Brain covariance selection: better individual functional connectivity models using population prior

Spontaneous brain activity, as observed in functional neuroimaging, has been shown to display reproducible structure that expresses brain architecture and carries markers of brain pathologies. An important view of modern neuroscience is that such large-scale structure of coherent activity reflects modularity properties of brain connectivity graphs. However, to date, there has been no demonstration that the limited and noisy data available in spontaneous activity observations could be used to learn full-brain probabilistic models that generalize to new data. Learning such models entails two main challenges: i) modeling full brain connectivity is a difficult estimation problem that faces the curse of dimensionality and ii) variability between subjects, coupled with the variability of functional signals between experimental runs, makes the use of multiple datasets challenging. We describe subject-level brain functional connectivity structure as a multivariate Gaussian process and introduce a new strategy to estimate it from group data, by imposing a common structure on the graphical model in the population. We show that individual models learned from functional Magnetic Resonance Imaging (fMRI) data using this population prior generalize better to unseen data than models based on alternative regularization schemes. To our knowledge, this is the first report of a cross-validated model of spontaneous brain activity. Finally, we use the estimated graphical model to explore the large-scale characteristics of functional architecture and show for the first time that known cognitive networks appear as the integrated communities of functional connectivity graph.Comment: in Advances in Neural Information Processing Systems, Vancouver : Canada (2010

Sparse PLS hyper-parameters optimisation for investigating brain-behaviour relationships

Unsupervised learning approaches, such as Partial Least Squares, can be used to investigate relationships between multiple sources of data, such as neuroimaging and behavioural data. In cases of high-dimensional datasets with limited number of examples (e.g. neuroimaging data) there is a need for regularisation to enable the solution of the ill-posed problem and prevent overfitting. Different approaches have been proposed to optimise the regularisation parameters in unsupervised models, however, so far, there has been no comparison between the different approaches using the same data. In this work, two optimisation frameworks (i.e. a permutation and a train/test framework) were compared using sparse PLS to investigate associations between brain connectivity and behaviour data. Both frameworks were able to identify at least one brain-behaviour associative effect. A second brain-behaviour effect was only found using the train/test framework. More importantly, the results show that the multivariate associative effects found with the train/test framework generalise better to new data, suggesting that results based on the permutation framework should be carefully interpreted

Genetic variations within human gained enhancer elements affect human brain sulcal morphology.

The expansion of the cerebral cortex is one of the most distinctive changes in the evolution of the human brain. Cortical expansion and related increases in cortical folding may have contributed to emergence of our capacities for high-order cognitive abilities. Molecular analysis of humans, archaic hominins, and non-human primates has allowed identification of chromosomal regions showing evolutionary changes at different points of our phylogenetic history. In this study, we assessed the contributions of genomic annotations spanning 30 million years to human sulcal morphology measured via MRI in more than 18,000 participants from the UK Biobank. We found that variation within brain-expressed human gained enhancers, regulatory genetic elements that emerged since our last common ancestor with Old World monkeys, explained more trait heritability than expected for the left and right calloso-marginal posterior fissures and the right central sulcus. Intriguingly, these are sulci that have been previously linked to the evolution of locomotion in primates and later on bipedalism in our hominin ancestors

Resting-state functional connectivity-based biomarkers and functional MRI-based neurofeedback for psychiatric disorders: a challenge for developing theranostic biomarkers

Psychiatric research has been hampered by an explanatory gap between psychiatric symptoms and their neural underpinnings, which has resulted in poor treatment outcomes. This situation has prompted us to shift from symptom-based diagnosis to data-driven diagnosis, aiming to redefine psychiatric disorders as disorders of neural circuitry. Promising candidates for data-driven diagnosis include resting-state functional connectivity MRI (rs-fcMRI)-based biomarkers. Although biomarkers have been developed with the aim of diagnosing patients and predicting the efficacy of therapy, the focus has shifted to the identification of biomarkers that represent therapeutic targets, which would allow for more personalized treatment approaches. This type of biomarker (i.e., theranostic biomarker) is expected to elucidate the disease mechanism of psychiatric conditions and to offer an individualized neural circuit-based therapeutic target based on the neural cause of a condition. To this end, researchers have developed rs-fcMRI-based biomarkers and investigated a causal relationship between potential biomarkers and disease-specific behavior using functional MRI (fMRI)-based neurofeedback on functional connectivity. In this review, we introduce recent approach for creating a theranostic biomarker, which consists mainly of two parts: (i) developing an rs-fcMRI-based biomarker that can predict diagnosis and/or symptoms with high accuracy, and (ii) the introduction of a proof-of-concept study investigating the relationship between normalizing the biomarker and symptom changes using fMRI-based neurofeedback. In parallel with the introduction of recent studies, we review rs-fcMRI-based biomarker and fMRI-based neurofeedback, focusing on the technological improvements and limitations associated with clinical use.Comment: 46 pages, 5 figure

IntrAnat Electrodes: A Free Database and Visualization Software for Intracranial Electroencephalographic Data Processed for Case and Group Studies

In some cases of pharmaco-resistant and focal epilepsies, intracranial recordings performed epidurally (electrocorticography, ECoG) and/or in depth (stereoelectroencephalography, SEEG) can be required to locate the seizure onset zone and the eloquent cortex before surgical resection. In SEEG, each electrode contact records brain’s electrical activity in a spherical volume of 3 mm diameter approximately. The spatial coverage is around 1% of the brain and differs between patients because the implantation of electrodes is tailored for each case. Group studies thus need a large number of patients to reach a large spatial sampling, which can be achieved more easily using a multicentric approach such as implemented in our F-TRACT project (f-tract.eu). To facilitate group studies, we developed a software—IntrAnat Electrodes—that allows to perform virtual electrode implantation in patients’ neuroanatomy and to overlay results of epileptic and functional mapping, as well as resection masks from the surgery. IntrAnat Electrodes is based on a patient database providing multiple search criteria to highlight various group features. For each patient, the anatomical processing is based on a series of software publicly available. Imaging modalities (Positron Emission Tomography (PET), anatomical MRI pre-implantation, post-implantation and post-resection, functional MRI, diffusion MRI, Computed Tomography (CT) with electrodes) are coregistered. The 3D T1 pre-implantation MRI gray/white matter is segmented and spatially normalized to obtain a series of cortical parcels using different neuroanatomical atlases. On post-implantation images, the user can position 3D models of electrodes defined by their geometry. Each electrode contact is then labeled according to its position in the anatomical atlases, to the class of tissue (gray or white matter, cerebro-spinal fluid) and to its presence inside or outside the resection mask. Users can add more functionally informed labels on contact, such as clinical responses after electrical stimulation, cortico-cortical evoked potentials, gamma band activity during cognitive tasks or epileptogenicity. IntrAnat Electrodes software thus provides a means to visualize multimodal data. The contact labels allow to search for patients in the database according to multiple criteria representing almost all available data, which is to our knowledge unique in current SEEG software. IntrAnat Electrodes will be available in the forthcoming release of BrainVisa software and tutorials can be found on the F-TRACT webpage

Robust estimation of sulcal morphology

While it is well established that cortical morphology differs in relation to a variety of inter-individual factors, it is often characterized using estimates of volume, thickness, surface area, or gyrification. Here we developed a computational approach for estimating sulcal width and depth that relies on cortical surface reconstructions output by FreeSurfer. While other approaches for estimating sulcal morphology exist, studies often require the use of multiple brain morphology programs that have been shown to differ in their approaches to localize sulcal landmarks, yielding morphological estimates based on inconsistent boundaries. To demonstrate the approach, sulcal morphology was estimated in three large sample of adults across the lifespan, in relation to aging. A fourth sample is additionally used to estimate test-retest reliability of the approach.This toolbox is now made freely available as supplemental to this paper: https://cmadan.github.io/calcSulc/

The reliability and heritability of cortical folds and their genetic correlations across hemispheres

Cortical folds help drive the parcellation of the human cortex into functionally specific regions. Variations in the length, depth, width, and surface area of these sulcal landmarks have been associated with disease, and may be genetically mediated. Before estimating the heritability of sulcal variation, the extent to which these metrics can be reliably extracted from in-vivo MRI must be established. Using four independent test-retest datasets, we found high reliability across the brain (intraclass correlation interquartile range: 0.65–0.85). Heritability estimates were derived for three family-based cohorts using variance components analysis and pooled (total N \u3e 3000); the overall sulcal heritability pattern was correlated to that derived for a large population cohort (N \u3e 9000) calculated using genomic complex trait analysis. Overall, sulcal width was the most heritable metric, and earlier forming sulci showed higher heritability. The inter-hemispheric genetic correlations were high, yet select sulci showed incomplete pleiotropy, suggesting hemisphere-specific genetic influences