Effects of mirror neuron system‐based training on rehabilitation of stroke patients

Abstract Objective To investigate the clinical effects of the mirror neuron system (MNS)‐based training on upper extremity motor function and cognitive function in stroke patients. Methods Sixty stroke patients (time from stroke onset 3–9 months) with upper extremity paresis (Brunnstrom stage II–IV) and cognitive impairment (MoCA score ≥ 15) were enrolled in this study. Patients were randomly allocated into MNS treatment group (N = 30) and control group (N = 30). Both groups underwent regular training for upper extremity motor function and cognitive function, and the MNS group was trained with a therapeutic apparatus named mirror neuron system training (MNST) including different levels of action observation training (AOT). Training lasted 20 min/day, 5 days/week for 8 weeks. MoCA, reaction time, and Wisconsin Card Sorting Test (WCST) were assessed at baseline and 8 weeks after training. Furthermore, Fugl‐Meyer assessment (FMA) and Modified Barthel index (MBI) were adopted to evaluated upper extremity motor function and daily life ability. Results After 8 consecutive weeks’ training, both groups showed significant improvements on the upper extremity motor function, cognitive function, and daily life ability score after training (p < .05). The MNS group showed significantly improved upper extremity motor function and cognitive function (p < .05) compared with control group. Conclusions Combining MNS‐based and conventional training can improve upper extremity motor function and cognitive function in stroke patients.


| INTRODUC TI ON
Stroke is a common central nervous system disease characterized with loss of brain function, such as motor disorders, perception disorders, language disorders, and sensory disturbances. As the aging population increased, the incidence of stroke continuously rising.
Studies showed that 75% of stroke patients suffer upper extremity dysfunction and 50% experience cognitive dysfunction (Huang & Yang, 2014;Serrano, Domingo, Rodriguez-Garcia, Castro, & del Ser, 2007), which severely influence quality of life and places considerable burden on the patient's family and society. Therefore, the upper limb dysfunction combined with cognitive impairment are two important factors in daily living that should be focused on the rehabilitation field.
Mirror neuron system-based training is one of the hot treatment technologies in recent years, which provides a motion-observation-execution matching mechanism and brings a new strategy for functional rehabilitation after stroke. In this study, we aim to further verify the effectiveness of mirror neuron-based training (by a new apparatus named MNST) on both motor and cognitive function for 60 stroke patients over a relatively long time period (8 weeks).

| Patients
Our study has been approved by Ethics Committee of Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine. We also registered our clinical trial at www.chictr.ogr. cn after got ethics permission. The clinical trial registration number is ChiCTR 1800017588. Sixty patients were enrolled in this study and randomly divided into MNS group and Control group, with 30 patients in each group by a computer-generated randomization list.
All assessments in both groups were performed by a certain therapist, who did not treat these enrolled patients and also blinded to the treatment allocation. All patients had signed informed consent before enrollment.

| Inclusion criteria
(a) First onset of stroke as confirmed with brain MRI, whose vital sign was stable and also with hemiplegia and cognitive impairment; (b) clinical course between 3-9 months; (c) age range from 40 to 80 years old; (d) signed informed consent and willing to attend our study; (e) right handed according to the Edinburgh Handedness Inventory; (f) >9 years of education (beyond junior middle school); (g) Brunnstrom stage II-IV of the upper extremity; (h) MoCA scores of 15 or above.

| Intervention method
A new apparatus named Mirror Neuron System Training (MNST, V1.0, Suzhou MNST Medical Science and Technology Co., LTD) based on mirror neuron theory was implemented to train the patients in this study (pictures shown in Figure 1).
Mirror neuron system training contains two primary parts: One involves virtual reality (VR) glasses, and the other is a system including hundreds of daily hand action videos, such as cracking a peanut, cutting a watermelon, and turning on an air conditioner. Using the VR glasses, the patients could see these hand action videos. This kind of action observation training (AOT) was reported to activate the mirror neuron system (overlap with motor, language, and cognition neural circuits) and therefore improve motor, language, and cognitive functions (Brooks & Rose, 2003;Cauraugh & Kim, 2002;Cui et al., 2014;Wang, Feng, et al., 2015).

| Outcome measurement
Patients were assessed at baseline and after 8-week treatment.  MoCA, simple response, FMA, and improved Barthel index results before and after treatment between the two groups were compared by an independent sample t test and paired t test within each group. Statistical significance was determined when p < .05. In control group, there were 23 infarcts and 7 hemorrhages.

| General information
While there were 24 infarcts and 6 hemorrhages in MNS group.

Baseline demographic characteristics between groups including
sex proportion, the average of age, education level, clinical course, and NIHSS score had no significant difference (Table 1) were not statistically different between the two groups (Tables 2   and 3).

| Effects compared between the two groups
The participants in both groups had improvement at the end of

| D ISCUSS I ON
The incidence of stroke has increased in recent years, with subsequent dysfunctions cognitive, swallowing, and motor ability commonly observed. With such high prevalence, loss of activity of daily living (ADL), and heavy family and societal burden (Buccino, Solodkin, & Small, 2006;Zhang & Ma, 2013), cognitive and upper extremity dysfunction are primary goals and challenges in stroke rehabilitation.
Several new treatment techniques such as action observation training (AOT) are based on the mirror neuron system (MNS) theory.

MNS involves an action observation-execution matching mecha-
nism that encompasses visual observation, motor imagination, imitation, and learning. This process stimulates neural plasticity by activating the brain MNS system following stroke.
Discovery of the mirror neuron is one of the most important advances in the field of neuropsychology. Mirror neurons will fire both when executing movement (e.g., hand movement) and observing the same movement (Luber & Lisanby, 2014). Mirror neurons are therefore considered an important neural substrate for understanding action, imitation, language learning, and empathy. The mirror neuron system (MNS) primarily consists of the inferior frontal gyrus (BA44), premotor cortex (BA6), and inferior parietal lobule (BA39, 40) of the TA B L E 1 Clinical baseline information of participants(gender, age, clinical course, NIHSS score, stroke type, education level) (Mean ± SD) Note: The two groups were compared using unpaired t tests.
brain (Luber & Lisanby, 2014). Mirror neurons system activation has been found to contribute to improved motor functions in stroke patients (Sale & Franceschini, 2012;Small, Buccino, & Solodkin, 2012), as well as language and spatial attention functions of stroke patients with aphasia and hemineglect Wang, Zhang, et al., 2015). Therefore, MNS-based training may potentially be a valuable new therapeutic strategy for functional recovery after stroke (Zhang & Ma, 2013). However, most studies regarding MNS-based training for stroke have assessed small sample sizes observed the effects after short periods of training (e.g., 3-4 weeks). Furthermore, few studies reported concurrent motor and cognitive function recovery following MNS-based training for stroke patients.
In the present study, we trained poststroke patients in utilizing their upper extremities and test cognitive disorders through AOT.
The goal was to confirm the efficacy of this new training program on motor and cognitive impairment for patients following stroke. studies have shown that MNS in these areas is also associated with understanding movement and touch perception, and repeated stimulation promotes remodeling of the cerebral cortex, thus promoting the recovery of impaired brain function (Iacoboni & Dapretto, 2006;Liu & Feng, 2012;Rizzolatti & Craighero, 2004).
We also found improvements in Wisconsin Card Sorting Test (WCST) results, which indicate that AOT treatment improved patients' concentration and ability for mental multitasking. The regions involved in these activities are located in the prefrontal cortex and temporal gyrus, which coincide with the areas of MNS distribution. Based on the results of the present study, we propose that treatment stimulating the MNS simultaneously activated these areas, improving aspects of patients' cognition. Concentration is an important part of cognitive function and plays a role in functional recovery of the upper extremities. We clinically noticed that patients with attention disorders could not understand and cooperate with the therapist. As a result, the effect of rehabilitation training was often very poor. Therefore, it is essential to improve concentration ability and attention span to aid in therapeutic rehabilitation and promote effective motor relearning.
To the best of our knowledge, this is the first report on the effectiveness of mirror neuron-based training (by a new apparatus) on both motor and cognition function in a cohort of stroke patients over a relatively long period of time (8 weeks). In addition, this therapeutic model is in accordance with the current popular "central-peripheral-central" closed-loop rehabilitation model, which conforms to the latest hand function and cognitive rehabilitation trends.
Due to the restriction of sample size, site, and equipment, our study was unable to provide mechanistic evidence concerning the TA B L E 3 Comparison of the Wisconsin Card Sorting Test (WCST) between the two groups before and after treatment Note: The two groups were compared using unpaired t tests.
relevant roles of different periods of onset in patients. Another limitation is the lack of follow-up because of not allowed so long-term evaluation, which may be prone to biases.
Future studies will further be established to address and resolve these questions.

| CON CLUS ION
Combining MNS-based and conventional training can improve upper extremity motor function and cognitive function in stroke patients.

ACK N OWLED G M ENTS
The study was supported by The Commission of Health and Family

CO N FLI C T O F I NTE R E S T
None declared.

AUTH O R CO NTR I B UTI O N S
HM, YL, and CS designed the study; HM, LT, LL, and JN performed the clinical management and data collection; HM and YC performed the data analysis; HM wrote the manuscript draft; and all authors reviewed the manuscript.

DATA AVA I L A B I L I T Y S TAT E M E N T
All original data will be available when contact the corresponding authors by email.