Very early brain damage leads to dopamine dysregulation in adulthood

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

In this thesis I aim to delineate some of the neurochemical and neuroanatomical alterations associated with very preterm birth (<32 weeks of gestation), which could help to elucidate the mechanisms conferring an increased vulnerability to develop cognitive and psychiatric problems in preterm-born individuals. I am particularly interested in studying the long-term effects of prematurity-related brain injuries (PBI), such as periventricular haemorrhage and ventricular dilatation, that are likely to affect neurodevelopment due to their impact on neighbouring developing and migrating cellular structures and thus likely to be of relevance to later life cognitive abilities and mental health.

I studied a cohort of individuals born very preterm (mean age 30 years) who were admitted consecutively to the Neonatal Unit of University College London Hospital in 1979-1984. These individuals have been taking part in a longitudinal study for their entire lives, allowing access to detailed neonatal and developmental information.

This thesis presents and integrates findings from a number of neuroimaging studies in combination with neurodevelopmental outcome data. Individuals who suffered PBI had reduced striatal dopamine synthesis capacity, particularly in the caudate nucleus. Dopamine function was significantly correlated with measures of whole-brain white matter organisation and corticostriatal tract microstructure, perhaps reflecting a role of dopamine in the development of brain connectivity. Individuals who suffered PBI also had reduced volume of a frontoparietal tract involved in working memory. This structural alteration was related to apparent disinhibition of perisylvian areas during working memory performance, which was positively associated with working memory function in this group, suggesting a possible novel compensatory adaptation.

This work indicates various ways in which VPT birth and PBI can have long term effects on the anatomy and function of the brain. Furthermore, it provides new evidence of the brain’s intrinsic means of adapting to early injury and shows how some of these adaptations may support cognitive functions that are commonly affected following VPT birth and PBI.
Date of Award1 Jul 2015
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorChiara Nosarti (Supervisor) & Oliver Howes (Supervisor)

Cite this

'