The overarching goal of this thesis was to examine the behavioral, computational, and neural mechanisms underlying social learning in adolescence. The first aim was to examine developmental... Show moreThe overarching goal of this thesis was to examine the behavioral, computational, and neural mechanisms underlying social learning in adolescence. The first aim was to examine developmental patterns across adolescence of two forms of social learning: (1) learning about other people, specifically, whether they are (un)cooperative and (un)trustworthy, and (2) learning for other people (prosocial learning) to know what actions may benefit or help others. I made use of multiple experimental paradigms based on well-known economic games and/or probabilistic reinforcement learning paradigms to assess these forms of social learning. Secondly, I aimed to examine underlying mechanisms and factors that account for age-related and individual differences in social learning. Applying computational modeling and functional neuroimaging as additional tools contributed to a better understanding of the underlying mechanisms and how these develop across adolescence. The findings in this thesis converge to early-to-mid adolescence as a key developmental period for developing well-adjusted social behaviors, and especially in the cooperative domain there are pronounced improvements. These studies make an important contribution to the literature on social development and learning, and may eventually contribute to interventions targeted at promoting well-adjusted behavior in typically developing adolescents, as well as youth with maladaptive social tendencies. Show less
The estimated accuracy of a classifier is a random quantity with variability. A common practice in supervised machine learning, is thus to test if the estimated accuracy is significantly better... Show moreThe estimated accuracy of a classifier is a random quantity with variability. A common practice in supervised machine learning, is thus to test if the estimated accuracy is significantly better than chance level. This method of signal detection is particularly popular in neuroimaging and genetics. We provide evidence that using a classifier's accuracy as a test statistic can be an underpowered strategy for finding differences between populations, compared to a bona fide statistical test. It is also computationally more demanding than a statistical test. Via simulation, we compare test statistics that are based on classification accuracy, to others based on multivariate test statistics. We find that the probability of detecting differences between two distributions is lower for accuracy-based statistics. We examine several candidate causes for the low power of accuracy-tests. These causes include: the discrete nature of the accuracy-test statistic, the type of signal accuracy-tests are designed to detect, their inefficient use of the data, and their suboptimal regularization. When the purpose of the analysis is the evaluation of a particular classifier, not signal detection, we suggest several improvements to increase power. In particular, to replace V-fold cross-validation with the Leave-One-Out Bootstrap. Show less
Verwer, E.E.; Golla, S.S.V.; Kaalep, A.; Lubberink, M.; Velden, F.H.P. van; Bettinardi, V.; ... ; Boellaard, R. 2021
Purpose In order to achieve comparability of image quality, harmonisation of PET system performance is imperative. In this study, prototype harmonisation criteria for PET brain studies were... Show morePurpose In order to achieve comparability of image quality, harmonisation of PET system performance is imperative. In this study, prototype harmonisation criteria for PET brain studies were developed.Methods Twelve clinical PET/CT systems (4 GE, 4 Philips, 4 Siemens, including SiPM-based "digital" systems) were used to acquire 30-min PET scans of a Hoffman 3D Brain phantom filled with similar to 33 kBq.mL(-1) [F-18]FDG. Scan data were reconstructed using various reconstruction settings. The images were rigidly coregistered to a template (voxel size 1.17 x 1.17 x 2.00 mm(3)) onto which several volumes of interest (VOIs) were defined. Recovery coefficients (RC) and grey matter to white matter ratios (GMWMr) were derived for eroded (denoted in the text by subscript e) and non-eroded grey (GM) and white (WM) matter VOIs as well as a mid-phantom cold spot (VOIcold) and VOIs from the Hammers atlas. In addition, left-right hemisphere differences and voxel-by-voxel differences compared to a reference image were assessed.Results Systematic differences were observed for reconstructions with and without point-spread-function modelling (PSFON and PSFOFF, respectively). Normalising to image-derived activity, upper and lower limits ensuring image comparability were as follows: for PSFON, RCGMe = [0.97-1.01] and GMWMr(e) = [3.51-3.91] for eroded VOI and RCGM = [0.78-0.83] and GMWMr = [1.77-2.06] for non-eroded VOI, and for PSFOFF, RCGMe = [0.92-0.99] and GMWMr(e) = [3.14-3.68] for eroded VOI and RCGM = [0.75-0.81] and GMWMr = [1.72-1.95] for non-eroded VOI.Conclusions To achieve inter-scanner comparability, we propose selecting reconstruction settings based on RCGMe and GMWMr(e) as specified in "Results". These proposed standards should be tested prospectively to validate and/or refine the harmonisation criteria. Show less
Drenth, N.; Grond, J. van der; Rombouts, S.A.R.B.; Buchem, M.A. van; Terwindt, G.M.; Wermer, M.J.H.; ... ; Rooden, S. van 2021
Cerebral amyloid angiopathy (CAA) is a major cause of intracerebral hemorrhage and neurological decline in the elderly. CAA results in focal brain lesions, but the influence on global brain... Show moreCerebral amyloid angiopathy (CAA) is a major cause of intracerebral hemorrhage and neurological decline in the elderly. CAA results in focal brain lesions, but the influence on global brain functioning needs further investigation. Here we study functional brain connectivity in patients with Dutch type hereditary CAA using resting state functional MRI. Twenty-four DNA-proven Dutch CAA mutation carriers (11 presymptomatic, 13 symptomatic) and 29 age-matched control subjects were included. Using a set of standardized networks covering the entire cortex, we assessed both within- and between-network functional connectivity. We investigated group differences using general linear models corrected for age, sex and gray matter volume. First, all mutation carriers were contrasted against control subjects and subsequently presymptomatic- and symptomatic mutation carriers against control subjects separately, to assess in which stage of the disease differences could be found. All mutation carriers grouped together showed decreased connectivity in the medial and lateral visual networks, default mode network, executive control and bilateral frontoparietal networks. Symptomatic carriers showed diminished connectivity in all but one network, and between the left and right frontoparietal networks. Presymptomatic carriers also showed diminished connectivity, but only in the frontoparietal left network. In conclusion, global brain functioning is diminished in patients with CAA, predominantly in symptomatic CAA and can therefore be considered to be a late consequence of the disease. Show less
In this thesis a literature review was conducted to map the results of earlier neuroimaging studies in minors who experienced childhood psychological trauma. Next, three different structural... Show moreIn this thesis a literature review was conducted to map the results of earlier neuroimaging studies in minors who experienced childhood psychological trauma. Next, three different structural neuroimaging techniques were employed to study the effects of childhood sexual trauma in youth .Main findings:1. Neuroimaging studies in traumatised children and adolescents are scarce and heterogeneous in design, in particular with regard to the sample studied and type of trauma.2. The results of structural neuroimaging studies in traumatised minors differ from those in adult populations, in particular with regard to findings on hippocampus and corpus callosum (CC).3. Paralleling the inconsistent findings on hippocampal volume reduction in traumatised minors, our VBM-study did not show differences between groups for hippocampal volume.4. VBM showed smaller volumes of key regions of the limbic system (ACC, amygdala) in the CSA-related PTSD group compared to controls.5. Adolescents with sexual abuse-related PTSD show no abnormalities in cortical thickness, in line with findings in adults. 6. Adolescents with CSA-related PTSD show less integrity of parts of the CC compared to healthy non-traumatised controls.7. Our structural neuroimaging studies showed limited associations with trauma symptomatology, in line with findings in studies in minors. Show less
Duchenne muscular dystrophy is a multifactorial disease including a cognitive phenotype. It is caused by mutations in the X-chromosomal DMD gene from which dystrophin is synthesized. Multiple... Show moreDuchenne muscular dystrophy is a multifactorial disease including a cognitive phenotype. It is caused by mutations in the X-chromosomal DMD gene from which dystrophin is synthesized. Multiple isoforms of dystrophin have been identified. The full length dystrophin isoform Dp427 m is expressed predominantly in muscle. Other isoforms include: Dp427(c), Dp427(p), Dp260, Dp140, Dp116, Dp71 and Dp40. The majority of these isoforms are expressed in brain and several hypotheses exist on their role in subtypes of neurons and astrocytes. However, their function in relation to cognition remains unclear. Unlike progressive muscle wasting, cognitive involvement is not seen in all DMD patients and the severity varies greatly. To achieve a better understanding of brain involvement in DMD, a multidisciplinary approach is required. Here, we review the latest findings on dystrophin isoform expression in the brain; specific DMD-associated learning and behavioural difficulties; and imaging and spectroscopy findings relating to brain structure, networks, perfusion and metabolism. The main challenge lies in determining links between these different findings. If we can determine which factors play a role in the differentiation between severe and minor cognitive problems in DMD in the near future, we can both provide better advise for the patients and also develop targeted therapeutic interventions. (C) 2020 The Author(s). Published by Elsevier B.V. Show less
*****This dissertation has been published as : "Love and Selfhood : Self-understanding Through Philosophy and Cognitive Neuroscience" and can be found at : https://link.springer.com/book/10.1007...Show more*****This dissertation has been published as : "Love and Selfhood : Self-understanding Through Philosophy and Cognitive Neuroscience" and can be found at : https://link.springer.com/book/10.1007/978-3-031-06801-0 *****‘Who am I really?’ When people ask themselves this question, they often find themselves in situations or dilemmas that may be labeled ‘existential’. They need to take an important decision, for example, and reflect on what is of fundamental importance to them. Also without explicit self-reflection, people’s behavior and experiences are influenced by what they care about most. Several philosophers have reflected on this existential aspect of selfhood. These days, cognitive neuroscientists too investigate e.g. love and self-reflection. What contributions to our understanding of the existential aspect of human lives can philosophy and cognitive neuroscience (CNS) make?I investigate existing CNS research into love and self-reflection and existing philosophies of existential selfhood, by Harry Frankfurt, Søren Kierkegaard and Charles Taylor, amongst others. I argue that CNS and philosophy are not in opposition with each other, as they address different types of questions. Moreover, CNS may benefit from cooperation with philosophy where reflection on moments of interpretation in its research process is concerned. I develop conceptual review as a tool to do so. I end with a philosophical view on existential selfhood and existential self-understanding that improves on existing philosophies and integrates insights from CNS where applicable. Show less
The human body is inherently designed to be able to adapt to challenging situations. However, some experiences are so severe that they can lead to substantial and longerlasting disturbances in an... Show moreThe human body is inherently designed to be able to adapt to challenging situations. However, some experiences are so severe that they can lead to substantial and longerlasting disturbances in an individuals’ behavioral, psychological and physiological functioning. Importantly, there is a degree of inter-individual variation, as not all individuals show similar reactions to severe stress. Neuroimaging techniques can help to unravel the brain characteristics related to vulnerability and resilience to severe stress. In the research for this dissertation several neuroimaging modalities were used to further explore the brain characteristics related to (dys)function after exposure to severe stress and after exposure to hypercortisolism, such as voxel-based morphometry and diffusion tensor imaging to study the structure of gray and white matter in the brain, and resting-state fMRI to study functional connectivity patterns. We studied brain characteristics in several groups consisting of: patients in long-term remission of Cushing’s disease, and individuals with a history of childhood emotional maltreatment to examine the effects of hypercortisolism and severe stress on the brain. In addition, we studied a group of police officers and a group of individuals with a history of childhood maltreatment to investigate the brain characteristics related to resilience to stress. Show less
This thesis describes neuroimaging techniques to investigate brain networks in healthy aging and dementia. Functional and structural brain networks change with healthy and pathological... Show more This thesis describes neuroimaging techniques to investigate brain networks in healthy aging and dementia. Functional and structural brain networks change with healthy and pathological aging, with differences in network degeneration between different types of dementia. These disease-specific network differences suggest the potential of brain networks to improve diagnostic accuracy. However, at this moment, our findings are only applicable for groups of patients and not yet suitable as a diagnostic tool on an individual basis. Show less
Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) can play a key role in understanding neurobiological mechanisms of diseases that affect the human brain. The specific changes that occur... Show moreDiffusion-weighted magnetic resonance spectroscopy (DW-MRS) can play a key role in understanding neurobiological mechanisms of diseases that affect the human brain. The specific changes that occur within neurons can be reflected as changes in the diffusivity of tNAA, whereas the changes in glial cells can cause pronounced changes in the diffusivities of tCr and tCho. This information combined with that obtained from diffusion tensor imaging (DTI) and other MRI tools can help elucidate various disease processes in the future. The main purposes of this thesis are (i) to investigate neuroanatomy in vivo with DW-MRS, (ii) to develop methodology to enable future clinical applications of the technique in human brain in vivo, and (iii) to characterize the microstructural deficit in neuropsychiatric systemic lupus erythematous (NPSLE) with DW-MRS and other microstructural tools such as DTI and magnetization transfer imaging. The studies presented in this thesis show the robustness and clinical relevance of microstructural information obtained via DW-MRS. The contributions of this thesis such as the optimized acquisition protocols for single volume DW-MRS, the robust DW-CSI and DW-MRS post-processing pipelines that comprise information from DTI, will all facilitate the applications of DW-MRS both for basic neuroscience research and clinical research studies. Show less
Klinefelter syndrome (47,XXY) is associated with a wide range of behavioral problems, including autism symptomatology. In the current thesis, brain structure and function were assesed in boys with... Show moreKlinefelter syndrome (47,XXY) is associated with a wide range of behavioral problems, including autism symptomatology. In the current thesis, brain structure and function were assesed in boys with 47,XXY, boys with idiopathic autism spectrum disorder, and non-clinical controls, using multiple imaging techniques. The goal was to assess the mechanisms underlying social dysfunction in 47,XXY, and to investigate to what degree these mechanisms differ from those in individuals with idiopathic autism. The results show that individuals with 47,XXY show characteristic deviations in brain structure and function associated with higher order cognitive functions, social emotional information processing, and language processing. Additionally, while boys with 47,XXY show considerable overlap with boys with idiopathic ASD in autism symptomatology, there are specific differences in the underlying neural mechanisms that revolve around the frontal lobes and insular cortices. These findings may have implications for intervention studies (e.g. focused on real time fMRI neurofeedback), as well as clinical practice. It may impact the selection of mental health care strategies that take into account this variability in mechanisms underlying social dysfunction in individuals with autism spectrum disorder. Show less
The aim of this thesis was to investigate the radiological phenotype of the human brain in familial longevity with regard to brain structure. This study was performed as part of the Leiden... Show moreThe aim of this thesis was to investigate the radiological phenotype of the human brain in familial longevity with regard to brain structure. This study was performed as part of the Leiden Longevity Study __ a study population consisting of offspring of long-lived Dutch people who are genetically predisposed to become long-lived as well and their environmentally and age-matched spouses. Dedicated MR imaging techniques were applied to study the phenotype of the human brain on the macrostructural as well as microstructural level. Both features which are most likely caused by early development and a lower susceptibility to known age-related structural brain changes on the macro- as well as microstructural level are hallmarks of the brain phenotype in longevity. The contributing mechanisms have yet to be identified but may involve homeostatic control and body function. Keeping in mind that there is a gradual transition from healthy brain aging to what is generally accepted as __normal__ brain aging and pathological brain changes as disease correlates, our study results implicate that the brains of offspring of nonagenarian siblings are less susceptible to neurodegenerative brain changes such as (vascular) dementia, Alzheimer__s disease and cerebrovascular disease. Our findings should be considered as starting points for future studies on the functional implications of the presented results and studies on the underlying pathways of brain structure preservation in human longevity. Show less
