1. Sex Differences in Brain Structure & Asymmetry in Healthy College Students Christiana M. Leonard 1, Stephen Towler 1, Laura K. Halderman 2, Suzanne Welcome 2, Ron Otto 3 & Christine Chiarello 2, University of Florida, Gainesville 1, University of California, Riverside 2, & Diagnostic Imaging Center, Riverside, CA 3 Introduction Acknowledgments This research was supported by NIDCD grant 5R01DC6957. Great thanks are due to Matthew Manry, Natalie Anne Hammond, Caroline Anderson, Dawn Joseph, Michelle Long, Gabrielle Messmer and Stephanie Demian. Conclusions Method This large-scale investigation provided little evidence for sex differences in the asymmetry of perisylvian structures. There were, however, significant sex differences in the coefficient of asymmetry of cerebral white matter, as well as the asymmetry of white matter proportions. Men had.7% more white matter in the right hemisphere than women (p <.001). Our findings on gray/white matter relations exactly replicate the report of Allen et al. (2003) using a different segmentation algorithm in a smaller sample. Past reports that the planum temporale is less asymmetrical in women may be due to inadequate sample sizes that are unrepresentative of the wider population. Based on the results shown here, it appears more likely that sex differences in behavior are due to the very large differences in brain volume than the extremely modest differences in asymmetry. It is frequently claimed that women have a more bilateral organization for language and reduced brain asymmetry compared to men. Experimental support for these claims have been mixed. Positive findings are less often seen in large scale studies (Watkins et al., 2001; Good et al., 2001). The current study, part of the Biological Substrates for Language Project, affords the opportunity to explore this issue in another large-scale investigation. In this project, selected brain structures and asymmetries were measured in 200 individuals whose behavioral asymmetries had been assessed with the divided visual field procedure. This interdisciplinary approach enables a powerful test of the hypothesis that reduced brain asymmetry is associated with more more bilateral language lateralization in women. The size of the sample also allowed us to address questions about the relative contribution of brain size to reported sex differences in white matter and relative corpus callosum area. We had three questions: 1. Are there any sex differences in the size or asymmetry of perisylvian regions thought to be associated with language function? 2. Is the reported sex difference in relative corpus callosum size due to sex differences in brain size (as Jancke and colleagues have reported, Jancke et al., 1996). 3. Do women have a relatively smaller proportion of white matter (Gur et al., 1999; Allen et al., 2003) or is this difference also attributable to differences in brain size? References Although the strength of the relationship between white matter proportion and cerebral volume is stronger in women, hierarchical multiple regression revealed no significant quadratic contribution from cerebral volume and the interaction between sex and volume did not approach significance. Cerebral volume contributed 25% with sex contributing an additional unique 3.4% of the variance to the relationship (model significant, p <.0001). Allen, J. S., Damasio, H., Grabowski, T. J., Bruss, J., & Zhang, W. (2003). Sexual dimorphism and asymmetries in the gray-white composition of the human cerebrum. Neuroimage, 18, 880-894. Good, C. D., Johnsrude, I., Ashburner, J., Henson, R. N., Friston, K. J., & Frackowiak, R. S. (2001). Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains. Neuroimage, 14, 685-700. Gur, R. C., Turetsky, B. I., Matsui, M., Yan, M., Bilker, W., Hughett, P., et al. (1999). Sex differences in brain gray and white matter in healthy young adults: correlations with cognitive performance. J Neurosci, 19, 4065-4072. Jancke, L., Staiger, J. F., Schlaug, G., Huang, Y., & Steinmetz, H. (1997). The relationship between corpus callosum size and forebrain volume. Cerebral Cortex, 7, 48-56. Leonard, C., Eckert, M., Givens, B., Berninger, V., & Eden, G. (2006). Individual differences in anatomy predict reading and oral language impairments in children. Brain, 129, 3329-3342. Watkins, K. E., Paus, T., Lerch, J. P., Zijdenbos, A., Collins, D. L., Neelin, P., et al. (2001). Structural asymmetries in the human brain: a voxel-based statistical analysis of 142 MRI scans. Cereb Cortex, 11, 868-877. PARTICIPANTS: 100 male, 100 female native English speakers 18-34 years of age 28 (14%) are not right-handed BRAIN MEASURES: SIZE & ASYMMETRY Volume: gray and white matter of the cerebral hemispheres Area: corpus callosum (seven subdivisions) Average length: planum temporale, planum parietale, Heschl’s gyrus, pars triangularis, pars opercularis PROCEDURE: Volumetric MRI scans (1.2 mm thick sagittal images) on 1.5 GE Scanner Brain tissue extracted, reoriented, and segmented into isometric voxels with FSL software http://www.fmrib.ox.ac.uk/http://www.fmrib.ox.ac.uk/ Surface and volume measurements made with scripts written in PVWave http://www.vni.com/ (Leonard, et al., 2007) http://www.vni.com/ At least two raters made each measurement, blind to hemisphere and subject characteristics. Differences were resolved by consensus. Reliability was >.99 for gray and white matter measures and >.85 for structure measures. Analyses were conducted with PC-SAS (SAS Institute, Cary NC). Results Although the shape of the function between proportional corpus callosum size and white matter volume differs for men and women, hierarchical multiple regression revealed that no significant quadratic contribution from brain volume and the interaction between sex and brain volume did not approach significance. Cerebral volume contributed 15% with no additional unique contribution from sex (model significant, p <.0001) Results of t tests on the effect of sex. Significant results (p <.01) are highlighted. Degrees of freedom = 198 except for gray matter asymmetry (df = 178) and left cerebellum (df = 187), where the variances were significantly different in men and women. The denominator for white matter proportion is total cerebral gray and white matter. The denominator for proportional corpus callosum size is total cerebral white matter.