Investigation of fetal brain function and implications for early child development

Abstract

During the last few decades, the “Theory of Developmental Origins of Health and Disease” has increased the interest in early exogenous influences on the life-time prevalence of non-communicable diseases. From conception onwards, sensitive periods in development are discussed. During these phases, the organism is susceptible to exogenous influences that can alter organs and their function. Especially the developing brain, an organ characterized by a high degree of plasticity and mutually affected by genetic preconditions and exogenous factors, is in the focus of interest. It influences numerous physiological processes during the entire life span, determines behavior and is thus closely linked to the preservation of health and to the development of diseases. Fetal magnetoencephalography enables to monitor brain function as early on as in utero and provides an unique opportunity to evaluate the course and performance of functional brain development from a very early age. The first study of this thesis systematically reviewed studies of event-related brain responses and habituation during child development. Neurophysiological measurements of event-related brain responses, their age-related changes and the role of neurophysiological habituation assessment for the evaluation of higher cognitive processes during child development were presented and critically discussed. As a result, age-related changes in event-related brain responses can be postulated. However, both event-related brain response studies and habituation studies had a wide diversity of subjects’ ages and stimulation protocols, and only very few longitudinal studies exist. A general conclusion is thereby limited and future studies should focus on longitudinal designs and methodical standardization. In line with these recommendations, the second study evaluated event-related brain responses to syllables arranged in a habituation paradigm recorded by fetal magnetoencephalography in fetuses and, later, in infants (0-3 months of age). Early syllable processing and basic learning abilities were investigated in both age groups with a comparable stimulation procedure. Neurophysiological habituation was shown in neither fetuses nor infants. In infants, however, a discriminative neural response to an inserted deviant syllable was observed. These results may be important for the investigation of early cognitive learning processes and may contribute to a better understanding of language acquisition mechanisms. In the third study, the impact of intrauterine growth restriction on the development of infantile brain function was investigated. Event-related brain responses in three study groups (fetuses with a pathological intrauterine growth restriction, fetuses that were too small for their gestational age and fetuses with an intrauterine growth appropriate to their gestational age) were recorded by fetal magnetoencephalography. A follow-up assessment of the participants with a psychological developmental test (Bayley Scales of Infant Development, Second Edition) was implemented after two years to examine long-term cognitive and motor development. Latencies of event-related brain responses to visual stimuli were longer in intrauterine growth-restricted fetuses than in the small-for-gestational-age- and appropriate-for-gestational-age group, but this difference did not reach statistical significance. In the follow-up assessment, cognitive capabilities of the intrauterine growth-restricted group were significantly lower than in former small-for-gestational-age and former appropriate-for-gestational-age infants. These findings confirm the hypothesis that intrauterine growth-restriction is a risk factor for cognitive development and future investigations should analyze the underlying neuropathological mechanisms and follow the development of intrauterine growth-restricted children to implement potential intervention strategies.