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: 7589377
• 负责人: Kathleen Margaret Friel
• 金额: $ 17.07万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7589377
• 关键词: Address; Affect; Affective; Anatomy; Animals; Area; Automobile Driving; Behavior; Behavior Therapy; Behavioral; Cerebral Palsy; Child; Childhood; Contralateral; Development; Distal; Effectiveness; Equilibrium; Felis catus; Forelimb; Hemiplegia; Human; Impairment; Incidence; Individual; Ipsilateral; Life; Limb structure; Live Birth; Magnetism; Manuals; Maps; Modeling; Motor; Motor Cortex; Motor Skills; Movement; Neurons; Numbers; Outcome; Perinatal; Physiology; Population; Positioning Attribute; Principal Investigator; Protocols documentation; Recovery; Rehabilitation therapy; Role; Shapes; Side; Spastic Hemiplegias; Structure; System; Task Performances; Thinking; Training; Translating; Upper arm; Week; Work; critical developmental period; disability; improved; motor control; motor impairment; nervous system disorder; postnatal; programs; response; restoration; restraint; size; skills; skills training; translational approach

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）：活动依赖性竞争驱动出生后早期皮质脊髓（CS）系统的发育。动物研究表明，两个半球运动皮层 (M1) 之间的活动不平衡会导致 CS 回路形成异常和运动障碍。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。人类偏瘫性脑瘫是一种以运动控制能力差为特征的神经系统疾病，其运动区域在围产期发育过程中受损。损害往往是单方面的。患侧 CS 系统活动的减少被认为对于偏瘫性 CP 的发展至关重要。据推测，恢复每侧 M1 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。改善偏瘫脑瘫儿童运动功能的一种有效治疗方法是训练患侧并同时约束未受影响的肢体。在治疗过程中，儿童用受影响的一侧进行熟练的重复运动，而未受影响的一侧则用吊带固定。这种行为治疗通过训练增加受影响一侧的活动，同时通过约束减少未受影响一侧的活动，从而平衡 M1 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。专注于精确远端控制和塑造增加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。了解行为改善背后的机制是开发新疗法的重要一步，这些新疗法可应用于更广泛的偏瘫儿童群体，特别是那些最需要有效治疗的衰弱性损伤更严重的儿童。该提案基于对猫运动系统发展的理解，采用转化方法来研究脑瘫康复。申请人将获得 TMS、人类运动技能评估和分析以及在动物和人类之间翻译假设的培训。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地位，可以将这些机制转化为改善 CP 治疗。