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

大脑的最外层，即大脑皮层，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。在许多疾病中，包括癫痫、学习困难和精神健康障碍，都发现了大脑皮层形状和组成及其活动的异常。这些异常可能出现在我们生命之初，当时大脑皮层正在迅速发育，因此对疾病或损伤非常敏感，尤其是那些在发育过程中损害其氧气供应的疾病或损伤。然而，目前医院使用的超声或标准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产生的，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成像扫描的最新进展来了解人类早期生活中皮质发育异常是如何产生的，以及这是如何导致儿童后期行为和学习困难的。这将通过研究90名从出生到两岁半的婴儿来实现。已知这些婴儿中有60人一生中大脑皮层发育发生改变的风险很高，最有可能的原因是在正常出生前的关键时期（通过早产或患有遗传性心脏病）大脑皮层缺氧。30个将是足月出生的健康婴儿，应该有正常的发育。通过研究这三个群体，我们不仅可以获得关于皮层如何正常形成和受疾病影响的新信息，还可以潜在地确定新的治疗靶点。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，该扫描仪提供的图像比标准核磁共振扫描仪详细得多，包括有关发育中的大脑皮层形状、血液供应、氧气水平和化学物质水平的额外信息。这些复杂的信息将与大脑皮层的活动联系起来，大脑皮层在出生前后迅速变化和成熟。至关重要的是，这些将是英国使用这种扫描仪从婴儿身上获得的第一张图像，因此将代表全新的知识。在蹒跚学步的时候，孩子们会发展出新的行为，使他们能够理解周围的世界，包括与他人互动。大脑是如何改变的尚不清楚，部分原因是研究这个年龄段的儿童极具挑战性，尤其是在核磁共振扫描仪内。为了克服这个问题，我们开发了一种新的虚拟现实（VR）系统，在进行核磁共振扫描时为儿童提供有趣和身临其境的体验，因此首次可以在儿童清醒并在VR环境中玩耍时从他们那里获得大脑的详细图片。这将使我们能够通过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大脑皮层结构和活动之间的关系。它还将为我们提供有关大脑皮层活动如何使儿童与周围世界互动的全新信息。总之，这项研究的结果将以前所未有的细节提供关于人类皮层如何在我们生命之初发育的重要信息，以及关于它如何使我们在童年时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，以便它们可以被科学界更广泛地用于回答有关皮层及其发育的基本问题。这一新知识将帮助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层异常，并将有助于了解它们是如何导致学习困难、自闭症谱系条件和精神健康障碍等疾病的。

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.