Abstract
Keywords
Introduction
Stroke patients cannot perform normal motor functions due to a decrease in afferent sensory input that affects the sensory motor feedback loop (Ghez et al., 1995). Moreover, excessive stretch reflex causes spasticity, which reflects the dominance of the extensors in the lower extremity (Thibaut et al., 2013). The dominant extensors decrease dorsiflexion in the swing phase during ambulation (Lamontagne et al., 2002). Stiffness of the ankle joint due to decreased dorsiflexion causes asymmetrical and slow ambulation, reduction of weight-bearing ability of the lower limbs, and decreased balance (Hirsch et al., 2005). Decrease in afferent sensory input and excessive stretch reflex in stroke patients restrict functional movements and cause difficulties in daily activities.
In order to stimulate functional movements in stroke patients, stimulation for voluntary movements through different afferent sensory inputs is necessary (Merians et al., 2006; Nudo & Miliken, 1996). Study on animal brain stimulation by Chen and Russo-Neustadt (2005) reported that voluntary movements stimulate synthesis of proteins related to neuroplasticity and positively affect recovery of the central nervous system. Voluntary movement stimulation through afferent sensory input is very important for brain recovery from damage.
In order to improve the effects of afferent sensory input on physiotherapy, functional electric stimulation (FES) treatment is conducted (Kesar et al., 2009; Sabut et al., 2010). Powell et al. (1999) reported that although FES is effective for brain reconstruction, inhibition of spasticity, increasing joint movement range, and increasing muscle strength, its effect on voluntary movement improvement is debatable, since FES provides cyclic stimulation. In other words, it is difficult to motivate voluntary movement through FES (Gabr et al., 2005).
Unlike conventional FES, electromyography-triggered functional electrical stimulation (ETFES) involves patient effort to voluntarily contract a specific muscle. ETFES sets the voluntary muscle contraction signal threshold beforehand and produces electrical stimulation whenever a signal greater than the threshold is received, allowing active electrical stimulation treatment (Bolton et al., 2004; Cauraugh et al., 2000). ETFES treatment requires more patient effort than FES. De Kroon and IJzerman (2008) reported that ETFES could be more effective than cyclic stimulation for motor function improvement. However, a positive effect of ETFES should not be expected if the patient does not exert effort above the threshold to produce voluntary movement. Most previous studies did not provide motivation for voluntary movement during ETFES stimulation (Hara et al., 2013; von Lewinski et al., 2009). Therefore, afferent sensory input is necessary to produce motivational stimuli for movement during ETFES.
In this study, action observational training was used as afferent sensory input to produce motivational stimuli for movement during ETFES. Action observational training provides motivation for movement and improves functional movement through imitation and practice of observed movements (Iacoboni, 2005). Celnik et al. (2006) reported that a group that practiced movements after observational training showed greater improvement in functional movement than the group that only practiced movements without observational training. Franceschini et al. (2010) reported that application of both observational and movement training can improve concentration in stroke patients, and can positively affect functional improvement. Gabr et al. (2005) also reported that a combination of ETFES and motivational training could easily induce voluntary movements in patients, and consequently improve their motor functions.
This study investigated the changes in the cerebral cortex and spinal motor neurons of stroke patients caused by a combination of ETFES and dual-afferent sensory input training that induces voluntary movement. The changes were investigated to determine whether or not they could improve motor function.
Methods
Participants
This study was conducted on 18 subjects who were diagnosed with left hemiplegia between 6 months and 24 months prior. The subjects were selected based on the following criteria: absence of visual problems, auditory problems, or aphasia; Grade 1 or 2 modified Ashworth scale (MAS) score for the ankle; poor to fair scores in ankle dorsiflexion manual muscle testing (MMT); and ability to walk independently for 10 m. The exclusion criteria were the following: presence of a cardiac pacemaker; neglect syndrome; skin lesion at the electrode site; and previous similar training. The patients were randomly assigned to a dual-afferent sensory input (DASI) group or a control group. All subjects volunteered for the study and the experiment was conducted after receiving approval from the Dongshin University Institutional Review Board (IRB No. BM-002-01). Subject characteristics are shown in Table 1.
General and clinical characteristics of subjects
General and clinical characteristics of subjects
All values are shown as mean ± standard deviation (SD). Control: functional electric stimulation; DASI: EMG-triggered functional electric stimulation with action observation; independent t-test was used.
Random group assignment was performed with sealed envelopes. Subjects in the DASI group underwent ETFES with action observational training for a period of 4 wk, 5 d/wk for 20 min per session; the control group underwent FES for the same period. All participants also received general physical therapy, including Bobath approach for 30 min/d, 5 d/wk.
Intervention
A Microstim device (Medel GmBH, Berlin, Germany) was used to apply FES in the control group. With the subject in a comfortable sitting position, the skin was disinfected with alcohol and the active electrode (–) was placed on the common peroneal nerve area 3 cm below the fibular head. Inactive electrodes (+) were placed on the tibialis anterior 5 cm above the ankle and on the outer ankle. Using bipolar placement of the electrodes, asymmetrical biphasic waves were applied for 20 min (Kesar et al., 2009). The pulse frequency was 40 pps, pulse duration was 250 μs, and the intensity was set to 30–70 mA, with valgus position and dorsiflexion confirmation by the physician, while making sure the patient did not feel discomfort (Kesar et al., 2009). The patients were instructed to dorsiflex upon FES application.
To provide motivational stimuli in the DASI group, dorsiflexion of the contralateral ankle was recorded in advance. The subjects watched their recordings for 20 min and were to imitate the movement. ETFES (EMGFES 3000, Cyber Medic Inc., Korea) was also applied with the subjects in a comfortable sitting position. The placement of the electrodes and the electrical current settings were identical to those for FES. In addition, an electromyography (EMG) electrode was placed on the tibialis anterior to detect muscle activity. The electrodes were set to assist muscle contraction when a voluntary signal above the threshold was detected. Movement of the contralateral foot induced by ETFES was also shown live to the subjects on a monitor. Subjects compared the live and previously recorded movements of the contralateral foot and performed movement during ETFES application.
Outcome measures
This study used the movement-related cortical potential (MRCP), H-reflex, EMG, and the Biorescue system (RM Ingenierie, France) for assessment of the effects of ETFES with action observational training in patients with stroke.
The QEEG-8 (LEX3208, Laxtha Inc., Korea) was used to measure the MRCP before training and 4 weeks after the stimulation. The electrodes were placed at C3, C4, and Cz of the supplementary motor area (SMA), which represent the primary motor area (M1), based on the 10/20 international electrode placement standard. The reference electrode was placed on the earlobe and the grounding electrode behind the neck (Wolpaw et al., 2002). EMG electrodes were placed on the ipsilateral tibial tuberosity and the outer proximal tibialis anterior. The initial EMG signal from the tibialis anterior with dorsiflexion of the foot was set as 0 ms. The MRCP measurements at – 2,000 ms and 1,000 ms were divided into the following 3 regions: bereitschaftspotential (BP) for – 1,500 ms to – 500 ms, negative slope (NS) for – 500 ms to 0 ms, and motor potential (MP) for 0 ms to 500 ms. The maximum values were recorded (Tarkka and Hallett, 1991; Sato et al., 2012). The sampling rate was 256 Hz, the band bass filter was 4–50 Hz, and the data were saved in the computer with a 12-bit A/D converter. Ten repetitions of ankle dorsiflexion were defined as 1 set and 6 sets were conducted, each with a 5-s interval between repetitions. The rest period between sets was 4 min.
The action potentials of spinal motor neurons were measured using the H reflexes with Neuro-EMG-Micro (Neurosoft Ltd., Russia). The action potentials were measured before training, immediately after training, 2 wk after training, and 4 wk after training. The subjects were relaxed in a prone position with the ankles outside the bed. The active electrode was placed on the head of the gastrocnemius medial to the tibial crest, the reference electrode was placed on the Achilles tendon, and the grounding electrode was placed midway between the active electrode and the reference electrode. Electrical stimulation was applied to the tibial nerve in the popliteal region. Submaximal stimulation was applied 20 times in the opposite direction. The sweep speed was set to 10 ms and the sensitivity was set to 500 μV. Filter range was set to 20–10,000 Hz (Tasi et al., 2001).
A wireless BTS Pocket EMG (BTS Co., Milan, Italy) was used to measure muscle activity. Measurements were taken before training and 4 wk after training. The sampling rate was 1,000 Hz and the filter range was 20–500 Hz. The root mean square (RMS) of the collected signals was calculated after full-wave rectification. The electrodes were placed on the tibialis anterior and medial gastrocnemius of the left leg. To standardize the signals, reference voluntary contractions (% RVC) were performed (Cram & Kasman, 1998). The values for specific movements were collected between the mid-stance phase and the terminal stance phase of the left lower limb while the subject was ambulating. The reference contraction values were collected for 10 s while the subjects were in a relaxed standing position; 2 s were subtracted from the values for each extremity and only the signals collected during the middle 6 s were used.
The Biorescue system was used to measure balance. The measurements were taken before and 4 wk after training. To measure static balance, the surface area ellipse (SAE) and surface area length (SAL) of the central pressure were measured for 60 s while the subjects were standing with their legs separated 30° and facing ahead. To measure the limit of stability (LOS) of dynamic balance, the changes in surface area from the center during weight transfer in 8 different directions (anterior, posterior, left, right, anterior-left, posterior-left, anterior-right, and posterior-right) were measured.
Data analysis
SPSS 18.0 Windows version was used for statistical analysis. The Kolmogorov-Smirnov test was conducted to confirm a normal distribution. Repeated measures analysis of variance (ANOVA) was conducted to determine the significance of the changes in spinal motor neuron excitation with time in each group, and a least significant difference (LSD) test was conducted for comparison. In addition, the MRCP, muscle activities, and balance measured before and after training were analyzed using a paired t-test. The variables in both groups were compared using an independent t-test. The statistical significance level was set to α= 0.05.
Results
Changes in MRCPs
BP, NS, and MP were increased above the reference level in both groups. The MP of Cz and C4 in the DASI group showed a significant increase (p < 0.05). Comparison of the 2 groups showed significant differences in the MP at C4 (p < 0.05) (Table 2).
Change in MRCP ( μV)
Change in MRCP ( μV)
All values are shown as mean ± SD. BP: bereitschaftspotential; NS: Negative slope; MP: motor potential; Control: functional electric stimulation; DASI: EMG-triggered functional electric stimulation with action observation; paired t-test was used (*p < 0.05, **p < 0.01); independent t-test (#p < 0.05).
The H-reflex was significantly reduced 4 wk after training in the control group (p < 0.05). The H-reflex was significantly reduced between the second and the fourth week after training in the DASI group (p < 0.05) (Table 3).
Change in H-reflex (mV)
Change in H-reflex (mV)
All values are show as mean ± SD. Control: functional electric stimulation; DASI: EMG-triggered functional electric stimulation with action observation; tested by repeated measure ANOVA (**p < 0.01) and post-hoc used LSD (†p < 0.05).
Tibialis anterior and medial gastrocnemius activities were increased in both groups compared to the activities before training. However, only the changes in tibialis anterior activities were statistically significant (p < 0.05) (Table 4).
Change in muscle activity (% RVC)
Change in muscle activity (% RVC)
All values are shown as mean ± SD. TA: tibialis anterior; MGCM: medial gastrocnemius; Control: functional electric stimulation; DASI: EMG-triggered functional electric stimulation with action observation; paired t-test was used (*p < 0.05).
Although SAE and SAL, which reflect static balance, were decreased after training in both groups, the changes were not significant (p > 0.05). LOS, which reflects dynamic balance, only showed a significant increase in the DASI group (p < 0.05). Comparison of the 2 groups revealed that LOS was significantly higher in the DASI group (p < 0.05) (Table 5).
Change in balance
Change in balance
All values are shown as mean ± SD. SAE: surface area ellipse; SAL: surface area length; LOS: limit of stability; Control: functional electric stimulation; DASI: EMG-triggered functional electric stimulation with action observation; paired t-test was used (*p < 0.05), independent t-test (#p < 0.05).
An increase in the variety of afferent peripheral sensory inputs improves concentration in stroke patients during treatment (Franceschini et al., 2010). The increased input is then transferred to the central nervous system, which affects efferent activities. The afferent sensory inputs will be transferred to the cerebral cortex through the spinal cord and will induce changes in the brain.
Studies on animal brain damage reported that voluntary movements increase neuronal mechanisms regulating nutritional factors such as brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 (Griesbach et al., 2004). The increase in these nutritional factors reduces loss of severed axonal neurons and promotes neuroplasticity by regulating synapses (Cotman & Berchtold, 2002).
Based on this classical theory, electroencephalography was used in this study to investigate the changes in the cerebral cortex of stroke patients when ETFES and observational training were simultaneously applied. The changes in activities of motor neurons at the spinal cord level were analyzed using H-reflex amplitude measurement (Tsai et al., 2001). A surface EMG was used to analyze the changes in muscle activities and the balance was measured to investigate the effects of the cerebral cortex and spinal cord on functional movements.
The MRCP, which is produced during voluntary movements, can be evaluated by non-invasively measuring cortex activity (Tarkka & Hallett, 1991; Sato et al., 2012). Although the results of this study showed an increase in MRCP in both groups, only the increases in MP at Cz and C4 of the DASI group were significant (p < 0.05). Comparison of the 2 groups showed that the increase of MP at C4 was greater in the DASI group (p < 0.05). The results indicate that the combination of ETFES and observational training is more effective in increasing the MRCP than simple electrical stimulation.
Brunia and Vingerhoets (1981) reported that NS and MP reflect the activities in the contralateral hemisphere of the brain. Shibasaki et al. (1980) also reported that NS reflects the contralateral more than the ipsilateral hemisphere. Ikeda and Shibasaki (2003) reported that the MP was increased in the contralateral brain hemisphere during movement. Similar to previous reports, this study showed that in a comparison of C3 and C4, which represent the primary motor area, an increase in MP was only observed at C4. It can be inferred that the increase in MRCP was caused by the dual-afferent sensory stimulation produced by DASI training, which improved the synapses between the neuron in the cerebral cortex and the activity of the brain during movement. The changes in MP at C4 showed significant differences between the 2 groups, which can be attributed to the fact that voluntary contraction stimulation in the DASI group increased the activity of the corticospinal tract. Wiese et al. in 2005 reported that the increase in MP in stroke patients represented functional recovery. The MP reflects the afferent sensory input and produces efferent motor signals through the spinal nerves (Ikeda & Shibasaki, 2003). The increase in MP in the DASI group represents an increase in activity of the damaged primary motor area caused by afferent sensory input.
As shown by the MRCP, the increase in brain activity was higher in the DASI group than in the control group. Samuelides et al. (1998) reported that training that simultaneously uses a variety of stimuli was more effective in inducing neuroplasticity than training that only used a single type of stimulus. Shulz et al. (2003) reported that cross-modal plasticity caused by simultaneous application of a variety of stimuli increased the activity of the cerebral cortex. Moreover, voluntary contraction efforts stimulated higher level neurons than electrical stimulation. Therefore, the activity of the cerebral cortex would have increased.
The amplitude of the H-reflex represents changes in spinal motor neurons and can be used to measure or evaluate spasticity (Tsai et al., 2001). In this study, the H amplitude showed a significant decrease 4 weeks after training in the control group and between the second and fourth week after training in the DASI group (p < 0.05). The results corroborate the statement by Chae et al. (2008), that afferent sensory input through electrical stimulation reduces stiffness. However, the DASI group showed a faster decrease in stiffness and greater effect. This suggests that the voluntary contractions in the DASI group stimulated proprioceptive senses and that observation training created new sensory and motor tracts that promote restructuring of the cerebral cortex (Cauraugh et al., 2000). Although the contractions produced voluntarily and through electrical stimulation both decrease spinal motor neuron activity in stroke patients, Tsuboi et al. (1995) reported that voluntary contraction was more strongly correlated with this effect.
Analysis of the surface EMG of the tibialis anterior and medial gastrocnemius was conducted during ambulation to investigate the effects of stimulation on muscle activities. The results showed that muscle activities were significantly increased for the tibialis anterior in both control and DASI groups (p < 0.05). These results are consistent with those of Kesar et al. (2009) and Sabut et al. (2010), which reported an increase in muscle activity after FES, and of Hara et al. (2008), which reported an increase in muscle activity after ETFES. The increase in muscle activity could have been caused by dorsiflexion of the ankle, which increases inhibitory postsynapses in the gastrocnemius (Crone & Nielsen, 1994) that reduce the stretch reflex and increase the activity of the tibialis anterior. The increase in tibialis anterior activity was insignificant between the 2 groups, consistent with the results of previous studies reporting that continuous voluntary contractions and electrically stimulated contractions do not show differences in muscle activities (Duchateau et al., 2002). Although the differences were not statistically significant, changes in muscle activity were higher in the DASI group, which reflects the potential for greater effect on functional improvement than with FES.
To investigate the effects of changes in the cerebral cortex and spinal cord on functional movements, static and dynamic balance was evaluated. LOS, which represents dynamic balance, was significantly increased in the DASI group (p < 0.05). In this study, balance was further increased in the DASI group by the effective reduction of stiffness produced by the increase in cerebral cortex activity (Crone & Nielsen, 1994).
The restructuring of the brain was improved in both the control and DASI groups. The excitation of spinal motor neurons was reduced and functional recovery was also improved. The DASI group showed faster activation of the damaged brain hemisphere, which caused faster reduction of spinal motor neuron excitation and improved motor function recovery. Compared to a single type of stimulus, dual-afferent sensory input improved neuroplasticity through performance of voluntary movements that combined the activities of the central and peripheral nervous systems. Therefore, dual-afferent sensory input, which can induce voluntary movement, is more effective than a single type of stimulus in the treatment of stroke patients.
Conflict of interest
The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.