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)
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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
Depression is a common, debilitating mental disorder. Due to its frequency and negative effects, there is a strong need for the development of efficient treatments. Especially since a large...Show moreDepression is a common, debilitating mental disorder. Due to its frequency and negative effects, there is a strong need for the development of efficient treatments. Especially since a large percentage of people is resistant to commonly prescribed antidepressant interventions. Rumination is an important symptom and predictor of depression, and it has been linked to dysfunctional default mode network (DMN) connectivity in depression. A better understanding of the relationship between the DMN and rumination may help us understand depression better, which may support the development of new interventions. This study focuses on rumination and its effects on the DMN during a working memory (WM) task in healthy participants. This was tested by inducing rumination in participants before the WM task, where DMN and DMN subsystem connectivity were compared to participants who did not receive rumination induction. Results showed that inducing rumination during tasks requiring external focus does not increase functional connectivity of the DMN. Both the overall DMN connectivity and subsystem connectivity did not show any significant differences between groups. Furthermore, time-related changes in DMN connectivity were explored, but results indicated no significant changes either. Studies with depression showed that DMN connectivity is increased during WM tasks which was linked to rumination. But in this study with healthy participants DMN connectivity was suppressed during the WM task, even after inducing rumination. Therefore, these findings suggest that inducing rumination does not lead to insufficient DMN suppression in healthy participants, and that insufficient depression may be exclusive to depression.Show less
Research master thesis | Psychology (research) (MSc)
closed access
Atomoxetine is a prescription drug often used to restore executive (or cognitive) functioning in patients with attention-deficit/hyperactivity disorder and other neuropsychiatric conditions....Show moreAtomoxetine is a prescription drug often used to restore executive (or cognitive) functioning in patients with attention-deficit/hyperactivity disorder and other neuropsychiatric conditions. Moreover, this drug may potentially be ingested by healthy individuals who seek to improve their cognitive performance. However, the effect of atomoxetine on healthy brain functioning remains largely unclear. Network approaches have become useful for studying how the functional connectivity between brain regions may enhance or hinder executive functioning. Accordingly, to further examine the underlying mechanisms of action of atomoxetine, it is relevant to explore how this drug influences the functional connectivity of a large-scale brain network involved in the control of top-down processes: the executive control network (ECN). The aim of this study was thus to investigate the effect of atomoxetine (40 mg) on the functional connectivity of the ECN in healthy volunteers (n = 15). Network analyses were conducted on unpublished functional magnetic resonance (fMRI)-data collected by Chamberlain and colleagues (2009) in a double-blind, placebo-controlled, within-subjects, crossover design in which participants completed a goal-directed fMRI-task (i.e., the temporal discounting task), probing the ECN. Contrary to expectations, a paired-samples permutation test, corrected for multiple comparisons by means of a threshold free cluster enhancement, revealed that the functional connectivity of the participants’ ECN does not increase significantly after ingesting atomoxetine as compared to placebo (p > .05 corrected). Nevertheless, exploratory analyses indicated that, relative to placebo, atomoxetine significantly strengthens the functional connectivity of a frontoparietal network highly associated with cognition and language paradigms (t(14) = 7.61, p = .003). Together, these results suggest that, in healthy individuals, atomoxetine might not have enhancing effects on the processes supported by the ECN but (potentially) on those supported by a frontoparietal network. Atomoxetine might thus have beneficial effects in the cognitive performance of healthy individuals by facilitating certain processes associated with both cognition and language. Further research is however warranted to corroborate these findings in confirmatory studies and enhance the understanding of the underlying mechanisms of action of atomoxetine in healthy brain functioning.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
