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

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.

The research of this senior fellowship will characterise and model how the human cortex develops in early human infancy and thus provides a framework for complex human behaviour. This will involve state-of-the-art neuroimaging and technology to answer important questions which are grounded in fundamental neuroscience, all within a unique research environment with colleagues at the forefront of their respective fields.

Current neuroimaging methods lack the spatial resolution for detailed study of the human cortex in the perinatal period and also sensitivity to understand the critical role of key physiological factors like vascular development and tissue oxygenation. These limitations can be overcome for the first time by MR imaging at ultra-high field (7 Tesla) which offers marked gains in signal-to-noise ratio, enabling the acquisition of detailed brain images with high spatial resolution and increased contrast for signal related to magnetic susceptibility (such as related to brain activity and oxygenation). This fellowship will involve systematic data collection through our world-leading (the first in the UK) 7T neonatal imaging programme which includes novel MR acquisition sequence development, MRI compatible technology and fMRI compatible robotics, and cutting-edge image processing methods. The resulting high quality data will be used to characterise how the cortex grows and develops in the neonatal period in unprecedented detail, and for the first time, to precisely model the relationship between this process with developmental changes in brain activity (with high resolution functional MRI) and physiology (vascular density, local tissue oxygenation, biochemical composition). I will relate this to later cortical structure and function by acquiring data in childhood using our novel MRI compatible Virtual Reality system, which allows both imaging without an anaesthetic and a novel means for studying brain activity during interactive and immersive activities.