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van Rooij, D.

Publications and source records attributed to van Rooij, D..

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Preprocessing Decisions Affect the Precision of P50 Estimates in the Paired-Click Paradigm

Sensory gating is commonly indexed by suppression of the auditory P50 component in the paired-click paradigm. However, P50 findings have varied considerably across studies, laboratories, and populations, prompting calls for the standardisation of methodological practice. EEG preprocessing represents one source of methodological variation that requires standardisation. To date, filtering is the only preprocessing step to have been examined empirically. Segmentation and artifact handling have varied across paired-click studies without empirical evaluation, and, to our knowledge, the standardized measurement error (SME) has not been applied to P50 paired-click estimates. The present study addressed both gaps. Fifty-six neurotypical adults completed a paired-click paradigm consisting of 120 trials. Four preprocessing pipelines were constructed by crossing Segmentation (Short vs Long) with Artifact Handling (threshold-based rejection vs rejection of non-ocular artifacts followed by Gratton and Coles ocular correction). A bootstrapped SME (bSME) was used to quantify the precision of peak-to-peak P50 amplitudes at Cz and FCz, alongside an analysis of trial retention. Correction pipelines retained more trials and produced lower bSME values (higher precision) than Rejection pipelines, at both electrodes and across S1, S2, and suppression score outcomes. Segmentation and Artifact Handling did not operate independently: Segmentation had a negligible impact under Correction, whereas Long segmentation consistently produced the highest bSME values (lowest precision) under Rejection. A regression analysis showed that trial retention accounted for the large majority of the pipeline differences in bSME. This study therefore recommends that future paired-click studies correct, rather than reject, trials containing ocular artifacts, and adopt Short segmentation where matched S1-S2 averaging is not required. Impact statementInconsistent P50 findings have long prompted calls for the standardisation of paired-click methodology, yet preprocessing decisions are rarely justified and, with the exception of filtering, have never been evaluated empirically. By quantifying the precision of P50 estimates, we show that artifact handling and segmentation affect data quality almost entirely through the trials they discard. Measurement precision, not convention or preference, should decide how P50 data are preprocessed.

neuroscience↗

Inhibitory control and error processing in Obsessive-Compulsive Disorder: A mega-analysis of task-based fMRI data by the ENIGMA-OCD consortium

ObjectiveObsessive-compulsive disorder (OCD) is a chronic condition in which impaired inhibitory control and excessive error monitoring may contribute to the maintenance of obsessions and compulsions. This mega-analysis investigates neural activation during response inhibition and error processing using adult and pediatric data from the ENIGMA-OCD consortium and the ABCD study. MethodsIndividual participant data was uniformly processed using HALFpipe to extract statistical maps for response inhibition and error processing contrasts. Bayesian multilevel models were used to assess regional and whole-brain effects of OCD, with additional analyses examining the association between the OCD clinical profile and task-related activation. ResultsAcross inhibitory control tasks, both individuals with OCD and control participants showed robust activation in regions implicated in response inhibition and error processing. During response inhibition, compared to controls, adults with OCD showed stronger somatomotor cortex activation, while children with OCD showed stronger occipital cortex activation. Children with likely OCD from the ABCD cohort showed reduced activity in the frontoparietal network in the anterior insula/frontal operculum region. During error processing, relative to controls, adults with OCD showed weaker activation in fronto-striatal regions, while children with OCD showed stronger activation in frontoparietal and attention networks. Greater OCD symptom severity was associated with weaker task-related activation in adults and stronger activation in children during response inhibition. ConclusionCase-control differences in brain activation during inhibitory control varied by age group and task contrast. Symptom severity emerged as the main clinical correlate of activation during inhibition, suggesting that inhibitory control deficits in OCD may be both state-dependent and developmentally specific.

neuroscience↗

Frontal theta power prospectively associated with response inhibition

A proactive mechanism has been postulated to promote successful inhibition (Kenemans, 2015). Specifically, this mechanism is thought to operate before any action demanding or countermanding event has occurred. In the current study, we investigated whether EEG theta power could reflect this mechanism, in a sample of healthy individuals performing a stop-signal paradigm. By comparing frontal theta power preceding failed versus successful stop trials, we tested whether frontal theta is predictive of inhibition success. We hypothesized that proactive cognitive control manifests in frontal theta power preceding a countermanding go-stop event. Our results demonstrate that frontal theta is indeed higher preceding successful as compared to preceding failed stopping events. We also show that frontal theta power preceding stopping events is associated with Stop-Signal Reaction Times (SSRT), with a higher theta being indicative of shorter SSRTs. This association was not present for go-RT. This study may be the first to reveal a relationship between lower frontal theta power and subsequent stopping failure, suggesting thetas role in proactive response inhibition.

neuroscience↗

Molecular and connectomic vulnerability shape cross-disorder cortical abnormalities

Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morphometry from the ENIGMA consortium, we construct maps of cortical abnormalities for thirteen neurodevelopmental, neurological, and psychiatric disorders from N = 21 000 patients and N = 26 000 controls, collected using a harmonized processing protocol. We systematically compare cortical maps to multiple micro-architectural measures, including gene expression, neurotransmitter density, metabolism, and myelination (molecular vulnerability), as well as global connectomic measures including number of connections, centrality, and connection diversity (connectomic vulnerability). We find that regional molecular vulnerability and macroscale brain network architecture interact to drive the spatial patterning of cortical abnormalities in multiple disorders. Local attributes, particularly neurotransmitter receptor profiles, constitute the best predictors of both disorder-specific cortical morphology and cross-disorder similarity. Finally, we find that cross-disorder abnormalities are consistently subtended by a small subset of network epicentres in bilateral sensory-motor, medial temporal lobe, precuneus, and superior parietal cortex. Collectively, our results highlight how local biological attributes and global connectivity jointly shape cross-disorder cortical abnormalities.

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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.

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Multilevel neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology

AO_SCPLOWBSTRACTC_SCPLOWIt is increasingly recognized that multiple psychiatric conditions are underpinned by shared neural pathways, affecting similar brain systems. Here, we assessed i) shared dimensions of alterations in cortical morphology across six major psychiatric conditions (autism spectrum disorder, attention deficit/hyperactivity disorder, major depression, obsessive-compulsive disorder, bipolar disorder, schizophrenia) and ii) carried out a multiscale neural contextualization, by cross-referencing shared anomalies against cortical myeloarchitecture and cytoarchitecture, as well as connectome and neurotransmitter organization. Pooling disease-related effects on MRI-based cortical thickness measures across six ENIGMA working groups, including a total of 28,546 participants (12,876 patients and 15,670 controls), we computed a shared disease dimension on cortical morphology using principal component analysis that described a sensory-fugal pattern with paralimbic regions showing the most consistent abnormalities across conditions. The shared disease dimension was closely related to cortical gradients of microstructure and intrinsic connectivity, as well as neurotransmitter systems, specifically serotonin and dopamine. Our findings embed the shared effects of major psychiatric conditions on brain structure in multiple scales of brain organization and may provide novel insights into neural mechanisms into transdiagnostic vulnerability.

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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.

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Structural Brain Imaging Studies Offer Clues about the Effects of the Shared Genetic Etiology among Neuropsychiatric Disorders

BackgroundGenomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. MethodsFrom the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, we acquired standardized mean differences (SMDs) in regional brain volume and cortical thickness between cases and controls. We had data on 41 brain regions for: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD) and schizophrenia (SCZ). These data had been derived from 24,360 patients and 37,425 controls. ResultsThe SMDs were significantly correlated between SCZ and BD, OCD, MDD, and ASD. MDD was positively correlated with BD and OCD. BD was positively correlated with OCD and negatively correlated with ADHD. These pairwise correlations among disorders were correlated with the corresponding pairwise correlations among disorders derived from genomewide association studies (r = 0.49). ConclusionsOur results show substantial similarities in sMRI phenotypes among neuropsychiatric disorders and suggest that these similarities are accounted for, in part, by corresponding similarities in common genetic variant architectures.

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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.

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Hyperactivity-impulsivity in ADHD is associated with white matter microstructure in the cingulum’s angular bundle

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by age-inappropriate levels of inattention and/or hyperactivity-impulsivity (HI). ADHD has been related to differences in white matter (WM) microstructure. However, much remains unclear regarding the nature of these WM differences, and which clinical aspects of ADHD they reflect. We systematically investigated if FA is associated with current and/or lifetime categorical diagnosis, impairment in daily life, and continuous ADHD symptom measures. MethodsDiffusion-weighted imaging (DWI) data were obtained from 654 participants (322 unaffected, 258 affected, 74 subthreshold; 7-29 years of age). We applied automated global probabilistic tractography on 18 major WM pathways. Linear mixed effects regression models were used to examine associations of clinical measures with overall brain and tract-specific fractional anisotropy (FA). ResultsThere were significant interactions of tract with all ADHD variables on FA. There were no significant associations of FA with current or lifetime diagnosis, nor with impairment. Lower FA in the right cingulums angular bundle (rCAB) was associated with higher hyperactivity/impulsivity symptom severity (PFWE=0.045). There were no significant effects for other tracts. ConclusionsThis is the first time global probabilistic tractography has been applied to an ADHD dataset of this size. We found no evidence for altered FA in association with ADHD diagnosis. Our findings indicate that associations of FA with ADHD are not uniformly distributed across WM tracts. Continuous symptom measures of ADHD may be more sensitive to FA than diagnostic categories. The rCAB in particular may play a role in symptoms of hyperactivity and impulsivity.

neuroscience↗

Subcortical brain volume, regional cortical thickness and cortical surface area across attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD): findings from the ENIGMA-ADHD, -ASD, and -OCD working groups

ObjectiveAttention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.\n\nMethodsStructural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures).\n\nResultsWe found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.\n\nConclusionOur findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.

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Altered structural brain asymmetry in autism spectrum disorder: large-scale analysis via the ENIGMA Consortium

BackgroundLeft-right asymmetry is an important organizing feature of the healthy brain. Various studies have reported altered structural brain asymmetry in autism spectrum disorder (ASD). However, findings have been inconsistent, likely due to limited sample sizes and low statistical power.\n\nMethodsWe investigated 1,774 subjects with ASD and 1,809 controls, from 54 datasets, for differences in the asymmetry of thickness and surface area of 34 cerebral cortical regions. We also examined global hemispheric measures of cortical thickness and area asymmetry, and volumetric asymmetries of subcortical structures. Data were obtained via the ASD Working Group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas.\n\nResultsASD was significantly associated with reduced leftward asymmetry of total hemispheric average cortical thickness, compared to controls. Eight regional thickness asymmetries, distributed over the cortex, also showed significant associations with diagnosis after correction for multiple comparisons, for which asymmetry was again generally lower in ASD versus controls. In addition, the medial orbitofrontal surface area was less rightward asymmetric in ASD than controls, and the putamen volume was more leftward asymmetric in ASD than controls. The largest effect size had Cohens d = 0.15. Most effects did not depend on age, sex, IQ, or disorder severity.\n\nConclusionAltered lateralized neurodevelopment is suggested in ASD, affecting widespread cortical regions with diverse functions. Large-scale analysis was necessary to reliably detect, and accurately describe, subtle alterations of structural brain asymmetry in this disorder.

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