Combined DTI Tractography and Functional MRI Study of the Language Connectome in Healthy Volunteers: Extensive Mapping of White Matter Fascicles and Cortical Activations.

François Vassal,Betty Jean,Jean-Jacques Lemaire,Anna Sontheimer,Fabien Schneider,Claire Boutet,Xi-Nian Zuo

doi:10.1371/journal.pone.0152614

Abstract

Despite a better understanding of brain language organization into large-scale cortical networks, the underlying white matter (WM) connectivity is still not mastered. Here we combined diffusion tensor imaging (DTI) fiber tracking (FT) and language functional magnetic resonance imaging (fMRI) in twenty healthy subjects to gain new insights into the macroscopic structural connectivity of language. Eight putative WM fascicles for language were probed using a deterministic DTI-FT technique: the arcuate fascicle (AF), superior longitudinal fascicle (SLF), uncinate fascicle (UF), temporo-occipital fascicle, inferior fronto-occipital fascicle (IFOF), middle longitudinal fascicle (MdLF), frontal aslant fascicle and operculopremotor fascicle. Specific measurements (i.e. volume, length, fractional anisotropy) and precise cortical terminations were derived for each WM fascicle within both hemispheres. Connections between these WM fascicles and fMRI activations were studied to determine which WM fascicles are related to language. WM fascicle volumes showed asymmetries: leftward for the AF, temporoparietal segment of SLF and UF, and rightward for the frontoparietal segment of the SLF. The lateralization of the AF, IFOF and MdLF extended to differences in patterns of anatomical connections, which may relate to specific hemispheric abilities. The leftward asymmetry of the AF was correlated to the leftward asymmetry of fMRI activations, suggesting that the lateralization of the AF is a structural substrate of hemispheric language dominance. We found consistent connections between fMRI activations and terminations of the eight WM fascicles, providing a detailed description of the language connectome. WM fascicle terminations were also observed beyond fMRI-confirmed language areas and reached numerous cortical areas involved in different functional brain networks. These findings suggest that the reported WM fascicles are not exclusively involved in language and might be related to other cognitive functions such as visual recognition, spatial attention, executive functions, memory, and processing of emotional and behavioral aspects.

Highlights

Seminal lesion studies in aphasiology [1] have provided a topological model of brain language organization where three cortical territories, i.e. Broca’s, Geschwind’s and Wernicke’s, play central roles in language production and comprehension
Three important findings emerge: (1) the structural white matter (WM) organization of the language network differs between the two hemispheres; (2) the bilateral variability of WM fascicle connection patterns underlines the high degree of anatomical variability among the normal population; (3) the cortical connections of language-related WM fascicles extend beyond the classical language areas revealed by functional magnetic resonance imaging (fMRI), which may reflect an involvement in several distinctive functional brain processes
diffusion tensor imaging (DTI)-fiber tracking (FT) carries several well-known technical biases that need to be considered when interpreting the results of this study: (1) very small fiber bundles were not identifiable due to the size of the voxels (1×1×3.5 mm3); (2) convergences of WM fascicles, e.g. inferior fronto-occipital fascicle (IFOF) and uncinate fascicle (UF) in the frontobasal lobe or IFOF and temporo-occipital fascicle (TOF) in the temporobasal lobe, made it difficult to get a finedgrained distinction between neighboring fibers; (3) FT within the gray–white matter interface was limited by the low anisotropy of this complex region

Summary

Introduction

Seminal lesion studies in aphasiology [1] have provided a topological model of brain language organization where three cortical territories, i.e. Broca’s, Geschwind’s and Wernicke’s, play central roles in language production and comprehension. In the past two decades, functional magnetic resonance imaging (fMRI) has changed our understanding of language organization into a network model by showing activations within a distributed set of regions that extend beyond these three cortical territories [2,3,4,5]. In this framework, language is underpinned by large-scale neuronal networks that co-interact in what is known as the language connectome [6]. Deeper knowledge of the anatomy of WM fascicles could yield critical insights into language and other cognitive skills

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