Biology subjects

Zwiers, M. P.

Publications and source records attributed to Zwiers, M. P..

9 recordsLinked to original sources

bioRxiv2024

Normative trajectories of R1, R2* and magnetic susceptibility in basal ganglia on healthy ageing

Quantitative MRI techniques, including R1, R2*, and magnetic susceptibility mapping, have emerged as promising tools for generating surrogate imaging markers of brain tissue microstructure, enabling non-invasive in vivo measurements associated with myelination and iron deposition. Gaining insights into how these quantitative measurements evolve throughout a normal lifespan can enhance our understanding of brain maturation processes and facilitate the study of disease-related microstructural changes by distinguishing pathological alterations from normal brain development. In this study, we established the normative trajectories of R1, R2*, and magnetic susceptibility in the basal ganglia at 3T. We used a healthy ageing cohort comprising 260 subjects with an evenly distributed age range and sex ratio throughout adulthood. Utilizing the non-parametric Gaussian Process Regression model to derive the normative trajectories, we found that R1 in these structures predominantly exhibit a quadratic shape over age, while R2* and magnetic susceptibility are primarily linear. We validated the normative trajectories of R2* and magnetic susceptibility using an independent cohort. Additionally, we demonstrated that the spatial distributions of the quantitative MRI parameters also change with age in the putamen and caudate nucleus. This study not only reinforces existing findings on the association between age and qMRI but also provides valuable resources for studying cognitive ageing, in conjunction with the behavioural data available in the same data collection.

neuroscience↗

bioRxiv2023

The Advanced BRain Imaging on ageing and Memory (ABRIM) data collection: Study protocol and rationale

To understand the neurocognitive mechanisms that underlie heterogeneity in cognitive ageing, recent scientific efforts have led to a growing public availability of imaging cohort data. The Advanced BRain Imaging on ageing and Memory (ABRIM) project aims to add to these existing datasets by taking an adult lifespan approach to provide a cross-sectional, normative database with a particular focus on connectivity, myelinization and iron content of the brain in concurrence with cognitive functioning, mechanisms of reserve, and sleep-wake rhythms. ABRIM freely shares MRI and behavioural data from 295 participants between 18-80 years, stratified by age decade and sex (median age 52, IQR 36-66, 53.20% females). The ABRIM MRI collection consists of both the raw and pre-processed structural and functional MRI data to facilitate data usage among both expert and non-expert users. The ABRIM behavioural collection includes measures of cognitive functioning (i.e., global cognition, processing speed, executive functions, and memory), proxy measures of cognitive reserve (e.g., educational attainment, verbal intelligence, and occupational complexity), and various self-reported questionnaires (e.g., on depressive symptoms, pain, and the use of memory strategies in daily life and during a memory task). In a sub-sample (n = 120), we recorded sleep-wake rhythms with an actigraphy device for a period of 7 consecutive days. Here, we provide an in-depth description of our study protocol, pre-processing pipelines, and data availability. ABRIM provides a cross-sectional database on healthy participants throughout the adult lifespan, including numerous parameters relevant to improve our understanding of cognitive ageing. Therefore, ABRIM enables researchers to model the advanced imaging parameters and cognitive topologies as a function of age, identify the normal range of values of such parameters, and to further investigate the diverse mechanisms of reserve and resilience.

neuroscience↗

bioRxiv2021

Longitudinal changes of ADHD symptoms in association with white matter microstructure: a tract-specific fixel-based analysis

BackgroundVariation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18 - 34 years), and using the more physiologically informative fixel-based analysis (FBA). MethodsData were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined ADHD and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. ResultsClinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (tmax=1.092, standardized effect[SE]=0.044, pFWE=0.016). Improvement in combined ADHD symptoms over time was associated with more fiber cross-section at follow-up in the lCST (tmax=3.775, SE=0.051, pFWE=0.019). Conclusions: Aberrant white matter development involves both lCST micro- and macrostructural alterations, and its path may be moderated by preceding symptom trajectory.

neuroscience↗

bioRxiv2020

Associations between ADHD symptom remission and white matter microstructure: a longitudinal analysis

BackgroundAttention-deficit hyperactivity disorder (ADHD) is associated with white matter (WM) microstructure. Our objective was to investigate how WM microstructure is longitudinally related to symptom remission in adolescents and young adults with ADHD. MethodsWe obtained diffusion-weighted imaging (DWI) data from 99 participants at two time points (mean age baseline: 16.91 years, mean age follow-up: 20.57 years). We used voxel-wise Tract-Based Spatial Statistics (TBSS) with permutation-based inference to investigate associations of inattention (IA) and hyperactivity-impulsivity (HI) symptom change with fractional anisotropy (FA) at baseline, follow-up, and change between time points. ResultsRemission of combined HI and IA symptoms was significantly associated with reduced FA at follow-up in the left superior longitudinal fasciculus and the left corticospinal tract (CST) (PFWE=0.038 and PFWE=0.044, respectively), mainly driven by an association between HI remission and follow-up CST FA (PFWE=0.049). There was no significant association of combined symptom decrease with FA at baseline or with changes in FA between the two assessments. ConclusionsIn this longitudinal DWI study of ADHD using dimensional symptom scores, we show that greater symptom decrease is associated with lower follow-up FA in specific WM tracts. Altered FA thus may appear to follow, rather than precede, changes in symptom remission. Our findings indicate divergent WM developmental trajectories between individuals with persistent and remittent ADHD, and support the role of prefrontal and sensorimotor tracts in the remission of ADHD.

neuroscience↗

bioRxiv2020

Atypical brain asymmetry in autism - a candidate for clinically meaningful stratification

BackgroundAutism Spectrum Disorder (henceforth autism) is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, however its potential of lateralization as a neural stratification marker has not been widely examined. MethodsIn order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical (NT) controls as well as a replication dataset from ABIDE (513 autism, 691 NT) using a promising approach that moves beyond mean-group comparisons. We derived grey matter voxelwise laterality values for each subject and modelled individual deviations from the normative pattern of brain laterality across age using normative modeling. ResultsResults showed that individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language-, motor- and visuospatial regions, associated with symptom severity. Language delay (LD) explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged with individuals with autism with LD showing more pronounced rightward deviations than autism individuals without LD. ConclusionOur analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism, and indicate atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.

neuroscience↗

bioRxiv2019

Reduced fronto-striatal volume in ADHD in two cohorts across the lifespan

ObjectiveNeuroimaging studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with altered brain anatomy. However, small and heterogeneous study samples, and the use of region-of-interest and tissue-specific analyses have limited the consistency and replicability of these effects. The present study uses a fully data-driven multivariate approach to investigate alterations in both gray and white matter simultaneously, and capture neuroanatomical features associated with ADHD in two large, independent, demographically different cohorts.\n\nMethodsThe study comprised two ADHD cohorts with structural magnetic resonance imaging data: the Dutch NeuroIMAGE cohort (n=890, average age 17.2 years, discovery sample) and the Brazilian IMpACT cohort (n=180, average age 44.2 years, cross validation sample). Using independent component analysis of whole-brain morphometry images in the NeuroIMAGE cohort, 375 independent components of neuroanatomical variations were extracted and assessed their association with ADHD. Afterwards, ADHD-associated components were cross validated in the Brazilian IMpACT cohort.\n\nResultsIn both discovery (corrected- p=0.020) and validation (p=0.033) cohorts, ADHD diagnosis was significantly associated with reduced brain volume in a component mapping to frontal lobes, striatum, and their interconnecting white-matter tracts. The most pronounced case-control differences were localized in white matter adjacent to the orbitofrontal cortex.\n\nConclusionIndependent component analysis is a sensitive approach to uncover neuroanatomical alterations in ADHD and avoid bias attributable to a priori region-of-interest based methods. Current results provide further evidence for the role of the fronto-striatal circuit in ADHD. The fact that the two cohorts are from different continents and comprising different age ranges highlights the robustness of the findings.

neuroscience↗

bioRxiv2019

Different Whole-Brain Functional Connectivity Correlates of Reactive-Proactive Aggression and Callous-Unemotional Traits in Disruptive Children and Adolescents

BackgroundDisruptive behavior in children and adolescents can manifest itself in reactive (RA) and proactive (PA) aggression and is modulated by callous-unemotional (CU) traits and comorbidity. Research on aggression subtype-specific neural correlates is limited and the role of comorbid symptoms largely neglected.\n\nMethodsThe current multi-center study extended previous efforts by investigating unrestricted resting state functional connectivity (rsFC) alterations. The large sample (n = 207) of children and adolescents aged 8 - 18 years (mean age = 13.30 {+/-} 2.60 years) included 118 cases with disruptive behavior (80 diagnosed with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptoms were added as covariates. We measured changes in global and local voxel-to-voxel rsFC using functional magnetic resonance imaging at 3T (mean acquisition time = 8 min 25 sec).\n\nResultsCompared to controls, cases demonstrated altered rsFC including frontal areas when anxiety but not ADHD symptoms were considered. Within cases, RA and PA scores related to changes in global and local rsFC in central gyrus and precuneus previously linked to aggression-related impairments. CU trait severity correlated with global rsFC alterations including inferior and middle temporal gyrus implicated in empathy, emotion, and reward-related activity. Importantly, most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety problems were also accounted for.\n\nConclusionsThe current study clarifies that distinct though overlapping brain connectivity measures can disentangle differing manifestations of aggressive behavior. Moreover, our results highlight the importance of considering comorbid symptoms for detecting aggression-related rsFC alterations.

neuroscience↗

bioRxiv2018

Reactive/proactive aggression specific cortical and subcortical alterations in children and adolescents with disruptive behavior

ObjectiveMaladaptive aggression, as present in conduct disorder (CD) and, to a lesser extent, oppositional defiant disorder (ODD), has been associated with structural alterations in various brain regions, such as ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), amygdala, insula and ventral striatum. Although aggression can be subdivided into reactive and proactive subtypes, no neuroimaging studies have yet investigated if any structural brain alterations are associated with either of the subtypes specifically. Here we investigated this association in predefined regions of interest.\n\nMethodT1-weighted magnetic resonance images were acquired from 158 children and adolescents with aggressive behavior (ODD/CD) and 96 controls in a multi-centre study. Aggression subtypes were assessed by questionnaires. Cortical volume and subcortical volumes and shape were determined using Freesurfer and the FMRIB integrated registration and segmentation tool. Associations between volumes and continuous measures of aggression were established using multilevel linear mixed effects models.\n\nResultsIn cases only proactive aggression was negatively associated with amygdala volume (b=-11.82, p=0.05), while reactive aggression was negatively associated with insula volume (b=-46.41, p=0.01). Classical group comparison showed that children and adolescents with aggressive behavior had smaller volumes than controls in (bilateral) ventral striatum (p=0.003), ACC (p=0.01), and vmPFC (p=0.003) with modest effect sizes.\n\nConclusionsAggression was associated with reduced volume in brain regions involved in decision making. Negative associations were found between reactive aggression and volumes in regions involved in threat responsivity and between proactive aggression and regions linked to empathy. This provides evidence for aggression subtype-specific alterations in brain structure.

neuroscience↗

bioRxiv2018

Aggression Subtypes Relate to Distinct Resting State Functional Connectivity in Disruptive Children and Adolescents

ObjectiveThere is increasing evidence to suggest altered resting state functional connectivity (rsFC) in adolescents with conduct problems. However, no rsFC studies have addressed the effects of reactive and proactive aggression. Herein, we examined the associations between these aggression subtypes along with subdimensions of callous-unemotional (CU) traits and rsFC using predefined seeds in aggression-related salience network (SN) and default mode network (DMN).\n\nMethodAggression subtype-specific whole-brain rsFC of SN and DMN seeds was investigated in a resting state sequence (mean acquisition time = 8 min 25 sec) acquired from 207 children and adolescents of both sexes aged 8 - 18 years (mean age (SD) = 13.30 (2.60) years; range = 8.02 - 18.35) in a multi-center study. One hundred eighteen individuals exhibited disruptive behavior (conduct disorder/oppositional defiant disorder) with different levels of comorbid ADHD symptoms, 89 were healthy.\n\nResultsCompared to healthy controls, cases demonstrated reduced DMN and - after controlling for ADHD scores - SN seed-based rsFC with left hemispheric frontal clusters. We found increased and distinct aggression-subtype specific rsFC patterns in brain regions linked to processes like emotion, empathy, moral, cognitive control, and decision-making. Specifically, reactive and proactive aggression correlated with distinct SN and DMN seed-based rsFC patterns. CU dimensions led to different DMN and SN rsFC with clusters including frontal, parietal, and cingulate areas, with uncaring-related clusters extended to cerebellar regions.\n\nConclusionsThis first study investigating reactive and proactive aggression along with CU dimensions reveals new subtype-specific whole-brain rsFC patterns, extending the knowledge of neural networks to further distinct forms of disruptive behavior.

neuroscience↗