Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with physical, emotional, and cognitive symptoms that substantially reduce participants’ overall quality of life (Amato et al., 2001; Benedict et al., 2005). Patients typically present with a relapsing-remitting course of the disease that is characterized by periodic exacerbations, followed by recovery and stretches of relative stability (Lublin and Reingold, 1996; Ajzen, 2013). The spectrum of the disease itself generates a range of manifestations and severities which mainly concern the central nervous system (Hauser and Oksenberg, 2006; Trapp and Nave, 2008).

Physical Activity (PA) may be interesting in people with MS. Initially, PA was discouraged in people with MS due to concerns about fatigue and temperature sensitivity (Petajan et al., 1996; Dalgas et al., 2008). However, a number of clinical investigators revealed that exercise is, in fact, beneficial for MS patients’ as it may slow down the disease process and ensure the stability and management of its symptoms (Hessen et al., 2006; Motl and Gosney, 2008; Khan et al., 2014) as long as it is designed to “activate working muscles, but avoid overload that results in conduction block” (Petajan and White, 1999). Physical activity is considered as a possible behavioral approach for managing MS symptoms and secondary health problems associated with an inactive lifestyle (Petajan et al., 1996; Dalgas et al., 2008; Motl and Gosney, 2008; Asano et al., 2009; Motl and Pilutti, 2012; Carter et al., 2014; Sá, 2014; Turner et al., 2015).

Recent MRI studies carried out on Murine animal models (Jensen et al., 2018) and human models (Negaresh et al., 2019) tend to demonstrate that PA practice would enhance axon remyelination. Moreover, PA participation may increase general self-efficacy (Kasser, 2009). The latter affects positively the psychological, psychosocial and cognitive outcomes (Barnwell and Kavanagh, 1997; Dlugonski et al., 2012; Ellis and Motl, 2013; Hughes et al., 2015). And yet this population is largely sedentary and inactive compared with the general population (Motl et al., 2006), even if they are mildly affected by MS (Ng and Kent-Braun, 1997; Stuifbergen and Roberts, 1997) and 80% of them do not meet recommended levels of moderate-to-vigorous physical activity (MVPA) (Motl, 2014). Research efforts have implicated several physical, mental and environmental barriers limited their participation in PA (Crayton et al., 2004; Dodd et al., 2006; Kerdoncuff et al., 2006; Aminian et al., 2019). This reality highlights the importance of developing behavior change interventions aiming at helping the patients to initiate and sustain his practice.

Many psychological interventions used with people with chronic conditions such as MS propose a deficit-oriented model in which psychotherapists assess and treat psychopathology and disease associated symptoms, without exploring and developing patients’ resources, strengths and positive emotions. Few interventions have explicitly attended to the positive resources of people with MS. The field of Positive Psychology (PP) proposes several empirically based interventions that focus on clients’ positive attributes, strengths, and positive emotions (Csillik, 2015). Positive psychology interventions (PPIs) are treatment methods or intentional activities that aim to cultivate positive feelings, behaviors, or cognitions. These forms of interventions (e.g., positive psychotherapy, well-being therapy, mindfulness based-interventions, etc.) consist mainly of structured forms of volitional activities (Sin and Lyubomirsky, 2009). Positive psychology interventions refer to systematic approaches to overcome everyday challenges and life’s difficulties and psychopathology by using clients’ strengths and by cultivating positive emotions. The aim of the PPIs is thus both to relieve suffering and psychopathology and increase well-being. PPIs essentially involve the reeducation of attention and memory (Rashid, 2009), by practicing mindfulness, kindness and forgiveness, expressing gratitude and using personal strengths etc. The PPIs have shown their effectiveness in increasing well-being, both in the general population and clinical samples (Sin and Lyubomirsky, 2009; Bolier et al., 2013). To date, to our knowledge no published study assessed the efficacy of positive psychology interventions associated with physical activity in people with MS. One of the first positive psychology interventions, Mindfulness or Meditation, “a family of self-regulation practices that focus on training attention and awareness in order to bring mental processes under greater voluntary control” (Walsh and Shapiro, 2006, p. 228), has shown encouraging results in relation to improving physical and mental health problems and increasing well-being (Brand et al., 2012; Davidson and McEwen, 2012; Willekens et al., 2018). One of the most popular meditative practices nowadays is mindfulness meditation, which cultivates a state of non-judgmental awareness of the present moment. Mindfulness is a practice that originate from ancient Buddhist meditation techniques, but have since been empirically tested, manualized, and adapted for use in a diverse range of clinical settings (Kabat-Zinn, 2003) so that it is now part of mainstream psychotherapeutic interventions (Williams and Kabat-Zinn, 2011).

In the context of MS, Mindfulness may help people to become conscious of repetitive perceptions about the past or disturbance thoughts about the unknown future without necessarily engaging or pursuing them. Nydahl (2012) has shown that the mindfulness training program has a positive effect on MS patients. When studying the idea that emotions are transitory and constantly changing, the intervention generates confidence in their ability to shape their lives. This training can minimize the emotional and psychological impact of chronically ill patients and help improve clinical conditions, such as reducing fatigue (Trojan et al., 2007; Bol et al., 2009). Furthermore, Mindfulness might be a way of dealing with varying common visible (mainly physical) and hidden MS symptoms at the same time (Senders et al., 2014). Indeed, Mindful people with MS reported reduced emotional distress (Hart et al., 2005; Mohr et al., 2007; Van Kessel et al., 2008; Bogosian et al., 2015), improved balance (Mills and Allen, 2000; Burschka et al., 2014), reduced pain (Tavee et al., 2011), improved quality of life and reduced depression and fatigue (Grossman et al., 2010). Mindful based-interventions (MBIs) might also positively affect accuracy of perception, acceptance of intractable health-related changes, realistic sense of control, and appreciation of available life experiences.

Implementation intention (II) (or if-then plan) was introduced by Gollwitzer (1999). The concept of II is rooted in the theory of self-regulation (Leventhal et al., 1998). The latter is so distinguished from the concept of goal intention. Goal intention specify what one wants to achieve (i.g., “I intend to achieve X!”). However, using this strategy people generally fail to translate their intention into action as research has perceived a pervasive gap between the intention formulated and the desired behavior (Ajzen, 1991). II, defined as a self-regulatory strategy in which a psychological link is established between a predefined future situation and a desired goal-oriented response (Gollwitzer, 1993, 1999), involves specifying the behavior one will perform in the service of the goal and the situational context in which one will enact it (e.g., “If I encounter situation X, then I will initiate action Y!”) (Sheeran et al., 2005). The success of II is assumed to be based on two processes. First, by making the critical situation highly accessible (i.g., the ‘if’ component), and second, by leading to the automatic initiation of the specified behavior (the ‘then’ component) (Webb and Sheeran, 2004). This strategy is centered on designating anteriorly, rigorously, and explicitly where, when, and how a goal-directed response will be executed, resulting in facilitated goal attainment (Gollwitzer and Sheeran, 2006; Cohen et al., 2007; De Vet et al., 2011). The II strategy have shown its effectiveness in promoting goal achievement (Sheeran and Orbell, 2000), with an effect size on goal achievement for health-related behavioral change estimated as medium to large (Gollwitzer and Sheeran, 2006). Numerous interventions have used II strategy in different fields and among varied populations even in people with chronic conditions such as cancer and diabetes (Verplanken and Faes, 1999; Sheeran and Orbell, 2000; White et al., 2012; Bélanger-Gravel et al., 2013). Findings were promising and positive, and all support the fact that II is a powerful strategy designed to facilitate goal attainment. For people with MS, If-then plans are advantageous in terms of planification and programming of action. In fact, patients’ knowledge, skill, walking speed, quality of life and confidence in managing their health or chronic condition were improved after an II intervention conducted by (Kersten et al., 2015). Also, Electroencephalography (EEG) and functional Magnetic Resonance Imaging (fMRI) studies have shown that II strategy modulates our perceptions and produces less activity in brain regions involved in effort-motivated behavioral control (Wieber et al., 2015).

The aim of our clinical study was to explore the efficacy of two types of psychological interventions – Mindfulness and Implementation of Intention (II) – delivered via internet among people with MS when associated and compared to a physical activity program. We investigated the hypothesis that combining a PA program with Mindfulness or Implementation Intention may be more beneficial than PA alone in decreasing fatigue and improving mobility and quality of life in people with MS.

The aim of this study was to assess the efficacy of a PA program compared to two types of psychological interventions – Mindfulness and Implementation Intention – delivered via internet, in reducing consequences of MS. Effects of practicing were unrelated to degree of impairment (i.e., EDSS level). Following the eight weeks intervention, the results of this study revealed that our PA program led to significant changes in the mobility of people with mild to moderate MS (EDSS < 5.5) in the three groups. The significant increase in distance covered in the 6-min walk test reflects these improvements. In their study, van Asch (2011) found that worsening locomotion was a major concern for both short and long-term MS patients (Heesen et al., 2008; van Asch, 2011). This indicates one of the most debilitating dysfunctions encountered by patients with MS (Motl et al., 2010). Mobility is impaired in up to 90% of people with MS (Zwibel and Smrtka, 2011), increasing the rates of falls and injuries (Nilsagård et al., 2009; Gunn et al., 2014) that may pose a threat to this population (Peterson et al., 2008; Cameron et al., 2011). Therefore, there is still a need to find strategies to increase mobility and maximize autonomy of these people, and the PA program has helped achieve this goal. This represents a significant extension of treatment options.

There was a significant decrease in the MSIS-29 physical component scores in the three groups, indicating a decrease of the impact of MS on patient’s day-to-day life. A broad range of studies have assessed the effects of exercise and PA on MSIS-29. Results revealed improvement in MSIS-29 sub-scales relative to controls (Tollár et al., 2020). Our findings are in line with the results found in the literature. However, our study provided evidence that a PA program combined with mindfulness and motivational interventions may be more promising and present more advantages in terms of amelioration of MS symptoms. Although our analysis did not reveal a significant change in the psychological component of MSIS-29, we noticed a decrease (about 20%) in the average scores, indicating that a longer practice over time may lead to significant changes in this component.

A contribution of this study was to observe that an Implementation Intention carried out in conjunction with the PA program resulted in significant reductions in Modified Fatigue Impact Scale (MFIS) for all factor scores (physical, cognitive, psychosocial) reviewed by some authors to be three important sub-scales in people with MS (D’Souza, 2016). It might be that fatigue had less impact on patients’ lives for the Implementation Intention group during the past 8 weeks. Finally, when it comes to the likelihood and speed of performance, the Implementation Intention intervention (if-then plan) seems to be more effective than simple intentions (“I intend to reach *!”). In fact, specific plans for when, where, and how to initiate behavior and solve difficult tasks almost automatically generate behaviors that help individuals translate their intentions into behaviors (Schwarzer et al., 2008). More specifically, the mental representation of the action becomes highly activated and thus more easily accessible (Gollwitzer and Sheeran, 2006). In contrast, Mindfulness Intervention associated with the PA program produced significant changes only in the physical component. There are many benefits of Mindfulness interventions mentioning the prevention of deteriorating of working memory during stressful periods (Jha et al., 2010).

In people with MS, impairments in working memory appears at the early stage of the disease (Pelosi et al., 1997). In addition, Mindfulness practice can elicit improved visuospatial processing efficiency (Kozhevnikov et al., 2009), enhanced attention (Brefczynski-Lewis et al., 2007) and reduce mind wandering caused by a reduced activation of the default mode network (Mrazek et al., 2013). According to literature (Wayne and Kaptchuk, 2008), mindfulness-related practices (e.g., tai chi) may more commonly engender the rehabilitation and prevention benefits after many years of practice. Thus, larger sample sizes and longer session durations (> 8 weeks) may lead to the discovery of statistical significance improvement of cognitive and sociopsychological factors. In addition, it is important to adapt Mindfulness Interventions to chronic condition such as MS since it may be challenging to find 1 h per day and focus. Some other forms of Mindfulness interventions such as Loving Kindness Meditation, a rich behavioral intervention easier to practice and implement (Galante, 2014) may be more suitable for people with MS. Moreover, the scores of the three components were unchanged for the control group who did not receive any psychological Intervention. Results indicate that 8 weeks Physical activity program by itself was not sufficient to produce modifications relating to the impact of fatigue in the patient’s life.

Fatigue is one of the most common symptoms, and studies conducted in patients with MS confirm that about 50–60% of them suffer from this most troublesome symptom (Costello and Harris, 2003; Trojan et al., 2007). Fatigue is defined as “a subjective lack of physical or mental energy that is perceived by the individual or caregiver to interfere with activities of daily living” (Kos et al., 2006). It can be caused by peripheral neuropathy (e.g., impaired neurotransmission) (Fisk et al., 1994). In addition to its negative effects on cognitive functions, decreasing individuals’ attention and concentration, fatigue may limit people with MS activities of daily living (Mollaòlu and Üstün, 2009) and pose a serious barrier to rehabilitation (Michael, 2002). Furthermore, fatigue may contribute to decline in cognitive performance (Krupp and Elkins, 2000). For the above-mentioned reasons, elaborating instant and effective strategies to reduce fatigue in people with MS must be a priority.

When it comes to MVPA, numerous studies provided clear evidence that people with MS are less physically active than healthy subjects (Motl et al., 2005; Sandroff et al., 2012). People with MS do not engage in sufficient amounts of MVPA recommended by the American College of Sports Medicine. This is a concern, since studies have demonstrated that people with MS only accrue health benefits when practicing MVPA (Garber et al., 2011). Klaren et al. (2015) exhibited the existence of a reconcilable link between MVPA (minutes/day), but there is no such case regarding light physical activity or sedentary behavior, and whole brain gray/white matter and deep gray matter structures including hippocampus, thalamus, caudate, putamen, and pallidum volumes. Those with MS who had high levels of MPVA (minutes/day) had also higher amounts of white matter and deep gray matter structures (Klaren et al., 2015). The deterioration of these subcortical structures occurs in people with MS (Hulst and Geurts, 2011; Gh Popescu and Lucchinetti, 2012). Such deterioration was associated with disability status (Shiee et al., 2012) and cognitive dysfunction (Rao et al., 1989; Sanfilipo et al., 2006) in people with MS. On the other hand, literature in this area have identified MS-related fatigue as the main cause of this restriction to participation in PA in MS (de Groot et al., 2005, 2008). Here, we provided data indicating that II combined with a PA program decreases fatigability among people with MS and that fatigue was strongly negatively associated to the time spent practicing MVPA in people with mild to moderate MS for the II group which was not the case with the control group. This result may indicate that PA combined with a psychological intervention such as II decreases fatigability among people with MS which allows the subject to spend more time in MVPA to better benefit from the multiple advantages previously mentioned in order to improve his condition.

This is the first with randomized controlled trial (RCT) assessing Mindfulness Interventions associated with physical activity with people with MS, a clinical population difficult to recruit due to the numerous impairments produced by the disease. There are no other clinical trials known to the authors that have reported the effects of combining PA with mindfulness and motivational interventions in people with MS. The results of this study show that such interventions are usable for people with MS, as they may improve mobility and other measures impaired by disease (e.g., fatigue) achievable in a very short period, and at a very low cost.

Nevertheless, this research has several limitations. Firstly, a small sample size and the lack of follow-up data to check the stability of the results over time. Additional studies with larger sample size and follow-up assessments are needed to confirm these initial findings, in order to add to the existing literature on combined interventions among people with MS. Finally, we emphasized the lack of follow-up of the Mindfulness training proper conduct. Unfortunately, the only information that was at our disposal is that patients were connected to the application. First, we do not know if they were really listening to the recordings, because being connected does not give reliable information, and if so, whether they listened to all the recordings or whether they were able to focus their attention on the instructions. Indeed, the cognitive impairment associated with the MS condition can make it really challenging to follow this type of Mindfulness training. Our application was not sufficiently developed to provide us all this type of information. In addition, for this pilot study, six pre-recorded sessions of 10 min each delivered via an internet application were used, six days per week. The training program was diversified, composed of a large number of situations aiming at developing one’s proprioception, situations aiming at developing balance and posture and finally situations aiming at developing awareness and rhythm while walking or breathing. However, 6 h home training per week seems to be a long and challenging activity for people with MS. Some other forms of Positive psychology interventions such as Loving Kindness Meditation may be more adapted to this population since there is a dose effect and equivalent result in a much shorter period (10 min per day), (Kirby and Laczko, 2017). Therefore, the procedure used for our MBI method should be reviewed to make it less burdensome for the patient. Additionally, in order to increase motivation, further studies may consider using live video sessions shared by several patients instead of using pre-recorded sessions. We also propose the use of daily reminders and boosters to encourage him to participate in the session. Finally, we also indicate that the actimetry was used “blind” for the patient who did not have access to his amount of daily physical activity. It would be better, in a future study, to inform the patients of the amount of daily physical activity and enable the set of daily goals. Finally, the disposition to full consciousness was not taken into account in this study which explains some of the results in the MBI group which would have made it possible to obtain results larger than the only physical component.

This randomized clinical trial clearly indicates that a PA program tailored to people with MS associated with psychological interventions could be beneficial for people with MS across a broad range of variables. This study reveals that PA could improve mobility and MSIS-29 physical scores in people with mild and moderate MS. Moreover, PA accompanied with Mindfulness Intervention seems to be effective in improving mobility and reducing the impact of the disease in patients’ life. Nevertheless, the mechanisms by which Mindfulness achieves these benefits remain unclear (Grossman et al., 2010). On the other hand, Implementation Intention associated with PA is also effective in enhancing mobility, but more beneficial in decreasing fatigue among people with MS. Another conclusion that we could draw from this study is that II was an activity that is easy to perform, and its practice does not require a long period of time, this was reflected by the percentages of the adhesion to the II questionnaire which were very high within the group. Our study showed that each of the two psychological interventions associated with a PA program has beneficial but different effects among people with mild to moderate MS. Clearly, results revealed that each combination induced a reduction of the specific disease symptoms.

We further propose two ways for improving this research in people with MS as an extension of this work. In this study, we did not seek to understand the mechanisms by which these psychological interventions achieve benefits. Functional magnetic resonance imaging (fMRI) may be a good way to identify the mechanisms by characterizing the brain regions and functional connectivity involved in these psychological states to shed light on its mechanisms of action. A neuroplasticity induced by a Mindfulness intervention has been observed in brain structures and functions. Gotink et al. (2016) showed, using a Mindfulness intervention, an increased connectivity and volume of the prefrontal cortex related to meta-awareness, emotion regulation (anterior cingulate cortex), body awareness (insula) and memory (hippocampus). The brain regions which were influenced by Mindfulness may induce changes that are of significance to emotional modulation and that might be pertinent to improve cognitive functions in people with MS (Willekens et al., 2018).

This is the first study to assess the efficacy of a positive psychology intervention associated with physical activity in people with MS. MS is a severe condition with multiple impairments (cognitive, chronic fatigue, mood disorders) and psychological interventions may be challenging for people with MS and need adjustments. A recent study assessed the feasibility and acceptability of a 5-week group positive psychology intervention for patients with MS. The results are promising, as they revealed a significant improvement in fatigue and depression after the intervention (P = 0.016 and 0.049, respectively). In addition, they showed the feasibility and acceptability of this type of intervention among MS population (Leclaire et al., 2018). However, the study was not randomized nor controlled, with a small sample (n = 17). A very recent RCT (Freedman et al., 2021) examined the feasibility, acceptability, and impact of a 5-week, telephone-delivered positive psychology (PP) intervention for individuals with Multiple Sclerosis (MS). The PP intervention was associated with significantly greater increases (p < 0.05) in positive affect, optimism, state and trait anxiety, general health, and resilience in the intervention group versus the control group (waitlist control). Moreover, the results were stable in time, since half of the PP participants maintained at least 50% of the improvement at 10 weeks. Randomized controlled trials (RCT) are thus necessary to further explore the effectiveness of the positive psychology interventions with people with MS.

We believe that positive psychology is a very promising method of psychological intervention for people with MS as they propose attractive and easy to implement strategies and focus on positive aspects. Studies assessing the effectiveness of the PPIs have shown a high level of heterogeneity: there is a wide variability in effect size across PPIs. It is therefore necessary to examine the specificities of the different interventions included in the PPIs (Csillik, 2015). Classical Mindfulness Interventions address both positive and negative aspects of human functioning. In recent years, Positive Psychology Interventions (PPIs) that integrate mindfulness elements have shown promising outcomes (Lomas and Ivtzan, 2016). Still, there is a lack of clarity in the implementation of Mindfulness-Based Positive Psychology Interventions (MPIs) and their impact on positive human functioning. A recent review aimed to find and analyze the mindfulness-based interventions from the existing literature which have also shown potentials to be a positive psychology intervention (Allen et al., 2021). The outcomes point out the positive potentials of MBIs and the endless possibilities of empirical studies on the application of MPIs and, emphasizes the need of future studies paying attention to positive outcomes when measuring the effects of Mindfulness Based Interventions. In line with these recommendations, we aim to further assess the effects of MBIs adapted to people with MS on other positive outcomes that are more sensitive to change such as eudemonic and hedonic well-being in addition to the quality-of-life measures that are less sensitive to change and to not specifically focus on the people’s own feelings and perceptions of their levels of happiness and well-being.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Ile de France XI (ID: 2016-A00537-44) authorized from the National Agency for the Safety of Medicines and Health (ASNM) and registered under the identification number ID: NCT03785483. The patients/participants provided their written informed consent to participate in this study.

ED, JS, ET, AC, M-CG, OH, DB, and GDM: organization and execution of the research project and review and critique. ED, JS, and ET: data collection. GDM, ET, and AC: statistical analysis and writing manuscript. All authors contributed to the article and approved the submitted version.

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.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.