In this letter, we present a new method for integration of sensor-based multifrequency bands of electroencephalography and magnetoencephalography data sets into a voxel-based structural-temporal magnetic resonance imaging analysis by utilizing the general joint estimation using entropy regularization (JESTER) framework. This allows enhancement of the spatial-temporal localization of brain function and the ability to relate it to morphological features and structural connectivity. This method has broad implications for both basic neuroscience research and clinical neuroscience focused on identifying disease-relevant biomarkers by enhancing the spatial-temporal resolution of the estimates derived from current neuroimaging modalities, thereby providing a better picture of the normal human brain in basic neuroimaging experiments and variations associated with disease states.

A primary goal of many neuroimaging studies that use magnetic resonance imaging (MRI) is to deduce the structure-function relationships in the human brain using data from the three major neuro-MRI modalities: high-resolution anatomical, diffusion tensor imaging, and functional MRI. To date, the general procedure for analyzing these data is to combine the results derived independently from each of these modalities. In this article, we develop a new theoretical and computational approach for combining these different MRI modalities into a powerful and versatile framework that combines our recently developed methods for morphological shape analysis and segmentation, simultaneous local diffusion estimation and global tractography, and nonlinear and nongaussian spatial-temporal activation pattern classification and ranking, as well as our fast and accurate approach for nonlinear registration between modalities. This joint analysis method is capable of extracting new levels of information that is not achievable from any of those single modalities alone. A theoretical probabilistic framework based on a reformulation of prior information and available interdependencies between modalities through a joint coupling matrix and an efficient computational implementation allows construction of quantitative functional, structural, and effective brain connectivity modes and parcellation. This new method provides an overall increase of resolution, accuracy, level of detail, and information content and has the potential to be instrumental in the clinical adaptation of neuro-MRI modalities, which, when jointly analyzed, provide a more comprehensive view of a subject’s structure-function relations, while the current standard, wherein single-modality methods are analyzed separately, leaves a critical gap in an integrated view of a subject’s neuorphysiological state. As one example of this increased sensitivity, we demonstrate that the jointly estimated structural and functional dependencies of mode power follow the same power law decay with the same exponent.

We present a quantitative statistical analysis of pairwise crossings for all fibers obtained from whole brain tractography that confirms with high confidence that the brain grid theory (Wedeen et al., 2012a ) is not supported by the evidence. The overall fiber tracts structure appears to be more consistent with small angle treelike branching of tracts rather than with near-orthogonal gridlike crossing of fiber sheets. The analysis uses our new method for high-resolution whole brain tractography that is capable of resolving fibers crossing of less than 10 degrees and correctly following a continuous angular distribution of fibers even when the individual fiber directions are not resolved. This analysis also allows us to demonstrate that the whole brain fiber pathway system is very well approximated by a lamellar vector field, providing a concise and quantitative mathematical characterization of the structural connectivity of the human brain.

The ability of functional magnetic resonance imaging (FMRI) to noninvasively measure fluctuations in brain activity in the absence of an applied stimulus offers the possibility of discerning functional networks in the resting state of the brain. However, the reconstruction of brain networks from these signal fluctuations poses a significant challenge because they are generally nonlinear and nongaussian and can overlap in both their spatial and temporal extent. Moreover, because there is no explicit input stimulus, there is no signal model with which to compare the brain responses. A variety of techniques have been devised to address this problem, but the predominant approaches are based on the presupposition of statistical properties of complex brain signal parameters, which are unprovable but facilitate the analysis. In this article, we address this problem with a new method, entropy field decomposition , for estimating structure within spatiotemporal data. This method is based on a general information field-theoretic formulation of Bayesian probability theory incorporating prior coupling information that allows the enumeration of the most probable parameter configurations without the need for unjustified statistical assumptions. This approach facilitates the construction of brain activation modes directly from the spatial-temporal correlation structure of the data. These modes and their associated spatial-temporal correlation structure can then be used to generate space-time activity probability trajectories, called functional connectivity pathways , which provide a characterization of functional brain networks.