The aim of this set of studies was to provide more insight in individual characteristics that influence care-giving abilities, in particular precursors of harsh and abusive parenting. We examined... Show moreThe aim of this set of studies was to provide more insight in individual characteristics that influence care-giving abilities, in particular precursors of harsh and abusive parenting. We examined how different subtypes of childhood abuse were related to child abuse potential in adulthood. Emotional neglect in childhood was related to child abuse potential, which is in line with earlier research showing the long-lasting effects of emotional maltreatment and neglect in childhood. With regard to the effects of oxytocin on the neural basis of parenting, we used fMRI to examine how oxytocin influenced emotion recognition using pictures of both adult and infant faces, taking experiences of maternal love withdrawal into account as potential moderator. Oxytocin enhanced neural activity in regions involved in emotion processing, such as the IFG, insula and STG. Our findings regarding the moderating role of experiences of maternal love withdrawal are inconsistent for emotion recognition in adult faces and in infant faces. Lastly, a new paradigm (LISSA) to observe sensitivity in response to standardized infant cues was developed and tested. Our results show that sensitivity can be reliably assessed using this procedure, making the LISSA a promising method for future research and clinical practice. Show less
As infants are fully dependent on their parents, correct perception and interpretation of infant signals is crucial for infant survival. It is therefore not surprising that specific brain circuits... Show moreAs infants are fully dependent on their parents, correct perception and interpretation of infant signals is crucial for infant survival. It is therefore not surprising that specific brain circuits and neuroendocrine processes have evolved to perceive infant signals correctly and to respond adequately. However, parents vary in their ability to respond to their infants in a sensitive way and several factors may be involved in parental sensitive responsiveness. One important factor influencing parenting behavior is the neuropeptide oxytocin. Of all the hormones involved in parenting and other social behaviors, oxytocin has received the most interest, as evidenced by the high number of scientific studies over the past decade (Bos, Panksepp, Bluthé, & Honk, 2012; Van IJzendoorn & Bakermans-Kranenburg, 2012). Many studies suggest that oxytocin is related to sensitive parenting (Bakermans-Kranenburg & Van IJzendoorn, 2008; Feldman, Weller, Zagoory-Sharon, & Levine, 2007), although the exact mechanism underlying this positive association is not entirely clear yet. Another factor that influences parenting behavior is adult state of mind with respect to attachment (Van IJzendoorn, 1995). In the current dissertation, the role of oxytocin and adult attachment in parenting is examined with a series of functional magnetic resonance imaging experiments. Show less
The aims of this thesis were to gain insight into specific disease processes in Huntington__s Disease (HD) and to identify biomarkers. To achieve these aims, cognitive functioning, structural brain... Show moreThe aims of this thesis were to gain insight into specific disease processes in Huntington__s Disease (HD) and to identify biomarkers. To achieve these aims, cognitive functioning, structural brain characteristics and intrinstic functional brain connectivity of premanifest and early HD subjects were examined. Cortical, subcortical and the intermediate white matter brain tissue shows evidence of structural and functional decline. We found evidence that disease processes, such as altered metabolism, excessive iron accumulation and cell loss, play a role in the changes. We conclude that changes occur throughout the brain from the earliest disease phase onwards. Hence, both premanifest and manifest HD should not be regarded as a disorder of the basal ganglia, but as a disease affecting the whole brain. Candidate biomarkers that have the potential to objectively reflect the early changes and the progressive nature of the disease are measures of subcortical atrophy, integrity of white matter pathways and of intrinsic functional brain connectivity. Iron, creatine, and N-acetylaspartate concentrations in the caudate nucleus and putamen may prove to be useful as markers of disease state for objectifying transitional disease processes from premanifest to manifest HD. Visuospatial working memory could be applied as a state marker for stage two HD. Show less
This thesis describes the development of a novel alcohol clamp, a new method to obtain stable plasma levels of alcohol and its application in CNS-research. The method might have several advantages... Show moreThis thesis describes the development of a novel alcohol clamp, a new method to obtain stable plasma levels of alcohol and its application in CNS-research. The method might have several advantages that were explored in subsequent studies described in this thesis. The stability of the alcohol clamp was used to examine functional effect profiles and time-dependence of different CNS-effects. The tests to examine these effects were chosen based upon a prior review of the literature, during which the most sensitive CNS-tests were selected. Hereafter, we studied the alcohol clamping method as a tool to compare alcohol disposition capacities between different (ethnic) populations and as a tool to compare their different CNS-responses to multiple stable alcohol levels. We also investigated whether the clamping method could be useful as a future benchmarking entity in CNS-research, based on its fMRI effects on the brain at rest and its efficacy on tremor symptoms. Finally, we employed the method in an interaction study with a compound that is in development for addictive disorders including alcoholism. This thesis has examined several examples of situations where the alcohol clamp has been a useful research instrument during alcohol research and in early drug development. Show less
The present thesis contains five experimental studies into the effects of stress on memory I healthy males. Hydrocortisone (and propranolol) administration or the induction of social stress are... Show moreThe present thesis contains five experimental studies into the effects of stress on memory I healthy males. Hydrocortisone (and propranolol) administration or the induction of social stress are used to heighten cortisol levels, and consequently to study its effects on working memory performance and memory retrieval. In addition, by using neutral and emotional distraction during working memory, effects of cortisol on emotional distraction were investigated, also with use of functional imaging. Overall, it was consistently found that high cortisol levels, by hydrocortisone administration or induced by stress, reduced the distraction by emotional irrelevant stimuli, hence improving working memory. The current findings might be relevant for patients suffering from posttraumatic stress disorder, who typically suffer from trauma-related intrusions. Show less
The research described in this thesis aimed to gain insight in risky behavior in adolescence, by examining the development of decision-making in relation to brain development. Chapter 1 describes... Show moreThe research described in this thesis aimed to gain insight in risky behavior in adolescence, by examining the development of decision-making in relation to brain development. Chapter 1 describes two existing possible explanations for adolescent risky behavior, the first explanation focuses on the development of cognitive control, and states that adolescents’ immature ability to control their impulses may bias them to act risky. The second explanation focuses on emotional/motivational processes, and suggests that adolescents engage in risky behavior because they respond stronger to the possible rewards associated with risks than children and adults do. Chapters 2, 3, and 7 describe studies on developmental changes in the processes that form the building blocks of more complex decision-making under risk; probability estimation, reward processing and working memory. Chapters 4, 5, and 6 explore the relative contributions of reward sensitivity and cognitive control to decision-making across development. This thesis shows knowledge about brain maturation can inform models of adolescent risky behavior. And that adolescent risk-taking can be explained as the consequence of the earlier maturation of reward related relative to cognitive control related brain circuitry. Show less
Top-down guidance of behavior in a complex and dynamically changing world is often based on information held in working memory. Such guidance serves to bias decision-making processes in directions... Show moreTop-down guidance of behavior in a complex and dynamically changing world is often based on information held in working memory. Such guidance serves to bias decision-making processes in directions consistent with externally set rules or internally maintained intentions. Orthogonal to this goal-driven guidance, decisions may be biased also by stimulus-driven factors, such as the automatic reactivation of episodic associations that accompanied the current stimulus in a previous instance. We investigated whether top-down and bottom-up processes account for variation in context based decision making as measured by the AX-CPT in a behavioral [1] and fMRI study [2]. Moreover, several behavioural studies have indicated that transiently induced positive affect modulates control processes in context-based decision making, generally leading to enhanced flexibility. Using ERPs in a classic AX-CPT, we studied the temporal dynamics of a positive affect induction on control processes in context-based decision making [3]. Additionally, we studied learning the associations between a situation, the response to it, and the outcome of that decision and the effect of basal ganglia modulations on this learning process by means of a Parkinson’s patient study. Studies [1] and [2] pointed out that in decisions with rapidly changing environmental demands, goal-driven preparation is often beneficial but may also hamper performance which can be overcome by applying increased control. Moreover, this top-down bias is regulated more efficiently when the specific stimulus is presented in the same context it was previously associated with, compared to when it is presented in a new and unusual context. Additionally, fMRI study shed light on the way these stimulus-driven performance changes may be represented in the brain. Study [3] showed that a positive affect induction influenced reactive and evaluative components of control (indexed by the N2 elicited by the target, and by the Error-Related Negativity elicited after incorrect responses) in an AX-CPT task, whereas cue-induced preparation and maintenance processes remained largely unaffected (as reflected in the P3b and the Contingent Negative Variation components of the ERP). The patient studies suggest that moderate dopaminergic medication and STN stimulation in Parkinson’s patients [chapter 5,6] both improve learning functions relying on caudate and putamen. However, the improvement induced by dopaminergic medication largely depended on individual patient characteristics. Show less
