Biological mechanism of sex differences in mental rotation: Evidence from multimodal MRI, transcriptomic and receptor/transporter data

Sex differences in mental rotation are a well-documented phenomenon in cognitive research, with implications for the differing prevalence of neuropsychiatric disorders such as autism spectrum disorder (ASD), Alzheimer's disease (AD) and major depressive disorder (MDD) between the sexes. Despite...

Full description

Saved in:
Bibliographic Details
Main Authors: Haixia Long, Hao Wu, Chaoliang Sun, Xinli Xu, Xu-Hua Yang, Jie Xiao, Mingqi Lv, Qiuju Chen, Ming Fan
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:NeuroImage
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S105381192400452X
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850247245211893760
author Haixia Long
Hao Wu
Chaoliang Sun
Xinli Xu
Xu-Hua Yang
Jie Xiao
Mingqi Lv
Qiuju Chen
Ming Fan
author_facet Haixia Long
Hao Wu
Chaoliang Sun
Xinli Xu
Xu-Hua Yang
Jie Xiao
Mingqi Lv
Qiuju Chen
Ming Fan
author_sort Haixia Long
collection DOAJ
description Sex differences in mental rotation are a well-documented phenomenon in cognitive research, with implications for the differing prevalence of neuropsychiatric disorders such as autism spectrum disorder (ASD), Alzheimer's disease (AD) and major depressive disorder (MDD) between the sexes. Despite extensive documentation, the biological mechanism underpinning these differences remain elusive. This study aimed to elucidate neural, genetic, and molecular bases of these disparities in mental rotation by integrating data from multimodal magnetic resonance imaging (MRI), transcriptomic and receptor/transporter. We first calculated the dynamic regional homogeneity (dReHo), gray matter volume (GMV) and fractional anisotropy (FA) in voxel-wise manner and parceled them into 246 brain regions based on Brainnetome Atlas. Subsequent analyses involved Pearson Correlations to examine the association between mental rotation performance and dReHo/GMV/FA and two-sample t-tests to delineate gender differences in these indices. Based on the above results, further mediation analysis was conducted to explore the relationship between sex, brain biomarkers and mental rotation. In addition, transcriptome-neuroimaging association analysis and correlation analysis between brain biomarkers and neurotransmitter receptor/transporter distribution were also performed to uncover genetic and molecular mechanisms contributing to the observed sex differences in mental rotation. We found correlations between mental rotation performance and dReHo, GMV and FA of the inferior parietal lobule (IPL) and superior temporal gyrus (STG) and sex effects on these brain biomarkers. Notably, the dReHo of the left IPL mediated the relationship between sex and mental rotation. Further correlation analysis revealed that the proton-coupled oligopeptide transporter PEPT2 (SLC15A2) and interleukin 17 receptor D (IL17RD) were associated with sex-related t-statistic maps and mental rotation-related r-statistic maps of dReHo. Moreover, γ-aminobutyric acid subtype A (GABAA) receptor availability was correlated with the r-statistic of dReHo, while norepinephrine transporter (NET) availability was correlated with its t-statistic. Serial mediation models revealed the indirect effect of these genes on the r-statistic maps through the transporter/receptor and t-statistic maps. Our findings provide novel insights into the biological mechanism underlying sex differences in mental rotation, identifying potential biomarkers for cognitive impairment and explaining variations in prevalence of certain mental disorders between the sexes. These results highlight the necessity of considering sex in research on mental health disorders.
format Article
id doaj-art-2a4b9f43717840cb89ef01ea7a0c04b6
institution OA Journals
issn 1095-9572
language English
publishDate 2024-12-01
publisher Elsevier
record_format Article
series NeuroImage
spelling doaj-art-2a4b9f43717840cb89ef01ea7a0c04b62025-08-20T01:59:00ZengElsevierNeuroImage1095-95722024-12-0130412095510.1016/j.neuroimage.2024.120955Biological mechanism of sex differences in mental rotation: Evidence from multimodal MRI, transcriptomic and receptor/transporter dataHaixia Long0Hao Wu1Chaoliang Sun2Xinli Xu3Xu-Hua Yang4Jie Xiao5Mingqi Lv6Qiuju Chen7Ming Fan8College of Computer Science and Technology, Zhejiang University of Technology, Hangzhou 310023, ChinaCollege of Computer Science and Technology, Zhejiang University of Technology, Hangzhou 310023, ChinaZhejiang Lab, Zhongtai Street, Yuhang District, Hangzhou 311100, ChinaCollege of Computer Science and Technology, Zhejiang University of Technology, Hangzhou 310023, ChinaCollege of Computer Science and Technology, Zhejiang University of Technology, Hangzhou 310023, ChinaCollege of Computer Science and Technology, Zhejiang University of Technology, Hangzhou 310023, ChinaCollege of Computer Science and Technology, Zhejiang University of Technology, Hangzhou 310023, ChinaSchool of Design and Architecture, Zhejiang University of Technology, Hangzhou 310023, ChinaInstitute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, Hangzhou 310018, China; Corresponding author at: Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, Hangzhou 310018, China.Sex differences in mental rotation are a well-documented phenomenon in cognitive research, with implications for the differing prevalence of neuropsychiatric disorders such as autism spectrum disorder (ASD), Alzheimer's disease (AD) and major depressive disorder (MDD) between the sexes. Despite extensive documentation, the biological mechanism underpinning these differences remain elusive. This study aimed to elucidate neural, genetic, and molecular bases of these disparities in mental rotation by integrating data from multimodal magnetic resonance imaging (MRI), transcriptomic and receptor/transporter. We first calculated the dynamic regional homogeneity (dReHo), gray matter volume (GMV) and fractional anisotropy (FA) in voxel-wise manner and parceled them into 246 brain regions based on Brainnetome Atlas. Subsequent analyses involved Pearson Correlations to examine the association between mental rotation performance and dReHo/GMV/FA and two-sample t-tests to delineate gender differences in these indices. Based on the above results, further mediation analysis was conducted to explore the relationship between sex, brain biomarkers and mental rotation. In addition, transcriptome-neuroimaging association analysis and correlation analysis between brain biomarkers and neurotransmitter receptor/transporter distribution were also performed to uncover genetic and molecular mechanisms contributing to the observed sex differences in mental rotation. We found correlations between mental rotation performance and dReHo, GMV and FA of the inferior parietal lobule (IPL) and superior temporal gyrus (STG) and sex effects on these brain biomarkers. Notably, the dReHo of the left IPL mediated the relationship between sex and mental rotation. Further correlation analysis revealed that the proton-coupled oligopeptide transporter PEPT2 (SLC15A2) and interleukin 17 receptor D (IL17RD) were associated with sex-related t-statistic maps and mental rotation-related r-statistic maps of dReHo. Moreover, γ-aminobutyric acid subtype A (GABAA) receptor availability was correlated with the r-statistic of dReHo, while norepinephrine transporter (NET) availability was correlated with its t-statistic. Serial mediation models revealed the indirect effect of these genes on the r-statistic maps through the transporter/receptor and t-statistic maps. Our findings provide novel insights into the biological mechanism underlying sex differences in mental rotation, identifying potential biomarkers for cognitive impairment and explaining variations in prevalence of certain mental disorders between the sexes. These results highlight the necessity of considering sex in research on mental health disorders.http://www.sciencedirect.com/science/article/pii/S105381192400452XSex differenceMental rotationMultimodal MRITranscriptome-neuroimaging association analysisNeurotransmitter receptors/transportersMediation analysis
spellingShingle Haixia Long
Hao Wu
Chaoliang Sun
Xinli Xu
Xu-Hua Yang
Jie Xiao
Mingqi Lv
Qiuju Chen
Ming Fan
Biological mechanism of sex differences in mental rotation: Evidence from multimodal MRI, transcriptomic and receptor/transporter data
NeuroImage
Sex difference
Mental rotation
Multimodal MRI
Transcriptome-neuroimaging association analysis
Neurotransmitter receptors/transporters
Mediation analysis
title Biological mechanism of sex differences in mental rotation: Evidence from multimodal MRI, transcriptomic and receptor/transporter data
title_full Biological mechanism of sex differences in mental rotation: Evidence from multimodal MRI, transcriptomic and receptor/transporter data
title_fullStr Biological mechanism of sex differences in mental rotation: Evidence from multimodal MRI, transcriptomic and receptor/transporter data
title_full_unstemmed Biological mechanism of sex differences in mental rotation: Evidence from multimodal MRI, transcriptomic and receptor/transporter data
title_short Biological mechanism of sex differences in mental rotation: Evidence from multimodal MRI, transcriptomic and receptor/transporter data
title_sort biological mechanism of sex differences in mental rotation evidence from multimodal mri transcriptomic and receptor transporter data
topic Sex difference
Mental rotation
Multimodal MRI
Transcriptome-neuroimaging association analysis
Neurotransmitter receptors/transporters
Mediation analysis
url http://www.sciencedirect.com/science/article/pii/S105381192400452X
work_keys_str_mv AT haixialong biologicalmechanismofsexdifferencesinmentalrotationevidencefrommultimodalmritranscriptomicandreceptortransporterdata
AT haowu biologicalmechanismofsexdifferencesinmentalrotationevidencefrommultimodalmritranscriptomicandreceptortransporterdata
AT chaoliangsun biologicalmechanismofsexdifferencesinmentalrotationevidencefrommultimodalmritranscriptomicandreceptortransporterdata
AT xinlixu biologicalmechanismofsexdifferencesinmentalrotationevidencefrommultimodalmritranscriptomicandreceptortransporterdata
AT xuhuayang biologicalmechanismofsexdifferencesinmentalrotationevidencefrommultimodalmritranscriptomicandreceptortransporterdata
AT jiexiao biologicalmechanismofsexdifferencesinmentalrotationevidencefrommultimodalmritranscriptomicandreceptortransporterdata
AT mingqilv biologicalmechanismofsexdifferencesinmentalrotationevidencefrommultimodalmritranscriptomicandreceptortransporterdata
AT qiujuchen biologicalmechanismofsexdifferencesinmentalrotationevidencefrommultimodalmritranscriptomicandreceptortransporterdata
AT mingfan biologicalmechanismofsexdifferencesinmentalrotationevidencefrommultimodalmritranscriptomicandreceptortransporterdata