http://informahealthcare.com/smr ISSN: 0899-0220 (print), 1369-1651 (electronic) Somatosens Mot Res, 2014; 31(4): 209–213 ! 2014 Informa UK Ltd. DOI: 10.3109/08990220.2014.923392
ORIGINAL ARTICLE
Phase-dependent modulation of corticospinal excitability during the observation of the initial phase of gait Makoto Takahashi1, Natsuko Uchida2, Mami Yoshida2, Nan Liang1, Kimitaka Nakazawa3, Kiyokazu Sekikawa1, Tsutomu Inamizu1, & Hironobu Hamada1 1
Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan, 2Institute of Health Sciences, Faculty of Medicine, Hiroshima University, Hiroshima, Japan, and 3Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan
Abstract
Keywords
This study was undertaken to identify the temporal characteristics of corticospinal excitability of tibialis anterior muscle during the observation of the initial phase of gait. For this purpose, using transcranial magnetic stimulation, we recorded motor evoked potentials (MEPs) during the observation of the second step of an actor’s first three steps of gait initiation with (complex gait) or without (normal gait) an obstacle and unstable surface. The results demonstrate that (1) MEPs during the observation of the initial phase of normal gait were significantly increased only at early swing phase, but not other phases (mid-swing, heel contact, mid-stance, and heel off) and (2) MEPs during the observation of the initial phase of complex gait were significantly increased at early swing and also at mid-swing and heel contact phases. These findings provide the first evidence that corticospinal excitability during the observation of gait, especially the initial phase, is modulated in phase- and motor-demanded-dependent manners.
Action observation, initial phase of gait, transcranial magnetic stimulation
Introduction Using transcranial magnetic stimulation (TMS), it has been shown that the passive observation of voluntary hand/arm movements is associated with increased corticospinal excitability, presumably reflecting activity within the human mirror neuron system (Fadiga et al. 1995; Strafella and Paus 2000; Gangitano et al. 2001; Borroni et al. 2005; Montagna et al. 2005). Corticospinal facilitation has also been found to be specific to the muscle involved in the observed action (Fadiga et al. 1995; Strafella and Paus 2000). Furthermore, the presence has been shown of a strict temporal coupling between the changes in corticospinal excitability during the observation of grasping movements and dynamics of the kinematics (Gangitano et al. 2001), and electromyography (EMG) recruitment profiles (Borroni et al. 2005; Montagna et al. 2005) during execution of the observed actions. These findings indicate that the time course of corticospinal facilitation during the observation of hand/arm movements follows that of movement execution. On the other hand, we have previously revealed that TMSinduced motor evoked potentials (MEPs) in tibialis anterior (TA) muscle are significantly increased during the observation of steady-state gait on a treadmill throughout the entire step cycle periods, but not during a specific step period Correspondence: M. Takahashi, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Tel: +81 82 257 5421. Fax: +81 82 257 5344. E-mail: [email protected]
History Received 3 February 2014 Revised 2 May 2014 Accepted 6 May 2014 Published online 10 June 2014
(Takahashi et al. 2008). This finding indicates that corticospinal excitability of TA muscle during the observation of steady-state gait was not temporally coupled with EMG activities of TA muscle during actual gait execution. Direct evidence for the involvement of the primary motor cortex during human gait comes from studies using TMS (Schubert et al. 1997, 1999; Capaday et al. 1999; Petersen et al. 2001) and coherence analysis of the coupling between electroencephalography (EEG) and EMG (Petersen et al. 2012). Despite these findings, however, once gait is initiated it does not require conscious control under normal conditions, suggesting that steady-state gait is a highly automated movement with little cortical involvement. Thus, one possible explanation for the different temporal characteristics between the observation of voluntary hand/arm movements and steady-state gait may be attributed to the difference in involvement of the primary motor cortex during execution of the observed actions. It is generally thought that the primary cortex plays a key role in gait initiation (Armstrong 1988; Wagner et al. 2008; Wang et al. 2009). Furthermore, rapid corticospinal intervention is needed in several situations during gait, for example, in avoidance of obstacles and voluntary control of foot position on irregular terrain (Schubert et al. 1997, 1999). Thus, it is reasonable to hypothesize that (1) corticospinal excitability during the observation of the initial phase of gait may be modulated in a phase-dependent manner and (2) corticospinal excitability during the observation of more complex patterns of gait initiation may be enhanced in a phase-dependent
210
M. Takahashi et al.
manner and also related to the functional motor demand of the observed actions. To test these hypotheses, we attempted to identify TMS-induced MEPs in TA muscle during the observation of the second step of an actor’s first three steps of gait initiation with (complex gait) or without (normal gait) an obstacle and unstable surface.
Materials and methods Subjects Eleven healthy right-handed volunteers (7 males and 4 females, mean age 26.1 years, range 21–33 years) participated in the experiments after giving their informed consent. The experiments were performed in accordance with the Declaration of Helsinki (1964) and with the approval of the institutional ethics committee. EMG recording and cortical stimulation The EMG activity of the right TA muscle was recorded with 7-mm diameter Ag–AgCl surface cup electrodes placed over the belly of the muscle. The EMG signals were amplified at a bandwidth of 15 Hz to 1 kHz, sampled at 2 kHz, and fed to a computer for offline analysis. TMS was applied by Magstim 200 (Magstim, Whitland, UK) using a double cone coil, external diameter of wings 13 cm. At the beginning of each experiment, the position of the coil was systematically adjusted to find the optimum location for the activation of the right TA muscle. In general, the optimum position was 1 cm lateral and 1 cm anterior to the vertex. Stimulus intensity was set at about 110% of the motor threshold (MT at rest, the lowest intensity evoking MEP with amplitudes of about 50 mV in at least three out of six successive trials). These intensities were 45–70% of the maximum stimulator output.
Somatosens Mot Res, 2014; 31(4): 209–213
Experimental protocols Subjects were seated in a comfortable chair in front of a 100-inch screen (SP-100, Izumi-Cosmo, Osaka, Japan) at a distance of about 1.5 m. The hip, knee, and ankle joint angles were approximately 100 , 120 , and 100 , respectively. Three experimental conditions were investigated: (1) observation of black screen (control), (2) observation of a video clip of an actor’s first three steps of gait initiation (normal gait), and (3) observation of a video clip of an actor’s first three steps of gait initiation while stepping over an obstacle and landing on an unstable surface (inflated rubber disk) (complex gait). Subjects were instructed to remain completely relaxed throughout the trials and to observe the video clips attentively. They were also requested not to focus on specific joint movements (i.e., ankle joint movement) but on the actor’s whole body movement. Movie presentation and TMS stimulus timing were simultaneously controlled by a custom-made program running under LabVIEW (National Instruments, Austin, TX, USA). Each video clip of normal and complex gait (frame rate: 30 fps) lasted 3927 and 4191 ms (Figure 1). In both gait conditions, the actor initiated gait with the left leg from quiet standing and was viewed with the right side in lateral view. In each trial during the observation of normal and complex gait, TMS was applied at one of the following five phases during the second step in random order: early swing (1914 ms from the beginning of the video clip), midswing (2079 ms), heel contact (2475 and 2574 ms), midstance (2937 and 2970 ms), and heel off (3432 and 3498 ms) of the right leg. The gait cycle is generally divided into seven phases (early swing, mid-swing, heel contact, foot flat, midstance, heel off, and toe off). Because early swing begins at toe off and it is difficult to divide the gait cycle of complex gait into heel contact and foot flat as seen in Figure 1, we chose early swing and heel contact, respectively, and the gait cycle was divided into the above-mentioned five phases.
Figure 1. Stimulus timing during the observation of the initial phase of normal and complex gait. Video clips were presented in color.
DOI: 10.3109/08990220.2014.923392
Motor facilitation while observing gait initiation
211
We recorded 6 MEP responses at the control condition and 10 MEPs during the observation of either normal or complex gait (2 stimulus 5 gait phases) in one session. We repeated five sessions for each condition in random order, thus in each subject we obtained 10 MEP responses at each gait phase in both gait conditions. The inter-trial interval was set at 10 s and the resting period between sessions was at least 3 min to prevent fatigue. Data and statistical analyses The peak-to-peak amplitudes of MEPs were measured. The individual mean MEP size during the observation of gait was expressed as a percentage of control values for each subject. The normalized resulting values were pooled for all subjects and then the group mean MEP size with standard errors were calculated. The background EMG activities were calculated from the rectified signals over a 50 ms window just prior to TMS. MEPs were analyzed using two-way repeated-measure ANOVA with factors of gait condition (normal and complex gait) and gait phase (five gait phases). If a significant difference was present between two gait conditions, post hoc analyses were done using the paired t-test with Bonferroni correction for multiple comparisons. In addition, MEP size and the background EMG activities for each gait condition were analyzed independently using one-way ANOVA with repeated measure (factor; baseline, five gait phases) to determine the significant differences under each gait condition. If a significant effect was obtained, Dunnett’s multiple comparison tests were used to compare the values obtained during the observation of gait with the control values. The level of statistical significance was defined as p50.05. The data are expressed as means ± SE.
Figure 2. Representative examples of the averaged MEP responses in TA muscle obtained from a single subject during control and the observation of the initial phase of (A) normal and (B) complex gait.
Results Figure 2 shows representative examples of MEPs in TA muscle during the observation of the second step of the first three steps of gait initiation obtained from a single subject. The group mean MEP size with standard errors across all subjects (n ¼ 11) are shown in Figure 3. The group mean control MEP amplitudes of normal and complex gait were 0.11 ± 0.02 and 0.10 ± 0.03 mV, respectively. Two-way ANOVA [condition (normal and complex gait) gait phase (five gait phases)] tests showed a significant effect of gait phase (F ¼ 4.17, p50.05), but no significant effect of condition (F ¼ 0.24, p ¼ 0.63) and condition gait phase interaction (F ¼ 0.38, p ¼ 0.83). One-way ANOVA (factor; baseline, five gait phases) tests showed significant effects in both gait conditions (normal gait: F ¼ 2.65, p50.05, complex gait: F ¼ 4.99, p50.05). Post hoc analysis revealed that during the observation of normal gait, the group mean MEP size was significantly increased at early swing phase, whereas those at the other four phases tended to be larger than the control value but their increases were not significant (Figures 2A and 3). On the other hand, during the observation of complex gait, the group mean MEP size was significantly increased at early swing and the significant increase was maintained at mid-swing and heel contact phases (Figures 2B and 3).
Figure 3. Means and standard errors of normalized MEP size obtained from 11 subjects during the observation of the initial phase of normal and complex gait. *Significant difference from the control value (Dunnett’s multiple comparison tests).
The amount of background EMG activities during the observation of both gait conditions were not significantly different from the control condition, suggesting that the modulation of MEP amplitudes could not be secondary effects due to the changes of background EMG activity levels during the observation of gait.
Discussion We have previously shown that corticospinal excitability in TA muscle is increased during the observation of steady-state gait on a treadmill throughout the entire step cycle periods, but not during a specific step period (Takahashi et al. 2008). On the other hand, the present study reveals that during the observation of the initial phase of normal gait, corticospinal excitability is significantly increased at a specific phase period, but not throughout the entire step cycle periods. Modification of the gait pattern during the initial phase is
212
M. Takahashi et al.
thought to depend in particular on supraspinal control (Armstrong 1988; Wagner et al. 2008; Wang et al. 2009), indicating that the primary motor cortex and corticospinal tract contribute more directly to the muscle activity during the initial phase of gait, compared with steady-state gait. Therefore, the difference between our previous and the present results should be attributed to the difference in involvement of the primary motor cortex between during the initial phase and steady-state gait. On the other hand, TA EMG activities during actual gait appear at the early swing (stance–swing transition, first burst) phase and additionally around heel contact (swing–stance transition, second burst) (den Otter et al. 2004). Although there is still no evidence regarding corticospinal facilitation during the actual initial phase of gait, TA MEP is increased at both early and late swing phases in parallel with TA EMG activities during steady-state gait (Schubert et al. 1997, 1999). However, it is unknown to what extent descending (cortical drive) and afferent inputs contribute to this corticospinal facilitation during gait. Recently, Petersen et al. (2012) have shown significant coupling between EEG recordings over the leg motor area and TA EMG in the frequency band 24–40 Hz, which originates from the corticospinal tract, during the early swing but not late swing phase of treadmill gait. This finding suggests that the corticospinal tract contributes more to the ongoing TA EMG activity at the early swing phase than that around the heel contact phase. Considering that corticospinal facilitation during the action observation is induced only by the cortical drive without afferent inputs, it is reasonable to conclude that corticospinal excitability is increased at the early swing phase but not around the heel contact phase during the observation of the initial phase of normal gait. MEPs during the observation of the initial phase of complex gait were significantly increased at early swing and also at mid-swing and heel contact phases, although the amount of increase in MEPs was not different at these three gait phases between during the observation of normal and complex gait. It has been shown that the rate of discharge of the corticospinal tract neurons in the cat is markedly increased when adjustments of the limb trajectory are required to overstep an obstacle or to place the foot on a definite spot on the ground (Drew 1988; Beloozerova and Sirota 1993; Widajewicz et al. 1994). In the present study, at mid-swing phase, greater ankle dorsiflexion assisted by TA is required when an obstacle is present, which might reflect preparation for the alterations in the swing limb trajectory required to step over an obstacle (Patla and Rietdyk 1993). Immediately after heel contact when the subject is about to move the weight of the body from one leg to the other, it is crucial for securing the stability of the supporting limb to minimize the impact of sudden perturbations (Christensen et al. 2000, 2001; Nakazawa et al. 2004). At this time, it would be essential for the subject to obtain promptly information of this, which may be provided by stretch sensitive afferents from the TA muscle projecting to the motor cortex (transcortical reflex pathway) (Christensen et al. 2000). On the other hand, in the present study, the unstable surface (inflated rubber disk) is visible before the initiation of gait, thus giving subjects ample time to implement the necessary changes preparing for predictable perturbations at
Somatosens Mot Res, 2014; 31(4): 209–213
heel contact phase. This proactive strategy securing the stability of the ankle joint likely originates from changes in the cortical drive that shape the gait pattern. Thus, it should be considered that the increases in MEPs during the observation of the initial phase of complex gait at mid-swing and heel contact phases reflect the cortical drive related to increased functional motor demand of the observed actions, that is, an obstacle avoidance and voluntary control of foot position on an unstable surface.
Conclusion We demonstrated that (1) MEPs during the observation of the initial phase of normal gait were increased only at early swing phase, but not other phases and (2) MEPs during the observation of the initial phase of complex gait were increased at early swing and also at mid-swing and heel contact phases. These findings indicate that corticospinal excitability during the observation of gait, especially the initial phase, is modulated in phase- and motor-demandeddependent manners.
Declaration of interest The authors report no conflicts of interest. This study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science.
References Armstrong DM. 1988. The supraspinal control of mammalian locomotion. J Physiol 405:1–37. Beloozerova IN, Sirota MG. 1993. The role of the motor cortex in the control of accuracy of locomotor movements in the cat. J Physiol 461: 1–25. Borroni P, Montagna M, Cerri G, Baldissera F. 2005. Cyclic time course of motor excitability modulation during the observation of a cyclic hand movement. Brain Res 1065:115–124. Capaday C, Lavoie BA, Barbeau H, Schneider C, Bonnard M. 1999. Studies on the corticospinal control of human walking. I. Responses to focal transcranial magnetic stimulation of the motor cortex. J Neurophysiol 81:129–139. Christensen LO, Petersen N, Andersen JB, Sinkjaer T, Nielsen JB. 2000. Evidence for transcortical reflex pathways in the lower limb of man. Prog Neurobiol 62:251–272. Christensen LO, Andersen JB, Sinkjaer T, Nielsen J. 2001. Transcranial magnetic stimulation and stretch reflexes in the tibialis anterior muscle during human walking. J Physiol 531:545–557. den Otter AR, Geurts AC, Mulder T, Duysens J. 2004. Speed related changes in muscle activity from normal to very slow walking speeds. Gait Posture 19:270–278. Drew T. 1988. Motor cortical cell discharge during voluntary gait modification. Brain Res 457:181–187. Fadiga L, Fogassi L, Pavesi G, Rizzolatti G. 1995. Motor facilitation during action observation: A magnetic stimulation study. J Neurophysiol 73:2608–2611. Gangitano M, Mottaghy FM, Pascual-Leone A. 2001. Phase-specific modulation of cortical motor output during movement observation. Neuroreport 12:1489–1492. Montagna M, Cerri G, Borroni P, Baldissera F. 2005. Excitability changes in human corticospinal projections to muscles moving hand and fingers while viewing a reaching and grasping action. Eur J Neurosci 22:1513–1520. Nakazawa K, Kawashima N, Akai M, Yano H. 2004. On the reflex coactivation of ankle flexor and extensor muscles induced by a sudden drop of support surface during walking in humans. J Appl Physiol (1985) 96:604–611.
DOI: 10.3109/08990220.2014.923392
Patla AE, Rietdyk S. 1993. Visual control of limb trajectory over obstacles during locomotion: Effect of obstacle height and width. Gait Posture 1:45–60. Petersen NT, Butler JE, Marchand-Pauvert V, Fisher R, Ledebt A, Pyndt HS, Hansen NL, Nielsen JB. 2001. Suppression of EMG activity by transcranial magnetic stimulation in human subjects during walking. J Physiol 537:651–656. Petersen TH, Willerslev-Olsen M, Conway BA, Nielsen JB. 2012. The motor cortex drives the muscles during walking in human subjects. J Physiol 590:2443–2452. Schubert M, Curt A, Jensen L, Dietz V. 1997. Corticospinal input in human gait: Modulation of magnetically evoked motor responses. Exp Brain Res 115:234–246. Schubert M, Curt A, Colombo G, Berger W, Dietz V. 1999. Voluntary control of human gait: Conditioning of magnetically evoked motor responses in a precision stepping task. Exp Brain Res 126:583–588.
Motor facilitation while observing gait initiation
213
Strafella AP, Paus T. 2000. Modulation of cortical excitability during action observation: A transcranial magnetic stimulation study. Neuroreport 11:2289–2292. Takahashi M, Kamibayashi K, Nakajima T, Akai M, Nakazawa K. 2008. Changes in corticospinal excitability during observation of walking in humans. Neuroreport 19:727–731. Wagner J, Stephan T, Kalla R, Bruckmann H, Strupp M, Brandt T, Jahn K. 2008. Mind the bend: Cerebral activations associated with mental imagery of walking along a curved path. Exp Brain Res 191: 247–255. Wang J, Wai Y, Weng Y, Ng K, Huang YZ, Ying L, Liu H, Wang C. 2009. Functional MRI in the assessment of cortical activation during gait-related imaginary tasks. J Neural Transm 116: 1087–1092. Widajewicz W, Kably B, Drew T. 1994. Motor cortical activity during voluntary gait modifications in the cat. II. Cells related to the hindlimbs. J Neurophysiol 72:2070–2089.
Copyright of Somatosensory & Motor Research is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
ORIGINAL ARTICLE
Phase-dependent modulation of corticospinal excitability during the observation of the initial phase of gait Makoto Takahashi1, Natsuko Uchida2, Mami Yoshida2, Nan Liang1, Kimitaka Nakazawa3, Kiyokazu Sekikawa1, Tsutomu Inamizu1, & Hironobu Hamada1 1
Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan, 2Institute of Health Sciences, Faculty of Medicine, Hiroshima University, Hiroshima, Japan, and 3Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan
Abstract
Keywords
This study was undertaken to identify the temporal characteristics of corticospinal excitability of tibialis anterior muscle during the observation of the initial phase of gait. For this purpose, using transcranial magnetic stimulation, we recorded motor evoked potentials (MEPs) during the observation of the second step of an actor’s first three steps of gait initiation with (complex gait) or without (normal gait) an obstacle and unstable surface. The results demonstrate that (1) MEPs during the observation of the initial phase of normal gait were significantly increased only at early swing phase, but not other phases (mid-swing, heel contact, mid-stance, and heel off) and (2) MEPs during the observation of the initial phase of complex gait were significantly increased at early swing and also at mid-swing and heel contact phases. These findings provide the first evidence that corticospinal excitability during the observation of gait, especially the initial phase, is modulated in phase- and motor-demanded-dependent manners.
Action observation, initial phase of gait, transcranial magnetic stimulation
Introduction Using transcranial magnetic stimulation (TMS), it has been shown that the passive observation of voluntary hand/arm movements is associated with increased corticospinal excitability, presumably reflecting activity within the human mirror neuron system (Fadiga et al. 1995; Strafella and Paus 2000; Gangitano et al. 2001; Borroni et al. 2005; Montagna et al. 2005). Corticospinal facilitation has also been found to be specific to the muscle involved in the observed action (Fadiga et al. 1995; Strafella and Paus 2000). Furthermore, the presence has been shown of a strict temporal coupling between the changes in corticospinal excitability during the observation of grasping movements and dynamics of the kinematics (Gangitano et al. 2001), and electromyography (EMG) recruitment profiles (Borroni et al. 2005; Montagna et al. 2005) during execution of the observed actions. These findings indicate that the time course of corticospinal facilitation during the observation of hand/arm movements follows that of movement execution. On the other hand, we have previously revealed that TMSinduced motor evoked potentials (MEPs) in tibialis anterior (TA) muscle are significantly increased during the observation of steady-state gait on a treadmill throughout the entire step cycle periods, but not during a specific step period Correspondence: M. Takahashi, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Tel: +81 82 257 5421. Fax: +81 82 257 5344. E-mail: [email protected]
History Received 3 February 2014 Revised 2 May 2014 Accepted 6 May 2014 Published online 10 June 2014
(Takahashi et al. 2008). This finding indicates that corticospinal excitability of TA muscle during the observation of steady-state gait was not temporally coupled with EMG activities of TA muscle during actual gait execution. Direct evidence for the involvement of the primary motor cortex during human gait comes from studies using TMS (Schubert et al. 1997, 1999; Capaday et al. 1999; Petersen et al. 2001) and coherence analysis of the coupling between electroencephalography (EEG) and EMG (Petersen et al. 2012). Despite these findings, however, once gait is initiated it does not require conscious control under normal conditions, suggesting that steady-state gait is a highly automated movement with little cortical involvement. Thus, one possible explanation for the different temporal characteristics between the observation of voluntary hand/arm movements and steady-state gait may be attributed to the difference in involvement of the primary motor cortex during execution of the observed actions. It is generally thought that the primary cortex plays a key role in gait initiation (Armstrong 1988; Wagner et al. 2008; Wang et al. 2009). Furthermore, rapid corticospinal intervention is needed in several situations during gait, for example, in avoidance of obstacles and voluntary control of foot position on irregular terrain (Schubert et al. 1997, 1999). Thus, it is reasonable to hypothesize that (1) corticospinal excitability during the observation of the initial phase of gait may be modulated in a phase-dependent manner and (2) corticospinal excitability during the observation of more complex patterns of gait initiation may be enhanced in a phase-dependent
210
M. Takahashi et al.
manner and also related to the functional motor demand of the observed actions. To test these hypotheses, we attempted to identify TMS-induced MEPs in TA muscle during the observation of the second step of an actor’s first three steps of gait initiation with (complex gait) or without (normal gait) an obstacle and unstable surface.
Materials and methods Subjects Eleven healthy right-handed volunteers (7 males and 4 females, mean age 26.1 years, range 21–33 years) participated in the experiments after giving their informed consent. The experiments were performed in accordance with the Declaration of Helsinki (1964) and with the approval of the institutional ethics committee. EMG recording and cortical stimulation The EMG activity of the right TA muscle was recorded with 7-mm diameter Ag–AgCl surface cup electrodes placed over the belly of the muscle. The EMG signals were amplified at a bandwidth of 15 Hz to 1 kHz, sampled at 2 kHz, and fed to a computer for offline analysis. TMS was applied by Magstim 200 (Magstim, Whitland, UK) using a double cone coil, external diameter of wings 13 cm. At the beginning of each experiment, the position of the coil was systematically adjusted to find the optimum location for the activation of the right TA muscle. In general, the optimum position was 1 cm lateral and 1 cm anterior to the vertex. Stimulus intensity was set at about 110% of the motor threshold (MT at rest, the lowest intensity evoking MEP with amplitudes of about 50 mV in at least three out of six successive trials). These intensities were 45–70% of the maximum stimulator output.
Somatosens Mot Res, 2014; 31(4): 209–213
Experimental protocols Subjects were seated in a comfortable chair in front of a 100-inch screen (SP-100, Izumi-Cosmo, Osaka, Japan) at a distance of about 1.5 m. The hip, knee, and ankle joint angles were approximately 100 , 120 , and 100 , respectively. Three experimental conditions were investigated: (1) observation of black screen (control), (2) observation of a video clip of an actor’s first three steps of gait initiation (normal gait), and (3) observation of a video clip of an actor’s first three steps of gait initiation while stepping over an obstacle and landing on an unstable surface (inflated rubber disk) (complex gait). Subjects were instructed to remain completely relaxed throughout the trials and to observe the video clips attentively. They were also requested not to focus on specific joint movements (i.e., ankle joint movement) but on the actor’s whole body movement. Movie presentation and TMS stimulus timing were simultaneously controlled by a custom-made program running under LabVIEW (National Instruments, Austin, TX, USA). Each video clip of normal and complex gait (frame rate: 30 fps) lasted 3927 and 4191 ms (Figure 1). In both gait conditions, the actor initiated gait with the left leg from quiet standing and was viewed with the right side in lateral view. In each trial during the observation of normal and complex gait, TMS was applied at one of the following five phases during the second step in random order: early swing (1914 ms from the beginning of the video clip), midswing (2079 ms), heel contact (2475 and 2574 ms), midstance (2937 and 2970 ms), and heel off (3432 and 3498 ms) of the right leg. The gait cycle is generally divided into seven phases (early swing, mid-swing, heel contact, foot flat, midstance, heel off, and toe off). Because early swing begins at toe off and it is difficult to divide the gait cycle of complex gait into heel contact and foot flat as seen in Figure 1, we chose early swing and heel contact, respectively, and the gait cycle was divided into the above-mentioned five phases.
Figure 1. Stimulus timing during the observation of the initial phase of normal and complex gait. Video clips were presented in color.
DOI: 10.3109/08990220.2014.923392
Motor facilitation while observing gait initiation
211
We recorded 6 MEP responses at the control condition and 10 MEPs during the observation of either normal or complex gait (2 stimulus 5 gait phases) in one session. We repeated five sessions for each condition in random order, thus in each subject we obtained 10 MEP responses at each gait phase in both gait conditions. The inter-trial interval was set at 10 s and the resting period between sessions was at least 3 min to prevent fatigue. Data and statistical analyses The peak-to-peak amplitudes of MEPs were measured. The individual mean MEP size during the observation of gait was expressed as a percentage of control values for each subject. The normalized resulting values were pooled for all subjects and then the group mean MEP size with standard errors were calculated. The background EMG activities were calculated from the rectified signals over a 50 ms window just prior to TMS. MEPs were analyzed using two-way repeated-measure ANOVA with factors of gait condition (normal and complex gait) and gait phase (five gait phases). If a significant difference was present between two gait conditions, post hoc analyses were done using the paired t-test with Bonferroni correction for multiple comparisons. In addition, MEP size and the background EMG activities for each gait condition were analyzed independently using one-way ANOVA with repeated measure (factor; baseline, five gait phases) to determine the significant differences under each gait condition. If a significant effect was obtained, Dunnett’s multiple comparison tests were used to compare the values obtained during the observation of gait with the control values. The level of statistical significance was defined as p50.05. The data are expressed as means ± SE.
Figure 2. Representative examples of the averaged MEP responses in TA muscle obtained from a single subject during control and the observation of the initial phase of (A) normal and (B) complex gait.
Results Figure 2 shows representative examples of MEPs in TA muscle during the observation of the second step of the first three steps of gait initiation obtained from a single subject. The group mean MEP size with standard errors across all subjects (n ¼ 11) are shown in Figure 3. The group mean control MEP amplitudes of normal and complex gait were 0.11 ± 0.02 and 0.10 ± 0.03 mV, respectively. Two-way ANOVA [condition (normal and complex gait) gait phase (five gait phases)] tests showed a significant effect of gait phase (F ¼ 4.17, p50.05), but no significant effect of condition (F ¼ 0.24, p ¼ 0.63) and condition gait phase interaction (F ¼ 0.38, p ¼ 0.83). One-way ANOVA (factor; baseline, five gait phases) tests showed significant effects in both gait conditions (normal gait: F ¼ 2.65, p50.05, complex gait: F ¼ 4.99, p50.05). Post hoc analysis revealed that during the observation of normal gait, the group mean MEP size was significantly increased at early swing phase, whereas those at the other four phases tended to be larger than the control value but their increases were not significant (Figures 2A and 3). On the other hand, during the observation of complex gait, the group mean MEP size was significantly increased at early swing and the significant increase was maintained at mid-swing and heel contact phases (Figures 2B and 3).
Figure 3. Means and standard errors of normalized MEP size obtained from 11 subjects during the observation of the initial phase of normal and complex gait. *Significant difference from the control value (Dunnett’s multiple comparison tests).
The amount of background EMG activities during the observation of both gait conditions were not significantly different from the control condition, suggesting that the modulation of MEP amplitudes could not be secondary effects due to the changes of background EMG activity levels during the observation of gait.
Discussion We have previously shown that corticospinal excitability in TA muscle is increased during the observation of steady-state gait on a treadmill throughout the entire step cycle periods, but not during a specific step period (Takahashi et al. 2008). On the other hand, the present study reveals that during the observation of the initial phase of normal gait, corticospinal excitability is significantly increased at a specific phase period, but not throughout the entire step cycle periods. Modification of the gait pattern during the initial phase is
212
M. Takahashi et al.
thought to depend in particular on supraspinal control (Armstrong 1988; Wagner et al. 2008; Wang et al. 2009), indicating that the primary motor cortex and corticospinal tract contribute more directly to the muscle activity during the initial phase of gait, compared with steady-state gait. Therefore, the difference between our previous and the present results should be attributed to the difference in involvement of the primary motor cortex between during the initial phase and steady-state gait. On the other hand, TA EMG activities during actual gait appear at the early swing (stance–swing transition, first burst) phase and additionally around heel contact (swing–stance transition, second burst) (den Otter et al. 2004). Although there is still no evidence regarding corticospinal facilitation during the actual initial phase of gait, TA MEP is increased at both early and late swing phases in parallel with TA EMG activities during steady-state gait (Schubert et al. 1997, 1999). However, it is unknown to what extent descending (cortical drive) and afferent inputs contribute to this corticospinal facilitation during gait. Recently, Petersen et al. (2012) have shown significant coupling between EEG recordings over the leg motor area and TA EMG in the frequency band 24–40 Hz, which originates from the corticospinal tract, during the early swing but not late swing phase of treadmill gait. This finding suggests that the corticospinal tract contributes more to the ongoing TA EMG activity at the early swing phase than that around the heel contact phase. Considering that corticospinal facilitation during the action observation is induced only by the cortical drive without afferent inputs, it is reasonable to conclude that corticospinal excitability is increased at the early swing phase but not around the heel contact phase during the observation of the initial phase of normal gait. MEPs during the observation of the initial phase of complex gait were significantly increased at early swing and also at mid-swing and heel contact phases, although the amount of increase in MEPs was not different at these three gait phases between during the observation of normal and complex gait. It has been shown that the rate of discharge of the corticospinal tract neurons in the cat is markedly increased when adjustments of the limb trajectory are required to overstep an obstacle or to place the foot on a definite spot on the ground (Drew 1988; Beloozerova and Sirota 1993; Widajewicz et al. 1994). In the present study, at mid-swing phase, greater ankle dorsiflexion assisted by TA is required when an obstacle is present, which might reflect preparation for the alterations in the swing limb trajectory required to step over an obstacle (Patla and Rietdyk 1993). Immediately after heel contact when the subject is about to move the weight of the body from one leg to the other, it is crucial for securing the stability of the supporting limb to minimize the impact of sudden perturbations (Christensen et al. 2000, 2001; Nakazawa et al. 2004). At this time, it would be essential for the subject to obtain promptly information of this, which may be provided by stretch sensitive afferents from the TA muscle projecting to the motor cortex (transcortical reflex pathway) (Christensen et al. 2000). On the other hand, in the present study, the unstable surface (inflated rubber disk) is visible before the initiation of gait, thus giving subjects ample time to implement the necessary changes preparing for predictable perturbations at
Somatosens Mot Res, 2014; 31(4): 209–213
heel contact phase. This proactive strategy securing the stability of the ankle joint likely originates from changes in the cortical drive that shape the gait pattern. Thus, it should be considered that the increases in MEPs during the observation of the initial phase of complex gait at mid-swing and heel contact phases reflect the cortical drive related to increased functional motor demand of the observed actions, that is, an obstacle avoidance and voluntary control of foot position on an unstable surface.
Conclusion We demonstrated that (1) MEPs during the observation of the initial phase of normal gait were increased only at early swing phase, but not other phases and (2) MEPs during the observation of the initial phase of complex gait were increased at early swing and also at mid-swing and heel contact phases. These findings indicate that corticospinal excitability during the observation of gait, especially the initial phase, is modulated in phase- and motor-demandeddependent manners.
Declaration of interest The authors report no conflicts of interest. This study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science.
References Armstrong DM. 1988. The supraspinal control of mammalian locomotion. J Physiol 405:1–37. Beloozerova IN, Sirota MG. 1993. The role of the motor cortex in the control of accuracy of locomotor movements in the cat. J Physiol 461: 1–25. Borroni P, Montagna M, Cerri G, Baldissera F. 2005. Cyclic time course of motor excitability modulation during the observation of a cyclic hand movement. Brain Res 1065:115–124. Capaday C, Lavoie BA, Barbeau H, Schneider C, Bonnard M. 1999. Studies on the corticospinal control of human walking. I. Responses to focal transcranial magnetic stimulation of the motor cortex. J Neurophysiol 81:129–139. Christensen LO, Petersen N, Andersen JB, Sinkjaer T, Nielsen JB. 2000. Evidence for transcortical reflex pathways in the lower limb of man. Prog Neurobiol 62:251–272. Christensen LO, Andersen JB, Sinkjaer T, Nielsen J. 2001. Transcranial magnetic stimulation and stretch reflexes in the tibialis anterior muscle during human walking. J Physiol 531:545–557. den Otter AR, Geurts AC, Mulder T, Duysens J. 2004. Speed related changes in muscle activity from normal to very slow walking speeds. Gait Posture 19:270–278. Drew T. 1988. Motor cortical cell discharge during voluntary gait modification. Brain Res 457:181–187. Fadiga L, Fogassi L, Pavesi G, Rizzolatti G. 1995. Motor facilitation during action observation: A magnetic stimulation study. J Neurophysiol 73:2608–2611. Gangitano M, Mottaghy FM, Pascual-Leone A. 2001. Phase-specific modulation of cortical motor output during movement observation. Neuroreport 12:1489–1492. Montagna M, Cerri G, Borroni P, Baldissera F. 2005. Excitability changes in human corticospinal projections to muscles moving hand and fingers while viewing a reaching and grasping action. Eur J Neurosci 22:1513–1520. Nakazawa K, Kawashima N, Akai M, Yano H. 2004. On the reflex coactivation of ankle flexor and extensor muscles induced by a sudden drop of support surface during walking in humans. J Appl Physiol (1985) 96:604–611.
DOI: 10.3109/08990220.2014.923392
Patla AE, Rietdyk S. 1993. Visual control of limb trajectory over obstacles during locomotion: Effect of obstacle height and width. Gait Posture 1:45–60. Petersen NT, Butler JE, Marchand-Pauvert V, Fisher R, Ledebt A, Pyndt HS, Hansen NL, Nielsen JB. 2001. Suppression of EMG activity by transcranial magnetic stimulation in human subjects during walking. J Physiol 537:651–656. Petersen TH, Willerslev-Olsen M, Conway BA, Nielsen JB. 2012. The motor cortex drives the muscles during walking in human subjects. J Physiol 590:2443–2452. Schubert M, Curt A, Jensen L, Dietz V. 1997. Corticospinal input in human gait: Modulation of magnetically evoked motor responses. Exp Brain Res 115:234–246. Schubert M, Curt A, Colombo G, Berger W, Dietz V. 1999. Voluntary control of human gait: Conditioning of magnetically evoked motor responses in a precision stepping task. Exp Brain Res 126:583–588.
Motor facilitation while observing gait initiation
213
Strafella AP, Paus T. 2000. Modulation of cortical excitability during action observation: A transcranial magnetic stimulation study. Neuroreport 11:2289–2292. Takahashi M, Kamibayashi K, Nakajima T, Akai M, Nakazawa K. 2008. Changes in corticospinal excitability during observation of walking in humans. Neuroreport 19:727–731. Wagner J, Stephan T, Kalla R, Bruckmann H, Strupp M, Brandt T, Jahn K. 2008. Mind the bend: Cerebral activations associated with mental imagery of walking along a curved path. Exp Brain Res 191: 247–255. Wang J, Wai Y, Weng Y, Ng K, Huang YZ, Ying L, Liu H, Wang C. 2009. Functional MRI in the assessment of cortical activation during gait-related imaginary tasks. J Neural Transm 116: 1087–1092. Widajewicz W, Kably B, Drew T. 1994. Motor cortical activity during voluntary gait modifications in the cat. II. Cells related to the hindlimbs. J Neurophysiol 72:2070–2089.
Copyright of Somatosensory & Motor Research is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
