Search bioRxiv⌕ Search

Biology subjects

Eickhoff, S. B.

Publications and source records attributed to Eickhoff, S. B..

At least 91 records · Page 5Linked to original sources

A Connectivity-based Psychometric Prediction Framework for Brain-behavior Relationship Studies

The recent availability of population-based studies with neuroimaging and behavioral measurements opens promising perspectives to investigate the relationships between interindividual variability in brain regions connectivity and behavioral phenotypes. However, the multivariate nature of connectivity-based prediction model severely limits the insight into brain-behavior patterns for neuroscience. To address this issue, we propose a connectivity-based psychometric prediction framework based on individual regions connectivity profiles. We first illustrate two main applications: 1) single brain regions predictive power for a range of psychometric variables, and 2) single psychometric variables predictive power variation across brain region. We compare the patterns of brain-behavior provided by these approaches to the brain-behavior relationships from activation approaches. Then, capitalizing on the increased transparency of our approach, we demonstrate how the influence of various data processing and analyses can directly influence the patterns of brain-behavior relationships, as well as the unique insight into brain-behavior relationships offered by this approach.

neuroscience↗

Common and distinct brain activity associated with risky and ambiguous decision-making

Two often-studied forms of uncertain decision-making (DM) are risky-DM (outcome probabilities known) and ambiguous-DM (outcome probabilities unknown). While DM in general is associated with activation of several brain regions, previous neuroimaging efforts suggest a dissociation between activity linked with risky and ambiguous choices. However, the common and distinct neurobiological correlates associated with risky- and ambiguous-DM, as well as their specificity when compared to perceptual-DM (as a control condition), remains to be clarified. We conducted multiple meta-analyses on neuroimaging results from 151 studies to characterize common and domain-specific brain activity during risky-, ambiguous-, and perceptual-DM. When considering all DM tasks, convergent activity was observed in brain regions considered to be consituents of the canonical salience, valuation, and executive control networks. When considering subgroups of studies, risky-DM (vs. perceptual-DM) was linked with convergent activity in the striatum and anterior cingulate cortex (ACC), regions associated with reward-related processes (determined by objective functional decoding). When considering ambiguous-DM (vs. perceptual-DM), activity convergence was observed in the lateral prefrontal cortex and insula, regions implicated in affectively-neutral mental processes (e.g., cognitive control and behavioral responding; determined by functional decoding). An exploratory meta-analysis comparing brain activity between substance users and non-users during risky-DM identified reduced convergent activity among users in the striatum, cingulate, and thalamus. Taken together, these findings suggest a dissociation of brain regions linked with risky- and ambiguous-DM reflecting possible differential functionality and highlight brain alterations potentially contributing to poor decision-making in the context of substance use disorders.

neuroscience↗

Searching for replicable associations between cortical thickness and psychometric variables in healthy adults: empirical facts.

The study of associations between inter-individual differences in brain structure and behaviour has a long history in psychology and neuroscience. Many associations between psychometric data, particularly intelligence and personality measures and local variations of brain cortical thickness (CT) have been reported. While the impact of such findings often go beyond scientific communities, resonating in the public mind, their replicability is rarely evidenced. Here, we empirically investigated the replicability of associations of an extended range of psychometric variables and CT in a large cohort of healthy adults. Our analyses revealed low likelihood of significant associations. Furthermore, significant associations from exploratory analyses showed overestimated effect sizes and were rarely replicable in an independent sample. We discuss the interpretation and implications of these findings within the context of accumulating evidence of the poor replicability of structural-brain-behaviour associations using grey matter volume, and more broadly of the replicability crisis of brain and behaviour sciences.

neuroscience↗

Transcription factor motifs in anterior insula gene-expression in mood disorder

BackgroundMood disorders represent a major cause of morbidity and mortality worldwide but the brain-related molecular pathophysiology in mood disorders remains largely undefined. MethodsBecause the anterior insula is reduced in volume in patients with mood disorders, RNA was extracted from postmortem mood disorder samples and compared with unaffected control samples for RNA-sequencing identification of differentially expressed genes (DEGs) in a) bipolar disorder (BD; n=37) versus (vs.) controls (n=33), and b) major depressive disorder (MDD n=30) vs controls, and c) low vs. high Axis-I comorbidity (a measure of cumulative psychiatric disease burden). Given the regulatory role of transcription factors (TFs) in gene expression via specific-DNA-binding domains (motifs), we used JASPAR TF binding database to identify TF-motifs. ResultsWe found that DEGs in BD vs. controls, MDD vs. controls, and high vs. low Axis-I comorbidity were associated with TF-motifs that are known to regulate expression of toll-like receptor genes, cellular homeostatic-control genes, and genes involved in embryonic, cellular/organ and brain development. DiscussionRobust imaging-guided transcriptomics (i.e., using meta-analytic imaging results to guide independent post-mortem dissection for RNA-sequencing) was applied by targeting the gray matter volume reduction in the anterior insula in mood disorders, to guide independent postmortem identification of TF motifs regulating DEG. TF motifs were identified for immune, cellular, embryonic and neurodevelopmental processes. ConclusionOur findings of TF-motifs that regulate the expression of immune, cellular homeostatic-control, and developmental genes provides novel information about the hierarchical relationship between gene regulatory networks, the TFs that control them, and proximate underlying neuroanatomical phenotypes in mood disorders.

genomics↗

Genetic factors influencing a neurobiological substrate for psychiatric disorders

A retrospective meta-analysis of magnetic resonance imaging voxel-based morphometry studies proposed that reduced gray matter volumes in the dorsal anterior cingulate and the left and right anterior insular cortex - areas that constitute hub nodes of the salience network - represent a common substrate for major psychiatric disorders. Here, we investigated the hypothesis that the common substrate serves as an intermediate phenotype to detect genetic risk variants relevant for psychiatric disease. To this end, after a data reduction step, we conducted genome-wide association studies of a combined common substrate measure in four population-based cohorts (n=2,271), followed by meta-analysis and replication in a fifth cohort (n=865). After correction for covariates, the heritability of the common substrate was estimated at 0.50 (standard error 0.18). The top single-nucleotide polymorphism (SNP) rs17076061 was associated with the common substrate at genome-wide significance and replicated, explaining 1.2% of the common substrate variance. This SNP mapped to a locus on chromosome 5q35.2 harboring genes involved in neuronal development and regeneration. In follow-up analyses, rs17076061 was not robustly associated with psychiatric disease, and no overlap was found between the broader genetic architecture of the common substrate and genetic risk for major depressive disorder, bipolar disorder, or schizophrenia. In conclusion, our study identified that common genetic variation indeed influences the common substrate, but that these variants do not directly translate to increased disease risk. Future studies should investigate gene-by-environment interactions and employ functional imaging to understand how salience network structure translates to psychiatric disorder risk.

genetics↗

Gray matter volume and estimated brain age gap are not associated with sleep-disordered breathing in subjects from the ADNI cohort

Alzheimers disease (AD) and sleep-disordered breathing (SDB) are prevalent conditions with rising burden. It is suggested that SDB may contribute to cognitive decline and advanced aging. Here, we assessed the link between self-reported SDB and gray matter volume in patients with AD, mild cognitive impairment (MCI) and healthy controls (HC). We further investigated whether SDB was associated with advanced brain aging. We included a total of 330 participants, divided based on self-reported history of SDB, and matched across diagnoses for age, sex and presence of the ApoE4 allele, from the Alzheimers Disease Neuroimaging Initiative. Gray-matter volume was measured using voxel-wise morphometry and differences reflecting SDB, cognitive status, and their interaction were evaluated. Further, using an age-prediction model fitted on gray-matter data of external datasets, we predicted study participants age from their structural scans. Cognitive decline (MCI/AD diagnosis) and advanced age were associated with lower gray matter volume in various regions, particularly in the bilateral temporal lobes. BrainAGE was well predicted from the morphological data in HC and, as expected, elevated in MCI and particularly in AD. However, there was neither a significant difference between regional gray matter volume in any diagnostic group related to the SDB status nor an SDB-by-cognitive status interaction. Also, we found neither a significant difference in BrainAGE gap (estimated - chronological age) related to SDB nor an SDB-by-cognitive status interaction. In summary, contrary to our expectations, we were not able to find a general nor a diagnostic specific effect on either gray-matter volumetric or brain aging.\n\nStatement of significanceDementia syndromes including Alzheimers disease (AD), are a major global concern, and unraveling modifiable predisposing risk factors is indispensable. Sleep-disordered breathing (SDB) and its most prevalent form, obstructive sleep apnea, are suggested as modifiable risk factors of AD, but their contribution to AD hallmarks, like brain atrophy and advanced brain aging, is not clear to this day. While self-reported SDB is suggested to propagate aging process and cognitive decline to AD in clinical studies, here, we demonstrated that, SDB might not necessarily associate to brain atrophy and the advanced brain aging assessed by morphological data, in AD progession. However, multimodal longitudinal studies with polysomnographic assessment of SDB are needed to confirm such fundings.

neuroscience↗

Neuro-transcriptomic signatures for mood disorder morbidity and suicide mortality

Suicidal behaviors are strongly linked with mood disorders, but the specific neurobiological and functional gene-expression correlates for this linkage remain elusive. We performed neuroimaging-guided RNA-sequencing in two studies to test the hypothesis that imaging-localized gray matter volume (GMV) loss in mood disorders, harbors gene-expression changes associated with disease morbidity and related suicide mortality in an independent postmortem cohort. To do so, first, we conducted study 1 using an anatomical likelihood estimation (ALE) MRI meta-analysis including a total of 47 voxel-based morphometry (VBM) publications (i.e. 26 control>major depressive disorder (MDD) studies, and 21 control>bipolar disorder (BD) studies) in 2387 (living) participants. Study 1 meta-analysis identified a selective anterior insula cortex (AIC) GMV loss in mood disorders. We then used this results to guide study 2 postmortem tissue dissection and RNA-Sequencing of 100 independent donor brain samples with a life-time history of MDD (N=30), BD (N=37) and control (N=33). In study 2, exploratory factor-analysis identified a higher-order factor representing number of Axis-1 diagnoses (e.g. substance use disorders/psychosis/anxiety, etc.), referred to here as morbidity and suicide-completion referred to as mortality. Comparisons of case-vs-control, and factor-analysis defined higher-order-factor contrast variables revealed that the imaging-identified AIC GMV loss sub-region harbors differential gene-expression changes in high morbidity-&-mortality versus low morbidity-&-mortality cohorts in immune, inflammasome, and neurodevelopmental pathways. Weighted gene co-expression network analysis further identified co-activated gene modules for psychiatric morbidity and mortality outcomes. These results provide evidence that AIC anatomical signature for mood disorders are possible correlates for gene-expression abnormalities in mood morbidity and suicide mortality.

neuroscience↗

Neurogenetic basis of personality

Local variation in cortical architecture is highly heritable and distinct genes are associated with specific cortical regions. Total surface area has been shown to be genetically correlated with complex cognitive capacities, suggesting cortical brain structure is a viable endophenotype linking genes to behavior. However, to what extend local brain structure has a genetic association with cognitive and emotional functioning is incompletely understood. Here, we study the genetic correlation between personality traits and local cortical structure in a large-scale twin sample (Human Connectome Project, n=1106, 22-37y). We found a genetic overlap between personality traits and local cortical structure in 10 of 17 observed phenotypic associations in predominantly frontal cortices. To evaluate the robustness of observed personality-brain associations we studied two independent age-matched samples (GSP: n=926, age=19-35y, eNKI: n=210, age: 19-39y). We observed anecdotal to moderate evidence for a successful replication of the negative association between surface area in medial prefrontal cortex and Neuroticism in both samples. Quantitative functional decoding indicated this region is implicated in emotional and socio-cognitive functional processes. In sum, our observations suggest that associations between local brain structure and personality are, in part, under genetic control. However, associations are weak and only the relation between frontal surface area and Neuroticism was consistently observed across three independent samples of young adults.

neuroscience↗

Sex classification by resting state brain connectivity

1A large amount of brain imaging research has focused on group studies delineating differences between males and females with respect to both cognitive performance as well as structural and functional brain organization. To supplement existing findings, the present study employed a machine learning approach to assess how accurately participants sex can be classified based on spatially specific resting state (RS) brain-connectivity, using two samples from the Human Connectome Project (n1 = 434, n2 = 310) and one fully independent sample from the 1000BRAINS study (n=941). The classifier, which was trained on one sample and tested on the other two, was able to reliably classify sex, both within sample and across independent samples, differing both with respect to imaging parameters and sample characteristics. Brain regions displaying highest sex classification accuracies were mainly located along the cingulate cortex, medial and lateral frontal cortex, temporo-parietal regions, insula and precuneus. These areas were stable across samples and match well with previously described sex differences in functional brain organization. While our data show a clear link between sex and regionally specific brain connectivity, they do not support a clear-cut dimorphism in functional brain organization that is driven by sex alone.

neuroscience↗

Ontological Dimensions of Cognitive-Neural Mappings

The growing literature reporting results of cognitive-neural mappings has increased calls for an adequate organizing ontology, or taxonomy, of these mappings. This enterprise is non-trivial, as relevant dimensions that might contribute to such an ontology are not yet agreed upon. We propose that any candidate dimensions should be evaluated on their ability to explain observed differences in functional neuroimaging activation patterns. In this study, we use a large sample of task-based functional magnetic resonance imaging (task-fMRI) results and a data-driven strategy to identify these dimensions. First, using a data-driven dimension reduction approach and multivariate distance matrix regression (MDMR), we quantify the variance among activation maps that is explained by existing ontological dimensions. We find that task paradigm categories explain the most variance among task-activation maps than other dimensions, including latent cognitive categories. Surprisingly, study ID, or the study from which each activation map was reported, explained close to 50% of the variance in activation patterns. Using a clustering approach that allows for overlapping clusters, we derived data-driven latent activation states, associated with re-occurring configurations of the canonical fronto-parietal/salience, sensory-motor, and default mode network activation patterns. Importantly, with only four data-driven latent dimensions, one can explain greater variance among activation maps than all conventional ontological dimensions combined. These latent dimensions may inform a data-driven cognitive ontology, and suggest that current descriptions of cognitive processes and the tasks used to elicit them do not accurately reflect activation patterns commonly observed in the human brain.

neuroscience↗

Do Deep Neural Networks Outperform Kernel Regression for Functional Connectivity Prediction of Behavior?

There is significant interest in the development and application of deep neural networks (DNNs) to neuroimaging data. A growing literature suggests that DNNs outperform their classical counterparts in a variety of neuroimaging applications, yet there are few direct comparisons of relative utility. Here, we compared the performance of three DNN architectures and a classical machine learning algorithm (kernel regression) in predicting individual phenotypes from whole-brain resting-state functional connectivity (RSFC) patterns. One of the DNNs was a generic fully-connected feedforward neural network, while the other two DNNs were recently published approaches specifically designed to exploit the structure of connectome data. By using a combined sample of almost 10,000 participants from the Human Connectome Project (HCP) and UK Biobank, we showed that the three DNNs and kernel regression achieved similar performance across a wide range of behavioral and demographic measures. Furthermore, the generic feedforward neural network exhibited similar performance to the two state-of-the-art connectome-specific DNNs. When predicting fluid intelligence in the UK Biobank, performance of all algorithms dramatically improved when sample size increased from 100 to 1000 subjects. Improvement was smaller, but still significant, when sample size increased from 1000 to 5000 subjects. Importantly, kernel regression was competitive across all sample sizes. Overall, our study suggests that kernel regression is as effective as DNNs for RSFC-based behavioral prediction, while incurring significantly lower computational costs. Therefore, kernel regression might serve as a useful baseline algorithm for future studies.

neuroscience↗

Brain-based ranking of cognitive domains to predict schizophrenia

Schizophrenia is a devastating brain disorder that disturbs sensory perception, motor action, and abstract thought. Its clinical phenotype implies dysfunction of various mental domains, which has motivated a series of theories regarding the underlying pathophysiology. Aiming at a predictive benchmark of a catalogue of cognitive functions, we developed a bottom-up machine-learning strategy and provide a proof of principle in a multi-site clinical dataset (n=324). Existing neuroscientific knowledge on diverse cognitive domains was first condensed into neuro-topographical maps. We then examined how the ensuing meta-analytic cognitive priors can distinguish patients and controls using brain morphology and intrinsic functional connectivity. Some affected cognitive domains supported well-studied directions of research on auditory evaluation and social cognition. However, rarely suspected cognitive domains also emerged as disease-relevant, including self-oriented processing of bodily sensations in gustation and pain. Such algorithmic charting of the cognitive landscape can be used to make targeted recommendations for future mental health research.

neuroscience↗

Accurate Nonlinear Mapping between MNI Volumetric and FreeSurfer Surface Coordinate Systems

The results of most neuroimaging studies are reported in volumetric (e.g., MNI152) or surface (e.g., fsaverage) coordinate systems. Accurate mappings between volumetric and surface coordinate systems can facilitate many applications, such as projecting fMRI group analyses from MNI152/Colin27 to fsaverage for visualization, or projecting resting-state fMRI parcellations from fsaverage to MNI152/Colin27 for volumetric analysis of new data. However, there has been surprisingly little research on this topic. Here, we evaluated three approaches for mapping data between MNI152/Colin27 and fsaverage coordinate systems by simulating the above applications: projection of group-average data from MNI152/Colin27 to fsaverage and projection of fsaverage parcellations to MNI152/Colin27. Two of the approaches are currently widely used. A third approach (registration fusion) was previously proposed, but not widely adopted. Two implementations of the registration fusion (RF) approach were considered, with one implementation utilizing the Advanced Normalization Tools (ANTs). We found that RF-ANTs performed the best for mapping between fsaverage and MNI152/Colin27, even for new subjects registered to MNI152/Colin27 using a different software tool (FSL FNIRT). This suggests that RF-ANTs would be useful even for researchers not using ANTs. Finally, it is worth emphasizing that the most optimal approach for mapping data to a coordinate system (e.g., fsaverage) is to register individual subjects directly to the coordinate system, rather than via another coordinate system. Only in scenarios where the optimal approach is not possible (e.g., mapping previously published results from MNI152 to fsaverage), should the approaches evaluated in this manuscript be considered. In these scenarios, we recommend RF-ANTs (https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/registration/Wu2017_RegistrationFusion).

neuroscience↗

Controlling for Intra-Subject and Inter-Subject Variability in Individual-Specific Cortical Network Parcellations

Resting-state functional magnetic resonance imaging (rs-fMRI) offers the opportunity to delineate individual-specific brain networks. A major question is whether individual-specific network topography (i.e., location and spatial arrangement) is behaviorally relevant. Here, we propose a multi-session hierarchical Bayesian model (MS-HBM) for estimating individual-specific cortical networks and investigate whether individual-specific network topography can predict human behavior. The multiple layers of the MS-HBM explicitly differentiate intra-subject (within-subject) from inter-subject (between-subject) network variability. By ignoring intra-subject variability, previous network mappings might confuse intra-subject variability for inter-subject differences. Compared with other approaches, MS-HBM parcellations generalized better to new rs-fMRI and task-fMRI data from the same subjects. More specifically, MS-HBM parcellations estimated from a single rs-fMRI session (10 minutes) showed comparable generalizability as parcellations estimated by two state-of-the-art methods using five sessions (50 minutes). We also showed that behavioral phenotypes across cognition, personality and emotion could be predicted by individual-specific network topography with modest accuracy, comparable to previous reports predicting phenotypes based on connectivity strength. Network topography estimated by MS-HBM was more effective for behavioral prediction than network size, as well as network topography estimated by other parcellation approaches. Thus, similar to connectivity strength, individual-specific network topography might also serve as a fingerprint of human behavior.

neuroscience↗

Neural Correlates of Motor Imagery, Action Observation, and Movement Execution: A Comparison Across Quantitative Meta-Analyses

There is longstanding interest in the relationship between motor imagery, action observation, and movement execution. Several models propose that these tasks recruit the same brain regions in a similar manner; however, there is no quantitative synthesis of the literature that compares their respective networks. Here we summarized data from neuroimaging experiments examining Motor Imagery (303 experiments, 4,902 participants), Action Observation (595 experiments, 11,032 participants), and related control tasks involving Movement Execution (142 experiments, 2,302 participants). Motor Imagery recruited a network of premotor-parietal cortical regions, alongside the thalamus, putamen, and cerebellum. Action Observation involved a cortical premotor-parietal and occipital network, with no consistent subcortical contributions. Movement Execution engaged sensorimotor-premotor areas, and the thalamus, putamen, and cerebellum. Comparisons across these networks highlighted key differences in their recruitment of motor cortex,and parietal cortex, and subcortical structures. Conjunction across all three tasks identified a consistent premotor-parietal and somatosensory network. These data amend previous models of the relationships between motor imagery, action observation, and movement execution, and quantify the relationships between their respective networks.\n\nHighlightsO_LIWe compared quantitative meta-analyses of movement imagery, observation, and execution\nC_LIO_LISubcortical structures were most commonly associated with imagery and execution\nC_LIO_LIConjunctions identified a consistent premotor-parietal-somatosensory network\nC_LIO_LIThese data can inform basic and translational work using imagery and observation\nC_LI

neuroscience↗

Assessing robustness against potential publication bias in coordinate based fMRI meta-analyses using the Fail-Safe N

The importance of integrating research findings is incontrovertible and coordinate based meta-analyses have become a popular approach to combine results of fMRI studies when only peaks of activation are reported. Similar to classical meta-analyses, coordinate based meta-analyses may be subject to different forms of publication bias which impacts results and possibly invalidates findings. We develop a tool that assesses the robustness to potential publication bias on cluster level. We investigate the possible influence of the file-drawer effect, where studies that do not report certain results fail to get published, by determining the number of noise studies that can be added to an existing fMRI meta-analysis before the results are no longer statistically significant. In this paper we illustrate this tool through an example and test the effect of several parameters through extensive simulations. We provide an algorithm for which code is freely available to generate noise studies and enables users to determine the robustness of meta-analytical results.

neuroscience↗

Cooperating yet distinct brain networks engaged during naturalistic paradigms: A meta-analysis of functional MRI results

Cognitive processes do not occur by pure insertion and instead depend on the full complement of co-occurring mental processes, including perceptual and motor functions. As such, there is limited ecological validity to human neuroimaging experiments that use highly controlled tasks to isolate mental processes of interest. However, a growing literature shows how dynamic, interactive tasks have allowed researchers to study cognition as it more naturally occurs. Collective analysis across such neuroimaging experiments may answer broader questions regarding how naturalistic cognition is biologically distributed throughout the brain. We applied an unbiased, data-driven, meta-analytic approach that uses k-means clustering to identify core brain networks engaged across the naturalistic functional neuroimaging literature. Functional decoding allowed us to, then, delineate how information is distributed between these networks throughout the execution of dynamical cognition in realistic settings. This analysis revealed seven recurrent patterns of brain activation, representing sensory, domain-specific, and attentional neural networks that support the cognitive demands of naturalistic paradigms. Though gaps in the literature remain, these results suggest that naturalistic fMRI paradigms recruit a common set of networks that that allow both separate processing of different streams of information and integration of relevant information to enable flexible cognition and complex behavior.

neuroscience↗

Beyond Consensus: Embracing Heterogeneity in Neuroimaging Meta-Analysis

Coordinate-based meta-analysis can provide important insights into mind-brain relationships. A popular approach for curated small-scale meta-analysis is activation likelihood estimation (ALE), which identifies brain regions consistently activated across a selected set of experiments, such as within a functional domain or mental disorder. ALE can also be utilized in meta-analytic co-activation modeling (MACM) to identify brain regions consistently co-activated with a seed region. Therefore, ALE aims to find consensus across experiments, treating heterogeneity across experiments as noise. However, heterogeneity within an ALE analysis of a functional domain might indicate the presence of functional sub-domains. Similarly, heterogeneity within a MACM analysis might indicate the involvement of a seed region in multiple co-activation patterns that are dependent on task contexts. Here, we demonstrate the use of the author-topic model to automatically determine if heterogeneities within ALE-type meta-analyses can be robustly explained by a small number of latent patterns. In the first application, the author-topic modeling of experiments involving self-generated thought (N = 179) revealed cognitive components fractionating the default network. In the second application, the author-topic model revealed that the left inferior frontal junction (IFJ) participated in multiple task-dependent co-activation patterns (N = 323). Furthermore, the author-topic model estimates compared favorably with spatial independent component analysis in both simulation and real data. Overall, the results suggest that the author-topic model is a flexible tool for exploring heterogeneity in ALE-type meta-analyses that might arise from functional sub-domains, mental disorder subtypes or task-dependent co-activation patterns. Code for this study is publicly available (https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/meta-analysis/Ngo2019_AuthorTopic).

neuroscience↗