Review articleSexual dimorphism in the human brain: evidence from neuroimaging
Introduction
Substantial evidence has been gathered from recent neuroimaging studies supporting a sexual dimorphism of the human brain. Given the significant sex-specific differences in the prevalence of a majority of neuropsychiatric disorders, a better understanding of the impact of sex on brain structure and function is of major importance to adequately address the sex differences in the management of risk factors, symptoms, course of disease and treatment. Above all, there is a clear need to integrate neuroimaging findings on brain structure, connectivity, neurochemistry and function in human studies in order to extract the essential comprehensive information on the effects of sex on neural phenotypes.
In this systematic review, we evaluate the literature of the past decade on sex-specific differences in the human brain found in gray matter by voxel-based magnetic resonance (MRI) studies; in white matter by diffusion tensor imaging (DTI); in neural activity and metabolism at baseline by resting-state functional magnetic resonance imaging (rs-fMRI), cerebral blood flow (CBF) and fludeoxyglucose positron emission tomography (FDG-PET); in neurochemistry by receptor-ligand PET and in functional activation in specific brain regions during emotional processing, memory tasks, fear conditioning and visuospatial performance by fMRI. The review of sex differences in neural activation is complemented by a quantitative assessment of functional neural networks that have been observed to differ between males and females during tasks of emotional processing. We applied activation likelihood estimation (ALE) [1], [2], [3], [4], [5] to quantitatively model reported brain coordinates in fMRI studies and identify brain regions where individual peak coordinates in standard brain space converge across studies. This facilitates a systematic quantitative review of the evidence for a sexual dimorphism in brain function that is robust across subject populations and consistent among multiple imaging centers.
Overall, this review provides a comprehensive view of structural, functional and neurochemical neural differences between men and women. The evidence calls for integrating sex as a possible contributing factor in neuroimaging studies.
Section snippets
Gray matter
Sexual dimorphism in human brain anatomy has been investigated by a wealth of studies, primarily addressing overall brain size, the ratio between gray and white matter, and regional brain volume, as well as neural microstructure.
The most agreed-upon difference between men's and women's brains is that men have larger brain volumes than women [6]. Considering the general sex difference in body weight, it is important to note that sex differences in absolute brain size were observed and
Resting states in fMRI and in PET
Rs-fMRI measurements provide an estimate for the functional connectivity in the brain at rest. They are based on coordinated and intrinsic spontaneous fluctuations in brain activity at baseline without performing a task [36]. Rs-fMRI provides insight into the unprompted activity that is naturally produced within the brain, which subsequently promotes communication across regions.
Comparisons of male and female brains during rs-fMRI studies have revealed that both sexes have robust functional
Summary and outlook
In this paper, we reviewed evidence on sex differences in neural structure, function, metabolism and chemistry of the human brain. Evidence for sex differences stems from anatomical studies examining gray and white matter, functional neural connectivity analyses, PET studies measuring differences in neurochemistry and fMRI studies examining differences in neural activation during tasks. Overall, the various methods highlight robust sex-specific differences in human neural anatomy and function,
Acknowledgments
This research received project and salary support from the Alexander von Humboldt Foundation (AvH) fellowship and from the Society in Science, The Branco Weiss Fellowship, administered by the ETH Zürich, to J.S. and the Federal Ministry of Education and Research (BMBF), Germany (FKZ: 01EO1001), research grant to J.N.
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