Successful participation in the social world requires a good comprehension of others’ thoughts, beliefs, and intentions, making accurate inferences about the contents of other people’s minds, and representing them in one’s mind. This complex process is made possible by Theory of Mind (ToM), the ability to understand and attribute mental states to ourselves and others (Premack and Woodruff, 1978), a foundational component of social cognition. ToM is developed throughout our entire life, but some clinical conditions or disturbances could have an impact on the development or maintenance of this ability. Among these, Multiple Sclerosis (MS), a chronic neurodegenerative disorder that impacts both the physical and cognitive status of people affected (pwMS). Recent literature has shown that pwMS show decreased performance in ToM tasks, both in its cognitive and affective domain (Raimo et al., 2017). Isernia et al. (2019) and Roca et al. (2014) suggest that only cognitive ToM is impaired in MS, while Cotter et al. (2016) highlighted a mainly affective ToM deficit in pwMS. Although there is still no agreement on which dimension is more involved, ToM deficit has a relevant impact on the life of pwMS, due to the strong association with reduced social and psychological quality of life (Giazkoulidou et al., 2019). For example, Bora et al. (2016) suppose that relational difficulties identified in pwMS could be related to the ToM deficit (Chiaravalloti and DeLuca, 2008). Considering that social support has an essential role in managing a disease that affects people at a young age (Costa et al., 2017), the treatment of ToM deficits for preserving interpersonal relationships in MS should be relevant in taking charge of this chronic condition. Considering the availability of a wide array of interventions targeted to the empowerment of ToM in other clinical conditions (Kurtz et al., 2016; Ashman et al., 2017; Edel et al., 2017; d’Arma et al., 2020) and in normal aging (featured by a decrease of ToM; Cavallini et al., 2015; Rosi et al., 2016), no training is currently established for the pwMS. For this reason, the present study aimed to design and preliminarily test the efficacy of a novel cultural ToM training (CToM; d’Arma et al., 2021) to promote emotional and cognitive mental state understanding in pwMS.

Table 3 reports the principal demographic characteristics of the participants and the group’s comparison. One subject was considered a drop out because of its exit from the study (the subject had to discontinue its hospitalization for the first Italian lockdown on March 2020).

The two groups did not differ significantly for any of the demographic variables considered; hence they are comparable. The age, the education, and the disease duration were normally distributed, except for the EDSS score.

In Table 4 results of the analysis of the variance were shown.

We found a statistically significant Time × Group effect on the RMET test (p = 0.015), on the False Belief II order task (p = 0.032), on the WLG test (p = 0.048), in the total score of the TAS-20 (p = 0.018) and the Description Subscale of the TAS-20 (p = 0.018) (Figures 1–5).

These results of our study show that our novel CToM training could be useful in the enhancement of ToM, in both affective and cognitive components. Regarding the affective ToM, the analysis showed a highly significant effect of the training on the RMET; the use of cultural stimuli improves ToM and particularly the affective component, as shown in the work of Kidd and Castano (2013). Specifically, our CToM training enhances the emotion recognition of the characters of the cultural stimuli presented (deriving from cinema and literature), contextualizing them in the several conditions displayed. We can assume that fictions (read or seen) propose narratives and frame significant for the subjects (Bruner and Bruner, 1990), motivating them to apply their ToM ability. To understand the stimuli of the CToM training, mainly important is to correctly attribute the emotions to the characters; this training is composed by situations in which the protagonists experience different emotions in the face of the same event and, as in real-life, the adequate interpretation of emotional states guide the understanding of the situation itself.

Regarding the cognitive ToM, our CToM training has also shown a significant effect on the second-order false-belief task, but not on the third-order reasoning. This is probably since that higher ToM reasoning is difficult to do even for non-clinical people (see, for example, Valle et al., 2015), then it is probably inaccessible in a clinical situation characterized by a ToM deficit. Instead, the second-order ToM, usually reached around 8 years of age (Perner and Wimmer, 1985), can be more sensitive to the CToM, that proposes multiple situations regarding, for example, gaffes or non-direct communications, requiring second-order recursive reasoning to be understood. Nevertheless, the CToM training does not seem to generalize its impact on the advanced ToM tasks, the Strange Stories, and the Faux pas test, for which we found a trend toward significance. This is probably due to the complexity of the advanced ToM tasks, that requires very high competences in the social context, that pwMS could not reach due to the MS disease. Furthermore, a very small number of the subjects have been included in this study: in the future, a sample’s enlargement could show a more evident impact on ToM abilities.

These results support the idea that a generic training rehabilitation, such as the Ct here proposed, is not enough to enhance the specific ability of ToM in a sample of clinical population: on the contrary, it seems that is precisely the work on the comprehension of emotions and mental states together with the enhancement of mental states inferences to be effective in enhancing basic ToM abilities (as happen also in other type of population, i.e., primary school children; Bianco et al., 2021). This result is corroborated by the fact that there was no statistically significant improvement in both groups in the neuropsychological evaluation.

Only in the WLG task, assessing verbal fluency, the control condition shows a higher performance at T1 respect to the T0. This effect could be due to the nature of the control condition: indeed, even though we pose particular attention to avoid the focus on mentalistic ability in the non-mentalistic training, the six control condition lessons were characterized by lengthy discussions on the different types of communication currently available. Although non-mentalistic training seems to be not effective on ToM domain and other executive functions, it is possible that the fluency could be enhanced by the discussion held in the control condition.

Our CToM also had a significant effect on the alexithymia, reduced in the experimental group, indicating an improvement of the alexithymia traits after the CToM. Alexithymia was a relevant issue in patients with MS (Eboni et al., 2018), and it was associated with increased severity of fatigue and depression (Bodini et al., 2008). The result obtained in the “Difficulty Describing Feelings subscale” of the TAS-20 in favor of the experimental group confirms that conversations and discussions about mental states and emotions in an ecological manner could help pwMS describe feelings and emotions. Because one of the problems in managing MS is the improvement of the patient-physician interaction (Alroughani, 2015), this result confirms the importance to set ToM trainings in order to translate the results from the research setting to clinical practice, overcoming the gap between research discoveries and routine practice of treatments (Rothwell, 2005).

There are several limits to be considered for the interpretation of these results. The Covid-19 pandemic emergency negatively impacted the recruitment of the subjects: subjects were recruited during their rehabilitation hospitalization in the Rehabilitation Unit of the Multiple Sclerosis Center of the Don Gnocchi Foundation that, for several months, were stopped to give priority to another kind of hospitalization most appropriate at that stage. So, at that moment we have been able to recruit only 13 subjects, of which one has been considered a drop out just due to anti-COVID 19 strategic measures (the subject had to discontinue its hospitalization for the first Italian lockdown on March 2020). To date, the rehabilitation unit is still open and resumed MS rehabilitation hospitalization, however not without some inevitable changes. Operators must wear several personal safety protection devices that could impact the relationship between the training and the inpatients even if they do not interfere with the training itself. Related to this limit, we have to pinpoint that we are aware of the limit in fitting a linear mixed model despite the small number of our populations; this is only a pilot study and we had the need to understand the effect of our ToM training controlling contents and methods of the treatment, in order to give an indication of differences among times × groups.

Furthermore, pwMS recruited from our Rehabilitation Unit is often in a stage of disease with moderate and severe disability, making it difficult to generalize these preliminary results to the MS population, which presents a greater degree of variability.

Our study provides preliminary findings on the efficacy of our CToM training for rehabilitating and enhancing the ToM abilities in pwMS. The effect is detectable not only on ToM tasks (both affective and cognitive), but also on alexithymia traits. Due to the crucial repercussions that they have on social interactions, social support networks, and QoL, the possibility to implement rehabilitation training for the empowerment of ToM ability in this population should be considered in clinical settings. However future studies are needed for verifying the effectiveness of four rehabilitation methods in samples with larger size and more representative of the MS population of patients.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by Comitato Etico - Fondazione Don Carlo Gnocchi. The patients/participants provided their written informed consent to participate in this study.

AV, FB, DM, and AM conceived and planned research and contributed to the management, the coordination of the research activity, the supervision of the evolution of the research goals and of the revision of the manuscript. Ad'A conceived and planned research, collected data and contributed to the data entry, to statistical analysis, to the synthesis and the presentation of study data, drafting and submitting the manuscript. GB contributed to data collection and data entry. SI contributed to data collection and revision of the manuscript. MR managed and cohordinated the patient recruitment and contributed to the revision of the manuscript. Ad'A and AV wrote the first draft of the manuscript. SDT that perform statistical analysis, revised the manuscript and contribute to the final form of the manuscript. All authors contributed to the article and approved the submitted version.

This work was funded by the Italian Ministry of Health (“Ricerca Corrente” - 2022-2024 Program).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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