Motor systems 279
Smooth pursuit eye movement preferentially facilitates motor-evoked potential elicited by anterior–posterior current in the brain Koichi Hiraoka, Minori Ae, Nana Ogura, Sayo Komuratani, Chisa Sano, Keigo Shiomi, Yuji Morita and Haruka Yokoyama Neural interaction between the eye and hand movement centers must be a critical part of the mechanism underlying eye–hand coordination. One of the previous findings supporting this view is smooth pursuit eye movementinduced suppression of motor-evoked potential (MEP) in the hand muscles. The purpose of this study was to determine which descending volleys contributing to MEP are preferentially modulated by smooth pursuit eye movement. MEP in the first dorsal interosseous muscle was elicited by different directions of current in the brain during the steady-state phase of smooth pursuit eye movement. Smooth pursuit eye movement facilitated MEP elicited by anterior–posterior (AP) current, but this effect was not seen in MEP elicited by lateromedial or posterior– anterior current. Latency of MEP elicited by AP current was significantly longer than latencies of MEPs elicited by other directions of current, indicating that AP current in the brain
predominantly elicited later I-waves. We conclude that smooth pursuit eye movement in the steady-state phase preferentially facilitates MEP predominantly elicited by later I-waves generated by AP current in the brain. NeuroReport c 2014 Wolters Kluwer Health | Lippincott 25:279–283 Williams & Wilkins.
Introduction
Methods
Neural interaction between the eye and hand movement centers is crucial for eye–hand coordination [1,2]. The activation of the ipsilateral cerebellum, the vermis, and the contralateral central sulcus induced by eye–hand coordination effort must reflect the interaction process [3]. Direct evidence supporting this view is suppression of motor-evoked potential (MEP), reflecting corticospinal excitability, in the hand muscles during smooth pursuit eye movement [4]. However, how smooth pursuit eye movement modulates MEP in the hand muscles has not been investigated. MEP is elicited by a sequence of descending volleys generated by transcranial magnetic stimulation (TMS). The descending volleys generated by TMS with an 8-shaped coil are altered through a change in coil direction [5,6]. Coil direction-dependent conditioning effects on MEP have been reported using this technique; cerebellar TMS-induced short-latency suppression of MEP elicited by AP current in the hand muscles is greater than that of MEP elicited by PA current [7], and short-latency afferent inhibition of MEP elicited by PA current is greater than that of MEP elicited by AP current [8]. The aim of this study was to determine which descending volleys are preferentially affected by smooth pursuit eye movement through observing MEPs elicited by different directions of current in the brain during smooth pursuit eye movement.
Participants
c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 0959-4965
NeuroReport 2014, 25:279–283 Keywords: descending volleys, D-wave, I-wave, motor-evoked potential, smooth pursuit eye movement College of Health and Human Sciences, Osaka Prefecture University, Habikino, Osaka Prefecture, Japan Correspondence to Koichi Hiraoka, PhD, College of Health and Human Sciences, Osaka Prefecture University, Habikino 3-7-30, Habikino, Osaka 583-8555, Japan Tel: + 81 72 950 2875; fax: + 81 72 950 2131; e-mail: [email protected] Received 26 September 2013 accepted 3 October 2013
Eleven healthy individuals (five men and six women) aged 20.1±0.2 years participated in this study. All participants were right handed according to the Edinburgh Handedness Inventory [9]. All participants gave written informed consent before the experiment. The experimental procedure was approved by the ethics committee of Osaka Prefecture University. Apparatus
Participants sat with the right forearm in a prone position on a table. The forearm and the hand were immobilized by a splint. The jaw was placed on a chin stand to minimize motion artifact of the head. A computer screen was placed 100 cm in front of the eyes. Horizontal movement of the right eye was measured using a corneal reflection device (TK2901; Takei Kiki Co., Tokyo, Japan). An illuminometer-cum-light sensor, sensitive to the reflection difference between the cornea and the sclera, was fixed on a goggle frame. Before recording eye movements, the sensor was calibrated from the midline to 101 in the horizontal visual angle at a distance of 100 cm from the individual. Surface electrodes capable of recording electromyographic (EMG) signals were placed over the first dorsal interosseous (FDI), abductor pollicis bravis, and abductor digiti minimi muscles in a DOI: 10.1097/WNR.0000000000000075
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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NeuroReport 2014, Vol 25 No 5
Fig. 1
2s End point (20°) AP TMS (13.3°) (Eye-movement condition) LM Warning cue 1s Fixation point (0°)
PA Eye movement onset
TMS (onset condition) Eye and target movements and coil position. The solid trace indicates the trajectory of the horizontal visual angle and the dashed trace indicates the trajectory of the visual target. A bird’s eye view of the coil position is presented on the right. Arrows beside the coils indicate direction of current in the brain induced by TMS. AP, anterior–posterior; LM, lateromedial; PA, posterior–anterior; TMS, transcranial magnetic stimulation.
belly–tendon montage. The EMG signals were amplified by EMG amplifiers (MEG-2100; Nihon Kohden, Tokyo, Japan) with a band-pass filter from 15 to 3 kHz. The analog signals from the corneal reflection device and EMG amplifiers were converted to digital signals at a sampling rate of 10 kHz using A/D converters (PowerLab800s; AD Instruments, Colorado Springs, Colorado, USA and PowerLab2/26; Unique Acquisition, Unique Medical, Tokyo, Japan) and stored in personal computers. Smooth pursuit eye movement
A warning cue appeared at a fixation point on the computer screen for 1 s (Fig. 1). The participant was instructed to gaze at the warning cue without blinking. The horizontal visual angle was 01 from the midline when the individual gazed at the warning cue. The warning cue changed to a target point 1 s later, and the target point moved to an end point at a constant velocity of 101/s. The individual tracked the target point with the eyes. When the target reached the end point, it stayed at that point for 1 s. The horizontal visual angle was 201 right to the midline when the individual was watching the end point. Before beginning the experiment, the individual practiced the smooth pursuit eye movement 20 times. Transcranial magnetic stimulation
TMS was delivered by an 8-shaped coil (YM-132B; Nihon Kohden) connected to a magnetic stimulator (SMN1200; Nihon Kohden). Maximum intensity of the coil was 1.03 T. The coil was positioned so that magnetic stimulation induced posterior–anterior (PA) current in the brain for the PA position (Fig. 1). Anterior–posterior (AP) current in the brain was induced by rotating the coil handle 1801 from the PA direction for the AP position. The coil was held in a direction that induced lateromedial
(LM) current in the brain for the LM position. An experimental session was conducted for each coil position. The coil in the AP position was placed 6 cm to the left of the vertex and moved little by little to find a hot spot where the averaged amplitude of five MEPs in the FDI muscle was greatest. TMS was delivered over this hot spot for all the coil positions, because it is known that the optimal site of the 8-shaped coil remains the same among coil positions [5]. TMS intensity was decreased trial by trial to determine the intensity that produced 300–400 mV of MEP amplitude in the FDI muscle when TMS was delivered with the coil in the AP position 0–100 ms before the onset of smooth pursuit eye movement. MEP amplitude 0–100 ms before the onset of smooth pursuit eye movement was matched among the coil positions. The probability of the involvement of D-waves in contributing to MEP increases with higherintensity TMS [10]. Thus, we considered that weak TMS eliciting low test MEP would be optimal for obtaining MEPs predominantly produced by I-waves, with minimum involvement of motor responses produced by D-waves in both the PA and AP positions. In the experimental sessions, TMS was delivered 0–100 ms before eye movement onset (onset condition) or when the eyes passed through 13.3±11 of horizontal visual angle (eye-movement condition), which was two-thirds of the horizontal visual angle at the end point. The horizontal visual angle, at which TMS was delivered in the eye-movement condition, was in the steady-state phase of smooth pursuit eye movement. TMS was delivered only at this angle in the eye-movement condition because of previous findings that modulation of MEP elicited by TMS with 8-shaped coil in the AP position, and modulation of MEP elicited by TMS with
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Eye movement modulates motor-evoked potential Hiraoka et al. 281
amplitude between the onset and eye-movement condition for each coil position independently. a level for these tests was 0.05/3 = 0.017. Data were expressed as mean values and SEM.
round coil during smooth pursuit eye movement, was not phase dependent [4,11]. The onset and eye-movement conditions were randomly assigned trial by trial. The trials in which background EMG was not silent in any of the three recorded muscles, eye movement was not successfully executed, or where the horizontal visual angle at which TMS was delivered was not optimal, were discarded. Furthermore, in the onset condition, trials with premature small deviations of horizontal visual angle before the onset of smooth pursuit eye movement were discarded, because we had observed in our preliminary experiments that MEP elicited immediately before eye movement onset is facilitated when premature small deviations of horizontal visual angle are present. The interval between each trial was more than 10 s. Each experimental session continued until 20 successful trials had been obtained for both the onset and eye-movement condition.
Results The latency of eye movement was 283±8 ms. Prestimulus background EMG amplitude was 3.9±0.4 mV in the FDI muscle, 3.8±0.8 mV in the abductor digiti minimi muscle, and 3.4±0.4 mV in the abductor pollicis bravis muscle. No significant differences were found in the prestimulus background EMG amplitude among the experimental conditions in any of the muscles. The hot spot was 6.3±0.4 cm lateral to and 1.0±0.3 cm anterior to the vertex. TMS intensity was 84.4±4.3% of maximum stimulator output in the AP position, 72.9±4.1% of that in the LM position, and 64.5±2.9% of that in the PA position. The ANOVA revealed significant differences in TMS intensity among the coil positions [F(2,20) = 29.28, P = 0.000]. The Bonferroni multiple comparison test revealed significant differences between the coil positions (P < 0.05). TMS was delivered 1270±31 ms after the target movement onset, and the horizontal visual angle at which TMS was delivered was 13.3±0.11 in the eye-movement condition.
Data analysis
Prestimulus background EMG amplitude was estimated from the full rectified EMG in the time window between 110 and 10 ms before TMS. MEP was analyzed only in the FDI muscle, because MEP amplitude was matched among the coil positions only in that muscle, and TMS was delivered over the hot spot of the FDI muscle. Change in MEP amplitude induced by eye movement was expressed as the percentage of MEP amplitude in the onset condition. MEP latency for each coil position in the onset condition was estimated from MEPs whose amplitudes were similar to mean MEP amplitudes elicited by TMS with the coil in the AP position in the onset condition. One-way repeated measures analysis of variance (ANOVA) was conducted, followed by the Bonferroni multiple comparison test. a level for these tests was 0.05. Multiple t-tests with the Bonferroni adjustment of a were conducted to compare MEP
MEP amplitude in the onset condition was 325±34 mV in the AP position, 364±59 mV in the LM position, and 369±32 mV in the PA position. The ANOVA failed to reveal significant differences in MEP amplitude among the coil positions [F(2,20) = 0.51, P = 0.607]. MEP latency in the onset condition was significantly different among the coil positions [F(2,20) = 21.45, P = 0.000], as shown in Fig. 2b. The Bonferroni multiple comparison test revealed that MEP latency in the AP position was significantly longer than MEP latencies in the LM or PA position (P < 0.05). MEP amplitude in the
Fig. 2
(b)
(c) 30
∗ ∗
10 ms
Latency (ms)
25
30 μV
MEP amplitude (% of onset)
(a)
20 15 10 5 0 AP
LM
PA
180 160 140 120 100 80 60 40 20 0
∗
∗
†
AP
LM
PA
Specimen record of MEPs induced by AP current (a), MEP latency (b), and change in MEP amplitude induced by eye movement (c). The solid trace indicates MEP in the onset condition and the dashed trace indicates MEP in the eye-movement condition (a). Bars indicate mean and error bars indicate SEM. wSignificant difference in MEP amplitude between the onset and the eye-movement condition by t-test (P < 0.017). *Significant differences between the coil positions by the Bonferroni multiple comparison test (P < 0.05). AP, anterior–posterior; LM, lateromedial; MEP, motorevoked potential; PA, posterior–anterior.
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282 NeuroReport 2014, Vol 25 No 5
eye-movement condition was significantly greater than that in the onset condition in the AP position, as shown in Fig. 2a and c (P = 0.012). In contrast, no significant difference in MEP amplitude between the onset and eyemovement condition was found in the other coil positions (Fig. 2c). The change in MEP amplitude induced by eye movement was 133±10% in the AP position, 106±11% in the LM position, and 99±12% in the PA position. The change in MEP amplitude induced by eye movement was therefore significantly different among the coil positions [F(2,20) = 5.68, P = 0.011]. The Bonferroni multiple comparison test revealed that the change in MEP amplitude induced by eye movement in the AP position was significantly greater than that in the LM or PA position (P < 0.05).
Discussion MEP elicited by LM current was not significantly modulated by smooth pursuit eye movement. LM current in the brain preferentially induces D-waves through direct stimulation of the corticospinal axons [12,13]. Thus, the present findings indicate that excitability of the subcortical elements of the corticospinal pathway is little modulated by smooth pursuit eye movement. In contrast, smooth pursuit eye movement facilitated MEP elicited by AP current. Latency of MEP elicited by AP current was significantly longer than that elicited by LM current, which is consistent with the results of a previous study [8]. This finding must be due to a difference in central conduction time, originating in the fact that AP current in the brain preferentially recruits later I-waves mediated through chains of interneurons in the motor cortex [5], whereas LM current preferentially stimulates the corticospinal axons directly. Furthermore, latency of MEP elicited by AP current was significantly longer than that elicited by PA current, which is consistent with previous findings that MEP elicited by AP current is 2–3 ms later than that elicited by PA current [5,14]. This is likely because of the fact that PA current preferentially elicits early I-waves [10], whereas AP current preferentially elicits later I-waves. Thus, selective facilitation of high MEP elicited by AP current must reflect preferential facilitation of later I-waves during the steady-state phase of smooth pursuit eye movement. It has been hypothesized that motor plan to the tested muscle is produced using the common descending pathway of the eye and hand movement centers during smooth pursuit eye movement when the direction of the eye movement is identical to the function of the tested muscle [4]. This was based on a finding that smooth pursuit eye movement-induced suppression of corticospinal excitability in the finger muscle was low when the function of the target muscle was identical to the direction of eye movement. However, the facilitation of MEP during smooth pursuit eye movement observed in the present study does not likely originate from the motor
plan as hypothesized by Maioli and colleagues, because the eye-movement direction was to the right, whereas the function of the right FDI muscle in prone position is a leftward movement (abduction) of the index finger. Further studies are needed to elucidate mechanisms underlying smooth pursuit eye movement-induced facilitation of MEP in the FDI muscle elicited by AP current in the brain. The insignificant modulation of MEP elicited by PA current during smooth pursuit eye movement in the present study conflicts with previous findings that MEP in the finger muscles elicited by PA current was suppressed during smooth pursuit eye movement [4]. Eye movement amplitude and velocity and position of the forearm were the same in both studies. The major difference between the two studies was test MEP amplitude; amplitude of MEPs at the central fixation point was as high as 1400 mV in the previous study, whereas low MEPs with amplitude of only 300–400 mV were elicited immediately before eye movement onset in the present study. Thus, the most likely explanation for the conflicting findings between the two studies is that smooth pursuit eye movement selectively suppresses high-threshold cortical elements contributing to high MEP elicited by PA current in the brain. On the basis of the facilitatory effect of smooth pursuit eye movement on relatively low MEP induced by AP current observed in the present study, and the inhibitory effect of that on relatively high MEP induced by PA current in the previous study, it is possible to suggest that smooth pursuit eye movement induces various modulatory inputs over the different motor cortical elements in the hand muscles.
Conclusion Smooth pursuit eye movement in the steady-state phase preferentially facilitates low MEP elicited by AP current in the brain, indicating that later I-waves that contribute to MEP are selectively facilitated by smooth pursuit eye movement. In contrast, low MEP preferentially elicited by early I-waves generated by PA current in the brain is little modulated by the steady-state phase of smooth pursuit eye movement.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
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Maioli C, Falciati L, Gianesini T. Pursuit eye movements involve a covert motor plan for manual tracking. J Neurosci 2007; 27:7168–7173. Sakai K, Ugawa Y, Terao Y, Hanajima R, Furubayashi T, Kanazawa I. Preferential activation of different I waves by transcranial magnetic stimulation with a figure-of-eight-shaped coil. Exp Brain Res 1997; 113:24–32. Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Dileone M, Mazzone P, et al. The physiological basis of transcranial motor cortex stimulation in conscious humans. Clin Neurophysiol 2004; 115:255–266. Ugawa Y, Iwata NK. Cerebellar stimulation in normal subjects and ataxic patients. In: Hallett M, Chokroverty S, editors. Magnetic stimulation in clinical neurophysiology. 2nd ed. Amsterdam: Elsevier BV; 2005. pp. 197–210. Ni Z, Charab S, Gunraj C, Nelson AJ, Udupa K, Yeh IJ, et al. Transcranial magnetic stimulation in different current directions activates separate cortical circuits. J Neurophysiol 2011; 105:749–756. Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 1971; 9:97–113.
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Di Lazzaro V, Oliviero A, Profice P, Saturno E, Pilato F, Insola A, et al. Comparison of descending volleys evoked by transcranial magnetic and electric stimulation in conscious humans. Electroencephalogr Clin Neurophysiol 1998; 109:397–401. Horino H, Mori N, Matsugi A, Kamata N, Hiraoka K. The effect of eye movement on the control of arm movement to a target. Somatosens Mot Res 2013; 30:153–159. Werhahn KJ, Fong JK, Meyer BU, Priori A, Rothwell JC, Day BL, et al. The effect of magnetic coil orientation on the latency of surface EMG and single motor unit responses in the first dorsal interosseous muscle. Electroencephalogr Clin Neurophysiol 1994; 93:138–146. Kaneko K, Kawai S, Fuchigami Y, Morita H, Ofuji A. The effect of current direction induced by transcranial magnetic stimulation on the corticospinal excitability in human brain. Electroencephalogr Clin Neurophysiol 1996; 101:478–482. Day BL, Dressler D, Maertens de Noordhout A, Marsden CD, Nakashima K, Rothwell JC, et al. Electric and magnetic stimulation of human motor cortex: surface EMG and single motor unit responses. J Physiol 1989; 412:449–473.
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Smooth pursuit eye movement preferentially facilitates motor-evoked potential elicited by anterior–posterior current in the brain Koichi Hiraoka, Minori Ae, Nana Ogura, Sayo Komuratani, Chisa Sano, Keigo Shiomi, Yuji Morita and Haruka Yokoyama Neural interaction between the eye and hand movement centers must be a critical part of the mechanism underlying eye–hand coordination. One of the previous findings supporting this view is smooth pursuit eye movementinduced suppression of motor-evoked potential (MEP) in the hand muscles. The purpose of this study was to determine which descending volleys contributing to MEP are preferentially modulated by smooth pursuit eye movement. MEP in the first dorsal interosseous muscle was elicited by different directions of current in the brain during the steady-state phase of smooth pursuit eye movement. Smooth pursuit eye movement facilitated MEP elicited by anterior–posterior (AP) current, but this effect was not seen in MEP elicited by lateromedial or posterior– anterior current. Latency of MEP elicited by AP current was significantly longer than latencies of MEPs elicited by other directions of current, indicating that AP current in the brain
predominantly elicited later I-waves. We conclude that smooth pursuit eye movement in the steady-state phase preferentially facilitates MEP predominantly elicited by later I-waves generated by AP current in the brain. NeuroReport c 2014 Wolters Kluwer Health | Lippincott 25:279–283 Williams & Wilkins.
Introduction
Methods
Neural interaction between the eye and hand movement centers is crucial for eye–hand coordination [1,2]. The activation of the ipsilateral cerebellum, the vermis, and the contralateral central sulcus induced by eye–hand coordination effort must reflect the interaction process [3]. Direct evidence supporting this view is suppression of motor-evoked potential (MEP), reflecting corticospinal excitability, in the hand muscles during smooth pursuit eye movement [4]. However, how smooth pursuit eye movement modulates MEP in the hand muscles has not been investigated. MEP is elicited by a sequence of descending volleys generated by transcranial magnetic stimulation (TMS). The descending volleys generated by TMS with an 8-shaped coil are altered through a change in coil direction [5,6]. Coil direction-dependent conditioning effects on MEP have been reported using this technique; cerebellar TMS-induced short-latency suppression of MEP elicited by AP current in the hand muscles is greater than that of MEP elicited by PA current [7], and short-latency afferent inhibition of MEP elicited by PA current is greater than that of MEP elicited by AP current [8]. The aim of this study was to determine which descending volleys are preferentially affected by smooth pursuit eye movement through observing MEPs elicited by different directions of current in the brain during smooth pursuit eye movement.
Participants
c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins 0959-4965
NeuroReport 2014, 25:279–283 Keywords: descending volleys, D-wave, I-wave, motor-evoked potential, smooth pursuit eye movement College of Health and Human Sciences, Osaka Prefecture University, Habikino, Osaka Prefecture, Japan Correspondence to Koichi Hiraoka, PhD, College of Health and Human Sciences, Osaka Prefecture University, Habikino 3-7-30, Habikino, Osaka 583-8555, Japan Tel: + 81 72 950 2875; fax: + 81 72 950 2131; e-mail: [email protected] Received 26 September 2013 accepted 3 October 2013
Eleven healthy individuals (five men and six women) aged 20.1±0.2 years participated in this study. All participants were right handed according to the Edinburgh Handedness Inventory [9]. All participants gave written informed consent before the experiment. The experimental procedure was approved by the ethics committee of Osaka Prefecture University. Apparatus
Participants sat with the right forearm in a prone position on a table. The forearm and the hand were immobilized by a splint. The jaw was placed on a chin stand to minimize motion artifact of the head. A computer screen was placed 100 cm in front of the eyes. Horizontal movement of the right eye was measured using a corneal reflection device (TK2901; Takei Kiki Co., Tokyo, Japan). An illuminometer-cum-light sensor, sensitive to the reflection difference between the cornea and the sclera, was fixed on a goggle frame. Before recording eye movements, the sensor was calibrated from the midline to 101 in the horizontal visual angle at a distance of 100 cm from the individual. Surface electrodes capable of recording electromyographic (EMG) signals were placed over the first dorsal interosseous (FDI), abductor pollicis bravis, and abductor digiti minimi muscles in a DOI: 10.1097/WNR.0000000000000075
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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NeuroReport 2014, Vol 25 No 5
Fig. 1
2s End point (20°) AP TMS (13.3°) (Eye-movement condition) LM Warning cue 1s Fixation point (0°)
PA Eye movement onset
TMS (onset condition) Eye and target movements and coil position. The solid trace indicates the trajectory of the horizontal visual angle and the dashed trace indicates the trajectory of the visual target. A bird’s eye view of the coil position is presented on the right. Arrows beside the coils indicate direction of current in the brain induced by TMS. AP, anterior–posterior; LM, lateromedial; PA, posterior–anterior; TMS, transcranial magnetic stimulation.
belly–tendon montage. The EMG signals were amplified by EMG amplifiers (MEG-2100; Nihon Kohden, Tokyo, Japan) with a band-pass filter from 15 to 3 kHz. The analog signals from the corneal reflection device and EMG amplifiers were converted to digital signals at a sampling rate of 10 kHz using A/D converters (PowerLab800s; AD Instruments, Colorado Springs, Colorado, USA and PowerLab2/26; Unique Acquisition, Unique Medical, Tokyo, Japan) and stored in personal computers. Smooth pursuit eye movement
A warning cue appeared at a fixation point on the computer screen for 1 s (Fig. 1). The participant was instructed to gaze at the warning cue without blinking. The horizontal visual angle was 01 from the midline when the individual gazed at the warning cue. The warning cue changed to a target point 1 s later, and the target point moved to an end point at a constant velocity of 101/s. The individual tracked the target point with the eyes. When the target reached the end point, it stayed at that point for 1 s. The horizontal visual angle was 201 right to the midline when the individual was watching the end point. Before beginning the experiment, the individual practiced the smooth pursuit eye movement 20 times. Transcranial magnetic stimulation
TMS was delivered by an 8-shaped coil (YM-132B; Nihon Kohden) connected to a magnetic stimulator (SMN1200; Nihon Kohden). Maximum intensity of the coil was 1.03 T. The coil was positioned so that magnetic stimulation induced posterior–anterior (PA) current in the brain for the PA position (Fig. 1). Anterior–posterior (AP) current in the brain was induced by rotating the coil handle 1801 from the PA direction for the AP position. The coil was held in a direction that induced lateromedial
(LM) current in the brain for the LM position. An experimental session was conducted for each coil position. The coil in the AP position was placed 6 cm to the left of the vertex and moved little by little to find a hot spot where the averaged amplitude of five MEPs in the FDI muscle was greatest. TMS was delivered over this hot spot for all the coil positions, because it is known that the optimal site of the 8-shaped coil remains the same among coil positions [5]. TMS intensity was decreased trial by trial to determine the intensity that produced 300–400 mV of MEP amplitude in the FDI muscle when TMS was delivered with the coil in the AP position 0–100 ms before the onset of smooth pursuit eye movement. MEP amplitude 0–100 ms before the onset of smooth pursuit eye movement was matched among the coil positions. The probability of the involvement of D-waves in contributing to MEP increases with higherintensity TMS [10]. Thus, we considered that weak TMS eliciting low test MEP would be optimal for obtaining MEPs predominantly produced by I-waves, with minimum involvement of motor responses produced by D-waves in both the PA and AP positions. In the experimental sessions, TMS was delivered 0–100 ms before eye movement onset (onset condition) or when the eyes passed through 13.3±11 of horizontal visual angle (eye-movement condition), which was two-thirds of the horizontal visual angle at the end point. The horizontal visual angle, at which TMS was delivered in the eye-movement condition, was in the steady-state phase of smooth pursuit eye movement. TMS was delivered only at this angle in the eye-movement condition because of previous findings that modulation of MEP elicited by TMS with 8-shaped coil in the AP position, and modulation of MEP elicited by TMS with
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Eye movement modulates motor-evoked potential Hiraoka et al. 281
amplitude between the onset and eye-movement condition for each coil position independently. a level for these tests was 0.05/3 = 0.017. Data were expressed as mean values and SEM.
round coil during smooth pursuit eye movement, was not phase dependent [4,11]. The onset and eye-movement conditions were randomly assigned trial by trial. The trials in which background EMG was not silent in any of the three recorded muscles, eye movement was not successfully executed, or where the horizontal visual angle at which TMS was delivered was not optimal, were discarded. Furthermore, in the onset condition, trials with premature small deviations of horizontal visual angle before the onset of smooth pursuit eye movement were discarded, because we had observed in our preliminary experiments that MEP elicited immediately before eye movement onset is facilitated when premature small deviations of horizontal visual angle are present. The interval between each trial was more than 10 s. Each experimental session continued until 20 successful trials had been obtained for both the onset and eye-movement condition.
Results The latency of eye movement was 283±8 ms. Prestimulus background EMG amplitude was 3.9±0.4 mV in the FDI muscle, 3.8±0.8 mV in the abductor digiti minimi muscle, and 3.4±0.4 mV in the abductor pollicis bravis muscle. No significant differences were found in the prestimulus background EMG amplitude among the experimental conditions in any of the muscles. The hot spot was 6.3±0.4 cm lateral to and 1.0±0.3 cm anterior to the vertex. TMS intensity was 84.4±4.3% of maximum stimulator output in the AP position, 72.9±4.1% of that in the LM position, and 64.5±2.9% of that in the PA position. The ANOVA revealed significant differences in TMS intensity among the coil positions [F(2,20) = 29.28, P = 0.000]. The Bonferroni multiple comparison test revealed significant differences between the coil positions (P < 0.05). TMS was delivered 1270±31 ms after the target movement onset, and the horizontal visual angle at which TMS was delivered was 13.3±0.11 in the eye-movement condition.
Data analysis
Prestimulus background EMG amplitude was estimated from the full rectified EMG in the time window between 110 and 10 ms before TMS. MEP was analyzed only in the FDI muscle, because MEP amplitude was matched among the coil positions only in that muscle, and TMS was delivered over the hot spot of the FDI muscle. Change in MEP amplitude induced by eye movement was expressed as the percentage of MEP amplitude in the onset condition. MEP latency for each coil position in the onset condition was estimated from MEPs whose amplitudes were similar to mean MEP amplitudes elicited by TMS with the coil in the AP position in the onset condition. One-way repeated measures analysis of variance (ANOVA) was conducted, followed by the Bonferroni multiple comparison test. a level for these tests was 0.05. Multiple t-tests with the Bonferroni adjustment of a were conducted to compare MEP
MEP amplitude in the onset condition was 325±34 mV in the AP position, 364±59 mV in the LM position, and 369±32 mV in the PA position. The ANOVA failed to reveal significant differences in MEP amplitude among the coil positions [F(2,20) = 0.51, P = 0.607]. MEP latency in the onset condition was significantly different among the coil positions [F(2,20) = 21.45, P = 0.000], as shown in Fig. 2b. The Bonferroni multiple comparison test revealed that MEP latency in the AP position was significantly longer than MEP latencies in the LM or PA position (P < 0.05). MEP amplitude in the
Fig. 2
(b)
(c) 30
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10 ms
Latency (ms)
25
30 μV
MEP amplitude (% of onset)
(a)
20 15 10 5 0 AP
LM
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180 160 140 120 100 80 60 40 20 0
∗
∗
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AP
LM
PA
Specimen record of MEPs induced by AP current (a), MEP latency (b), and change in MEP amplitude induced by eye movement (c). The solid trace indicates MEP in the onset condition and the dashed trace indicates MEP in the eye-movement condition (a). Bars indicate mean and error bars indicate SEM. wSignificant difference in MEP amplitude between the onset and the eye-movement condition by t-test (P < 0.017). *Significant differences between the coil positions by the Bonferroni multiple comparison test (P < 0.05). AP, anterior–posterior; LM, lateromedial; MEP, motorevoked potential; PA, posterior–anterior.
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282 NeuroReport 2014, Vol 25 No 5
eye-movement condition was significantly greater than that in the onset condition in the AP position, as shown in Fig. 2a and c (P = 0.012). In contrast, no significant difference in MEP amplitude between the onset and eyemovement condition was found in the other coil positions (Fig. 2c). The change in MEP amplitude induced by eye movement was 133±10% in the AP position, 106±11% in the LM position, and 99±12% in the PA position. The change in MEP amplitude induced by eye movement was therefore significantly different among the coil positions [F(2,20) = 5.68, P = 0.011]. The Bonferroni multiple comparison test revealed that the change in MEP amplitude induced by eye movement in the AP position was significantly greater than that in the LM or PA position (P < 0.05).
Discussion MEP elicited by LM current was not significantly modulated by smooth pursuit eye movement. LM current in the brain preferentially induces D-waves through direct stimulation of the corticospinal axons [12,13]. Thus, the present findings indicate that excitability of the subcortical elements of the corticospinal pathway is little modulated by smooth pursuit eye movement. In contrast, smooth pursuit eye movement facilitated MEP elicited by AP current. Latency of MEP elicited by AP current was significantly longer than that elicited by LM current, which is consistent with the results of a previous study [8]. This finding must be due to a difference in central conduction time, originating in the fact that AP current in the brain preferentially recruits later I-waves mediated through chains of interneurons in the motor cortex [5], whereas LM current preferentially stimulates the corticospinal axons directly. Furthermore, latency of MEP elicited by AP current was significantly longer than that elicited by PA current, which is consistent with previous findings that MEP elicited by AP current is 2–3 ms later than that elicited by PA current [5,14]. This is likely because of the fact that PA current preferentially elicits early I-waves [10], whereas AP current preferentially elicits later I-waves. Thus, selective facilitation of high MEP elicited by AP current must reflect preferential facilitation of later I-waves during the steady-state phase of smooth pursuit eye movement. It has been hypothesized that motor plan to the tested muscle is produced using the common descending pathway of the eye and hand movement centers during smooth pursuit eye movement when the direction of the eye movement is identical to the function of the tested muscle [4]. This was based on a finding that smooth pursuit eye movement-induced suppression of corticospinal excitability in the finger muscle was low when the function of the target muscle was identical to the direction of eye movement. However, the facilitation of MEP during smooth pursuit eye movement observed in the present study does not likely originate from the motor
plan as hypothesized by Maioli and colleagues, because the eye-movement direction was to the right, whereas the function of the right FDI muscle in prone position is a leftward movement (abduction) of the index finger. Further studies are needed to elucidate mechanisms underlying smooth pursuit eye movement-induced facilitation of MEP in the FDI muscle elicited by AP current in the brain. The insignificant modulation of MEP elicited by PA current during smooth pursuit eye movement in the present study conflicts with previous findings that MEP in the finger muscles elicited by PA current was suppressed during smooth pursuit eye movement [4]. Eye movement amplitude and velocity and position of the forearm were the same in both studies. The major difference between the two studies was test MEP amplitude; amplitude of MEPs at the central fixation point was as high as 1400 mV in the previous study, whereas low MEPs with amplitude of only 300–400 mV were elicited immediately before eye movement onset in the present study. Thus, the most likely explanation for the conflicting findings between the two studies is that smooth pursuit eye movement selectively suppresses high-threshold cortical elements contributing to high MEP elicited by PA current in the brain. On the basis of the facilitatory effect of smooth pursuit eye movement on relatively low MEP induced by AP current observed in the present study, and the inhibitory effect of that on relatively high MEP induced by PA current in the previous study, it is possible to suggest that smooth pursuit eye movement induces various modulatory inputs over the different motor cortical elements in the hand muscles.
Conclusion Smooth pursuit eye movement in the steady-state phase preferentially facilitates low MEP elicited by AP current in the brain, indicating that later I-waves that contribute to MEP are selectively facilitated by smooth pursuit eye movement. In contrast, low MEP preferentially elicited by early I-waves generated by PA current in the brain is little modulated by the steady-state phase of smooth pursuit eye movement.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
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