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

 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.

 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.