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

• 批准号: 8996726
• 负责人: Nico Dosenbach
• 金额: $ 17.74万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 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/8996726
• 关键词: Accelerometer; Adult; Affect; Algorithms; Attention; Behavior; Biological Models; Biometry; Biosensor; Brain; Brain Injuries; Brain Mapping; Brain region; Characteristics; Child; Childhood; Chronic; Chronic Brain Injury; Clinical; Cognitive; Communities; Complex; Data; Development; Development Plans; Dose; Driving neuroplasticity; Environment; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Health; Human; Injury; Institution; Kinesiology; Lead; Learning; Lesion; Link; Magnetic Resonance Imaging; Maps; Measures; Mentors; Motion; Motor; Movement; Neurologist; Neuropsychology; Neurorehabilitation; Occupational Therapy; Outcome; Paresis; Parietal; Patients; Pediatric Brain Injury; Pediatric Neurology; Pharmacotherapy; Physical therapy; Physicians; Process; Recovery; Recovery of Function; 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 control; motor deficit; motor function improvement; motor learning; neglect; network architecture; neurofeedback; neuroimaging; neuromechanism; neuropsychological; news; novel; statistics; stem; success; treatment response; Accelerometer; Adult; Affect; Algorithms; Attention; Behavior; Biological Models; Biometry; Biosensor; Brain; Brain Injuries; Brain Mapping; Brain region; Characteristics; Child; Childhood; Chronic; Chronic Brain Injury; Clinical; Cognitive; Communities; Complex; Data; Development; Development Plans; Dose; Driving neuroplasticity; Environment; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Health; Human; Injury; Institution; Kinesiology; Lead; Learning; Lesion; Link; Magnetic Resonance Imaging; Maps; Measures; Mentors; Motion; Motor; Movement; Neurologist; Neuropsychology; Neurorehabilitation; Occupational Therapy; Outcome; Paresis; Parietal; Patients; Pediatric Brain Injury; Pediatric Neurology; Pharmacotherapy; Physical therapy; Physicians; Process; Recovery; Recovery of Function; 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 control; motor deficit; motor function improvement; motor learning; neglect; network architecture; neurofeedback; neuroimaging; neuromechanism; neuropsychological; news; novel; statistics; stem; success; treatment response

 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（由应用提供）：脑损伤是儿童的主要原因，并且在任何儿科疾病中都带有最大的疾病伯嫩。脑损伤的儿童通常可以很好地补偿，并且可以发展能够受到现在受损的脑结构支持的能力。人们认为，这种恢复的大部分是由大脑复杂功能网络体系结构的使用驱动驱动的重组引起的。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居治疗并改善现有疗法至关重要。因此，我们的长期目标是发现脑损伤儿童使用驱动的功能网络可塑性的系统级基础。约束诱导的运动疗法（CIMT）是一种偏瘫的治疗方法，为研究使用驱动脑重组提供了出色的研究模型。用CIMT治疗的患者在三周内限制了上肢更强的上肢，同时练习受影响的一侧的艰巨任务。 CIMT从根本上改变了上肢的使用，因此在处理的一侧持续改善功能。当前建议的目的是了解约束诱导的运动疗法（CIMT）如何改善慢性脑损伤儿童的运动功能。具体目的是1）确定对于改善上肢使用最重要的功能网络变化，2）建立可预测治疗反应的神经心理测定标记，以及3）研究治疗剂量对结局的影响。这项研究将检验我们的假设，即大部分CIMT益处来自大脑注意力与运动网络之间的功能连接的重量，并且这些变化是通过注意力障碍和治疗剂量调节的。为了实现这些目标，我们将在患有CIMT的儿童中反复评估使用多模式MRI（功能，功能连接）和可穿戴加速度计生物传感器的功能网络和运动行为。受试者内部设计和新型的单个受试者网络分析将首次使我们能够排除病变不均匀性，并提取患者的治疗驱动变化的共同点。这项研究将通过识别应针对大脑刺激和神经反馈的有益联系，并有可能揭示可改变的患者（注意力障碍）和治疗因素（剂量）（剂量），从而强烈影响与健康相关的研究。候选人：候选人Nico Dosenbach博士是一名系统神经科学家和儿科神经科医生，其先前使用功能性MRI（FMRI）和功能连通性MRI（FCMRI）的研究对了解注意力控制网络和功能网络的发展有了显着贡献。在他对改进小儿脑损伤康复治疗的临床兴趣的推动下，多森巴赫博士正在寻求运动科学，开发神经心理学，生物统计学和临床​​小儿神经治治疗法的其他培训。多森巴赫博士的职业目标是提高对儿科脑损伤功能网络重组的科学理解，以开发新的神经居住治疗，并优化当前治疗方法。他的职业发展计划包括与Lang博士进行运动科学培训，与Barch博士一起开发神经心理学，与Shannon博士的生物统计学以及Noetzel博士的临床小儿神经康复。多森巴赫博士的主要导师，儿科神经科医生和发展认知神经科学家布拉德利·施拉格加（Bradley Schlaggar）博士也将提供运动的培训。科学与发展神经心理学，并传达成功，独立的身体科学家的品质和策略。 Dosenbach博士将完成运动科学，神经心理学，生物统计学和研究伦理的课程。环境：华盛顿大学（WU）神经影像学研究界是最大，最受欢迎的研究界之一，并以开放性和强烈支持年轻研究者而闻名。许多研究人类功能网络的主要神经科学家，例如DRS。 Marcus Raichle，Steven Petersen，Maurizio Corbetta和Bradley Schlaggar在Wu工作。由David Van Essen博士和Deanna Barch博士领导的人类ConnectMe项目（HCP）为WU带来了更大的神经影像资源和专业知识。此外，WU在儿科神经病学（＃5），占领治疗（＃2）和物理疗法（＃3）方面是全国高度排名的（美国新闻和世界报道）。总体而言，WU是Dosenbach博士研究职业发展和拟议项目成功的最佳机构。