This thesis describes a cross-sectional behavioral and neuroimaging study in a sample of n=85 adolescents with a history of childhood sexual abuse related PTSD (CSA-related PTSD), anxiety and/or... Show moreThis thesis describes a cross-sectional behavioral and neuroimaging study in a sample of n=85 adolescents with a history of childhood sexual abuse related PTSD (CSA-related PTSD), anxiety and/or depressive disorders or no psychiatric symptoms. We assessed attachment representation as well as psychopathological symptoms, attentional bias and emotional face processing among diagnostic groups. We also correlated unresolved-disorganized attachment representation (Ud) and psychopathology using a general psychopathology factor (GPF) to grey matter (volume), white matter (tracts) and resting state functional connectivity (RSFC) of the brain in the entire sample. We found that clinical groups did not significantly differ in psychopathology. The unresolved-disorganized cannot classify category (Ud/CC) was overrepresented in the CSA-related PTSD group. Coherence of mind also differentiated the clinical groups, but Ud did not. The CSA-related PTSD group had a negative attention bias for neutral and fearful faces, the anxiety/depressive disorders group only for fearful faces. No differences were found for emotional face processing among diagnostic groups. We found a differential relationship of Ud and a GPF to grey matter volume, white matter integrity of white matter tracts and RSFC for Ud. Ud was associated with lateralization of the brain to the left with regard to amygdala RSFC and hippocampal volume. Show less
In neuroscience, clustering subjects based on brain dysfunctions is a promising avenue to subtype mental disorders as it may enhance the development of a brain-based categorization system for... Show moreIn neuroscience, clustering subjects based on brain dysfunctions is a promising avenue to subtype mental disorders as it may enhance the development of a brain-based categorization system for mental disorders that transcends and is biologically more valid than current symptom-based categorization systems. As changes in functional connectivity (FC) patterns have been demonstrated to be associated with various mental disorders, one appealing approach in this regard is to cluster patients based on similarities and differences in FC patterns. To this end, researchers collect three-way fMRI data measuring neural activation over time for different patients at several brain locations and apply Independent Component Analysis (ICA) to extract FC patterns from the data. However, due to the three-way nature and huge size of fMRI data, classical (two-way) clustering methods are inadequate to cluster patients based on these FC patterns. Therefore, a two-step procedure is proposed where, first, ICA is applied to each patient’s fMRI data and, next, a clustering algorithm is used to cluster the patients into homogeneous groups in terms of FC patterns. As some clustering methods used operate on similarity data, the modified RV-coefficient is adopted to compute the similarity between patient specific FC patterns. An extensive simulation study demonstrated that performing ICA before clustering enhances the cluster recovery and that hierarchical clustering using Ward’s method outperforms complete linkage hierarchical clustering, Affinity Propagation and Partitioning Around Medoids. Moreover, the proposed two-step procedure appears to recover the underlying clustering better than (1) a two-step procedure that combines PCA with clustering and (2) Clusterwise SCA-ECP, which performs PCA and clustering in a simultaneous fashion. Additionally, the good performance of the proposed two-step procedure using ICA and Ward’s hierarchical clustering is illustrated in an empirical fMRI data set regarding dementia patients. Show less
Insufficient response to treatment is the main cause of prolonged suffering from major depressive disorder (MDD). Early identification of insufficient response could result in faster and more... Show moreInsufficient response to treatment is the main cause of prolonged suffering from major depressive disorder (MDD). Early identification of insufficient response could result in faster and more targeted treatment strategies to reduce suffering. We therefore explored whether baseline alterations within and between resting state functional connectivity networks could serve as markers of insufficient response to antidepressant treatment in two years of follow-up. We selected MDD patients (N = 17) from the NEtherlands Study of Depression and Anxiety (NESDA), who received >= two antidepressants, indicative for insufficient response, during the two year follow-up, a group of MDD patients who received only one antidepressant (N = 32) and a healthy control group (N = 19) matched on clinical characteristics and demographics. An independent component analysis (ICA) of baseline resting-state scans was conducted after which functional connectivity within the components was compared between groups. We observed lower connectivity of the right insula within the salience network in the group with >= two anti-depressants compared to the group with one antidepressant. No difference in connectivity was found between the patient groups and healthy control group. Given the suggested role of the right insula in switching between task-positive mode (activation during attention-demanding tasks) and task-negative mode (activation during the absence of any task), we explored whether right insula activation differed during switching between these two modes. We observed that in the 2 anti-depressant group, the right insula was less active compared to the group with one antidepressant, when switching from task-positive to task-negative mode than the other way around. These findings imply that lower right insula connectivity within the salience network may serve as an indicator for prospective insufficient response to antidepressants. This result, supplemented by the diminished insula activation when switching between task and rest related networks, could indicate an underlying mechanism that, if not sufficiently targeted by current antidepressants, could lead to insufficient response. When replicated, these findings may contribute to the identification of biomarkers for early detection of insufficient response. Show less
This chapter describes neurolinguistic aspects of morphology, morphological theory, and especially morphological processing. It briefly mentions the main processing models in the literature and how... Show moreThis chapter describes neurolinguistic aspects of morphology, morphological theory, and especially morphological processing. It briefly mentions the main processing models in the literature and how they deal with morphological issues, i.e. full-listing models (all morphologically related words are listed separately in the lexicon and are processed individually), full-parsing or decompositional models (morphologically related words are not listed in the lexicon but are decomposed into their constituent morphemes, each of which is listed in the lexicon), and hybrid, so-called dual route, models (regular morphologically related words are decomposed, irregular words are listed). The chapter also summarizes some important findings from the literature that bear on neurolinguistic aspects of morphological processing, from both language comprehension and language production, taking into consideration neuropsychological patient studies as well as studies employing neuroimaging methods. Show less
Meulen, M. van der; Steinbeis, N.A.J.; Achterberg, M.; IJzendoorn, M.H. van; Crone, E.A.M. 2018
Experiencing and observing social exclusion and inclusion, as well as prosocial behavior, are important aspects of social relationships in childhood. However, it is currently unknown to what extent... Show moreExperiencing and observing social exclusion and inclusion, as well as prosocial behavior, are important aspects of social relationships in childhood. However, it is currently unknown to what extent these processes and their neural correlates differ in heritability. We investigated influences of genetics and environment on experiencing social exclusion and compensating for social exclusion of others with the Prosocial Cyberball Game using fMRI in a twin sample (aged 7–9; N = 500). Neuroimaging analyses (N = 283) revealed that experiencing possible self-exclusion resulted in activity in inferior frontal gyrus and medial prefrontal cortex, which was influenced by genetics and unique environment. Experiencing self-inclusion was associated with activity in anterior cingulate cortex, insula and striatum, but this was not significantly explained by genetics or shared environment. We found that children show prosocial compensating behavior when observing social exclusion. Prosocial compensating behavior was associated with activity in posterior cingulate cortex/precuneus, and showed unique environmental effects or measurement error at both behavioral and neural level. Together, these findings show that in children neural activation for experiencing possible self-exclusion and self-inclusion, and for displaying prosocial compensating behavior, is accounted for by unique environmental factors and measurement error, with a small genetic effect on possible self-exclusion. Show less
Peer relationships play an important role in adolescent social development. Adolescence is also a sensitive period for reward-related processing where Nucleus Accumbens (NAcc) shows peak levels of... Show morePeer relationships play an important role in adolescent social development. Adolescence is also a sensitive period for reward-related processing where Nucleus Accumbens (NAcc) shows peak levels of activity. To investigate the role of reward-related neural processes in peer relationships, we scanned 31 adolescents (16 boys, 15 girls) from 12 to 17 years old and had their classmates rate their likability and dislikability. Using these ratings, we calculated levels of peer acceptance (i.e., likability minus dislikability scores). Participants played a social gambling paradigm in the scanner where we examined NAcc responses to winning for self and winning for best friends. We showed that acceptance by peers was related negatively to activation patterns in the NAcc when winning money for self. Peer acceptance was not related to NAcc activity during vicarious reward processing where participants won money for their best friend. These results point in the direction of an underlying neural mechanism indicating that peer interactions of well-liked adolescents are characterized by a lower focus on benefits for self. Show less
Ai, H.; Tol, M.J. van; Marsman, J.B.C.; Veltman, D.J.; Ruhe, H.G.; Wee, N.J.A. van der; ... ; Aleman, A. 2018
Sensory function is impaired in adults with conservatively treated OBPL. There is widespread motor misrouting together with motor functional impairment in conservatively treated OBPL, not... Show moreSensory function is impaired in adults with conservatively treated OBPL. There is widespread motor misrouting together with motor functional impairment in conservatively treated OBPL, not explained by muscle weakness. There were no differences in the degree of cocontraction between OBPL patients and healthy subjects for either the triceps or deltoid muscles during supramaximal biceps stimulation. However, elbow stiffness was approximately 1.7 times higher in OBPL patients than in control subjects during voluntary levels of contraction, suggesting a significant effect of misrouting in the patients. In children with OBPL the deficit during automatic arm abduction was not observed during voluntary movements and therefore cannot be explained by a peripheral deficit, suggesting a central component. In adults OBPL affected imagined but not actual elbow flexion suggested an impairment of motor planning. Show less
Although the majority of our social interactions are with people we know, few studies have investigated the neural correlates of sharing valuable resources with familiar others. Using an... Show moreAlthough the majority of our social interactions are with people we know, few studies have investigated the neural correlates of sharing valuable resources with familiar others. Using an ecologically valid research paradigm, this functional magnetic resonance imaging study examined the neural correlates of prosocial and selfish behavior in interactions with real-life friends and disliked peers in young adults. Participants (N = 27) distributed coins between themselves and another person, where they could make selfish choices that maximized their own gains or prosocial choices that maximized outcomes of the other. Participants were more prosocial toward friends and more selfish toward disliked peers. Individual prosociality levels toward friends were associated negatively with supplementary motor area and anterior insula activity. Further preliminary analyses showed that prosocial decisions involving friends were associated with heightened activity in the bilateral posterior temporoparietal junction, and selfish decisions involving disliked peers were associated with heightened superior temporal sulcus activity, which are brain regions consistently shown to be involved in mentalizing and perspective taking in prior studies. Further, activation of the putamen was observed during prosocial choices involving friends and selfish choices involving disliked peers. These findings provide insights into the modulation of neural processes that underlie prosocial behavior as a function of a positive or negative relationship with the interaction partner. Show less
Van der Cruijsen, R.; Peters, S.; Aar, L.P.E. van der; Crone, E.A. 2018
Neuroimaging studies in adults showed that cortical midline regions including medial prefrontal cortex (mPFC) and posterior parietal cortex (PPC) are important in self-evaluations. The goals of... Show moreNeuroimaging studies in adults showed that cortical midline regions including medial prefrontal cortex (mPFC) and posterior parietal cortex (PPC) are important in self-evaluations. The goals of this study were to investigate the contribution of these regions to self-evaluations in late childhood, adolescence, and early adulthood, and to examine whether these differed per domain (academic, physical and prosocial) and valence (positive versus negative). Also, we tested whether this activation changes across adolescence. For this purpose, participants between ages 11–21-years (N = 150) evaluated themselves on trait sentences in an fMRI session. Behaviorally, adolescents rated their academic traits less positively than children and young adults. The neural analyses showed that evaluating self-traits versus a control condition was associated with increased activity in mPFC (domain-general effect), and positive traits were associated with increased activity in ventral mPFC (valence effect). Self-related mPFC activation increased linearly with age, but only for evaluating physical traits. Furthermore, an adolescent-specific decrease in striatumactivation for positive self traits was found. Finally, we found domain-specific neural activity for evaluating traits in physical (dorsolateral PFC, dorsal mPFC) and academic (PPC) domains. Together, these results highlight the importance of domain distinctions when studying self-concept development in late childhood, adolescence, and early adulthood. Show less
The human brain is able to flexibly adapt its information processing capacity to meet a variety of cognitive challenges. Recent evidence suggests that this flexibility is reflected in the dynamic... Show moreThe human brain is able to flexibly adapt its information processing capacity to meet a variety of cognitive challenges. Recent evidence suggests that this flexibility is reflected in the dynamic reorganization of the functional connectome. The ascending catecholaminergic arousal systems of the brain are a plausible candidate mechanism for driving alterations in network architecture, enabling efficient deployment of cognitive resources when the environment demands them. We tested this hypothesis by analyzing both resting-state and task-based fMRI data following the administration of atomoxetine, a noradrenaline reuptake inhibitor, compared with placebo, in two separate human fMRI studies. Our results demonstrate that the manipulation of central catecholamine levels leads to a reorganization of the functional connectome in a manner that is sensitive to ongoing cognitive demands. Show less
Van der Cruijsen, R.; Peters, S.; Crone, E.A. 2017
Behavioral studies showed that self-concept can be distinguished into different domains, but few neuroimaging studies have investigated either domain-specific or valence-specific activity. Here, we... Show moreBehavioral studies showed that self-concept can be distinguished into different domains, but few neuroimaging studies have investigated either domain-specific or valence-specific activity. Here, we investigated whether evaluating self- and mother-traits in three domains (physical, academic, prosocial) relies on similar or distinct brain regions. Additionally, we explored the topical discussion in the literature on whether vmPFC activity during self-evaluations is induced by valence or importance of traits. Participants evaluated themselves and their mothers on positive and negative traits in three domains. Across all domains, evaluating traits resulted in right dlPFC, left middle temporal cortex, bilateral thalamus, and right insula activity. For physical traits, we found specific neural activity in brain regions typically implicated in mentalizing (dmPFC, IPL). For academic traits, we found a brain region typically implicated in autobiographical memories (PCC), and for prosocial traits, social brain regions (temporal pole, TPJ) were activated. Importantly, these patterns were found for both self and mother evaluations. Regarding valence, rACC/vmPFC showed stronger activation for positive than for negative traits. Interestingly, activation in this region was stronger for highly important traits compared to low/neutral important traits. Thus, this study shows that distinct neural processes are activated for evaluating positive and negative traits in different domains. Show less
The prevalence of obesity, defined as a body mass index (BMI) > 30 kg/m2, is increasing to epidemic proportions. In 2014, 11% of men and 15% of women worldwide were obese. Thus, more than... Show moreThe prevalence of obesity, defined as a body mass index (BMI) > 30 kg/m2, is increasing to epidemic proportions. In 2014, 11% of men and 15% of women worldwide were obese. Thus, more than half a billion adults worldwide are classed as obese. The fundamental cause of obesity is an imbalance between energy intake (excessive intake of energy-dense foods) and energy expenditure (reduced physical activity). People with obesity are at risk for a range of chronic conditions including cardiovascular disease (CVD) and nonalcoholic fatty liver disease (NAFLD). Furthermore, obesity is a major risk factor for the development of type 2 diabetes, which is one of the most common chronic diseases in nearly all countries. According to the World Health Organization, the global prevalence of diabetes in 2014 was estimated to be 9%, of which 90% was comprised of type 2 diabetes. This thesis focuses on cardiovascular and cerebral dimensions and function in people with obesity and type 2 diabetes. State-of-the-art imaging techniques are used to investigate links between the heart, liver, abdominal fat, and brain to elucidate parts of the complex relationships between these organs. Show less
Klapwijk, E.T.; Aghajani, M.; Lelieveld, G.J.; Lang, N.D.J. van; Popma, A.; Wee, N.J.A. van der; ... ; Vermeiren, R.R.J.M. 2017
