Measurement of locus coeruleus : noradrenergic function in the human brain and its influence on executive function

Abstract

The brainstem nucleus locus coeruleus (LC) projects to nearly the entire brain, and has the capacity to dramatically affect neural processing via release of the neurochemical noradrenaline (NE). Although recent theories of LC-NE function have postulated highly specific roles in a variety of cognitive processes, our understanding of the noradrenergic control of human cognition has been impeded by the methodological challenges inherent in studying this system in the human brain. This thesis aims to advance our understanding of human LC-NE function by exploring two core questions. The first is whether candidate indirect measures of LC activity can be validated to provide a window into human LC-NE function (Chapters 1-3). The second part of this thesis is concerned with investigating whether these measures can be specifically applied to elucidate the neural substrates and potential noradrenergie basis of performance monitoring and error awareness (Chapters 4-6). Chapter 1 begins by providing a broad overview of existing knowledge about the LC-NE system and its role in behaviour, and outlines three potential proxies for LC activity in humans: functional magnetic resonance imaging (fMRI), pupil diameter, and the P3 event-related potential (ERP).