Background Alzheimer's dementia (AD) and mild cognitive impairment (MCI) are neurodegenerative conditions associated with cognitive decline. Previous research suggests that motor impairments are...Show moreBackground Alzheimer's dementia (AD) and mild cognitive impairment (MCI) are neurodegenerative conditions associated with cognitive decline. Previous research suggests that motor impairments are also present in individuals with MCI and AD. This thesis study aims to evaluate motor sequence learning abilities in patients with amnestic MCI (aMCI) and AD compared to healthy controls. This thesis study also explores the relationship between amyloid-β burden, a known biomarker for MCI and AD, and motor sequence learning to study whether such motor learning could also be a behavioral biomarker. This is because measuring amyloid-β is very costly and invasive, and thus the search for other biomarkers is important. Methods A cross-sectional design was employed, and participants included 28 AD patients, 33 aMCI patients, and 53 healthy controls. Motor sequence learning was assessed using a computerized task measuring reaction time and accuracy per trial, and with this information the rate and final amount of learning was calculated, i.e. how fast and how much information the participants are able to learn, respectively. Amyloid-β burden was measured using PET imaging, with higher burden reflecting more severity of the symptoms of aMCI and AD. Results The final amount of learning was not different amongst the groups, and the rate of learning was only significantly different between the AD and aMCI groups, with the AD groups showing a faster rate of learning. The AD and healthy control group did not, however, differ significantly in terms of rate of learning. The amount of amyloid-β in the brain was not associated with motor sequence learning abilities. Conclusion The findings suggest that motor sequence learning abilities are preserved in individuals with aMCI and AD, both in terms of how fast and how much they learn. In fact, patients with AD showed a faster rate of learning than patients with aMCI, although this was not found when comparing the AD patients with the healthy individuals. It is possible that this finding is because patients had more to learn by the end of the task than the aMCI group given that their memory is worse, and displayed a faster rate of learning due to this. This thesis study also suggests that motor sequence learning is not a behavioral biomarker for aMCI and AD. The search for less invasive and more easily measurable biomarkers continues to be imperative.Show less
Goal-directed behaviour and error-monitoring are believed to be interrelated, because it is often seen that people with executive dysfunction show problems in strategic behaviour and outcome...Show moreGoal-directed behaviour and error-monitoring are believed to be interrelated, because it is often seen that people with executive dysfunction show problems in strategic behaviour and outcome monitoring, including the inability to recognise and keep track of one’s own errors. Prior research has demonstrated Parkinson’s disease-related impairments in both of these functions. However, their relationship has not yet been investigated. This study aims to compare the relationship between error-monitoring and goal-directed behaviour in healthy adults versus those with Parkinson's disease (PD). The sample included 30 healthy participants (Mage=65.7; 19 female, 11 male) and 6 participants with PD (Mage=61; 1 female, 5 male). Goal-directed behaviour was assessed using the Tower Test, and error-monitoring was measured using a modified version of the Attentional Network Task. MANOVA was conducted to examine whether the healthy control group and PD group differed significantly from each other in their average outcomes on error-monitoring and goal-directed behaviour. Multiple regression analysis was conducted to determine if there was a difference in the relationship between healthy adults and people with PD. To account for assumption violations and the small sample size, we additionally used Bayesian and non-parametrical approaches. higher compared to individuals with PD on the Attentional Network Task. (H(1)=4.222, p=.040, g=.843), but no significant differences were found in the performances on the Tower Test. The results showed no significant difference between the relationship in error-monitoring and goal-directed behaviour between healthy adults and people with PD. Additionally, the present data provide moderate evidence that the performance on error-monitoring and goal-directed behaviour did not differ between people with PD and healthy adults (R2=.058, BF01=5.422). Overall, the findings suggest that there is no difference in the relationship between error-monitoring and goal-directed behaviour in individuals with PD compared to healthy controls. Additionally, the results suggest that error-monitoring, but not goal-directed behaviour, in individuals with PD is impaired. Our findings imply that future interventions should focus on improving executive functioning, particularly error-monitoring, in individuals with PD.Show less
The valuation of one’s self-worth, i.e., self-esteem, is derived from social feedback throughout life. During adolescence, the period between ages 10 to 19, many changes occur in one's social...Show moreThe valuation of one’s self-worth, i.e., self-esteem, is derived from social feedback throughout life. During adolescence, the period between ages 10 to 19, many changes occur in one's social environment– peers gain importance, and dependency on parents decreases. However, parents continue to influence self-esteem. Although the early parent-child relationship has been linked to self-esteem formation, it is unclear how perceived parenting climate influences self-esteem updating in adolescence in response to peer feedback, as these mechanisms have only been studied in young adults (individuals aged 18–25). This study used self-reports about perceived parenting, alongside computational modelling and functional magnetic resonance imaging (fMRI) to investigate how parenting climate co-varies with neurocognitive mechanisms supporting self-esteem formation in 61 healthy adolescents (Mage = 15.8; SD age = 1.42). The adolescents performed a social evaluation task during fMRI scanning which required them to predict “likes” or “dislikes” from two groups of raters and to rate their self-esteem every 2 to 3 trials. Using a computational model, we extracted a set of variables about the adolescents’ self-esteem in response to the task and performed a canonical correlation analysis to link it to a set of self-reports collected about parenting climate. The canonical correlation analysis yielded a single significant canonical dimension, Wilks’s λ = 0.04, F(117,305) = 1.35, p = 0.022, which we labelled “positive parenting”. “Positive parenting” was associated with high levels of perceived maternal care, low maternal conflict, and low emotional abuse. Adolescents scoring higher on this dimension exhibited more responsive, fluctuating self-esteem (higher self-esteem instability) compared to their lower-scoring peers, 𝑠𝑡𝑎𝑛𝑑𝑎𝑟𝑑𝑖𝑠𝑒𝑑 𝑐𝑎𝑛𝑜𝑛𝑖𝑐𝑎𝑙 𝑐𝑜𝑒𝑓𝑓𝑖𝑐𝑖𝑒𝑛𝑡 = 0.31. Our study in adolescents did not find activation in 𝑤1 neural regions that were previously proposed to represent the neural processes underlying self-esteem formation in young adults (VS/sgACC: z = 1.84, p = 0.065; vmPFC: z = 0.50, p = 0.618). Lastly, adolescents scoring lower on this dimension did not present with a neural phenotype of psychiatric vulnerability previously found in young adults (AI responses to SPEs ρ(59) = 0.028, p = 0.831; insula-vmPFC functional connectivity ρ(59) = 0.045, p = 0.731). This study suggests that more responsive, fluctuating self-esteem associated with the “positive parenting” dimension may be adaptive in the developmental stage of adolescence, and that developmental differences may be present in neurocognitive mechanisms supporting self-esteem updating in adolescents versus in young adults.Show less
Apart from its motor symptoms, Parkinson´s disease (PD) is characterized by cognitive deficits; among these, executive functioning (EF) deficits are common. Stroke studies have shown a role of the...Show moreApart from its motor symptoms, Parkinson´s disease (PD) is characterized by cognitive deficits; among these, executive functioning (EF) deficits are common. Stroke studies have shown a role of the whole thalamus, and specifically the medial nuclear group (Mng), in EF. Although in PD studies have shown volume loss in the thalamus and Mng, little is known about the relationship between this phenomenon and EF deficits in PD. We aimed to address this gap and examine the relationship between thalamic and Mng volumes and EF in PD. As the thalamus is difficult to segment due to poor tissue contrast, we also aimed to explore whether using Phase-Sensitive Inversion Recovery MRI scans in addition to T1 MRI scans (T1+PSIR MRI) would optimize automatic thalamic segmentation over using T1 MRI scans alone. A total of 76 PD participants underwent T1 and PSIR MRI scans and completed tests measuring verbal fluency, resistance to cognitive interference and planning abilities, which were used to calculate an EF composite score. We found that using T1+PSIR MRI scans resulted in a more accurate thalamic segmentation as shown by less thalamic overestimation especially in the lateral and anteroventral nuclear groups, and smaller thalamic and nuclear groups volumes. We used the derived volumes to relate to global EF performance. Results showed that total thalamic and total Mng volumes were not significantly related to global EF performance (β = .08, t = 1.24, p = .22; β = .16, t = 1.71, p = .09, respectively). Results of exploratory analyses showed a positive significant relationship between left (β = .16, t = 2.26, p = .02) and right (β = .18, t = 2.67, p = .01) thalamic volumes and left (β = .25, t = 2.84, p = .01) Mng volume and verbal fluency performance. In this thesis project we demonstrated that automatic thalamic segmentation can be optimized by using PSIR MRI scans. Although the association between thalamic and Mng volumes and global EF in PD is not supported in this thesis project, volumes seem to be specifically associated with verbal fluency. We propose that this could be due to the role of the Mng in cognitive flexibility. Supported by future longitudinal studies, our findings could have implications for early diagnosis and effective management of verbal fluency deficits in PD.Show less
This study focuses on neurodegenerative diseases inherited in an autosomal dominant manner for which offspring are 50% at-risk of disease. Being at-risk of a genetic neurodegenerative disease has...Show moreThis study focuses on neurodegenerative diseases inherited in an autosomal dominant manner for which offspring are 50% at-risk of disease. Being at-risk of a genetic neurodegenerative disease has been shown to impact psychological well-being as some studies have reported significant levels of anxiety and depression in mutation carriers. Other studies have found no significant psychological impact in mutation carriers. In addition to conflicting results, few studies have examined the psychological impact in those atrisk before predictive-testing. The aim of this study was to examine the effect of being 50% at risk of an autosomal dominant neurodegenerative disease, defined by having a positive family history, on depression and anxiety as compared to healthy controls with no family history of dominant neurodegenerative disease. Additionally, we aimed to examine levels of depression and anxiety in different at-risk awareness groups (mutation carrier, mutation non-carrier or unaware) and different types of disease (Huntington’s disease and “Other”, e.g., familial Alzheimer’s disease and frontotemporal dementia) compared to healthy controls. Seventy-two articles were included in the systematic review, 10 articles were included in the depression meta-analysis and seven articles were included for the anxiety meta-analysis. The systematic review showed that some studies reported significantly higher levels of anxiety and depression in at-risk individuals, particularly mutation carriers, compared to controls while other studies reported no significant difference. The systematic review also showed that; a) mutation non-carriers and partners of those at-risk were used as healthy controls; b) studies used similar instruments to measure depression and anxiety; and c) most studies were on Huntington’s disease. The meta-analysis for depression showed that those at-risk do experience significantly higher levels of depression compared to healthy controls (p = .05). The anxiety meta-analysis was non-significant. This study highlights the psychological needs for individuals at-risk and suggests future research to have; a) healthy controls that do not include non-mutation carriers and partners of those at-risk; b) better instruments to measure anxiety and depression in those at-risk; and c) to examine other neurodegenerative diseases in addition to Huntington’s disease.Show less
The valuation of one’s self-worth, i.e., self-esteem, is derived from social feedback throughout life. During adolescence, the period between ages 10 to 19, many changes occur in one's social...Show moreThe valuation of one’s self-worth, i.e., self-esteem, is derived from social feedback throughout life. During adolescence, the period between ages 10 to 19, many changes occur in one's social environment– peers gain importance, and dependency on parents decreases. However, parents continue to influence self-esteem. Although the early parent-child relationship has been linked to self-esteem formation, it is unclear how perceived parenting climate influences self-esteem updating in adolescence in response to peer feedback, as these mechanisms have only been studied in young adults (individuals aged 18–25). This study used self-reports about perceived parenting, alongside computational modelling and functional magnetic resonance imaging (fMRI) to investigate how parenting climate co-varies with neurocognitive mechanisms supporting self-esteem formation in 61 healthy adolescents (Mage = 15.8; SD age = 1.42). The adolescents performed a social evaluation task during fMRI scanning which required them to predict “likes” or “dislikes” from two groups of raters and to rate their self-esteem every 2 to 3 trials. Using a computational model, we extracted a set of variables about the adolescents’ self-esteem in response to the task and performed a canonical correlation analysis to link it to a set of self-reports collected about parenting climate. The canonical correlation analysis yielded a single significant canonical dimension, Wilks’s λ = 0.04, F(117,305) = 1.35, p = 0.022, which we labelled “positive parenting”. “Positive parenting” was associated with high levels of perceived maternal care, low maternal conflict, and low emotional abuse. Adolescents scoring higher on this dimension exhibited more responsive, fluctuating self-esteem (higher self-esteem instability) compared to their lower-scoring peers, 𝑠𝑡𝑎𝑛𝑑𝑎𝑟𝑑𝑖𝑠𝑒𝑑 𝑐𝑎𝑛𝑜𝑛𝑖𝑐𝑎𝑙 𝑐𝑜𝑒𝑓𝑓𝑖𝑐𝑖𝑒𝑛𝑡 𝑤1 = 0.31. Our study in adolescents did not find activation in neural regions that were previously proposed to represent the neural processes underlying self-esteem formation in young adults (VS/sgACC: z = 1.84, p = 0.065; vmPFC: z = 0.50, p = 0.618). Lastly, adolescents scoring lower on this dimension did not present with a neural phenotype of psychiatric vulnerability previously found in young adults (AI responses to SPEs ρ(59) = 0.028, p = 0.831; insula-vmPFC functional connectivity ρ(59) = 0.045, p = 0.731). This study suggests that more responsive, fluctuating self-esteem associated with the “positive parenting” dimension may be adaptive in the developmental stage of adolescence, and that developmental differences may be present in neurocognitive mechanisms supporting self-esteem updating in adolescents versus in young adults.Show less
Being bullied has shown to negatively influence the normal development. Victims of bullying may develop a disrupted image of the social world. According to the social defeat hypothesis of psychosis...Show moreBeing bullied has shown to negatively influence the normal development. Victims of bullying may develop a disrupted image of the social world. According to the social defeat hypothesis of psychosis, being mistreated by other people, changes how the brain functions, which manifest in psychotic like experiences. These experiences (e.g. seeing or hearing things that are not there), are probably the first signs of a lifelong psychotic disorder such as schizophrenia. The first aim of this study was to test this hypothesis in in a high-risk group (youth with a greater chance to develop a psychiatric disorder). This study offers support for the social defeat hypothesis of psychosis, as the results indicated that being bullied is associated with more psychotic like experiences. It is however possible that the same factors (e.g. genes) that caused PLEs, increased the chance of being bullied. In this case the association is not due to social defeat. One study found that youth with PLEs were more likely to bully others compared to youth without PLEs. Therefore, the second aim of this study was to investigate whether being socially defeated by being bullied, causes youth to bully others. The results showed that being bullied was associated with bullying others. However, having PLEs was not associated with bullying others. It is possible that being socially defeated by peers, only leads to PLEs in youth with psychosis liability (genetically a greater chance to develop a psychotic disorder), while leading to bullying others in youth without psychosis liability. Another explanation is that bullying others when being bullied yourself, has other underlying reasons then social defeat (e.g. learned to become the bully). By including factors that increase the risk for PLEs in future research, the role of social defeat on PLEs can be further investigated.Show less
Aim: This study aimed to determine whether qualitative assessment of the verbal fluency test could help in differentiating between the behavioral subtype of frontotemporal dementia (bvFTD) and the...Show moreAim: This study aimed to determine whether qualitative assessment of the verbal fluency test could help in differentiating between the behavioral subtype of frontotemporal dementia (bvFTD) and the three primary progressive aphasia variants, semantic (svPPA), non-fluent (nfvPPA) and logopenic (lvPPA). We examined differences in clustering of words, switching between strategies, lexical frequency, age of acquisition, neighborhood density and word length. Method: Patients diagnosed with bvFTD (N = 51) or PPA (27 svPPA, 25 nfvPPA, and 34 lvPPA) and a control group (N = 25) performed a semantic and letter fluency task. Clustering and switching were assessed by two independent raters. Lexical frequency, age of acquisition, neighborhood density and word length were derived from existing databases. Between-group differences were examined and diagnostic performance was assessed. Lastly, associations with memory, language, processing speed and executive functioning were examined. Results: Patients with bvFTD produced more words on semantic fluency, more clusters and larger total cluster size compared to svPPA. svPPA patients produced words with higher lexical frequency and lower age of acquisition on letter fluency compared to all groups. nfvPPA patients produced fewer words on letter fluency compared to svPPA patients, but had larger cluster sizes. lvPPA patients produced shorter words with a higher neighborhood density on letter fluency compared to bvFTD patients. The qualitative measures were successful in discriminating bvFTD patients from PPA patients and svPPA patients from lvPPA patietns and nfvPPA patients. Distinction between nfvPPA patients and lvPPA patients was significant only after adding total number of words. Lexical frequency, age of acquisition, neighborhood density and word length were positively related to language and semantic fluency. Conclusion: The differences found on the qualitative variables are in line with what is known about the type of impairments in each subtype of FTD. Our findings show the wealth of information that can be obtained from the verbal fluency test and its usefulness in discriminating between subtypes of FTD. Qualitative variables alone are insufficient in discriminating between lvPPA and nfvPPA, however together with the quantative measures differentiation is possible. This highlights the usefulness of extensive analysis of the verbal fluency test.Show less
Sensorimotor adaptation is needed to adjust motor behaviour to the needs of different situations. A distinction can be made between early and late adaptation. Early adaptation means a fast...Show moreSensorimotor adaptation is needed to adjust motor behaviour to the needs of different situations. A distinction can be made between early and late adaptation. Early adaptation means a fast improvement, where mainly cognitive processes are of importance. Fast adaptation is slower and more automatic. This master thesis study examined when the ability to adapt movements is developed in children and from which age declines start to occur in adults. While former studies looked into one side of the age range, this study took both the developmental and aging perspective into account. A sample of 463 participants between 8 and 73 years old took part in the experiment, conducted in the NEMO Science Museum in Amsterdam. The participants completed a motor task in which they had to use a joystick to move a cursor towards a target that was presented on a computer screen. In the baseline phase they received normal visual feedback. In the adaptation phase a 45 degree rotation was introduced, causing a different response when moving the joystick. The participants had to adapt their movements to this rotation in order to still be able to hit the targets. After the adaptation phases, the feedback returned back to normal. Participants needed to de-adapt in order to hit the targets again. The typical adaptation pattern was replicated, meaning that participants performed well in the baseline phase, had difficulty hitting the targets in the adaptation phase but improved after practicing. In the de-adaptation phase the participants again had some difficulty and also improved after some practice. In all phases an effect of age was found, meaning that young children and older adults both had more difficulty to successfully adapt. Children are able to adapt from their early teenage years. Declines in adults occur around their fourth decade of life. De-adaptation develops a bit later in children compared to adaptation. In adults declines in de-adaptation occur from the third decade of life. This knowledge can be used during treatment of motor problems, where treatments can be longer or more frequent for certain groups because they have more difficulty with adaptation.Show less
Novelty exposure has been found to elicit a positive impact on declarative learning. It is currently unknown whether this effect is also present in procedural learning. This study aimed to evaluate...Show moreNovelty exposure has been found to elicit a positive impact on declarative learning. It is currently unknown whether this effect is also present in procedural learning. This study aimed to evaluate the effect of spatial novelty exposure and age on sensorimotor adaptation learning by using a mixed between-within subjects, cross-sectional design. A total of 463 healthy participants aged from 8 to 73 years (M = 23.8, SD = 16.5) were divided into 5 age groups: children (8-12), adolescents (13- 18), young adults (19-34), middle-aged adults (35-54), and older adults (≥ 55). Participants explored either a novel or familiar virtual environment before completing a manual adaptation task in which they were exposed to a perturbation in visuomotor feedback. Direction Error (DE), the angle between the optimal trajectory of the joystick and the actual trajectory at peak movement velocity was measured for each movement. A mixed factorial ANOVA was run on DEs and showed a significant difference between age groups F(4, 453) = 2.70, p = .030, ηp 2 = .03. A typical adaptation pattern was present F(7, 6.46) = 434.26, p < .001, η² = .49 and was found to be significantly different between age groups F(28, 3171) = 2.86, p < .001, η² = .03. The learning rate was determined by calculating the decay constant for the early adaptation, late adaptation, and de-adaptation phase of the sensorimotor adaptation task and was fit using an exponential decay function. A mixed factorial ANOVA was run on learning rate and showed a significant difference between all three phases F(1.56, 704.43) = 146.24, p < .001, ηp 2 = .24. Age groups differed in their learning rate per phase F(6.22, 704.43) = 12.00, p < .001, ηp 2 = .10. Novelty exposure did not significantly influence DE or learning rate, nor was age found to be an influencing factor on this. The results from this study did not find that spatial novelty influences sensorimotor adaptation. In conjunction with previous research results, this implies that novelty exposure does not elicit the same positive effect on procedural learning as it has been found to have on declarative learning.Show less
Objective: In addition to the well-known motor symptoms, Parkinson’s disease (PD) patients also frequently experience disabling non-motor symptoms, such as impulse control disorders (ICDs). The...Show moreObjective: In addition to the well-known motor symptoms, Parkinson’s disease (PD) patients also frequently experience disabling non-motor symptoms, such as impulse control disorders (ICDs). The present study aimed to assess the predictive value of depression and anxiety, and the interaction of these factors with dopaminergic replacement therapy (DRT), for ICD development in de novo PD patients. Methods: Using the Parkinson’s Progression Markers Initiative database, a total of 334 de novo PD patients with a negative ICD screen at baseline (assessed with the Questionnaire for Impulsive‐ Compulsive Disorders short form QUIP-S) were included in the present study. Baseline depression and anxiety were measured by the Geriatric Depression Scale (GDS-15) and the State-Trait-Anxiety Inventory (STAI-Y), respectively. The outcome measures were ICD presence (a positive QUIP-S score) at follow-up visits, and ICD onset duration (time in months from baseline until ICD development). Binominal logistic regression and multiple regression analyses were performed to assess predictors for ICD presence and duration until ICD onset, respectively. Results: In total, 149 participants (44.6%) developed an ICD and the time of ICD onset was on average 34.54 months (SD=24.74) after baseline. Baseline STAI-Y scores were a significant predictor of ICD presence at follow-up visits, and higher scores were associated with an increased likelihood of developing an ICD (OR=1.02, 95% CI 1.00,1.05, p=.036). The first DRT type also significantly predicted ICD incidence, and dopamine agonists were associated with 2.34 higher odds (95% CI 1.45,3.86, p=.001) of developing an ICD, compared to levodopa or other medication types. Both effects were not confounded by age, gender or UPDRS motor score. GDS-15 scores and the interaction terms GDS-15 x DRT type and STAI-Y x DRT type did not significantly predict ICD presence (all ps>.299). None of the investigated factors significantly predicted ICD onset duration (all ps>.091). Implications: The finding that increased anxiety levels in de novo PD patients represent an ICD risk factor highlights the need for early and routine based anxiety screening in these patients. Additionally, clinicians should carefully consider the first choice of DRT, given that patients who received dopamine agonists as their first medication type encountered an increased ICD risk.Show less
