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Tiego, J.

Publications and source records attributed to Tiego, J..

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An Evaluation of the Efficacy of Single-Echo and Multi-Echo fMRI Denoising Strategies

Resting-state functional magnetic resonance imaging (rsfMRI) is commonly used to study brain-wide patterns of inter-regional functional coupling (FC). However, the resulting signals are vulnerable to multiple sources of noise, such as those related to non-neuronal physiological fluctuations and head motion, which can alter FC estimates and influence their associations with behavioral outcomes. The best strategy for acquiring and processing rsfMRI data to mitigate noise remains an open question. In this study of 358 healthy individuals, we compared the denoising efficacy of 60 multi-echo (ME) and 30 single-echo (SE) rsfMRI preprocessing pipelines across six distinct measures of data quality. We also evaluated how each pipeline influences the effect sizes of FC-based predictive models of personality and cognitive measures estimated via cross-validated kernel ridge regression. We found that ME pipelines generally showed superior denoising efficacy to SE pipelines, but that no single pipeline was associated with both superior denoising efficacy and behavioural prediction. Using a heuristic scheme to rank pipelines across benchmark evaluations, we found that an ME acquisition combined with Automatic Removal of Motion Artifacts Independent Component Analysis (ICA-AROMA) and Regressor Interpolation at Progressive Time Delays (RIPTiDe) offered a reasonable compromise between denoising efficacy and brain-behavior predictions for both ME and SE data. In general, ME pipelines ranked more highly than SE pipelines. These findings support the use of ME acquisitions in future work but suggest that no single denoising pipeline should be considered optimal for all purposes.

neuroscience↗

Geometric influences on the regional organization of the mammalian brain

The mammalian brain comprises anatomically and functionally distinct regions, yet the principles governing their organization across scales remain unclear. Efforts to map regional boundaries use expert judgement or data-driven clustering of functional, connectional, and/or architectonic properties, but these approaches are often descriptive, have limited generalizability, and do not elucidate generative mechanisms. Here, we develop a geometrically constrained framework for the hierarchical, multiscale regional organization of neocortical and non-neocortical structures. The framework yields parcels at any resolution with high internal homogeneity across hundreds of anatomical, functional, cellular, and molecular properties in humans, macaques, marmosets, and mice, and it generalizes to understudied mammalian species. Finally, we demonstrate that the framework captures the essence of a reaction-diffusion mechanism in which brain geometry shapes the spatial expression of putative patterning molecules that establish a blueprint of regional identity during development. Our findings point to a conserved, universal influence of geometry on mammalian brain organization.

neuroscience↗

Multiscale heterogeneity of white matter morphometry in psychiatric disorders

BackgroundInter-individual variability in neurobiological and clinical characteristics in mental illness is often overlooked by classical group-mean case-control studies. Studies using normative modelling to infer person-specific deviations of grey matter volume have indicated that group means are not representative of most individuals. The extent to which this variability is present in white matter morphometry, which is integral to brain function, remains unclear. MethodsWe applied Warped Bayesian Linear Regression normative models to T1- weighted magnetic resonance imaging data and mapped inter-individual variability in person-specific white matter volume deviations in 1,294 cases (58% male) diagnosed with one of six disorders (attention-deficit/hyperactivity, autism, bipolar, major depressive, obsessive-compulsive and schizophrenia) and 1,465 matched controls (54% male) recruited across 25 scan sites. We developed a framework to characterize deviation heterogeneity at multiple spatial scales, from individual voxels, through inter- regional connections, specific brain regions, and spatially extended brain networks. ResultsThe specific locations of white matter volume deviations were highly heterogeneous across participants, affecting the same voxel in fewer than 8% of individuals with the same diagnosis. For autism and schizophrenia, negative deviations (i.e., areas where volume is lower than normative expectations) aggregated into common tracts, regions and large-scale networks in up to 35% of individuals. ConclusionsThe prevalence of white matter volume deviations was lower than previously observed in grey matter, and the specific location of these deviations was highly heterogeneous when considering voxel-wise spatial resolution. Evidence of aggregation within common pathways and networks was apparent in schizophrenia and autism but not other disorders.

neuroscience↗

Can hubs of the human connectome be identified consistently with diffusion MRI?

Recent years have seen a surge in the use of diffusion MRI to map connectomes in humans, paralleled by a similar increase in processing and analysis choices. Yet these different steps and their effects are rarely compared systematically. Here, in a healthy young adult population (n=294), we characterized the impact of a range of analysis pipelines on one widely studied property of the human connectome; its degree distribution. We evaluated the effects of 40 pipelines (comparing common choices of parcellation, streamline seeding, tractography algorithm, and streamline propagation constraint) and 44 group-representative connectome reconstruction schemes on highly connected hub regions. We found that hub location is highly variable between pipelines. The choice of parcellation has a major influence on hub architecture, and hub connectivity is highly correlated with regional surface area in most of the assessed pipelines ({rho}>0.70 in 69% of the pipelines), particularly when using weighted networks. Overall, our results demonstrate the need for prudent decision-making when processing diffusion MRI data, and for carefully considering how different processing choices can influence connectome organization. Author SummaryThe increasing use of diffusion MRI for mapping white matter connectivity has been matched by a similar increase in the number of ways to process the diffusion data. Here, we assess how diffusion processing affects hubs across 1760 pipeline variations. Many processing pipelines do not show a high concentration of connectivity within hubs. When present, hub location and distribution vary based on processing choices. The choice of probabilistic or deterministic tractography has a major impact on hub location and strength. Finally, node strength in weighted networks can correlate highly with node size. Overall, our results illustrate the need for prudent decision-making when processing and interpreting diffusion MRI data. Code and data availabilityAll the data used in this study is openly available on Figshare at https://doi.org/10.26180/c.6352886.v1. Scripts to analyze these data are available on GitHub at https://github.com/BMHLab/DegreeVariability. Competing InterestsThe authors declare that they have no competing interests.

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Working memory and reaction time variability mediate the relationship between polygenic risk and ADHD traits in a general population sample

Endophenotypes are heritable and quantifiable traits indexing genetic liability for a disorder. Here, we examined three potential endophenotypes, working memory function, response inhibition and reaction time variability, for attention-deficit hyperactivity disorder (ADHD) measured as a dimensional latent trait in a large general population sample derived from the Adolescent Brain and Cognition Developmental study. The genetic risk for ADHD was estimated using polygenic risk scores (PRS) whereas ADHD traits were quantified as a dimensional continuum using Bartlett factor score estimates, derived from Attention Problems items from the Child Behaviour Checklist and Effortful Control items from the Early Adolescent Temperament Questionnaire-Revised. The three candidate cognitive endophenotypes were quantified using task-based performance measures. Higher ADHD PRSs were associated with higher ADHD traits, as well as poorer working memory performance and increased reaction time variability. Lower working memory performance, poorer response inhibition, and increased reaction time variability were associated with more pronounced ADHD traits. Working memory and reaction time variability partially statistically mediated the relationship between ADHD PRS and ADHD traits, explaining 14% and 16% of the association, respectively. The mediation effect was specific to the genetic risk for ADHD and did not generalise to genetic risk for four other major psychiatric disorders. Together, these findings provide robust evidence from a large general population sample that working memory and reaction time variability can be considered endophenotypes for ADHD that mediate the relationship between ADHD PRS and ADHD traits.

neuroscience↗

Task-related changes in aperiodic activity are related to visual working memory capacity independent of event-related potentials and alpha oscillations

Research using electroencephalography (EEG) has shown that individual differences in visual working memory capacity are related to slow-wave event-related potentials (ERPs) and suppression of alpha-band oscillatory power during the delay period of memory tasks. However, recent evidence suggests that changes in non-oscillatory (aperiodic) features of the EEG signal are related to working memory performance. We assessed several features of task-related changes in aperiodic activity including its spatial distribution, the effect of memory load, and the relationships between aperiodic activity, memory capacity, slow-wave ERPs, and alpha suppression. Eighty-four healthy individuals performed a continuous recall working memory (WM) task consisting of 2, 4 or 6 coloured squares while EEG was recorded. Aperiodic activity during a baseline and WM delay period was quantified by fitting a model to the background of the EEG power spectra, which returned parameters describing the slope (exponent) and broadband offset of the spectra. The aperiodic exponent decreased (i.e., slope flattened) in lateral parieto-occipital electrodes but increased (i.e., slope steepened) in fronto-central electrodes during the WM delay period, whereas the offset decreased over parieto-occipital electrodes. These task-related changes in aperiodic activity did not differ between memory loads. Larger increases in the aperiodic exponent were associated with higher working memory capacity measured from both the WM task and a separate battery of complex span tasks, a relationship that was independent of slow-wave ERPs and alpha suppression. Our findings suggest that WM task-related changes in aperiodic activity are region specific and reflect an independent neural mechanism that is important for general working memory ability.

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Examining the Neural Correlates of Error Awareness in a Large fMRI Study

Goal-directed behaviour is dependent upon the ability to detect errors and implement appropriate post-error adjustments. Accordingly, several studies have explored the neural activity underlying error-monitoring processes, identifying the insula cortex as crucial for error awareness and reporting mixed findings with respect to the anterior cingulate cortex. Variable patterns of activation have previously been attributed to insufficient statistical power. We therefore sought to clarify the neural correlates of error awareness in a large event-related functional magnetic resonance imaging (MRI) study. Four hundred and two healthy participants undertook the error awareness task, a motor Go/No-Go response inhibition paradigm in which participants were required to indicate their awareness of commission errors. Compared to unaware errors, aware errors were accompanied by significantly greater activity in a network of regions including the insula cortex, supramarginal gyrus, and midline structures such as the anterior cingulate cortex and supplementary motor area. Error awareness activity was related to indices of task performance and dimensional measures of psychopathology in selected regions including the insula, supramarginal gyrus and supplementary motor area. Taken together, we identified a robust and reliable neural network associated with error awareness.

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Genetic influences on hub connectivity of the human connectome

Brain network hubs are both highly connected and highly inter-connected, forming a critical communication backbone for coherent neural dynamics. The mechanisms driving this organization are poorly understood. Using diffusion-weighted imaging in twins, we identify a major role for genes, showing that they preferentially influence connectivity strength between network hubs of the human connectome. Using transcriptomic atlas data, we show that connected hubs demonstrate tight coupling of transcriptional activity related to metabolic and cytoarchitectonic similarity. Finally, comparing over thirteen generative models of network growth, we show that purely stochastic processes cannot explain the precise wiring patterns of hubs, and that model performance can be improved by incorporating genetic constraints. Our findings indicate that genes play a strong and preferential role in shaping the functionally valuable, metabolically costly connections between connectome hubs.

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The efficacy of different preprocessing steps in reducing motion-related confounds in diffusion MRI connectomics

Head motion is a major confounding factor in neuroimaging studies. While numerous studies have investigated how motion impacts estimates of functional connectivity, the effects of motion on structural connectivity measured using diffusion MRI have not received the same level of attention, despite the fact that, like functional MRI, diffusion MRI relies on elaborate preprocessing pipelines that require multiple choices at each step. Here, we report a comprehensive analysis of how these choices influence motion-related contamination of structural connectivity estimates. Using a healthy adult sample (N = 252), we evaluated 240 different preprocessing pipelines, devised using plausible combinations of different choices related to explicit head motion correction, tractography propagation algorithms, track seeding methods, track termination constraints, quantitative metrics derived for each connectome edge, and parcellations. We found that an approach to motion correction that includes outlier replacement and within-slice volume correction led to a dramatic reduction in cross-subject correlations between head motion and structural connectivity strength, and that motion contamination is more severe when quantifying connectivity strength using mean tract fractional anisotropy rather than streamline count. We also show that the choice of preprocessing strategy can significantly influence subsequent inferences about network organization, with the location of network hubs varying considerably depending on the specific preprocessing steps applied. Our findings indicate that the impact of motion on structural connectivity can be successfully mitigated using recent motion-correction algorithms that include outlier replacement and within-slice motion correction. HighlightsO_LIWe assess how motion affects structural connectivity in 240 preprocessing pipelines C_LIO_LIMotion contamination of structural connectivity depends on preprocessing choices C_LIO_LIAdvanced motion correction tools reduce motion confounds C_LIO_LIFA edge weighting is more susceptible to motion effects than streamline count C_LI

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Fractionation of impulsive and compulsive trans-diagnostic phenotypes and their longitudinal associations

ObjectiveYoung adulthood is a crucial neurodevelopmental period during which impulsive and compulsive problem behaviours commonly emerge. While traditionally considered diametrically opposed, impulsive and compulsive symptoms tend to co-occur. The objectives of this study were: (i) to identify the optimal trans-diagnostic structural framework for measuring impulsive and compulsive problem behaviours; and (ii) to use this optimal framework to identify common/distinct antecedents of these latent phenotypes.\n\nMethods654 young adults were recruited as part of the Neuroscience in Psychiatry Network (NSPN), a population-based cohort in the United Kingdom. The optimal trans-diagnostic structural model capturing 33 types of impulsive and compulsive problem behaviours was identified. Baseline predictors of subsequent impulsive and compulsive trans-diagnostic phenotypes were characterised, along with cross-sectional associations, using Partial Least Squares (PLS).\n\nResultsCurrent problem behaviours were optimally explained by a bi-factor model, which yielded dissociable measures of impulsivity and compulsivity, as well as a general disinhibition factor. Impulsive problem behaviours were significantly explained by prior antisocial and impulsive personality traits, male gender, general distress, perceived dysfunctional parenting, and teasing/arguments within friendships. Compulsive problem behaviours were significantly explained by prior compulsive traits, and female gender.\n\nConclusionsThis study demonstrates that trans-diagnostic phenotypes of 33 impulsive and compulsive problem behaviours are identifiable in young adults, utilizing a bi-factor model based on responses to a single questionnaire. Furthermore, these phenotypes have different antecedents. The findings yield a new framework for fractionating impulsivity and compulsivity; and suggest different early intervention targets to avert emergence of problem behaviours. This framework may be useful for future biological and clinical dissection of impulsivity and compulsivity.

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Functional Connectivity of Corticostriatal Circuitry and Psychosis-Like Experiences in the General Community

BackgroundPsychotic symptoms are proposed lie on a continuum, ranging from isolated psychosis-like experiences (PLEs) in non-clinical populations to frank disorder. Here, we investigate neurobiological correlates of this symptomatologic continuum by examining whether functional connectivity of dorsal corticostriatal circuitry, which is disrupted in patients and high-risk individuals, is associated with the severity of subclinical PLEs.\n\nMethodsA community sample of 672 adults with no history of psychiatric or neurological illnesses completed a battery of seven questionnaires spanning various PLE domains. Principal component analysis (PCA) estimated major dimensions of PLEs from the questionnaires. PCA dimension scores were then correlated with whole-brain voxelwise functional connectivity (FC) maps of the striatum in a subset of 353 participants who completed a resting-state neuroimaging protocol.\n\nResultsPCA identified two dimensions of PLEs accounting for 62.57% of variance in the measures, corresponding to positive and negative PLEs. Reduced FC between the dorsal striatum and prefrontal cortex correlated with higher positive PLEs. Negative PLEs correlated with increased FC between the dorsal striatum and visual and sensorimotor areas. In the ventral corticostriatal system, positive and negative PLEs were both associated with FC between the ventro-rostral putamen and sensorimotor cortices.\n\nConclusionsConsistent with past findings in patients and high-risk individuals, subthreshold positive symptomatology is associated with reduced FC of the dorsal circuit. These findings suggest that the connectivity of this circuit tracks the expression of psychotic phenomena across a broad spectrum of severity, extending from the subclinical domain to clinical diagnosis.

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Transdiagnostic variations in impulsivity and compulsivity in obsessive-compulsive disorder and gambling disorder correlate with effective connectivity in cortical-striatal-thalamic-cortical circuits.

BackgroundIndividual differences in impulsivity and compulsivity is thought to underlie vulnerability to a broad range of disorders and are closely tied to cortical-striatal-thalamic-cortical (CSTC) function. However, whether impulsivity and compulsivity in clinical disorders is continuous with the healthy population and explains CSTC dysfunction across different disorders remains unclear.\n\nMethodsWe characterized the relationship between CSTC effective connectivity, estimated using dynamic causal modelling of functional magnetic resonance imaging data, and dimensional phenotypes of impulsivity and compulsivity in two symptomatically distinct but phenotypically related disorders, obsessive-compulsive disorder (OCD) and gambling disorder (GD). 487 online participants provided data for modelling of dimensional phenotypes. These data were combined with 34 OCD patients, 22 GD patients, and 39 healthy controls, who underwent functional magnetic resonance imaging.\n\nResultsThree core dimensions were identified: disinhibition, impulsivity, and compulsivity. Patients scores on these dimensions were continuously distributed with the healthy participants, supporting a continuum model of psychopathology. Across all participants, higher disinhibition correlated with lower bottom-up connectivity in the dorsal circuit and increased bottom-up connectivity in the ventral circuit, and higher compulsivity correlated with reduced bottom-up connectivity in the dorsal circuit. Similar changes in effective connectivity were observed with increasing clinical severity that were not accounted for by phenotypic variation, demonstrating convergence towards behaviourally and clinically relevant changes in brain dynamics. Effective connectivity did not differ as a function of traditional diagnostic labels.\n\nConclusionsCSTC dysfunction across OCD and GD is better characterized by dimensional phenotypes than diagnostic comparisons, supporting investigation of quantitative liability phenotypes.

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