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Mechanisms of disrupted memory encoding in epilepsy patients - Resubmission - 1

癫痫患者记忆编码破坏的机制 - 重新提交 - 1

基本信息

批准号：
10433853
负责人：
Anli A Liu
金额：
$ 19.75万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10433853
关键词：
Address Antiepileptic Agents Behavioral Biometry Biostatistical Methods Chronic Clinical Clinical Investigator Clinical Research Cognition Cognitive Communication Communities Computing Methodologies Coupled Coupling Data Data Science Development Electric Stimulation Electrocorticogram Electrodes Electroencephalography Epilepsy Event Face Failure Foundations Frequencies Functional disorder Funding Future Goals High Frequency Oscillation Hippocampus (Brain)Hour Immediate Recalls Impairment Implant Implanted Electrodes International Intervention Knowledge Learning Location Medical Memory Memory Loss Memory impairment Mentored Patient-Oriented Research Career Development Award Mentors Modeling Neocortex Neurologist Neurology Operative Surgical Procedures Outcome Pathologic Patients Performance Persons Pharmaceutical Preparations Physiological Physiology Population Process Protocols documentation Public Health Research Research Design Research Personnel Research Proposals Science Seizures Specialist Structure Techniques Temporal Lobe Testing Time Training base brain abnormalities career classical conditioning design entorhinal cortex experimental study improved in vivo innovation medical schools memory encoding memory process neocortical neurophysiology neuroregulation neurotransmission novel patient oriented research patient subsets physiologic model prospective relating to nervous system remediation restoration side effect signal processing skills success therapeutic target therapy development time interval

项目摘要

This is a K23 award application for Dr. Anli Liu, a neurologist at NYU School of Medicine. Dr. Liu’s long- term career goals are to become a leading clinical investigator in describing the mechanisms of memory dysfunction in epilepsy patients and developing neuromodulation techniques for memory restoration. The K23 award will support her short-term career goals which are: (1) to conduct prospective patient-oriented research in epilepsy patients; (2) to gain expertise in signal processing; (3) to implement biostatistical and computational methods relevant to behavioral and neurophysiological data; and (4) to transition into an independent R01-funded research career. To achieve these goals, Dr. Liu has assembled an outstanding team of a primary mentor, Dr. György Buzsáki, an internationally recognized expert in neural oscillations, memory and advanced in vivo recording techniques, and two co-mentors: Dr. Orrin Devinsky, a leader in epilepsy and cognition, and Dr. Lucas Parra, a specialist in neural signal processing. She will have two scientific advisors: Dr. Lila Davachi, a leading scholar in mesial temporal lobe and memory, and Dr. Laura Balcer, an expert in clinical research design and biostatistics. Dr. Liu has strong institutional support from the Department of Neurology and the Division of Epilepsy. She will receive comprehensive training from NYU’s vibrant scientific and medical communities, including the NYU School of Medicine, Center for Neural Science, and Data Science Center. There is a fundamental gap in mechanistic understanding of why encoding fails in epilepsy patients. The overall objective of this proposal is to develop a model of encoding function, explaining the coordinated events in a mesial temporal-neocortical network necessary to form associative memories. Dr. Liu will test the central hypothesis that coupled rhythms between hippocampus, entorhinal cortex, and neocortex are required to encode information, and that pathological interictal events and electrical stimulation can disrupt these rhythms. In Aim 1, 40 patients undergoing intracranial electroencephalography (iEEG) for epilepsy surgery will participate in an associative memory task, followed by comparison of the neurophysiological differences between successful and failed learning trials. In Aim 2, 16 patients with chronically implanted hippocampal depth electrodes will perform the same task with recall tested after more prolonged time intervals. The proposal is innovative because Dr. Liu will: (1) establish a relationship between abnormal neural activity and normal encoding processes; (2) test this relationship with prospective interventions to perturb normal rhythms; (3) utilize a novel, clinically meaningful associative memory task; and (4) include patients with chronic ambulatory electrocorticography, which permits serial testing under controlled experimental conditions. The expected outcomes will include a detailed mechanistic model of encoding function, which explains how pathological events contribute to impaired learning in an epilepsy population, and a rational foundation for development of neurostimulation protocols and behavioral strategies to restore memory dysfunction.

这是一份K23奖的申请，申请人是纽约大学医学院的神经学家刘安丽博士。刘博士的长期职业目标是成为描述癫痫患者记忆功能障碍机制和开发记忆恢复神经调节技术的领先临床研究者。K23奖将支持她的短期职业目标，即：（1）在癫痫患者中进行前瞻性的以患者为导向的研究;（2）获得信号处理方面的专业知识;（3）实施与行为和神经生理数据相关的生物统计和计算方法;以及（4）过渡到独立的R 01资助的研究生涯。为了实现这些目标，刘博士组建了一支优秀的团队，主要导师是国际公认的神经振荡，记忆和先进体内记录技术专家György Buzsáki博士，以及两位共同导师：癫痫和认知领域的领导者Orrin Devinsky博士和神经信号处理专家Lucas Parra博士。她将有两名科学顾问：内侧颞叶和记忆领域的领先学者Lila Davachi博士和临床研究设计和生物统计学专家Laura Balcer博士。刘医生得到了神经内科和癫痫科的强有力的机构支持。她将接受纽约大学充满活力的科学和医学界的全面培训，包括纽约大学医学院、神经科学中心和数据科学中心。对于癫痫患者编码失败的原因，在机械理解方面存在根本性的差距。这个建议的总体目标是开发一个模型的编码功能，解释协调事件的内侧颞-新皮层网络必要的，以形成联想记忆。Liu博士将测试中心假设，即海马体，内嗅皮层和新皮层之间的耦合节律是编码信息所必需的，并且病理性发作间期事件和电刺激可以破坏这些节律。在目标1中，40例接受颅内脑电图（iEEG）癫痫手术的患者将参与联想记忆任务，然后比较成功和失败的学习试验之间的神经生理学差异。在目标2中，16名长期植入海马深度电极的患者将执行相同的任务，并在更长的时间间隔后进行回忆测试。该提案具有创新性，因为Liu博士将：（1）建立异常神经活动与正常编码过程之间的关系;（2）通过前瞻性干预来扰乱正常节律来测试这种关系;（3）利用一种新的、具有临床意义的联想记忆任务;（4）包括慢性动态皮质电描记术患者，这允许在受控实验条件下进行系列测试。预期的结果将包括编码功能的详细机制模型，该模型解释了病理事件如何导致癫痫人群的学习受损，以及神经刺激方案和行为策略的合理基础，以恢复记忆功能障碍。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Learning hierarchical sequence representations across human cortex and hippocampus.

DOI：
10.1126/sciadv.abc4530
发表时间：
2021-03
期刊：
Science advances
影响因子：
13.6
作者：
Henin S;Turk-Browne NB;Friedman D;Liu A;Dugan P;Flinker A;Doyle W;Devinsky O;Melloni L
通讯作者：
Melloni L

Machine Learning to Classify Relative Seizure Frequency From Chronic Electrocorticography.

DOI：
10.1097/wnp.0000000000000858
发表时间：
2023-02-01
期刊：
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society
影响因子：
0
作者：
Sun Y;Friedman D;Dugan P;Holmes M;Wu X;Liu A
通讯作者：
Liu A

Time-dependent transformations of memory representations differ along the long axis of the hippocampus.

DOI：
10.1101/lm.053438.121
发表时间：
2021-09
期刊：
Learning & memory (Cold Spring Harbor, N.Y.)
影响因子：
0
作者：
Cowan ET;Liu AA;Henin S;Kothare S;Devinsky O;Davachi L
通讯作者：
Davachi L

Is formal scoring better than just looking? A comparison of subjective and objective scoring methods of the Rey Complex Figure Test for lateralizing temporal lobe epilepsy.

正式得分不仅比寻找更好吗？ REY复合物数测试的主观和客观评分方法的比较，用于横向颞叶癫痫。

DOI：
10.1080/13854046.2020.1865461
发表时间：
2022-10
期刊：
The Clinical neuropsychologist
影响因子：
0
作者：
LeMonda BC;MacAllister W;Morrison C;Vaurio L;Blackmon K;Maiman M;Liu A;Liberta T;Bar WB
通讯作者：
Bar WB

Application of RNS in refractory epilepsy: Targeting insula.