Neuroscience Letters 600 (2015) 1–5
Contents lists available at ScienceDirect
Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet
Research article
Effect of tactile stimulation on primary motor cortex excitability during action observation combined with motor imagery Megumi Tanaka a , Shinji Kubota a,b , Yusuke Onmyoji a , Masato Hirano a , Kazumasa Uehara a,b , Takuya Morishita a,b , Kozo Funase a,∗ a Human Motor Control Laboratory, Graduate School of Integrated Arts and Sciences, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima 739-8521, Japan b Research Fellow of the Japan Society for the Promotion of Science, Japan
h i g h l i g h t s • Effect of tactile input during action observation on M1 excitability was examined. • That effect on M1 excitability was decreased in muscle worked in action observed. • The decreased M1 excitability was reversed to facilitation by motor imagery.
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Article history: Received 20 January 2015 Received in revised form 19 May 2015 Accepted 22 May 2015 Available online 29 May 2015 Keywords: Action observation Tactile stimulation Motor imagery Primary motor cortex excitability
a b s t r a c t We aimed to investigate the effects of the tactile stimulation to an observer’s fingertips at the moment that they saw an object being pinched by another person on the excitability of observer’s primary motor cortex (M1) using transcranial magnetic stimulation (TMS). In addition, the above effects were also examined during action observation combined with the motor imagery. Motor evoked potentials (MEP) were evoked from the subjects’ right first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles. Electrical stimulation (ES) inducing tactile sensation was delivered to the subjects’ first and second fingertips at the moment of pinching action performed by another person. Although neither the ES nor action observation alone had significant effects on the MEP amplitude of the FDI or ADM, the FDI MEP amplitude which acts as the prime mover during pinching was reduced when ES and action observation were combined; however, no such changes were seen in the ADM. Conversely, that reduced FDI MEP amplitude was increased during the motor imagery. These results indicated that the M1 excitability during the action observation of pinching action combined with motor imagery could be enhanced by the tactile stimulation delivered to the observer’s fingertips at the moment corresponding to the pinching being observed. © 2015 Elsevier Ireland Ltd. All rights reserved.
1. Introduction When a person is learning a new motor skill, observing the action being performed well by another person, imitating the action, and then executing it can be a useful strategy. This approach is employed not only during motor skill learning, but also for neural rehabilitation aimed at improving the movements of stroke patients. In fact, significant improvements in stroke patients’ upper arm movements have been reported after so-called action observation therapy [1]. In terms of the neurophysiological basis of this
∗ Corresponding author. Tel.: +81 82 424 6590; fax: +81 82 424 6590. E-mail address: [email protected] (K. Funase). http://dx.doi.org/10.1016/j.neulet.2015.05.057 0304-3940/© 2015 Elsevier Ireland Ltd. All rights reserved.
approach, the effects of action observation therapy are attributed to activation of the mirror neuron system. Mirror neurons were originally found in region F5 of the ventral premotor cortex in monkeys during action observation and imitation [2,3]. In humans, several brain cortices; i.e., the premotor ventral cortex, inferior frontal gyrus, superior temporal sulcus, and inferior parietal lobe, are considered to be involved in the mirror neuron system [4]. In addition, previous transcranial magnetic stimulation (TMS) studies have reported that the primary motor cortex (M1) is activated as part of the mirror neuron system during action observation [5,6]. Other previous studies have reported that the M1 excitability is hardly activated by the action observation only, and the motor imagery of an observed action combined with action observation was much effective to enhance the M1 excitability innervating the
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muscle activated during the performance of the observed action [7,8]. Motor imagery is a covert cognitive process controlled by a forward internal model that does not involve any actual movement, but rather involves the generation of sensory information that simulates the sensory information that would be produced if the imaged movement were actually performed [9–16]. Studies suggest that a higher brain system is involved in motor imagery and that sensory information could affect M1 excitability during action observation. In fact, it has been reported that a mirror neuron system that performs the cross-modal processing required to integrate visual and tactile information exists in the somatosensory area [17]. In the present study, we aimed to investigate the effects of tactile stimulation of a subject’s fingertips at the moment that they saw another person performing a pinching motion; i.e., action observation, on the subject’s M1 excitability, in order to identify the neural factors that enhance the activation of the mirror neuron system. This study might aid the development of much more effective types of action observation therapy for neural rehabilitation.
2.3. Electrical stimulation (ES) to induce tactile sensations in the fingertips Bar type stimulus electrodes (length: 55 mm, width: 15 mm, diameter of each electrode: 6 mm) were attached to the first and second fingers (one on each finger). For both fingers, the cathode was attached to the fingertip, and the anode was attached to the second joint of the finger. A burst-type electrical stimulus (ES), composed of five 1 ms square pulses at 200 Hz, was simultaneously administered to the first and second fingertips to induce a tactile sensation using a constant current isolator (SS-102J, Nihon Koden Co., Ltd., Japan) coupled with an electrical stimulator (SEN7203, Nihon Koden Co., Ltd., Japan). The ES was delivered at the moment that another person pinched a horizontal U-shaped metal plate. The intensity of the ES was set at 130% of the tactile sensation threshold of each fingertip. In a preliminary experiment, we confirmed that the ES induced a similar tactile sensation to that experienced when the subject pinched the horizontal U-shaped metal plate themselves. 2.4. Action observation and the ES trigger
2. Materials and methods 2.1. Subjects Eight (8 males, 22–29 years old) and 10 (7 males and 3 females, 22–9 years old) normal healthy right-handed subjects participated in experiments 1 and 2, respectively, after giving their written informed consent. The handedness of each subject was evaluated using the Edinburgh Handedness Inventory [18]. All experimental procedures were carried out in accordance with the Declaration of Helsinki and were approved by the ethics committee of Hiroshima University. The subjects sat in a reclining chair and put both hands in a pronated position on a horizontal plate attached to the chair’s armrests.
2.2. TMS application and MEP recording A magnetic stimulator (Model 200, Magstim, Whitland, UK) and a figure-of-eight coil were used to deliver the electromagnetic stimuli. The coil was placed tangential to the scalp with its handle pointing backward and was rotated approximately 45◦ away from the mid-sagittal line. In experiment 1, the optimal coil position for evoking motor evoked potentials (MEPs) in both the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) of the right hand was found on the left side of the scalp above the M1 and marked on a swimming cap worn by the subjects with a softtip pen to ensure reliable coil placement between the trials. In experiment 2, MEP was only recorded from the FDI, based on the results of experiment 1. The resting motor threshold of the FDI was determined and defined as the minimum TMS intensity required to produce an MEP of at least 50 V in the resting FDI muscle in five of ten trials. The TMS intensity was set at 120–130% of the resting motor threshold. As a result, the mean amplitude of the control MEP induced in the FDI was approximately 1 mV. All electromyographic (EMG) signals were recorded using paired Ag/AgCl surface electrodes (diameter: 9 mm) and amplified and filtered at bandwidths of 5–3 kHz (7S12, NEC San-ei Co., Ltd., Japan). Analog EMG signals were digitized at a sampling rate of 10 kHz and saved on a computer for off-line analysis (PowerLab system, AD Instruments Pty., Ltd., Australia). Throughout the experiments, the subjects were instructed to avoid producing background EMG. The MEP recordings that exhibited the background EMG (less than 1% of all MEP recordings) were excluded from the data analysis. 10–15 MEP were recorded in each of the conditions described below.
The subjects were instructed to watch a 26 in. computer display placed on a desk approximately 1 m in front of them. They repeatedly watched a short live movie clip (approximately 1.5 s) on the display, which showed the horizontal U-shaped metal plate (the gap between the 2 plates was 30 mm) being pinched by another person, who used the first and second fingers of their right hand to perform the action (OBS). The pinching action was performed from the right to left direction on a display. A strain gauge attached to the U-shaped metal plate detected the deflecting force produced as it was pinched, which was used to trigger the ES. Thus, the subjects felt the ES-evoked tactile sensation at the same time as they observed the pinching action on the short live movie. The TMS was triggered 25 ms after the onset of the ES, based on the interval between the ES and the associated signals reaching the M1. Fig. 1 shows the 3 phases of the observed pinching action, and a schema of the MEP recording and the ES protocol. 2.5. Experimental conditions In experiment 1, we examined the effects of “ES”, “OBS”, and “OBS + ES” on the MEP amplitude of the FDI, which acts as the prime mover during pinching, and the ADM, which is relaxed during pinching. In experiment 2, to examine the effects of motor imagery on the FDI MEP amplitude in the “OBS + ES” conditions, the subjects were instructed to imagine themselves performing the motor action being observed. 2.6. Evaluation of motor imagery Just after each motor imagery trial, the subjects were asked to evaluate the quality of their motor imagery using a six-point-grade visual-analog scale (VAS) sheet. The subjects marked a number on the VAS sheet, which was labeled from 0 (the motor imagery was a failure) to 5 (the motor imagery was a success), according to their view of the quality of the motor imagery. 2.7. Statistical analysis Two-way repeated measures ANOVA was carried out to analyze the effects of “condition × muscle” (Fig. 2) and “condition × imagery” (Fig. 3) on the MEP amplitude evoked in the target muscles. As a post-hoc test, a paired t-test was performed to find the significant difference between two MEP amplitudes in each condition, respectively.
M. Tanaka et al. / Neuroscience Letters 600 (2015) 1–5
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Fig. 1. The upper panel shows 3 stills taken from the live movie clip representing the 3 phases of the pinching movement. The ES was triggered at the moment that the U-shaped metal plate was pinched. The TMS was triggered at 25 ms after the ES was triggered. The lower panel shows a schema for the MEP recording and the ES triggering protocol.
Fig. 2. Mean MEP amplitudes (mean ± SE, % of control) evoked in the FDI (black bar) and ADM (white bar) in the “ES”, “OBS”, and “OBS + ES” conditions. *p < 0.05, † p < 0.05 vs. the baseline control.
The significance of the differences between the recorded MEP amplitudes and the baseline control, and the differences between the motor imagery VAS scores obtained in the “OBS” and “OBS + ES” conditions were analyzed using the paired t-test. In all analyses, the level of statistical significance was set at p < 0.05. 3. Results Fig. 2 shows the mean MEP amplitude (% of control, ±SE) recorded in the FDI and ADM in the “ES”, “OBS”, and “OBS + ES” conditions. There were no significant differences between the muscles (F1,14 = 0.58, p = 0.46) or the conditions (F2,28 = 0.72, p = 0.50),
Fig. 3. Mean FDI MEP amplitudes (mean ± SE, % of control) evoked in the experiments with (white bar) and without (black bar) the motor imagery in the “OBS” and “OBS + ES” conditions. *p < 0.05, † p < 0.05 vs. the baseline control.
and the effect of the interaction between these factors was not significant (F2,28 = 1.35, p = 0.28). Paired t-test detected a significantly lower MEP amplitude in FDI than ADM (t = 2.55, *p < 0.05) in the “OBS + ES” conditions. Also, the FDI MEP amplitude exhibited a significantly lower compared to the baseline control (t = 2.55, †p < 0.05) in the “OBS + ES” condition. Taking into account the results of experiment 1, which suggested that the FDI MEP amplitude were only affected by the combined effects of the ES and action observation, we focused on the effects of motor imagery on the FDI MEP amplitude in the “OBS + ES” conditions in experiment 2. Fig. 3 shows the
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mean FDI MEP amplitude (% of control, ±SE) in the “OBS” and “OBS + ES” conditions with and without the motor imagery. Although no significant difference was found between the “OBS” and “OBS + ES” conditions (F1,18 = 0.001, p = 0.98), a significant difference was detected between the imagery and no-imagery conditions (F1,18 = 10.21, **p < 0.01). The interaction between “condition” and the “motor imagery” was not significant (F1,18 = 3.48, p = 0.08). Paired t-test detected a significant difference between the MEP amplitudes recorded with and without the motor imagery in the “OBS + ES” conditions (t = 3.00, *p < 0.05). In addition, the MEP amplitudes recorded in the “OBS” (t = 2.53, †p < 0.05) and “OBS + ES” (t = 2.29, †p < 0.05) conditions with the motor imagery exhibited significantly greater amplitudes than the baseline control, respectively. In the “OBS + ES” condition without the motor imagery, the MEP amplitude showed a marginal decrease (t = 2.14, p = 0.06) compared to the baseline control, although it exhibited a significant decrease in Fig. 2 as mentioned previously. The subjects’ mean VAS scores (mean ± SD) were 4.3 ± 1.1 and 4.4 ± 1.1 in the “OBS” and “OBS + ES” conditions, respectively. These two values did not differ significantly (t = 0.68, p = 0.52).
4. Discussion In the present study, we obtained the following findings: (1) The MEP amplitudes evoked in the FDI and ADM were not affected by the “ES” or “OBS” conditions alone. (2) In the “OBS” conditions, the FDI MEP amplitude was increased compared with the baseline control during motor imagery. (3) In the “OBS + ES” conditions, a reduction in the FDI MEP amplitude was observed without the motor imagery, whereas it showed an increased amplitude with the motor imagery. In the previous studies, it was reported that the somatosensory inputs combined with the motor imagery enhanced the M1 excitability [19,20]. Therefore, the experimental condition in which the ES effect combined during the motor imagery for the pinching action without action observation should be examined. In the present study, however, we focused to the effect of the motor imagery for the observed pinching action together with the timing-matched somatosensory inputs on the M1 excitability. It is methodologically difficult to make sure the delivering of the ES corresponding to the moment of pinching action during the motor imagery. Thus, we excluded the experimental condition in which the somatosensory inputs combined with the motor imagery. Consequently, we found that the excitability of the M1 innervating FDI as a prime mover for a pinching action was inhibited during the observation of that action and the simultaneous delivery of a tactile sensation to the observer’s fingertips with no motor imagery. However, the above-mentioned protocol had the opposite effect; i.e., the FDI MEP amplitude was increased compared with the baseline, during the motor imagery. The tactile sensation evoked by the ES per se did not have any effect on the MEP amplitude. MEP induced after the delivery of a peripheral somatosensory stimulus followed by TMS exhibited a lower amplitude than MEP evoked by TMS alone, and the mechanism responsible for this reduction in MEP amplitude is known as short-latency afferent inhibition (SAI) [21,22]. In the established method for measuring SAI in the FDI, the inter-stimulus interval (ISI) between median nerve stimulation of the wrist and TMS is set at N20 + 2 ms; i.e., approximately 20–23 ms, and the stimulus intensity of the nerve stimulus is usually set at 300% of the perception threshold. In the present study, we adopted a rather weak stimulus intensity for the ES (130% of the tactile sensation threshold), and the ES was administered to the skin of the fingertips, not to the peripheral nerve. Thus, the induced sensory input evoked by the ES was experienced as a tactile sensation detected by the fingertips. In addition, the ISI between the delivery of the ES to the
fingertips and the TMS was set at 25 ms, based on the location of the stimulation site; i.e., the fingertips which are located distal to the wrist and the fact that the ES was composed of 5 pulses. As a result, a reduction in the FDI MEP amplitude was only observed in the “OBS + ES” conditions; i.e., no change in MEP amplitude was seen in the “ES” conditions. Furthermore, such decreases were seen in the FDI which is activated during pinching, but not in the ADM which is not involved in pinching. This means that action observation was essential for the inhibitory effect seen in the “OBS + ES” conditions. Therefore, we consider that the reduction in the FDI MEP amplitude observed in the “OBS+ES” conditions was not caused by an SAI-like effect. A previous study reported that the intervention of the transcutaneous ES (0.25 ms square pulse at 90 Hz) at stimulus intensity below the motor threshold over the right thenar eminence for 15 min, which produced the tingling sensation for in the stimulated area without muscle twitch or pain, induced the transient reduction of MEP amplitudes of the right FDI and abductor pollicis brevis [23]. It shows that short-term transcutaneous ES might have an inhibitory effect of the M1 excitability. The neural mechanism for such a inhibitory effect on M1 excitability was unknown. The ES adopted in the present study did not affect the MEP amplitude, because of the weak intensity inducing the tactile sensation compared to the previous study mentioned above. The FDI MEP amplitude, however, was decreased in the “ES + OBS” condition. We speculate that some gating mechanisms to attenuate the tactile sensation could be activated in the “OBS” condition. Anyway, further study should be done to address the neural mechanisms for the combined effect of “ES + OBS”. Interestingly, the motor imagery reversed the inhibitory effect of the “OBS + ES” conditions on the FDI MEP amplitude. It has been reported that the cross-modal interactions are involved in visuotactile enhancement of the mirror neuron system [24–27]. For example, the sensory threshold of the index finger was significantly decreased after a movie clip of the relevant hand being touched with a stick was shown; however, no such decrease of sensory threshold was seen after a movie clip showing the stick touching the space beneath the hand was presented. The observed decrease of sensory threshold was specific to the index finger shown in the movie clip. This suggests that the visuotactile enhancement was induced by the observation of the finger being touched rather than the depiction of the finger itself [24]. Furthermore, another group found that the somatosensory cortices were activated during the observation of a hand being touched from the egocentric and allocentric perspectives [27]. Cross-modal interactions in the mirror neuron system might explain our findings because the present study employed a similar paradigm to those used in the abovementioned studies; i.e., tactile stimulation was administered to the subject’s fingertips at the exact moment at which they saw another person perform a pinching action. As a result, it is suggested that the cross-modal interactions between the neural signals generated by the action observation with simultaneous tactile sensation were significantly enhanced by motor imagery. During action observation combined with motor imagery, the mirror neuron system and other brain areas, including those involved in processing sensory information related to motor imagery, may be activated simultaneously. Some recent neuroimaging studies have detected greater cortical activity during action observation combined with motor imagery than during action observation or motor imagery alone [28–30]. In addition, several recent TMS studies, which focused on M1 excitability, have discussed the different effects of and interactions between action observation and motor imagery [7,8,31–35]. These previous studies strongly suggest that the neural mechanisms responsible for action observation and motor imagery are activated simultaneously, resulting in enhanced M1 excitability. This suggestion might be supported by the results of the present study, which showed that
M. Tanaka et al. / Neuroscience Letters 600 (2015) 1–5
the M1 excitability during action observation combined with motor imagery was significantly increased by the tactile stimulation that corresponded to the action being observed. In terms of the clinical application of our findings to therapy, we consider that they might lead to the development of improved action observation-based therapeutic interventions that are more effective to modulate the M1 excitability of stroke patients. Acknowledgment SK, KU, TM were supported as Research Fellows of the Japan Society for the Promotion of Science. References [1] D. Ertelt, S. Small, A. Solodkin, C. Dettmers, A. McNamara, F. Binkofski, G. Buccino, Action observation has a positive impact on rehabilitation of motor deficits after stroke, Neuroimage 36 (2007) 164–173. [2] G. Rizzolatti, L. Fadiga, V. Gallese, L. Fogassi, Premotor cortex and the recognition of motor actions, Cogn. Brain Res. 3 (1996) 131–141. [3] G. Rizzolatti, L. Craighero, The mirror-neuron system, Ann. Rev. Neurosci. 27 (2004) 169–192. [4] M. Iacoboni, J.C. Mazziotta, Mirror neuron system: basic findings and clinical applications, Ann. Neurol. 62 (2007) 213–218. [5] M. Iacoboni, R.P. Woods, M. Brass, H. Bekkering, J.C. Mazziotta, G. Rizzolatti, Cortical mechanisms of human imitation, Science 286 (1999) 2526–2528. [6] M.A. Umilta, E. Kohler, V. Gallese, L. Fogassi, L. Fadiga, C. Keysers, G. Rizzolatti, I know what you are doing: a neurophysiological study, Neuron 31 (2001) 155–165. [7] M. Sakamoto, T. Muraoka, N. Mizuguchi, K. Kanosue, Combining observation and imagery of an action enhances human corticospinal excitability, Neurosci. Res. 65 (2009) 23–27. [8] I. Tsukazaki, K. Uehara, T. Morishita, M. Ninomiya, K. Funase, Effect of observation combined with motor imagery of a skilled hand-motor task on motor cortical excitability: difference between novice and expert, Neurosci. Lett. 518 (2012) 96–100. [9] M. Jeannerod, Neural simulation of action: a unifying mechanism for motor cognition, Neuroimage 14 (2001) 103–109. [10] R.C. Miall, D.M. Wolpert, Forward models for physiological motor control, Neural Netw. 9 (1996) 1265–1279. [11] D.M. Wolpert, Z. Ghahramani, M.I. Jordan, An internal model for sensorimotor integration, Science 269 (1995) 1880–1882. [12] D.M. Wolpert, J.R. Flanagan, Motor prediction, Curr. Biol. 11 (2001) 729–732. [13] J. Annett, On knowing how to do things: a theory of motor imagery, Cogn. Brain Res. 3 (1996) 65–69. [14] D.L. Feltz, D.M. Landers, The effects of mental practice on motor skill learning and performance: a meta-analysis, J. Psychol. 5 (1983) 25–57. [15] M. Jeannerod, The representing brain: neural correlates of motor intention and imagery, Behav. Brain Sci. 17 (1994) 187–202. [16] E. Naito, T. Kochiyama, R. Kitada, S. Nakamura, M. Matsumura, Y. Yonekura, N. Sadato, Internally simulated movement sensations during motor imagery activate cortical motor areas and the cerebellum, J. Neurosci. 22 (2002) 3683–3691.
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[17] N. Bolognini, A. Rossetti, A. Maravita, C. Miniussi, Seeing touch in the somatosensory cortex: a tms study of the visual perception of touch, Hum. Brain Mapp. 32 (2011) 2104–2114. [18] R. Oldfield, The assessment and analysis of handedness: the Edinburgh inventory, Neuropsychology 9 (1971) 97–113. [19] F. Kaneko, T. Hayami, T. Aoyama, T. Kizuka, Motor imagery and electrical stimulation reproduce corticospinal excitability at levels similar to voluntary muscle contraction, J. NeuroEng. Rehabil. (2015), http://dx.doi.org/10.1186/ 1743-0003-11-94 [20] N. Mizuguchi, M. Sakamoto, T. Muraoka, K. Kanosue, Infuence of touching an object on corticospinal excitability during motor imagery, Exp. Brain Res. 196 (2009) 529–535. [21] H. Alle, T. Heidegger, L. Kriváneková, U. Ziemann, Interactions between short-interval intracortical inhibition and short-latency afferent inhibition in human motor cortex, J. Physiol. 587 (21) (2009) 5163–5176. [22] H. Tokimura, V. Di Lazzaro, Y. Tokimura, A. Oliviero, P. Profice, A. Insola, P. Mazzone, P. Tonali, J.C. Rothwel, Short latency inhibition of human hand motor cortex by somatosensory input from the hand, J. Physiol. 523 (2) (2000) 503–513. [23] T. Mima, T. Oga, J. Rothwell, T. Satow, J. Yamamoto, K. Toma, H. Fukuyama, H. Shibasaki, T. Nagamine, Short-term high-frequency transcutaneous electrical nerve stimulation decreases human motor cortex excitability, Neurosci. Lett. 355 (2004) 85–88. [24] M. Schaefer, H.J. Heinze, M. Rotte, Viewing touch improves tactile sensory threshold, Neroreport 16 (2005) 367–370. [25] M. Schaefer, H.J. Heinze, M. Rotte, Seeing the hand being touched modulates the primary somatosensory cortex, Neroreport 16 (2005) 1101–1105. [26] M. Schaefer, H. Flor, H.J. Heinze, M. Rotteb, Dynamic modulation of the primary somatosensory cortex during seeing and feeling a touched hand, Neuroimage 29 (2006) 587–592. [27] M. Schaefer, B. Xu, H. Flor, L.G. Cohen, Effects of different viewing perspectives on somatosensory activations during observation of touch, Hum. Brain Mapp. 30 (2009) 2722–2730. [28] V. Nedelko, T. Hassa, F. Hamzei, M.A. Schoenfeld, C. Dettmers, Action imagery combined with action observation activates more corticomotor regions than action observation alone, J. Neurol. Phys. Ther. 36 (2012) 182–188. [29] H.I. Berends, R. Wolkorte, M.J. Ijzerman, M.J.A.M. van Putten, Differential cortical activation during observation and observation-and-imagination, Exp. Brain Res. 229 (2013) 337–345. [30] M. Villiger, N. Estévez, M.C. Hepp-Reymond, D. Kiper, S.S. Kollias, K. Eng, S. Hotz-Boendmaker, Enhanced activation of motor execution networks using action observation combined with imagination of lower limb movements, PLoS ONE 8 (2013) e72403. [31] S. Clark, F. Tremblay, D. Ste-Marie, Differential modulation of corticospinal excitability during observation, mental imagery and imitation of hand actions, Neuropsychology 42 (2004) 105–112. [32] G. Leonard, F. Tremblay, Corticomotor facilitation associated with observation, imagery and imitation of hand actions: a comparative study in young and old adults, Exp. Brain Res. 177 (2007) 167–175. [33] M. Conson, M. Sarà, F. Pistoia, L. Trojano, Action observation improves motor imagery: specific interactions between simulative processes, Exp. Brain Res. 199 (2009) 71–81. [34] J. Liepert, N. Neveling, Motor excitability during imagination and observation of foot dorsiflexions, J. Neural. Transm. 116 (2009) 1613–1619. [35] F. Battaglia, S.H. Lisanby, D. Freedberg, Corticomotor excitability during observation and imagination of a work of art, Front. Hum. Neurosci. 5 (2011) 79.
Contents lists available at ScienceDirect
Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet
Research article
Effect of tactile stimulation on primary motor cortex excitability during action observation combined with motor imagery Megumi Tanaka a , Shinji Kubota a,b , Yusuke Onmyoji a , Masato Hirano a , Kazumasa Uehara a,b , Takuya Morishita a,b , Kozo Funase a,∗ a Human Motor Control Laboratory, Graduate School of Integrated Arts and Sciences, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima 739-8521, Japan b Research Fellow of the Japan Society for the Promotion of Science, Japan
h i g h l i g h t s • Effect of tactile input during action observation on M1 excitability was examined. • That effect on M1 excitability was decreased in muscle worked in action observed. • The decreased M1 excitability was reversed to facilitation by motor imagery.
a r t i c l e
i n f o
Article history: Received 20 January 2015 Received in revised form 19 May 2015 Accepted 22 May 2015 Available online 29 May 2015 Keywords: Action observation Tactile stimulation Motor imagery Primary motor cortex excitability
a b s t r a c t We aimed to investigate the effects of the tactile stimulation to an observer’s fingertips at the moment that they saw an object being pinched by another person on the excitability of observer’s primary motor cortex (M1) using transcranial magnetic stimulation (TMS). In addition, the above effects were also examined during action observation combined with the motor imagery. Motor evoked potentials (MEP) were evoked from the subjects’ right first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles. Electrical stimulation (ES) inducing tactile sensation was delivered to the subjects’ first and second fingertips at the moment of pinching action performed by another person. Although neither the ES nor action observation alone had significant effects on the MEP amplitude of the FDI or ADM, the FDI MEP amplitude which acts as the prime mover during pinching was reduced when ES and action observation were combined; however, no such changes were seen in the ADM. Conversely, that reduced FDI MEP amplitude was increased during the motor imagery. These results indicated that the M1 excitability during the action observation of pinching action combined with motor imagery could be enhanced by the tactile stimulation delivered to the observer’s fingertips at the moment corresponding to the pinching being observed. © 2015 Elsevier Ireland Ltd. All rights reserved.
1. Introduction When a person is learning a new motor skill, observing the action being performed well by another person, imitating the action, and then executing it can be a useful strategy. This approach is employed not only during motor skill learning, but also for neural rehabilitation aimed at improving the movements of stroke patients. In fact, significant improvements in stroke patients’ upper arm movements have been reported after so-called action observation therapy [1]. In terms of the neurophysiological basis of this
∗ Corresponding author. Tel.: +81 82 424 6590; fax: +81 82 424 6590. E-mail address: [email protected] (K. Funase). http://dx.doi.org/10.1016/j.neulet.2015.05.057 0304-3940/© 2015 Elsevier Ireland Ltd. All rights reserved.
approach, the effects of action observation therapy are attributed to activation of the mirror neuron system. Mirror neurons were originally found in region F5 of the ventral premotor cortex in monkeys during action observation and imitation [2,3]. In humans, several brain cortices; i.e., the premotor ventral cortex, inferior frontal gyrus, superior temporal sulcus, and inferior parietal lobe, are considered to be involved in the mirror neuron system [4]. In addition, previous transcranial magnetic stimulation (TMS) studies have reported that the primary motor cortex (M1) is activated as part of the mirror neuron system during action observation [5,6]. Other previous studies have reported that the M1 excitability is hardly activated by the action observation only, and the motor imagery of an observed action combined with action observation was much effective to enhance the M1 excitability innervating the
2
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muscle activated during the performance of the observed action [7,8]. Motor imagery is a covert cognitive process controlled by a forward internal model that does not involve any actual movement, but rather involves the generation of sensory information that simulates the sensory information that would be produced if the imaged movement were actually performed [9–16]. Studies suggest that a higher brain system is involved in motor imagery and that sensory information could affect M1 excitability during action observation. In fact, it has been reported that a mirror neuron system that performs the cross-modal processing required to integrate visual and tactile information exists in the somatosensory area [17]. In the present study, we aimed to investigate the effects of tactile stimulation of a subject’s fingertips at the moment that they saw another person performing a pinching motion; i.e., action observation, on the subject’s M1 excitability, in order to identify the neural factors that enhance the activation of the mirror neuron system. This study might aid the development of much more effective types of action observation therapy for neural rehabilitation.
2.3. Electrical stimulation (ES) to induce tactile sensations in the fingertips Bar type stimulus electrodes (length: 55 mm, width: 15 mm, diameter of each electrode: 6 mm) were attached to the first and second fingers (one on each finger). For both fingers, the cathode was attached to the fingertip, and the anode was attached to the second joint of the finger. A burst-type electrical stimulus (ES), composed of five 1 ms square pulses at 200 Hz, was simultaneously administered to the first and second fingertips to induce a tactile sensation using a constant current isolator (SS-102J, Nihon Koden Co., Ltd., Japan) coupled with an electrical stimulator (SEN7203, Nihon Koden Co., Ltd., Japan). The ES was delivered at the moment that another person pinched a horizontal U-shaped metal plate. The intensity of the ES was set at 130% of the tactile sensation threshold of each fingertip. In a preliminary experiment, we confirmed that the ES induced a similar tactile sensation to that experienced when the subject pinched the horizontal U-shaped metal plate themselves. 2.4. Action observation and the ES trigger
2. Materials and methods 2.1. Subjects Eight (8 males, 22–29 years old) and 10 (7 males and 3 females, 22–9 years old) normal healthy right-handed subjects participated in experiments 1 and 2, respectively, after giving their written informed consent. The handedness of each subject was evaluated using the Edinburgh Handedness Inventory [18]. All experimental procedures were carried out in accordance with the Declaration of Helsinki and were approved by the ethics committee of Hiroshima University. The subjects sat in a reclining chair and put both hands in a pronated position on a horizontal plate attached to the chair’s armrests.
2.2. TMS application and MEP recording A magnetic stimulator (Model 200, Magstim, Whitland, UK) and a figure-of-eight coil were used to deliver the electromagnetic stimuli. The coil was placed tangential to the scalp with its handle pointing backward and was rotated approximately 45◦ away from the mid-sagittal line. In experiment 1, the optimal coil position for evoking motor evoked potentials (MEPs) in both the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) of the right hand was found on the left side of the scalp above the M1 and marked on a swimming cap worn by the subjects with a softtip pen to ensure reliable coil placement between the trials. In experiment 2, MEP was only recorded from the FDI, based on the results of experiment 1. The resting motor threshold of the FDI was determined and defined as the minimum TMS intensity required to produce an MEP of at least 50 V in the resting FDI muscle in five of ten trials. The TMS intensity was set at 120–130% of the resting motor threshold. As a result, the mean amplitude of the control MEP induced in the FDI was approximately 1 mV. All electromyographic (EMG) signals were recorded using paired Ag/AgCl surface electrodes (diameter: 9 mm) and amplified and filtered at bandwidths of 5–3 kHz (7S12, NEC San-ei Co., Ltd., Japan). Analog EMG signals were digitized at a sampling rate of 10 kHz and saved on a computer for off-line analysis (PowerLab system, AD Instruments Pty., Ltd., Australia). Throughout the experiments, the subjects were instructed to avoid producing background EMG. The MEP recordings that exhibited the background EMG (less than 1% of all MEP recordings) were excluded from the data analysis. 10–15 MEP were recorded in each of the conditions described below.
The subjects were instructed to watch a 26 in. computer display placed on a desk approximately 1 m in front of them. They repeatedly watched a short live movie clip (approximately 1.5 s) on the display, which showed the horizontal U-shaped metal plate (the gap between the 2 plates was 30 mm) being pinched by another person, who used the first and second fingers of their right hand to perform the action (OBS). The pinching action was performed from the right to left direction on a display. A strain gauge attached to the U-shaped metal plate detected the deflecting force produced as it was pinched, which was used to trigger the ES. Thus, the subjects felt the ES-evoked tactile sensation at the same time as they observed the pinching action on the short live movie. The TMS was triggered 25 ms after the onset of the ES, based on the interval between the ES and the associated signals reaching the M1. Fig. 1 shows the 3 phases of the observed pinching action, and a schema of the MEP recording and the ES protocol. 2.5. Experimental conditions In experiment 1, we examined the effects of “ES”, “OBS”, and “OBS + ES” on the MEP amplitude of the FDI, which acts as the prime mover during pinching, and the ADM, which is relaxed during pinching. In experiment 2, to examine the effects of motor imagery on the FDI MEP amplitude in the “OBS + ES” conditions, the subjects were instructed to imagine themselves performing the motor action being observed. 2.6. Evaluation of motor imagery Just after each motor imagery trial, the subjects were asked to evaluate the quality of their motor imagery using a six-point-grade visual-analog scale (VAS) sheet. The subjects marked a number on the VAS sheet, which was labeled from 0 (the motor imagery was a failure) to 5 (the motor imagery was a success), according to their view of the quality of the motor imagery. 2.7. Statistical analysis Two-way repeated measures ANOVA was carried out to analyze the effects of “condition × muscle” (Fig. 2) and “condition × imagery” (Fig. 3) on the MEP amplitude evoked in the target muscles. As a post-hoc test, a paired t-test was performed to find the significant difference between two MEP amplitudes in each condition, respectively.
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Fig. 1. The upper panel shows 3 stills taken from the live movie clip representing the 3 phases of the pinching movement. The ES was triggered at the moment that the U-shaped metal plate was pinched. The TMS was triggered at 25 ms after the ES was triggered. The lower panel shows a schema for the MEP recording and the ES triggering protocol.
Fig. 2. Mean MEP amplitudes (mean ± SE, % of control) evoked in the FDI (black bar) and ADM (white bar) in the “ES”, “OBS”, and “OBS + ES” conditions. *p < 0.05, † p < 0.05 vs. the baseline control.
The significance of the differences between the recorded MEP amplitudes and the baseline control, and the differences between the motor imagery VAS scores obtained in the “OBS” and “OBS + ES” conditions were analyzed using the paired t-test. In all analyses, the level of statistical significance was set at p < 0.05. 3. Results Fig. 2 shows the mean MEP amplitude (% of control, ±SE) recorded in the FDI and ADM in the “ES”, “OBS”, and “OBS + ES” conditions. There were no significant differences between the muscles (F1,14 = 0.58, p = 0.46) or the conditions (F2,28 = 0.72, p = 0.50),
Fig. 3. Mean FDI MEP amplitudes (mean ± SE, % of control) evoked in the experiments with (white bar) and without (black bar) the motor imagery in the “OBS” and “OBS + ES” conditions. *p < 0.05, † p < 0.05 vs. the baseline control.
and the effect of the interaction between these factors was not significant (F2,28 = 1.35, p = 0.28). Paired t-test detected a significantly lower MEP amplitude in FDI than ADM (t = 2.55, *p < 0.05) in the “OBS + ES” conditions. Also, the FDI MEP amplitude exhibited a significantly lower compared to the baseline control (t = 2.55, †p < 0.05) in the “OBS + ES” condition. Taking into account the results of experiment 1, which suggested that the FDI MEP amplitude were only affected by the combined effects of the ES and action observation, we focused on the effects of motor imagery on the FDI MEP amplitude in the “OBS + ES” conditions in experiment 2. Fig. 3 shows the
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mean FDI MEP amplitude (% of control, ±SE) in the “OBS” and “OBS + ES” conditions with and without the motor imagery. Although no significant difference was found between the “OBS” and “OBS + ES” conditions (F1,18 = 0.001, p = 0.98), a significant difference was detected between the imagery and no-imagery conditions (F1,18 = 10.21, **p < 0.01). The interaction between “condition” and the “motor imagery” was not significant (F1,18 = 3.48, p = 0.08). Paired t-test detected a significant difference between the MEP amplitudes recorded with and without the motor imagery in the “OBS + ES” conditions (t = 3.00, *p < 0.05). In addition, the MEP amplitudes recorded in the “OBS” (t = 2.53, †p < 0.05) and “OBS + ES” (t = 2.29, †p < 0.05) conditions with the motor imagery exhibited significantly greater amplitudes than the baseline control, respectively. In the “OBS + ES” condition without the motor imagery, the MEP amplitude showed a marginal decrease (t = 2.14, p = 0.06) compared to the baseline control, although it exhibited a significant decrease in Fig. 2 as mentioned previously. The subjects’ mean VAS scores (mean ± SD) were 4.3 ± 1.1 and 4.4 ± 1.1 in the “OBS” and “OBS + ES” conditions, respectively. These two values did not differ significantly (t = 0.68, p = 0.52).
4. Discussion In the present study, we obtained the following findings: (1) The MEP amplitudes evoked in the FDI and ADM were not affected by the “ES” or “OBS” conditions alone. (2) In the “OBS” conditions, the FDI MEP amplitude was increased compared with the baseline control during motor imagery. (3) In the “OBS + ES” conditions, a reduction in the FDI MEP amplitude was observed without the motor imagery, whereas it showed an increased amplitude with the motor imagery. In the previous studies, it was reported that the somatosensory inputs combined with the motor imagery enhanced the M1 excitability [19,20]. Therefore, the experimental condition in which the ES effect combined during the motor imagery for the pinching action without action observation should be examined. In the present study, however, we focused to the effect of the motor imagery for the observed pinching action together with the timing-matched somatosensory inputs on the M1 excitability. It is methodologically difficult to make sure the delivering of the ES corresponding to the moment of pinching action during the motor imagery. Thus, we excluded the experimental condition in which the somatosensory inputs combined with the motor imagery. Consequently, we found that the excitability of the M1 innervating FDI as a prime mover for a pinching action was inhibited during the observation of that action and the simultaneous delivery of a tactile sensation to the observer’s fingertips with no motor imagery. However, the above-mentioned protocol had the opposite effect; i.e., the FDI MEP amplitude was increased compared with the baseline, during the motor imagery. The tactile sensation evoked by the ES per se did not have any effect on the MEP amplitude. MEP induced after the delivery of a peripheral somatosensory stimulus followed by TMS exhibited a lower amplitude than MEP evoked by TMS alone, and the mechanism responsible for this reduction in MEP amplitude is known as short-latency afferent inhibition (SAI) [21,22]. In the established method for measuring SAI in the FDI, the inter-stimulus interval (ISI) between median nerve stimulation of the wrist and TMS is set at N20 + 2 ms; i.e., approximately 20–23 ms, and the stimulus intensity of the nerve stimulus is usually set at 300% of the perception threshold. In the present study, we adopted a rather weak stimulus intensity for the ES (130% of the tactile sensation threshold), and the ES was administered to the skin of the fingertips, not to the peripheral nerve. Thus, the induced sensory input evoked by the ES was experienced as a tactile sensation detected by the fingertips. In addition, the ISI between the delivery of the ES to the
fingertips and the TMS was set at 25 ms, based on the location of the stimulation site; i.e., the fingertips which are located distal to the wrist and the fact that the ES was composed of 5 pulses. As a result, a reduction in the FDI MEP amplitude was only observed in the “OBS + ES” conditions; i.e., no change in MEP amplitude was seen in the “ES” conditions. Furthermore, such decreases were seen in the FDI which is activated during pinching, but not in the ADM which is not involved in pinching. This means that action observation was essential for the inhibitory effect seen in the “OBS + ES” conditions. Therefore, we consider that the reduction in the FDI MEP amplitude observed in the “OBS+ES” conditions was not caused by an SAI-like effect. A previous study reported that the intervention of the transcutaneous ES (0.25 ms square pulse at 90 Hz) at stimulus intensity below the motor threshold over the right thenar eminence for 15 min, which produced the tingling sensation for in the stimulated area without muscle twitch or pain, induced the transient reduction of MEP amplitudes of the right FDI and abductor pollicis brevis [23]. It shows that short-term transcutaneous ES might have an inhibitory effect of the M1 excitability. The neural mechanism for such a inhibitory effect on M1 excitability was unknown. The ES adopted in the present study did not affect the MEP amplitude, because of the weak intensity inducing the tactile sensation compared to the previous study mentioned above. The FDI MEP amplitude, however, was decreased in the “ES + OBS” condition. We speculate that some gating mechanisms to attenuate the tactile sensation could be activated in the “OBS” condition. Anyway, further study should be done to address the neural mechanisms for the combined effect of “ES + OBS”. Interestingly, the motor imagery reversed the inhibitory effect of the “OBS + ES” conditions on the FDI MEP amplitude. It has been reported that the cross-modal interactions are involved in visuotactile enhancement of the mirror neuron system [24–27]. For example, the sensory threshold of the index finger was significantly decreased after a movie clip of the relevant hand being touched with a stick was shown; however, no such decrease of sensory threshold was seen after a movie clip showing the stick touching the space beneath the hand was presented. The observed decrease of sensory threshold was specific to the index finger shown in the movie clip. This suggests that the visuotactile enhancement was induced by the observation of the finger being touched rather than the depiction of the finger itself [24]. Furthermore, another group found that the somatosensory cortices were activated during the observation of a hand being touched from the egocentric and allocentric perspectives [27]. Cross-modal interactions in the mirror neuron system might explain our findings because the present study employed a similar paradigm to those used in the abovementioned studies; i.e., tactile stimulation was administered to the subject’s fingertips at the exact moment at which they saw another person perform a pinching action. As a result, it is suggested that the cross-modal interactions between the neural signals generated by the action observation with simultaneous tactile sensation were significantly enhanced by motor imagery. During action observation combined with motor imagery, the mirror neuron system and other brain areas, including those involved in processing sensory information related to motor imagery, may be activated simultaneously. Some recent neuroimaging studies have detected greater cortical activity during action observation combined with motor imagery than during action observation or motor imagery alone [28–30]. In addition, several recent TMS studies, which focused on M1 excitability, have discussed the different effects of and interactions between action observation and motor imagery [7,8,31–35]. These previous studies strongly suggest that the neural mechanisms responsible for action observation and motor imagery are activated simultaneously, resulting in enhanced M1 excitability. This suggestion might be supported by the results of the present study, which showed that
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