Comparing the effectiveness of bimanual and unimanual mirror therapy in unilateral neglect after stroke: A pilot study

Abstract

BACKGROUND:

Unilateral neglect in stroke patients is a major obstacle to rehabilitation, which is a great challenge for therapists.

OBJECTIVE:

This study aimed to compare the effectiveness of bimanual mirror therapy (BMT) and unimanual mirror therapy (UMT), the two protocols of mirror therapy, for the reduction of the symptoms of unilateral neglect in stroke patients.

METHODS:

Twenty-eight individuals were randomly assigned to the BMT or UMT groups. Both groups received mirror therapy for 30 minutes per day, 5 days a week, for a period of 4 weeks. The Star Cancelation Test (SCT), Line Bisection Test (LBT), Picture Scanning Test (PST), and Korean Catherine Bergego Scale (K-CBS) were used to measure the change in unilateral neglect, and the Korean version of the Modified Barthel Index (K-MBI) was used to evaluate activities of daily living (ADL).

RESULTS:

The results of SCT, LBT, PST, and K-CBS showed significant decreases in unilateral neglect in both groups (p < 0.05). K-MBI improved significantly in both groups (p < 0.05). There were significant differences between the two groups in the unilateral neglect tests (p < 0.05), but no significant difference in ADL evaluation (p > 0.05).

CONCLUSIONS:

Mirror therapy protocols can be applied to treat unilateral neglect in stroke patients. However, BMT may be more beneficial for reducing the symptoms of unilateral neglect.

Keywords

Stroke mirror therapy unilateral neglect activities of daily living

1 Introduction

Unilateral neglect is a severe disability caused by stroke. Its symptoms include reduced attention, perception, and response to stimuli presented to the contralesional side of the cerebral hemisphere (Selzer et al., 2006). Consequently, patients with unilateral neglect face various challenges in their activities of daily living (ADL). Some of the challenges that result from reduced awareness of the neglected side include getting dressed without being aware of the limbs on the other side, eating food from one side of the plate and neglecting the other side, walking with not being aware of the other limb, and difficulty in changing directions or bumping into a wall (Baylis et al., 2004; Robertson & Halligan, 1999; Saevarsson et al., 2009).

Various interventions have been designed to reduce the symptoms of unilateral neglect. Behavioral interventions included awareness training, sustained attention training, limb activation, constraint-induced therapy, and smooth pursuit eye movement training (Tham et al., 2001; Robertson & North, 1993; Bollea et al., 2007; Kerkhoff et al., 2013). Partial visual occlusion and prism adaptation training were introduced to further alleviate the symptoms associated with unilateral neglect (Rossi et al., 1990; Butter & Kirsch, 1992). Neck muscle vibration and galvanic-vestibular stimulation have been used for sensory stimulation (Karnath et al., 1993; Kerkhoff et al., 2011). Noninvasive brain stimulation therapies included transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and theta-burst stimulation (TBS) (Utz et al., 2010; Cazzoli et al., 2010; Koch et al., 2012). Recently, mirror therapy, mental practice, and virtual reality have been used to treat unilateral neglect (Pandian et al., 2014; Park & Lee., 2015; Kim et al., 2011). Interventions based on the mirror neuronal system in terms of neurological aspects include action observational training, mirror therapy, and virtual reality (Ertelt et al., 2007; Shih et al., 2013; Buccino et al., 2006).

Mirror therapy was first used to treat phantom limb pain in patients after amputation (Ramachandran & Rogers-Ramachandran, 1996); however, recently, it has been widely applied in stroke rehabilitation (Altschuler et al., 1999). This intervention is based on the mirror neuron system, which shows activation of the ventral premotor cortex upon performing a goal-oriented movement or observing the movement of another individual (Hamzei et al., 2012; Rizzolatti et al, 1996; Thieme et al., 2018). The activation of the human mirror neuron system has been verified using fMRI (Buccino et al., 2001). Mirror therapy aims for the functional recovery of the paretic limb caused by stroke and induces the movement of the paretic limb while observing the movement of the non-paretic limb reflected on the mirror. In the field of rehabilitation, mirror therapy has been used to physically restore the function of paretic upper and lower limb (Stevens & Stoykov, 2003; Xu et al., 2017), improve the performance of ADL (Yang et al., 2018), and reduce unilateral neglect symptoms (Pandian et al., 2014) and pain (Wittkopf & Johnson, 2017).

There are two protocols for mirror therapy: the bimanual protocol (BMT) and the unimanual protocol (UMT). Basic setting of the two protocols is identical; however, the movement of the non-paretic limb behind the mirror determines whether the therapy provided is BMT or UMT. In BMT, the patient observes the paretic upper limb and attempts to perform the same movement with the paretic upper limb, which is positioned behind the mirror. BMT combines UMT with limb activation training (Geller, 2018). UMT allows the patient to observe the movement of the non-paretic upper limb through the mirror while maintaining the paretic upper limb in a static position behind the mirror. BMT effectively reduces the symptoms of unilateral neglect, improves the performance of ADL, and facilitates upper limb functional recovery (Lee et al., 2012; Pandian et al., 2014; Samuelkamal-Eshkumar et al., 2014). UMT effectively improves the performance of ADL and facilitates the upper limb functional recovery when compared with conventional treatments (Arya et al., 2015; Kim et al., 2016; Park et al., 2015); however, studies on the effect on the reduction of the symptoms of unilateral neglect are scarce. In a study by Geller (2018), the effects of BMT and UMT on the recovery of upper extremity function were compared, and UMT was shown to produce a moderate to high effect size, while BMT was shown to produce a low effect size, as determined by the action research arm test, Fugl-Meyer Assessment, and ABILHAND scores. Thus, UMT was found to be more advantageous than BMT for upper limb functional recovery in patients with chronic stroke.

Although studies have compared the upper limb functional recovery between the two protocols of mirror therapy, few have examined the use of mirror therapy in unilateral neglect, which occurs frequently in stroke patients. This study aimed to compare the effectiveness of BMT and UMT in reducing the symptoms of unilateral neglect in patients with stroke.

2 Methods

2.1 Participants

This study recruited 30 patients with subacute or chronic stroke for more than 3 months to minimize the effects of spontaneous recovery on the outcomes. However, due to the early discharge of two patients, the final number of participants reduced to 28. Inclusion criteria were as follows: diagnosis of stroke based on computed tomography or magnetic resonance imaging, no comorbidity, onset date≥3 months, Korean version of Mini-Mental State Examination (MMSE-K) score≥24, unilateral neglect based on the Motor-Free Visual Perception Test (MVPT), paretic upper limb function≥Brunnstrom stage II, and the ability to understand the purpose of the study, to know that they were being recruited for this study, and to voluntarily agree to participate. The exclusion criteria were as follows: wrist or figure contracture, motor difficulties due to apraxia, speech difficulties due to aphasia, visual or auditory dysfunction that could reduce the ability to observe objects in the mirror or to follow instructions. This study was approved by the Research and Ethics Committee of Cheongju University (approval NO. 1041107-201902-HR-006-01).

2.2 Study design

After obtaining written consent from patients, a preliminary test was performed. All data on patient characteristics, inclusion criteria, and the preliminary tests used to measure the level of unilateral neglect were sent to the Occupational Therapy Division at a general hospital in Cheongju area. The chief of research who received the patient data used block randomization scheme to randomly allocate each patient into either the BMT or UMT group. Each group originally consisted of 15 patients, but due to early discharge of two, the final number of patients was 28. Throughout the double-blinded randomized study, the participants were not conveyed the reasons for grouping and received intervention in an independent space with only a therapist giving them instructions in a one-on-one setting. The information of the group allocation was also blinded for the study investigators, and the test results were managed by a trained occupational therapist with 5 years of clinical experience in patients with stroke. The chief of the research was not anonymized to the allocation but did not participate in either the intervention process or the evaluation of test results.

The BMT and UMT groups received 30 minutes of mirror therapy, 5 days a week, for a period of 4 weeks. Patients in both groups received the same rehabilitation treatments (occupational and physical therapy) as part of the standard hospital treatment. All patients were administered pre- and post-intervention tests to evaluate the effectiveness of the reduction of the symptoms of unilateral neglect such as the Star Cancelation Test (SCT), Line Bisection Test (LBT), Picture Scanning Test (PST), and Korean Catherine Bergego Scale (K-CBS). The Korean version of the Modified Barthel Index (K-MBI) was used to compare ADL performance. The mirror therapy program used in this study was applied by modifying the mirror treatment program of Arya et al. (2015), in both the BMT and UMT groups (Fig. 1).

Fig. 1

Flowchart of the study.

2.3 Measurements

The tools used in selecting the patients were as follows: the MVPT (Colarusso & Hammill, 1996) (to assess the presence of unilateral neglect), the K-MMSE (Kwon & Park, 1989) (to assess the patient’s cognitive level), and a survey on sex, age, disease type, paralysis type, and disease duration (to collect data on the patient’s general characteristics). The Behavioural Inattention Test (BIT) (Wilson et al., 1987) was used to measure the level of unilateral neglect. BIT has six conventional sub-tests (BIT-C) based on pencil-paper work and nine behavioral sub-tests (BIT-B) based on activity. To keep the efficiency of evaluation high and measure both aspects of unilateral neglect, SCT and LBT in BIT-C, and PST in BIT-B were selected instead of performing the entire BIT battery. To measure unilateral neglect in relation to daily living, K-CBS (Lee et al., 2015) was used. In addition, to measure functional ADL, K-MBI (Jung et al., 2007) was used.

2.4 Intervention

Each group received five 30-minute sessions of mirror therapy per week for four weeks. To deliver the mirror therapy, a table mirror of 57.5 cm×57.5 cm was vertically set up on a table that was positioned 10 cm away from the patient. The mirror was moved from the center toward the paretic side by 15 cm to allow the patient to observe the movement of the non-paretic upper limb in the mirror. The non-paretic upper limb was positioned in front of the mirror for reflection, and the paretic upper limb was hidden from the back view. For the UMT protocol, the same setting as above was used: the paretic upper limb in the back and the non-paretic upper limb in front of the mirror. The patient was instructed to fix the position of the paretic limb without mimicking the movement in the mirror, while the non-paretic limb performed the tasks in front of the mirror. For the BMT protocol, the patient was instructed to use the paretic limb as much as possible to perform the same tasks as the non-paretic limb, by following the movements reflected in the mirror. For each task, five sets (20 times per set) were performed, with a 2-minute rest between each set (Lee et al., 2014) (Fig. 2) (Fig. 3).

Fig. 2

Unimanual mirror therapy.

Fig. 3

Bimanual mirror therapy.

In this study, mirror therapy consisted of the items used in the task-based mirror therapy program of Arya et al. (2015); however, the procedures were adjusted to suit the present study. The items of the program were as follows: drinking water, turning a wooden block, grasping and lifting a rectangular block using the wrist, cleaning a table with a duster using the wrist, grasping or releasing a soft ball, picking up paper clips, beads, coins, and cereal; and clay activities (ball making, rolling, pressing, pinching, and breaking). Villiger et al. (2011) demonstrated that task-based training is far more effective for functional recovery than simple movements, as cerebral activities are enhanced. Further, it was found that task-based training employs a client-centered approach that motivates patients in a realistic setting during the process of active task performance to solve a specific, functional challenge, with a consequent positive effect on motor learning. Although mirror therapy was used to enhance upper and lower limb functions, it was not used as a unilateral neglect intervention.

2.5 Statistical analyses

The data collected in this study were analyzed using SPSS (version 22.0; IBM Corp., Armonk, NY, USA). Chi-squared tests were performed to confirm homogeneity between the two groups before the intervention. The Shapiro-Wilk test was performed to test the normality of the data; the normality assumption was not satisfied, and hence, non-parametric statistics were used. Frequency analysis, descriptive statistics, and the Mann–Whitney U test were used to analyze the general patient characteristics. The Mann-Whitney U test was used to compare pre- and post-intervention functional changes between the two groups, and the Wilcoxon signed-rank test was used for within-group comparisons. Statistical significance was set at p < 0.05.

3 Results

3.1 Functional homogeneity

No significant differences between the BMT and UMT groups were found in the general characteristics measured in this study (sex, age, disease type, paralysis type, and disease duration [p > 0.05]). The BMT group comprised four men and 10 women, and the UMT group comprised three men and 11 women. The average age in the BMT and UMT group was 69.29±8.02 years and 69.14±6.92 years, respectively. With regards to disease type, five and nine patients had infarction and hemorrhage, respectively in the BMT group, while four and 10 patients had infarction and hemorrhage, respectively, in the UMT group. The paralysis type in both the BMT and UMT groups was left hemiplegia, and the mean disease duration was 7.86±4.34 months and 10.36±3.00 months in the BMT and UMT group, respectively. Functional homogeneity was confirmed before intervention for all indicators examined in this study (SCT, LBT, PST, K-CBS, and K-MBI [p > 0.05]) (Table 1).

Table 1
Patient characteristics pre-intervention

BMT (n = 14) UMT (n = 14) p

Sex

Man 4 3 1.00

Woman 10 11

Age 69.29±8.02 69.14±6.92 0.71

Type of stroke

Infarction 5 4 0.69

Hemorrhage 9 10

Paretic side

Right – – 1.00

Left 14 14

Time since onset of stroke months 7.86±4.34 10.36±3.00 0.79

Brunnstrom stage 2.50±0.51 2.21±0.42 0.12

MMSE-K 24.92±1.14 25.64±1.27 0.10

MVPT 15.14±1.61 14.57±1.15 0.08

SCT 46.86±1.29 46.64±1.15 0.61

LBT 16.19±1.86 16.84±3.06 0.73

PST 4.98±1.29 4.64±1.44 0.56

K-CBS 17.85±4.01 17.5±4.18 0.61

K-MBI 35.64±16.08 30.92±11.57 0.50

	BMT (n = 14)	UMT (n = 14)	p
Sex
Man	4	3	1.00
Woman	10	11
Age	69.29±8.02	69.14±6.92	0.71
Type of stroke
Infarction	5	4	0.69
Hemorrhage	9	10
Paretic side
Right	–	–	1.00
Left	14	14
Time since onset of stroke months	7.86±4.34	10.36±3.00	0.79
Brunnstrom stage	2.50±0.51	2.21±0.42	0.12
MMSE-K	24.92±1.14	25.64±1.27	0.10
MVPT	15.14±1.61	14.57±1.15	0.08
SCT	46.86±1.29	46.64±1.15	0.61
LBT	16.19±1.86	16.84±3.06	0.73
PST	4.98±1.29	4.64±1.44	0.56
K-CBS	17.85±4.01	17.5±4.18	0.61
K-MBI	35.64±16.08	30.92±11.57	0.50

Values are expressed as Mean±SD, MMSE-K, Korean version of Mini-Mental State Examination; MVPT, Motor-Free Visual Perception Test; SCT, Star Cancellation Test; LBT, Line Bisection Test; PST, Picture Scanning Test; K-CBS, Korean Catherine Bergego Scale; K-MBI, Korean version of Modified Barthel Index.

3.2 Comparison of the BMT and UMT groups

In the post-intervention between-group comparison, a significant difference was found for SCT, a tool to measure unilateral neglect (p < 0.05), and for the LBT (p < 0.05). Both the BMT and UMT groups showed severe unilateral neglect before intervention; however, post-intervention, the BMT group showed recovery to normal levels, whereas the UMT group showed improvement toward mild unilateral neglect. A significant difference was also observed for the PST in the post-intervention between-group comparison (p < 0.05). The results of the K-CBS, a tool to measure levels of functional ADL in relation to unilateral neglect, showed a significant difference in the between-group comparison (p < 0.05). A significant difference was not found in the between-group comparison for the K-MBI, which measures ADL performance (p > 0.05) (Table 2).

Table 2
Changes in parameters before and after intervention

BMT UMT P

SCT Pre 46.86±1.29 46.64±1.15 0.61

Post 51.78±1.42 50.64±1.08 0.02^*

p 0.001^ 0.001^

LBT Pre 16.19±1.86 16.84±3.06 0.73

Post 5.86±2.02 8.85±4.02 0.04^*

p 0.001^ 0.001^

PST Pre 4.98±1.29 4.64±1.44 0.56

Post 8.14±1.16 6.92±1.15 0.02^*

p 0.001^ 0.001^

K-CBS Pre 17.85±4.01 17.5±4.18 0.61

Post 13.07±3.26 16.14±3.41 0.03^*

p 0.001^ 0.001^

K-MBI Pre 35.64±16.08 30.92±11.57 0.50

Post 48.14±14.73 40.42±11.14 0.16

p 0.001^ 0.001^

		BMT	UMT	P
SCT	Pre	46.86±1.29	46.64±1.15	0.61
	Post	51.78±1.42	50.64±1.08	0.02^*
	p	0.001^**	0.001^**
LBT	Pre	16.19±1.86	16.84±3.06	0.73
	Post	5.86±2.02	8.85±4.02	0.04^*
	p	0.001^**	0.001^**
PST	Pre	4.98±1.29	4.64±1.44	0.56
	Post	8.14±1.16	6.92±1.15	0.02^*
	p	0.001^**	0.001^**
K-CBS	Pre	17.85±4.01	17.5±4.18	0.61
	Post	13.07±3.26	16.14±3.41	0.03^*
	p	0.001^**	0.001^**
K-MBI	Pre	35.64±16.08	30.92±11.57	0.50
	Post	48.14±14.73	40.42±11.14	0.16
	p	0.001^**	0.001^**

Values are expressed as Mean±SD ^*Significant difference (p < 0.05) ^**Significant difference (p < 0.01); SCT, Star Cancellation Test; LBT, Line Bisection Test; PST, Picture Scanning Test; K-CBS, Korean Catherine Bergego Scale; K-MBI, Korean version of Modified Barthel Index.

4 Discussion

This study compared the effectiveness of two mirror therapy protocols, BMT and UMT in reducing the symptoms of unilateral neglect and improving ADL performance in stroke patients. A comparison of pre- and post-intervention test scores indicated significant improvement in both the BMT and UMT groups. Changes in SCT, LBT, PST, and K-CBS scores indicated significant reduction in unilateral neglect symptoms, and changes in K-MBI scores indicated significant improvement in ADL performance. Between-group comparisons showed that although there were no significant differences in pre-intervention test scores, all of the post-intervention tests except K-MBI showed a significant difference.

In the present study, BMT was more effective than UMT in reducing the symptoms of unilateral neglect. However, Geller (2018) reported that UMT was more effective than BMT in the recovery of upper limb function and improvement in ADL performance. The conflicting results between the two studies may be due to the difference in the nature of the key indicator measured in each study; unilateral neglect in this study is a cognitive factor, whereas upper limb function is a physical factor. For the latter, Selles et al. (2014) suggested that in interventions based on BMT, the proprioceptive senses stimulated by the movement of the paretic upper limb behind the mirror may cause a visual illusion as a result of a discrepancy with the visual feedback from the mirror to decrease the effectiveness of mirror therapy. The results of the present study, however, indicate that the movement of the paretic upper limb behind the mirror during BMT may have been due to limb activation. Regarding unilateral neglect as a cognitive factor, Halligan (1991) reported that the movement of the paretic upper limb when a patient with unilateral neglect performs a task may stimulate the somatosensory system to reduce the symptoms of unilateral neglect. In a study by Luukkainen et al. (2009), the movement of the paretic upper limb was effective in reducing the symptoms of unilateral neglect. In the present study, the limb activation effect via stimulated proprioceptive senses of the paretic upper limb may have combined with the visual feedback effect from the mirror therapy, wherein the patient gives attention to the paretic side to see the movement of the non-paretic upper limb on the mirror, thereby increasing the positive effect of reducing the symptoms of unilateral neglect. The findings of Tai et al. (2020) that BMT led to greater activations of primary motor cortex (M1) than UMT also support our study.

In the present study, tests were performed to assess the ADL and the results showed significant difference in terms of K-CBS for between-group comparison before and after the intervention, but not for K-MBI. This was in contrast to a study conducted by Cho & Kwon (2019), in which both K-CBS and K-MBI showed an improvement and also reduced the symptoms of unilateral neglect. The K-CBS is a test that directly evaluates the level of unilateral neglect by measuring it in activities such as getting dressed, eating, using a wheelchair, and personal hygiene. However, the K-MBI is a test that indirectly evaluates the level of unilateral neglect by measuring its influence on the performance of the ADL such as climbing steps, cleaning after defecation and control of urination, and movements on a chair or in bed. While intensive treatment for a short period of 4 weeks caused a short-term increase in K-CBS scores via reduced unilateral neglect, the K-MBI scores showed no difference, as its functions require a long time for improvement. Thus, further studies should investigate the effects of reduced the symptoms of unilateral neglect on long-term functional changes.

In addition, the intervention outcome of reduced unilateral neglect in the present study was achieved by setting the intervention duration to 30 minutes, as in Lee et al. (2014), rather than 1 to 2 hours, as in Arya et al. (2015). Continuous monitoring by the occupational therapist during the intervention of the movement of the paretic limb behind the mirror might have increased the attention of the patients, thereby, leading to the same positive effect as reported in previous studies. Thus, it is suggested that the intervention time could be set to 30 min in clinical practice

The mirror therapy used in this study was not a simple program used by Yavuzer et al. (2008), but the task-based program of Arya et al. (2015). Task-based training is widely used in stroke rehabilitation (Veerbeek et al., 2014). In task-based training, goal-oriented repetitive practices are employed to facilitate motor recovery (Arya et al., 2012). Villiger et al. (2011) claimed that a neuron in the mirror neuron system is activated upon observing or mimicking an action. This activation is further increased upon combining objects, as opposed to simply mimicking a given motion. Arya et al. (2015) reported that task-based training is far more effective in functional recovery than simple movements, as cerebral activities are enhanced with the recovery of actual motor skills through neuroplasticity. In addition, task-based training uses a client-centered approach in which patients are motivated in a realistic setting during the process of active task performance to solve a specific, functional challenge, with a consequent positive effect on motor learning (Carr & Shepherd, 2003). This form of training likely influenced the participation and attention of participants.

The limitations of this study are as follows: First, the small sample size prevents generalization of the observed positive effect of the two mirror therapy protocols on unilateral neglect. Second, the intervention was carried out for a short period of 4 weeks; therefore, only a short-term effect could be verified. Third, no follow-up was performed to verify the continuity of the effect after the completion of intervention. Therefore, the number of participants should be increased to determine whether the intervention effect can be generalized, the period of intervention should be increased to verify long-term effects, and follow-up monitoring should be carried out to verify the continuity of the intervention effect after completion.

The clinical significance of this study lies in the fact that the positive effect of BMT or UMT as an intervention to improve unilateral neglect in stroke patients has been verified. Notably, in this study, BMT was more effective in reducing unilateral neglect. Furthermore, the findings of this study suggest that these two protocols of mirror therapy will prove useful as an intervention in stroke rehabilitation to reduce the symptoms of unilateral neglect and improve ADL performance.

5 Conclusions

This study investigated the effect of two mirror therapy protocols (BMT and UMT) in reducing the symptoms of unilateral neglect in stroke patients. Pre- and post-test comparisons indicated significant reduction of unilateral neglect and significant improvement in ADL performance in both the BMT and UMT groups. In addition, BMT was more effective than UMT in reducing the symptoms of unilateral neglect and improving ADL performance. These findings suggest that while the two protocols of mirror therapy can be applied in the treatment of stroke patients with unilateral neglect, task-based BMT is a more effective treatment method for reducing the symptoms of the symptoms of unilateral neglect.

Footnotes

Acknowledgments

This paper was written by revising and supplementing the first author’s master’s thesis.

Conflict of interest

The authors declare that there is no conflict of interest.

Funding

This study received no funding.

References

Altschuler,

E. L.

, Wisdom,

S. B.

, Stone,

, Foster,

, Galasko

, Llewellyn,

D. M. E.

, & Ramachandran,

(1999) Rehabilitation of hemiparesis after stroke with a mirror. The Lancet, 353(9169), 2035–2036. doi:. https://doi.org/10.1016/S0140-6736(99)00920-4

Arya,

K. N.

, Pandian,

, Kumar,

, & Puri,

(2015) Task-Based Mirror Therapy Augmenting Motor Recovery in Poststroke Hemiparesis: A Randomized Controlled Trial, Stroke and Cerebrovascular Disease, 24(8), 1738–1748. doi: 10.1016/j.jstrokecerebrovasdis.2015.03.026

Baylis,

G. C.

, Baylis,

L. L.

, & Gore,

C. L.

(2004) Visual Neglect can be Object-Based or Scene-Based Depending on Task Representation, Cortex, 40(2), 237–246. doi: 10.1016/s0010-9452(08)70119-9

Bollea,

, Rosa,

G. D.

, Gisondi,

, Guidi,

, Petrarca,

, Giannarelli,

, & Castelli,

(2007) Recovery from hemiparesis and unilateral spatial neglect after neonatal stroke. Case report and rehabilitation of an infant, Brain Injury, 21, 81–91. doi: 10.1080/02699050601148882

Buccino,

, Binkofski,

, Fink,

G. R.

, Fadiga,

, Fogassi,

, Gallese,

, Seitz,

R. J.

, Zilles,

, Rizzolatti,

, & Freund,

H. J.

(2001) Action observation activates premotor and parietal areas in a somatotopic manner: an fMRI study, The European joiurnal of neuroscience, 13(2), 400–404. doi: .

Buccino,

, Solodkin,

, & Small,

S. L.

(2006) Functions of the Mirror Neuron System: Implications for Neurorehabilitation, Cognitive and Behavioral Neurology, 19(1), 55–63. doi: 10.1097/00146965-200603000-00007

Butter,

, & Kirsch,

(1992) Combined and Separate Effects of Eye Patching and Visual Stimulation on Unilateral Neglect Following Stroke, Archives of Physical Medicine and Rehabilitation, 73(12), 1133–1139.

Carr,

J. H.

, & Shepherd,

R. B.

(2003). Stroke Rehabilitation: guidelines for exercise and training to optimize motor skill. Oxford: Buttlerworth-Heinemann.

Cazzoli,

, Müri,

R. M.

, Hess,

C. W.

, & Nyffeler,

(2010). Treatment of hemispatial neglect by means of rTMS - a review. Restorative Neurology and Neuroscience, 28(4), 499–510. https://doi.org/10.3233/RNN-2010-0560

10.

Cho

Y. J.

, & Kwon

J. S.

(2019) The Feasibility of Audio Visual Biofeedback Training on Unilateral Neglect of Stroke: The Pilot Study, The Journal of Korean Society of Cognitive Rehabilitation, 8(1), 37–58.

11.

Colarusso,

R. P.

, & Hammill,

D. D.

(1996). Motor-Free Visual Perception Test-Revised Manual. California: Academic therapy Publications.

12.

Ertelt,

, Small,

, Solodkin,

, Dettmers,

, McNamara,

, Binkofski,

, & Buccino,

(2007) Action observation has a positive impact on rehabilitation of motor deficits after stroke, Neuroimage, 36, 164–173. doi: 10.1016/j.neuroimage.2007.03.043

13.

Geller,

D. L.

(2013). HomeMirror Therapy:ARandomized Control Study Comparing Unimanual and Bimanual Mirror Therapy for Improved Arm and Hand Function Post-stroke, Columbia University, USA.

14.

Halligan,

P. W.

, Manning,

, & Marshall,

J. C.

(1991) Hemispheric activation vs spatio-motor cueing in visual neglect: A case study, Neuropsychologia, 29(2), 165–176. doi: 10.1016/0028-3932(91)90018-4

15.

Hamzei,

, Läpchen,

C. H.

, Glauche,

, Mader,

, Rijntjes,

, & Weiller,

(2012) Functional Plasticity Induced by Mirror Training, Neurorehabilitation and Neural Repair, 26(5), 484–496. doi: 10.1177/1545968311427917

16.

Jung,

H. Y.

, Park,

B. K.

, Shin,

H. S.

, Kang,

Y. K.

, Pyun,

S. B.

, Paik,

N. J.

,. . . Han,

T. R.

(2007) Development of the Korean version of Modified Barthel Index(K-MBI): Multi-center study for subjects with stroke, Journal of Korean Academy of Rehabilitation Medicine, 31, 283–297.

17.

Karnath,

H.-O.

, Christ,

, & Hartje,

(1993) Decrease of contralateral neglect by neck muscle vibration and spatial orientation of trunk midline, Brain, 116, 383–396.

18.

Kerkhoff,

, Hildebrandt,

, Reinhart,

, Kardinal,

, Dimova,

, & Utz,

K. S.

(2011) A long-lasting improvement of tactileextinction after galvanic vestibular stimulation: TwoSham-stimulation controlled case studies. Neuropsychologia, 49(2), 186–195. https://doi.org/10.1016/j.neuropsychologia.2010.11.014

19.

Kerkhoff,

, Reinhart,

, Ziegler,

, Artinger,

, Marquardt,

, & Keller,

(2013) Smooth Pursuit Eye Movement TrainingPromotes Recovery From Auditory and Visual Neglect: A RandomizedControlled Study. Neurorehabilitation and Neural Repair, 27(9), 789–798. https://doi.org/10.1177/1545968313491012

20.

Kim,

Y. M.

, Chun,

M. H.

, Yun,

G. J.

, Song,

Y. J.

, & Young,

H. E.

(2011) The Effect of Virtual Reality Training on Unilateral SpatialNeglect in Stroke Patients. Annals of Rehabilitation Medicine, 35(3), 309. https://doi.org/10.5535/arm.2011.35.3.309

21.

Kim,

, Lee,

, Kim,

, Lee,

, & Kim,

(2016) Effects of mirror therapy combined with motor tasks on upper extremity function and activities daily living of stroke patients, Journal of Physical Therapy Science, 28(2), 483–487. doi: 10.1589/jpts.28.483

22.

Koch,

, Bonni,

, Giacobbe,

, Bucchi,

, Basile,

, Lupo,

, Versace,

, Bozzali,

, & Caltagirone,

(2012) Theta-burststimulation of the left hemisphere accelerates recovery ofhemispatial neglect. Neurology, 78(1), 24–30. https://doi.org/10.1212/WNL.0b013e31823ed08f

23.

Kwon,

Y. C.

, & Park,

J. H.

(1989) Korean version of Mini-Mental State Examination (MMSE-K). Part I: Development of the test for the elderly, Journal of Korean Neuropsychiatric Association, 28(1), 125–135.

24.

Lee,

B. E.

, Choi,

H. S.

, & Han,

S. J.

(2015) Reliability and Validity of Korean Catherine Bergego Scale for Evaluation of Unilateral Neglect in Stroke Patients, The Journal of Korean Society of Occupational Therapy, 23(2), 45–56. doi: 10.14519/jksot.2015.23.2.04

25.

Lee,

M. M.

, Cho,

, & Song,

C. H.

(2012) The Mirror Therapy Program Enhances Upper-Limb Motor Recovery and Motor Function in Acute Stroke Patients, American Journal of Physical Medicine & Rehabilitation, 91(8), 689–700. doi: 10.1097/phm.0b013e31824fa86d

26.

Lee, , Seul-A., , Kim , Hee-Jung., , Hong, , Ki-Hoon, , Lee, , & Chun-Yeop, (2014) Effect of Upper Extremity Function and Activities of Daily Living of Mirror Therapy on Patients Who Have a Stroke, with or without Unilateral Neglect, The Journal ofKorean Society of Community-Based Occupational Therapy, 54(1), 33–45.

27.

Luukkainen-Markkula,

, Tarkka,

I. M.

, Pitkänen,

, Sivenius

, & Hämäläinen,

(2009) Rehabilitation ofhemispatial neglect: A randomized study using either arm activationor visual scanning training, Restorative Neurology and Neuroscience, 27(6), 665–674. https://doi.org/10.3233/RNN-2009-0520

28.

Narayan Arya,

, Verma,

, Garg,

R. K.

, Sharma,

V. P.

, Agarwal,

, & Aggarwal,

G. G.

(2012) Meaningful Task-Specific Training (MTST) for Stroke Rehabilitation: A Randomized Controlled Trial, Topics in Stroke Rehabilitation, 19(3), 193–211. doi: 10.1310/tsr1903-193

29.

Pandian,

J. D.

, Arora,

, Kaur,

, Sharma,

, Vishwambaran,

D. K.

, & Arima,

(2014) Mirror Therapy in Unilateral Neglect After Stroke (MUST trial): A randomized controlled trial, Neurology, 83(11), 1012–1017. doi: 10.1212/wnl.0000000000000773

30.

Park,

J. H.

, & Lee,

J. H.

(2015) The effects of mental practice onunilateral neglect in patients with chronic stroke: A randomizedcontrolled trial. Journal of Physical Therapy Science, 27(12), 3803–3805.https://doi.org/10.1589/jpts.27.3803

31.

Park,

, Chang,

, Kim,

K.-M.

, & An,

D.-H.

(2015) The effects of mirror therapy with tasks on upper extremity function and self-care in stroke patients, Journal of Physical Therapy Science, 27(5), 1499–1501. doi: 10.1589/jpts.27.1499

32.

Ramachandran,

V. S.

, & Rogers-Ramachandran,

(1996) Synaesthesia in Phantom Limbs Induced with Mirrors. Proceedings of the Royal Society B, Biological Sciences, 263(1369), 377–386. doi: 10.1098/rspb.1996.0058

33.

Rizzolatti,

, Fadiga,

, Gallese,

, & Fogassi,

(1996) Premotor cortex and the recognition of motor actions, Cognitive Brain Research, 3(2), 131–141. doi: 10.1016/0926-6410(95)00038-0

34.

Robertson,

I. H.

, & Halligan,

P. W.

(1999). Spatial neglect: a clinical handbook for diagnosis and treatment. Hove: Psychology Press.

35.

Robertson,

I. H.

, North,

(1993) Active and passive activation of left limbs: influence on visual and sensory neglect, Neuro psychologia, 31(3), 293–300. doi: 10.1016/0028-3932(93)90093-f

36.

Rossi,

P. W.

, Kheyfets,

, & Reding,

M. J.

(1990). Fresnel prismsimprove visual perception in stroke patients with homonymoushemianopia or unilateral visual neglect, Neurology, 40(10), 1597. https://doi.org/10.1212/WNL.40.10.1597

37.

Saevarsson,

, Kristja'nsson,

A'.

, & Hjaltason,

, (2009b). Unilateral neglect: A review of causes, anatomical localization, theories and interventions, Laeknabladid, 95, 27–33.

38.

Samuelkamal-Eshkumar,

, Reethajanetsureka,

, Pauljebaraj,

, Benshamir,

, Padankatti,

S. M.

, & David,

J. A.

(2014) Mirror Therapy Enhances Motor Performance in the Paretic Upper Limb After Stroke: A Pilot Randomized Controlled Trial, Medicine and Rehabilitation, 95(11), 2000–2005. doi: 10.1016/j.apmr.2014.06.020

39.

Selles,

R. W.

, Michielsen,

M. E.

, Bussmann,

J. B. J.

, Stam,

H. J.

, Hurkmans,

H. L.

, Heijnen,

,. . . Ribbers,

G. M.

(2014) Effects of a Mirror-Induced Visual Illusion on a Reaching Task in Stroke Patients, Neuro rehabilitation and Neural Repair, 28(7), 652–659. doi: 10.1177/1545968314521005

40.

Selzer,

M. E.

, Clarke,

, Cohen,

L. G.

, Duncan,

P. W.

, & Gage,

F. H.

(2006). Textbook of neural repair and rehabilitation. New York, NY: Cambridge University Press.

41.

Shih,

, Wu,

, Lin,

, Cheng,

, Hsieh,

, Chen,

, Lai,

, & Chen,

(2017). Effects of action observation therapy and mirrortherapy after stroke on rehabilitation outcomes and neuralmechanisms by MEG: Study protocol for a randomized controlled trial. Trials, 18(1), 459. https://doi.org/10.1186/s13063-017-2205-z

42.

Stevens,

J. A.

, & Stoykov,

M. E. P.

(2003) Using Motor Imagery in the Rehabilitation of Hemiparesis No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated, Archives of Physical Medicine and Rehabilitation, 84(7), 1090–1092. doi: 10.1016/s0003-9993(03)00042-x

43.

Tai,

R.-Y.

, Zhu,

J.-D.

, Cheng,

C.-H.

, Tseng,

Y.-J.

, Chen,

C.-C.

, & Hsieh,

Y.-W.

(2020) Cortical neural activity evoked by bilateraland unilateral mirror therapy after stroke. Neurophysiology, 131(10), 2333–2340. https://doi.org/10.1016/j.clinph.2020.06.030

44.

Tham,

, Ginsburg,

, Fisher,

A.G.

, & Tegner,

(2001) Training to improve awareness of disabilities in clients with unilateral neglect, American Journal of Occupational Therapy, 55, 46–54. doi: 10.5014/ajot.55.1.46

45.

Thieme,

, Morkisch,

, Mehrholz,

, Pohl,

, Behrens,

, Borgetto,

, & Dohle,

(2018). Mirror therapy for improving motor function after stroke. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd008449.pub3

46.

Utz,

K. S.

, Dimova,

, Oppenländer,

, & Kerkhoff,

(2010) Electrified minds: Transcranial direct current stimulation (tDCS)and Galvanic Vestibular Stimulation (GVS) as methods of non-invasivebrain stimulation in neuropsychology—A review of current dataand future implications, Neuropsychologia, 48(10), 2789–2810. https://doi.org/10.1016/j.neuropsychologia.2010.06.002

47.

Xu,

, Guo,

, Salem,

H. M. A.

, Chen,

, & Huang,

(2017) Effects of mirror therapy combined with neuromuscular electricalstimulation on motor recovery of lower limbs and walking ability ofpatients with stroke: A randomized controlled study. Clinical Rehabilitation, 31(12), 1583–1591. https://doi.org/10.1177/0269215517705689

48.

Yang,

, Zhao,

, Zhang,

, Wu,

, Jiang,

, & Cheng,

(2018) Effect of Mirror Therapy on Recovery of Stroke Survivors: ASystematic Review and Network Meta-analysis. Neuroscience, 390,, 318–336. https://doi.org/10.1016/j.neuroscience.2018.06.044

49.

Veerbeek,

J. M.

, van Wegen,

, van Peppen,

, van der Wees,

P. J.

, Hendriks,

, Rietberg,

, & Kwakkel,

(2014) What Is theEvidence for Physical Therapy Poststroke? A Systematic Review andMeta-Analysis. PLoS ONE, 9(2), e87987. https://doi.org/10.1371/journal.pone.0087987

50.

Villiger,

, Chandrasekharan,

, & Welsh,

T. N.

(2011) Activity of human motor system during action observation is modulated by object presence, Experimental Brain Research, 209, 85–93. doi: 10.1007/s00221-010-2522-x

51.

Wilson,

, Cockburn,

, & Halligan,

(1987). Behavioural Inattention Test. Fareham, UK: Thames Valley Test Company.

52.

Wittkopf,

P. G.

, & Johnson,

M. I.

(2017). Mirror therapy: A potential intervention for pain management. Revista DaAssociaçãoMédica Brasileira, 63(11), 1000–1005. https://doi.org/10.1590/1806-9282.63.11.1000

53.

Yavuzer,

, Selles,

, Sezer,

, Sübeyaz,

, Bussmann,

J.B.

, Köeoğelu,

,. . . Stam,

H. J.

(2008) Mirror TherapyImproves Hand Function in Subacute Stroke: A Randomized ControlledTrial, Archives of Physical Medicine and Rehabilitation, 89(3), 393–398. doi: 10.1016/j.apmr.2007.08.162