{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:58:47Z","timestamp":1790657927413,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Social cognition (SC) has emerged as a relevant neurocognitive domain in people with Multiple Sclerosis (pwMS), given its impact on everyday functioning. However, the neural mechanisms supporting SC performance in pwMS remain underexplored, highlighting the need for ecologically valid assessment paradigms capable of capturing both behavioral and neural aspects of social-cognitive functioning. In this study, we addressed this gap by investigating the clinical application of an fMRI-adapted version of the Edinburgh Social Cognition Test (ESCoT) to explore the neural correlates of SC functioning in pwMS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In total, 59 subjects (27 pwMS, mean EDSS\u202f=\u202f3.74, and 32 healthy controls) were enrolled in this study and underwent a comprehensive neuropsychological assessment, including SC tests, and the fMRI-adapted version of the ESCoT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No significant between-group differences were observed during the fMRI task performance. Across groups, the paradigm elicited activation within a network involving the bilateral middle temporal poles, left dorsomedial prefrontal cortex, and precuneus, regions consistently implicated in social-cognitive processing. Within the pwMS group, a significant association was identified between neural activation and behavioral SC performance (rho\u202f=\u202f\u22120.447,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.032), linking poorer SC performance with greater activation of the left dorsomedial prefrontal cortex.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings support the applicability of the ESCoT as an ecologically valid neuropsychological paradigm for capturing the neural processes underlying SC abilities in a clinical population. The observed relationship suggests that increased activation of an executive neural hub may support SC proficiency in pwMS, potentially reflecting an early compensatory strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpsyg.2026.1905506","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:39:21Z","timestamp":1790656761000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Left dorsomedial prefrontal cortex hyperactivation reflects early compensation for emerging social cognition difficulties in multiple sclerosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Sara","family":"Isernia","sequence":"first","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Pirastru","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego Michael","family":"Cacciatore","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS","place":["Milan, Italy"]},{"name":"Department of Psychology, Universit\u00e0 Cattolica del Sacro Cuore","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Rossetto","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Smecca","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Pedrini","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Rovaris","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Toselli","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Blasi","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Baglio","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2971","DOI":"10.1016\/j.neuropsychologia.2011.07.012","article-title":"Neuroanatomical and neurochemical bases of theory of mind","volume":"49","author":"Abu-Akel","year":"2011","journal-title":"Neuropsychologia"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/nrn1884","article-title":"Meeting of minds: the medial frontal cortex and social cognition","volume":"7","author":"Amodio","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"101167","DOI":"10.1016\/j.dr.2024.101167","article-title":"Executive functions and social cognition from early childhood to pre-adolescence: a systematic review","volume":"74","author":"Badarneh","year":"2024","journal-title":"Dev. Rev."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e0195818","DOI":"10.1371\/journal.pone.0195818","article-title":"The Edinburgh social cognition test (ESCoT): examining the effects of age on a new measure of theory of mind and social norm understanding","volume":"13","author":"Baksh","year":"2018","journal-title":"PLoS One"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1212\/wnl.0000000000004060","article-title":"Disconnection as a mechanism for social cognition impairment in multiple sclerosis","volume":"89","author":"Batista","year":"2017","journal-title":"Neurology"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1177\/1352458516680750","article-title":"Impairment of social cognition in multiple sclerosis: amygdala atrophy is the main predictor","volume":"23","author":"Batista","year":"2017","journal-title":"Mult. Scler."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"276","DOI":"10.3389\/fnbeh.2019.00276","article-title":"Resting-state functional correlates of social cognition in multiple sclerosis: an explorative study","volume":"13","author":"Bisecco","year":"2019","journal-title":"Front. Behav. Neurosci."},{"key":"ref8","first-page":"111","article-title":"A short version of the Stroop test: normative data in an Italian population sample","volume":"12","author":"Caffarra","year":"2002","journal-title":"Nuova Riv. Neurol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1017\/s1355617716001156","article-title":"Deficits in social cognition: an unveiled signature of multiple sclerosis","volume":"23","author":"Chalah","year":"2017","journal-title":"J. Int. Neuropsychol. 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Sci."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.nic.2008.08.004","article-title":"Functional MR imaging in multiple sclerosis","volume":"19","author":"Filippi","year":"2009","journal-title":"Neuroimaging Clin. N. Am."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41386-021-01132-0","article-title":"The role of prefrontal cortex in cognitive control and executive function","volume":"47","author":"Friedman","year":"2022","journal-title":"Neuropsychopharmacology"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/bf01997792","article-title":"Trail making test: normative values from 287 normal adult controls","volume":"17","author":"Giovagnoli","year":"1996","journal-title":"Ital. J. Neurol. 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Scler. Relat. Disord."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"111278","DOI":"10.1016\/j.brainresbull.2025.111278","article-title":"FMRI insights into the neural alterations and clinical correlates in multiple sclerosis: a comprehensive overview of systematic reviews and meta-analyses","volume":"223","author":"Rahnemayan","year":"2025","journal-title":"Brain Res. Bull."},{"key":"ref35","author":"Rao","year":"1990"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"5799","DOI":"10.1002\/hbm.22586","article-title":"Functional correlates of cognitive dysfunction in multiple sclerosis: a multicenter fMRI study","volume":"35","author":"Rocca","year":"2014","journal-title":"Hum. Brain Mapp."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1080\/13854046.2024.2446026","article-title":"Time efficiency in mental state reasoning of people with multiple sclerosis: the double-sided affective and cognitive theory of mind disturbances","volume":"39","author":"Rossetto","year":"2025","journal-title":"Clin. Neuropsychol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s10072-014-1995-y","article-title":"Normative data for the Montreal cognitive assessment in an Italian population sample","volume":"36","author":"Santangelo","year":"2015","journal-title":"Neurol. Sci."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.acn.2005.07.003","article-title":"Normative symbol digit modalities test performance in a community-based sample","volume":"21","author":"Sheridan","year":"2006","journal-title":"Arch. Clin. Neuropsychol."},{"key":"ref40","volume-title":"A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary","author":"Strauss","year":"2006"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"117164","DOI":"10.1016\/j.neuroimage.2020.117164","article-title":"Sample size evolution in neuroimaging research: an evaluation of highly-cited studies (1990-2012) and of latest practices (2017-2018) in high-impact journals","volume":"221","author":"Szucs","year":"2020","journal-title":"NeuroImage"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/s1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1016\/j.neuroimage.2010.09.043","article-title":"A dissociation between social mentalizing and general reasoning","volume":"54","author":"Van Overwalle","year":"2011","journal-title":"NeuroImage"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"103156","DOI":"10.1016\/j.msard.2021.103156","article-title":"Theory of mind and its neuroanatomical correlates in people with multiple sclerosis","volume":"55","author":"Yokote","year":"2021","journal-title":"Mult. 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