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

• 批准号: 8549321
• 负责人: DAVID EIDELBERG
• 金额: $ 168.47万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8549321
• 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; 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; 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

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）：帕金森病（PD）的特征是运动和非运动症状（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，这种疾病的表现不能归因于基底神经节的孤立功能障碍。相反，黑质多巴胺细胞的高度局部化的损失与广泛的，空间分布的功能异常，涉及皮质-纹状体-苍白球-丘脑皮质（CSPTC）环路和相关途径。通过量化空间分布（大规模）功能性脑网络（包括多个相互连接的脑区域）的活动，基于图像的现代分析技术可以提供有关神经退行性疾病（如PD）的广泛电路异常的有价值信息。由艾德尔伯格博士领导的范斯坦研究所神经科学中心的研究人员率先使用功能性脑成像和网络分析来研究帕金森病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，我们强调从统计和经验的角度严格验证疾病相关的功能模式。事实上，在定量网络测量可以被认为是疾病过程及其对治疗的反应的潜在生物标志物之前，需要高水平的测量精度。 在这项提案中，我们试图通过采用严格验证的PD相关网络来解决一些严重影响当今PD患者护理的重要问题，从而将这种方法提升到一个新的水平。项目1解决了左旋多巴诱导的运动障碍的严重临床问题，这最终影响到几乎所有的PD患者。项目2研究了多巴胺能治疗认知反应个体差异的网络基础，以期预测哪些患者在不同治疗条件下会出现不良认知副作用。项目3旨在建立一种新的基于网络的算法的可行性，以提供比目前更早，更准确的鉴别诊断。