This thesis generated insights into the neural and affective signatures of connectedness between parents and adolescents and between people in general, which is operationalized by responses to eye... Show moreThis thesis generated insights into the neural and affective signatures of connectedness between parents and adolescents and between people in general, which is operationalized by responses to eye contact and empathy. Overall, our findings show that during adolescence, parents are still highly attuned to their child at the neural and affective level. In addition, adolescents report to feel more connected with their parents than with unknown others, although this was not directly reflected in stronger neural responses. Another interesting finding is that making eye contact for a prolonged period generally enhanced the socio-emotional connection between people, both between parents and adolescents and with unknown others. For individuals with a history of CEM and depressed adolescents eye contact is less socially rewarding, however, and does not seem to foster a stronger connectedness with others. Studying the psychobiological underpinnings of affiliative bonding, including the parent-adolescent bond, brings us a step closer to unraveling how such bonds are established and maintained during adolescence. And even more important: Once we know how these bonds are established, we might be better able to modify and repair these bonds in situations in which they for some reason got disrupted. Show less
Complex Regional Pain Syndrome (CRPS) is a severely disabling pain syndrome. Patients report a poorer quality of life than patients with other chronic pain conditions, particularly in the physical... Show moreComplex Regional Pain Syndrome (CRPS) is a severely disabling pain syndrome. Patients report a poorer quality of life than patients with other chronic pain conditions, particularly in the physical domains (chapter 2). Sex differences are small, although male patients experience a higher psychological burden than female CRPS patients (chapter 3).Considering the pathophysiology CRPS, we could not reproduce previous MRI findings of altered brain function and structure in rest (Chapter 4). We did find increased salience detecting during the application of a painful stimulus with opposite activation of brain regions involved in reducing the affected burden of pain (chapter 5). Lastly, cortical motor activations during motor tasks differ from previously published results in patients with functional movement disorders (chapter 6). Show less
This thesis describes brain function and brain responses that play a role in the maintenance of energy balance. The responses of the brain to various factors influencing energy balance in... Show moreThis thesis describes brain function and brain responses that play a role in the maintenance of energy balance. The responses of the brain to various factors influencing energy balance in healthy lean participants are described. The factors investigated include the effects of the ingestion various sugars and sweeteners, the effects of consumption temperature, the effect of added flavoring and the effect of hormones involved in energy balance. Furthermore, brain function is investigated in conditions showing a disrupted energy balance by determining brain responses in both Anorexia Nervosa and obesity. Show less
PurposeSystems for magnetic resonance (MR-) guided radiotherapy enable daily MR imaging of cancer patients during treatment, which is of interest for treatment response monitoring and biomarker... Show morePurposeSystems for magnetic resonance (MR-) guided radiotherapy enable daily MR imaging of cancer patients during treatment, which is of interest for treatment response monitoring and biomarker discovery using quantitative MRI (qMRI). Here, the performance of a 1.5 T MR-linac regarding qMRI was assessed on phantoms. Additionally, we show the feasibility of qMRI in a prostate cancer patient on this system for the first time.Materials and methodsFour 1.5 T MR-linac systems from four institutes were included in this study. T1 and T2 relaxation times, and apparent diffusion coefficient (ADC) maps, as well as dynamic contrast enhanced (DCE) images were acquired. Bland–Altman statistics were used, and accuracy, repeatability, and reproducibility were determined.ResultsMedian accuracy for T1 ranged over the four systems from 2.7 to 14.3%, for T2 from 10.4 to 14.1%, and for ADC from 1.9 to 2.7%. For DCE images, the accuracy ranged from 12.8 to 35.8% for a gadolinium concentration of 0.5 mM and deteriorated for higher concentrations. Median short-term repeatability for T1 ranged from 0.6 to 5.1%, for T2 from 0.4 to 1.2%, and for ADC from 1.3 to 2.2%. DCE acquisitions showed a coefficient of variation of 0.1–0.6% in the signal intensity. Long-term repeatability was 1.8% for T1, 1.4% for T2, 1.7% for ADC, and 17.9% for DCE. Reproducibility was 11.2% for T1, 2.9% for T2, 2.2% for ADC, and 18.4% for DCE.ConclusionThese results indicate that qMRI on the Unity MR-linac is feasible, accurate, and repeatable which is promising for treatment response monitoring and treatment plan adaptation based on daily qMRI. Show less
Although the outcomes of our daily-life risky decisions are often unknown (e.g., receiving or not receiving a fine after running a red light), the probabilities of these outcomes may also vary in... Show moreAlthough the outcomes of our daily-life risky decisions are often unknown (e.g., receiving or not receiving a fine after running a red light), the probabilities of these outcomes may also vary in uncertainty. That is, the probabilities may be known (risk) or unknown (ambiguity), which influences risk taking behavior to a great extent. A developmental phase associated with heightened risk taking is adolescence, yet how adolescents process risk and ambiguity, and the relation with real-life risk taking, remain elusive. Moreover, individual differences in observed risk taking behavior remain largely overlooked. In this PhD thesis risk and ambiguity processing in adolescents were decomposed using behavioral economics and fMRI, and related to real-life risk taking. The results indicated that risk and ambiguity differentially impact risk-taking behavior, and are processed by different neural mechanisms. In addition, individual variation in task-related and real-life risk taking highlighted that adolescence is not a phase of heightened risk taking for everyone. Moreover, it was found that real-life risk-taking and prosocial tendencies were both predicted by fun seeking, suggesting this trait may make individuals differentially susceptible to positive or negative outcomes. Together, this thesis points towards a more nuanced perspective on adolescent risk taking and its underlying components. Show less
The aim of this thesis is to increase our knowledge of individual differences in the neural processing and appraisal of children’s faces that differ in their degree of resemblance with the... Show moreThe aim of this thesis is to increase our knowledge of individual differences in the neural processing and appraisal of children’s faces that differ in their degree of resemblance with the participant’s face. Chapter 2 focuses on participants’ neural responses to child faces that differ in their degree of resemblance with the participant’s face, both in neutral and threatening contexts. Moderating effects of love withdrawal and empathy are examined to explore associations between participants’ experiences with love withdrawal, their levels of empathy and their neural processing of facial resemblance. In Chapter 3, we examine how participants’ evaluations of the different child faces on a range of negative and positive criteria are affected by children’s degree of resemblance with the participant’s face. In addition, we explore how experiences of love withdrawal and FFA activity moderate participants’ appraisal of these child faces. Chapter 4 focuses on the test-retest reliability of the fMRI data acquired during the face processing paradigm we used to examine the effects of facial resemblance on participants’ brain activity. Show less
The various models proposed for the mediation of auditory verbal hallucinations (AVH) implicate a considerable number of brain areas and mechanisms. To establish which of those mechanisms are... Show moreThe various models proposed for the mediation of auditory verbal hallucinations (AVH) implicate a considerable number of brain areas and mechanisms. To establish which of those mechanisms are actually involved in the mediation of AVH, we developed a novel method to analyze functional MRI data, which allows for the detection of the full network of mutually interacting brain states, and the identification of those states that are relevant to the mediation of AVH, while applying a minimum number of preconceived assumptions. This method is comparable to the draining of a pond to lay bare the full ecosystem that affects the presence of a particular fish species. We used this model to analyze the fMRI data of 85 psychotic patients experiencing AVH. The data were decomposed into 98 independent components (ICs) representing all major functions active in the brain during scanning. ICs involved in mediating AVH were identified by associating their time series with the hallucination time series as provided by subjects within the scanner. Using graph theory, a network of interacting ICs was created, which was clustered into IC modules. We used causal reasoning software to determine the direction of links in this network, and discover the chain of events that leads to the conscious experience of hallucinations. Hallucinatory activity was linked to three of the seven IC clusters and 11 of the 98 ICs. ICs with the most influential roles in producing AVH-related activity were those within the so-called salience network (comprising the anterior cingulate gyrus, right insula, Broca's homologue, premotor cortex, and supramarginal gyrus). Broca's area and the cerebellar regions were significantly, but more distantly involved in the mediation of AVH. These results support the notion that AVH are largely mediated by the salience network. We therefore propose that the mediation of AVH in the context of schizophrenia spectrum disorders involves the attribution of an excess of negative salience by anterior-cingulate areas to linguistic input from Broca's right homologue, followed by subsequent processing errors in areas further ‘downstream’ the causal chain of events. We provide a detailed account of the origin of AVH for this patient group, and make suggestions for selective interventions directed at the most relevant brain areas. Show less
Coppen, E.M.; Grond, J. van der; Hafkemeijer, A.; Barkey Wolf, J.J.H.; Roos, R.A.C. 2018
Huntington's disease (HD) is an autosomal‐dominant inherited neurodegenerative disorder characterized by motor disturbances, psychiatric disturbances, and cognitive impairment. Visual cognitive... Show moreHuntington's disease (HD) is an autosomal‐dominant inherited neurodegenerative disorder characterized by motor disturbances, psychiatric disturbances, and cognitive impairment. Visual cognitive deficits and atrophy of the posterior cerebral cortex are additionally present in early disease stages. This study aimed to assess the extent of structural and functional brain alterations of the visual cortex in HD gene carriers using different neuroimaging modalities. Structural and functional magnetic resonance imaging data were acquired from 18 healthy controls, 21 premanifest, and 20 manifest HD gene carriers. Voxel‐based morphometry (VBM) analysis and cortical thickness measurements were performed to assess structural changes in the visual cortex. Brain function was measured by assessing neuronal connectivity changes in response to visual stimulation and at rest in visual resting‐state networks. Multiple linear regression analyses were performed to examine the relationship between visual cognitive function and structural imaging measures. Compared to controls, pronounced atrophy and decreased neuronal function at rest were present in associative visual cortices in manifest HD. The primary visual cortex did not show group differences in cortical thickness and in vascular activity after visual stimulation. Thinning of the associative visual cortex was related to worse visual perceptual function. Premanifest HD gene carriers did not show any differences in brain structure or function compared to controls. This study improves the knowledge on posterior brain changes in HD, as our findings suggest that the primary visual cortex remains preserved, both structurally and functionally, while atrophy of associative visual cortices is present in early HD and linked to clinical visual deficits. Show less
In this thesis we examined several effects of fasting in lean and obese individuals. As expected, both the hormonal response as well as the metabolic shift from glucose towards lipid oxidation was... Show moreIn this thesis we examined several effects of fasting in lean and obese individuals. As expected, both the hormonal response as well as the metabolic shift from glucose towards lipid oxidation was impaired in obese individuals. At baseline, mitochondrial protein content in skeletal muscle of obese subjects was significantly reduced compared to lean individuals. We assessed the neuronal response to fasting by fMRI scanning. We found a different neuronal response to fasting between lean and obese individuals in terms of functional connectivity between the hypothalamus and respectively the dACC and insula. Since these regions are part of the saliency network, these differences may reflect distinct perception of calorie imbalance between lean and obese subjects. The effects of fasting on sympathetic tone (estimated by heart rate variability) were studied. Our data suggests that fasting decreases sympathetic tone in lean subjects, whereas it increases sympathetic activity in obese individuals. Weight loss in obese individuals increased HRV parameters that reflect the postprandial sympathetic tone. Finally, we studied the effects of fasting in the presence and absence of food-odors since this has been shown to reduce the fasting-induced increase in life span in fruit flies __ no differences were found in our human subjects. Show less
