The locus coeruleus, a small brainstem nucleus, is the main source of the chemical norepineprine in the brain and is involved in a number of cognitive functions as well as several neurological and... Show moreThe locus coeruleus, a small brainstem nucleus, is the main source of the chemical norepineprine in the brain and is involved in a number of cognitive functions as well as several neurological and psychiatric disorders. In this dissertation we study the human LC-NE system, the anatomy of this tiny brainstem nucleus and the involvement of the LC-NE system in stress, arousal, cognitive flexibility and physiology (hormones & pupil responses). To date, the LC-NE system has been studied in animals or ex vivo (dead donors). This dissertation is among the first ones to study and visualize the LC-NE system in humans in vivo (alive volunteers) and to approach the human cognition and the study of the LC-NE system in a holistic manner: from central neuromodulators to hormones that are secreted in the body, from anatomy to physiology and cognition. To this end, all chapters were written by taking into consideration theoretical knowledge about the LC-NE system with regard to brain anatomy, cognitive functions, neuromodulation, physiological responses, and clinical applications. Chapters 2 and 3 deal mainly with the anatomy of the LC, while Chapters 4, 5 and 6 concentrate on cognition and human physiology. Additionally Chapters 5 and 6 take also a clinical approach. Show less
Warren C.M., Tona K.D., Ouwerkerk L., Paridon J. van, Poletiek F., Steenbergen H. van, Bosch J.A., Nieuwenhuis S. 2018
The locus coeruleus (LC) is a nucleus in the brainstem, and projects widely to the forebrain where it releases norepinephrine (NE). Catecholamines such as NE do not have a unitary effect on their... Show moreThe locus coeruleus (LC) is a nucleus in the brainstem, and projects widely to the forebrain where it releases norepinephrine (NE). Catecholamines such as NE do not have a unitary effect on their target neurons, but instead influence the function of other neurotransmitters, a process that is known known as neuromodulation. By virtue of the LC’s wide projection profile and the neuromodulatory properties of NE, the LC-NE system profoundly influences neural firing characteristics and associated cognitive processes. The work presented in this thesis addresses the role of the LC-NE system in various aspects of human cognition, and the modulation of brain state. Show less
Rover, M. de; Brown, S.B.R.E.; Band, G.P.; Giltay, E.J.; Noorden, M.S. van; Wee, N.J.A. van der; Nieuwenhuis, S. 2015
The studies described in this thesis address a range of topics related to arousal, exploration, temporal attention, and the locus coeruleus-norepinephrine (LC-NE) system. Chapters 2 and 3 report... Show moreThe studies described in this thesis address a range of topics related to arousal, exploration, temporal attention, and the locus coeruleus-norepinephrine (LC-NE) system. Chapters 2 and 3 report two studies that investigated a recent theory about the role of the LC-NE system in the regulation of the exploration-exploitation trade-off. Chapter 4 reports a study on neurocognitive function in patients with dopamine-β-hydroxylase (DβH) deficiency. Chapter 5 reports an fMRI study on the neural correlates of perceptual curiosity. Chapter 6 and 7 reported several experiments investigating the effects of ‘accessory stimuli’ and temporal certainty on information processing, using scalp electrophysiology and sequential-sampling models of decision making. Taken together, the studies reported in this thesis suggest that arousal, exploration and temporal attention are closely related, which is likely due to a shared neural basis. Show less
The objective of this thesis was to validate serial position effects (SPE__S) scoring in the Rey Auditory Verbal Learning Test (RAVLT). The RAVLT is a much used clinical method for assessing memory... Show moreThe objective of this thesis was to validate serial position effects (SPE__S) scoring in the Rey Auditory Verbal Learning Test (RAVLT). The RAVLT is a much used clinical method for assessing memory performance, but the method of scoring obfuscates that two memory processes underlie free recall. This is suggested by SPE__S of single-trial free recall , although the extent of the effects are not defined. The internal and external validity of SPE__S of the RAVLT is studied. The internal validity of SPE__S is studied by means of confirmatory factor analysis. It is shown that the recency effect comprises two to three items, while the primacy effect and middle (prerecency) comprise the remaining items in a list, implying that they arise from two memory functions. Studies testing their external validity show that they play a variant role in memory impairment of Alzheimer__s disease and Major Depression patients and are found to be differentially related to stress hormone activity in these patients, and in healty human subjects. Scoring of accurately determined SPE__S in the RAVLT is a valid improvement of clinical memory assessment. As serial position effects are further found in the recall of a variety of types of information, and also found in the animal, it is argued that they are general to temporal information processing. Show less
