Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Scientific Reports
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. scientific reports
  3. articles
  4. article
A novel ecological approach to assess theory of Mind and social norm understanding for social cognition phenotyping in multiple sclerosis
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 02 February 2026

A novel ecological approach to assess theory of Mind and social norm understanding for social cognition phenotyping in multiple sclerosis

  • Isernia Sara  ORCID: orcid.org/0000-0002-0849-39841,
  • Smecca Giulia  ORCID: orcid.org/0009-0007-8396-96241,
  • Rossetto Federica  ORCID: orcid.org/0000-0001-6336-26481,
  • Borgnis Francesca  ORCID: orcid.org/0000-0001-8237-61641 &
  • …
  • Baglio Francesca  ORCID: orcid.org/0000-0002-6145-52741 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Neurology
  • Neuroscience
  • Psychology

Abstract

Social cognition (SC) impairment is a hallmark of the cognitive profile in Multiple Sclerosis (MS). However, there is a still no consensus on recommended measures for SC phenotyping in this clinical population, limiting our understanding of underlying mechanism and the development of targeted intervention. This study evaluated the suitability of the Edinburgh Social Cognition test (ESCoT), a novel ecologically valid tool assessing affective (ToMA) and cognitive (ToMc) Theory of Mind, as well as interpersonal (SNUINTER) and intrapersonal (SNUINTRA) social norm understanding, for SC phenotyping in MS. Seventy-one participants (39 with MS and 32 healthy controls) completed a neuropsychological battery including both non-social (Stroop test, Digit Span) and socio-cognitive (Eyes Test, ESCoT) measures. ESCoT demonstrated strong diagnostic validity (AUC = 0.803), outperforming the Eyes test (AUC = 0.653). Notably, ESCoT captured the peculiarity SC impairment profile in MS, marked by a dissociation between affective and cognitive ToM (ToMA< ToMc; group*ToM domain interaction: F = 21.87, p < 0.001), and between interpersonal and intrapersonal SNU (SNUINTER< SNUINTRA: group*SNU domain interaction: F = 22.76, p < 0.001). In the MS group, ToMA and ToMc scores were associated with the working memory, while SNUINTRA score was linked to executive functioning. These findings support ESCoT as a valid tool for SC phenotyping in MS.

Data availability

Data can be obtained upon reasonable request to the corresponding author.

References

  1. Chalah, M. A. & Ayache, S. S. A scope of the social brain in multiple sclerosis: insights from neuroimaging studies. Cogn. Behav. Neurol. 33 (2), 90–102. https://doi.org/10.1097/wnn.0000000000000227 (2020).

    Google Scholar 

  2. Lin, X. et al. Social cognition in multiple sclerosis and its subtypes: A meta-analysis. Mult Scler. Relat. Disord. 52, 102973. https://doi.org/10.1016/j.msard.2021.102973 (2021).

    Google Scholar 

  3. Bergien, S. O., Siersma, V. D., Kristiansen, M. & Skovgaard, L. Social relations and leisure activities as predictors of wellbeing among older adults with multiple sclerosis: A cross-sectional survey study in Denmark. Mult Scler. Relat. Disord. 77, 104878. https://doi.org/10.1016/j.msard.2023.104878 (2023).

    Google Scholar 

  4. Phillips, L. H. et al. Difficulties with emotion regulation in multiple sclerosis: links to executive function, mood, and quality of life. J. Clin. Exp. Neuropsychol. 36 (8), 831–842. https://doi.org/10.1080/13803395.2014.946891 (2014).

    Google Scholar 

  5. Radlak, B., Cooper, C., Summers, F. & Phillips, L. H. Multiple sclerosis, emotion perception and social functioning. J. Neuropsychol. 15 (3), 500–515. https://doi.org/10.1111/jnp.12237 (2021).

    Google Scholar 

  6. Carotenuto, A. et al. Communication in multiple sclerosis: pragmatic deficit and its relation with cognition and social cognition. Arch. Clin. Neuropsychol. 33 (2), 194–205. https://doi.org/10.1093/arclin/acx061 (2018).

    Google Scholar 

  7. Ayache, S. S. & Chalah, M. A. Moral judgment: an overlooked deficient domain in multiple sclerosis? Behav. Sci. (Basel). 8 (11). https://doi.org/10.3390/bs8110105 (2018).

  8. Rossetto, F., Isernia, S., Smecca, G., Rovaris, M. & Baglio, F. Time efficiency in mental state reasoning of people with multiple sclerosis: the double-sided affective and cognitive theory of Mind disturbances. Clin. Neuropsychol. 1–18. https://doi.org/10.1080/13854046.2024.2446026 (2024).

  9. Henry, A., Tourbah, A., Chaunu, M. P., Bakchine, S. & Montreuil, M. Social cognition abilities in patients with different multiple sclerosis subtypes. J. Int. Neuropsychol. Soc. 23 (8), 653–664. https://doi.org/10.1017/s1355617717000510 (2017).

    Google Scholar 

  10. Cerami, C. et al. Understanding barriers and optimizing socio-cognitive assessment in the diagnosis of neurocognitive disorders. J. Neuropsychol. https://doi.org/10.1111/jnp.12431 (2025).

    Google Scholar 

  11. McDonald, S., Wearne, T. & Kelly, M. Calling on clinicians to get social and emotional. Clin. Neuropsychol. 37 (3), 506–544. https://doi.org/10.1080/13854046.2022.2085176 (2023).

    Google Scholar 

  12. Genova, H. M. & McDonald, S. Social cognition in individuals with progressive multiple sclerosis: A pilot study using TASIT-S. J. Int. Neuropsychol. Soc. 26 (5), 539–544. https://doi.org/10.1017/s1355617719001371 (2020).

    Google Scholar 

  13. Realmuto, S. et al. Moral cognition and multiple sclerosis: A neuropsychological study. Arch. Clin. Neuropsychol. 34 (3), 319–326. https://doi.org/10.1093/arclin/acy047 (2019).

    Google Scholar 

  14. Rao, S. M., & Cognitive Function Study Group of the National Multiple Sclerosis Society. (1990). A manual for the Brief Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis. Medical College of Wisconsin.

  15. Baron-Cohen, S., Wheelwright, S., Hill, J., Raste, Y. & Plumb, I. The reading the Mind in the eyes test revised version: a study with normal adults, and adults with asperger syndrome or high-functioning autism. J. Child. Psychol. Psychiatry. 42 (2), 241–251 (2001).

    Google Scholar 

  16. Dodich, A. et al. A novel task assessing intention and emotion attribution: Italian standardization and normative data of the Story-based empathy task. Neurol. Sci. 36 (10), 1907–1912. https://doi.org/10.1007/s10072-015-2281-3 (2015).

    Google Scholar 

  17. Shamay-Tsoory, S. G. & Aharon-Peretz, J. Dissociable prefrontal networks for cognitive and affective theory of mind: a lesion study. Neuropsychologia 45 (13), 3054–3067. https://doi.org/10.1016/j.neuropsychologia.2007.05.021 (2007).

    Google Scholar 

  18. Baron-Cohen, S., O’Riordan, M., Stone, V., Jones, R. & Plaisted, K. Recognition of faux Pas by normally developing children and children with asperger syndrome or high-functioning autism. J. Autism Dev. Disord. 29 (5), 407–418. https://doi.org/10.1023/a:1023035012436 (1999).

    Google Scholar 

  19. Redcay, E. & Moraczewski, D. Social cognition in context: A naturalistic imaging approach. Neuroimage 216, 116392. https://doi.org/10.1016/j.neuroimage.2019.116392 (2020).

    Google Scholar 

  20. Msika, E. F., Despres, M., Piolino, P. & Narme, P. Dynamic and/or multimodal assessments for social cognition in neuropsychology: results from a systematic literature review. Clin. Neuropsychol. 38 (4), 922–962. https://doi.org/10.1080/13854046.2023.2266172 (2024).

    Google Scholar 

  21. Baksh, R. A., Abrahams, S., Auyeung, B. & MacPherson, S. E. The Edinburgh social cognition test (ESCoT): examining the effects of age on a new measure of theory of Mind and social norm Understanding. PLoS One. 13 (4), e0195818. https://doi.org/10.1371/journal.pone.0195818 (2018).

    Google Scholar 

  22. Baksh, R. A. et al. Social cognition in adults with autism spectrum disorders: validation of the Edinburgh social cognition test (ESCoT). Clin. Neuropsychol. 35 (7), 1275–1293. https://doi.org/10.1080/13854046.2020.1737236 (2021).

    Google Scholar 

  23. Poveda, B., Abrahams, S., Baksh, R. A., MacPherson, E. S. & Evans, J. J. An investigation of the validity of the Edinburgh social cognition test (ESCoT) in acquired brain injury (ABI). Journal Int. Neuropsychological Society 2021:1–13. https://doi.org/10.1017/S1355617721001223

  24. Isernia, S. et al. Italian adaptation of the Edinburgh social cognition test (ESCoT): A new tool for the assessment of theory of Mind and social norm Understanding. Front. Psychol. 13, 971187. https://doi.org/10.3389/fpsyg.2022.971187 (2022).

    Google Scholar 

  25. Isernia, S. et al. Human reasoning on social interactions in ecological contexts: insights from the theory of Mind brain circuits. Front. Neurosci. 18, 1420122. https://doi.org/10.3389/fnins.2024.1420122 (2024).

    Google Scholar 

  26. Stafford, O. et al. A 20-Year Systematic Review of the ‘Reading the Mind in the Eyes’ Test across Neurodegenerative Conditions. Brain Sci. 13 (9). https://doi.org/10.3390/brainsci13091268 (2023).

  27. Cotter, J. et al. Social cognition in multiple sclerosis: A systematic review and meta-analysis. Neurology 87 (16), 1727–1736. https://doi.org/10.1212/wnl.0000000000003236 (2016).

    Google Scholar 

  28. Bora, E., Özakbaş, S., Velakoulis, D. & Walterfang, M. Social cognition in multiple sclerosis: a Meta-Analysis. Neuropsychol. Rev. 26 (2), 160–172. https://doi.org/10.1007/s11065-016-9320-6 (2016).

    Google Scholar 

  29. Roheger, M., Grothe, L., Hasselberg, L., Grothe, M. & Meinzer, M. A systematic review and meta-analysis of socio-cognitive impairments in multiple sclerosis. Sci. Rep. 14 (1), 7096. https://doi.org/10.1038/s41598-024-53750-5 (2024).

    Google Scholar 

  30. Isernia, S. et al. Social Mind and Long-Lasting disease: focus on affective and cognitive theory of Mind in multiple sclerosis. Front. Psychol. 10, 218. https://doi.org/10.3389/fpsyg.2019.00218 (2019).

    Google Scholar 

  31. Ehrlé, N., Hody, A., Lecrique, M., Gury, P. & Bakchine, S. Social norms in patients with relapsing-remitting multiple sclerosis: impairment of the moral/conventional distinction? Soc. Neurosci. 15 (6), 630–640. https://doi.org/10.1080/17470919.2020.1834449 (2020).

    Google Scholar 

  32. Abu-Akel, A. & Shamay-Tsoory, S. Neuroanatomical and neurochemical bases of theory of Mind. Neuropsychologia 49 (11), 2971–2984. https://doi.org/10.1016/j.neuropsychologia.2011.07.012 (2011).

    Google Scholar 

  33. Isernia, S. et al. Theory of Mind network in multiple sclerosis: A double Disconnection mechanism. Soc. Neurosci. 1–14. https://doi.org/10.1080/17470919.2020.1766562 (2020).

  34. Panchal, H. et al. Neuropsychological and neuroanatomical correlates of the social norms questionnaire in frontotemporal dementia versus alzheimer’s disease. Am. J. Alzheimers Dis. Other Demen. 31 (4), 326–332. https://doi.org/10.1177/1533317515617722 (2016).

    Google Scholar 

  35. Isernia, S. et al. Differential roles of neural Integrity, physical activity and depression in frailty: Sex-Related differences. Brain Sci. 13 (6). https://doi.org/10.3390/brainsci13060950 (2023).

  36. Dziobek, I. et al. Introducing MASC: a movie for the assessment of social cognition. J. Autism Dev. Disord. 36 (5), 623–636. https://doi.org/10.1007/s10803-006-0107-0 (2006).

    Google Scholar 

  37. Filippi, M. et al. Towards a biological view of multiple sclerosis from early subtle to clinical progression: an expert opinion. J. Neurol. 272 (2), 179. https://doi.org/10.1007/s00415-025-12917-4 (2025).

    Google Scholar 

  38. Argento, O. et al. Relapsing-remitting and secondary-progressive multiple sclerosis patients differ in decoding others’ emotions by their eyes. Eur. J. Neurol. 29 (2), 505–514. https://doi.org/10.1111/ene.15155 (2022).

    Google Scholar 

  39. Thompson, A. J. et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 17 (2), 162–173. https://doi.org/10.1016/s1474-4422(17)30470-2 (2018).

    Google Scholar 

  40. Santangelo, G. et al. Normative data for the Montreal cognitive assessment in an Italian population sample. Neurol. Sci. 36 (4), 585–591. https://doi.org/10.1007/s10072-014-1995-y (2015).

    Google Scholar 

  41. Strauss, E., Sherman, E. M. & Spreen, O. A Compendium of Neuropsychological Tests: Administration, norms, and Commentary (Society AC, 2006).

  42. Caffarra, P., Vezzadini, G., Dieci, F., Zonato, F. & Venneri, A. Una versione abbreviata Del test Di stroop: Dati normativi Nella popolazione Italiana. Nuova Rivista Di Neurologia. 12 (4), 111–115 (2002).

    Google Scholar 

  43. Monaco, M., Costa, A., Caltagirone, C., Carlesimo, G. A. & Forward and backward span for verbal and visuo-spatial data: standardization and normative data from an Italian adult population. Neurol. Sci. ;34(5):749–754. https://doi.org/10.1007/s10072-012-1130-x (2013).

  44. McHugh, M. L. Interrater reliability: the kappa statistic. Biochem. Med. (Zagreb). 22 (3), 276–282 (2012).

    Google Scholar 

  45. Mandrekar, J. N. Receiver operating characteristic curve in diagnostic test assessment. J. Thorac. Oncol. 5 (9), 1315–1316. https://doi.org/10.1097/JTO.0b013e3181ec173d (2010).

    Google Scholar 

  46. Perkins, N. J. & Schisterman, E. F. The Youden index and the optimal cut-point corrected for measurement error. Biom J. 47 (4), 428–441. https://doi.org/10.1002/bimj.200410133 (2005).

    Google Scholar 

Download references

Acknowledgements

The authors thank all participants who agreed to take part in the research.

Funding

This work was supported by the Italian Ministry of Health – Ricerca Corrente program 2025–2027.

Author information

Authors and Affiliations

  1. IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy

    Isernia Sara, Smecca Giulia, Rossetto Federica, Borgnis Francesca & Baglio Francesca

Authors
  1. Isernia Sara
    View author publications

    Search author on:PubMed Google Scholar

  2. Smecca Giulia
    View author publications

    Search author on:PubMed Google Scholar

  3. Rossetto Federica
    View author publications

    Search author on:PubMed Google Scholar

  4. Borgnis Francesca
    View author publications

    Search author on:PubMed Google Scholar

  5. Baglio Francesca
    View author publications

    Search author on:PubMed Google Scholar

Contributions

FBa and SI conceived the study; GS and SI performed formal analysis; FR and FBo enrolled participants and carried out neuropsychological evaluations; GS and SI wrote the first draft of the manuscript; FBa, FR and FBo reviewed and edited the manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Smecca Giulia.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sara, I., Giulia, S., Federica, R. et al. A novel ecological approach to assess theory of Mind and social norm understanding for social cognition phenotyping in multiple sclerosis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38016-6

Download citation

  • Received: 25 September 2025

  • Accepted: 28 January 2026

  • Published: 02 February 2026

  • DOI: https://doi.org/10.1038/s41598-026-38016-6

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • Multiple sclerosis
  • Social cognition
  • Social norms
  • Theory of mind
  • Cognitive functions
  • Diagnostic validity
Download PDF

Advertisement

Explore content

  • Research articles
  • News & Comment
  • Collections
  • Subjects
  • Follow us on Facebook
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • About Scientific Reports
  • Contact
  • Journal policies
  • Guide to referees
  • Calls for Papers
  • Editor's Choice
  • Journal highlights
  • Open Access Fees and Funding

Publish with us

  • For authors
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Scientific Reports (Sci Rep)

ISSN 2045-2322 (online)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing