Sex-linked neurofunctionnal basis of psychological resilience in late adolescence
Cheng Yang1, Song Wang1, and Qiyong Gong1

1Huaxi MR Research Center, West China Hospital, Sichuan University, Chengdu, China


Psychological resilience refers to the ability to bounce back from adversity and previous studies have shown sex differences in psychological resilience. Here, we employed amplitude of low-frequency fluctuations (ALFF) to investigate sex differences in the relationship between resting-state brain activity and psychological resilience in 231 healthy adolescents. Behaviorally, we found that males were more resilient than females. Neurally, a positive correlation between psychological resilience and the ALFF in the right orbitofrontal cortex was detected among males while a negative correlation was observed among females. Together, our study provided the first evidence of sex-specific neurofunctional substrates underlining psychological resilience in adolescents.


Psychological resilience is the ability to cope effectively in face of adverse events1. Previous studies have suggested that psychological resilience plays a protective role in many mental disorders, such as post-traumatic stress disorder and depression2-4. Although converging evidence has shown that males are more resilient than females5, little is known about the sex-linked neural basis of psychological resilience. In this research, we aimed to investigate sex differences in the association between resting-state brain activity and psychological resilience in a large sample of healthy adolescents by estimating amplitude of low-frequency fluctuations (ALFF) measured by resting-state functional magnetic resonance imaging (RS-fMRI).


234 adolescent students (122 females; mean age = 18.60 years, SD = 0.78) from several local public high schools were recruited in this research. Three participants were removed due to the unusual brain structure. Therefore, 231 participants (121 females; mean age = 18.48 years, SD = 0.54) were included in the data analysis. To assess psychological resilience, each participant completed the Chinese version of the 10-Item Connor Davidson Resilience Scale (CD-RISC)6,7. The MRI data were acquired using a Siemens-Trio Erlangen 3.0T MRI system with a 12-channel head coil. The RS-fMRI data were obtained using the echo-planar imaging (EPI) sequence: repetition time, 2000 ms; echo time, 30ms; flip angle, 90°; 30 slices; slice thickness, 5 mm; interslice gap, 0; voxel size, 3.75 × 3.75 × 5mm3; field of view, 240 × 240mm2; matrix, 64×64, 240 volumes. During the image acquisition, we asked participants to close their eyes and remain awake without thinking about anything purposely. The DPARSF toolbox8 was employed to preprocess the RS-fMRI data, with the following steps: discarding the first ten images, slice timing and head motion correction, realignment, normalization with 3 × 3 × 3 mm3 resolution, smoothing using an 8-mm FWHM Gaussian kernel, and removing linear trends. Next, the ALFF of each participant was calculated using the methods similar to those in an earlier study8 by DPARSF software. To detect the sex-specific relationship between the ALFF and psychological resilience, a voxel-wise condition-by-covariate interaction analysis9 was performed with Statistical Parametric Mapping program (SPM8). In this analysis, sex was treated as a condition, and age and head motion were treated as covariates. T-contrasts were used to assess the interaction effects of sex and psychological resilience on ALFF. For multiple comparisons correction, we set the threshold for significant regions to p < 0.05 at the cluster level and p < 0.001 at the voxel level (Gaussian random field approach10). Finally, we used Fisher’s z test to investigate if there are significant sex differences in the association between psychological resilience and the ALFF in the identified brain regions11.


Behaviorally, consistent with previous findings5, we observed that males scored significantly higher than females in CD-RISC (t229 = 3.609, P < 0.001, Cohen’s d = 0.475). Neurally, we found an interaction effect of sex and psychological resilience on ALFF in the right orbitofrontal cortex (OFC; MNI coordinates: 15, 51,-21; cluster size = 111 voxels; Z = 4.50; P < 0.001; Figure 1), after controlling for age and head motion. Specifically, CD-RISC scores were positively correlated with the ALFF in the right OFC among males (r = 0.308, p < 0.001), but negatively correlated with the right OFC spontaneous activity among females (r = -0.277, p < 0.001), after controlling for age and head motion. Fisher’s z-test further showed significant sex differences in the correlation between psychological resilience and the ALFF in the right OFC (Z = 4.515, p < 0.05).


The current study was conducted to examine the sex differences in the association between psychological resilience and resting-state brain activity. First, we revealed that males were more resilient than females, which is in line with previous studies12,13. Second, we found that psychological resilience showed a positive association with the ALFF in the right OFC among men and a negative correlation was observed among women. The OFC is widely considered to be involved in self-regulation, emotion-regulation, cognitive reappraisal, reward sensitivity and motivation7, which were important constructs closely related to psychological resilience14. Previous resting-state functional study has reported that the brain function of OFC is closely linked to psychological resilience in healthy subjects7. Moreover, the effects of biological factors such as sex hormonal level15, the different development of brain in adolescents16 and different social environment17 between two sexes might contribute to the sex difference between resting-state brain activity and psychological resilience in our study.


In conclusion, our study might provide the first evidence for the sex-linked functional neural substrates underlying psychological resilience in adolescence.


No acknowledgements.


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Sex-specific correlation between psychological resilience and ALFF. A: The whole brain condition-by-covariate interaction study showed the significant sex-specific correlation between the psychological resilience and ALFF in the right OFC. B: Correlations between psychological resilience and ALFF in the right OFC, with a positive correlation in males (r= 0.308, p < 0.001), but a negative correlation in females (r= -0.277, p < 0.001). Age and head motion were adjusted for in these analyses. Abbreviations: ALFF, amplitude of low-frequency fluctuations; OFC, orbitofrontal cortex.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)