MOTOR LEARNING AND COORDINATION IN HIGH RISK INFANTS

描述（由申请人提供）：由于早产儿数量不断增加和长期残疾的风险，早产儿仍然是一个全国性的公共卫生问题。本项目的目的是确定功能障碍高危早产儿的运动学习和协调障碍水平（目的1和2），并通过颅超声、定量脑MRI和随访临床检查将这些行为障碍与神经功能障碍联系起来（目的3）。该项目重点关注极低体重（1000-1500克，VLBW）和极低体重（<1000克，ELBW）的早产儿，因为高达50%的这些婴儿将表现出一种或多种主要的神经发育障碍，如脑瘫和发育协调障碍相关的障碍。围产期脑损伤是这些损伤的基础，并且很容易通过先进的颅脑超声（CUS）和磁共振成像（MRI）成像技术检测到。在成年神经学人群中，这种脑成像通常与运动学习和协调评估有关。由此产生的脑-运动行为关系为基础科学提供了信息，并促进了成人神经康复。儿科临床医生缺乏对非常年幼的婴儿的运动学习和协调评估。因此，人们对婴儿群体中大脑-运动行为的关系知之甚少。更重要的是，临床医生和家庭往往被迫等到第二年，才会在大肌肉运动里程碑的持续延迟前确认婴儿时期注意到的脑损伤的功能结果。在最近的一系列研究中，我们使用了发育科学中两种成熟的学习范式——眨眼条件反射范式和移动范式，来研究足月健康婴儿和VLBW早产儿的运动学习和协调障碍（Heathcock et al. 2004, 2005; Herbert et al. 2004）。在本提案中，我们直接扩展了我们之前的工作，以测试关于VLBW和更高风险的ELBW早产儿在3个月和6个月时的运动学习和协调的特定假设（目的1和2）。我们还会将其与出生时的CUS， 6个月时的MRI以及3至24个月期间每3个月的临床检查联系起来。成像将重点关注早产儿常见的神经学诊断，如PVL和IVH，以及运动学习和协调相关区域（小脑、基底神经节、海马、额叶和顶叶灰质和白质）的变化，其中许多通常在高危早产儿中被报道为受损。这些结果将为幼儿的标准化评估提供基础，并将其与特定的神经损伤联系起来。这些标准使儿科临床医生能够更好地理解生命最初几个月神经损伤和功能障碍之间的复杂关系。

DESCRIPTION (provided by applicant): Infants born preterm continue to be a national public health concern due to their rising numbers and risk for long term disability. The purpose of this project is to determine the level of motor learning and coordination impairment in preterm infants at high risk for functional disabilities (Aims 1 and 2), and relate these behavioral impairments to their neurological impairment as assessed by cranial ultrasound, quantitative brain MRI and follow-up clinical examinations (Aim 3). The project focuses on preterm infants born at very low weight (1000-1500 grams, VLBW) and extremely low weight (<1000grams, ELBW) as up to 50% of these infants will display one or more major neurodevelopmental impairments such as those associated with cerebral palsy and developmental coordination disorder. Perinatal brain injuries underlie these impairments and are readily detected by advancing imaging technology of cranial ultrasound (CUS) and magnetic resonance imaging (MRI). In adult neurological populations, such brain imaging is routinely linked to motor learning and coordination assessments. The resulting brain-motor behavior relationships inform basic science and advance adult neurorehabilitation. Pediatric clinicians lack motor learning and coordination assessments for very young infants. As a result, extremely little is known about the brain-motor behavior relationships in infant populations. More importantly, clinicians and families are often forced to wait into the 2nd year before persistent delays in gross motor milestones confirm the functional results of brain impairments noted in infancy. In a recent series of studies, we used the Eye Blink Conditioning paradigm and the Mobile paradigm, two well established learning paradigms from developmental science, to study motor learning and coordination impairments in both full-term healthy infants and VLBW preterm infants (Heathcock et al 2004, 2005; Herbert et al., 2004). In this proposal, we directly extend our previous work to test specific hypotheses regarding motor learning and coordination in both VLBW and the even higher risk ELBW preterm infants at 3 and 6 months of age (Aim 1 and 2). We will also relate this to CUS at birth, MRI at 6 months and clinical examinations every 3rd month from 3 to 24 months of age. Imaging will focus on common neurological diagnoses in preterm infants such as PVL and IVH, as well as changes in motor learning and coordination-related areas (cerebellum, basal ganglia, hippocampus, frontal and parietal gray and white matter), many of which are commonly reported as impaired in high risk preterm infants. These results will provide the foundation whereby standardized assessments for the very young infant may be developed and linked with specific neurological injury. Such standards enable pediatric clinicians to better understand the complex relationship between neurological injury and functional impairment in the first months of life.