MR connectomics: a conceptual framework for studying the developing brain

Abstract

THE COMBINATION OF ADVANCED NEUROIMAGING TECHNIQUES AND MAJOR DEVELOPMENTS IN COMPLEX NETWORK SCIENCE, HAVE GIVEN BIRTH TO A NEW FRAMEWORK FOR STUDYING THE BRAIN: "connectomics." This framework provides the ability to describe and study the brain as a dynamic network and to explore how the coordination and integration of information processing may occur. In recent years this framework has been used to investigate the developing brain and has shed light on many dynamic changes occurring from infancy through adulthood. The aim of this article is to review this work and to discuss what we have learned from it. We will also use this body of work to highlight key technical aspects that are necessary in general for successful connectome analysis using today's advanced neuroimaging techniques. We look to identify current limitations of such approaches, what can be improved, and how these points generalize to other topics in connectome research.

Keywords: connectivity; development; diffusion MRI; human brain; networks; resting state functional MRI; tractography.

Figure 1

Computational model of functional connectivity. (A) Scatter plot of empirical resting state functional connectivity versus simulated resting state functional connectivity obtained from the nonlinear model, downsampled to the low resolution. (B) Comparison of structural connectivity, emprirical resting state functional connectivity and nonlinear model of resting state functional connectivity for two single seed regions, the posterior cingulate in the right hemisphere (rPC) and the precuneus in the left hemisphere (lPCUN). (C) Mapping of structural, empirical resting state functional connectivity and modeled resting state functional connectivity within the default mode network (DMN). Within the posterior cingulated/precuneus, medial orbitofrontal cortex and lateral parietal cortex in both hemispheres were selected clusters of five ROIs at positions that most closely matched the coordinates of peak foci of the DMN. These 30 ROIs served as the seeds from which SC and rsFC were determined. (D) Structural connectivity within the DMN. Adapted from Honey et al. (2009).

Figure 2

Sagittal tractography image of an 18 week gestational age fetal pathology specimen shows highly radial coherence of the cerebral mantel consistent with radial migration [courtesy of Emi Takahashi (Takahashi et al., 2011a)].

Figure 3

Changes in thalamo-cortical connectivity across age. The color-coded thalamus, based on the winner take all strategy (Zhang et al., 2008), in adults shows a functional organization that is remarkably similar to known nuclear groupings in the primate thalamus. However, the picture is different in adolescents and children. In both adolescents and to a greater extent children, thalamo-temporal interactions encompass a greater portion of anterior and midline thalamus, while the frontal lobe interactions encompass much less of the anterior portions of the thalamus. In children, thalamo-temporal interactions not only encroach on areas that, in adults, are dominated by thalamo-frontal interactions, but also impinge on thalamic zones that later become functionally more connected with motor/premotor, somatosensory, and occipical/parietal cortex; Transverse Z = +8, Sagittal X = −12, Coronal Y = −27.

Figure 4

Modularity and structure-function correlation. (A) Cortical (N = 241) structural and functional connectivity matrices averaged over young (<4 years) and older (>13 years) subjects. Structural modules are delineated by the superimposed white grid. While modules are highly conserved (normalized mutual information = 0.82), there is a notable increase in structure-function correspondence from younger to older brains. Modules are centered on the following anatomical locations: M1, occipital cortex; M2, parietal cortex; M3, parietal cortex; M4, orbitofrontal cortex; M5, frontal cortex; M6, temporal cortex; M7, occipital cortex; M8, parietal cortex; M9, orbitofrontal cortex; M10, frontal cortex; M11, temporal cortex. (B) Increasing statistical relationship between structural and functional connectivity across age (R = 0.74, p < 0.005). Adapted from Hagmann et al. (2010b).