**5. Impairment of social cognitive abilities in patients with MS**

Social cognition is considered a main determinant of the functional outcome in many psychi‐ atric and neurologic degenerative diseases, including MS. Social cognitive impairments have been registered even in the first clinical episode prior to conversion to MS.

Decreased empathy was reported in patients with MS (cohort of 34 MS subjects) compared to healthy controls of the same age and education level (*p* < 0.01) [55]. These results were obtained from a study by Benedict et al., which is the first of its kind. It matched self‐reports of patients with MS on their level of empathy against external evaluation by informants. The authors found large discrepancies between the responses from the two groups—the scores obtained from patients were significantly higher (*p* < 0.01) than those of the informants. Personal abnormalities, such as elevated neuroticism, agreeableness and conscientiousness, were also registered in the patients. The authors emphasize the predictive role of executive control over the manifestation of these anomalies and suggest frontal lobe syndrome [55]. Ten years later, Kraemer et al. also revealed a significantly lower level of empathy in patients with MS assessed by self‐rating questionnaire (*p* < 0.02). A study of Banati et al. registered a higher level of empathy, attributed by ambulatory MS subjects to themselves by using self‐assessment questionnaire. The patients (*n* = 40) showed 14 times better empathizing abilities to themselves compared to control individuals (*p* < 0.05) [56]. Ot self‐compassion mechanisms suppress anxiety and negative thinking [57]. When self‐compassion is lowered, mild symptoms of depression and anxiety could escalate into more severe ones.

A systematic review of 72 studies provides evidence of worse adjustment in MS, which is associated with emotional stress and specific emotionally focused coping strategies in these patients. The authors stress the need for further research in this direction because of insufficient evidence on the relation between adjustment outcomes and level of cognition, interaction with others, disease symptoms, social support obtained [58].

Significantly reduced self‐perception in different subcategories was established in patients with MS as compared to healthy controls with similar demographic characteristics. Perception of emotional and social functioning (including global health perception) is impaired but mental characteristics are preserved [59].

Incorrect recognition of emotional information during the daily activities of patients with MS hinders the performance of social cognitive skills [60]. Alexithymia, the impaired ability to verbalize emotions due to violation of their processing, might have a significant impact on self‐ perception, emotion regulation, behavior control and interaction with others in these patients [61]. Alexithymia is a personal construct, characterized by subclinical inability to identify and describe the emotions in the self [62]. It is a common finding in patients with MS and further hinders social cognition [63], making them nonempathic and ineffective in emotional respond‐ ing [64]. For example, in a study comparing 40 MS patients with the same number of normal volunteers, Montreuil and Petropoulo registered alexithymia in 50% of the patients and only in 9% of controls [65]. No correlation was found between alexithymia, on the one hand, and cognitive impairment, mood disorders and disease duration in MS patients, on the other. However, MRI studies established a significant connection between alexithymia and atrophy of the posterior part of corpus callosum [66]. This result supports the hypothesis of interhe‐ mispheric transfer dysfunction in patients with alexithymic MS [67].

One of the most sensitive indications of social cognition impairment, in particular in MS, is the difficulty in facial expression recognition [68, 69]. Most MS research detects a deficiency in emotional facial expression recognition. Beatty studied patients with MS and established impaired identification not only of facial affect, but also of neutral facial expressions [60]. Testing this ability in patients with MS again (cohort of 22 patients with MS and 11 healthy controls), Krause et al. detected unequivocal emotion recognition deficits in patients with MS who had shown no difficulties in face identification. In line with current findings, these impairments were most common in the recognition of unpleasant facial emotions, while deficits in the recognition of happy expression were not observed. Furthermore, the reaction times to happy facial expressions were significantly faster (*p* < 0.001) compared to that to negative emotional expressions. One reason may be that it is usually easier to recognize a happier facial expression, and consequently, these impairments can be better compensated for [70]. Based on specific tests for perception from facial photographs, Philips expanded and supplemented the currently available data with the conclusion that MS leads to an impaired ability for processing emotional information from both static and dynamic images [71]. However, differences in emotion recognition are discreet and subtle, and according to some researchers, correlate significantly with cognitive functioning, suggesting a global deficiency in the speed of information processing [50]. Despite some variability in findings, several contemporary studies support the thesis that ToM impairments are independent from neuropsychological functioning in adult patients with MS [49, 56]. A correlation between impaired emotional perception and the physiological and social aspects of quality of life was found in MS [71]. Some studies have shown a correlation between the inability to recognize facial emotions from presented photographs and alexithymia [72–74].

Kraemer et al. also revealed a significantly lower level of empathy in patients with MS assessed by self‐rating questionnaire (*p* < 0.02). A study of Banati et al. registered a higher level of empathy, attributed by ambulatory MS subjects to themselves by using self‐assessment questionnaire. The patients (*n* = 40) showed 14 times better empathizing abilities to themselves compared to control individuals (*p* < 0.05) [56]. Ot self‐compassion mechanisms suppress anxiety and negative thinking [57]. When self‐compassion is lowered, mild symptoms of

A systematic review of 72 studies provides evidence of worse adjustment in MS, which is associated with emotional stress and specific emotionally focused coping strategies in these patients. The authors stress the need for further research in this direction because of insufficient evidence on the relation between adjustment outcomes and level of cognition, interaction with

Significantly reduced self‐perception in different subcategories was established in patients with MS as compared to healthy controls with similar demographic characteristics. Perception of emotional and social functioning (including global health perception) is impaired but mental

Incorrect recognition of emotional information during the daily activities of patients with MS hinders the performance of social cognitive skills [60]. Alexithymia, the impaired ability to verbalize emotions due to violation of their processing, might have a significant impact on self‐ perception, emotion regulation, behavior control and interaction with others in these patients [61]. Alexithymia is a personal construct, characterized by subclinical inability to identify and describe the emotions in the self [62]. It is a common finding in patients with MS and further hinders social cognition [63], making them nonempathic and ineffective in emotional respond‐ ing [64]. For example, in a study comparing 40 MS patients with the same number of normal volunteers, Montreuil and Petropoulo registered alexithymia in 50% of the patients and only in 9% of controls [65]. No correlation was found between alexithymia, on the one hand, and cognitive impairment, mood disorders and disease duration in MS patients, on the other. However, MRI studies established a significant connection between alexithymia and atrophy of the posterior part of corpus callosum [66]. This result supports the hypothesis of interhe‐

One of the most sensitive indications of social cognition impairment, in particular in MS, is the difficulty in facial expression recognition [68, 69]. Most MS research detects a deficiency in emotional facial expression recognition. Beatty studied patients with MS and established impaired identification not only of facial affect, but also of neutral facial expressions [60]. Testing this ability in patients with MS again (cohort of 22 patients with MS and 11 healthy controls), Krause et al. detected unequivocal emotion recognition deficits in patients with MS who had shown no difficulties in face identification. In line with current findings, these impairments were most common in the recognition of unpleasant facial emotions, while deficits in the recognition of happy expression were not observed. Furthermore, the reaction times to happy facial expressions were significantly faster (*p* < 0.001) compared to that to negative emotional expressions. One reason may be that it is usually easier to recognize a happier facial expression, and consequently, these impairments can be better compensated for

depression and anxiety could escalate into more severe ones.

others, disease symptoms, social support obtained [58].

mispheric transfer dysfunction in patients with alexithymic MS [67].

characteristics are preserved [59].

234 Trending Topics in Multiple Sclerosis

In a study of patients with MS in 2003, which was the first of its kind, Beatty revealed affective prosody comprehension deficits not due to a hearing loss, cognitive decline, aphasia or depression (47 patients, 19 demographic controls). MRI studies of these patients did not detect a connection between affective prosody violations and the size of the corpus callosum or lesion load [75].

Empathy reflects the ability to infer and share the emotional state of others, therefore it is strongly related to ToM [76]. ToM (mentalization) refers to the perception of the mental condition of ourselves and others, which may serve for understanding and predicting their behavior [77].

ToM disorders are often detected in patients with MS. Their ability to read thoughts is reduced due to their impaired decoding of nonverbal signs such as facial expressions, gestures, gaze fixation and comprehensive processing of abstract verbal information.

The first study assessing ToM abilities in patients with MS was conducted in 2009 by Henry et al. [45], who applied both a test for basic recognition of emotional facial expressions and ToM tests (27 patients with MS and 30 controls). The "Reading the Mind in the Eyes" test (belonging to ToM tests) allowed the differentiation of more complex emotional states often associated with social relationships (e.g., attraction or repulsion, friendly or hostile attitude, noticing or ignoring the tested). The authors found impaired recognition of anger and fear in patients with MS but did not establish intergroup differences between subjects and controls in the recognition of surprise, sadness, disgust and happiness. A significant correlation was registered between dealing successfully with facial emotion recognition and ToM tasks. For both groups, a statistical correlation was discovered between the level of coping and executive control.

In the same year, Ouellet arrived at the conclusion that patients with MS suffering from cognitive deficits tend not to recognize the mental state of others unlike MS patients with preserved cognition (15 cognitively intact and 26 cognitively impaired patients) [49], while Henry (64 patients with relapsing‐remitting MS (RRMS), 30 controls) [78] and Pöttgen (45 patients with MS, 45 healthy controls) [21] found that ToM deficits in MS appear independently of the well‐known cognitive deficits. Emotion recognition impairments were more pro‐ nounced in patients with MS than impairments in thought and intention recognition [21, 79]. More errors of interpretation and lower total scores were reported in patients with MS when using nonverbal tests [56]. Subjects performed worse than controls (*p* < 0.05) at the facial symbol test (FST) [80].

In their pilot study, Genova et al. used a dynamic sociocognitive task—The Awareness of Social Inference Test (TASIT)—and established an impaired ability in patients with MS to interpret and understand lies and sarcasm. These impairments correlated with severe cognitive disorders in information processing speed, working memory, learning and memory and with premorbid IQ [50].

Charvet et al. devoted their scientific work on social cognition in patients with MS, which has debuted in childhood. The authors reported significantly worse results of the pediatric onset MS patients (*n* = 28) compared to those of healthy peers (*n* = 32) in the following three domains of social cognition: facial affect recognition (*p* = 0.008), detection of social faux pas (*p* = 0.009), perspective taking (*p* = 0.06) [81].

#### **5.1. Social cognition impairments in different clinical subtypes of MS**

Studies exploring the relatedness of social cognition impairments to clinical subtypes of MS are still insufficient. The available data indicate significant variation in the degree of cognitive impairment among individual phenotypes of the disease.

#### *5.1.1. Clinically isolated syndrome (CIS)*

In 2010, Jehna et al. conducted a study in which they established significant slower speed of emotional facial expression processing in patients with CIS compared to healthy persons (*p* <  0.01). They suggested storage of facial emotion recognition based on the lack of significant differences in the number of correct answers. Since response time is an indicator of cognitive processing speed, the authors interpreted these results as evidence of general delay in information processing in MS [80].

#### *5.1.2. Relapsing‐remitting multiple sclerosis (RRMS)*

Patients with RRMS demonstrated significantly lower levels of empathy toward others and fantasy compared to healthy subjects [82]. An earlier study by Beatty conducted in 1989 with MS patients assessed their ability to identify facial affect by viewing photographs depicting basic emotional states. Patients with RRMS fulfilled these tasks properly [60]. The findings of a new study, conducted by Kraemer et al. in 2013, with a homogeneous cohort of 25 patients with RRMS in the early stages of the disease (less than two years' duration) and with low levels of disability Expanded Disability Status Scale- <2 (EDSS <2) showed significantly worse results in affective prosody comprehension in MS subjects compared to the same number healthy controls. Patients gave less accurate solutions to "discrimination of affective prosody" and more incorrect responses in the subtest "matching of affective prosody to facial expression" for the emotion "anger". Paradoxically, regarding the emotion "fear" they showed better results than controls [6]. Gleichgerrcht et al found that MS subjects (patients *n* = 38; controls *n*

= 38) had significantly higher self‐oriented personal distress (*p* < 0.01) and higher levels of alexithymia compared to controls [82].

So far the only available study in patients with MS examining the cognitive and affective components of ToM separately is that of Roca et al. from 2014. Using faux pas and executive function tests in 18 RRMS patients with low grade of disability, Roca et al. found deficits in the cognitive component of ToM in the presence of a stored affective component. Such dissociation between the cognitive and affective components of ToM has also been reported in other neurological and psychiatric disorders [83].

#### *5.1.3. Primary progressive MS (PPMS)*

More errors of interpretation and lower total scores were reported in patients with MS when using nonverbal tests [56]. Subjects performed worse than controls (*p* < 0.05) at the facial

In their pilot study, Genova et al. used a dynamic sociocognitive task—The Awareness of Social Inference Test (TASIT)—and established an impaired ability in patients with MS to interpret and understand lies and sarcasm. These impairments correlated with severe cognitive disorders in information processing speed, working memory, learning and memory and with

Charvet et al. devoted their scientific work on social cognition in patients with MS, which has debuted in childhood. The authors reported significantly worse results of the pediatric onset MS patients (*n* = 28) compared to those of healthy peers (*n* = 32) in the following three domains of social cognition: facial affect recognition (*p* = 0.008), detection of social faux pas (*p* = 0.009),

Studies exploring the relatedness of social cognition impairments to clinical subtypes of MS are still insufficient. The available data indicate significant variation in the degree of cognitive

In 2010, Jehna et al. conducted a study in which they established significant slower speed of emotional facial expression processing in patients with CIS compared to healthy persons (*p* <  0.01). They suggested storage of facial emotion recognition based on the lack of significant differences in the number of correct answers. Since response time is an indicator of cognitive processing speed, the authors interpreted these results as evidence of general delay in

Patients with RRMS demonstrated significantly lower levels of empathy toward others and fantasy compared to healthy subjects [82]. An earlier study by Beatty conducted in 1989 with MS patients assessed their ability to identify facial affect by viewing photographs depicting basic emotional states. Patients with RRMS fulfilled these tasks properly [60]. The findings of a new study, conducted by Kraemer et al. in 2013, with a homogeneous cohort of 25 patients with RRMS in the early stages of the disease (less than two years' duration) and with low levels of disability Expanded Disability Status Scale- <2 (EDSS <2) showed significantly worse results in affective prosody comprehension in MS subjects compared to the same number healthy controls. Patients gave less accurate solutions to "discrimination of affective prosody" and more incorrect responses in the subtest "matching of affective prosody to facial expression" for the emotion "anger". Paradoxically, regarding the emotion "fear" they showed better results than controls [6]. Gleichgerrcht et al found that MS subjects (patients *n* = 38; controls *n*

**5.1. Social cognition impairments in different clinical subtypes of MS**

impairment among individual phenotypes of the disease.

symbol test (FST) [80].

236 Trending Topics in Multiple Sclerosis

premorbid IQ [50].

perspective taking (*p* = 0.06) [81].

*5.1.1. Clinically isolated syndrome (CIS)*

information processing in MS [80].

*5.1.2. Relapsing‐remitting multiple sclerosis (RRMS)*

Patients with primary progressive MS (PPMS) have experienced considerable difficulties in identifying the emotions of others, as well as their own emotions. Patients from this subgroup gave lower results in faux pas tasks compared to RRMS patients [84].

#### *5.1.4. Secondary progressive multiple sclerosis (SPMS)*

Patients with secondary progressive MS (SPMS) are significantly more alexithymic compared to healthy controls [61]. Beatty's study in 1989 revealed that the patients with chronic progra‐ dient MS experienced difficulties in the discrimination of facial affect and neutral faces, unlike those with RRMS. Error analysis demonstrated that patients had the same difficulties in depicting each of the represented seven emotional states without serious errors in indicating their polar opposites [60]. Current studies have not shown abnormal identification of neutral faces by subjects with SPMS. In patients with this subtype, lower accuracy has been reported in performing tasks for perception of fear, surprise, anger and sadness [61], while difficulties in identifying disgust and happiness were not reported. Compared to healthy controls, patients took less time in recognizing fear and surprise, while detecting anger and sadness took them longer.

A retrospective longitudinal review with 1845 MS patients, 351 of whom with chronic progradient multiple sclerosis (CPMS), 636 — with RRMS and 858 — with mixed or nonspecific MS, compared to 265 healthy individuals registered worse results in patients with CPMS than in RRMS patients at the Benton Facial Recognition Test (BFRT) [85].

#### **5.2. Social cognition impairments depending on MS duration**

A positive correlation was detected between duration of MS and level of empathy, that is, the greater the duration of the disease, the lower the empathy quotient [55, 56, 86]. Banati et al. found profoundly increasing of the empathizing quotient (*p* 0.03) among patients with short‐ term MS (*n* = 40) compared to controls (*n* = 35). In addition, Pakenham and Cox in longitudinal study of 388 persons with MS and 232 caregivers registered positive correlation between the time since diagnosis and compassion/empathy (*p* < 0.01), mindfulness (*p* < 0.01) and personal growth (*p* < 0.01). Contrarily, other studies found a significant decrease in the empathy level in patients with MS who are still in the early stages of the disease and with a low degree of disability compared to healthy subjects. The authors explain the unrealistic self‐assessment results of most subjects with the greater impairment of ToM skills and partly with the higher emotional stress they were experiencing [22, 86].

In 2010, Banati et al. found more prominent ToM deficits in patients with longer disease duration (*p* = 0.05) [56]. In some research, the duration of the disease did not correlate with the emotional and cognitive scores from nonverbal tests [80], while Kraemer reported positive correlation between impaired social cognitive skills and executive function deficits in the early stages of the disease in fully ambulatory patients [6].

#### **5.3. Social cognition impairments in MS depending on the grade of physical disability**

Paradoxically, patients with more severe physical disorders relatively often show a higher level of empathy compared to controls and patients with mild neurological deficits. A positive correlation was found between the difficulty in emotional facial expression recognition and the degree of disability [44]. Patients with a higher grade of disability demonstrated greater difficulties in affective prosody recognition [75]. More interpretation errors and lower scores were reported for patients with MS when nonverbal tests were used [56]. With deterioration of the disability the results from ToM verbal tests also get worse [87]. In a study of Jehna, EDSS scores did not correlate significantly with scores from emotion recognition tests or with results from FST in MS subjects (sample of 20 patients: CIS *n* = 12, RRMS = 7, SPMS = 1) [80]. Results from other recent studies indicate that the severity of the disease (respectively the degree of physical disability) does not correlate with the degree of impaired emotion recognition or with the psychological and social aspects of the quality of life [71, 88]. Therefore, some researchers consider social cognition as a separate domain of cognition which could independently affect the quality of life of the individual, in particular, that of patients with MS. Based on the extensive review of the literature available, we can conclude that social cognition impairments in these patients require further in‐depth research.
