BDNF Polymorphism and TBS on Practice Dependent Plasticity in Lower Limb

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。由于伊拉克战争受伤，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。

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.