Mechanisms of cerebral palsy recovery induced by balancing motor cortex activity

描述(由申请人提供)：依赖活动的竞争在出生后早期推动皮质脊髓(CS)系统的发展。动物研究表明，两个大脑半球运动皮质(ML)的活动不平衡会导致CS回路的异常形成和运动障碍。在发育后期，重新平衡两侧的ML活动可以恢复正常的CS连接和运动功能。在人类偏瘫CP中，一种以运动控制不良为特征的神经疾病，运动区域在围产期发育过程中受到损害。损害往往具有单边优势。患侧CS系统活性降低被认为是偏瘫CP发生的关键。假设恢复两侧ML活动之间的平衡对于恢复正常的CS回路和运动技能是必不可少的。改善偏瘫CP儿童运动功能的一种有效治疗方法是对患侧进行训练，同时约束健侧肢体。在治疗期间，儿童与情感侧进行熟练的重复动作，而未受影响的一侧则用吊带约束。这种行为疗法通过训练增加患侧的活动，同时通过约束减少非患侧的活动来平衡ML的活动。这项拟议的工作还将审查不同强度的技能训练如何影响康复。集中于精确的远端控制和提高技能难度的动作训练是否比不增加技能难度的重复任务表现更有效这一重要问题尚未得到解决。了解行为改善的机制是开发新疗法的重要一步，这些疗法可以应用于更广泛的偏瘫儿童群体，特别是那些有更多衰弱障碍的儿童，他们最需要有效的治疗。这项建议采用翻译的方法来研究脑瘫康复，建立在对猫运动系统发展的理解基础上。申请者将接受TMS、人类运动技能评估和分析以及动物和人类之间的假设翻译方面的培训。通过了解康复机制，特别是训练和CS系统可塑性之间的相互作用，申请者将处于独特的地位，将这些机制转化为改善CP治疗。

DESCRIPTION (provided by applicant): Activity-dependent competition drives development of the corticospinal (CS) system during early postnatal life. Animal studies have demonstrated that imbalance of activity between the motor cortex (Ml) in the two hemispheres causes aberrant CS circuit formation and motor impairments. Rebalancing Ml activity on the two sides later in development restores normal CS connections and motor function. In human hemiplegic CP, a neurological disorder characterized by poor motor control, motor areas become damaged during perinatal development. The damage tends to have a unilateral predominance. Decreased CS system activity on the affected side is thought to be crucial to development of hemiplegic CP. It is hypothesized that restoring balance between the activity of Ml on each side is essential for restitution of normal CS circuitry and motor skill. One treatment effective in improving motor function in children with hemiplegic CP is training of the affected side with concurrent restraint of the unaffected limb. During treatment, children engage in skilled, repetitive movements with the affective side, while the unaffected side is restrained with a sling. This behavioral treatment balances Ml activity by increasing activity of the affected side through training while decreasing activity of the unaffected side through restraint. The proposed work will also examine how different intensities of skill training influence recovery. The important issue of whether training of movements focusing on precise distal control and shaping of increasing skill difficulty is more effective than repetitive task performance without increasing skill difficulty has not been addressed. Understanding the mechanisms underlying behavioral improvements is an important step towards developing new therapies that can be applied to a broader population of children with hemiplegia, especially those with more debilitating impairments who have the greatest need for an effective treatment. This proposal takes a translational approach to the study of CP rehabilitation, built upon an understanding of the development of the cat motor system. The applicant will obtain training in TMS, human motor skill assessment and analysis, and translating hypotheses between the animal and the human. By understanding the mechanisms of recovery, particularly the interplay between training and CS system plasticity in recovery, the applicant will be in the unique position to translate these mechanisms to improve CP treatment.