Mapping cortical gray matter in the young adult brain: Effects of gender
Introduction
Although numerous sexually dimorphic characteristics have been identified in the human brain, observations of larger total brain volumes (TBV) in men compared to women are most replicated. Post mortem data further suggest that neuronal number and density are modulated by gender (Pakkenberg and Gundersen, 1997, Rabinowicz et al., 1999, Witelson et al., 1995). Similarly, neuroimaging studies show sexual dimorphisms in the major cranial tissue compartments, although results lack consistency. For example, global gray matter (GM) and white matter (WM) volumes are reported as larger in males (Blatter et al., 1995, Luders et al., 2002), but when GM is computed as a percentage of TBV, females show larger GM ratios irrespective of TBV corrections (Gur et al., 1999). Other studies show larger GM percentages in males (Good et al., 2001a), or fail to detect significant gender effects in GM and WM percentages (Nopoulos et al., 2000, Schlaepfer et al., 1995).
Gender differences in regional (as oppose to global) GM distributions have also been examined where traditional region-of-interest studies are complemented by voxelwise comparisons using methods like voxel-based morphometry (VBM). For example, region-of-interest analyses have revealed increased GM percentages in the dorsolateral prefrontal cortex and superior temporal gyrus in females (Schlaepfer et al., 1995). Furthermore, increased GM volumes in cingulate cortices in females and paracingulate cortices in males were observed after transforming images into standardized stereotaxic space to control for TBV (Paus et al., 1996). Studies employing VBM have revealed GM volume increases in females in parietal, temporal, inferior frontal and cingulate cortices and GM concentration increases across the cortex and surrounding the parahippocampal, cingulate and calcarine sulci. In contrast, males showed GM volume increases in mesial/lateral temporal and cerebellar regions, but no significant increases in GM concentration (Good et al., 2001a).
Taken together, previous analyses of global and regional tissue volumes clearly indicate gender differences, albeit findings lack consistency. These inconsistencies may stem from differences in measurement methods (e.g., measurement of GM volume versus GM concentration; whole-brain versus region-of-interest analyses using contiguous brain slices or a single brain slice only). Another major contributor to discrepancies in findings is the failure of some studies to take brain size differences between men and women into account. Moreover, even when brain size is taken into account, the different strategies used to correct for individual brain volumes may lead to different results.
The present study was designed to address these issues. We set out to complement analyses of global tissue volumes (GM, WM and CSF) with examinations of regional GM in the same set of data. Furthermore, identical procedures to correct for individual brain volumes were applied for global and regional analyses and achieved through a 12-parameter linear transformation into the standard co-ordinate system of the template of the International Consortium for Brain Mapping (ICBM-305) (Mazziotta et al., 1995). Analyses in a scaled standard space – a method frequently used in VBM studies – might be a better approach to control for individual brain size than including TBV as covariate in (log)linear statistical models if the relationship between TBV and tissue compartment lacks linearity. In order to compare our findings with others in the literature, gender effects on global GM, WM and CSF volumes were additionally examined in raw scanner space without controlling for individual differences in TBV.
Regional GM, hereafter referred to as GM concentration, was defined as the number of GM voxels relative to the total number of voxels within spheres of 15 mm on the cortical surface. Cortical-pattern matching methods were used to map regional GM concentration differences across the cortex (Ashburner et al., 2003, Thompson et al., 2000). This methodological approach was chosen to isolate local GM changes, given that traditional region-of-interest studies cannot characterize group-related differences elsewhere in the cortex, while in VBM studies, data from corresponding cortical regions cannot always be accurately mapped across subjects (Good et al., 2001a). In contrast, cortical pattern matching allows the highly accurate alignment of surface anatomy using manually delineated features in each subject such that local measures of GM can be compared at thousands of homologous cortical surface locations across the entire cortical surface. Finally, we set out to generate spatially detailed maps of (a) average GM distributions and (b) GM variability across the entire cortex in ICBM-305 space given that these descriptors are not well characterized in the normative literature.
Section snippets
Subjects
We analyzed the brains of 60 right-handed healthy subjects selected from a database of high-resolution anatomical MR images acquired at the Center for Neuroscientific Innovation and Technology (ZENIT), Magdeburg. Male and female subjects were matched in terms of numbers (30 women, 30 men) and age (women: 24.32 ± 4.35 years; men: 25.45 ± 4.72 years). Young adults with a relatively narrow age range were recruited so as to minimize the influences of age and possible interactions of age with
Global tissue volumes
Table 1 shows the means and standard deviations of TBV and tissue volumes obtained in raw scanner space (left column) and ICBM-305 space3 (right column). The repeated measurement ANOVAs resulted in a
Global tissue volumes
Statistical analyses of major cranial tissue component measures in raw scanner space yielded significant gender differences with males having larger volumes of GM, WM and CSF than females which agrees with earlier findings (Blatter et al., 1995, Good et al., 2001a, Luders et al., 2002). Furthermore, as consistent with previous findings, we detected significantly larger TBVs in males than in females. Importantly, sex is genotype, and genes influence brain size accounting for larger male and
Summary
The present analysis shows that gender is a major contributor to regional and global GM differences between individuals. Gender-specific amounts of GM in particular regions of the cortex may have functional significance and are possibly related to gender differences in cognition and behavior. However, further studies are clearly necessary to systematically evaluate to what extent such a relationship exists.
Acknowledgments
This work was supported by Deutsche Forschungsgemeinschaft (DFG, JA 737/8-1), research grants from the National Library of Medicine and National Institute on Aging (R01 LM05639), National Institute of Mental Health and National Institute of Neurological Disorders and Stroke (P20 MH065166), resource grants from the National Center for Research Resources (P41 RR013642 and M01 RR000865), a NARSAD Young Investigator Award (to KLN) and R21 grants RR19771 and EB01561 (to PT). Additional support was
References (38)
- et al.
Voxel-based morphometry—the methods
NeuroImage
(2000) - et al.
Computer-assisted imaging to assess brain structure in healthy and diseased brains
Lancet Neurol.
(2003) - et al.
Mapping cortical asymmetry and complexity patterns in normal children
Psychiatry Res.
(2001) - et al.
Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains
NeuroImage
(2001) - et al.
A voxel-based morphometric study of ageing in 465 normal adult human brains
NeuroImage
(2001) - et al.
Effects of age on tissues and regions of the cerebrum and cerebellum
Neurobiol. Aging
(2001) - et al.
A probabilistic atlas of the human brain: theory and rationale for its development. The International Consortium for Brain Mapping (ICBM)
NeuroImage
(1995) - et al.
Three-dimensional mapping of temporo-limbic regions and the lateral ventricles in schizophrenia: gender effects
Biol. Psychiatry
(2001) - et al.
Sexual dimorphism in the human brain: evaluation of tissue volume, tissue composition and surface anatomy using magnetic resonance imaging
Psychiatry Res.
(2000) - et al.
The LONI pipeline processing environment
NeuroImage
(2003)