Mechanisms of cerebral palsy recovery induced by balancing motor cortex activity

平衡运动皮层活动诱导脑瘫康复的机制

• 批准号: 8650070
• 负责人: Kathleen Margaret Friel
• 金额: $ 17.07万
• 依托单位: WINIFRED MASTERSON BURKE MED RES INST
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8650070
• 关键词: Mechanisms; cerebral; palsy; recovery; induced

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.

描述（由申请人提供）：与活动有关的竞争推动了产后早期生活期间皮质脊髓（CS）系统的发展。动物研究表明，两个半球运动皮层（ML）之间活性不平衡会导致异常CS电路形成和运动障碍。在开发过程中，两侧的重新平衡ML活性恢复了正常的CS连接和运动功能。在人体偏瘫CP中，一种以运动控制不良为特征的神经系统疾病，运动​​区域在围产期发育过程中受损。损害往往具有单方面的优势。 CS系统在受影响方面的活动降低被认为对偏瘫CP的发展至关重要。假设ML在两侧的活动之间的平衡对于恢复正常CS电路和运动技能至关重要。一种有效改善偏瘫CP儿童运动功能的治疗方法是训练受影响的一侧，并同时约束未受影响的肢体。在治疗过程中，儿童从事情感方面进行熟练的重复运动，而未受影响的一侧则受到吊索的约束。这种行为治疗通过通过训练来增加受影响的一侧的活性，同时通过约束来减少未受影响的一侧的活性来平衡ML活性。拟议的工作还将研究技能训练的不同强度如何影响恢复。在没有提高技能难度的情况下，培训专注于精确远端控制和提高技能难度的运动的训练是否比重复的任务表现更有效。了解行为改善的基本机制是迈向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，尤其是那些对有效治疗最需要损害的障碍更令人衰弱的人。该提议采用了对CP康复研究的转化方法，这是基于对CAT运动系统发展的理解。申请人将获得TMS，人类运动技能评估和分析的培训，并在动物与人之间翻译假设。通过了解恢复的机制，尤其是训练与CS系统可塑性之间的相互作用，申请人将处于独特的位置，可以转化这些机制以改善CP治疗。