Microscopic brain white matter alterations in premature born adults

• Applicant: Dr. Aurore Menegaux
• Subject Area: Human Cognitive and Systems Neuroscience ; Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 505139976

Premature birth affects the neurocognitive development of individuals with lasting effects on, for example, IQ, which is on average 12 points lower in very premature born young adults. The current proposal addresses the question of how these unfavorable effects arise, with special focus on microscopic white matter brain development and the modulatory impact of both birth-related impairments and social environmental factors during development.Hypoxic-ischemic adverse events of premature birth disturb pre-oligodendrocyte maturation with secondary neuroinflammation and lastingly impair white matter development. This model is so far supported by microscopic post-mortem evidence in premature born infants and diffusion-weighted imaging studies in premature born children, adolescents, and young adults, observing aberrant fractional anisotropy (FA) of white matter water diffusion. However, FA is unspecific to underpinning microscopic changes such as neurite density or myelin content, leaving the question open which microscopic features are lastingly altered in prematurity. Furthermore, white matter development is remarkably prolonged in humans into fourth decade of life with critical peaks for several microscopic white matter features. Therefore, the first aim of our proposal is to investigate microscopic white matter changes of very premature born adults of fourth life decade using advanced microscopic white matter MRI combined with biophysical modelling.Previous FA imaging studies demonstrated that white matter changes mediate impaired cognitive performance after premature birth. Furthermore, very recent studies demonstrated a more complex model of cognitive development in prematurity with substantially modulatory effects on IQ changes of both the degree of birth-related impairments and the quality of social environmental factors during development such as socio-economic status or parent-infant relationship. Therefore, the second aim of the proposal is to study how microscopic white matter changes mediate IQ outcomes in mid-aged very premature born adults and how this mediation is modulated by birth-related and social environmental factors.Taken together, the proposal will provide a complex neurocognitive developmental model of human prematurity into the fourth decade of life centered around microscopic white matter development and modulatory birth-related and social environmental factors. As a result, this model will not only fill our knowledge gap about white matter development but also give first insights about potential stratifying effects of microscopic white matter development in prematurity, with implications for more targeted treatment.

• DFG Programme: Research Grants