Functional Brain Networks: A Novel Approach to Address Clinical Challenges in PD

功能性大脑网络：解决帕金森病临床挑战的新方法

基本信息

批准号：
8741996
负责人：
DAVID EIDELBERG
金额：
$ 194.22万
依托单位：
FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8741996
关键词：
Address Adverse effects Affect Algorithms Animal Model Animals Area Arts Authorship Autopsy Back Basal Ganglia Basic Science Behavior assessment Behavioral Bioinformatics Biological Markers Biological Process Biomedical Research Biometry Blood - brain barrier anatomy Blood flow Brain Brain imaging Brain region Caring Cells Cerebrovascular Circulation Cerebrum Clinic Clinical Clinical Research Cognition Cognitive Collaborations Comorbidity Complex Complication Corpus striatum structure Data Development Diagnostic Differential Diagnosis Disadvantaged Disease Dissociation Doctor of Philosophy Dopamine Dopamine Agonists Dyskinetic syndrome Early Diagnosis Endothelium Event Experimental Animal Model Functional Imaging Functional disorder Funding Future Genes Goals Growth Health Benefit Human Image Image Analysis Imaging Device Imaging Techniques Impaired cognition Individual Individual Differences Informatics Institutes Investigation Knowledge Lead Leadership Learning Levodopa Magnetic Resonance Imaging Maps Measurement Measures Mediating Medical Research Medicine Memory Metabolism Methods Mission Modeling Molecular Molecular Medicine Mood Disorders Motor Movement Disorders Nafion Nerve Degeneration Network-based Neurodegenerative Disorders Neurology Neurosciences Noise Outcome Parkinson Disease Parkinsonian Disorders Pathogenesis Pathway Analysis Pathway interactions Patients Pattern Peripheral Permeability Pharmaceutical Preparations Physicians Population Principal Investigator Process Property Psychometrics Psychophysics Publications Radiochemistry Rattus Recruitment Activity Research Research Infrastructure Research Personnel Residencies Rest Rewards Rodent Model Role Rubidium Scientist Signal Transduction Sorting - Cell Movement Staging Sweden Symptoms System Systems Biology Testing Time Tracer Training Training Support Training and Education Translating Translational Research Translations Twin Multiple Birth United States National Institutes of Health Universities Validation Vasomotor Whole Organism Work angiogenesis authority base bench to bedside career clinical practice clinically relevant cognitive change cognitive neuroscience computer science data sharing effective therapy experience follower of religion Jewish graduate student hemodynamics high risk human disease improved indexing innovation insight instrument interdisciplinary collaboration medical schools medical specialties member neuroimaging new therapeutic target non-motor symptom north shore long island novel novel strategies patient oriented patient oriented research patient population programs public health relevance relating to nervous system research study response success tool translational approach treatment response vasculogenesis

项目摘要

DESCRIPTION (provided by applicant): Parkinson's disease (PD) is characterized by both motor and non-motor symptoms (cognitive impairment, affective disorder, and other clinical features). Data from experimental animal models and patients with PD indicate that the manifestations of this disease cannot be attributed to isolated dysfunction of the basal ganglia. Rather, the highly localized loss of nigral dopamine cells is associated with a broad, spatially distributed set of functional abnormalities involving cortico-striato-pallido-thalamocortical (CSPTC) loops and related pathways. By quantifying the activity of spatially distributed (large-scale) functional brain networks, comprising multiple interconnected brain regions, modern techniques of image-based analysis can provide valuable information concerning the widespread circuit abnormalities that underlie neurodegenerative disorders such as PD. The investigators at the Center for Neurosciences at The Feinstein Institute, led by Dr. Eidelberg, have pioneered the use of functional brain imaging and network analysis for the study of PD and related neurodegenerative diseases. Because of the noise inherent in "small signals" analyses of this sort, we have emphasized rigorous validation of the disease-related functional patterns from both statistical and empiric standpoints. Indeed, high levels of measurement precision are needed before quantitative network measures can be considered as potential biomarkers of the disease process and its response to treatment. In this proposal, we seek to take this approach to a new level by employing rigorously validated PD-related networks to address a number of vital issues that impact heavily on the care of today's PD patients. Project 1 addresses the serious clinical problem of levodopa-induced dyskinesias, which ultimately affect nearly all PD patients. Project 2 examines the network basis for individual differences in the cognitive response to dopaminergic treatment with a view to predicting which patients will develop untoward cognitive side effects under different treatment conditions. Project 3 aims to establish the feasibility of a new network-based algorithm for providing earlier and more accurate differential diagnosis than is currently possible.

描述（由申请人提供）：帕金森氏病（PD）的特征是运动症状和非运动症状（认知障碍，情感障碍和其他临床特征）。来自实验动物模型和PD患者的数据表明，该疾病的表现不能归因于基底神经节的孤立功能障碍。相反，高度局部的多巴胺细胞的局部损失与涉及涉及皮质 - 纹状体 - 甲状腺皮质皮质皮质（CSPTC）环路的宽阔，空间分布的功能异常相关。通过量化空间分布的（大尺度）功能性脑网络的活性，包括多个相互连接的大脑区域，基于图像的分析的现代技术可以提供有关神经退行性疾病基于PD等神经退行性疾病的广泛电路异常的有价值信息。由Eidelberg博士领导的Feinstein Institute神经科学中心的研究者开创了功能性脑成像和网络分析的使用，用于研究PD和相关的神经退行性疾病。由于这种“小信号”分析中固有的噪声，我们从统计和经验的角度强调了对疾病相关功能模式的严格验证。实际上，在定量网络措施被视为疾病过程的潜在生物标志物及其对治疗的反应之前，需要高水平的测量精度。在此提案中，我们试图通过使用严格验证的与PD相关的网络来解决许多重要问题，这些问题对当今的PD患者的护理产生了严重影响，将这种方法提高到了新的水平。项目1解决了左旋多巴引起的运动障碍的严重临床问题，最终影响了几乎所有PD患者。项目2研究了对多巴胺能治疗的认知反应中个体差异的网络基础，以预测哪些患者在不同的治疗条件下会发展出不良的认知副作用。 Project 3旨在建立一种新的基于网络的算法的可行性，以提供比目前可能的更早，更准确的鉴别诊断。

项目成果

期刊论文数量（38）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Blood-brain barrier permeability in Parkinson's disease patients with and without dyskinesia.

有或没有运动障碍的帕金森病患者的血脑屏障通透性。

DOI：
10.1007/s00415-021-10411-1
发表时间：
2021
期刊：
Journal of neurology
影响因子：
6
作者：
Fujita,Koji;Peng,Shichun;Ma,Yilong;Tang,ChrisC;Hellman,Matthew;Feigin,Andrew;Eidelberg,David;Dhawan,Vijay
通讯作者：
Dhawan,Vijay

A multivariate metabolic imaging marker for behavioral variant frontotemporal dementia.

DOI：
10.1016/j.dadm.2018.07.009
发表时间：
2018-01-01
期刊：
Alzheimer's & dementia (Amsterdam, Netherlands)
影响因子：
0
作者：
Nazem, Amir;Tang, Chris C;Eidelberg, David
通讯作者：
Eidelberg, David

What light have resting state fMRI studies shed on cognition and mood in Parkinson's disease?

DOI：
10.1186/2054-7072-1-4
发表时间：
2014
期刊：
Journal of clinical movement disorders
影响因子：
0
作者：
YorkWilliams S;Poston KL
通讯作者：
Poston KL

Parkinson's disease-related network topographies characterized with resting state functional MRI.

DOI：
10.1002/hbm.23260
发表时间：
2017-02
期刊：
HUMAN BRAIN MAPPING
影响因子：
4.8
作者：
Vo, An;Sako, Wataru;Fujita, Koji;Peng, Shichun;Mattis, Paul J.;Skidmore, Frank M.;Ma, Yilong;Ulug, Aziz M.;Eidelberg, David
通讯作者：
Eidelberg, David

Functional brain networks and abnormal connectivity in the movement disorders.