Regular articleCharacterization of sexual dimorphism in the human corpus callosum
Introduction
Differences in higher cortical functioning between males and females have been the target of considerable investigation for a number of decades. Cognitive and functional imaging studies have suggested a greater degree of hemispheric lateralization in males compared to females, while females displayed increased bilateral hemispheric activity for a variety of cognitive tasks Harshman and Remington, 1976, McGlone, 1980, Bryden, 1979, Kimura and Harshman, 1984, Shaywitz et al., 1995. These studies seem to suggest enhanced interhemispheric communication in females and have motivated investigation into sexual dimorphism of the corpus callosum. The corpus callosum is the brain's largest white-matter tract and the primary means of communication between the two cerebral hemispheres, prompting investigators to hypothesize that differences in callosal size exist between males and females. Most investigators have examined the shape and size of the mid-sagittal section of the callosum as a surrogate for the structure's overall shape. To date, however, no consensus has been reached on the presence of such gender-based differences in the callosum. De Lacoste and Holloway (1982) reported in 1982 that the female splenium was more bulbous than the tubual male splenium. Follow-up studies by De Lacoste-Utamsing et al., 1986, Yoshi et al., 1986, and Allen et al. (1991) all found increased size in the female splenium. In contrast, Weis and colleagues Weis et al., 1989, Going and Dixson, 1990, and Witelson (1985) all reported no such differences between the callosa of males and females.
One possible reason for this prevailing controversy may be the lack of standards in callosal analysis. While cross-sectional area and callosal length are the more traditional indices reported in gender studies, there is little agreement over how to normalize these indices. Furthermore, gross dimensional measures will miss regional shape variations in callosa. Some investigators have divided the callosa into partitions and compared the area of corresponding partitions between study groups (Witelson, 1985). The difficulty here is that the selection of the partitioning method is arbitrary and subpartition size differences may escape detection.
We used template deformation morphometry (TDM) Machado and Gee, 1998, Machado, et al., 2000, Davatzikos et al., 1996, which avoids many of the pitfalls associated with more traditional measures of the callosum. By registering each subject to a template callosum and normalizing over that callosum's area, we avoid the issue of normalizing measurements to some arbitrary index of overall brain size (Bermudez and Zatorre, 2001). In addition, TDM gives a pointwise measure of expansion or contraction and so is more sensitive to regional morphologic differences than any partitioning method. Finally, TDM is a general strategy for comparing shape, and so can be used to analyze any part of the brain, indeed the whole brain, in principle.
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Subjects and data acquisition
The Schizophrenia Center at the University of Pennsylvania maintains a database containing hundreds of prospectively accrued cranial MRIs of psychiatric patients and healthy volunteers. The sample selection procedures have been detailed in Shtasel et al. (1991), the MRI acquisition protocol has been described in detail in Gur et al. (1999b), and results of volumetric segmentation analysis for this sample have been reported Gur et al., 1998, Gur et al., 1999a, Gur et al., 1999b. Our selection
Results
Our query of the Schizophrenia Center database yielded a total of 189 cranial MRI's, 94 male and 95 female. The average age among the male and female subgroups was 29.3 ± 10 years (range 18 to 84) and 26.8 ± 9.3 years (range 18 to 74), respectively. Fig. 2 shows the results of the pointwise comparison of mean adjusted Jacobians using raw P values as well as cluster analysis. There is a statistically significant area of expansion in the splenium in females with respect to males (P < 0.001) and
Discussion
Our results with template deformation morphometry demonstrate sexual dimorphism in the splenium of the corpus callosum. This result is consistent with earlier reports using planimetric methods (Shaywitz et al., 1995). We also found relatively larger genu of the callosum in men, suggesting more bihemispheric communication of the motor tasks likely to be mediated through this region of the callosum. In addition, our results suggest that the female splenium expands with age to a greater degree
Acknowledgements
This work was supported in part by the USPHS under Grants NS-33662, LM-03504, MH-62100, AG-15116, AG-17586, and DA-14418.
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