Neuroanatomical and neurofunctional brain basis of cognitive deficits in adolescent subjects who were born preterm. Structural and functional magnetic resonance study

Abstract

[eng] The general aim of this thesis is to study the cerebral basis of cognitive disturbances in adolescents with history of premature birth (PB). As previous manual volumetric investigations in PB samples, we quantitatively demonstrated the presence of volumetric abnormalities in the hippocampus. This hippocampal atrophy was related to different neuropsychological measures, such as verbal learning and long-term retention, remaining visual memory preserved. In addition to the hippocampal reductions, this work is the first to demonstrate bilateral quantitative reductions in thalamus in 22 adolescents with very PB. The second study of this thesis found positive correlations between semantic and phonetic fluency performance and the volume of thalamus, especially in the preterm group. We found that semantic and phonetic fluency showed differential thalamic-related patterns. Our third study demonstrated the presence of not only periventricular white matter (WM) injury, but also of other distal subtle WM brain abnormalities in 50 very preterm adolescents without visual evidence of WM damage. These new results support the evidence that preterm samples show WM damage further over the classical periventricular injury and provide new argument to the notion of a more generalized WM injury in immature samples. Our findings seem to involve intrahemispheric association fiber tracts. These subtle brain abnormalities could be partly related to impairments in different neuropsychological findings previously found in part of this sample. The WM integrity at adolescence seems to be related to gestational age. Until now, the impact of very preterm birth on sulcal depth development at adolescence remains unknown. In our four study we could demonstrated that orbitofrontal secondary sulci depth (developed at late gestational stages) was altered by a very PB. In contrast, the olfactory primary sulcus depth (developed at 16 weeks' gestation) was similar in the preterm and control group. Interestingly, the sulcal depth alteration was related to cortical gray matter reduction in the same region. These results provide evidences of an alteration in the normal sulci and gyri development that is not reversible during childhood. In the aim to broad the study of metabolic cerebral characteristics in a healthy sample of preterm with normal magnetic resonance imaging (MRI) we conducted a new investigation. On it, a metabolic depletion pattern in the preterm group in the medial temporal lobe was found compared to controls, just as hippocampal volume reductions. Our metabolic and volumetric findings in the preterm sample were related to gestational age. With this, we demonstrated long term neurochemical alterations in adolescents with PB and normal standard MRI, maybe providing support for either neuronal dysfunction or neuronal loss in the medial temporal lobe region. Apart from metabolic analyses, we designed a study to evaluate the brain activity in a declarative memory task in adolescents with PB and hippocampal damage, with left predominance. Our results showed a greater activation in preterm subjects compared to controls exclusively in the right hippocampus. This activation was related with the volume of the right hippocampus and with the recognition test of the functional MRI task in the premature group. There is growing evidence that abnormal development of the brain in prematurity contributes to behavioural, neurological and psychological anomalies that manifest throughout different life stages. As a whole, the integration of the studies presented in this thesis demonstrates that long term follow-up of infants born prematurely from different methodological points of view is necessary to determine neurodevelopmental and neuropsychological outcomes related to brain neuroanatomical and neurofunctional findings.