Elsevier

NeuroImage

Volume 32, Issue 3, September 2006, Pages 989-994
NeuroImage

Topography of the human corpus callosum revisited—Comprehensive fiber tractography using diffusion tensor magnetic resonance imaging

https://doi.org/10.1016/j.neuroimage.2006.05.044Get rights and content

Abstract

Several tracing studies have established a topographical distribution of fiber connections to the cortex in midsagittal cross-sections of the corpus callosum (CC). The most prominent example is Witelson's scheme, which defines five vertical partitions mainly based on primate data. Conventional MRI of the human CC does not reveal morphologically discernable structures, although microscopy techniques identified myelinated axons with a relatively small diameter in the anterior and posterior third of the CC as opposed to thick fibers in the midbody and posterior splenium. Here, we applied diffusion tensor imaging (DTI) in conjunction with a tract-tracing algorithm to gain cortical connectivity information of the CC in individual subjects. With DTI-based tractography, we distinguished five vertical segments of the CC, containing fibers projecting into prefrontal, premotor (and supplementary motor), primary motor, and primary sensory areas as well as into parietal, temporal, and occipital cortical areas. Striking differences to Witelson's classification were recognized in the midbody and anterior third of the CC. In particular, callosal motor fiber bundles were found to cross the CC in a much more posterior location than previously indicated. Differences in water mobility were found to be in qualitative agreement with differences in the microstructure of transcallosal fibers yielding the highest anisotropy in posterior regions of the CC. The lowest anisotropy was observed in compartments assigned to motor and sensory cortical areas. In conclusion, DTI-based fiber tractography of healthy human subjects suggests a modification of the widely accepted Witelson scheme and a new classification of vertical CC partitions.

Introduction

The corpus callosum (CC) is by far the largest fiber bundle in the human brain interconnecting the two cerebral hemispheres with more than 300 million fibers. Surgical transection of the CC in humans provides evidence of its important role in interhemispheric functional integration communicating perceptual, cognitive, learned, and volitional information. Most of the fibers serve homotopic interconnections between the hemispheres, but a number of heterotopic fibers also asymmetrically link functionally different cortical areas (Clarke and Zaidel, 1994, De Lacoste et al., 1985, Witelson, 1989). The CC is one of the few white matter tracts that can be discretely identified by conventional MRI. It has been the target of extensive studies (e.g., see Thompson et al., 2003) indicating that its morphology may be related to dyslexia (von Plessen et al., 2002), Tourette's syndrome (Plessen et al., 2004), Down's syndrome (Teipel et al., 2003), depression (Lacerda et al., 2005), schizophrenia (Narr et al., 2002), and HIV/AIDS (Thompson et al., 2006).

Due to the fact that there are no macroscopic anatomical landmarks that clearly delimit distinct callosal areas in a midsagittal cross-section, several geometric partitioning schemes have been designed to subdivide the CC (Duara et al., 1991, Larsen et al., 1992, Weis et al., 1993, Rajapakse et al., 1996). In fact, most studies rely on Witelson's classification, although the underlying data predominantly originates from non-human primates (Witelson, 1989). This scheme defines five vertical callosal segments based on specific arithmetic fractions of the maximum anterior–posterior extent. In particular, the CC is subdivided into regions comprising the anterior third, the anterior and posterior midbody, the posterior third, and the posterior one-fifth. Compartments of the anterior third, including the rostrum, genu, and rostral body, are assigned to prefrontal, premotor, and supplementary motor cortical areas. Fibers originating in the motor cortex are assumed to cross the CC through the anterior midbody, whereas somaesthetic and posterior parietal fiber bundles cross the CC through the posterior midbody. Compartments of the posterior third, including the isthmus and splenium, are assigned to temporal, parietal, and occipital cortical regions. It should be noted, however, that neither Witelson's classification nor other geometric partitioning schemes exactly mirror the texture of the CC at the cellular level.

Light microscopic examinations of the fiber composition in the human CC (Aboitz et al., 1992) revealed a well-defined microstructure with a consistent pattern of regional differentiation. The density of fibers with a small diameter is most pronounced in the anterior CC (genu), decreases to a minimum in the posterior midbody, and increases again toward the posterior CC (splenium). In contrast, fibers with a large diameter show a diametrically opposed pattern with a peak density in the posterior midbody. Absolute fiber density decreases from the genu to the posterior midbody, increases when entering the splenium, and is diminished again in the most posterior splenial region.

The development of magnetic resonance diffusion tensor imaging (DTI) in conjunction with fiber tractography has opened new possibilities in the research of white matter anatomy. The approach provides unique access to in vivo information about the topography of major fiber tracts and even their maturation during ontogeny (Huang et al., 2005, Dougherty et al., 2005, Ramnani et al., 2004). The method is based on the fact that the MRI-detectable diffusivity of water molecules depends on the principal orientation of the fiber tracts within white matter. Diffusion-weighted MRI sequences probe such mobility along multiple directions in order to fully characterize its orientational distribution within an image voxel. Under the assumption that this distribution may be mathematically represented by a tensor, the principle axis of the corresponding diffusion ellipsoid coincides with the direction of the greatest diffusion coefficient, which then can be identified with the orientation of the underlying fiber bundle. Anisotropy measures reflect the degree to which diffusion is preferred along this direction relative to other directions. Here, fractional anisotropy (FA) values have been used as scalar indicators of the directionality and coherence of fiber tracts (Basser and Pierpaoli, 1996).

The goal of this study was to complement structural assessments of the CC by cortical connectivity information in individual subjects by means of a geometrically undistorted DTI technique without sensitivity to susceptibility differences (Nolte et al., 2000, Rieseberg et al., 2005) in conjunction with a simple algorithm for tract tracing (Mori et al., 1999). A region-of-interest (ROI) to ROI tractography method was employed to identify all trajectories that cross individual pixels within the entire CC (first ROI) and penetrate selective cortex areas (second ROI). This strategy resulted in a detailed separation of transcallosal fiber tracts with respect to their specific cortical projections. In addition, the approach allowed for an assignment of the distribution of FA values to functionally distinct CC regions.

Section snippets

Participants

A total of eight right-handed human subjects (4 female, 4 male; age range 21−47 years) participated in the study. None of them had any history of neurological abnormality. Handedness was assessed in accordance to the hand preference score reported by Oldfield (1971). All subjects gave written informed consent before each MRI examination.

Data acquisition

MRI studies were conducted at 2.9 T (Siemens Trio, Erlangen, Germany) using an 8-channel phased-array head coil. Acquisitions were performed at 2 mm isotropic

Topography of callosal fiber tracts

DTI-based tractography allowed us to reconstruct comprehensive sets of callosal fiber bundles projecting to the cortical hemispheres in all subjects. By classifying tracts according to their cortical projections, we could distinguish between fibers associated with prefrontal, premotor (combined with supplementary motor), primary motor, primary sensory, parietal, temporal and occipital cortical regions. The resulting topology of fiber bundles in the CC is demonstrated in Figs. 1A–C for a single

Concluding remarks

DTI of water molecules within the human brain offers unique access to the microstructure of white matter in vivo (Basser and Pierpaoli, 1996). Here, by means of DTI-based fiber tractography, the topographic arrangement of transcallosal fiber tracts projecting into specific cortical areas was re-evaluated, and striking differences were found to previous classifications in a consistent manner. Nevertheless, current methodologies still face a number of challenges. As an example, lateral

Acknowledgments

SH was supported by the Bundesminister für Bildung und Forschung of the Federal Republic of Germany (grant 01 GQ 0432). The authors thank Matthias Küntzel for his software developments and helpful comments regarding the manuscript.

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