Preterm birth and the burden of long-term cognitive impairments: neural mediators of risk and resilience

• Applicant: Privatdozent Dr. Christian Sorg, since 6/2020
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 432285169

Why do some preterm born individuals develop into normally functioning adults while others suffer from life-long cognitive and behavioral impairments? To unravel this problem, it is crucial to understand how the brain translates early injurious (‘risk factors’) and protective (‘resilience factors’) events associated with preterm birth into long-term cognitive impairments and preserved cognitive abilities, respectively. Therefore, in the proposed project, we will comprehensively investigate how the brain mediates the association of neonatal risk/resilience factors and long-term cognitive development. For that purpose, we will analyze previously collected clinical, cognitive and multimodal magnetic resonance imaging (MRI) data from a large sample of preterm (N=104) and term (N=110) born adults within an epidemiological study from birth to adulthood, the Bavarian Longitudinal Study. Clinical variables were collected during the first weeks of life. Cognitive (full-scale IQ) and MRI data (T1-weigthed MRI, diffusion-weighted MRI, resting-state functional MRI) were assessed in young adulthood (at 25 to 27 years of age). We will conduct distinct mediation models using different combinations of risk/resilience factors, MRI data, and cognitive abilities in adulthood. For example, due to its lasting clinical relevance in modern neonatal intensive care particularly for very and extremely preterm infants, the duration of mechanical ventilation will represent a paradigmatic critical risk factor, while a good parent-infant relationship will represent resilience factors. Candidate brain systems are the cholinergic basal forebrain, the thalamo-cortical system, lateral and medial systems of the temporal lobe, as well as the default mode network. For instance, we will investigate whether prematurity-related differences in thalamo-cortical connectivity mediate the association between the duration of mechanical ventilation and cognitive impairments in adulthood. Here, we are asking for funding to conduct the advanced analyses regarding the triangular relationship between neonatal risk/resilience factors, long-term cognitive outcomes and associated brain alterations. This highly cost-effective, low-risk project will not only identify brain systems that are causally involved in preterm born individuals’ cognitive impairments, it will further provide biomarkers to understand why some preterm born individuals develop into normally functioning adults despite adverse events related to prematurity. Our findings will have important implications for the development and testing of future therapies aimed at preventing cognitive underachievement in preterm born individuals.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Dr. Josef Georg Bäuml, until 6/2020