Cerebral cortex: An MRI-based study of volume and variance with age and sex

Abstract

The aim of the present study was to examine quantitative differences in lobar cerebral cortical volumes in a healthy adult population. Quantitative volumetric MRI of whole brain, cerebral and cerebellar volumes was performed in a cross-sectional analysis of 97 normal volunteers, with segmented frontal, temporal, parietal and occipital cortical volumes measured in a subgroup of 60 subjects, 30 male and 30 female, matched for age and sex. The right cerebral hemisphere was larger than the left across the study group with a small (<1%) but significant difference in symmetry (P < 0.001). No difference was found between volumes of right and left cerebellar hemispheres. Rightward cerebral cortical asymmetry (right larger than left) was found to be significant across all lobes except parietal. Males had greater cerebral, cerebellar and cerebral cortical lobar volumes than females. Larger male cerebral cortical volumes were seen in all lobes except for left parietal. Females had greater left parietal to left cerebral hemisphere and smaller left temporal to left cerebral hemisphere ratios. There was a mild reduction in cerebral volumes with age, more marked in males. This study confirms and augments past work indicating underlying structural asymmetries in the human brain, and provides further evidence that brain structures in humans are differentially sensitive to the effects of both age and sex.

Introduction

Studies on the size of the human brain have been performed for many years, spurred on by obvious differences in behaviour, between old and young, and male and female, and the desire to find underlying anatomical correlates. Although it has been known for more than 100 years that male brains are in general larger than female,¹ with more sophisticated techniques, especially advances in imaging methodology, it has been possible to detect ever smaller but significant structural differences.² The cause of these differences remains unclear, but possibly includes genetic, hormonal, psychosocial, and environmental influences. The anatomical level at which they occur also remains obscure: whether individual cells, cortical laminae, distinct cytoarchitectonic regions, specific nuclei, neurotransmitter systems or vascular territories are involved is undecided.

The functional significance of such differences also remains unclear. Studies have revealed subtle but significant cognitive differences between sexes, for example men show more facility with spatial reasoning tasks such as mental rotation,[3], [4], [5] whereas women display more ability in verbal fluency tasks, and more often show evidence of bilateral activation on metabolic studies.[6], [7] Neuropsychological studies have suggested less hemispheric specialisation in women compared with men.⁸

Although many studies have indicated that males have larger brains than females, the overall size or activity of the brain may not be important. The average male brain exceeds the female brain in volume by only approximately one standard deviation of the mean (approximately 100 g). This size difference is argued to be due to proportionately greater white matter volume,⁹ with the suggestion that there may be similar cerebral cortical volume, but proportionately longer white matter tracts to fill the larger male cranium. Functional studies, however, have demonstrated that the metabolic rate per unit volume of brain tissue is virtually the same in both sexes.¹⁰

It is possible that functional activity is not related to morphological difference at all. For instance, it is unclear if sex differences in brain regions, if detected, cause differences in thinking, or if they are merely correlates of different socially prescribed behaviours.

The effect of age on human cerebral volume has also been extensively investigated, with most studies indicating an overall decline in brain volume with age, with a proportionately larger decline in males, largely due to a reduction in grey matter volume.¹¹ The differential regional effects of aging have been the subject of much speculation, for example, it has been suggested that association areas are more vulnerable to age-related atrophy than primary somatosensory areas. Post mortem and in vivo studies have suggested that the prefrontal[12], [13], [14] and temporal regions¹⁴ are most vulnerable to age-related atrophy, whereas the primary visual and somatosensory cortices may be more resistant. Again, the underlying reasons for differential regional atrophy with age remain speculative, with the proportional contributions from genetic and environmental influences unclear.

Although it is unclear what is primary and what is secondary in relation to cerebral volume and function, it is through accurate localisation of any structural asymmetries, in combination with knowledge of regional specialisation of function, that future studies can be designed to further characterise the relationship between structure and function, age and sex. Therefore, the present study was designed to accurately quantify, using a reliable and reproducible method, volume measures in healthy adults of both sexes, of various ages.