By monitoring ongoing actions and performance outcomes, we are able to detect errors or mismatches between our intentions or predictions. Disturbances in such performance-monitoring processes may... Show moreBy monitoring ongoing actions and performance outcomes, we are able to detect errors or mismatches between our intentions or predictions. Disturbances in such performance-monitoring processes may importantly contribute to impaired adaptive behavior in clinical disorders, such as excessively impulsive behavior in externalizing disorders or excessively rigid or careful behavior in anxiety- and obsessive-compulsive disorders. In daily life, performance monitoring often takes place in a social context, where our actions have consequences not only for ourselves, but also for others. The investigation of (alterations in) such (pro)social performance-monitoring processes may help explain functional and social impairments across a wide range of clinical disorders. In this dissertation, we used various neuroimaging paradigms to examine subclinical and neurochemical influences on performance monitoring when errors had consequences for oneself or others. The studies in this dissertation indicate that neural performance-monitoring correlates are modulated by social, subclinical, and neurochemical factors, including social (responsibility) context, obsessive-compulsive symptoms, ovarian hormones, and pharmacological manipulations of dopamine and oxytocin. These findings have implications for the potential and utility of error-related brain activity as a clinical biomarker or endophenotype, our insight into social symptoms and impairments in obsessive-compulsive disorder, and for our understanding of the neurochemical mechanisms underlying performance monitoring. Show less
Central neuraxial blockade (CNB) is a well-known and relative easy way to perform surgerywithout pain and it can be used to achieve good postoperative analgesia. The two mostfrequently used... Show moreCentral neuraxial blockade (CNB) is a well-known and relative easy way to perform surgerywithout pain and it can be used to achieve good postoperative analgesia. The two mostfrequently used techniques, spinal and epidural anesthesia, are the main subject of this thesis.Both spinal and epidural anesthesia are worldwide applied in tens of thousands patients on a daily basis and consequently in millions each year. Still many effects of especially the deafferentation caused by neuraxial blockade is poorly studied and poorly understood. Neuraxial blockade results in disruption of ascending and descending input to the brain, i.e., deafferentation, and has an impact on a range of factors such as the pharmacology of anesthetics (e.g., propofol) and the balance between the excitatory and inhibitory modulation of afferent stimuli. These effects will cause changes in pharmacokinetics andpharmacodynamics of general anesthetics, pain perception and connectivity in functional brain networks. This thesis describes a subset of topics related to temporary deafferentation in patients and healthy volunteers. The aim of the studies is understanding the effect of neuraxial blockade and the subsequent short-term deafferentation on the development of propofol anesthesia and pain perception. Show less
To comprehend texts readers build mental representations. To establish coherence and protect these representations against inaccuracies readers routinely monitor and validate textual information... Show moreTo comprehend texts readers build mental representations. To establish coherence and protect these representations against inaccuracies readers routinely monitor and validate textual information against two main informational sources –what they just read (the text itself) and what they know (their background knowledge). This dissertation focuses on validation processes in the context of reading comprehension. Texts today vary in accuracy and trustworthiness. To better understand how readers validate (written) materials against various sources of information, the experimental studies in this dissertation employed different research methods to examine the (neuro)cognitive architecture of the processes involved in validating against prior text (i.e., text-based validation) and validating against background knowledge (i.e., knowledge-based validation) and how these processes affect readers;’ memory for text information.Results illustrate that readers validate incoming information against these two sources in dissociable, (partially) interactive, text-based and knowledge-based validation processes. Moreover, these processes seem to protect readers’ memory against inaccuracies or incongruencies. These observations deepen our understanding of validation processes, provide starting points for investigations of people’s susceptibility to false information and how inaccurate knowledge can be revised and provide insight into the complex interplay between recently acquired knowledge from the text itself and background knowledge in constructing meaning from language. 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
Bas-Hoogendam, J.M.; Steenbergen, H. van; Wee, N.J.A. van der; Westenberg, P.M. 2020
Social anxiety disorder (SAD) runs in families, but the neurobiological pathways underlying the genetic susceptibility towards SAD are largely unknown. Here, we employed an endophenotype approach,... Show moreSocial anxiety disorder (SAD) runs in families, but the neurobiological pathways underlying the genetic susceptibility towards SAD are largely unknown. Here, we employed an endophenotype approach, and tested the hypothesis that amygdala hyperreactivity to faces conditioned with a social-evaluative meaning is a candidate SAD endophenotype. We used data from the multiplex, multigenerational Leiden Family Lab study on Social Anxiety Disorder (eight families, n = 105) and investigated amygdala activation during a social-evaluative conditioning paradigm with high ecological validity in the context of SAD. Three neutral faces were repeatedly presented in combination with socially negative, positive or neutral sentences. We focused on two endophenotype criteria: co-segregation of the candidate endophenotype with the disorder within families, and heritability. Analyses of the fMRI data were restricted to the amygdala as a region of interest, and association analyses revealed that bilateral amygdala hyperreactivity in response to the conditioned faces co-segregated with social anxiety (SA; continuous measure) within the families; we found, however, no relationship between SA and brain activation in response to more specific fMRI contrasts. Furthermore, brain activation in a small subset of voxels within these amygdala clusters was at least moderately heritable. Taken together, these findings show that amygdala engagement in response to conditioned faces with a social-evaluative meaning qualifies as a neurobiological candidate endophenotype of social anxiety. Thereby, these data shed light on the genetic vulnerability to develop SAD. Show less
Individuals with autism spectrum disorder (ASD) and individuals with conduct disorder (CD) are characterized by notable impairments in social-emotional functioning. In this thesis social-emotional... Show moreIndividuals with autism spectrum disorder (ASD) and individuals with conduct disorder (CD) are characterized by notable impairments in social-emotional functioning. In this thesis social-emotional impairments were investigated using a cognitive neuroscience perspective (i.e., studying cognitive mechanisms and associated neural processes and structures). First, we directly compared groups of ASD and CD to test the hypothesized dissociable deficits in understanding other’s emotions in ASD in contrast to deficits in feeling other’s emotions in CD. This was done by comparing brain activity during basic emotion processing to assess cognitive and affective aspects of empathy, and by comparing white matter tracts that may underlie social-emotional processing. Second, we examined the neural processes at the level of social interactions in ASD and in CD, which has been overlooked by prior work, by studying interactive decision-making in response to other’s emotions. The results of the first part of this thesis show that different neural mechanisms underlie social-emotional difficulties in ASD and CD. Results of the second part imply that uncovering the neural correlates of interacting with others might lead to refined models of social-emotional deficits in ASD and CD that are different from previous accounts based on merely observing other’s emotions. Show less
Dissociation, emotion dysregulation, and cognitive disturbances are key features of Borderline Personality Disorder (BPD). The aim of this thesis was to investigate associations between... Show moreDissociation, emotion dysregulation, and cognitive disturbances are key features of Borderline Personality Disorder (BPD). The aim of this thesis was to investigate associations between dissociation and activity in networks relevant to affective-cognitive processing in patients with BPD compared to healthy controls. In the first part of this thesis, associations between self-reported dissociation and functional connectivity of the amygdala and anterior cingulate during resting-state and during an Emotional Working Memory Task (EWMT) were examined. The second part of this neuroimaging research combined script-driven imagery with the EWMT and with an Emotional Stroop Task. Findings suggest a detrimental effect of dissociation on cognitive functioning in BPD. After dissociation induction, patients showed reduced activity in the amygdala, posterior cingulate, superior temporal gyrus, and occipital areas (cuneus, fusiform gyrus, lingual gyrus), along with increased activity in frontal areas (inferior frontal gyrus, dlPFC). Altered interactions between the amygdala and the afore-mentioned regions may underlie disturbed information processing during dissociation in BPD. Further research with larger sample sizes and clinical control groups is needed to gain more insight into the neural mechanisms of stress-related dissociation in BPD. A combination of neuroimaging techniques with subjective, behavioral, and psychophysiological measurements may be a helpful step into this direction. Show less
Bas-Hoogendam, J.M.; Andela, C.D.; Werff, S.J.A. van der; Pannekoek, J.N.; Steenbergen, H. van; Meijer, O.C.; ... ; Pereira, A.M. 2015
It is well known that complex mental abilities develop at least until late adolescence. Yet, there are also skills that children master perfectly, sometimes even better than adults. The goal of... Show moreIt is well known that complex mental abilities develop at least until late adolescence. Yet, there are also skills that children master perfectly, sometimes even better than adults. The goal of this thesis was to learn more about the possibilities of cognitive functioning in children and young adults, and the constraints set by the developing brain. An fMRI training approach was used to examine age- and experience-related effects in the development of working memory and resting-state functional connectivity. More specifically, we studied age differences on task performance and brain activation during a working memory task with various demands and difficulty levels, both before and after 6 weeks of practice with the task. In addition, to learn more about the interaction between different brain regions, we also examined age differences and practice effects on functional connectivity during resting-state. Show less
Depressie en angststoornissen zijn veel voorkomende psychiatrische stoornissen die een hoge __comorbiditeit__ vertonen, d.w.z. pati_nten lijden zeer veelvuldig tegelijkertijd aan deze stoornissen.... Show moreDepressie en angststoornissen zijn veel voorkomende psychiatrische stoornissen die een hoge __comorbiditeit__ vertonen, d.w.z. pati_nten lijden zeer veelvuldig tegelijkertijd aan deze stoornissen. Mede hierdoor is voorgesteld dat de stoornissen neurobiologische overlap vertonen. Welke abnormaliteiten in het brein gedeeeld worden bij angst en depressie, is tot op heden nooit goed onderzocht. De bevindingen in dit proefschrift ondersteunen de gedachte dat depressie en angst gekenmerkt worden door gedeelde afwijkingen in zowel hersenfunctie als in structuur. Tegelijkertijd werden stoornis-specifieke afwijkingen vastgesteld. Onze bevindingen kunnen deels de hoge comorbiditeit tussen angst en depressie verklaren. Ook geven de resultaten aanwijzingen voor een kwetsbaarheid die kan verklaren dat mensen terugvallen in een nieuwe episode. Verder suggereren de resultaten dat in mensen met comorbide depressie en angst, niet de depressie, maar de angststoornis de primaire pathologie is. Tenslotte toonden we aan dat persoonlijkheidsfactoren en het meemaken van emotionele jeugdmishandeling samenhangen met volume van een aantal emotiegerelateerde structuren in het brein. Deze samenhang kan verklaren waarom mensen met jeugdtrauma_s, of een bepaalde persoonlijkheidsstructuur, meer of minder kans hebben om een affectieve stoornis te ontwikkelen. Dit is de eerste studie waarin zowel de hersenfunctie als __structuur is onderzocht in een grote groep pati_nten met depressie en/of angststoornissen. Show less
