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. 2024 Jan;229(1):47-61.
doi: 10.1007/s00429-023-02720-0. Epub 2023 Oct 20.

Different cortical connectivities in human females and males relate to differences in strength and body composition, reward and emotional systems, and memory

Ruohan Zhang  1 , Edmund T Rolls  2   3   4 , Wei Cheng  5 , Jianfeng Feng  1   5
Affiliations

Different cortical connectivities in human females and males relate to differences in strength and body composition, reward and emotional systems, and memory

Ruohan Zhang et al. Brain Struct Funct. 2024 Jan.

Abstract

Sex differences in human brain structure and function are important, partly because they are likely to be relevant to the male-female differences in behavior and in mental health. To analyse sex differences in cortical function, functional connectivity was measured in 36,531 participants (53% female) in the UK Biobank (mean age 69) using the Human Connectome Project multimodal parcellation atlas with 360 well-specified cortical regions. Most of the functional connectivities were lower in females (Bonferroni corrected), with the mean Cohen's d = - 0.18. Removing these as covariates reduced the difference of functional connectivities for females-males from d = - 0.18 to - 0.06. The lower functional connectivities in females were especially of somatosensory/premotor regions including the insula, opercular cortex, paracentral lobule and mid-cingulate cortex, and were correlated with lower maximum workload (r = 0.17), and with higher whole body fat mass (r = - 0.17). But some functional connectivities were higher in females, involving especially the ventromedial prefrontal cortex and posterior cingulate cortex, and these were correlated with higher liking for some rewards such as sweet foods, higher happiness/subjective well-being, and with better memory-related functions. The main findings were replicated in 1000 individuals (532 females, mean age 29) from the Human Connectome Project. This investigation shows the cortical systems with different functional connectivity between females and males, and also provides for the first time a foundation for understanding the implications for behavior of these differences between females and males.

Keywords: Functional connectivity; Liking for sweet foods; Sex differences in the brain; Somatosensory and motor cortex; Ventromedial prefrontal cortex.

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Conflict of interest statement

The authors have not disclosed any competing interests.

Figures

Fig. 1
Fig. 1
Workflow and summary of findings. Functional connectivity was calculated, and differences for females minus males were calculated with Bonferroni correction for multiple comparisons. Association analyses with measures in the UK Biobank showed that many of the lower functional connectivities in females were for somatosensory/motor cortical regions, and were correlated with lower maximal workload and higher body fat mass. The higher functional connectivities in females were correlated with higher liking for sweet food, happiness, and better memory scores
Fig. 2
Fig. 2
The main cortical regions with lower (a) or higher (b) functional connectivity in females (n = 19,396) compared to males (n = 17,135). The regions in the HCP-MMP atlas shown in color are from the results shown in Fig. 3, and were selected by showing cortical regions for which the number of significant links was in the top 25%
Fig. 3
Fig. 3
The lower left triangle shows the matrix of functional connectivity differences for females—males with the Cohen’s d values showing the effect size of the differences. The matrix is for the functional connectivities in the left hemisphere, as listed in Table S1, with V1, V2, V3 … at the top of the y axis and the left of the x axis. The upper triangle matrix shows the Cohen’s d values of the top 20% significant negative links and all significant positive links after Bonferroni correction (corrected p < 3.1e−6). These results were from 19,396 females and 17,135 males. The negative values shown in the upper right triangle had d <  − 0.29, and all the values shown in the matrix were in the range from − 0.5 to 0.5. The standard covariates regressed out in this analysis were Age, BMI, education qualifications, smoking status, drinker status, Townsend deprivation index, head motion, and imaging site information. The cortical regions in the HCP-MMP atlas are illustrated in Figs. S1 and S2, and their names and divisions are shown in Table S1. The cortical divisions are separated by thick lines, and labelled at the bottom of the figure
Fig. 4
Fig. 4
Prediction of sex from the functional connectivity using SVM. AUCs and the accuracy of the sex classification based on the functional connectivities in the HCPex atlas which were used as the features to train the model. The functional connectivity links for this test were selected from the top percentage of significant links after Bonferroni correction shown on the x axis in the training set. The results are shown for prediction in the group not used for training in the split data design. The accuracy and AUC increased as more of the significantly different links between females and males were used
Fig. 5
Fig. 5
The lower left triangle shows the matrix of functional connectivity differences for females—males with the Cohen’s d values showing the effect size of the differences. The standard covariates were regressed out, but also so too were Field 6032 Maximum workload during fitness test and Field 23,100 Whole body fat mass as covariates in the two-sample t-tests. The matrix is for the functional connectivities in the left hemisphere, as listed in Table S1, with V1, V2, V3 … at the top of the y axis and the left of the x axis. The upper triangle matrix shows the Cohen’s d values of top 20% significant negative links and all significant positive links after Bonferroni correction (corrected p < 3.1e−6). These results were from 2099 females and 1889 males. All the values shown in the matrix were in the range from − 0.5 to 0.5
Fig. 6
Fig. 6
Differences in resting state functional connectivity in females—males with data from 1000 individuals (532 females) in the Human Connectome Project. The lower left triangle shows the Cohen’s d values for the differences, and the upper right triangle shows the differences that were significant after Bonferroni correction for the number of comparisons made in the 180×180 functional connectivity matrices for the left hemisphere. Negative values in this matrix indicate lower functional connectivities in females. All the values shown in the matrix were in the range from − 0.5 to 0.5. The conventions are as in Fig. 3
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