Exploration of cortical structure and function in human infancy with advanced MRI methods

大脑最外层的大脑处理，称为皮质，对日常行为至关重要，包括我们如何与周围的世界和其他人互动。大脑皮质的形状和组成及其活动的异常，在许多疾病中都会被发现，包括癫痫、学习困难和精神健康障碍。这些异常很可能出现在我们生命的开始，当时大脑皮层正在快速发育，因此对疾病或伤害非常敏感，特别是那些在发育过程中危及其氧气供应的疾病或伤害。然而，目前医院使用的超声波或标准MRI扫描等方法无法提供足够的细节来确定这些皮质异常是如何发生的，或者它们与疾病过程的确切关系。因此，这项研究的目标是利用核磁共振扫描的最新进展来了解人类早期大脑皮质发育异常的原因，以及这如何导致儿童后期的行为和学习困难。这将通过对90个婴儿从出生到两岁半的研究来实现。已知这些婴儿中有60人在一生中都有大脑皮质发育改变的高风险，最有可能的原因是在正常出生前的关键时期(由于早产或患有遗传性心脏病)，大脑皮质缺乏氧气供应。30将是健康的足月出生的婴儿，他们应该有正常的发育。通过对这三组婴儿的研究，我们不仅将获得有关大脑皮质正常形成和受疾病影响的新信息，还可能确定新的治疗靶点。招募的婴儿将在出生后不久使用超高场(7特斯拉)核磁共振扫描仪进行研究，该扫描仪提供比标准核磁共振扫描仪更详细的图像，包括发育中皮质的形状、血液供应、氧气水平和化学水平的额外信息。这些复杂的信息将与大脑皮层的活动有关，大脑皮层的活动在出生前后迅速变化和成熟。至关重要的是，这将是英国第一批使用这种扫描仪从婴儿身上获取的图像，因此将代表着全新的知识。作为蹒跚学步的孩子，儿童发展出新的行为，使他们能够理解周围的世界，包括与其他人互动。目前尚不清楚大脑是如何发生这种变化的，部分原因是研究这个年龄段的儿童非常具有挑战性，特别是在核磁共振扫描仪中。为了克服这一点，我们开发了一种新的虚拟现实(VR)系统，它可以在儿童进行核磁共振扫描的同时为他们提供有趣和身临其境的体验，因此第一次可以从儿童在VR环境中清醒和玩耍时获得他们大脑的详细图片。这将使我们能够利用计算机建模和机器学习来比较婴儿时期的大脑皮层与儿童后期的结构和活动之间的关系。它还将为我们提供关于大脑皮层活动如何允许儿童与他们周围的世界互动的全新信息。总而言之，这项研究的结果将提供有关人类大脑皮质如何在我们生命之初以前所未有的详细方式发育的重要信息，以及关于它如何让我们在童年时期与他人和环境互动的新知识。我将公开分享这些信息和方法，以便科学界能够更广泛地使用它们来回答关于大脑皮层及其发育的基本问题。这一新知识将有助于医生和科学家确定哪些儿童在以后的生活中可能会有困难，设计并开始新的治疗方法来预防或治疗他们的皮质异常，并将有助于了解他们可能如何导致学习困难、自闭症谱系疾病和精神健康障碍等疾病。

Brain processing in the outermost layer of the brain, known as the cortex, is essential for everyday behaviour including how we interact with the world around us and other people. Abnormalities in the shape and composition of the cortex and its activity, are found in many illnesses including epilepsy, learning difficulties, and mental health disorders. These abnormalities likely arise at the start of our lives, when the cortex is rapidly developing and thus very senstive to diseases or injuries, especially those which compromise its supply of oxygen during development. However, current methods like ultrasound or standard MRI scans used in hospitals cannot provide enough detail to identify how these cortical abnormalities arise or their exact relationship to disease processes. The goal of this research is therefore to use the latest advances in MRI scanning to learn how abnormal cortical development can arise in early human life and how this can lead to difficulties with behaviour and learning in later childhood. This will be achieved by studying 90 babies from birth up to 2 and half years of age. 60 of these babies are known to be at high risk for having altered development of their cortex throughout their lives, most likely to a lack of oxygen delivered to the cortex during the crucial time leading up to the normal time of birth (through being born prematurely or having a genetic heart disease). 30 will be healthy babies born at full term who should have normal development. By studying these 3 groups, we will not only gain new information about how the cortex normally forms and is affected by diseases, but also potentially identify new targets for treatments.The recruited babies will be studied soon after birth using an ultra-high field (7 Tesla) MRI scanner, which provides far more detailed images than standard MRI scanners including extra information about the developing cortex's shape, blood supply, oxygen levels, and chemical levels. This complex information will then be related to the cortex's activity which is rapidly changing and maturing in the time around birth. Crucially, these will be the first images acquired from babies using this type of scanner in the UK and so will represent entirely new knowledge.As toddlers, children develop new behaviours which allow them to understand the world around them including interact with other people. How the brain changes to allow this is happen is not known, partly because it is extremely challenging to study children at this age, especially inside an MRI scanner. To overcome this, we have developed a new virtual reality (VR) system that provides a fun and immersive experience for a child whilst having a MRI scan, and so for the first time, can allow detailed pictures of the brain to be acquired from a child whilst they are awake and playing in the VR environment. This will allow us to compare how the cortex as a baby is related to its structure and activity in later childhood using computer modelling and machine learning. It will also give us completely new information about how the cortex's activity allows children to interact with the world around them. Together, the results of this research will provide important information about how the human cortex develops at the start of our lives in unprecedented detail, and new knowledge about how it allows us to interact with other people and the environment in childhood. I will openly share this information and the methods so that they can be used by the scientific community more widely to answer fundamental questions about the cortex and its development. This new knowledge will help doctors and scientists identify which children may have difficulties later in life, devise and start new treatments to prevent or treat abnormalities in their cortex, and will help to understand how they may cause conditions such as learning difficulties, autism spectrum conditions, and mental health disorders.