Individual differences in white matter microstructure reflect variation in functional connectivity during action choice.

The relation between brain structure and function is of fundamental importance in neuroscience. Comparisons between behavioral and brain imaging measures suggest that variation in brain structure correlates with the presence of specific skills[1-3]. Behavioral measures, however, reflect the integrated function of multiple brain regions. Rather than behavior, a physiological index of function could be a more sensitive and informative measure with which to compare structural measures. Here, we test for a relationship between a physiological measure of functional connectivity between two brain areas during a simple decision making task and a measure of structural connectivity. Paired-pulse transcranial magnetic stimulation indexed functional connectivity between two regions important for action choices: premotor and motor cortex. Fractional anisotropy (FA), a marker of microstructural integrity, indexed structural connectivity. Individual differences in functional connectivity during action selection show highly specific correlations with FA in localised regions of white matter interconnecting regions including the premotor and motor cortex. Probabilistic tractography[4, 5], a technique for identifying fibre pathways from diffusion-weighted imaging (DWI), reconstructed the anatomical networks linking the component brain regions involved in making decisions. These findings demonstrate a relationship between individual differences in functional and structural connectivity within human brain networks central to action choice

Development Of Human Brain Network Architecture Underlying Executive Function

The transition from late childhood to adulthood is characterized by refinements in brain structure and function that support the dynamic control of attention and goal-directed behavior. One broad domain of cognition that undergoes particularly protracted development is executive function, which encompasses diverse cognitive processes including working memory, inhibitory control, and task switching. Delineating how white matter architecture develops to support specialized brain circuits underlying individual differences in executive function is critical for understanding sources of risk-taking behavior and mortality during adolescence. Moreover, neuropsychiatric disorders are increasingly understood as disorders of brain development, are marked by failures of executive function, and are linked to the disruption of evolving brain connectivity. Network theory provides a parsimonious framework for modeling how anatomical white matter pathways support synchronized fluctuations in neural activity. However, only sparse data exists regarding how the maturation of white matter architecture during human brain development supports coordinated fluctuations in neural activity underlying higher-order cognitive ability. To address this gap, we capitalize on multi-modal neuroimaging and cognitive phenotyping data collected as part of the Philadelphia Neurodevelopmental Cohort (PNC), a large community-based study of brain development. First, diffusion tractography methods were applied to characterize how the development of structural brain network topology supports domain-specific improvements in cognitive ability (n=882, ages 8-22 years old). Second, structural connectivity and task-based functional connectivity approaches were integrated to describe how the development of anatomical constraints on functional communication support individual differences in executive function (n=727, ages 8-23 years old). Finally, the systematic impact of head motion artifact on measures of structural connectivity were characterized (n=949, ages 8-22 years old), providing important guidelines for studying the development of structural brain network architecture. Together, this body of work expands our understanding of how developing white matter connectivity in youth supports the emergence of functionally specialized circuits underlying executive processing. As diverse types of psychopathology are increasingly linked to atypical brain maturation, these findings could collectively lead to earlier diagnosis and personalized interventions for individuals at risk for developing mental disorders

Implications of Inconsistencies between fMRI and dMRI on Multimodal Connectivity Estimation

International audienceThere is a recent trend towards integrating resting state functional magnetic resonance imaging (RS-fMRI) and diffusion MRI (dMRI) for brain connectivity estimation, as motivated by how estimates from these modalities are presumably two views reflecting the same underlying brain circuitry. In this paper, we show on a cohort of 60 subjects that conventional functional connectivity (FC) estimates based on Pearson's correlation and anatomical connectivity (AC) estimates based on fiber counts are actually not that highly correlated for typical RS-fMRI (~7 min) and dMRI (~32 gradient directions) data. The FC-AC correlation can be significantly increased by considering sparse partial correlation and modeling fiber endpoint uncertainty, but the resulting FC-AC correlation is still rather low in absolute terms. We further exemplify the inconsistencies between FC and AC estimates by integrating them as priors into activation detection and demonstrating significant differences in their detection sensitivity. Importantly, we illustrate that these inconsistencies can be useful in fMRI-dMRI integration for improving brain connectivity estimation

Genetic and Neuroanatomical Support for Functional Brain Network Dynamics in Epilepsy

Focal epilepsy is a devastating neurological disorder that affects an overwhelming number of patients worldwide, many of whom prove resistant to medication. The efficacy of current innovative technologies for the treatment of these patients has been stalled by the lack of accurate and effective methods to fuse multimodal neuroimaging data to map anatomical targets driving seizure dynamics. Here we propose a parsimonious model that explains how large-scale anatomical networks and shared genetic constraints shape inter-regional communication in focal epilepsy. In extensive ECoG recordings acquired from a group of patients with medically refractory focal-onset epilepsy, we find that ictal and preictal functional brain network dynamics can be accurately predicted from features of brain anatomy and geometry, patterns of white matter connectivity, and constraints complicit in patterns of gene coexpression, all of which are conserved across healthy adult populations. Moreover, we uncover evidence that markers of non-conserved architecture, potentially driven by idiosyncratic pathology of single subjects, are most prevalent in high frequency ictal dynamics and low frequency preictal dynamics. Finally, we find that ictal dynamics are better predicted by white matter features and more poorly predicted by geometry and genetic constraints than preictal dynamics, suggesting that the functional brain network dynamics manifest in seizures rely on - and may directly propagate along - underlying white matter structure that is largely conserved across humans. Broadly, our work offers insights into the generic architectural principles of the human brain that impact seizure dynamics, and could be extended to further our understanding, models, and predictions of subject-level pathology and response to intervention

Test-retest reliability of structural brain networks from diffusion MRI

Structural brain networks constructed from diffusion MRI (dMRI) and tractography have been demonstrated in healthy volunteers and more recently in various disorders affecting brain connectivity. However, few studies have addressed the reproducibility of the resulting networks. We measured the test–retest properties of such networks by varying several factors affecting network construction using ten healthy volunteers who underwent a dMRI protocol at 1.5 T on two separate occasions. Each T1-weighted brain was parcellated into 84 regions-of-interest and network connections were identified using dMRI and two alternative tractography algorithms, two alternative seeding strategies, a white matter waypoint constraint and three alternative network weightings. In each case, four common graph-theoretic measures were obtained. Network properties were assessed both node-wise and per network in terms of the intraclass correlation coefficient (ICC) and by comparing within- and between-subject differences. Our findings suggest that test–retest performance was improved when: 1) seeding from white matter, rather than grey; and 2) using probabilistic tractography with a two-fibre model and sufficient streamlines, rather than deterministic tensor tractography. In terms of network weighting, a measure of streamline density produced better test–retest performance than tract-averaged diffusion anisotropy, although it remains unclear which is a more accurate representation of the underlying connectivity. For the best performing configuration, the global within-subject differences were between 3.2% and 11.9% with ICCs between 0.62 and 0.76. The mean nodal within-subject differences were between 5.2% and 24.2% with mean ICCs between 0.46 and 0.62. For 83.3% (70/84) of nodes, the within-subject differences were smaller than between-subject differences. Overall, these findings suggest that whilst current techniques produce networks capable of characterising the genuine between-subject differences in connectivity, future work must be undertaken to improve network reliability

Building connectomes using diffusion MRI: why, how and but

Why has diffusion MRI become a principal modality for mapping connectomes in vivo? How do different image acquisition parameters, fiber tracking algorithms and other methodological choices affect connectome estimation? What are the main factors that dictate the success and failure of connectome reconstruction? These are some of the key questions that we aim to address in this review. We provide an overview of the key methods that can be used to estimate the nodes and edges of macroscale connectomes, and we discuss open problems and inherent limitations. We argue that diffusion MRI-based connectome mapping methods are still in their infancy and caution against blind application of deep white matter tractography due to the challenges inherent to connectome reconstruction. We review a number of studies that provide evidence of useful microstructural and network properties that can be extracted in various independent and biologically-relevant contexts. Finally, we highlight some of the key deficiencies of current macroscale connectome mapping methodologies and motivate future developments

Mapping Topographic Structure in White Matter Pathways with Level Set Trees

Fiber tractography on diffusion imaging data offers rich potential for describing white matter pathways in the human brain, but characterizing the spatial organization in these large and complex data sets remains a challenge. We show that level set trees---which provide a concise representation of the hierarchical mode structure of probability density functions---offer a statistically-principled framework for visualizing and analyzing topography in fiber streamlines. Using diffusion spectrum imaging data collected on neurologically healthy controls (N=30), we mapped white matter pathways from the cortex into the striatum using a deterministic tractography algorithm that estimates fiber bundles as dimensionless streamlines. Level set trees were used for interactive exploration of patterns in the endpoint distributions of the mapped fiber tracks and an efficient segmentation of the tracks that has empirical accuracy comparable to standard nonparametric clustering methods. We show that level set trees can also be generalized to model pseudo-density functions in order to analyze a broader array of data types, including entire fiber streamlines. Finally, resampling methods show the reliability of the level set tree as a descriptive measure of topographic structure, illustrating its potential as a statistical descriptor in brain imaging analysis. These results highlight the broad applicability of level set trees for visualizing and analyzing high-dimensional data like fiber tractography output

A Novel Sparse Graphical Approach for Multimodal Brain Connectivity Inference

International audienceDespite the clear potential benefits of combining fMRI and diffusion MRI in learning the neural pathways that underlie brain functions, little methodological progress has been made in this direction. In this paper, we propose a novel multimodal integration approach based on sparse Gaussian graphical model for estimating brain connectivity. Casting functional connectivity estimation as a sparse inverse covariance learning problem, we adapt the level of sparse penalization on each connection based on its anatomical capacity for functional interactions. Functional connections with little anatomical support are thus more heavily penalized. For validation, we showed on real data collected from a cohort of 60 subjects that additionally modeling anatomical capacity significantly increases subject consistency in the detected connection patterns. Moreover, we demonstrated that incorporating a connectivity prior learned with our multimodal connectivity estimation approach improves activation detection