Gender differences of brain glucose metabolic networks revealed by FDG-PET: evidence from a large cohort of 400 young adults

Abstract

Background: Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample.

Materials and methods: FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25:45 years, mean age ± SD: 40.9 ± 3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders.

Results: Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study.

Conclusion: This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients.

Figure 1. The gender difference maps of regional brain glucose metabolism.

Yellow to red areas represent regions where the values of glucose metabolism were higher in females than in males (corrected p<0.05) [height threshold of p<0.05 FDR corrected (T>2.26) and extend threshold of p<0.001 (cluster size > 30 voxels)]; The converse is shown as cyan to blue (corrected p<0.05) [height threshold of p<0.05 FDR corrected (T>2.26) and extend threshold of p<0.001 (cluster size >30 voxels)]. The white circles indicated the specific ROIs.

Figure 2. Seven specific brain glucose metabolic network maps of each gender and their differences.

The left column displays the locations of the ROIs. The middle two columns show the metabolic networks of both genders. The areas with warm color represented positive correlations with the ROIs, and cold color represented negative correlations (r>0.21, corrected p<0.05; height threshold of p<0.05, Bonferroni corrected, and extend threshold of p<0.001, cluster size >30 voxels). The right column exhibits the main areas of gender differences in brain metabolic networks. The areas with warm color represent increased functional connectivity with each ROI in females than in males; the converse is shown as cold color (corrected p<0.05; height threshold of p<0.05, Bonferroni corrected, and extend threshold of p<0.001, cluster size > 30 voxels).

Figure 3. Nine classic brain glucose metabolic network maps of each gender and their differences.

The left column displays the locations of the ROIs. The middle two columns show the metabolic networks of both genders. The areas with warm color represented positive correlations with the ROIs, and cold color represented negative correlations (r>0.21, corrected p<0.05; height threshold of p<0.05, Bonferroni corrected, and extend threshold of p<0.001, cluster size > 30 voxels). The right column exhibits the main brain regions of gender differences in brain metabolic networks. The areas with warm color represent increased functional connectivity with each ROI in females than in males; the converse is shown as cold color (corrected p<0.05; height threshold of p<0.05, Bonferroni corrected, and extend threshold of p<0.001, cluster size > 30 voxels).

Figure 4. Correlation matrices of 16 ROIs for the females, males and gender differences.

A) Inter-subject correlation matrix of females; B) Inter-subject correlation matrix of males; C) corrected gender differences correlation matrix (females-males) (p<0.05, Bonferroni correction). In the Figure A and B, warm colors represent positive correlation between a pair of seeds, cold colors represent negative correlation, and gray color represents no correlation. In the Figure C, warm colors represent higher correlations between a pair of seeds in females than in males, cold colors represent lower correlations, and gray color represents that there is not significant differences between genders.