PEDIATRIC BRAIN INJURY RECOVERY VIA USE-DRIVEN FUNCTIONAL NETWORK REORGANIZATION

通过使用驱动的功能网络重组实现小儿脑损伤康复

基本信息

批准号：
9244075
负责人：
Nico Dosenbach
金额：
$ 17.74万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9244075
关键词：
Accelerometer Adult Affect Algorithms Attention Behavior Biological Models Biometry Biosensor Brain Brain Injuries Brain region Characteristics Child Childhood Chronic Chronic Brain Injury Clinical Cognitive Communities Complex Data Development Development Plans Dose Environment Functional Magnetic Resonance Imaging Functional disorder Goals Health Human Injury Institution Kinesiology Lead Learning Lesion Link Magnetic Resonance Imaging Maps Measures Mentors Methodology Modality Modeling Motion Motor Movement Neurologist Neuronal Plasticity Neuropsychology Neurorehabilitation Occupational Therapy Outcome Paresis Parietal Patients Pediatric Brain Injury Pediatric Neurology Pharmacotherapy Physical therapy Physicians Process Recovery Recovery of Function Recruitment Activity Rehabilitation therapy Reporting Research Research Ethics Research Personnel Resources Science Scientist Sensory Side Stroke Structure Study models System Task Performances Testing Therapeutic Time Training Treatment Factor Universities Upper Extremity Washington Work attentional control burden of illness career career development connectome constraint induced movement therapy design disability dosage functional gain functional improvement hemiparesis improved improved functioning individual patient interest motor deficit motor function improvement motor learning neglect network architecture neurofeedback neuroimaging neuromechanism news novel predictive marker predictive of treatment response public health relevance statistics stem success

项目摘要

DESCRIPTION (provided by applicant): Brain injury is the main cause auf long-term disability in children and carries the greatest disease burden out of any pediatric condition. Children with brain injury often compensate remarkably well and can develop abilities typically supported by brain structures now damaged. It is thought that much of this recovery results from the use-driven reorganization of the brain's complex functional network architecture. A better understanding of the links between activity, network organization and functional recovery is paramount to developing much needed novel neurorehabilitative treatments and improving existing ones. Therefore, it is our long-term objective to uncover the systems-level fundamentals of use-driven functional network plasticity in children with brain injury. Constraint-induced movement therapy (CIMT), a treatment for hemiparesis, provides an excellent research model for studying use-driven brain reorganization. Patients treated with CIMT have their stronger upper extremity restrained in a cast for three weeks while practicing difficult tasks with the affected side. CIMT radically alters upper extremity use, thus lastingly improving function on the treated side. The objective of the current proposal is to learn how constraint-induced movement therapy (CIMT) improves motor function in children with chronic brain injury. The specific aims are to 1) identify those functional network changes most important for improved upper extremity use, 2) establish neuropsychometric markers that predict treatment response, and 3) investigate the effect of therapy dose on outcomes. This study will test our hypothesis that much of CIMTs benefit derives from a reweighting of functional connections between the brain's attention and motor networks towards the treated side and that these changes are modulated by attentional dysfunction and therapy dose. To achieve these aims we will repeatedly assess functional networks and motor behavior with multi-modal MRI (functional, functional connectivity) and wearable accelerometer biosensors, in children undergoing CIMT. A within-subject design and novel single-subject network analytics will for the first time allow us to factor out lesion inhomogeneity and extract commonalities of therapy-driven changes across patients. This study will strongly impact health-related research by identifying beneficial connections that should be targeted with brain stimulation and neurofeedback and potentially revealing modifiable patient (attentional dysfunction) and therapy factors (dose) critical to therapy success. Candidate: Dr. Nico Dosenbach, the candidate, is a systems neuroscientist and pediatric neurologist whose prior research using functional MRI (fMRI) and functional connectivity MRI (fcMRI) has contributed significantly to the understanding of attentional control networks and functional network development. Driven by his clinical interest in advancing rehabilitative treatments for pediatric brain injury, Dr. Dosenbach is seeking additional training in movement science, developmental neuropsychology, biostatistics and clinical pediatric neurorehabilitation. Dr. Dosenbach's career goal is to improve the scientific understanding of functional network reorganization in pediatric brain injury in order to develop novel neurorehabilitative treatments, as well as to optimize current treatments. His career development plan includes training in movement science with Dr. Lang, developmental neuropsychology with Dr. Barch, biostatistics with Dr. Shannon and in clinical pediatric neurorehabilitation with Dr. Noetzel. Dr. Dosenbach's principal mentor, Dr. Bradley Schlaggar, a pediatric neurologist and developmental cognitive neuroscientist, will also provide training in movement science and developmental neuropsychology and convey the qualities and strategies of a successful, independent physician-scientist. Dr. Dosenbach will complete classes in movement science, neuropsychology, biostatistics and Research Ethics. Environment: Washington University's (WU) neuroimaging research community is one of the largest and most highly regarded and has a reputation for openness and strongly supporting young investigators. Many of the leading neuroscientists studying human functional networks, such as Drs. Marcus Raichle, Steven Petersen, Maurizio Corbetta and Bradley Schlaggar, work at WU. The Human Connectome Project (HCP) led by Dr. David Van Essen and Dr. Deanna Barch has brought even greater neuroimaging resources and expertise to WU. In addition, WU is nationally highly ranked (US News and World Report) in pediatric neurology (# 5), occupational therapy (#2) and physical therapy (#3). Overall, WU is the single best institution imaginable for Dr. Dosenbach's research career development and the success of the proposed project.

描述（由申请人提供）：脑损伤是儿童长期残疾的主要原因，并且是所有儿科疾病中最严重的疾病负担。患有脑损伤的儿童通常能够很好地补偿，并且现在可以发展通常由大脑结构支持的能力。人们认为，这种恢复很大程度上是由使用驱动的大脑复杂功能网络架构的重组造成的。更好地理解活动、网络组织和功能恢复之间的联系对于开发急需的新型神经康复治疗和改善至关重要。现有的。因此，我们的长期目标是揭示脑损伤儿童使用驱动的功能网络可塑性的系统级基础，这是一种偏瘫的治疗方法，为研究提供了一个很好的研究模型。使用驱动的大脑重组。CIMT 患者将其更强壮的上肢固定在石膏上三周，同时 CIMT 从根本上改变了上肢的使用，从而持久改善治疗侧的功能。当前提案的目的是了解约束诱导运动疗法 (CIMT) 如何改善慢性脑损伤儿童的运动功能，具体目标是 1) 确定对改善上肢使用最重要的功能网络变化，2) 建立神经心理测量。预测治疗反应的标记物，以及 3) 研究治疗剂量对结果的影响这项研究将检验我们的假设，即 CIMT 的大部分益处来自于对治疗侧大脑注意力和运动网络之间的功能连接进行重新加权。变化为实现这些目标，我们将通过多模态 MRI（功能、功能连接）和可穿戴加速度计生物传感器反复评估接受 CIMT 的儿童的功能网络和运动行为。单受试者网络分析将首次使我们能够排除病变的不均匀性并提取患者之间治疗驱动的变化的共性。这项研究将通过确定应针对大脑刺激的有益联系来强烈影响健康相关的研究。候选人：Nico Dosenbach 博士是一位系统神经科学家和儿科神经学家，他之前的研究使用功能性 MRI (fMRI) 和功能性 MRI。连接性 MRI (fcMRI) 为理解注意力控制网络和功能网络发展做出了重大贡献。出于对推进儿科脑损伤康复治疗的临床兴趣，Dosenbach 博士正在寻求额外的培训。 Dosenbach 博士拥有运动科学、发育神经心理学、生物统计学和临床儿科神经康复领域的博士学位，其职业目标是提高对儿科脑损伤功能网络重组的科学理解，以开发新的神经康复治疗方法，并优化当前的治疗方法。发展计划包括与 Lang 博士一起进行运动科学培训、与 Barch 博士一起进行发育神经心理学培训、与 Shannon 博士一起进行生物统计学培训以及与 Noetzel 博士一起进行临床儿科神经康复培训。多森巴赫的首席导师 Bradley Schlaggar 博士是一位儿科神经学家和发育认知神经科学家，他还将提供运动科学和发育神经心理学方面的培训，并传达多森巴赫博士将完成运动课程的成功、独立医师科学家的品质和策略。科学、神经心理学、生物统计学和研究伦理学环境：华盛顿大学 (WU) 的神经影像研究社区是最大、最受尊敬的社区之一，以开放性和大力支持年轻研究人员而闻名。由 Marcus Raichle 博士、Steven Petersen 博士、Maurizio Corbetta 博士和 Bradley Schlaggar 博士等研究人类功能网络的顶尖神经科学家在 David Van Essen 博士和 Deanna Barch 博士领导的人类连接组计划 (HCP) 中取得了成果。此外，WU 在儿科神经病学（#5）、职业治疗（#2）和物理治疗方面在全国排名靠前（《美国新闻与世界报道》）。 (#3) 总体而言，对于 Dosenbach 博士的研究职业发展和拟议项目的成功而言，WU 是可以想象的最佳机构。