Psy<'hobiology 1988, Vol. 16 (4), 41/-415 The human corpus callosum and the controversy about a sexual dimorphism

SERGE WEIS Medical University of Lübeck, Lübeck, Federal Republic of Germany

GERMAIN WEBER Ludwig Boltzmann Institute of Research on Brain-Damaged Children, Vienna, Austria and EMANUEL WENGER and MELITI'A KIMBACHER Austrian Academy of Sciences, Vienna, Austria

The human corpus callosum was investigated with regard to sexual dimorphism by means of morphometry. At the macroBCopicallevel, no part ofthe corpus callosum showed significant differ­ ences between the sexes. The concept that sex-related functional hemispherical discrepancies are correlated with the gross anatomy of the human corpus callosum was not confirmed.

De Lacoste-Utamsing and Holloway (1982) reported each sex), also failed to replicate de Lacoste's results. gender differences in the shape and cross-sectional area Although measurements of the maximal splenial width and of the posterior part of the human corpus callosum. They the totallength, cross-sectional area of the posterior third, described the female splenium to be more bulbous and fourth, and fifth of the corpus callosum were done, no larger than its male counterpart. They supposed that their significant differences between the sexes could be re­ findings, based on nine male and five female autopsy vealed. An additional form factor, evaluated for the brains, could be related to possible gender differences in splenium, also failed to show sex differences. The data the degree of lateralization for visuospatial functions. In of these parameters were processed by means of a dis­ an extension and replication, Holloway and de Lacoste criminant analysis, with sex as a classification variable. (1986), using eight brains of each sex, reproduced the However, only 58% of the cases were correctly classi­ same results. In addition, they reported that the total area fied. It was concluded that the size and shape of the of the corpus callosum of females was absolutely, as well splenium corporis callosi vary widely from one person as relatively, larger than that of males. Similar sex-related to another, but not significantly between the sexes. These differences in the morphology of the callosal splenium results recently have been confirmed by Demeter, Ringo, have been reported in human fetuses (Baack, de Lacoste­ and Doty (1988). Utamsing, & Woodward, 1982; de Lacoste, Holloway, Using nuclear magnetic resonance (NMR) imaging as & Woodward, 1986) and in other primates (de Lacoste a method to study the issues of gross-anatomical gender & Woodward, 1983). The results of de Lacoste-Utamsing differences in the brain, it is possible to investigate a liv­ and Holloway's (1982) study have already been introduced ing population and to avoid the high average age of an as facts by Kelly (1985) in a major neuroscience textbook. autopsy sampie, thus eliminating two major sources of Although Witelson (1985) found differences in the size artifacts in this research field. of the corpus callosum between left- and right-handers, Bleier, Houston, and Byne (1986) measured the corpus she could not demonstrate gender differences in the cal- callosum on NMR images in 17 men and 22 women. Their 10sal splenium of her autopsy brains. Bell and Variend results did not confirm gender-associated differences in (1985) investigated a sampie of 28 male and 16 female splenial area or maximum splenial width; rather, they ob­ autopsy brains of white children aged from birth to 14 served large variations in callosal size and shape among years. A one-way analysis of covariance, with age and individuals irrespective of sex and age. brain weight as covariates, did not show differences in Oppenheim, Lee, Nass, and Gazzaniga (1987) calcu­ splenial width or area between males and females under lated relative measurements for the corpus callosum of 2 years of age. Furthermore, Weber and Weis (1986), 40 men and 40 women. They did not find significant sex­ using a larger sampie of autopsied brains (18 brains of related differences for callosal areas, maximal callosal width, or callosal curvature. Kertesz, Polk, Howell, and Black (1987) reported on a magnetic resonance imaging This paper is dedicated to Herbert Haug on the occasion of his 68th birthday. Correpondence may be addressed to Serge Weis, Institute of study of the corpus callosum, using a large sampie (52 Anatomy, Medical University of Lübeck, Ratzeburger Allee 160, subjects of each sex). They did not detect sex differences D-2400 Lübeck I, Federal Republic of Germany. in callosal area ratios for the sagittal cross-sectional area,

411 Copyright 1988 Psychonomic Society, Inc. 412 WEIS, WEBER, WENGER, AND KIMBACHER but found large individual variations in callosal size and 3, 4, and 5 parts, are listed in Table 1. No significant shape. Recently, Byne, Bleier, and Houston (1988) differences between the sexes could be found. reported on an NMR-imaging investigation ofthe corpus The results obtained by the rotatory diameter measure­ callosum carried out on 15 males and 22 females. Their ments are listed in Table 2. No significant differences study confirmed the previous observation that individual could be detected between the male and female groups. variability was more important than the variability be­ tween the sexes. DISCUSSION In the present paper, additional data on the corpus cal­ losum, obtained by NMR imaging, is presented. The In the present study, sex differences could not be measurements were extended to include an evaluation of demonstrated in any part of the corpus callosum. None the total corpus callosum and some new parameters. ofthe classical parameters (i.e., proflle area and callosal length) nor rotatory diameter measurements were found METHOD to differ between males and females. These results are consistent with the morphometric measurements of Bleier The subjects were 20 males and 26 females aged 24-83 years. et al. (1986), Oppenheim et al. (1987), Kertesz et al. The average ages of the male and female groups were 44.1 (SD (1987), and Byne et al. (1988), although the evaluation = 17.1) and 48.9 (SD = 17.4) years, respectively. The subjects procedures differed in various ways between the research were selected from a sampie that had undergone NMR imaging be­ cause of neurological disturbances, but whose neuroradiological groups. The paper of Bleier et al. (1986) lacked infor­ reports were free of neuropathological signs. Thus, people with dis­ mation on the quantification procedure. It seems that one ease states involving the corpus callosum, such as multiple sclero­ crucial point is how splenial width is defined. Although sis (Huber et al., 1987) and demented states (Y oshii et al., 1986), they presented results on splenial width, Byne et al. (1988) and cases with brain tumors and hydrocephalus were not included failed to indicate their measure of splenial width on the in the subject sampie. Since material was delivered by routine NMR figures ofthe corpus callosum. Oppenheim et al. (1987) imaging, no information on hand preference could be obtained. Median-sagittal images were produced with the 0.5 Tesla super­ divided the corpus callosum into five parts and defined conductivity system GYROSCAN S5 (PhilJips) using short TE/TR the splenial width in a manner similar to the present work. (30/350) spin echo sequences, and then subjected to digital image They did not, however, present absolute measurements analysis. of splenial width; rather, their measurement of callosal The outline of the corpus callosum was traced with the digitizer. distance and area were presented as relative data (i.e., The metric scale and the lowest points of the rostrum and the as apercentage of the total callosal area or distance). It splenium were transmitted to the system. can only be assumed that the images from which they The quantification was performed as iIlustrated in Figure lA, in which HI 1 = horizontal inferior 1 tangent to the most inferior point made their measurements were lacking a metric scale. Fi­ of the rostrum and the splenium; VAl = vertical anterior I tan­ nally, Kertesz et al. (1987) presented results on a cross­ gent to the most anterior point of the genu and right-angled to HI 1; sectional area of the corpus callosum without consider­ VP 1 = vertical posterior 1 tangent to the most posterior point of ing quantification data of its subdivided parts. the splenium and right-angled to HI 1; HS 1 = horizontal superior 1 Recently, some functional differences in inter­ tangent to the most superior point ofthe trunk, parallel to HI 1 and hemispheric transfer have been reported. St. John, right-angled to VA 1 and VP 1. The callosal height was defined as the distance between HI 1 and Shields, Krahn, and Tirnney (1987) assessed the reliabil­ HS 1; the callosallength was defined as the distance between VAl ity of estimates in interhemispheric transmission time de­ and VP 1. The callosallength was subdivided into 2, 3,4, and 5 rived from verbal and unimanual responses. They found parts. The profile area of these different parts was evaluated con­ that, for unimanual response conditions, interhemispheric secutively (see Figure lA). transmission times for the female subjects were estimated To avoid the vague definition of the "maximal spJenial width" to be longer and exhibited poorer reliabilities than for the given by de Lacoste-Utamsing and Holloway (1982) and to make male subjects. However, the verbal response conditions the evaluation reproducible, we measured the width of the posterior fifth of the corpus callosum by calculating the maximal diameter showed no differences in the mean duration of the esti­ of the splenium parallel to HI 1, called MDX, and the maximal mates between females and males. diameter of the splenium parallel to VP 1, called MDY. In another study, St. lohn and Tirnney (1986) exarnined The crossing point of MDX and MDY served as a reference point the transmission of information through callosal fibers by for the rotatory diameter measurement. Starting from MDY, at regu­ simple unimanual reaction time in human strabismics. lar intervals of 10 0, lines connecting the splenial outlines and passing They observed that the estimates of cross-callosal trans­ through the crossing point were traced. The lengths of these 10 lines were measured. This procedure allowed reproducible measurements mission time for strabismics were distinctly longer than of the maximal diameters of the splenium (see Figure IB). for the normal controls. St. lohn and Tirnney concluded that human strabismics had abnormalities in the callosal fibers that are involved in interhemispheric transmission RESULTS of visual information. Byne et al. (1988) argued that if variations in callosal The results of the measurements for the callosal height, size or shape are interpreted as parameters of cognitive length, and proflle area, as weIl as for the proflle areas functions, then such interpretations must be based on of the different subdivisions of the callosallength in 2, known correlations between callosal size or shape and par- A B

MDY

JO.

VA1 vp1

VAl - VPl ~o· distance

_____ 70

Hs1 80· ,..". =---~ • "'!O\

tU 1 ~ m e5PAl eSPA2 esp,,) eSPM eSPA5 C5PA5 ::r:: A4 c:: ~ >z n o :;t! '""Cl c:: CI) n l'> 5 CI) c:: ~ YJgUre 1. (A) Subdivisioo of tbe corpus calIosum ioto five parts. (8) Tbe "rotatory diameter measuremeot."

-~""'" 414 WEIS, WEBER, WENGER, AND KIMBACHER

ticular cognitive functions. At present, there is no evi­ Table 2 dence for such correlations. Indeed, Kertesz et al. (1987) Mean Values (Ms) and Standard Deviations (SDs) of the Splenial showed that callosal area did not correlate with brain size Parameters Obtained by the Rotatory Diameter Measurement or with measures of lateralization for hand performance, Female Group Male Group dichotic listening, or visuaI field preference. They did not Parameters M SD M SD indicate, however, what quantification procedure was used MDY 13.13 1.83 13.09 1.82 to estimate brain size. +10 0 12.02 1.99 12.15 1.82 +200 11.49 2.40 11.73 1.83 In spite of the fact that this investigation and others have 0 +30 11.26 2.69 11.53 1.80 not found reliable sex differences in the gross anatomy +40 0 11.40 2.96 11.53 1.84 ofthe human corpus callosum, functional differences be­ +500 11.71 3.12 11.75 1.82 tween the sexes in interhemispheric transfer have been +60 0 12.30 3.30 12.44 1.70 0 described. Functional interhemispheric differences may +70 13.36 3.33 13.61 1.60 +80 0 14.98 3.42 15.07 1.79 result either in a changed electrophysiological transmis­ MSX 17.78 2.41 17.26 2.65 sion pattern or in variations of the diameters of callosal Note-All splenial diameters are expressed in millimeters. Using the axons. Whether these possible changes in the microstruc­ Mann-Whitney U test, no significant differences could be detected be­ ture of call0sal fibers could provide a basis for theories tween the male and female groups. MDY = the maximal diameter of of sex differences in cognitive functions must be con­ the splenium parallel to vertical posterior 1. MDX = the maximal di­ sidered in careful investigations, since to our present ameter of the splenium parallel to horizontal interior I. knowledge only 2 % of cortical neurons have cornmissural axons (Creutzfeldt, 1983). Although many researchers obtain similar findings, there The existing scientific trend of trying to relate nonpatho­ remain differences in the way the neuroanatomical logical behavioral differences to differences in gross anat­ parameters are measured. Before any definitive conclu­ omy appears to be premature and of debatable value. sions can be reached, it will be necessary to clearly de­ fine the quantification procedure used. We adhere to the conviction that the functional neuroanatomical issue can Table 1 Mean Values (Ms) and Standard Deviations (SDs) of the only be approached seriously after the major method­ Evaluated Parameters Compared in 80th Sex Groups ological issues are resolved. Female Group Male Group Parameters M SD M SD REFERENCES CH 26.84 2.91 26.66 3.14 BAACK, J., OE LACOSTE-UTAMSlNG, M. C., & WOOOWARD, D. J. (1982). CL 76.72 6.51 74.61 5.41 Sexual dimorphism in the human fetal corpora callosa. Neuroscience CPA 665.20 96.30 669.92 122.49 Abstracts, 8, 18. C2PAI 331.77 51.02 341.64 66.28 BELL, A. D., & VARIENO, S. (1985). Failure to demonstrate sexual C2PA2 333.43 51.92 327.98 62.47 dimorphism of the corpus callosum in childhood. Journal oi Anat­ C3PAI 255.65 41.12 267.02 54.22 omy, 143, 143-147. C3PA2 148.07 23.19 144.84 26.82 BLEIER, R., HOUSTON, L., & BYNE, W. (1986). Can the corpus callo­ C3PA3 261.48 42.22 257.75 50.69 sum predict gender , age, handedness, or cognitive differences? Trends C4PAI 216.62 33.86 224.07 44.03 in Neurosciences, 9, 391-394. C4PA2 114.22 19.51 115.99 24.02 BYNE, W., BLEIER, R., & HOUSTON, L. (1988). Variations in human C4PA3 107.15 18.76 107.81 20.89 corpus callosum do not predict gender: A study using magnetic C4PA4 226.28 37.96 220.16 43.99 resonance imaging. Behavioral Neuroscience, 102,222-227. C5PAI 185.15 26.87 187.95 33.96 CREUTZFELDT, O. D. (1983). Cortex cerebri. Berlin: Springer­ C5PA2 93.00 16.61 98.78 23.64 Verlag. C5PA3 89.32 14.69 86.05 14.91 OE LACOSTE, M. C., & WOOOWARD, D. J. (1983). Neocortical com­ C5PA4 89.26 17.25 93.97 21.54 rnissural size and sex differences in primate brain. Neuroscience C5PA5 199.95 34.52 191.54 38.06 Abstracts, 9, 45. Note-CH and CL are expressed in millimeters; allother parameters OE LACOSTE, M. C., HOLWWAY, R. L., & WOOOWARD, D. J. (1986). are expressed in square millimeters. Using the Mann-Whitney U test, Sex differences in the fetal human corpus callosum. Human Neurobi­ no signiticant differences could be detected between the male and fe­ ology, S, 93-96. male groups. List of abbreviations for callosal parameters: CH, callosal OE LACOSTE-UTAMSING, M. C., & HOLWWAY, R. L. (1982). Sexual height; CL, callosallength; CPA, callosal profile area; C2PAl, pro­ dimorphism in the human corpus callosum. Science, 216, 1431-1432. file area of the first callosal half; C2PA2, profile area of the second DEMETER, S., RINGO, J. L., & DoTY, R. W. (1988). Morphometric callosal half; C3PAl, profile area of the first callosal third; C3PA2, analysis of the human corpus callosum and anterior comrnissure. Hu­ profile area of the second callosal third; C3 P A3, profile area of the third man Neurobiology, 6, 219-226. callosal third; C4PAl, profile area ofthe first callosal fourth; C4PA2, HOLWWAY, R. L., & OE LACOSTE, M. C. (1986). Sexual dimorphism profile area of the second callosal fourth; C4PA3, profile area of the in the human corpus callosum: An extension and replication study. third callosal fourth; C4PA4, profIle area ofthe fourth callosal fourth; Human Neurobiology, S, 87-91. C5PAl, profIle area of the first callosal fifth; C5PA2, profIle area of HUBER, S. J., PAULSON, G. L., SHUTILEWORTH, E. C., CHAKERES, D., the second callosal tifth; C5PA3, profIle area of the third callosal fifth; CLAPP, L. E., PAKALNIS, A., WEISS, K., & RAMMOHAN, K. (1987). C5PA4, profIle area of the fourth callosal fifth; C5PA5, profIle area Magnetic resonance imaging correlates of dementia in multiple scle­ of the tifth callosal fifth. rosis. Archives oi Neurology, 44, 732-736. THE HUMAN CORPUS CALLOSUM 415

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