe; Testing; Therapeutic Intervention; Tracer; Training; Translational Research; Universities; Work; Writing; abeta accumulation; abeta deposition; brain behavior; career; career development; clinical training; cognitive ability; comparison control; design; experience; follow-up; imaging study; innovation; insight; knowledge base; molecular imaging; molecular marker; multimodal neuroimaging; multimodality; network dysfunction; neural; neural circuit; neural patterning; neurobehavioral; neurodegenerative dementia; neuroimaging; neuronal circuitry; neurophysiology; neuroregulation; novel; novel therapeutic intervention; progressive neurodegeneration; spatiotemporal; targeted treatment; tau Proteins; tau aggregation; uptake

PROJECT SUMMARY This is an application for a K08 Mentored Clinical Scientist Research Career Development Award to promote the candidate's development as an independent researcher in clinical neuroscience, with a focus on understanding the neurophysiological abnormalities in Alzheimer's disease (AD), and eventually, in other dementia syndromes. Dr. Ranasinghe's long-term career goal is to develop a deep knowledge base on brain- behavior relationships associated with specific pathophysiological processes in neurodegenerative diseases. The current research project proposes a multimodal, longitudinal brain imaging study, integrating magnetoencephalographic imaging (MEGI) with positron emission tomography (PET), and with progressive trajectories of neurodegenerative processes, in AD patients. AIM-1 examines the distinct patterns of network synchronization deficits in patients with AD using MEGI, and their specific associations to PET-derived molecular markers of amyloid beta and tau. AIM-2 conducts longitudinal MEGI assessments of network deficits combined with cognitive and volumetric measures with annual follow-ups for two years. The results will uncover neurophysiological signatures of aberrant neuronal functions in AD, in humans, and will have important implications for translational research and clinical trials. This K08 will provide Dr. Ranasinghe with the support necessary to accomplish the following goals: (1) Training in application and analysis of multimodal neuroimaging techniques; (2) Clinical training in patient evaluations and longitudinal follow-up; (3) Gaining greater depth of knowledge in mechanisms of AD; (4) Training in advanced biostatistical analyses in clinical research; (5) Training in grant writing, career development, and research ethics. To achieve these goals, Dr. Ranasinghe has assembled a mentoring team including her primary mentor: Dr. Katherine Rankin (a neuropsychologist with expertise in neurodegenerative diseases); and two co-mentors: Drs. Gil Rabinovici (a behavioral neurologist with expertise in molecular imaging), and Srikantan Nagarajan (a neuroscientist with expertise in magnetoencephalography). The collaborators of Dr. Ranasingh'e project include Drs. Maria Luisa Gorno-Tempini (a behavioral neurologist with expertise in neuroimaging), Joel Kramer (a neuropsychologist with expertise in cognitive ageing), Lea Grinberg (a neuropathologist with expertise in neurobiology of AD), and Maria Glymour (a biostatistician). The candidate is a physician-scientist with a strong commitment to a career in neurodegenerative dementia research. The University of California San Francisco Memory and Aging Center is an ideal environment for the proposed training, being a top dementia research institute in the nation with access to world leading experts in clinical and translational research. The research and training experience described in this proposal will enable the candidate's goal of developing a strong independent research career in the field of neurophysiological assessments in neurodegenerative diseases.

项目概要 这是 K08 指导临床科学家研究职业发展奖的申请，以促进 候选人作为临床神经科学独立研究员的发展，重点是 了解阿尔茨海默病 (AD) 以及最终其他疾病中的神经生理学异常 痴呆综合症。拉纳辛格博士的长期职业目标是建立关于大脑的深厚知识基础 与神经退行性疾病特定病理生理过程相关的行为关系。 当前的研究项目提出了一项多模式、纵向脑成像研究，整合 脑磁图成像 (MEGI) 与正电子发射断层扫描 (PET) 以及渐进式 AD 患者神经退行性过程的轨迹。 AIM-1 检查网络的不同模式 使用 MEGI 治疗 AD 患者的同步缺陷及其与 PET 衍生的特定关联 β 淀粉样蛋白和 tau 淀粉样蛋白的分子标记。 AIM-2 对网络缺陷进行纵向 MEGI 评估 结合认知和体积测量以及两年的年度随访。结果将 揭示人类 AD 中异常神经元功能的神经生理学特征，并将 对转化研究和临床试验具有重要意义。这台 K08 将为拉纳辛格博士提供 实现以下目标所需的支持： (1) 多模式应用和分析培训 神经影像技术； (2) 患者评估和纵向随访的临床培训； (3) 收获 对 AD 机制有更深入的了解； (4) 临床高级生物统计分析培训 研究; (5) 资助写作、职业发展和研究道德方面的培训。为了实现这些目标，博士。 拉纳辛哈组建了一个指导团队，其中包括她的主要导师：凯瑟琳·兰金 (Katherine Rankin) 博士（一位 具有神经退行性疾病专业知识的神经心理学家）；和两位共同导师：博士。吉尔·拉宾诺维奇（ 具有分子成像专业知识的行为神经学家）和 Srikantan Nagarajan（具有分子成像专业知识的神经科学家） 脑磁图专业知识）。 Ranasingh'e 博士项目的合作者包括博士。玛丽亚·路易莎 Gorno-Tempini（具有神经影像学专业知识的行为神经学家）、Joel Kramer（神经心理学家） Lea Grinberg（具有 AD 神经生物学专业知识的神经病理学家），以及 玛丽亚·格利摩（生物统计学家）。候选人是一位对职业有坚定承诺的医师科学家 从事神经退行性痴呆研究。加州大学旧金山分校记忆与衰老 该中心是全国顶尖的痴呆症研究机构，是拟议培训的理想环境 可以接触到世界领先的临床和转化研究专家。研究与培训 本提案中描述的经验将使候选人能够实现发展强大的独立能力的目标 神经退行性疾病的神经生理学评估领域的研究生涯。

项目成果

Network connectivity predicts effectiveness of responsive neurostimulation in focal epilepsy.

• DOI: 10.1093/braincomms/fcac104
• 发表时间: 2022
• 期刊: BRAIN COMMUNICATIONS
• 影响因子: 4.8
• 作者: Fan, Joline M.;Lee, Anthony T.;Kudo, Kiwamu;Ranasinghe, Kamalini G.;Morise, Hirofumi;Findlay, Anne M.;Kirsch, Heidi E.;Chang, Edward F.;Nagarajan, Srikantan S.;Rao, Vikram R.
• 通讯作者: Rao, Vikram R.