Achtergrond: Anatomische MRI blijkt een goede voorspeller te zijn van Alzheimer, het is echter nog niet heel duidelijk wat de rol van functionele MRI (fMRI) in Alzheimer classificatie is en of dit...Show moreAchtergrond: Anatomische MRI blijkt een goede voorspeller te zijn van Alzheimer, het is echter nog niet heel duidelijk wat de rol van functionele MRI (fMRI) in Alzheimer classificatie is en of dit een toevoeging op anatomische MRI kan zijn. Doel: In dit onderzoek wordt onderzocht of fMRI van toegevoegde waarde is op anatomische MRI in het classificeren van Alzheimer. Methode: Om dit te kunnen onderzoeken worden er 3 classificatiemodellen met elkaar vergeleken, namelijk een model met alleen anatomische MRI-predictoren bestaande uit de grijze stofdichtheid en subcorticale volumes en een model met alleen fMRI-predictoren bestaande uit de functionele connectiviteit tussen 20 hersengebieden; en ten slotte een multimodaal model met zowel de anatomische als fMRI-predictoren. Om de meest relevante predictoren in de modellen te selecteren wordt er een LASSO algoritme toegepast. Daarnaast wordt er kruisvalidatie toegepast om de modellen te kunnen generaliseren. Om de prestatie van de modellen te evalueren worden de AUC-waardes van de modellen vergeleken. Resultaten: Het model dat alleen gebruikmaakt van anatomische MRI-predictoren kan Alzheimer accuraat classificeren met een AUC-waarde van 0.92. Het model dat alleen fMRIpredictoren gebruikt kan Alzheimer redelijk goed classificeren, maar niet beter dan model 1, met een AUC-waarde van 0.74. Het multimodale model classificeert Alzheimer het beste met een AUC-waarde van 0.93. Conclusie: Een multimodaal classificatiemodel bestaande uit anatomische MRI en fMRI presteert beter dan een model met alleen één van deze modaliteiten. Dit is echter een kleine verbetering ten opzichte van de anatomische MRI alleen, en het is niet duidelijk of dit klinisch relevant kan zijn.Show less
Placebo effects are known phenomena in medical and psychological research. They illustrate how a strong belief can create positive effects regarding well-being and health. However, a strong enough...Show morePlacebo effects are known phenomena in medical and psychological research. They illustrate how a strong belief can create positive effects regarding well-being and health. However, a strong enough negative belief may also have real effects on an individual. This phenomenon is known as a nocebo effect and research into nocebo effects, particularly related to symptoms of itch, has been sparse. Further understanding nocebo itch and its associated brain regions may help patients with chronic itch or psychosomatic afflictions. The aim of this study was to explore the impact of learning and negative outcome expectations on itch sensitivity. We hypothesized that participants would be conditioned to experience more itch in the presence of a sham electrical pulse compared to its absence, and that significant activity would be measured in the periaqueductal gray, insula, and rolandic operculum, which were studied using fMRI imaging techniques. Healthy participants (49) were involved in a two-phase task to acquire and evoke the nocebo itch. This process was reinforced through an on/off monitor and verbal instructions from researchers. In the acquisition phase, participants learned to associate itch stimuli with an electrical pulse (nocebo stimulus), expecting more itch during nocebo trials and less during control trials. Itch was induced using varying histamine concentrations for both types of trials and the electric pulse was never activated. In the evocation phase, nocebo itch was evoked using equal histamine concentrations in both control and nocebo trials. The nocebo itch was measured through subjective itch ratings and brain activity was measured with a 3T fMRI scanner. Evocation nocebo ratings were significantly higher than evocation control ratings, despite equal histamine concentrations (p < 0.001). However, no significant brain activity was found when data from the nocebo condition was compared with the control condition. The absence of conclusive fMRI data may be due to a possible extinction effect nullifying the measurement of nocebo activation, fMRI analysis of areas that were too broad, or overly conservative analysis methodology. These findings indicate the efficacy of the nocebo itch evocation methodology used in this study and future research into additional brain areas associated with nocebo itch.Show less
Alzheimer’s dementia (AD) is a neurodegenerative brain disorder that impacts females substantially more than men. However, not much research has been conducted on the classification possibilities...Show moreAlzheimer’s dementia (AD) is a neurodegenerative brain disorder that impacts females substantially more than men. However, not much research has been conducted on the classification possibilities of functional MRI (fMRI) on the basis of sex, although fMRI may be a better classifier of AD in women as functional connectivity (FC) research has shown that women with mild cognitive impairment (MCI) show weaker connectivity in the hippocampal area as compared to males. This research investigated if 1) functional connectivity is a better classifier of AD for females compared to males and 2) the addition of functional connectivity to grey matter density for AD classification improves accuracy more for females than for males. The measures grey matter density (GMD), functional connectivity between brain regions (FC) and a combined model of the two measures predicted the classification of AD or control, analyzed separately for males (AD = 30, controls = 74) and females (AD = 46, controls = 99). This was done with a logistic regression analysis with LASSO penalty. The results found that, unlike expected, males increased their AUC value (AUC = 0.941) when the FC measure was combined with the GMD measure (AUC = 0.959). The females however showed a decrease in their AUC value (AUC = 0.876) when the FC measure was combined with the GMD measure (AUC = 0.860). The FC measure also had a higher AUC value on its own in males (AUC = 0.723) versus females (AUC = 0.626). This shows that the FC measure used in this research increases accuracy of AD classification in males and implies that fMRI is not a better classifier of Alzheimer in females and does not improve diagnosis when compared to solely using structural MRI (sMRI).Show less
Research master thesis | Psychology (research) (MSc)
closed access
Introduction: Selective serotonin reuptake inhibitors (SSRI’s) are an effective treatment for many depressed patients, but their disadvantages include a wide range of side effects and a delayed...Show moreIntroduction: Selective serotonin reuptake inhibitors (SSRI’s) are an effective treatment for many depressed patients, but their disadvantages include a wide range of side effects and a delayed treatment response. In contrast, subanesthetic doses of ketamine show acute antidepressant effects. Previous functional connectivity findings implicate the ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), key areas of the default mode network (DMN), in ketamine’s acute antidepressant effect. In addition, psilocybin has also shown acute antidepressant effects with a potential role for the claustrum, an area functionally connected to the DMN. However, pharmacological fMRI findings concerning acute antidepressant drug action may be moderated by the decision to include or exclude a controversial preprocessing step called global signal regression (GSR). In this study, we investigated ketamine’s acute effects on functional connectivity patterns in the brain in order to probe the underlying mechanism of its acute antidepressant effects. Hypotheses: Ketamine acutely decreases functional connectivity between the vmPFC and PCC and between the DMN and claustrum. In addition, these findings will not be affected by the decision to include or exclude GSR. Method: Twenty volunteers were administered ketamine as well as a placebo on separate days in a randomized, double-blind, crossover design. We acquired resting-state functional magnetic resonance imaging (fMRI) data before, during and immediately after the acute phase of administration. Results: No differences in functional connectivity patterns were found between ketamine and placebo. These results were unaffected by the inclusion or exclusion of GSR. Conclusion: It remains unclear which changes in functional connectivity occur in the acute phase of ketamine administration. Future research should investigate the influence of GSR on fMRI findings.Show less
Het is voor behandeling en medicijnonderzoek van belang om goede biomarkers te vinden voor de ziekte van Alzheimer. Atrofie op structurele MRI scans is zo een biomarker. Functionele connectiviteit ...Show moreHet is voor behandeling en medicijnonderzoek van belang om goede biomarkers te vinden voor de ziekte van Alzheimer. Atrofie op structurele MRI scans is zo een biomarker. Functionele connectiviteit (FC) van het Default Mode Network (DMN) via functionele MRI scans kan echter een vroeger waarneembare biomarker zijn. Deze studie heeft dit onderzocht met als hypothesen dat fMRI beter alzheimer kan classificeren dan sMRI in een vroeg stadium, en dat sMRI beter kan classificeren dan fMRI in een laat stadium van alzheimer. Hiervoor is een classificatieanalyse gedaan met als maten voor de structurele MRI: subcorticale volumes, corticale dikte en grijze stof dichtheid (130 predictoren); voor de functionele MRI: functionele connectiviteit van het DMN met 19 andere resting state netwerken, gedefinieerd aan de hand van een Independent Components Analysis (19 predictoren). De classificatieanalyse is gedaan voor zes modellen, waarvan drie voor vroeg stadium en drie voor laat stadium alzheimer. Voor beide stadia zitten in het eerste model de sMRI maten, in het tweede de fMRI maten en in het derde allebei de MRI maten gecombineerd. De steekproef bevatte 249 participanten, waarvan 173 controles en 76 alzheimerpatiënten. De alzheimerpatiënten zijn opgedeeld in vroeg en laat stadium op basis van alzheimerduur en MMSE score en bestond respectievelijk uit 39 en 37 participanten. Uit de resultaten blijkt dat functionele MRI op zichzelf voor zowel vroeg als laat stadium (AUC resp. = 0.46 en 0.71) slechter classificeert dan structurele MRI (AUC resp. = 0.84 en 0.89). Hiermee is de eerste hypothese verworpen en de tweede bevestigd. Opvallend was wel dat het model met zowel structurele als functionele MRI maten beter classificeerde dan structurele MRI op zichzelf voor vroeg stadium data (AUC resp. = 0.86 en 0.84). Hoewel het een kleine verbetering is, suggereert dit wellicht dat FC iets toe kan voegen aan een gecombineerd classificatiemodel voor vroeg stadium alzheimer.Show less
Background: rumination is both a symptom and predictor of major depressive disorder (MDD). In MDD patients, rumination is correlated with depression severity, and for healthy people rumination is a...Show moreBackground: rumination is both a symptom and predictor of major depressive disorder (MDD). In MDD patients, rumination is correlated with depression severity, and for healthy people rumination is a predictor of the onset and duration of a depressive episode. Recently, rumination was shown to be correlated to functional connectivity in the default mode network (DMN) in the brain. During working memory (WM) tasks, the central executive network (CEN) shows high connectivity and the DMN shows low connectivity, whereas during rest this is the other way around. This ‘switching’ between DMN and CEN connectivity is blunted in MDD patients, but it is still unknown whether this ‘switch’ is affected by acute rumination in healthy participants. The aim of the current study is to determine the effect of acute rumination on the switching between the DMN and the CEN in healthy participants. Methods: 36 healthy females, randomly assigned to the acute-rumination group (n=18) or the no-rumination group (n=18) underwent fMRI assessment during a rest-WM task (alternating rest and WM conditions). Only for the acute-rumination group, an acute rumination phase immediately preceded the rest-WM task. Pearson’s correlation was performed to analyze the correlation between the DMN and the CEN in each participant. A mixed ANOVA was performed to analyze the effects of acute rumination. Results: Negative Pearson correlation coefficients were found between DMN and CEN for both groups. A statistically significant interaction effect was found for network (CEN versus DMN) × condition (rest versus WM). However, no statistically significant main effect was found for group (acute-rumination versus no-rumination). Conclusion: Consistent with previous studies an interaction in the expected direction was found between the DMN and CEN. However, this study does not support the effect of acute rumination on this interaction. The current study contributes to an increased understanding of the effect of rumination, and contributes to research of this prominent symptom of MDD and other psychological disorders.Show less
BACKGROUND: Cortical correlates to heart rate variability (HRV) are assumed to involve interconnectivity between single brain areas and large-scale brain networks (LSN) in the extended...Show moreBACKGROUND: Cortical correlates to heart rate variability (HRV) are assumed to involve interconnectivity between single brain areas and large-scale brain networks (LSN) in the extended neurovascular integration model (NVI). Among those are the CEN and the DMN from the triple network model (TNM) and the anterior insula (AI) and the dorsal anterior cingulate cortex (DACC). This study aimed to test if AI and DACC are involved as the SN in FC patterns that correlate to HRV. Second, it was tested if LSN show FC patterns in accordance with the TNM during experimental tasks. METHODS: 27 female participants (18- 35 years) took part in this cross-sectional fMRI study. Experimentally induced FC patterns of the three LSN with HRV as a covariate were used for the statistical model. RESULTS: As hypothesised, the CEN showed significantly more intrinsic FC during the WMT which was associated with HRV. Further, there was an association between HRV and the FC between the CEN and AI/ACC, respectively. Against the hypothesis, an involvement of the full SN could not be confirmed. The results concerning the DMN disconfirm the hypothesis of an increased FC during the rumination condition. Lastly, a trend was visible for lower HRV during the WMT compared to the rumination condition, but this difference did not reach the significance level. CONCLUSION: The present results confirm the AI and ACC as autonomous brain regions involved in FC patterns associated with HRV. This confirmation of the NVI opposes the unexpectedly high FC pattern of the DMN during the WMT, which points to explanatory gaps in the external validity of the model and the role of LSN vs. single brain regions as associates of HRV.Show less
Research master thesis | Psychology (research) (MSc)
closed access
Introduction: The default mode network (DMN) is a large intrinsic network in the brain, which seems to be affected in depressed patients. Also, aberrant heart rate variability (HRV) is often found...Show moreIntroduction: The default mode network (DMN) is a large intrinsic network in the brain, which seems to be affected in depressed patients. Also, aberrant heart rate variability (HRV) is often found in this population. Ketamine is thought to be a fast-acting antidepressant and has shown to have an effect on HRV and intrinsic brain connectivity. In this study, the effect of HRV on resting-state functional connectivity of the DMN and brain activity of areas within the DMN that were significantly correlated with HRV was examined. Also, it was investigated whether ketamine moderated this relationship. Method: Twelve healthy men received an intravenous ketamine or placebo infusion on two occasions. Resting-state functional connectivity and HRV were measured before, during, and after infusion. Dual-regression was used to obtain DMN connectivity scores, while a whole brain analysis was done to determine which brain areas were correlated with HRV. Raw digitized electrocardiogram (EKG), obtained with a pulse oximeter, was analyzed in order to extract HRV data. Multilevel analysis was used to determine the effect of HRV and ketamine on resting-state functional connectivity in the DMN and brain activity in the subgenual anterior cingulate cortex (sgACC), right dorsolateral prefrontal cortex (dlPFC), and the left postcentral gyrus. Results: DMN connectivity strength was negatively related to HRV, but positively related to activity of the right dlPFC and the left postcentral gyrus for the placebo condition. Ketamine was associated with a more profound effect of HRV on DMN connectivity and brain activity within the postcentral gyrus. Discussion: The present results complement recent studies that show that HRV is associated with connectivity strength in the DMN. Implications for the relevance of using ketamine in depressed patients are discussed. Initial increases of DMN connectivity are followed by a decrease in the DMN, which may be beneficial for depressed patients who generally show hyperconnectivity within the DMN. Results thus imply that ketamine has a moderating role in this.Show less
Research master thesis | Developmental Psychopathology in Education and Child Studies (research) (MSc)
open access
2016-12-16T00:00:00Z
This study investigated an aspect of cognitive functioning or more specifically of executive functioning, that appears to be strongly affected in NF1: working memory. The primary goal of this...Show moreThis study investigated an aspect of cognitive functioning or more specifically of executive functioning, that appears to be strongly affected in NF1: working memory. The primary goal of this functional MRI study was to investigate whether or not the neuronal activity during working memory performance differs between NF1 children and controls. A second aim was to investigate the working memory performance outside the scanner. Participants included children with NF1 (N=21, 7 female), and controls (N=18, 10 female). Ages ranged between 8.2 and 19.1 (Mage= 13.12, SD=3.17). Neuronal activity was measured during the N-back task, and working memory performance outside the scanner was measured with the Memory Search 2D task of the ANT program. With respect to the main aim, the group means comparisons revealed non-significant differences. Though, the participants with NF1 had greater activity in the prefrontal cortex, and less activation in the posterior brain regions compared with controls. Overall, the NF1 children performed poorer on the working memory task outside the scanner. They performed even worse on the second, more demanding condition than the controls. These results may be explained by the dysfunction of the protein neurofibromin and a possible compensatory function of brain regions in individuals with NF1. These insights in brain functioning of individuals with NF1 might contribute to the development of intervention or treatment programs, medication and gene therapy.Show less
