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Brain structure underlying the empathizing–systemizing difference in children with autism spectrum disorder

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Abstract

Background

Behavioral research has shown that children with autism spectrum disorder (ASD) have a higher empathizing–systemizing difference (D score) than normal children. However, there is no research about the neuroanatomical mechanisms of the empathizing–systemizing difference in children with ASD.

Methods

Participants comprised 41 children with ASD and 39 typically developing (TD) children aged 6‒12 years. Empathizing–systemizing difference was estimated using the D score from the Chinese version of Children’s Empathy Quotient and Systemizing Quotient. We quantified brain morphometry, including global and regional brain volumes and surface-based cortical measures (cortical thickness, surface area, and gyrification) via structural magnetic resonance imaging.

Results

We found that the D score was significantly negatively associated with amygdala gray matter volume [β =  −0.16; 95% confidence interval (CI): −0.30,  −0.02; P value = 0.030] in children with ASD. There was a significantly negative association between D score and gyrification in the left lateral occipital cortex (LOC) in children with ASD (B =  −0.10; SE = 0.03; cluster-wise P value = 0.006) and a significantly positive association between D score and gyrification in the right fusiform in TD children (B = 0.10; SE = 0.03; cluster-wise P value = 0.022). Moderation analyses demonstrated significant interactions between D score and diagnosed group in amygdala gray matter volume (β = 0.19; 95% CI 0.04, 0.35; P value = 0.013) and left LOC gyrification (β = 0.11; 95% CI 0.05, 0.17; P value = 0.001) but not in right fusiform gyrification (β = 0.08; 95% CI −0.02, 0.17; P value = 0.105).

Conclusions

Neuroanatomical variation in amygdala volume and gyrification of LOC could be potential biomarkers for the empathizing–systemizing difference in children with ASD but not in TD children. Large-scale neuroimaging studies are necessary to test the replicability of our findings.

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Data availability

The raw data in the manuscript are only available on request from those who wish to collaborate with us by emailing the corresponding authors. All requests for data will be reviewed by the Ethical Review Committee for Biomedical Research at Sun Yat-Sen University and that data sharing will be conducted in compliance with relevant ethical guidelines and regulations.

References

  1. Masi A, DeMayo MM, Glozier N, Guastella AJ. An overview of autism spectrum disorder, heterogeneity and treatment options. Neurosci Bull. 2017;33:183–93.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Baron-Cohen S. Autism: the empathizing-systemizing (E-S) theory. Ann N Y Acad Sci. 2009;1156:68–80.

    Article  PubMed  Google Scholar 

  3. Baron-Cohen S, Lombardo MV, Auyeung B, Ashwin E, Chakrabarti B, Knickmeyer R. Why are autism spectrum conditions more prevalent in males? PLoS Biol. 2011;9:e1001081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wang X, Dai M, Murray A, Liu S, Chen J, Lin L, et al. Psychometric properties of the Chinese version of the children’s empathy quotient and systemizing quotient: 4–12 years. Autism Res. 2022;15:1675–85.

    Article  PubMed  Google Scholar 

  5. Wang X, Auyeung B, Pan N, Lin LZ, Chen Q, Chen JJ, et al. Empathy, theory of mind, and prosocial behaviors in autistic children. Front Psychiatry. 2022;13:844578.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Pan N, Auyeung B, Wang X, Lin L, Li H, Zhan X, et al. Empathizing, systemizing, empathizing-systemizing difference and their association with autistic traits in children with autism spectrum disorder, with and without intellectual disability. Autism Res. 2022;15:1348–57.

    Article  PubMed  Google Scholar 

  7. Baron-Cohen S, Belmonte M. Autism: a window onto the development of the social and the analytic brain. Annu Rev Neurosci. 2005;28:109–26.

    Article  CAS  PubMed  Google Scholar 

  8. Kobayashi A, Yokota S, Takeuchi H, Asano K, Asano M, Sassa Y, et al. Increased grey matter volume of the right superior temporal gyrus in healthy children with autistic cognitive style: a VBM study. Brain Cogn. 2020;139:105514.

    Article  PubMed  Google Scholar 

  9. Lai MC, Lombardo MV, Chakrabarti B, Ecker C, Sadek SA, Wheelwright SJ, et al. Individual differences in brain structure underpin empathizing–systemizing cognitive styles in male adults. Neuroimage. 2012;61:1347–54.

    Article  PubMed  Google Scholar 

  10. Takeuchi H, Taki Y, Thyreau B, Sassa Y, Hashizume H, Sekiguchi A, et al. White matter structures associated with empathizing and systemizing in young adults. Neuroimage. 2013;77:222–36.

    Article  PubMed  Google Scholar 

  11. Takeuchi H, Taki Y, Sassa Y, Hashizume H, Sekiguchi A, Fukushima A, et al. Regional gray matter volume is associated with empathizing and systemizing in young adults. PLoS ONE. 2014;9:e84782.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lord C, Brugha TS, Charman T, Cusack J, Dumas G, Frazier T, et al. Autism spectrum disorder. Nat Rev Dis Primer. 2020;6:5.

    Article  Google Scholar 

  13. Raschle NM, Lee M, Buechler R, Christodoulou JA, Chang M, Vakil M, et al. Making MR imaging child’s play-pediatric neuroimaging protocol, guidelines and procedure. JoVE. 2009;29:e1309.

    Google Scholar 

  14. Tziraki M, Garg S, Harrison E, Wright NB, Hawkes R, Akhtar K, et al. A neuroimaging preparation protocol tailored for autism. Autism Res. 2021;14:65–74.

    Article  PubMed  Google Scholar 

  15. Fischl B. FreeSurfer. NeuroImage. 2012;62:774–81.

    Article  PubMed  Google Scholar 

  16. Fischl B. Automatically parcellating the human cerebral cortex. Cereb Cortex. 2004;14:11–22.

    Article  PubMed  Google Scholar 

  17. Desikan RS, Ségonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage. 2006;31:968–80.

    Article  PubMed  Google Scholar 

  18. Klapwijk ET, van de Kamp F, van der Meulen M, Peters S, Wierenga LM. Qoala-T: a supervised-learning tool for quality control of FreeSurfer segmented MRI data. Neuroimage. 2019;189:116–29.

    Article  PubMed  Google Scholar 

  19. Lamballais S, Muetzel RL. QDECR: a flexible, extensible vertex-wise analysis framework in R. Front Neuroinformatics. 2021;15:561689.

    Article  Google Scholar 

  20. Dennis M, Francis DJ, Cirino PT, Schachar R, Barnes MA, Fletcher JM. Why IQ is not a covariate in cognitive studies of neurodevelopmental disorders. J Int Neuropsychol Soc. 2009;15:331–43.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol. 1995;57:289–300.

    Google Scholar 

  22. Hagler DJ Jr, Saygin AP, Sereno MI. Smoothing and cluster thresholding for cortical surface-based group analysis of fMRI data. Neuroimage. 2006;33:1093–103.

    Article  PubMed  Google Scholar 

  23. Greve DN, Fischl B. False positive rates in surface-based anatomical analysis. Neuroimage. 2018;171:6–14.

    Article  PubMed  Google Scholar 

  24. Huang H. Psychometric properties of the children’s empathy quotient and systemizing quotient. National Taiwan University; 2015. https://hdl.handle.net/11296/9cuhbu. Accessed 8 May 2023.

  25. Kim MJ, Loucks RA, Palmer AL, Brown AC, Solomon KM, Marchante AN, et al. The structural and functional connectivity of the amygdala: from normal emotion to pathological anxiety. Behav Brain Res. 2011;223:403–10.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Schumann CM, Hamstra J, Goodlin-Jones BL, Lotspeich LJ, Kwon H, Buonocore MH, et al. The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. J Neurosci. 2004;24:6392–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Havighurst SS, Choy R, Ulker A, Otterpohl N, Aghaie Meybodi F, Edrissi F, et al. A preliminary evaluation of the cultural appropriateness of the tuning in to kids parenting program in Germany, Turkey, Iran and China. Int J Environ Res Public Health. 2022;19:10321.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Fang Y, Gopinathan S. Teachers and teaching in Eastern and Western schools: a critical review of cross-cultural comparative studies. International Handbook of Research on Teachers and Teaching. 2009; pp. 557–72.

  29. Amaral DG, Schumann CM, Nordahl CW. Neuroanatomy of autism. Trends Neurosci. 2008;31:137–45.

    Article  CAS  PubMed  Google Scholar 

  30. Kleinhans NM, Johnson LC, Richards T, Mahurin R, Greenson J, Dawson G, et al. Reduced neural habituation in the amygdala and social impairments in autism spectrum disorders. Am J Psychiatry. 2009;166:467–75.

    Article  PubMed  Google Scholar 

  31. Baribeau DA, Dupuis A, Paton TA, Hammill C, Scherer SW, Schachar RJ, et al. Structural neuroimaging correlates of social deficits are similar in autism spectrum disorder and attention-deficit/hyperactivity disorder: analysis from the POND Network. Transl Psychiatry. 2019;9:72.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Albin RL. Tourette syndrome: a disorder of the social decision-making network. Brain. 2018;141:332–47.

    Article  PubMed  Google Scholar 

  33. Nacewicz BM, Dalton KM, Johnstone T, Long MT, McAuliff EM, Oakes TR, et al. Amygdala volume and nonverbal social impairment in adolescent and adult males with autism. Arch Gen Psychiatry. 2006;63:1417–28.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kliemann D, Dziobek I, Hatri A, Baudewig J, Heekeren HR. The role of the Amygdala in atypical gaze on emotional faces in autism spectrum disorders. J Neurosci. 2012;32:9469–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mosconi MW, Cody-Hazlett H, Poe MD, Gerig G, Gimpel-Smith R, Piven J. Longitudinal study of amygdala volume and joint attention in 2- to 4-year-old children with autism. Arch Gen Psychiatry. 2009;66:509–16.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Fletcher-Watson S, Bird G. Autism and empathy: what are the real links? Autism. 2020;24:3–6.

    Article  PubMed  Google Scholar 

  37. Dziobek I, Fleck S, Rogers K, Wolf OT, Convit A. The ‘amygdala theory of autism’ revisited: linking structure to behavior. Neuropsychologia. 2006;44:1891–9.

    Article  PubMed  Google Scholar 

  38. Baron-Cohen S, Lombardo MV. Autism and talent: the cognitive and neural basis of systemizing. Dialogues Clin Neurosci. 2017;19:345–53.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Tallon-Baudry C, Bertrand O, Hénaff M-A, Isnard J, Fischer C. Attention modulates gamma-band oscillations differently in the human lateral occipital cortex and fusiform gyrus. Cereb Cortex. 2005;15:654–62.

    Article  PubMed  Google Scholar 

  40. Kim JG, Biederman I, Juan C-H. The Benefit of object interactions arises in the lateral occipital cortex independent of attentional modulation from the intraparietal sulcus: a transcranial magnetic stimulation study. J Neurosci. 2011;31:8320–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fornito A, Harrison BJ, Zalesky A, Simons JS. Competitive and cooperative dynamics of large-scale brain functional networks supporting recollection. Proc Natl Acad Sci. 2012;109:12788–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Jung M, Tu Y, Lang CA, Ortiz A, Park J, Jorgenson K, et al. Decreased structural connectivity and resting-state brain activity in the lateral occipital cortex is associated with social communication deficits in boys with autism spectrum disorder. Neuroimage. 2019;190:205–12.

    Article  PubMed  Google Scholar 

  43. Pitskel NB, Bolling DZ, Hudac CM, Lantz SD, Minshew NJ, Vander Wyk BC, et al. Brain mechanisms for processing direct and averted gaze in individuals with autism. J Autism Dev Disord. 2011;41:1686–93.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Gadgil M, Peterson E, Tregellas J, Hepburn S, Rojas DC. Differences in global and local level information processing in autism: an fMRI investigation. Psychiatry Res Neuroimaging. 2013;213:115–21.

    Article  Google Scholar 

  45. Palejwala AH, O’Connor KP, Pelargos P, Briggs RG, Milton CK, Conner AK, et al. Anatomy and white matter connections of the lateral occipital cortex. Surg Radiol Anat. 2020;42:315–28.

    Article  PubMed  Google Scholar 

  46. Iuculano T, Rosenberg-Lee M, Supekar K, Lynch CJ, Khouzam A, Phillips J, et al. Brain organization underlying superior mathematical abilities in children with autism. Biol Psychiatry. 2014;75:223–30.

    Article  PubMed  Google Scholar 

  47. Ecker C, Bookheimer SY, Murphy DGM. Neuroimaging in autism spectrum disorder: brain structure and function across the lifespan. Lancet Neurol. 2015;14:1121–34.

    Article  PubMed  Google Scholar 

  48. Xu P, Peng S, Luo Y, Gong G. Facial expression recognition: a meta-analytic review of theoretical models and neuroimaging evidence. Neurosci Biobehav Rev. 2021;127:820–36.

    Article  PubMed  Google Scholar 

  49. Griffin JW, Bauer R, Scherf KS. A quantitative meta-analysis of face recognition deficits in autism: 40 years of research. Psychol Bull. 2021;147:268–92.

    Article  PubMed  Google Scholar 

  50. Nickl-Jockschat T, Rottschy C, Thommes J, Schneider F, Laird AR, Fox PT, et al. Neural networks related to dysfunctional face processing in autism spectrum disorder. Brain Struct Funct. 2015;220:2355–71.

    Article  CAS  PubMed  Google Scholar 

  51. Nomi JS, Uddin LQ. Face processing in autism spectrum disorders: from brain regions to brain networks. Neuropsychologia. 2015;71:201–16.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Valla JM, Ganzel BL, Yoder KJ, Chen GM, Lyman LT, Sidari AP, et al. More than maths and mindreading: sex differences in empathizing/systemizing covariance. Autism Res. 2010;3:174–84.

    Article  PubMed  Google Scholar 

  53. Nagy K, Greenlee MW, Kovács G. The lateral occipital cortex in the face perception network: an effective connectivity study. Front Psychol. 2012;3:141.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Scherf KS, Luna B, Minshew N, Behrmann M. Location, location, location: alterations in the functional topography of face- but not object- or place-related cortex in adolescents with autism. Front Hum Neurosci. 2010;4:26.

    PubMed  PubMed Central  Google Scholar 

  55. Li Z, Yang L, Chen H, Fang Y, Zhang T, Yin X, et al. Global, regional and national burden of autism spectrum disorder from 1990 to 2019: results from the global burden of disease study 2019. Epidemiol Psychiatr Sci. 2022;31:e33.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors gratefully thank the parents and children who have been generous with their time for participating in our research.

Funding

This work was supported by the Key-Area Research and Development Program of Guangdong Province (2019B030335001), the National Natural Science Foundation of China (82273649, 81872639, 82103794), Guangdong Basic and Applied Basic Research Foundation (2021A1515011757, 2022B1515130007).

Author information

Authors and Affiliations

  1. Department of Maternal and Child Health, School of Public Health, Sun Yat-Sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, 510080, China

    Ning Pan, Yu-Ying Jin, Si Tan, Xiao-Jing Song, Jin Jing & Xiu-Hong Li

  2. Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China

    Li-Zi Lin

  3. Key Laboratory of Brain, Cognition and Education Science, Ministry of Education, Guangzhou, China

    Xin Wang

  4. Institute for Brain Research and Rehabilitation, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, 510631, China

    Xin Wang

  5. JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China

    Lei Shi

  6. Chinese Institute for Brain Research, Beijing, 102206, China

    Xiao-Yu Xu

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  1. Ning Pan
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Contributions

PN: conceptualization, methodology, formal analysis, software, validation, resources, investigation, data curation, writing–original draft, writing–review and editing. LLZ: methodology, formal analysis, software, validation, funding acquisition, writing–review and editing. WX: investigation, writing–review and editing. XXY, JYY: software, validation, resources, investigation. TS, SXJ: data curation, investigation. SL, JJ: funding acquisition, writing–review and editing. LXH: conceptualization, supervision, project administration, funding acquisition, writing–review and editing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xiu-Hong Li.

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No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

Ethical approval

The study was approved by the Ethical Review Committee for Biomedical Research Sun Yat-Sen University (2015-No.29). Informed consent to participate in the study has been obtained from participants (or their parent or legal guardian in the case of children under 16).

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Pan, N., Lin, LZ., Wang, X. et al. Brain structure underlying the empathizing–systemizing difference in children with autism spectrum disorder. World J Pediatr 19, 782–792 (2023). https://doi.org/10.1007/s12519-023-00732-8

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