Development of functional somatosensory circuits in the human infant brain

Our senses are essential for interpreting and interact with the world around us. The brain has specialised areas dedicated to decoding different stimuli and allowing us to distinguish between a light touch, a firm squeeze or a sharp needle. However, how the brain acquires these capabilities and when, during development, remains unclear. The brain of a newborn, especially if premature, is not merely a down-sized version of that of an adult, but has different structures and functions that can change week by week in an adaptable way. Some of these early changes are necessary for the maturation of the brain, while some, especially those caused in prematurity by stimuli that do not naturally occur in the womb, may be detrimental. I plan to explore the maturation of sensory functions in premature infants. In particular, I will study the developing human brain in order to understand how we normally learn to feel different sensations and, how this is affected by prematurity and subsequent experience in intensive care. The results will contribute to fundamental knowledge of the developing human brain and help to establish methods of ensuring healthy brain maturation in premature infants.

I intend to establish a London based research program to study the mechanisms underlying the formation of early somatosensory cortical networks and the role of spontaneous and evoked neuronal activity in the developing human infant brain. The work will be cross-disciplinary involving neurophysiology, imaging, statistical analysis and neonatology at UCL, King's College London and their hospitals. I plan to record non-invasive electrophysiological activity (EEG) and the structural and functional brain correlates (MRI and fMRI) in premature and term infants of 28-42 weeks corrected gestational age in the neonatal units at UCLH and St Thomas' Hospital. I will: (i) compare the development of the EEG signal at rest with the structural and functional MRI within the same infants to establish the involvement of developing brain structures in generating the endogenous neuronal activity responsible for the initial formation of the somatosensory cortical circuits; (ii) compare the scalp topography and related cortical functional activation of different activity patterns to establish how early spontaneous and somatosensory-evoked activity shape and refine local and global cortical networks; (iii) explore the emerging organization of the somatosensory cortical maps using fMRI and sensory evoked potentials ; (iv) study the effect of early postnatal intensive care experience upon the development of cortical somatosensory function.

The primary beneficiaries will be preterm and term infants which are exposed to excessive somatosensory stimulation as part of their clinical care during a very critical period in their development.
The rate of premature births is rising in many European countries and especially in the UK, where the number of babies born at 22-25 weeks gestation and admitted to intensive care increased by 44% between 1995 and 2006. At the same time, the survival rates of these infants have increased thanks to recent advances in perinatal care, however are exposed to a greater risk of neurodevelopmental impairments, and long-term adverse outcomes. A better understanding and monitoring of the developmental trajectory of brain function in prematurity is therefore important in order to target these issues. This project will provide new insight into somatosensory processing in this group of individuals and provide a platform for studies of different neuroprotective interventions or pharmacologic agents and better patient care.
Clinicians responsible for the care of these infants will also benefit from this research: neonatologists, paediatricians, paediatric anaesthetists and all health professionals involved in the management and treatment of premature infants will have a better scientific basis upon which to devise their hospital care.
Families of these infants will benefit from an increased understanding and interest in what their babies are experiencing and the drive towards better clinical care.
In the longer term, there will be economic benefits for society in general. Increasing evidence suggests that abnormalities in the brain developmental trajectory of preterm-born infants persist through adulthood. Perinatal brain injuries or more subtle disturbances in brain maturation may underlie the development of major motor disabilities, such as cerebral palsy, and impairment of cognitive, language and social functions. Infants who are born too young or too small and who have to spend time in intensive care will therefore benefit from this research, not only at the time but also in later life. The increased understanding of how the brain processes external inputs in early life in individual infants will not only lead to better treatment and management of this vulnerable group, but also have long term benefits in terms of better health and therefore quality of life over their whole lifespan. Considering that neurodevelopmental and cognitive disabilities are a huge financial burden on society in terms of educational support and the provision of care, better health outcomes for a growing subset of the population will also potentially have a large impact on society as a whole, helping to relieve this burden.
Neuroimaging protocols, especially combining multimodal imaging techniques, could ultimately identify biomarkers to be targeted therapeutically. Moreover, neuroimaging will have an invaluable screening scope in identifying those individuals at higher risk of abnormal neurodevelopment.