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Physical activity interventions can improve emotion regulation and dimensions of empathy in persons with multiple sclerosis: An exploratory study

  • Dena Sadeghi Bahmani
    Correspondence
    Corresponding author at: University of Basel, Psychiatric Clinics; Center of Affective, Stress and Sleep Disorders, Basel, Switzerland.
    Affiliations
    University of Basel, Psychiatric Clinics (UPK), Center of Affective, Stress and Sleep Disorders (ZASS), Basel, Switzerland

    Kermanshah University of Medical Sciences (KUMS), Department of Psychiatry, Substance Abuse Prevention Research Center, Health Institute, Kermanshah, Iran

    Kermanshah University of Medical Sciences (KUMS), Department of Psychiatry, Sleep Disorders Research Center, Kermanshah, Iran

    Isfahan Neurosciences Research Center, Alzahra Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

    Tehran University of Medical Sciences, School of Medicine, Tehran, Iran
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  • Nazanin Razazian
    Affiliations
    Kermanshah University of Medical Sciences, Neurology Department, Kermanshah, Iran
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  • Robert W. Motl
    Affiliations
    Departments of Physical Therapy, University of Alabama at Birmingham, Birmingham, AL, USA
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  • Vahid Farnia
    Affiliations
    Kermanshah University of Medical Sciences (KUMS), Department of Psychiatry, Substance Abuse Prevention Research Center, Health Institute, Kermanshah, Iran
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  • Mostafa Alikhani
    Affiliations
    Kermanshah University of Medical Sciences (KUMS), Department of Psychiatry, Substance Abuse Prevention Research Center, Health Institute, Kermanshah, Iran
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  • Uwe Pühse
    Affiliations
    University of Basel, Department of Sport, Exercise, and Health, Division of Sport Science and Psychosocial Health, Basel, Switzerland
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  • Markus Gerber
    Affiliations
    University of Basel, Department of Sport, Exercise, and Health, Division of Sport Science and Psychosocial Health, Basel, Switzerland
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  • Serge Brand
    Affiliations
    University of Basel, Psychiatric Clinics (UPK), Center of Affective, Stress and Sleep Disorders (ZASS), Basel, Switzerland

    Kermanshah University of Medical Sciences (KUMS), Department of Psychiatry, Substance Abuse Prevention Research Center, Health Institute, Kermanshah, Iran

    Kermanshah University of Medical Sciences (KUMS), Department of Psychiatry, Sleep Disorders Research Center, Kermanshah, Iran

    University of Basel, Department of Sport, Exercise, and Health, Division of Sport Science and Psychosocial Health, Basel, Switzerland

    Tehran University of Medical Sciences, School of Medicine, Tehran, Iran
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Published:August 31, 2019DOI:https://doi.org/10.1016/j.msard.2019.101380

      Highlights

      • In individuals with MS, regulation and control of emotions and empathy improved over time.
      • Exercising had no impact on perception and acknowledgement of emotions and emotional expressivity.
      • Depending from the measurement, exercising impacted also on empathy.
      • Exercising has the potential to impact on emotion regulation and social interactions.

      Abstract

      Background

      Persons with multiple sclerosis (PwMS) report difficulties with emotion regulation and empathy. Regular physical activity (RPA) improves dimensions of psychological well-being in PwMS, but it remains unclear if regular physical activity has effects on emotion regulation and empathy. The present study investigated the effect of regular physical activity on emotion regulation and empathy, and explored, if endurance training or coordinative training are better than an active control condition.

      Methods

      92 female PwMS (mean age: 37.4 years; age range: 20–57 years; mean EDSS: 2.43) took part in this study. Participants were randomly assigned into endurance training, coordinative training, or active control conditions that all lasted 8 weeks and were yoked on frequency, duration, and social contact. Participants completed questionnaires on emotion regulation, empathy, depression and fatigue before and after the 8-week conditions.

      Results

      Regulation and control of emotions and empathy improved over time, but more so in the exercising groups, compared to the active control group. No changes over time and between groups were observed for perception and acknowledgement of emotions, emotional expressivity, and empathy, as measured with Reading in the Eyes test. These changes were not influenced by control for depression and fatigue as covariates.

      Conclusions

      Both endurance and coordinative exercise training had favorable effects on some aspects of emotion regulation and social cognition such as empathy in PwMS. Such initial results support for examination of exercise training for the treatment of issues of emotion regulation and social interactions in PwMS.

      Keywords

      1. Introduction

      Multiple sclerosis (MS) is a common chronic inflammatory degenerative autoimmune disease of the central nervous system (
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      ). Typically, persons with MS (PwMS) report both physical and psychological symptoms and impairments (
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      ). Psychological complaints involve symptoms of cognitive impairments (
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      In patients with multiple sclerosis, both objective and subjective sleep, depression, fatigue, and paresthesia improved after 3 weeks of regular exercise.
      ). These problems often coincide with modification (
      • Sadeghi Bahmani D.
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      • Shaygannejad V.
      • et al.
      Stability of mental toughness, sleep disturbances, and physical activity in patients with multiple sclerosis (MS)-A longitudinal and pilot study.
      ) or decrease in physical activity levels (
      • Latimer-Cheung A.E.
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      • Hicks A.L.
      • et al.
      Effects of exercise training on fitness, mobility, fatigue, and health-related quality of life among adults with multiple sclerosis: a systematic review to inform guideline development.
      ;
      • Motl R.W.
      • Sandroff B.M.
      • Kwakkel G.
      • et al.
      Exercise in patients with multiple sclerosis.
      ;
      • Pilutti L.A.
      • Platta M.E.
      • Motl R.W.
      • Latimer-Cheung A.E
      The safety of exercise training in multiple sclerosis: a systematic review.
      ;
      • Platta M.E.
      • Ensari I.
      • Motl R.W.
      • Pilutti L.A
      Effect of exercise training on fitness in multiple sclerosis: a meta-analysis.
      ;
      • Motl R.W.
      • Dlugonski D.
      • Pilutti L.
      • Sandroff B.
      • McAuley E
      Premorbid physical activity predicts disability progression in relapsing-remitting multiple sclerosis.
      ;
      • Veldhuijzen van Zanten J.J.
      • Pilutti L.A.
      • Duda J.L.
      • Motl R.W
      Sedentary behaviour in people with multiple sclerosis: is it time to stand up against ms.
      ), and emotional and social impairments (see below for more details) (
      • Chalah M.A.
      • Ayache S.S.
      Deficits in social cognition: an unveiled signature of multiple sclerosis.
      ;
      • Cotter J.
      • Firth J.
      • Enzinger C.
      • et al.
      Social cognition in multiple sclerosis: a systematic review and meta-analysis.
      ;
      • Phillips L.H.
      • Henry J.D.
      • Nouzova E.
      • Cooper C.
      • Radlak B.
      • Summers F
      Difficulties with emotion regulation in multiple sclerosis: links to executive function, mood, and quality of life.
      ;
      • Phillips L.H.
      • Saldias A.
      • McCarrey A.
      • et al.
      Attentional lapses, emotional regulation and quality of life in multiple sclerosis.
      ).
      To date, there is research supporting the favorable influence of regular physical activity on psychological well-being, including depression, fatigue, paresthesia (
      • Latimer-Cheung A.E.
      • Pilutti L.A.
      • Hicks A.L.
      • et al.
      Effects of exercise training on fitness, mobility, fatigue, and health-related quality of life among adults with multiple sclerosis: a systematic review to inform guideline development.
      ;
      • Motl R.W.
      • Sandroff B.M.
      • Kwakkel G.
      • et al.
      Exercise in patients with multiple sclerosis.
      ;
      • Pilutti L.A.
      • Platta M.E.
      • Motl R.W.
      • Latimer-Cheung A.E
      The safety of exercise training in multiple sclerosis: a systematic review.
      ;
      • Platta M.E.
      • Ensari I.
      • Motl R.W.
      • Pilutti L.A
      Effect of exercise training on fitness in multiple sclerosis: a meta-analysis.
      ;
      • Razazian N.
      • Yavari Z.
      • Farnia V.
      • et al.
      Exercising impacts on fatigue, depression, and paresthesia in female patients with multiple sclerosis.
      ;
      • Sandroff B.M.
      • Motl R.W.
      • Scudder M.R.
      • DeLuca J
      Systematic, evidence-based review of exercise, physical activity, and physical fitness effects on cognition in persons with multiple sclerosis.
      ), and subjective and objective sleep quality (
      • Sadeghi Bahmani D.
      • Kesselring J.
      • Papadimitriou M.
      • et al.
      In patients with multiple sclerosis, both objective and subjective sleep, depression, fatigue, and paresthesia improved after 3 weeks of regular exercise.
      ;
      • Sadeghi Bahmani D.
      • Razazian N.
      • Farnia V.
      • Alikhani M.
      • Tatari F.
      • Brand S
      Compared to an active control condition, in persons with multiple sclerosis two different types of exercise training improved sleep and depression, but not fatigue, paresthesia, and intolerance of uncertainty.
      ) among PwMS. To illustrate, in a previous publication (
      • Sadeghi Bahmani D.
      • Razazian N.
      • Farnia V.
      • Alikhani M.
      • Tatari F.
      • Brand S
      Compared to an active control condition, in persons with multiple sclerosis two different types of exercise training improved sleep and depression, but not fatigue, paresthesia, and intolerance of uncertainty.
      ) we showed that compared to an active control condition, both endurance and coordinative training improved sleep complaints and symptoms of depression, while no improvements were observed for fatigue, paresthesia, and intolerance of uncertainty. However, to our knowledge, research on the influence of regular physical activity on emotion regulation, social competences, and social cognition is scarce. This is surprising, if we consider that following the science of evolutionary psychology (
      • Dunbar R.I.
      The social brain hypothesis and its implications for social evolution.
      ;
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      The social brain meets neuroimaging.
      ), our brain evolved and increased to its current dimensions and complexity to cope with social environments, including complex interaction information processing (
      • Cosmides L.
      • Tooby J.
      • Fiddick L.
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      Detecting cheaters.
      ).
      Social competences and social cognition are understood as the ability to infer the intentions, dispositions, and beliefs of other persons (
      • Phillips L.H.
      • Henry J.D.
      • Nouzova E.
      • Cooper C.
      • Radlak B.
      • Summers F
      Difficulties with emotion regulation in multiple sclerosis: links to executive function, mood, and quality of life.
      ;
      • Phillips L.H.
      • Saldias A.
      • McCarrey A.
      • et al.
      Attentional lapses, emotional regulation and quality of life in multiple sclerosis.
      ), whereas emotional regulation is understood as the ability to perceive, regulate, and express one's own emotions appropriately, and to perceive the emotions of others correctly (
      • Pfeifer J.H.
      • Blakemore S.J
      Adolescent social cognitive and affective neuroscience: past, present, and future.
      ;
      • Adolphs R.
      Cognitive neuroscience of human social behaviour.
      ;
      • Rindermann H.
      Emotionale Kompetenz-Fragebogen (Emotional Competences Questionnaire).
      ). Empathy is understood as the ability to recognize emotions that are being experienced by another person (
      • Decety J.
      • Jackson P.L.
      The functional architecture of human empathy.
      ;
      • Decety J.
      • Michalska K.J.
      • Akitsuki Y.
      • Lahey B.B
      Atypical empathic responses in adolescents with aggressive conduct disorder: a functional MRI investigation.
      ), and to share another person's emotions (
      • Sucksmith E.
      • Allison C.
      • Baron-Cohen S.
      • Chakrabarti B.
      • Hoekstra R.A
      Empathy and emotion recognition in people with autism, first-degree relatives, and controls.
      ).
      Social and emotional competencies are highly intertwined and particularly important in coping with the social environment. To illustrate,
      • Visted E.
      • Vollestad J.
      • Nielsen M.B.
      • Schanche E
      Emotion regulation in current and remitted depression: a systematic review and meta-analysis.
      ) speculated that among individuals with a history of major depressive disorders, poor emotion regulation and lower social competencies might be a latent risk factor for relapses. Moreover, functional deficits in emotion processing and the respective response selection have been associated with poor social functioning (
      • Marsh A.A.
      • Blair R.J.
      Deficits in facial affect recognition among antisocial populations: a meta-analysis.
      ). In the same vein, impairments in emotion processing have been associated with difficulties in building up relationships, resulting in rejection by peers and/or in solitary play, at least in children (
      • Marryat L.
      • Thompson L.
      • Minnis H.
      • Wilson P
      Associations between social isolation, pro-social behaviour and emotional development in preschool aged children: a population based survey of kindergarten staff.
      ). Further, among adolescents,
      • Ding C.
      • Zhang J.
      • Yang D
      A pathway to psychological difficulty: perceived chronic social adversity and its symptomatic reactions.
      ) underlined that perceived chronic social adversities may lead to symptoms of stress, along with depression and anxiety.
      As regards emotional competences and social cognition in PwMS,
      • Cotter J.
      • Firth J.
      • Enzinger C.
      • et al.
      Social cognition in multiple sclerosis: a systematic review and meta-analysis.
      ) performed a systematic review and meta-analysis and compared 722 PwMS with 635 healthy controls. Compared to healthy controls, PwMS had more deficits in facial emotion recognition and dimensions of empathy (
      • Cotter J.
      • Firth J.
      • Enzinger C.
      • et al.
      Social cognition in multiple sclerosis: a systematic review and meta-analysis.
      ). Further, deficits in social cognition were not as severe as those identified in individuals with schizophrenia or in other neurodegenerative disorders such as Parkinson's Disease, but worse than those reported in individuals with attention-deficit/hyperactivity disorders (ADHD) or with major depressive disorders. Similarly,
      • Chalah M.A.
      • Ayache S.S.
      Deficits in social cognition: an unveiled signature of multiple sclerosis.
      ) summarized in their review that deficits in social cognition appeared to be highly under recognized in PwMS, and that such scarce attention is astonishing, given that poor social cognition is associated with deficits in personal interactions and relationships.
      • Chalah M.A.
      • Ayache S.S.
      Deficits in social cognition: an unveiled signature of multiple sclerosis.
      ) further mentioned that little attention has been paid so far on social cognition in PwMS.
      • Phillips L.H.
      • Saldias A.
      • McCarrey A.
      • et al.
      Attentional lapses, emotional regulation and quality of life in multiple sclerosis.
      ) investigated the associations between attentional lapses and failures to use effective emotion regulation on quality of life in PwMS, and showed that both a higher rate of attentional lapses and failures in emotion regulation predicted lower scores of quality of life. Further,
      • Phillips L.H.
      • Henry J.D.
      • Nouzova E.
      • Cooper C.
      • Radlak B.
      • Summers F
      Difficulties with emotion regulation in multiple sclerosis: links to executive function, mood, and quality of life.
      ) showed that compared to 31 age- and gender-matched healthy controls, 31 PwMS reported more difficulties in emotion regulation and lower scores of quality of life.
      • Phillips L.H.
      • Henry J.D.
      • Nouzova E.
      • Cooper C.
      • Radlak B.
      • Summers F
      Difficulties with emotion regulation in multiple sclerosis: links to executive function, mood, and quality of life.
      ) further showed that symptoms of depression mediated the associations between poor emotion regulation and poor quality of life. We took this result into consideration and assessed symptoms of depression and fatigue as possible confounders.
      Given the importance of emotion regulation and social cognition, surprisingly, research on the influence of regular physical activity or single bouts of physical activity on emotion regulation and social competences is scarce, and there in none in PwMS.
      • Brand S.
      • Colledge F.
      • Ludyga S.
      • et al.
      Acute bouts of exercising improved mood, rumination and social interaction in inpatients with mental disorders.
      ) reported that a single intervention of physical activity improved the interests on social interaction, understood as a proxy of social competence among individuals with psychiatric issues.
      • Brand S.
      • Gerber M.
      • Colledge F.
      • Holsboer-Trachsler E.
      • Puhse U.
      • Ludyga S
      Acute exercise and emotion recognition in young adolescents.
      ) further reported that a single bout of physical activity, compared to a control condition, altered facial emotion recognition, understood as a proxy of social competences, among healthy adolescents. To our knowledge, this was the very first study to show the direct influence of physical activity on emotion processing and social cognition. While the
      • Brand S.
      • Gerber M.
      • Colledge F.
      • Holsboer-Trachsler E.
      • Puhse U.
      • Ludyga S
      Acute exercise and emotion recognition in young adolescents.
      ) had no direct evidence of the underlying psychophysiological processes to explain the direct influence of physical activity on emotion processing and social cognition, they speculated that perhaps more efficient cognitive-emotional processes in the prefrontal cortex (PFC) could be responsible for such a result (see also more details in the Discussion section).
      To summarize, there is some research on dimensions of emotion regulation and social cognition in PwMS (
      • Chalah M.A.
      • Ayache S.S.
      Deficits in social cognition: an unveiled signature of multiple sclerosis.
      ;
      • Cotter J.
      • Firth J.
      • Enzinger C.
      • et al.
      Social cognition in multiple sclerosis: a systematic review and meta-analysis.
      ;
      • Phillips L.H.
      • Henry J.D.
      • Nouzova E.
      • Cooper C.
      • Radlak B.
      • Summers F
      Difficulties with emotion regulation in multiple sclerosis: links to executive function, mood, and quality of life.
      ;
      • Phillips L.H.
      • Saldias A.
      • McCarrey A.
      • et al.
      Attentional lapses, emotional regulation and quality of life in multiple sclerosis.
      ) though it is surprising to see the small research efforts, if it is considered that emotion regulation and social cognition are tightly related to quality of life and interpersonal relationships. Further, as mentioned, while there is extant research that acute and regular physical activity favorably impact on cognitive processes such as attention and further dimensions of executive functions (
      • Ludyga S.
      • Brand S.
      • Gerber M.
      • et al.
      An event-related potential investigation of the acute effects of aerobic and coordinative exercise on inhibitory control in children with ADHD.
      ;
      • Ludyga S.
      • Gerber M.
      • Kamijo K.
      • Brand S.
      • Puhse U
      The effects of a school-based exercise program on neurophysiological indices of working memory operations in adolescents.
      a,
      • Ludyga S.
      • Gerber M.
      • Mucke M.
      • et al.
      The acute effects of aerobic exercise on cognitive flexibility and task-related heart rate variability in children with adhd and healthy controls.
      ;
      • Pesce C.
      Shifting the focus from quantitative to qualitative exercise characteristics in exercise and cognition research.
      ;
      • Best J.R.
      Effects of physical activity on children's executive function: contributions of experimental research on aerobic exercise.
      ;
      • Carson V.
      • Hunter S.
      • Kuzik N.
      • et al.
      Systematic review of physical activity and cognitive development in early childhood.
      ;
      • Shields G.S.
      • Sazma M.A.
      • Yonelinas A.P
      The effects of acute stress on core executive functions: a meta-analysis and comparison with cortisol.
      ;
      • van Uffelen J.G.
      • Chin A.P.M.J.
      • Hopman-Rock M.
      • van Mechelen W
      The effects of exercise on cognition in older adults with and without cognitive decline: a systematic review.
      ;
      • Voss M.W.
      • Heo S.
      • Prakash R.S.
      • et al.
      The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: results of a one-year exercise intervention.
      ) research on the impact of acute and regular physical activity on emotion recognition and social cognition is scarce for healthy samples and non-existent for PwMS. Accordingly, the aims of the present study were to fill these gaps of knowledge and to investigate a possible new avenue to improve emotion regulation and social cognition in PwMS. The research question was if, and if so, to what extent two types of regular physical activity (endurance training; coordinative training) improve emotion regulation and empathy in PwMS, compared to an active control condition.

      2. Methods

      2.1 Procedures

      A total of 145 female PwMS of the MS Society of Kermanshah province, located in the Farabi University-Hospital of the Kermanshah University of Medical Sciences (KUMS; Kermanshah, Iran) were approached to participate in the present intervention study. Eligible participants were fully informed about the aims of the study and the confidential nature of the data handling. Thereafter, participants signed the written informed consent. Next, participants were randomly assigned either to endurance training (ET), coordinative training (CT), or to an active control condition (ACC). At baseline, and eight weeks later at the end of study, participants completed questionnaires covering emotion regulation, empathy, and depression and fatigue (see below). Experts rated participants’ degree of impairment with the Expanded Disability Status Scale (EDSS) (
      • Kurtzke J.F.
      Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).
      ). Irrespective from the study conditions, sessions took place 3 times/week for about 45–60 min for eight consecutive weeks. The ethical committee of the Kermanshah University of Medical Sciences (KUMS; Kermanshah, Iran; IRCT 2016062423705N4;ww.irct.ir; KUMS.REC.1395.127) approved the study, which was performed in accordance with the ethical principles laid down in the seventh and current edition (2013) of the Declaration of Helsinki.
      The present data are part of an ongoing larger study on the impact of regular physical activity interventions on physical and psychological well-being in PwMS (
      • Sadeghi Bahmani D.
      • Razazian N.
      • Farnia V.
      • Alikhani M.
      • Tatari F.
      • Brand S
      Compared to an active control condition, in persons with multiple sclerosis two different types of exercise training improved sleep and depression, but not fatigue, paresthesia, and intolerance of uncertainty.
      ), though, the present data are novel.

      2.2 Participants

      A total of 92 female PwMS were consecutively enrolled in the study. Fig. 1 is the CONSORT flow chart and shows the number of assessed participants, the number of included and excluded participants, along with the number of randomized, allocated, and analyzed participants. Inclusion criteria were: 1. Age between 18 and 65 years; 2. Status of MS, as ascertained by a trained neurologist and based on Mc Donald's criteria; 3. EDSS score < 6; 4. Willing and able to comply with the study conditions; 5. Signed written informed consent. Exclusion criteria were: 1. Other neurological disease; 2. Severe psychiatric comorbidities based on a clinical psychiatric interview (
      • Sheehan D.V.
      • Lecrubier Y.
      • Sheehan K.H.
      • et al.
      The mini-international neuropsychiatric interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.
      ); 3. Acute suicidality; 4. Musculoskeletal issues which did not allow regular PA; 5. Participants withdraw from the study more than 3 sessions; 6. The principle investigator excluded participants from the study, if a participant showed adverse events, which might have been associated with the interventions. 7. Undergoing further PA, psychotherapy, or undergoing surgery; 8. Pregnancy and/or breast feeding.
      Fig 1
      Fig. 1Recruitment, eligibility, randomization, patients’ group assignments, and number of patients per group at baseline, week 4 and week 8.
      We have excluded women who were pregnant, as changes in hormones, and sleep and physical activity patterns could have biased the present pattern of results (cf.
      • Jahangard L.
      • Mikoteit T.
      • Bahiraei S.
      • et al.
      Prenatal and postnatal hair steroid levels predict post-partum depression 12 weeks after delivery.
      ). Further, even though the physical activity interventions were safe and easy to comply, we did not want to risk accidents and injuries to the expecting mother and her unborn baby. Similarly, we excluded breastfeeding women, as breastfeeding mothers might have had irregular sleep-wake and physical activity patterns.
      No sample size calculation was performed for the current explorative study and its outcomes, and the sample size was defined in the previous study (
      • Sadeghi Bahmani D.
      • Razazian N.
      • Farnia V.
      • Alikhani M.
      • Tatari F.
      • Brand S
      Compared to an active control condition, in persons with multiple sclerosis two different types of exercise training improved sleep and depression, but not fatigue, paresthesia, and intolerance of uncertainty.
      ).

      2.2.1 Randomization

      Randomization occurred with the software randomization.com. Based on this list, a psychologist not otherwise involved in the study prepared 3 × 15 envelops with the specific study conditions. Envelops were sealed, with no further identification, put in an opaque and closed ballot box and stirred. Next, the responsible drew an envelope and assigned participants to one of the three study conditions. Once an envelope was drawn, it was put aside. Fig. 1 shows the CONSORT flow-chart of participants’ study allocations. Randomization occurred after the initial assessment.

      2.3 Tools

      2.3.1 Sociodemographic and MS-related information

      Participants reported age, and MS-related information such as duration of MS and medication regimen were obtained from medical records.
      Experts rating participants’ EDSS scores were blind to participants’ study condition assignments.

      2.3.2 Emotion regulation

      As already described elsewhere (
      • Brand S.
      • Kirov R.
      • Kalak N.
      • et al.
      Poor sleep is related to lower emotional competence among adolescents.
      ), to assess emotion regulation, we used the Emotionale–Kompetenz–Fragebogen (emotional competencies inventory (
      • Rindermann H.
      Emotionale Kompetenz-Fragebogen (Emotional Competences Questionnaire).
      )). The Farsi version has been translated and psychometric properties were satisfactory (
      • Jahangard L.
      • Sadeghi A.
      • Ahmadpanah M.
      • et al.
      Influence of adjuvant omega-3-polyunsaturated fatty acids on depression, sleep, and emotion regulation among outpatients with major depressive disorders - Results from a double-blind, randomized and placebo-controlled clinical trial.
      ). The inventory consists of 62 items and assesses the following four dimensions: (a) perception and acknowledgement of own emotions (“Sometimes I feel sad without knowing why”); (b) regulation and control of own emotions (“When I feel myself getting angry, I know how to cool down again”); (c) emotional expressivity (“I can express my feelings very well”); and (d) perception of others’ emotions (“I can perceive and describe my friends’ emotions very well”). Answers are on five-point Likert scales from 1 (never/not at all true) to 5 (practically always/definitely true). Higher scores reflect a higher position on each of the dimensions described above. The overall score reflects general competency in emotion regulation (Cronbach's alpha = 0.87).

      2.3.3 Empathy

      To assess empathy, that is, the ability to imagine what another person is currently feeling and thinking, the Reading the Mind in the Eyes (RME) test was applied (
      • 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.
      ). The Farsi version has been translated, and psychometric properties were satisfactory (
      • Khorashad B.S.
      • Baron-Cohen S.
      • Roshan G.M.
      • et al.
      The "Reading the Mind in the Eyes" test: investigation of psychometric properties and test-retest reliability of the Persian version.
      ). Briefly, the test consists of 36 vignettes showing the eye region in black-and-white. The rationale underlying the test is that people preferentially attend to the eyes and extract complex meaning from them as salient cues in human social communication and social categorization (
      • Emery N.J.
      The eyes have it: the neuroethology, function and evolution of social gaze.
      ;
      • Zebrowitz L.
      • Finally A.
      • Favor Faces Find
      ). Every vignette has four alternative descriptors of what the person in the vignette might be thinking or feeling. Each vignette is presented separately, and participants have to choose among the four descriptors. For every correct answer, one point is given; the maximum score is 36 points. Vignettes are also divided into pleasant mental states (n = 26; e.g., playful, friendly, fantasizing) and unpleasant mental states (n = 10; e.g., distrustful, preoccupied, hostile; Cronbach's alpha = 0.79).

      2.3.4 Depressive symptoms

      To assess symptoms of depression, we used the Beck Depression Inventory-Fast Screen (BDI-FS) (
      • Benedict R.H.
      • Fishman I.
      • McClellan M.M.
      • Bakshi R.
      • Weinstock-Guttman B
      Validity of the beck depression inventory-fast screen in multiple sclerosis.
      ). The BDI-FS is a brief self-report inventory designed to evaluate depression in patients with medical illness. It consists of seven items, and every item has a set of four possible responses, representing different levels of symptom severity (e.g., or sadness: 0 = “I don't feel sad”; 1 = “I feel sad”; 2 = “I'm sad all the time and I can't snap out of it”. 3 = “I'm so sad/unhappy, that I can't stand it”). Higher scores reflect a greater severity of depressive symptoms (range:0–21). Cronbach's alpha = 0.87.

      2.3.5 Fatigue

      To assess the level of fatigue, participants completed the Fatigue Severity Scale (FSS
      • Krupp L.B.
      • LaRocca N.G.
      • Muir-Nash J.
      • Steinberg A.D
      The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus.
      ). The FSS consists of nine items, and answers are given on 7-point rating scales ranging from 1 (=not at all) to 7 (=definitively/almost always), with higher scores reflecting higher levels of fatigue. Cronbach's alpha=0.91.

      2.4 Interventions

      2.4.1 Endurance training

      As previously described (
      • Sadeghi Bahmani D.
      • Razazian N.
      • Farnia V.
      • Alikhani M.
      • Tatari F.
      • Brand S
      Compared to an active control condition, in persons with multiple sclerosis two different types of exercise training improved sleep and depression, but not fatigue, paresthesia, and intolerance of uncertainty.
      ), endurance training condition lasted for eight consecutive weeks and consisted of three weekly supervised, guided group sessions per week. The sessions lasted 30–45 min in duration. After 5 min of warming-up and stretching, participants exercised for 25–35 min on treadmill, exercise bicycles or walking/jogging overground. Participants were encouraged to keep the pace during the intervention, though, they were allowed to pause individually for 1–2 min. After the intervention, it followed a cooling down of 5 min. At the end of a session, participants should have had the feeling to be slightly exhausted, but not severely exhausted (4–6 points of intensity on the Borg scale (
      • Borg G.
      Borg's Perceived Exertion and Pain Scales.
      )). Professional instructors monitored the sessions and participants’ level of performance and exhaustion.

      2.4.2 Coordinative training

      As previously described (
      • Sadeghi Bahmani D.
      • Razazian N.
      • Farnia V.
      • Alikhani M.
      • Tatari F.
      • Brand S
      Compared to an active control condition, in persons with multiple sclerosis two different types of exercise training improved sleep and depression, but not fatigue, paresthesia, and intolerance of uncertainty.
      ), coordinative training consisted of three supervised, guided group sessions per week for eight weeks. The sessions lasted 30–45 min in duration. After 5 min of warming up, exercises focused on CT such as balancing on a small bar, mirroring and imitating movements of others (such as dancing steps), balancing balls, ‘football-tennis’, balancing with closed eyes on a rope on the floor and similar exercises. The CT required a higher level of object control and locomotor skills as well as interactions with other participants. Such exercise characteristics are suggested to increase coordinative demands and cognitive engagement (
      • Pesce C.
      Shifting the focus from quantitative to qualitative exercise characteristics in exercise and cognition research.
      ;
      • Best J.R.
      Effects of physical activity on children's executive function: contributions of experimental research on aerobic exercise.
      ). At the end of a session, participants should have had the feeling to be slightly exhausted, but not severely exhausted (4–6 points of intensity on the Borg scale (
      • Borg G.
      Borg's Perceived Exertion and Pain Scales.
      )). Professional instructors monitored the sessions and level of performance and exhaustion. Cooling down lasted for about 5 min.

      2.4.3 Active control condition (ACC)

      As previously described (
      • Sadeghi Bahmani D.
      • Razazian N.
      • Farnia V.
      • Alikhani M.
      • Tatari F.
      • Brand S
      Compared to an active control condition, in persons with multiple sclerosis two different types of exercise training improved sleep and depression, but not fatigue, paresthesia, and intolerance of uncertainty.
      ), for eight consecutive weeks, participants of the ACC met three times/week for 30–45 min/session at the hospital center to ensure that frequency, duration, and the degree social contacts of the control condition were identical to the endurance and resistance training conditions. The control condition was not a ‘bona fide’ psychotherapeutic intervention, which would have been actually intended to elicit change (
      • Goyal M.
      • Singh S.
      • Sibinga E.M.
      • et al.
      Meditation programs for psychological stress and well-being: a systematic review and meta-analysis.
      ;
      • Wampold B.E.
      • Mondin G.W.
      • Moody M.
      • Stich F.
      • Benson K.
      • Ahn H-n
      A meta-analysis of outcome studies comparing bona fide psychotherapies: empiricially, "all must have prizes".
      ;
      • Jasbi M.
      • Sadeghi Bahmani D.
      • Karami G.
      • et al.
      Influence of adjuvant mindfulness-based cognitive therapy (MBCT) on symptoms of post-traumatic stress disorder (PTSD) in veterans - results from a randomized control study.
      ). Most importantly, in the control condition, topics such as successful coping strategies were not treated and not proactively proposed by the clinical psychologist responsible to monitor the content of the control conditions. Rather, participants were encouraged to proposing and exchanging daily experiences (
      • Sadeghi Bahmani D.
      • Razazian N.
      • Farnia V.
      • Alikhani M.
      • Tatari F.
      • Brand S
      Compared to an active control condition, in persons with multiple sclerosis two different types of exercise training improved sleep and depression, but not fatigue, paresthesia, and intolerance of uncertainty.
      ).

      2.5 Statistical analysis

      Data were analyzed per protocol. We first compared study completers and study non-completers on as regards socio-demographic, illness-related and psychological dimensions, using a series of t-tests and χ2-tests. We then compared initial differences in sociodemographic data between the three groups using a series of χ2-tests. We examined changes over time between groups using a series of mixed factor ANCOVAs on emotion regulation and empathy as dependent variables. The mixed factors were Time (baseline, week 8) and Group (ET, CT, ACC), and depression and fatigue were covariates. The nominal level of significance was set at alpha <  05. Effect sizes for F-statistics were reported as partial eta squared (ηp2), with 0.01 <ηp2 < 0.059 indicating small [S], 0.06 < ηp2 < 0.139 indicating medium [M], and ηp2  ≥  0.14 indicating large [L] effect sizes. Cohen's d effect sizes were reported for the pre-post change within each of the three groups, and effect sizes were reported with Cohen's d (
      • Cohen J.
      Statistical Power Analysis For the Behavioral Sciences.
      ) values ranges: ds 0–0.19: trivial effect sizes; ds 0.20–0.49: small effect sizes; ds: 0.50–0.79: medium effect sizes; ds: 0.80 and greater: large effect sizes. Statistical analyses were performed with SPSS® 25.0 (IBM Corporation, Armonk NY, USA) for Apple Mac®.

      3. Results

      3.1 Completers and non-completers

      Completers (n = 71) and non-completers (n = 21) did not differ in age, EDSS, emotion regulation, empathy, depression, or fatigue (all t's < 1.2, p's > 0.42).

      3.2 Sociodemographic and MS-related information

      Participants in the three groups did not descriptively nor statistically initially differ in age, civil status, and educational level (F and all χ2-tests < 1.00, p's > 0.50). There was a significant Group effect on EDSS (F(2, 70) = 3.62, p = .032). The post-hoc analysis indicated that participants in the coordinative condition had higher EDSS scores than participants in the ACC (Table 1).
      Table 1Sociodemographic and clinical data of participants, separately for participants in the coordination, the workout and the active control condition.
      DimensionsGroups
      CoordinationWorkoutActive control
      N242621
      M (SD)M (SD)M (SD)
      Age (years)39.17 (8.66)37.96 (8.69)37.90 (9.91)
      EDSS3.38 (1.87)2.46 (1.50)2.02 (1.84)
      Disease duration (years)8.13 (6.37)6.92 (6.81)7.21 (6.57)
      n/nn/nn/n
      Civil status (married/single)12/1220/615/6
      Highest educational level (high school/higher education)19/520/617/4
      Notes: EDSS = Expanded Disability Status Scale.

      3.3 Emotion regulation and empathy

      Table 2, Table 3, Table 4 report the descriptive and inferential statistical indices regarding group by time interactions and main effects on emotion regulation and empathy (Reading the Mind in the Eyes) measures.
      Table 2Descriptive statistics of dimensions of emotion regulation and empathy, separately for the two time points (baseline; week 6/study end) for the three study conditions (endurance training; coordinative training; active control condition).
      Groups
      Groups/study conditionsEndurance trainingCoordinative trainingActive control condition
      Time pointsBaselineStudy endBaselineStudy endBaselineStudy end
      N262624242121
      M (SD)M (SD)M (SD)M (SD)M (SD)M (SD)M (SD)
      Emotion regulation
      Perception and Acknowledgement46.19 (8.42)47.50 (8.81)47.68 (14.62)48.00 (11.55)47.48 (10.35)48.29 (6.19)
      Regulation and Control37.16 (9.47)40.23 (9.53)37.67 (11.42)40.67 (9.87)37.38 (8.33)36.91 (8.97)
      Emotional Expressivity40.50 (7.28)39.73 (8.15)39.87 (11.18)40.00 (7.28)41.62 (10.35)42.24 (8.37)
      Empathy31.50 (6.74)34.97 (6.40)33.46 (9.29)37.71 (9.04)37.67 (12.18)37.00 (8.75)
      Reading the Mind in the Eyes
       Total score17.28 (5.08)17.76 (5.61)15.29 (5.39)16.54 (4.99)16.38 (4.28)15.67 (4.03)
       Positive emotions5.00 (1.83)4.20 (1.61)4.71 (1.99)4.33 (1.88)4.43 (1.91)4.29 (1.93)
       Negative emotions13.08 (4.11)12.76 (4.44)11.33 (3.76)11.83 (3.95)12.09 (3.45)11.24 (2.88)
      Table 3Inferential statistical indices: overview of dimensions of emotion regulation.
      Factors
      TimeGroupTime by Group interaction
      FPartial eta2FPartial eta2FPartial eta2
      Degrees of freedom1, 661, 662, 66
      Emotion regulation
       Perception and Acknowledgement0.69.010 [S]0.46.014 [S]0.66.002 [T]
       Regulation and Control13.52***.166 [L]0.28.008 [T]5.04**.129 [M]
       Emotional Expressivity0.03.000 [T]1.23.035 [M]1.23.035 [S]
       Empathy5.65*.078 [M]1.55.023 [S]2.99*.071 [M]
      Reading the Mind in the Eyes
       Total score0.31.005 [T]1.07.031 [S]0.85.025 [S]
       Positive emotions2.99.049 [S]0.12.004 [T]0.96.028 [S]
       Negative emotions0.20.003 [T]1.34.038 [S]0.45.017 [S]
      Notes: Statistics always controlling for symptoms of depression and symptoms of fatigue. * = p < .05; ** = p < .01; *** = p < .001. [T] = trivial effect size; [S] = small effect size; [M] = medium effect size; [L] = large effect size.
      Table 4Effect sizes for mean comparisons (emotion regulation: Perception and Acknowledgement; Regulation and Control; Emotional Expressivity; Empathy; Reading the mind in the eyes/Empathy; positive and negative emotions) from baseline to the study end, separately for the three groups (workout and coordination, and active control groups).
      Groups
      Endurance trainingCoordinative trainingActive control condition
      Cohen's d's: Baseline vs. study end
      Emotion regulation
      Perception and Acknowledgement0.15 (T)0.02 (T)0.08 (T)
      Regulation and Control0.52 (M)0.50 (M)0.05 (T)
      Emotional Expressivity0.10 (T)0.01 (T)0.07 (T)
      Empathy0.52 (M)0.51 (M)0.06 (T)
      Reading the Mind in the Eyes
       Total score0.09 (T)0.24 (S)0.17 (T)
       Positive emotions0.46 (S)0.09 (T)0.07 (T)
        Negative emotions0.07 (T)0.13 (T)0.28 (S)
      Notes: (T) = trivial effect size; (S) = small effect size; (M) = medium effect size.
      Regulation and control of emotions, and empathy improved over time, but more so in the two physical activity intervention conditions, compared to the active control condition (significant interactions with medium effect size).
      For Perception and Acknowledgment of emotions, Emotional expressivity, and for empathy, as assessed with the Reading the Mind in the Eyes test, no statistical or descriptive mean differences between the three study conditions and over time were observed. Note that all statistical procedures were performed controlling for symptoms of depression and fatigue.
      Single effect size calculations further confirmed that dimensions of Regulation and Control of emotions and Empathy increased in the endurance training and coordinative training condition, but not in the active control condition.

      4. Discussion

      The key findings of the present study were that both endurance and coordinative training lasting for eight weeks improved dimensions of emotion regulation and empathy, compared to an active control condition, and even, when controlling for symptoms of depression and fatigue among a sample of female PwMS. The present study adds in an important way to the sparse research on the influence of regular physical activity on dimensions of emotion regulation and social cognition in PwMS.
      This was an exploratory study and no hypotheses were formulated a priori, but the data analyses indicated that regular physical activity might have the power to favorably influence dimensions of emotion regulation and empathy. However, as shown in Table 2, Table 3, Table 4 improvements were only observed in the dimensions of regulation and control of emotions and empathy. By contrast, no statistically or descriptively significant mean differences were observed for perception and acknowledgement and emotional expressivity, and for Empathy, as measured with the Reading the Mind in the Eyes test.
      Thus, while for the very first time, we were able to show that regular physical activity improved some, but not all dimensions of emotion regulation and empathy as a proxy of social cognition, the quality of the data does not allow a deeper understanding, as to why this happened. For want of data, we advance the following explanations:
      First,
      • Brand S.
      • Colledge F.
      • Ludyga S.
      • et al.
      Acute bouts of exercising improved mood, rumination and social interaction in inpatients with mental disorders.
      ) showed among a sample of inpatients with psychiatric issues that already single bouts of physical activity interventions reduced rumination and increased the interest on social interactions. Next, the intervention of 35 min of moderate exercising improved the performance of facial emotion recognition, compared to a passive control condition, at least among a sample of healthy adolescents (
      • Brand S.
      • Gerber M.
      • Colledge F.
      • Holsboer-Trachsler E.
      • Puhse U.
      • Ludyga S
      Acute exercise and emotion recognition in young adolescents.
      ).
      Overall, these studies suggest that emotional information processing appear to favorably improve both after a single bout of exercising or after regular physical activity. Likewise, we speculate that similar emotional processes occurred also in female PwMS of the present study. Importantly, statistical comparisons of changes of emotion regulation and empathy from baseline to the end of the study were statistically controlled for symptoms of depression and fatigue; in doing so, we avoided that possible improvements in emotion regulation and social cognition would have been associated with improvements in depression and fatigue. In this regard, there is some evidence that regular physical activity improved symptoms of depression and fatigue in PwMS (
      • Sadeghi Bahmani D.
      • Kesselring J.
      • Papadimitriou M.
      • et al.
      In patients with multiple sclerosis, both objective and subjective sleep, depression, fatigue, and paresthesia improved after 3 weeks of regular exercise.
      ;
      • Razazian N.
      • Yavari Z.
      • Farnia V.
      • et al.
      Exercising impacts on fatigue, depression, and paresthesia in female patients with multiple sclerosis.
      ).
      Second, there is substantive evidence showing that (acute) exercise enhances performance on tasks that rely on the prefrontal cortex, such as those that involve executive functions (
      • Ludyga S.
      • Gerber M.
      • Brand S.
      • Holsboer-Trachsler E.
      • Puhse U
      Acute effects of moderate aerobic exercise on specific aspects of executive function in different age and fitness groups: a meta-analysis.
      ). Given that the prefrontal cortex plays an important role in emotion processing (
      • Etkin A.
      • Egner T.
      • Kalisch R
      Emotional processing in anterior cingulate and medial prefrontal cortex.
      ), it seems reasonable to suggest that exercise-induced improvements might be due to favorable activation patterns within this region (
      • Fumoto M.
      • Oshima T.
      • Kamiya K.
      • et al.
      Ventral prefrontal cortex and serotonergic system activation during pedaling exercise induces negative mood improvement and increased alpha band in EEG.
      ). Likewise, it can be supposed that in the present study, dimensions of emotion regulation and empathy were associated with such improved cognitive processes, although this does not explain why such improvements were not observed for perception and acknowledgement, emotional expressivity, and empathy, as assessed with the Reading the Mind in the Eyes-test. However, in a broader extent,
      • Tottenham N.
      • Hare T.A.
      • Casey B.J
      Behavioral assessment of emotion discrimination, emotion regulation, and cognitive control in childhood, adolescence, and adulthood.
      ). define emotional competencies as the ability to maintain cognitive control in the context of potentially interfering emotional information. Accordingly, cognitive processes continuously modulate and regulate emotional processes (
      • Tottenham N.
      • Hare T.A.
      • Casey B.J
      Behavioral assessment of emotion discrimination, emotion regulation, and cognitive control in childhood, adolescence, and adulthood.
      ). Thus, it is likely that emotion generation and emotion regulation are by no means exclusively emotional processes; rather, these involve a sophisticated and highly intertwined cognition–emotion interaction. As regards the present study, it remains unclear whether or to what extent the cognition–emotion interaction might be associated. Other researchers (
      • Kirov R.
      • Brand S.
      • Kolev V.
      • Yordanova J
      The sleeping brain and the neural basis of emotions.
      ;
      • Lindquist K.A.
      • Barrett L.F.
      A functional architecture of the human brain: emerging insights from the science of emotion.
      ;
      • Lindquist K.A.
      • Wager T.D.
      • Kober H.
      • Bliss-Moreau E.
      • Barrett L.F
      The brain basis of emotion: a meta-analytic review.
      ) have emphasized that emotions are generated, controlled, and regulated within different brain regions, and we speculate that brain regions, such as the prefrontal cortex and the amygdala, might be up- or downregulated during and immediately after an acute bout of exercising, depending on the intensity.
      Third and again speculatively, one might assume that regular physical activity might have triggered a different degree of cognitive involvement (
      • Tottenham N.
      • Hare T.A.
      • Casey B.J
      Behavioral assessment of emotion discrimination, emotion regulation, and cognitive control in childhood, adolescence, and adulthood.
      ;
      • Phillips M.L.
      • Drevets W.C.
      • Rauch S.L.
      • Lane R
      Neurobiology of emotion perception I: the neural basis of normal emotion perception.
      ), different stages of emotion regulation (
      • Gross J.J
      Emotion regulation: taking stock and moving forward.
      ;
      • Gross J.J.
      • Sheppes G.
      • Urry H.L
      Cognition and emotion lecture at the 2010 SPSP emotion preconference.
      ), or differential activation of neural networks (
      • Lindquist K.A.
      • Wager T.D.
      • Kober H.
      • Bliss-Moreau E.
      • Barrett L.F
      The brain basis of emotion: a meta-analytic review.
      ;
      • Casey B.J.
      • Durston S.
      From behavior to cognition to the brain and back: what have we learned from functional imaging studies of attention deficit hyperactivity disorder.
      ). In this view, it is conceivable that completing the questionnaires and tasks might have triggered differential activation of neural networks: Specifically, completing the Reading the Mind in the Eyes involves linguistic, and semantic emotional memory processes, which might have led to some zero-results.
      Fourth, focusing again on brain networks and specifically on prefrontal network, wake-EEG-studies with individuals with major depressive disorders showed that symptom improvements were associated with both the down-regulation of the right prefrontal cortex associated with negative emotion perception and negative emotion generation, and the upregulation of the left prefrontal cortex associated with positive emotion perception and positive emotion generation (
      • Haghighi M.
      • Ludyga S.
      • Rahimi B.
      • et al.
      In patients suffering from major depressive disorders, quantitative EEG showed favorable changes in left and right prefrontal cortex.
      ;
      • Davidson R.J
      Affective neuroscience and psychophysiology: toward a synthesis.
      ;
      • Davidson R.J.
      • Jackson D.C.
      • Kalin N.H
      Emotion, plasticity, context, and regulation: perspectives from affective neuroscience.
      ;
      • Davidson R.J.
      • McEwen B.S.
      Social influences on neuroplasticity: stress and interventions to promote well-being.
      ;
      • Davidson R.J.
      • Pizzagalli D.
      • Nitschke J.B.
      • Putnam K
      Depression: perspectives from affective neuroscience.
      ;
      • Sutton S.K.
      • Davidson R.J.
      Prefrontal brain electrical asymmetry predicts the evaluation of affective stimuli.
      ). However, again, the quality of the present data does not allow to further testing these hypotheses among the present sample.
      The results of the active control condition demand some attention. Although participants of the ACC met 3×/week for 30–45 min/session, no changes in participants’ emotion regulation and empathy were observed. It follows that mere social interactions and social contact do not necessarily lead to changes (neither improvements, nor decreases) in an individual's cognitive-emotional and social information processing.
      Despite the novelty of the results, the following limitations warrant against the overgeneralization of the results. First, exclusively female PwMS were assessed, and accordingly it remains unclear, if the pattern of results is also transferrable to male or to pediatric PwMS. Second, we fully relied on participants’ self-ratings, while it would have been interesting to assess, if people living with the participants did observe changes in participants’ behavior, and specifically in their degree of empathy. It follows that future studies might introduce the so-called one-for-many procedure (
      • Holtzman N.S.
      • Strube M.J
      Above and beyond short-term mating, long-term mating is uniquely tied to human personality.
      ) , where family members and peers are asked to evaluate behavior of a study participant. Third, latent and unassessed factors such as sleep, stress steroid concentrations, or critical life events could have biased two or more variables in the same or opposite directions. As regards sleep, this dimension was already introduced and discussed in the previous study (
      • Sadeghi Bahmani D.
      • Razazian N.
      • Farnia V.
      • Alikhani M.
      • Tatari F.
      • Brand S
      Compared to an active control condition, in persons with multiple sclerosis two different types of exercise training improved sleep and depression, but not fatigue, paresthesia, and intolerance of uncertainty.
      ); further, it appears that symptoms of insomnia and performance of facial recognition were completely unrelated. (
      • Brand S.
      • Schilling R.
      • Ludyga S.
      • et al.
      Further evidence of the zero-association between symptoms of insomnia and facial emotion recognition-results from a sample of adults in their late 30s.
      ) It follows that sleep quality might have been a confounder, though, results from previous studies rather rule out this possibility. Fourth, a follow-up would have allowed to evaluate, if and to what extent the effects observed at the end of the present study would have remained stable or would have vanished over time.

      5. Conclusions

      The present study provides initial evidence that regular physical activity might favorably impact dimensions of emotion regulation and empathy among PwMS. This is clinically relevant for the quality of life of persons with MS because, also because regular physical activity is an easy and cost-effective intervention with virtually no side-effects and virtually no restrictions.

      Declaration of Competing Interest

      All authors declare no conflicts of interest. The entire study has been performed without external funding.

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