Mechanisms of cerebral palsy recovery induced by balancing motor cortex activity

描述（由申请人提供）：出生后早期，活动依赖性竞争驱动皮质脊髓（CS）系统的发育。动物研究已经证明，两个半球中的运动皮层（Ml）之间的活动不平衡导致异常CS回路形成和运动损伤。在发育后期重新平衡两侧的Ml活动恢复正常的CS连接和运动功能。在人类偏瘫型CP中，一种以运动控制不良为特征的神经系统疾病，运动区域在围产期发育期间受损。损害往往具有单方面的优势。受影响侧的CS系统活动减少被认为是偏瘫CP发展的关键。假设恢复每侧Ml活动之间的平衡对于恢复正常CS电路和运动技能是必不可少的。一种有效改善偏瘫型脑瘫儿童运动功能的治疗方法是患侧训练，同时约束健侧肢体。在治疗过程中，儿童与情感侧进行熟练的重复运动，而未受影响的一侧则用吊带限制。这种行为治疗通过训练增加受影响侧的活动，同时通过约束减少未受影响侧的活动，从而平衡Ml活动。拟议的工作还将研究不同强度的技能训练如何影响恢复。重点关注精确远端控制和增加技能难度的成形的运动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。了解行为改善的潜在机制是开发新疗法的重要一步，该疗法可应用于更广泛的偏瘫儿童人群，特别是那些最需要有效治疗的更衰弱的障碍儿童。这项建议需要一个转化的方法来研究CP康复，建立在对猫运动系统的发展的理解。申请人将获得TMS、人类运动技能评估和分析以及动物和人类之间假设翻译的培训。通过了解恢复机制，特别是恢复过程中训练与CS系统可塑性之间的相互作用，申请人将处于独特的位置，可以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.