BDNF Polymorphism and TBS on Practice Dependent Plasticity in Lower Limb

BDNF 多态性和 TBS 对下肢实践依赖性可塑性的影响

• 批准号: 8466765
• 负责人: Maxwell Boakye
• 金额: --
• 依托单位: VETERANS ADMIN PALO ALTO HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8466765
• 关键词: Affect; American; Ankle; Behavior; Behavioral; Brain; Codon Nucleotides; Development; Direct Costs; Effectiveness; Future; Gait; Genes; Genetic Polymorphism; Genotype; Goals; Growth Factor Gene; Healthcare Systems; Impairment; Individual; Injury; Iraq; Knowledge; Learning; Life; Long-Term Potentiation; Lower Extremity; Magnetism; Measures; Mediating; Medical; Methionine; Modeling; Motor; Motor Evoked Potentials; Movement; Muscle; Nerve Growth Factors; Neuraxis; Output; Patients; Performance; Recovery; Rehabilitation Outcome; Rehabilitation therapy; Residual state; Societies; Spinal cord injury; Spinal cord injury patients; Structure; Task Performances; Therapeutic; Training; United States; Valine; Veterans; War; abstracting; disability; healthy volunteer; improved; motor impairment; motor learning; motor skill learning; neurological recovery; preconditioning; socioeconomics; theories; tibialis anterior muscle; valylvaline; visual motor

DESCRIPTION (provided by applicant): Project Summary/Abstract There are over 10,000 new cases of SCI each year in the USA. The direct cost to society is over $8 billion each year. Despite best maximal therapy, recovery is limited with most patients having severe impairment and disability. The long-term goal of this project is to investigate the effectiveness of magnetic brain stimulation to augment behavioral gains after motor training in SCI patients. We have developed a model of activity dependent plasticity of the motor lower limb that will be used to study the effects of magnetic brain stimulation on the learning of a skilled motor task. Using this model we plan to examine two potential critical influences on the effect of brain stimulation on task learning. First we will evaluate the effects of homeostatic metaplasticity which refers to the impact a prior induction of plasticity has on the development of additional plasticity. Metaplasticity theory suggests that the effects of rehabilitation may be augmented if cortical plasticity is first reduced or downregulated using magnetic brain stimulation prior to motor training. Second we will evaluate the effects of Val66met polymorphisms involving a substitution of methionine for valine at codon 66 of the brain derived nerve growth factor (BDNF) gene. Recent studies indicate that activity dependent plasticity and homeostatic metaplasticity are significantly reduced in individuals with the Val66Met BDNF polymorphism. Therefore we plan to evaluate the effects priming inhibitory or excitatory magnetic brain stimulation has on skilled motor learning in the lower limb in healthy volunteers and in SCI patients. It is hoped that the results of this study will open up new vistas of understanding and therapeutic opportunities for rehabilitation of SCI individuals. Of the estimated 250,000 patients living in the United States with spinal cord injury, approximately 25% of these are Veterans. This number is likely to increase in the near future as a result of the Iraq war injuries. By including veterans with spinal cord injury in this study the results will be directly relevant to the large number of Veterans with spinal cord injury.

描述（由申请人提供）： 项目摘要/摘要 美国每年新增 SCI 病例超过 10,000 例。每年给社会造成的直接成本超过80亿美元。尽管有最佳的最大治疗，但由于大多数患者有严重的损伤和残疾，康复仍然有限。该项目的长期目标是研究脑磁刺激对增强 SCI 患者运动训练后行为增益的有效性。我们开发了一种运动下肢活动依赖性可塑性模型，该模型将用于研究磁脑刺激对学习熟练运动任务的影响。我们计划使用这个模型来研究大脑刺激对任务学习的影响的两个潜在关键影响。首先，我们将评估稳态变塑性的影响，这是指先前诱导可塑性对额外可塑性发展的影响。再生性理论表明，如果在运动训练之前首先使用磁脑刺激来减少或下调皮质可塑性，则康复的效果可能会增强。其次，我们将评估 Val66met 多态性的影响，涉及用蛋氨酸取代脑源性神经生长因子 (BDNF) 基因密码子 66 处的缬氨酸。最近的研究表明，具有 Val66Met BDNF 多态性的个体的活动依赖性可塑性和稳态化塑性显着降低。因此，我们计划评估启动抑制性或兴奋性磁脑刺激对健康志愿者和 SCI 患者下肢熟练运动学习的影响。希望这项研究的结果将为 SCI 患者的康复开辟新的理解和治疗机会。据估计，美国有 250,000 名脊髓损伤患者，其中约 25% 是退伍军人。由于伊拉克战争造成的伤害，这个数字在不久的将来可能会增加。通过将患有脊髓损伤的退伍军人纳入这项研究，结果将与大量患有脊髓损伤的退伍军人直接相关。