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.

项目总结

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.