Mechanisms of cerebral palsy recovery induced by balancing motor cortex activity

描述（由申请人提供）：活动依赖性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，两个半球运动皮层（Ml）之间的活动不平衡导致异常的CS回路形成和运动损伤。在发育后期重新平衡两侧的Ml活动可以恢复正常的CS连接和运动功能。人类偏瘫CP是一种以运动控制能力差为特征的神经系统疾病，运动区域在围产期发育期间受损。损害往往具有单侧优势。受损侧脑脊液系统活性降低被认为对偏瘫CP的发展至关重要。据推测，恢复两侧脑脊液活性之间的平衡对于恢复正常脑脊液回路和运动技能至关重要。一种有效改善儿童偏瘫CP运动功能的治疗方法是训练患侧，同时约束未受影响的肢体。在治疗期间，儿童从事熟练的，重复的运动与情感的一面，而未受影响的一面是用吊带限制。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来平衡Ml活动。建议的工作还将检查不同强度的技能训练如何影响恢复。关注精确远端控制和塑造增加技能难度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。了解行为改善的机制是开发新疗法的重要一步，这些新疗法可以应用于更广泛的偏瘫儿童，特别是那些最需要有效治疗的具有更强致残性损伤的儿童。该建议采用一种转化方法来研究CP康复，建立在对cat运动系统发展的理解之上。申请人将接受经颅磁刺激，人类运动技能评估和分析，以及在动物和人类之间转换假设的培训。通过了解康复机制，特别是训练和CS系统可塑性在康复中的相互作用，申请人将处于独特的位置，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.