Showing papers by "Bertrand Thirion published in 2020"

Variability in the analysis of a single neuroimaging dataset by many teams

Abstract: Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2-5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.

Variability in the analysis of a single neuroimaging dataset by many teams (Preprint)

Abstract: Summary Data analysis workflows in many scientific domains have become increasingly complex and flexible. To assess the impact of this flexibility on functional magnetic resonance imaging (fMRI) results, the same dataset was independently analyzed by 70 teams, testing nine ex-ante hypotheses. The flexibility of analytic approaches is exemplified by the fact that no two teams chose identical workflows to analyze the data. This flexibility resulted in sizeable variation in hypothesis test results, even for teams whose statistical maps were highly correlated at intermediate stages of their analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Importantly, meta-analytic approaches that aggregated information across teams yielded significant consensus in activated regions across teams. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset. Our findings show that analytic flexibility can have substantial effects on scientific conclusions, and demonstrate factors related to variability in fMRI. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for multiple analyses of the same data. Potential approaches to mitigate issues related to analytical variability are discussed.

NeuroQuery: comprehensive meta-analysis of human brain mapping

Abstract: Reaching a global view of brain organization requires assembling evidence on widely different mental processes and mechanisms. The variety of human neuroscience concepts and terminology poses a fundamental challenge to relating brain imaging results across the scientific literature. Existing meta-analysis methods perform statistical tests on sets of publications associated with a particular concept. Thus, large-scale meta-analyses only tackle single terms that occur frequently. We propose a new paradigm, focusing on prediction rather than inference. Our multivariate model predicts the spatial distribution of neurological observations, given text describing an experiment, cognitive process, or disease. This approach handles text of arbitrary length and terms that are too rare for standard meta-analysis. We capture the relationships and neural correlates of 7 547 neuroscience terms across 13 459 neuroimaging publications. The resulting meta-analytic tool, neuroquery.org, can ground hypothesis generation and data-analysis priors on a comprehensive view of published findings on the brain.

NeuroQuery: comprehensive meta-analysis of human brain mapping

Abstract: Reaching a global view of brain organization requires assembling evidence on widely different mental processes and mechanisms. The variety of human neuroscience concepts and terminology poses a fundamental challenge to relating brain imaging results across the scientific literature. Existing meta-analysis methods perform statistical tests on sets of publications associated with a particular concept. Thus, large-scale meta-analyses only tackle single terms that occur frequently. We propose a new paradigm, focusing on prediction rather than inference. Our multivariate model predicts the spatial distribution of neurological observations, given text describing an experiment, cognitive process, or disease. This approach handles text of arbitrary length and terms that are too rare for standard meta-analysis. We capture the relationships and neural correlates of 7 547 neuroscience terms across 13 459 neuroimaging publications. The resulting meta-analytic tool, this http URL, can ground hypothesis generation and data-analysis priors on a comprehensive view of published findings on the brain.

Inference and prediction diverge in biomedicine

Abstract: Summary In the 20th century, many advances in biological knowledge and evidence-based medicine were supported by p values and accompanying methods. In the early 21st century, ambitions toward precision medicine place a premium on detailed predictions for single individuals. The shift causes tension between traditional regression methods used to infer statistically significant group differences and burgeoning predictive analysis tools suited to forecast an individual's future. Our comparison applies linear models for identifying significant contributing variables and for finding the most predictive variable sets. In systematic data simulations and common medical datasets, we explored how variables identified as significantly relevant and variables identified as predictively relevant can agree or diverge. Across analysis scenarios, even small predictive performances typically coincided with finding underlying significant statistical relationships, but not vice versa. More complete understanding of different ways to define “important” associations is a prerequisite for reproducible research and advances toward personalizing medical care.

Multi-scale network regression for brain-phenotype associations.

Abstract: Brain networks are increasingly characterized at different scales, including summary statistics, community connectivity, and individual edges. While research relating brain networks to behavioral measurements has yielded many insights into brain‐phenotype relationships, common analytical approaches only consider network information at a single scale. Here, we designed, implemented, and deployed Multi‐Scale Network Regression (MSNR), a penalized multivariate approach for modeling brain networks that explicitly respects both edge‐ and community‐level information by assuming a low rank and sparse structure, both encouraging less complex and more interpretable modeling. Capitalizing on a large neuroimaging cohort (n = 1, 051), we demonstrate that MSNR recapitulates interpretable and statistically significant connectivity patterns associated with brain development, sex differences, and motion‐related artifacts. Compared to single‐scale methods, MSNR achieves a balance between prediction performance and model complexity, with improved interpretability. Together, by jointly exploiting both edge‐ and community‐level information, MSNR has the potential to yield novel insights into brain‐behavior relationships.

Functional Annotation of Human Cognitive States using Deep Graph Convolution

Abstract: A key goal in neuroscience is to understand brain mechanisms of cognitive functions. An emerging approach is “brain decoding”, which consists of inferring a set of experimental conditions performed by a participant, using pattern classification of brain activity. Few works so far have attempted to train a brain decoding model that would generalize across many different cognitive tasks drawn from multiple cognitive domains. To tackle this problem, we proposed a domain-general brain decoder that automatically learns the spatiotemporal dynamics of brain response within a short time window using a deep learning approach. By leveraging our prior knowledge on network organization of human brain cognition, we constructed deep graph convolutional neural networks to annotate cognitive states by first mapping the task-evoked fMRI response onto a brain graph, propagating brain dynamics among interconnected brain regions and functional networks, and generating state-specific representations of recorded brain activity. We evaluated the decoding model on a large population of 1200 participants, under 21 different experimental conditions spanning 6 different cognitive domains, acquired from the Human Connectome Project task-fMRI database. Using a 10s window of fMRI response, the 21 cognitive states were identified with a test accuracy of 89% (chance level 4.8%). Performance remained good when using a 6s window (82%). It was even feasible to decode cognitive states from a single fMRI volume (720ms), with the performance following the shape of the hemodynamic response. Moreover, a saliency map analysis demonstrated that the high decoding performance was driven by the response of biologically meaningful brain regions. Together, we provide an automated tool to annotate human brain activity with fine temporal resolution and fine cognitive granularity. Our model shows potential applications as a reference model for domain adaptation, possibly making contributions in a variety of domains, including neurological and psychiatric disorders.

Individual Brain Charting dataset extension, second release of high-resolution fMRI data for cognitive mapping.

Abstract: We present an extension of the Individual Brain Charting dataset –a high spatial-resolution, multi-task, functional Magnetic Resonance Imaging dataset, intended to support the investigation on the functional principles governing cognition in the human brain. The concomitant data acquisition from the same 12 participants, in the same environment, allows to obtain in the long run finer cognitive topographies, free from inter-subject and inter-site variability. This second release provides more data from psychological domains present in the first release, and also yields data featuring new ones. It includes tasks on e.g. mental time travel, reward, theory-of-mind, pain, numerosity, self-reference effect and speech recognition. In total, 13 tasks with 86 contrasts were added to the dataset and 63 new components were included in the cognitive description of the ensuing contrasts. As the dataset becomes larger, the collection of the corresponding topographies becomes more comprehensive, leading to better brain-atlasing frameworks. This dataset is an open-access facility; raw data and derivatives are publicly available in neuroimaging repositories. Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.12958181

Beyond brain age: Empirically-derived proxy measures of mental health

Abstract: Biological aging is revealed by physical measures, e.g., DNA probes or brain scans. Individual differences in personal functioning are instead explained by psychological constructs.Constructs such as intelligence or neuroticism are typically assessed by specialized workforce through tailored questionnaires and tests. Similar to how brain age captures biological aging, intelligence and neuroticism may provide empirical proxies for mental health. Could the combination of brain imaging and sociodemographic information yield measures for these constructs that do not rely on human judgment? Here, we built proxy measures by applying machine learning on multimodal MR images and rich sociodemographic information from the largest brain-imaging cohort to date: the UK Biobank. Objective comparisons revealed that all proxies captured the target constructs and related to health-contributing habits beyond the measures they were derived from. Our results demonstrate that proxies targeting classical psychological constructs reveal facets of mental health complementary to information conveyed by brain age.

Patterns of autism symptoms: hidden structure in the ADOS and ADI-R instruments

Abstract: We simultaneously revisited the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) with a comprehensive data-analytics strategy. Here, the combination of pattern-analysis algorithms and extensive data resources (n = 266 patients aged 7–49 years) allowed identifying coherent clinical constellations in and across ADI-R and ADOS assessments widespread in clinical practice. Our clustering approach revealed low- and high-severity patient groups, as well as a group scoring high only in the ADI-R domains, providing quantitative contours for the widely assumed autism subtypes. Sparse regression approaches uncovered the most clinically predictive questionnaire domains. The social and communication domains of the ADI-R showed convincing performance to predict the patients’ symptom severity. Finally, we explored the relative importance of each of the ADI-R and ADOS domains conditioning on age, sex, and fluid IQ in our sample. The collective results suggest that (i) identifying autism subtypes and severity for a given individual may be most manifested in the ADI-R social and communication domains, (ii) the ADI-R might be a more appropriate tool to accurately capture symptom severity, and (iii) the ADOS domains were more relevant than the ADI-R domains to capture sex differences.

Aggregation of Multiple Knockoffs

Abstract: We develop an extension of the Knockoff Inference procedure, introduced by Barber and Candes (2015). This new method, called Aggregation of Multiple Knockoffs (AKO), addresses the instability inherent to the random nature of Knockoff-based inference. Specifically, AKO improves both the stability and power compared with the original Knockoff algorithm while still maintaining guarantees for False Discovery Rate control. We provide a new inference procedure, prove its core properties, and demonstrate its benefits in a set of experiments on synthetic and real datasets.

An empirical evaluation of functional alignment using inter-subject decoding

Abstract: Inter-individual variability in the functional organization of the brain presents a major obstacle to identifying generalizable neural coding principles. Functional alignment—a class of methods that matches subjects’ neural signals based on their functional similarity—is a promising strategy for addressing this variability. At present, however, a range of functional alignment methods have been proposed and their relative performance is still unclear. In this work, we benchmark five functional alignment methods for inter-subject decoding on four publicly available datasets. Specifically, we consider piecewise Procrustes, searchlight Procrustes, piecewise Optimal Transport, Shared Response Modelling (SRM), and intra-subject alignment; as well as associated methodological choices such as ROI definition. We find that functional alignment generally improves inter-subject decoding accuracy though the best performing method depends on the research context. Specifically, SRM performs best within a region-of-interest while piecewise Optimal Transport performs best at a whole-brain scale. We also benchmark the computational efficiency of each of the surveyed methods, providing insight into their usability and scalability. Taking inter-subject decoding accuracy as a quantification of inter-subject similarity, our results support the use of functional alignment to improve inter-subject comparisons in the face of variable structure-function organization. We provide open implementations of the methods used.

Statistical control for spatio-temporal MEG/EEG source imaging with desparsified multi-task Lasso

Abstract: Detecting where and when brain regions activate in a cognitive task or in a given clinical condition is the promise of non-invasive techniques like magnetoencephalography (MEG) or electroencephalography (EEG). This problem, referred to as source localization, or source imaging, poses however a high-dimensional statistical inference challenge. While sparsity promoting regularizations have been proposed to address the regression problem, it remains unclear how to ensure statistical control of false detections. Moreover, M/EEG source imaging requires to work with spatio-temporal data and autocorrelated noise. To deal with this, we adapt the desparsified Lasso estimator -- an estimator tailored for high dimensional linear model that asymptotically follows a Gaussian distribution under sparsity and moderate feature correlation assumptions -- to temporal data corrupted with autocorrelated noise. We call it the desparsified multi-task Lasso (d-MTLasso). We combine d-MTLasso with spatially constrained clustering to reduce data dimension and with ensembling to mitigate the arbitrary choice of clustering; the resulting estimator is called ensemble of clustered desparsified multi-task Lasso (ecd-MTLasso). With respect to the current procedures, the two advantages of ecd-MTLasso are that i)it offers statistical guarantees and ii)it allows to trade spatial specificity for sensitivity, leading to a powerful adaptive method. Extensive simulations on realistic head geometries, as well as empirical results on various MEG datasets, demonstrate the high recovery performance of ecd-MTLasso and its primary practical benefit: offer a statistically principled way to threshold MEG/EEG source maps.

Modeling Shared Responses in Neuroimaging Studies through MultiView ICA

Abstract: Group studies involving large cohorts of subjects are important to draw general conclusions about brain functional organization. However, the aggregation of data coming from multiple subjects is challenging, since it requires accounting for large variability in anatomy, functional topography and stimulus response across individuals. Data modeling is especially hard for ecologically relevant conditions such as movie watching, where the experimental setup does not imply well-defined cognitive operations. We propose a novel MultiView Independent Component Analysis (ICA) model for group studies, where data from each subject are modeled as a linear combination of shared independent sources plus noise. Contrary to most group-ICA procedures, the likelihood of the model is available in closed form. We develop an alternate quasi-Newton method for maximizing the likelihood, which is robust and converges quickly. We demonstrate the usefulness of our approach first on fMRI data, where our model demonstrates improved sensitivity in identifying common sources among subjects. Moreover, the sources recovered by our model exhibit lower between-session variability than other methods.On magnetoencephalography (MEG) data, our method yields more accurate source localization on phantom data. Applied on 200 subjects from the Cam-CAN dataset it reveals a clear sequence of evoked activity in sensor and source space. The code is freely available at this https URL.

Modeling Shared responses in Neuroimaging Studies through MultiView ICA

Abstract: Group studies involving large cohorts of subjects are important to draw general conclusions about brain functional organization. However, the aggregation of data coming from multiple subjects is challenging, since it requires accounting for large variability in anatomy, functional topography and stimulus response across individuals. Data modeling is especially hard for ecologically relevant conditions such as movie watching, where the experimental setup does not imply well-defined cognitive operations. We propose a novel MultiView Independent Component Analysis (ICA) model for group studies, where data from each subject are modeled as a linear combination of shared independent sources plus noise. Contrary to most group-ICA procedures, the likelihood of the model is available in closed form. We develop an alternate quasi-Newton method for maximizing the likelihood, which is robust and converges quickly. We demonstrate the usefulness of our approach first on fMRI data, where our model demonstrates improved sensitivity in identifying common sources among subjects. Moreover, the sources recovered by our model exhibit lower between-session variability than other methods.On magnetoencephalography (MEG) data, our method yields more accurate source localization on phantom data. Applied on 200 subjects from the Cam-CAN dataset it reveals a clear sequence of evoked activity in sensor and source space. The code is freely available at https://github.com/hugorichard/multiviewica.

Fine-grain atlases of functional modes for fMRI analysis.

Abstract: Population imaging markedly increased the size of functional-imaging datasets, shedding new light on the neural basis of inter-individual differences. Analyzing these large data entails new scalability challenges, computational and statistical. For this reason, brain images are typically summarized in a few signals, for instance reducing voxel-level measures with brain atlases or functional modes. A good choice of the corresponding brain networks is important, as most data analyses start from these reduced signals. We contribute finely-resolved atlases of functional modes, comprising from 64 to 1024 networks. These dictionaries of functional modes (DiFuMo) are trained on millions of fMRI functional brain volumes of total size 2.4TB, spanned over 27 studies and many research groups. We demonstrate the benefits of extracting reduced signals on our fine-grain atlases for many classic functional data analysis pipelines: stimuli decoding from 12,334 brain responses, standard GLM analysis of fMRI across sessions and individuals, extraction of resting-state functional-connectomes biomarkers for 2,500 individuals, data compression and meta-analysis over more than 15,000 statistical maps. In each of these analysis scenarii, we compare the performance of our functional atlases with that of other popular references, and to a simple voxel-level analysis. Results highlight the importance of using high-dimensional "soft" functional atlases, to represent and analyse brain activity while capturing its functional gradients. Analyses on high-dimensional modes achieve similar statistical performance as at the voxel level, but with much reduced computational cost and higher interpretability. In addition to making them available, we provide meaningful names for these modes, based on their anatomical location. It will facilitate reporting of results.

Multivariate Analysis is Sufficient for Lesion-Behaviour Mapping

Abstract: Lesion-behaviour mapping aims at predicting individual behavioural deficits, given a certain pattern of brain lesions It also brings fundamental insights on brain organization, as lesions can be understood as interventions on normal brain function We focus here on the case of stroke The most standard approach to lesion-behaviour mapping is mass-univariate analysis, but it is inaccurate due to correlations between the different brain regions induced by vascularisation Recently, it has been claimed that multivariate methods are also subject to lesion-anatomical bias, and that a move towards a causal approach is necessary to eliminate that bias In this paper, we reframe the lesion-behaviour brain mapping problem using classical causal inference tools We show that, in the absence of additional clinical data and if only one region has an effect on the behavioural scores, suitable multivariate methods are sufficient to address lesion-anatomical bias This is a commonly encountered situation when working with public datasets, which very often lack general health data We support our claim with a set of simulated experiments using a publicly available lesion imaging dataset, on which we show that adequate multivariate models provide state-of-the art results

Computer-implemented method of building a database of pulse sequences for magnetic resonance imaging, and a method of performing magnetic resonance imaging using such a database

Abstract: A computer-implemented method of building a database of pulse sequences for parallel-transmission magnetic resonance imaging, includes a) for each of a plurality of subjects, determining an optimal sequence for the subject; b) for each subject, computing the values of the or of a different cost or merit function obtained by playing the optimal sequences for all the subjects; c) aggregating the subjects into a plurality of clusters using a clustering algorithm taking the values, or functions thereof, as metrics; d) for each cluster, determining an averaged optimal sequence for the cluster; e) receiving, as input, a set of features characterizing an imaging subject, comprising at least a morphological feature of the subject; f) associating the subject to one pulse sequence of the database based on the set of features using the computer-implemented classifier algorithm; and g) performing magnetic resonance imaging using the pulse sequence. A magnetic resonance imaging apparatus for carrying out steps e)-g) of such a method is also provided.

Statistical control for spatio-temporal MEG/EEG source imaging with desparsified mutli-task Lasso

Abstract: Detecting where and when brain regions activate in a cognitive task or in a given clinical condition is the promise of non-invasive techniques like magnetoencephalography (MEG) or electroencephalography (EEG). This problem, referred to as source localization, or source imaging, poses however a high-dimensional statistical inference challenge. While sparsity promoting regularizations have been proposed to address the regression problem, it remains unclear how to ensure statistical control of false detections. Moreover, M/EEG source imaging requires to work with spatio-temporal data and autocorrelated noise. To deal with this, we adapt the desparsified Lasso estimator -- an estimator tailored for high dimensional linear model that asymptotically follows a Gaussian distribution under sparsity and moderate feature correlation assumptions -- to temporal data corrupted with autocorrelated noise. We call it the desparsified multi-task Lasso (d-MTLasso). We combine d-MTLasso with spatially constrained clustering to reduce data dimension and with ensembling to mitigate the arbitrary choice of clustering; the resulting estimator is called ensemble of clustered desparsified multi-task Lasso (ecd-MTLasso). With respect to the current procedures, the two advantages of ecd-MTLasso are that i)it offers statistical guarantees and ii)it allows to trade spatial specificity for sensitivity, leading to a powerful adaptive method. Extensive simulations on realistic head geometries, as well as empirical results on various MEG datasets, demonstrate the high recovery performance of ecd-MTLasso and its primary practical benefit: offer a statistically principled way to threshold MEG/EEG source maps.