While it is well understood that the brain experiences changes across short-term experience/learning and long-term development, it is unclear how these two mechanisms interact to produce... Show moreWhile it is well understood that the brain experiences changes across short-term experience/learning and long-term development, it is unclear how these two mechanisms interact to produce developmental outcomes. Here we test an interactive model of learning and development where certain learning-related changes are constrained by developmental changes in the brain against an alternative development-as-practice model where outcomes are determined primarily by the accumulation of experience regardless of age. Participants (8-29 years) participated in a three-wave, accelerated longitudinal study during which they completed a feedback learning task during an fMRI scan. Adopting a novel longitudinal modeling approach, we probed the unique and moderated effects of learning, experience, and development simultaneously on behavioral performance and network modularity during the task. We found nonlinear patterns of development for both behavior and brain, and that greater experience supported increased learning and network modularity relative to naive subjects. We also found changing brain-behavior relationships across adolescent development, where heightened network modularity predicted improved learning, but only following the transition from adolescence to young adulthood. These results present compelling support for an interactive view of experience and development, where changes in the brain impact behavior in context-specific fashion based on developmental goals. Show less
While it is well understood that the brain experiences changes across short-term experience/learning and long-term development, it is unclear how these two mechanisms interact to produce... Show moreWhile it is well understood that the brain experiences changes across short-term experience/learning and long-term development, it is unclear how these two mechanisms interact to produce developmental outcomes. Here we test an interactive model of learning and development where certain learning-related changes are constrained by developmental changes in the brain against an alternative development-as-practice model where outcomes are determined primarily by the accumulation of experience regardless of age. Participants (8–29 years) participated in a three-wave, accelerated longitudinal study during which they completed a feedback learning task during an fMRI scan. Adopting a novel longitudinal modeling approach, we probed the unique and moderated effects of learning, experience, and development simultaneously on behavioral performance and network modularity during the task. We found nonlinear patterns of development for both behavior and brain, and that greater experience supported increased learning and network modularity relative to naïve subjects. We also found changing brain-behavior relationships across adolescent development, where heightened network modularity predicted improved learning, but only following the transition from adolescence to young adulthood. These results present compelling support for an interactive view of experience and development, where changes in the brain impact behavior in context-specific fashion based on developmental goals. Show less
Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a... Show moreArterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners.The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. To facilitate collaboration and data-exchange, the toolbox follows several standards and recommendations for data structure, provenance, and best analysis practice.ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow.ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts which may increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice. Show less
Nagtegaal, M.; Koken, P.; Amthor, T.; Bresser, J. de; Madler, B.; Vos, F.; Doneva, M. 2020
Demyelination is the key pathological process in multiple sclerosis (MS). The extent of demyelination can be quantified with magnetic resonance imaging by assessing the myelin water fraction (MWF).... Show moreDemyelination is the key pathological process in multiple sclerosis (MS). The extent of demyelination can be quantified with magnetic resonance imaging by assessing the myelin water fraction (MWF). However, long computation times and high noise sensitivity hinder the translation of MWF imaging to clinical practice. In this work, we introduce a more efficient and noise robust method to determine the MWF using a joint sparsity constraint and a pre-computed B-1(+)-T-2 dictionary.A single component analysis with this dictionary is used in an initial step to obtain a B-1(+) map. The T-2 distribution is then determined from a reduced dictionary corresponding to the estimated B-1(+) map using a combination of a non-negativity and a joint sparsity constraint.The non-negativity constraint ensures that a feasible solution with non-negative contribution of each T-2 component is obtained. The joint sparsity constraint restricts the T-2 distribution to a small set of T-2 relaxation times shared between all voxels and reduces the noise sensitivity.The applied Sparsity Promoting Iterative Joint NNLS (SPIJN) algorithm can be implemented efficiently, reducing the computation time by a factor of 50 compared to the commonly used regularized non-negative least squares algorithm. The proposed method was validated in simulations and in 8 healthy subjects with a 3D multiecho gradient- and spin echo scan at 3 T. In simulations, the absolute error in the MWF decreased from 0.031 to 0.013 compared to the regularized NNLS algorithm for SNR = 250. The in vivo results were consistent with values reported in literature and improved MWF-quantification was obtained especially in the frontal white matter. The maximum standard deviation in mean MWF in different regions of interest between subjects was smaller for the proposed method (0.0193) compared to the regularized NNLS algorithm (0.0266). In conclusion, the proposed method for MWF estimation is less computationally expensive and less susceptible to noise compared to state of the art methods. These improvements might be an important step towards clinical translation of MWF measurements. Show less
Nagtegaal, M.; Koken, P.; Amthor, T.; Bresser, J. de; Madler, B.; Vos, F.; Doneva, M. 2020
During adolescence, self-concept develops profoundly, accompanied by major changes in hormone levels. Self-evaluations become more complex, and peers and their opinions increasingly salient.... Show moreDuring adolescence, self-concept develops profoundly, accompanied by major changes in hormone levels. Self-evaluations become more complex, and peers and their opinions increasingly salient. Neuroimaging studies have investigated self- and other-related processing in adolescents, however, the influence of similarity of peers on these processes is still unclear, as well as functional connectivity underlying such processes. We investigated the effect of peer similarity on neural activity and connectivity underlying self- and other-referential processing, by distinguishing between a similar and dissimilar peer when making other-evaluations. Moreover, we explored the association between testosterone and brain activity during self-evaluations. Sixty-six young adolescents underwent functional MRI while performing a trait judgement task in which they indicated whether an adjective described themselves, a similar or a dissimilar classmate. The ventral medial prefrontal cortex (MPFC) showed increased engagement in self-referential processing, and the posterior cingulate cortex and right temporal parietal junction during other-evaluations. However, activity did not differ between the similar and dissimilar other conditions. Functional connectivity of the ventral MPFC included the striatum when evaluating the similar peer and frontoparietal regions when evaluating the dissimilar peer. Furthermore, inter-individual differences in testosterone levels were positively associated with dorsal MPFC activity in males. This study provides insight into the influence of peer similarity on activity and connectivity underlying other-referential processing in young adolescents, and suggests that testosterone affects neural correlates of self-referential processing. Show less
An increasing number of healthy people use methylphenidate, a psychostimulant that increases dopamine and noradrenaline transmission in the brain, to help them focus over extended periods of time.... Show moreAn increasing number of healthy people use methylphenidate, a psychostimulant that increases dopamine and noradrenaline transmission in the brain, to help them focus over extended periods of time. While methylphenidate has been shown to facilitate some cognitive functions, like focus and distractor-resistance, the same drug might also contribute to cognitive impairment, for example, in creativity. In this study, we investigated whether acute administration of a low oral dose (20 mg) of methylphenidate affected convergent and divergent creative processes in a sample of young healthy participants. Also, we explored whether such effects depended on individual differences in ADHD symptoms and working memory capacity. Contrary to our expectations, methylphenidate did not affect participants’ creative performance on any of the tasks. Also, methylphenidate effects did not depend on individual differences in trait hyperactivity–impulsivity or baseline working memory capacity. Thus, although the effects of methylphenidate on creativity might be underestimated in our study due to several methodological factors, our findings do not suggest that methylphenidate impairs people’s ability to be creative. Show less
The human brain is active during rest and hierarchically organized into intrinsic functional networks. These functional networks are largely established early in development, with reports of a... Show moreThe human brain is active during rest and hierarchically organized into intrinsic functional networks. These functional networks are largely established early in development, with reports of a shift from a local to more distributed organization during childhood and adolescence. It remains unknown to what extent genetic and environmental influences on functional connectivity change throughout adolescent development. We measured functional connectivity within and between eight cortical networks in a longitudinal resting-state fMRI study of adolescent twins and their older siblings on two occasions (mean ages 13 and 18 years). We modelled the reliability for these inherently noisy and head-motion sensitive measurements by analyzing data from split-half sessions. Functional connectivity between resting-state networks decreased with age whereas functional connectivity within resting-state networks generally increased with age, independent of general cognitive functioning. Sex effects were sparse, with stronger functional connectivity in the default mode network for girls compared to boys, and stronger functional connectivity in the salience network for boys compared to girls. Heritability explained up to 53% of the variation in functional connectivity within and between resting-state networks, and common environment explained up to 33%. Genetic influences on functional connectivity remained stable during adolescent development. In conclusion, longitudinal age-related changes in functional connectivity within and between cortical resting-state networks are subtle but wide-spread throughout adolescence. Genes play a considerable role in explaining individual variation in functional connectivity with mostly stable influences throughout adolescence. Show less
Klaassens, B.L.; Gerven, J.M.A. van; Klaassen, E.S.; Grond, J. van der; Rombouts, S.A.R.B. 2019
Disruption of cholinergic and serotonergic neurotransmitter systems is associated with cognitive, emotional and behavioural symptoms of Alzheimer's disease (AD). To investigate the responsiveness... Show moreDisruption of cholinergic and serotonergic neurotransmitter systems is associated with cognitive, emotional and behavioural symptoms of Alzheimer's disease (AD). To investigate the responsiveness of these systems in AD we measured the effects of a single-dose of the selective serotonin reuptake inhibitor citalopram and acetylcholinesterase inhibitor galantamine in 12 patients with AD and 12 age-matched controls on functional brain connectivity with resting state functional magnetic resonance imaging. In this randomized, double blind, placebo-controlled crossover study, functional magnetic resonance images were repeatedly obtained before and after dosing, resulting in a dataset of 432 scans. Connectivity maps of ten functional networks were extracted using a dual regression method and drug vs. placebo effects were compared between groups with a multivariate analysis with signals coming from cerebrospinal fluid and white matter as covariates at the subject level, and baseline and heart rate measurements as confound regressors in the higher-level analysis (at p < 0.05, corrected). A galantamine induced difference between groups was observed for the cerebellar network. Connectivity within the cerebellar network and between this network and the thalamus decreased after galantamine vs. placebo in AD patients, but not in controls. For citalopram, voxelwise network connectivity did not show significant group x treatment interaction effects. However, we found default mode network connectivity with the precuneus and posterior cingulate cortex to be increased in AD patients, which could not be detected within the control group. Further, in contrast to the AD patients, control subjects showed a consistent reduction in mean connectivity with all networks after administration of citalopram. Since AD has previously been characterized by reduced connectivity between the default mode network and the precuneus and posterior cingulate cortex, the effects of citalopram on the default mode network suggest a restoring potential of selective serotonin reuptake inhibitors in AD. The results of this study also confirm a change in cerebellar connections in AD, which is possibly related to cholinergic decline. Show less
Klaassens, B.L.; Gerven, J.M.A. van; Klaassen, E.S.; Grond, J. van der; Rombouts, S.A.R.B. 2019
Disruption of cholinergic and serotonergic neurotransmitter systems is associated with cognitive, emotional and behavioural symptoms of Alzheimer's disease (AD). To investigate the responsiveness... Show moreDisruption of cholinergic and serotonergic neurotransmitter systems is associated with cognitive, emotional and behavioural symptoms of Alzheimer's disease (AD). To investigate the responsiveness of these systems in AD we measured the effects of a single-dose of the selective serotonin reuptake inhibitor citalopram and acetylcholinesterase inhibitor galantamine in 12 patients with AD and 12 age-matched controls on functional brain connectivity with resting state functional magnetic resonance imaging. In this randomized, double blind, placebo-controlled crossover study, functional magnetic resonance images were repeatedly obtained before and after dosing, resulting in a dataset of 432 scans. Connectivity maps of ten functional networks were extracted using a dual regression method and drug vs. placebo effects were compared between groups with a multivariate analysis with signals coming from cerebrospinal fluid and white matter as covariates at the subject level, and baseline and heart rate measurements as confound regressors in the higher-level analysis (at p < 0.05, corrected). A galantamine induced difference between groups was observed for the cerebellar network. Connectivity within the cerebellar network and between this network and the thalamus decreased after galantamine vs. placebo in AD patients, but not in controls. For citalopram, voxelwise network connectivity did not show significant group x treatment interaction effects. However, we found default mode network connectivity with the precuneus and posterior cingulate cortex to be increased in AD patients, which could not be detected within the control group. Further, in contrast to the AD patients, control subjects showed a consistent reduction in mean connectivity with all networks after administration of citalopram. Since AD has previously been characterized by reduced connectivity between the default mode network and the precuneus and posterior cingulate cortex, the effects of citalopram on the default mode network suggest a restoring potential of selective serotonin reuptake inhibitors in AD. The results of this study also confirm a change in cerebellar connections in AD, which is possibly related to cholinergic decline. Show less
Klaassens, B.L.; Van Gerven, J.M.A.; Klaassen, E.S.; Van der Grond, J.; Rombouts, S.A.R.B. 2019
Our mistakes often have negative consequences for ourselves, but may also harm the people around us. Continuous monitoring of our performance is therefore crucial for both our own and others’ well... Show moreOur mistakes often have negative consequences for ourselves, but may also harm the people around us. Continuous monitoring of our performance is therefore crucial for both our own and others’ well-being. Here, we investigated how modulations in responsibility for other’s harm affects electrophysiological correlates of performance-monitoring, viz. the error-related negativity (ERN) and error positivity (Pe). Healthy participants (N = 27) performed a novel social performance-monitoring paradigm in two responsibility contexts. Mistakes made in the harmful context resulted in a negative consequence for a co-actor, i.e., hearing a loud aversive sound, while errors in the non-harmful context were followed by a soft non-aversive sound. Although participants themselves did not receive auditory feedback in either context, they did experience harmful mistakes as more distressing and reported higher effort to perform well in the harmful context. ERN amplitudes were enhanced for harmful compared to non-harmful mistakes. Pe amplitudes were unaffected. The present study shows that performing in a potentially harmful social context amplifies early automatic performance-monitoring processes and increases the impact of the resulting harmful mistakes. These outcomes not only further our theoretical knowledge of social performance monitoring, but also demonstrate a novel and useful paradigm to investigate aberrant responsibility attitudes in various clinical populations. Show less
In cognitive neuroscience there is a growing interest in individual differences. We propose the Multiple Indicators Multiple Causes (MIMIC) model of combined behavioral and fMRI data to determine... Show moreIn cognitive neuroscience there is a growing interest in individual differences. We propose the Multiple Indicators Multiple Causes (MIMIC) model of combined behavioral and fMRI data to determine whether such differences are quantitative or qualitative in nature. A simulation study revealed the MIMIC model to have adequate power for this goal, and parameter recovery to be satisfactory. The MIMIC model was illustrated with a re-analysis of Van Duijvenvoorde et al. (2016) and Blankenstein et al. (2018) decision making data. This showed individual differences in Van Duijvenvoorde et al. (2016) to originate in qualitative differences in decision strategies. Parameters indicated some individuals to use an expected value decision strategy, while others used a loss minimizing strategy, distinguished by individual differences in vmPFC activity. Individual differences in Blankenstein et al. (2018) were explained by quantitative differences in risk aversion. Parameters showed that more risk averse individuals preferred safe over risky choices, as predicted by heightened vmPFC activity. We advocate using the MIMIC model to empirically determine, rather than assume, the nature of individual differences in combined behavioral and fMRI datasets. Show less
Karch, J.D.; Fivelich, E.; Wenger, E.; Lisofski, N.; Becker, M.; Butler, O.; ... ; Kühn, S. 2019
Adequate reliability of measurement is a precondition for investigating individual differences and age-related changes in brain structure. One approach to improve reliability is to identify and... Show moreAdequate reliability of measurement is a precondition for investigating individual differences and age-related changes in brain structure. One approach to improve reliability is to identify and control for variables that are predictive of within-person variance. To this end, we applied both classical statistical methods and machine-learning-inspired approaches to structural magnetic resonance imaging (sMRI) data of six participants aged 24–31 years gathered at 40–50 occasions distributed over 6–8 months from the Day2day study. We explored the within-person associations between 21 variables covering physiological, affective, social, and environmental factors and global measures of brain volume estimated by VBM8 and FreeSurfer. Time since the first scan was reliably associated with Freesurfer estimates of grey matter volume and total cortex volume, in line with a rate of annual brain volume shrinkage of about 1 percent. For the same two structural measures, time of day also emerged as a reliable predictor with an estimated diurnal volume decrease of, again, about 1 percent. Furthermore, we found weak predictive evidence for the number of steps taken on the previous day and testosterone levels. The results suggest a need to control for time-of-day effects in sMRI research. In particular, we recommend that researchers interested in assessing longitudinal change in the context of intervention studies or longitudinal panels make sure that, at each measurement occasion, (a) a given participant is measured at the same time of day; (b) all participants are measured at about the same time of day. Furthermore, the potential effects of physical activity, including moderate amounts of aerobic exercise, and testosterone levels on MRI-based measures of brain structure deserve further investigation. Show less
Gong, N.J.; Dibb, R.; Bulk, M.; Weerd, L. van der; Liu, C.L. 2019
