MRC Transition Support Award CSF Tomoki Arichi

The goal of the research is to understand how injury to the brain during the crucial stages of early life in the womb and around the time of birth can lead to life-long difficulties with brain function. Damage at this time to the specific areas of the brain which control how the body moves in particular, can result in cerebral palsy, leading to life-long difficulties such as limb paralysis or painful uncontrolled movements. There is currently no cure for cerebral palsy, perhaps due to a basic lack of knowledge about how the brain and its activity actually develop the ability to control how the body moves in the earliest stages of life. Importantly, although current medical tests (such as brain scans) can identify brain injuries in babies, they cannot accurately identify which of these babies will develop cerebral palsy later in childhood. This means that treatments cannot be started as soon as an injury is seen and that families are often left with several months of stressful uncertainty.

We know that the earliest stages of human life are important for the development of the brain and body systems that control movement as even during the earliest stages of pregnancy, babies can be seen and felt to be moving inside the womb. After birth, they continue to move in a seemingly random way until 6 months of age when they begin to make clearer controlled and purposeful movements. In addition, our research suggests that even at this early stage, the brain can alter how it controls movement through simple learning. This is all important as in this crucial early period of life, the human brain is undergoing more dramatic changes in size, shape, and structure than at any other time, and therefore there must also be enormous changes in how its activity evolves to allow these new patterns of movement.

The research therefore plans to use specialist techniques such as robotic devices and highly accurate sensors to precisely measure how babies move (both inside and outside the womb) and then identify and locate the accompanying brain activity using brain scanning. I will study how this changes as a baby grows during their first 6 months, and explore how the relationship is affected by early brain injury. I have also carried out studies to understand how brain activity and movements are altered through learning by gently stimulating the babies.

Together, the results of the studies will provide new and important insights about how the brain matures through and then controls movements in the first year. This fundamental knowledge will help doctors and scientists understand how to try and ensure healthy brain development and movements in early life. It will also help them to diagnose, potentially prevent and treat conditions like cerebral palsy which affect the control of movement in children.

The research of the fellowship and transition award uses non-invasive neuroimaging techniques to study the maturation of human brain activity related to early spontaneous motor behaviour. This is being carried out through inter-institutional (KCL, Imperial College London, UCL, INSERM, Oxford University) and multi-disciplinary collaboration (Neonatal medicine, Imaging Sciences, Bioengineering, Neuroscience). This unique comprehensive approach ensures that state-of-the-art techniques are used to answer important questions grounded in fundamental neuroscience, all being carried out within a research environment with colleagues at the forefront of their respective fields.

This will include using foetal fMRI to study the brain activity associated with emerging patterns of motor behaviour. Although challenging, across the 4 years of the fellowship, we have built a comprehensive pipeline of acquisition and processing methods (multi-slice and multi-shot acquisition sequence, dynamic B0 field correction, motion-tolerant reconstruction) and an analysis pipeline (denoising of physiological noise and motion correction). The TSA will provide entirely novel world-first insights into the earliest stages of in-utero human brain activity by systematically apply this methodology. I am also studying the neural correlates of emerging motor behaviour in early human infancy using novel sensor technology and fMRI compatible robotics. The associated brain activity is characterised with simultaneous EEG-fMRI, which provides complimentary information about both temporal (EEG) and spatial (fMRI) features. I have already performed the first-ever infant studies using this method (Arichi et al. eLife 2017) and have optimised the methods further over the fellowship.

In the TSA, I will build on this with multi-contrast tissue information and normative growth curves (developed using Gaussian Process Regression) and make the data open for dissemination to academic and clinical colleagues.