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: 7871220
• 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/7871220
• 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. PUBLIC HEALTH RELEVANCE: Project Narrative Spinal cord injury affects thousands of Americans each year and exerts a significant medical and socioeconomic burden on the health care system. Of the estimated 250,000 SCI patients living in the US, approximately 25% are Veterans. The study results will be directly relevant to the large number of Veterans with spinal cord injury. Therapeutic opportunities for SCI have been limited and new avenues of therapies are desperately needed to improve recovery after SCI. Recovery from SCI may be related to changes in brain structure and function called plasticity. In this project we hope to show that magnetic brain stimulation, known to change brain plasticity, is an effective way to facilitate or augment behavioral gains after rehabilitation. We also hope to elucidate the impact of specific genes implicated in cortical plasticity on motor training after injury and on the impact of brain stimulation on motor training. It is hoped that the results of this study will open up new vistas of understanding and therapeutic opportunities for rehabilitation of SCI individuals.

描述（由申请人提供）： 在美国每年有超过10，000例新的SCI病例。每年给社会造成的直接损失超过80亿美元。尽管最好的最大治疗，恢复是有限的，大多数患者有严重的损害和残疾。本项目的长期目标是研究脑磁刺激对SCI患者运动训练后行为增益的有效性。我们已经开发了一个模型的活动依赖可塑性的运动下肢，将被用来研究磁脑刺激的影响，学习一个熟练的运动任务。使用这个模型，我们计划研究两个潜在的关键影响的脑刺激任务学习的效果。首先，我们将评估稳态亚可塑性的影响，这是指先前诱导的可塑性对额外可塑性发展的影响。后可塑性理论表明，如果在运动训练之前使用磁脑刺激首先降低或下调皮质可塑性，康复的效果可能会增强。第二，我们将评估Val66met多态性的影响，包括脑源性神经生长因子（BDNF）基因密码子66处的蛋氨酸取代缬氨酸。最近的研究表明，活动依赖的可塑性和稳态的metaplasticity显着降低与Val66Met BDNF多态性的个人。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。我们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，生活在美国的25万脊髓损伤患者中，约25%是退伍军人。由于伊拉克战争的伤害，这一数字在不久的将来可能会增加。通过将脊髓损伤的退伍军人纳入本研究，结果将与大量脊髓损伤的退伍军人直接相关。 公共卫生关系： 脊髓损伤每年影响成千上万的美国人，并对医疗保健系统造成重大的医疗和社会经济负担。据估计，生活在美国的250，000名SCI患者中，约25%是退伍军人。研究结果将直接关系到大量的退伍军人与脊髓损伤。SCI的治疗机会有限，迫切需要新的治疗方法来改善SCI后的恢复。SCI的恢复可能与大脑结构和功能的变化有关，称为可塑性。在这个项目中，我们希望表明，磁脑刺激，已知改变大脑的可塑性，是一种有效的方法，以促进或增强康复后的行为收益。我们还希望阐明与皮层可塑性有关的特定基因对损伤后运动训练的影响以及脑刺激对运动训练的影响。我们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。