Intrinsic Brain Activity Responsible for Sex Differences in Shyness and Social Anxiety

Abstract

Male and female show significant differences in important behavioral features such as shyness, yet the neural substrates of these differences remain poorly understood. Previous neuroimaging studies have demonstrated that both shyness and social anxiety in healthy subjects are associated with increased activation in the fronto-limbic and cognitive control areas. However, it remains unknown whether these brain abnormalities would be shared by different genders. Therefore, in the current study, we used resting-state fMRI (r-fMRI) to investigate sex differences in intrinsic cerebral activity that may contribute to shyness and social anxiety. Sixty subjects (28 males, 32 females) participated in r-fMRI scans, and the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) were used to measure the spontaneous regional cerebral activity in all subjects. We first compared the differences between male and female both in the ALFF and fALFF and then we also examined the whole brain correlation between the ALFF/fALFF and the severity of shyness as well as social anxiety by genders. Referring to shyness measure, we found a significant positive correlation between shyness scores (CBSS) and ALFF/fALFF value in the frontoparietal control network and a negative correlation in the cingulo-insular network in female; while in male, there is no such correlation. For the social anxiety level, we found positive correlations between Leibowitz Social Anxiety Scale (LSAS) scores and spontaneous activity in the frontal-limbic network in male and negative correlation between the frontal-parietal network; however, such correlation was not prominent in female. This pattern suggests that shy female individuals engaged a proactive control process, driven by a positive association with activity in frontoparietal network and negative association in cingulo-insular network, whereas social anxiety males relied more on a reactive control process, driven by a positive correlation of frontal-limbic network and negative correlation of frontoparietal network. Our results reveal that shyness or social anxiety is associated with disrupted spontaneous brain activity patterns and that these patterns are influenced by sex.

Keywords: ALFF; fALFF; resting fMRI; sex differences; shyness; social anxiety.

FIGURE 1

Regions showing significantly increased and decreased ALFF activity between males and females, with age and CBSS score as covariates. Yellow color indicates increased activity of the brain in males compared to females, and blue color indicates decreased activity of the brain in females compared to males. (A) Left Inferior Frontal Gyrus (LIFG), (B) Right Inferior Frontal Gyrus (RIFG), (C) Left Cerebellum Posterior Lobe (LCPL), (D) Left Inferior Parietal lobule (LIPL). The statistical threshold was set at p-value < 0.001, cluster size > 22 mm³ (AlphaSim corrected). The figure is shown according to radiological convention.

FIGURE 2

The comparisons in the high, low, and middle shy subgroup showed significant ALFF differences in LIFG, RIFG and LCPL between males and females and low and middle shy subgroup showed significant ALFF difference in LIPL between males and females. LIFG, left inferior frontal gyrus; RIFG, right inferior frontal gyrus; LCPL, left cerebellum posterior lobe; LIPL, left inferior parietal lobule; L, low; M, middle; H, high.

FIGURE 3

Brain regions showing a significant correlation between ALFF and fALFF maps and shyness in males and females using voxel-based regression analysis, with age and LSAS as covariates. Yellow color indicates positive correlation, and blue color indicates negative correlation. The statistical threshold was set at p-value < 0.01, cluster size > 80 mm³ (with AlphaSim corrected). The figure is shown according to radiological convention.

FIGURE 4

Brain regions showing a significant correlation between ALFF and fALFF maps and social anxiety in males and females using voxel-based regression analysis, with age and CBSS as covariates. Yellow color indicates positive correlation, and blue color indicates negative correlation. The statistical threshold was set at p-value < 0.01, cluster size > 80 mm³ (with AlphaSim corrected). The figure is shown according to radiological convention.