Effect of task-oriented circuit training on motor and cognitive performance in patients with multiple sclerosis: A single-blinded randomized controlled trial

Abstract

BACKGROUND:

Exercise training has positive effects on motor and cognitive performance which deteriorates over time in patients with Multiple Sclerosis (MS). The effects of task-oriented circuit training (TOCT) on motor and cognitive performance in patients with MS are not yet clear.

OBJECTIVE:

The aims of this study are to investigate the effects of TOCT on balance, walking, manual dexterity, cognitive performance, and to determine the extent to which patients are able to transfer changes in their performance to activities of daily living.

METHODS:

Twenty patients with MS (EDSS: 2–5.5), were randomly assigned to two groups; the task-oriented circuit training group (TOCTG, n:10) and the control group (CG, n:10). The TOCTG received TOCT twice a week for six weeks while the CG performed the relaxation exercises at home. All patients were assessed by using Modified Sensory Organization Test, Berg Balance Scale, Activities-specific Balance Confidence, Timed Up and Go, Functional Gait Assessment, 12-item Multiple Sclerosis Walking Scale, Nine-Hole Peg Test, Brief Repeatable Battery of Neuropsychological Tests, Multiple Sclerosis Neuropsychological Questionnaire.

RESULTS:

Balance and walking performance were improved after TOCT (p < 0.05), whereas manual dexterity and cognitive performance except for verbal memory did not change significantly (p > 0.05). The CG showed no changes in any measurements (p > 0.05).

CONCLUSIONS:

TOCT is quite effective to improve balance and walking in patients with MS. However, further studies are needed to determine the effect of TOCT on cognitive performance.

Keywords

Multiple sclerosis task-oriented circuit training balance walking cognition

1 Introduction

Multiple Sclerosis (MS) is an autoimmune and neurodegenerative disease affecting the Central Nervous System (CNS). Various symptoms arise due to neurodegeneration as time progresses in patients with MS. The most common symptoms in MS are fatigue (76%), abnormal sensations (60%), imbalance (54%) and walking disorder (% 41), respectively (Larocca, 2011).

Novel reviews have reported that different rehabilitation approaches have beneficial effects on these symptoms in patients with MS (Khan & Amatya, 2017; Straudi & Basaglia, 2017). However, there is a lack of sufficient evidence of current neuro-rehabilitation interventions such as task-oriented circuit training (TOCT) (Straudi & Basaglia, 2017). TOCT is based on motor learning methods that increase neural plasticity in CNS and requires intensive repetition of the tasks in line with patients’ needs so that the patient can perform motor tasks by adapting to different conditions during activities of daily life (ADLs) (Hubbard, Parsons, Neilson, & Carey, 2009).

From the MS patients’ perspective, mobility is the most valuable function among the 13 functions frequently disrupted, and mobility disorder is limiting, challenging and frustrating during ADLs (Heesen et al., 2008; Van Asch, 2011). A few studies have examined the effects of TOCT for mobility and have demonstrated improvements in balance and walking performance of patients with MS (Chisari, Venturi, Bertolucci, Fanciullacci, & Rossi, 2014; Salci et al., 2017; Straudi et al., 2014). However, these studies have focused on the disorders of body functions and body structures rather than activity limitations and participation restriction. Hence, although TOCT improves motor functions, whether the patient transfers these gains to ADLs has been uncertain yet.

Another factor limiting ADLs is upper limb dysfunction, which is reported to affect 66% of MS (Johansson et al., 2007). The beneficial effects of TOCT on upper limb performance have also been reported in patients with MS (Boffa et al., 2019; Bonzano et al., 2014; Lamers et al., 2019). In the mentioned studies, the TOCT program consisted of either mobility or upper limb tasks (Boffa et al., 2019; Bonzano et al., 2014; Chisari et al., 2014; Lamers et al., 2019; Salci et al., 2017; Straudi et al., 2014). The effect of a TOCT program involving both has not been investigated yet in patients with MS.

Moreover, the cognitive disorder has been reported in 40–70% of MS patients (Chiaravalloti & DeLuca, 2008). One study that questioned the patient perception stated that cognition was the most valuable function after mobility and vision (Heesen et al., 2008). Moreover, another study stated that cognitive disorder restricted patients’ participation more than physical limitations (Cattaneo, Lamers, Bertoni, Feys, & Jonsdottir, 2017).

In recent years, neuroimaging studies showed that common brain regions are activated in both motor and cognitive processes (Buckner, 2013; Holtzer et al., 2011). Therefore, exercise training may be a suitable approach for increasing cognitive performance in patients with MS. In a recent review, the effects of exercise training such as yoga, aerobic and resistance training on cognitive functions were examined in patients with MS and it was stated that the information reached was as yet insufficient (Sandroff, Motl, Scudder, & DeLuca, 2016). To our knowledge, the effects of task-oriented circuit training on cognitive function have not been investigated yet in patients with MS.

Overall, the aims of this study are (1) to investigate the effects of TOCT on the balance, walking and manual dexterity, (2) to evaluate the extent to which patients are able to transfer changes in their performance to ADLs through patient self-report measures, and (3) to determine whether TOCT, composed of motor tasks, ameliorates cognitive performance in patients with MS.

2 Methods

2.1 Participants

Sixty-eight patients with MS were invited to this study which was conducted at Gazi University, Department of Physiotherapy and Rehabilitation. The inclusion criteria were (1) the diagnosis of definite MS according to the revised McDonald criteria 2010 (Polman et al., 2011), (2) 18–65 years of age, (3) having mild to moderate disability according to the Expanded Disability Status Scale (EDSS) score between 2–5.5 (Kurtzke, 1983). Exclusion criteria were patients (1) suffering from relapses in the last 3 months, (2) having a disease in which exercise is contraindicated (3) having orthopedic, vision, hearing, or perception problems. The participants did not receive a concurrent rehabilitation program during the study.

Written informed consent was obtained from each participant. The study was approved by Gazi University Clinical Research Ethics Committee and registered at ClinicalTrials.gov (NCT03505294) before the recruitment started.

We calculated sample size based on the significant difference of the Berg Balance Scale (BBS) and the 12-item Multiple Sclerosis Walking Scale (MSWS-12) declared by similar studies in patients with MS (Chisari et al., 2014; Straudi et al., 2014). The differences provided a Cohen’s d effect size of 0.78 for BBS and 0.76 for MSWS-12, respectively. To achieve % 80 power with a two-sided level of 5%, the total sample size was estimated at a minimum of 16 (n:8 per group) for both effect size using G*Power 3.1 power analysis software (Faul, Erdfelder, Lang, & Buchner, 2007).

2.2 Study design

The study was designed as a randomized, controlled, single-blind trial. 23 of 68 patients were included in this study and they were randomly assigned to the task-oriented circuit training group (TOCTG, n:12) and the control group (CG, n:11) using a minimisation method with an allocation ratio of 1 : 1. Minimisation is a randomization method that aims to maintain the balance of the groups in prognostic factors of the participants (Scott, McPherson, Ramsay, & Campbell, 2002). Therefore, a minimization program (MinimPy) was used to balance the gender and clinical course of participants (Saghaei & Saghaei, 2011). One of the researchers was responsible for the randomization but did not take part in data collection or data analysis. Two physical therapists blinded on patient randomization recorded demographics (age, gender, length, body weight, EDSS, disease duration, a number of relapses) and assessed all the patients at baseline (T0) and after six weeks of training (T1). The allocation was concealed from participants until after baseline assessment. The patients were asked not to discuss their intervention with the assessors during the last assessment. The study design and participants are shown in Fig. 1.

Fig. 1

CONSORT flow diagram illustrating the participants in the study. CG: control group, TOCTG: Task-oriented circuit training group.

2.3 Interventions

2.3.1 Task-oriented circuit training

The TOCTG participated in TOCT twice a week for 6 weeks. The training included 10 different tasks. The patients performed each task for 4 minutes and rested for 2 minutes before starting the next task. Each session was completed in about 60 minutes. In order to adapt the motor task to different environments, motor tasks were made difficult by altering sensory inputs. The first six tasks were repeated with eyes closed or sunglasses for reducing visual input, with head movements for stimulating the vestibular system and on the soft surface for reducing somatosensory input. The content of the training is shown in Table 1.

Table 1
Task-oriented circuit training program

1- Sitting balance* 6- Walking up and down stairs*

•Quiet sitting •Without holding the railings

•Reach as far as possible •Alternate stepping

•Alternate leg lifting •Stairs of different heights

•Alternate arm raising

•Alternate cross arm and leg lifting

2- Sit to stand* 7- Mat activity

•Stand up from chairs of different heights •Lie down on a mat

•Alternate arm raising •Turn several times on the mat

•Narrow base and tandem •Get up off the mat

3- Standing* 8- Dressing

•Quiet standing •Wear a jacket and button up

•Reach as far as possible •Wear wide pants

•Alternate arm raising •Wear socks

•Narrow base and tandem •Wear shoes

•Single leg stance

4- Four square steps* 9- Writing

•Alternate arm raising •Write by using a pen (unilateral)

•Step over obstacles of different height between squares •Write by using a keyboard (bilateral)

5- Walking* 10- Eating

•Narrow base and tandem •Pour water from a jug into a glass

•Step over obstacles of different height •Make different shapes with play dough

•Slalom walk •Cut the dough using a fork and a knife

•Run a short distance at a self-paced speed •Make small balls with the dough

•Backward walk •Put the balls on another plate with a spoon

*The tasks were repeated with eyes closed or sunglasses for reducing visual input, with head movements for stimulating the vestibular system and on the soft surface for reducing somatosensory input.

2.3.2 Relaxation exercises

A physiotherapist taught the patients in CG the Jacobson’s progressive relaxation exercise once and they were asked to practice 15–20 minutes of the relaxation exercise twice for 6 weeks at home. The main aim of relaxation exercise is to gain the ability to relax muscles voluntarily and to increase body awareness. During this exercise, the patient lay down comfortably and progressively isometrically contracted and relaxed the muscles (Jacobson, 1938).

2.4 Measurements

Each motor and cognitive performance of the patients were evaluated by functional tests in a clinical environment. Additionally, balance, walking and cognitive performance in ADLs were evaluated with self-reported questionnaires.

2.4.1 Balance

Modified Sensory Organization Test (MSOT): Postural sway and sensory organization were assessed by posturography (Biodex Balance System-BioSway™) (Cachupe, Shifflett, Kahanov, & Wughalter, 2001). The patients were asked to stand on both feet for 30 seconds under altered sensory conditions; 1. Eyes open-firm surface, 2. Eyes closed-firm surface; 3. Eyes open-foam surface, 4. Eyes closed-foam surface.

Berg Balance Scale (BBS): The BBS assesses clinically static and dynamic balance performance via 14 different functional activities. Each item is scored from 0 (the lowest level) to 4 (highest level) and the total maximum score is 56 (Berg, Wood-Dauphinee, Williams, & Maki, 1992). If the total score increases by 3 points or more, this indicates a clinically significant improvement for balance (Gervasoni, Jonsdottir, Montesano, & Cattaneo, 2017).

Activities-specific Balance Confidence (ABC): In the ABC scale, the patients rate their perceived level of balance confidence during 16 different balance related daily ambulatory activities between 0 (no confidence) and 100 (complete confidence) (Powell & Myers, 1995). The Turkish version of the scale was used in this study (Karapolat et al., 2010).

2.4.2 Walking performance

Timed Up and Go (TUG) test: Functional mobility was evaluated by using TUG. The patients were asked to stand up from a chair, walk 3 m, turn around and sit on the chair. The test duration was recorded in seconds by using a stopwatch (Sebastiao, Sandroff, Learmonth, & Motl, 2016).

The Functional Gait Assessment (FGA): FGA is a clinical gait test including 10 items: walk at normal speeds, at fast and slow speeds, with vertical and horizontal head turns, with eyes closed, over obstacles, in tandem, backward, and while ascending and descending stairs. Each item is scored from 0 (severe impairment) to 3 (normal performance) (Forsberg, Andreasson, & Nilsagård, 2017; Wrisley, Marchetti, Kuharsky, & Whitney, 2004).

The 12-item Multiple Sclerosis Walking Scale (MSWS-12): MSWS-12 is a self-assessment scale and assesses the impacts of MS on walking performance in daily life during the last 2 weeks. Each item is scored from 1 (no limitation) to 5 (extreme limitation) (Hobart, Riazi, Lamping, Fitzpatrick, & Thompson, 2003). If the total score increases by 10.4 points or more, this indicates a clinically significant improvement for walking performance (Baert et al., 2014).

2.4.3 Manual dexterity

The Nine Hole Peg Test (NHPT): NHPT assesses the manual dexterity of both dominant and non-dominant hands. The patient picks up nine pegs one at a time as quickly as possible, puts them in nine holes, and then removes them again as quickly as possible one at a time. The test duration was recorded in seconds by using a stopwatch (Feys et al., 2017; Mathiowetz, Weber, Kashman, & Volland, 1985).

2.4.4 Cognitive performance

Brief Repeatable Battery of Neuropsychological Tests (BRB-N): Cognitive performance was assessed by BRB-N. The battery assesses the cognitive domains and includes the following tests: 10/36 Spatial Recall Test (SPART), for visual memory acquisition and delayed recall; Selective Reminding Test (SRT), for verbal memory acquisition and delayed recall; Word List Generation (WLG), for semantic verbal fluency; The Symbol Digit Modalities Test (SDMT) and Paced Auditory Serial Addition Test (PASAT-3) for attention, concentration, and information processing speed (Rao, 1990).

Neuropsychological Questionnaire: Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) is a 15-item self-report measure of perceived neuropsychological impairment. The items include attention and processing speed, memory, and other cognitive functions in daily living (Benedict et al., 2003).

2.5 Statistical analysis

Statistical analysis was performed by using the SPSS software version 15 (SPSS Inc. Chicago, IL, USA). The variables were determined by the measurements (histograms, probability plots, Shapiro-Wilk test) and were expressed as the median and Interquartile Range (IQR) because of non-normal distribution. A Chi-square test was used to compare categorical variables between the groups. A Mann-Whitney U Test was used to compare baseline values between the groups. After 6 weeks, the changes between pre-test and post-test values were calculated and pre-post values within groups were compared with a Wilcoxon Test. The significance level was set at p < 0.05 for all the analyses. The effect sizes were evaluated according to Cohen’s d standards within groups pre-post differences. The effect size results were interpreted as small (≥0.2), medium (≥0.5), or large (≥0.8) according to guidelines (Cohen, 2013).

3 Results

Two patients could not continue to exercise training because of work intensity and family problems in TOCTG and so 10 patients completed the study. In the CG, one patient could not come to the last measurement. The missing data were handled using listwise deletion. In total, the data of 20 patients were analyzed and 3 patients dropped out. Figure 1 shows the CONSORT flow diagram illustrating the participants in the study. During the training, no adverse or harmful events were reported. The participation rate for the training sessions was an average of 93.33% (83.33–100) in TOCTG.

The demographic characteristics of the participants were similar between the two groups and there were no differences in baseline measurements between the groups (p > 0.05, Tables 2 –4). In addition, a post hoc power analysis using G*Power 3.1 power analysis software showed the statistical power of 0.99 for the effect sizes of both BBS score and MSWS-12 score in TOCTG.

Table 2
Demographic characteristics of participants

TOCTG (n:10) CG (n:10) p

Age (years) 46 (29–47) 41.5 (28.25–47.25) 0.908

BMI (kg/m²) 25.89 (24.39–26.70) 24.28 (22.39–27.67) 0.425

Gender (f/m) 6/4 6/4 1

Clinical course (PP/RR) 4/6 4/6 1

EDSS score 4 (3.375–4.25) 3.75 (3–4.25) 0.531

Disease duration (years) 16 (7–20.75) 13.5 (6.75–20) 0.758

Number of relapses 4 (1–8) 2.5 (1–4.25) 0.376

	TOCTG (n:10)	CG (n:10)	p
Age (years)	46 (29–47)	41.5 (28.25–47.25)	0.908
BMI (kg/m²)	25.89 (24.39–26.70)	24.28 (22.39–27.67)	0.425
Gender (f/m)	6/4	6/4	1
Clinical course (PP/RR)	4/6	4/6	1
EDSS score	4 (3.375–4.25)	3.75 (3–4.25)	0.531
Disease duration (years)	16 (7–20.75)	13.5 (6.75–20)	0.758
Number of relapses	4 (1–8)	2.5 (1–4.25)	0.376

Data are presented as Median (IQR), *p < 0.05. BMI: Body mass index, CG: Control group, EDSS: Expanded Disability Status Scale, PP: Primary progressive, RR: Relapsing-remitting, TOCTG: Task-oriented circuit training group.

Table 3

Motor performtaance in the groups

		Pre-test Median (IQR)	p (between groups)	Post-test Median (IQR)	Change Median (IQR)	p (within group)	Effect size
Balance
Modified sensory organisation test, score
Eyes open, firm surface	TOCTG	0.87 (0.69–1.02)	0.472	0.87 (0.59–0.96)	–0.24 (–0.38–0.2)	0.333	0.22
	CG	0.95 (0.73–1.22)		0.84 (0.58–1.43)	–0.01 (–0.14–0.33)	0.759	0.18
Eyes closed, firm surface	TOCTG	1.48 (1.15–2.14)	0.623	1.25 (0.78–1.7)	–0.33 (–0.82––0.17)	0.012*	1.14
	CG	1.24 (1.16–2.3)		1.41 (0.94–2.05)	0.03 (–0.37–0.61)	0.721	0.16
Eyes open, foam surface	TOCTG	1.72 (1.51–2.35)	0.364	1.5 (1.21–1.92)	–0.14 (–0.43––0.06)	0.037*	0.85
	CG	1.55 (1.12–2.03)		1.59 (1.19–2.51)	0.12 (–0.25–0.36)	0.508	0.33
Eyes closed, foam surface	TOCTG	4.52 (3.75–5.76)	0.131	3.65 (2.93–4.04)	–1.37 (–1.91––0.49)	0.009*	1.34
	CG	3.77 (3.44–4.66)		4.09 (3.45–5.18)	0.41 (–0.24–0.71)	0.262	0.28
BBS, score	TOCTG	35 (34.25–43.25)	0.416	40 (34.75–46.5)	3.5 (2.5–4.25)	0.007*	1.98
	CG	39 (35–44.25)		39.5 (33.75–45)	0 (–2–1)	0.566	0.14
ABC, score	TOCTG	48.44 (29.06–85.94)	0.241	62.19 (49.22–90.31)	125 (60–457.5)	0.028*	0.82
	CG	71.72 (54.38–85.63)		64.69 (58.28–84.53)	0 (–161.25–75)	0.575	0.22
Walking performance
TUG, seconds	TOCTG	10.88 (7.56–13.25)	0.326	9.31 (6.6–12.23)	–1.20 (–2.39––0.51)	0.007*	1.23
	CG	8.01 (6.89–12.53)		9.22 (7.79–11.55)	0.71 (–0.49–1.43)	0.285	0.10
FGA, score	TOCTG	8.5 (3.75–11.25)	0.543	12 (10.5–13.25)	5 (2–6)	0.007*	1.91
	CG	7.5 (5.5–14.25)		10.5 (7.25–12.75)	1 (–0.5–2)	0.319	0.39
MSWS-12, score	TOCTG	53.50 (34–60)	0.462	25 (22–31.5)	–20 (–30.75––13)	0.008*	1.81
	CG	46 (30–60)		45 (30–58.5)	0 (–2 –0)	0.258	0.39
Manual dexterity
NHPT- D, seconds	TOCTG	26.01 (19.74–28.63)	0.29	23.86 (20.72–32.45)	–1.48 (–5.55–3.94)	0.646	0.05
	CG	21 (18.63–26.17)		20.84 (19.45–23.98)	0.07 (–1.06–2.4)	0.594	0.12
NHPT-ND, seconds	TOCTG	34.93 (28.9–42.71)	0.05	30.03 (25.26–38.19)	–3.82 (–7.75–1.11)	0.114	0.6
	CG	27.89 (22.84–36.86)		28.06 (21.7–35.81)	–0.51 (–2.03–0.28)	0.26	0.27

Data are presented as Median (IQR), *p < 0.05 between two groups for baseline values (Mann Whitney U Test) and within the group after 6 weeks (Wilcoxon Test). ABC: Activities-specific Balance Confidence, BBS: Berg Balance Scale, CG: Control Group, FGA: Functional Gait Assessment, MSWS-12 : 12-item Multiple Sclerosis Walking Scale, NHPT: Nine Hole Peg Test, NHPT-D: NHPT-dominant hand, NHPT-ND: NHPT-non dominant hand, TOCTG: Task-oriented circuit training group, TUG: Timed Up and Go.

Table 4

Cognitive performance in the groups

		Pre-test Median (IQR)	p (between groups)	Post-test Median (IQR)	Change Median (IQR)	p (within group)	Effect size
Brief Repeatable Battery of Neuropsychological Tests, score
SPARTT, score	TOCTG	15 (11–27.25)	0.761	23.5 (13–29.25)	1 (–1.25 –7.5)	0.312	0.40
	CG	17.5 (11.5–29.25)		18 (8.75–30)	–0.5 (–2.25 –1)	0.473	0.24
SPARTD, score	TOCTG	5 (3–9.25)	1	9.5 (4.75–10)	0 (–0.25 –3.25)	0.223	0.46
	CG	4 (3–10)		7.5 (2.75–10)	0 (–0.25 –1)	0.680	0.26
SRT-ST, score	TOCTG	64.5 (61.25–68.25)	0.384	67 (63.75–70.25)	4.5 (–2.75 –7.75)	0.114	0.51
	CG	61.5 (44–67.25)		58 (42.25–62.25)	0 (–7.5 –2.5)	0.475	0.34
SRT-LT, score	TOCTG	10 (8–11.25)	0.969	11 (10.75–12)	1.5 (0 –2)	0.016*	1.23
	CG	10.5 (7.75–11.25)		10.5 (9.75–12)	1 (–0.25 –2.5)	0.117	0.49
WLG, score	TOCTG	25.5 (22.75–28.25)	0.545	25.5 (23.25–31)	2.5 (–3.75 –6.25)	0.414	0.14
	CG	23 (20.75–32.5)		23.5 (21–28.5)	–2 (–4.5 –3.5)	0.475	0.26
SDMT, score	TOCTG	17 (6.5–35)	0.596	18.5 (12–37.5)	4 (–2.25 –9)	0.482	0.19
	CG	15.5 (3.25–30.75)		12 (3.5–20.5)	0 (–14.25 –1.25)	0.481	0.52
PASAT, score	TOCTG	31 (25.25–45.75)	0.791	34.5 (27.75–45.25)	2.5 (0.25 –3.25)	0.072	0.67
	CG	35.5 (14.25–47.5)		34 (16.5–48)	0.5 (–4 –2.25)	0.721	0.07
MSNQ, score	TOCTG	18 (7–23.5)	0.85	15 (7.75–19)	–2.5 (–9.75–3)	0.201	0.35
	CG	17.5 (9–30)		18.5 (10.5–31.25)	0 (0 –2)	0.336	0.37

Data are presented as Median (IQR). *p < 0.05 between two groups for baseline values (Mann Whitney U Test) and within the group after 6 weeks (Wilcoxon Test). CG: Control Group, MSNQ: Multiple Sclerosis Neuropsychological Questionnaire, PASAT: Paced Auditory Serial Addition Test, SDMT: Symbol Digit Modalities Test, SPARTD: 10/36 Spatial Recall Test-delayed, SPARTT: 10/36 Spatial Recall Test-three trials, SRT-LT: Selective Reminding Test-long term, SRT-ST: Selective Reminding Test-short term, TOCTG: Task-oriented circuit training group, WLG: Word List Generation.

3.1 Balance

Postural sway decreased under altered sensory conditions on MSOT, except for eyes open-firm surface, and ABC scores increased in TOCTG (p < 0.05, Table 3). Besides that, an increase in the BBS score of 5 points indicated a statistically and clinically significant improvement for balance in TOCTG (p < 0.05, Table 3). A significant difference was not found in CG (p > 0.05, Table 3).

3.2 Walking performance

TUG decreased and FGA score increased in TOCTG (p < 0.05, Table 3). Also, after TOCT a decrease in the MSWS-12 score of 28.5 points indicated that the negative impact of MS on walking was significantly reduced both statistically and clinically (p < 0.05, Table 3). The walking performance in CG remained the same (p > 0.05, Table 3).

3.3 Manual dexterity

The NHPT test duration of both dominant and non-dominant hands did not change in both groups (p > 0.05, Table 3).

3.4 Cognitive performance

SRT-LT score enhanced in toctg (p < 0.05, Table 4). However, other domains of cognitive functions and MSNQ score did not change in both groups (p > 0.05, Table 4).

4 Discussion

To date, a few studies have examined the effects of TOCT in patients with MS. In this study, balance and walking performance were improved in patients with MS after TOCT and these improvements in functions were reflected in balance-related activities. Despite significant improvements in balance and walking after TOCT, there was no significant change in manual dexterity and cognitive functions other than long-term verbal memory. On the other hand, there was no change in CG after 6 weeks.

4.1 Balance and walking performance

In this study, postural sway under altered sensory conditions decreased and the balance was better maintained during functional activities evaluated with BBS in TOCTG. For BBS, the minimal clinically significant change score is 3 and the 3.5-point increase in BBS score of TOCTG indicated that the balance was improved clinically (Gervasoni, Jonsdottir, Montesano, & Cattaneo, 2017). Additionally, the increment of ABC score in TOCTG showed that these improvements in clinical tests were also transferred to the balance-related activities.

In addition to the improvements in balance, functional mobility assessed by TUG and walking ability in different conditions assessed by FGA enhanced after TOCT in this study. Furthermore, the patients were questioned with the MSWS-12 and they stated that the negative impacts of the disease on walking decreased. For MSWS-12, the minimal clinically significant change score is 10.4 points and the 20-point decrease in MSWS-12 score indicated that the improvement in walking performance was not only statistically but also clinically significant (Baert et al., 2014).

When the literature was examined, there were only three studies investigating the effects of TOCT on balance and mobility in patients with MS (Chisari et al., 2014; Straudi et al., 2014; Salci et al., 2017). Salci et al. demonstrated that combined with balance training, TOCT for 6 weeks improved the balance and walking performance on the clinical tests in MS patients (Salci et al., 2017). In the other two studies examining the effects of task-oriented training in MS patients, a more intensive training program in addition to gait training on a treadmill was applied for two weeks in a total of 10 sessions, unlike the methodology of our study (Chisari et al., 2014; Straudi et al., 2014). Chisari et al. found that balance and walking performance were improved in the training group, which is similar to the results of our study (Chisari et al., 2014). On the other hand, Straudi et al. stated that there was an improvement in MSWS-12, but there was no improvement in TUG, DGI, 10-meter walk test and six-minute walk test (Straudi et al., 2014).

Unlike previous studies involving balance or gait training on a treadmill in addition to motor tasks, TOCT consisting of only motor tasks was performed in this study. Therefore, in fact, the training intensity in this study was lower compared to these studies. Nevertheless, this study showed that even only TOCT had a large effect on improving balance and walking in patients with MS. In relation to this beneficial effect, we thought that different sensory inputs during training may have an important role in the improvement of balance and walking at the end of TOCT because, sensory integration is a crucial determinant of both balance and walking performance, and moreover, ADLs require individuals to adapt to different sensory conditions. These thoughts are supported by the study of Cattaneo et al., showing 75% of patients with MS had higher postural sway than healthy individuals and this rate increased to 82% even if only one sensation was eliminated. In particular, it was emphasized that the postural sway of almost all patients were abnormal when changing the vestibular system input (Cattaneo & Jonsdottir, 2009).

On the other hand, there was no change in CG at the end of 6 weeks. Previous studies demonstrated that progressive relaxation exercise reduced complaints such as quality of life, fatigue and sleep quality (Dayapoğlu & Tan, 2012; Saghaei & Saghaei, 2011). However, in line with the result of this study, Bulguroglu et al. reported that relaxation exercise did not have adequate power to be effective on physical performance such as strength, balance, and mobility (Bulguroglu et al., 2017).

4.2 Manual dexterity

Manual dexterity disorders limit the participation of patients almost as much as balance and walking disorders (Cattaneo et al., 2017). For this reason, we added upper limb tasks as well as balance and walking oriented tasks to our TOCT program. However, we did not observe an improvement in manual dexterity after TOCT. Similarly, Boffa et al. reported that both task-oriented training and passive mobilization in progressive MS did not have an effect on manual dexterity, assessed by NHPT. However, they showed that task-oriented training increased motor finger performance assessed by the engineered glove and functional connectivity within the cerebellar and thalamic resting-state networks analyzed by magnetic resonance imaging (MRI) (Boffa et al., 2019). Unfortunately, we only used NHPT in this study and did not strengthen the assessment of upper-limb performance with more sensitive measuring devices, and so we could not comment on neural changes. On the other hand, Bonzano et al. showed that the motor performance assessed by the Action Research Arm, NHPT, and grip strength was improved in both training group and control group, which received passive mobilization. However, bimanual coordination and white matter integrity in the corpus callosum and corticospinal fiber bundles were preserved only in the training group (Bonzano et al., 2014). Their study revealed the necessity of functional tasks to influence both motor and neural structures.

Moreover, in the study by Lamers et al., patients with MS received task-oriented training at 100% or 50% of their individual maximal number of repetitions or conventional therapy. The results showed an improvement in activity level and functions of the upper extremity in all groups, but a higher improvement was observed in the task-oriented group training at 100% intensity (Lamers et al., 2019).

Compared to the previous studies that applied only upper limb tasks for a total of 24–40 training sessions of 1 h, the TOCT program in this study consisted of quite a few upper limb tasks which were dressing, writing, and eating for a total of 12 sessions. Therefore, our training was low intensity and the TOCTG may not have repeated the tasks sufficiently. In addition, we should have assessed manual dexterity with a test that evaluates ADLs to observe whether these tasks were improved. On the other hand, the patients in both groups had no significant disability specific to the manual dexterity, and so it may be more difficult to achieve an increase in those whose manual dexterity was already close to normal.

4.3 Cognitive performance

To the best of our knowledge, the effect of TOCT on cognitive performance has not been examined before. This study showed that a significant improvement was found only in the SRT-LT score, which assesses verbal learning and long-term memory. However, other cognitive domains and perceived cognitive impairment did not ameliorate.

A case study with MS patients showed that aerobic exercise training increased hippocampal volume and memory but non-memory cognitive functions (executive functions, processing speed, working memory) did not improve (Leavitt et al., 2014). Although the possible mechanism of exercise on cognitive functions has not yet been fully explained, exercises are thought to increase the cognitive functions by improving neurogenesis and vascular adaptations (Barnes, 2015). In addition, a recent study illustrated that verbal memory was influenced by transcranial magnetic stimulation targeting the motor cortex but not by sham stimulation or transcranial magnetic stimulation targeting the visual cortex. This result suggests that motor activation contributes to verbal memory (Liao, Kronemer, Yau, Desmond, & Marvel, 2014). Moreover, the study of Chein et al. demonstrated that supplementary motor and premotor areas were active across all processes in verbal working memory (Chein & Fiez, 2001). In other words, TOCT can also activate cognitive domains, especially verbal memory even if it includes only motor tasks. The recent neuroimaging studies have shown that the brain areas associated with some motor and cognitive functions overlap (Buckner, 2013; Holtzer et al., 2011). The researchers explain this by the fact that each motor task requires cognitive control. Especially, new, difficult, complex motor tasks require more cognitive control than automatized, well-learned, gross motor tasks. This evidence suggested that training involving motor tasks may also affect cognitive performance (Leisman, Moustafa, & Shafir, 2016).

In our study, TOCT consisted of the most commonly used motor tasks in daily life, and the tasks were made difficult only by altering sensory inputs. In addition, we avoided giving concurrently cognitive tasks for patients in order to let them focus on the motor task. For this reason, motor tasks in our training program may not have activated sufficiently cognitive processing to improve other cognitive domains excluding verbal learning and long-term memory. In view of this, it is worth investigating whether the training that involves more complex tasks such as dual-task training affects cognitive functions.

4.4 Limitations

Although this study has sufficient power according to the performed analysis considering walking performance, it did not have enough power to make a definitive judgment about manual dexterity and cognitive performance due to the small sample size. In addition, the effectiveness of this training, which was asserted to increase neural plasticity, was not investigated by using neuroimaging techniques. Lastly, follow-up was not performed to assess the sustainability of skill acquisition.

4.5 Conclusion

The present results show that 6-week task-oriented training may have a favorable effect on improving balance, walking, and related daily activities in patients with MS. Although task-oriented training has no significant effect on manual dexterity and cognitive performance other than long-term verbal memory in this study, further studies are needed for precise information.

Conflict of interest

No potential conflict of interest was reported by the authors.

Ethics

Ethics committee approval was received for this study from the ethics committee of Gazi University (no: 229).

Funding

The authors acknowledge that they received no external funding in support of this study.

Informed consent

Written informed consent was obtained from the subjects who participated in this study.

Footnotes

Acknowledgments

The authors are grateful to all participants in this study. Trial Registration: NCT03505294.

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1- Sitting balance*	6- Walking up and down stairs*
•Quiet sitting	•Without holding the railings
•Reach as far as possible	•Alternate stepping
•Alternate leg lifting	•Stairs of different heights
•Alternate arm raising
•Alternate cross arm and leg lifting
2- Sit to stand*	7- Mat activity
•Stand up from chairs of different heights	•Lie down on a mat
•Alternate arm raising	•Turn several times on the mat
•Narrow base and tandem	•Get up off the mat
3- Standing*	8- Dressing
•Quiet standing	•Wear a jacket and button up
•Reach as far as possible	•Wear wide pants
•Alternate arm raising	•Wear socks
•Narrow base and tandem	•Wear shoes
•Single leg stance
4- Four square steps*	9- Writing
•Alternate arm raising	•Write by using a pen (unilateral)
•Step over obstacles of different height between squares	•Write by using a keyboard (bilateral)
5- Walking*	10- Eating
•Narrow base and tandem	•Pour water from a jug into a glass
•Step over obstacles of different height	•Make different shapes with play dough
•Slalom walk	•Cut the dough using a fork and a knife
•Run a short distance at a self-paced speed	•Make small balls with the dough
•Backward walk	•Put the balls on another plate with a spoon