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Time and direction preparation of the long latency stretch reflex
Human Movement Science 47 (2016) 38–48
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Full Length Article
Time and direction preparation of the long latency stretch reflex Yasutaka Nikaido a, Ryota Hatanaka a, Yasutomo Jono a, Yoshifumi Nomura a, Keisuke Tani a, Yuta Chujo a, Koichi Hiraoka b,⇑ a b
Graduate School of Comprehensive Rehabilitation, Osaka Prefecture University, Japan College of Health and Human Sciences, Osaka Prefecture University, Japan
a r t i c l e
i n f o
Article history: Received 11 December 2013 Revised 18 September 2015 Accepted 31 January 2016
Keywords: Perturbation Force load Long latency stretch reflex First dorsal interosseous muscle Prediction
a b s t r a c t This study investigated time and direction preparation of motor response to force load while intending to maintain the finger at the initial neutral position. Force load extending or flexing the index finger was given while healthy humans intended to maintain the index finger at the initial neutral position. Electromyographic activity was recorded from the first dorsal interosseous muscle. A precue with or without advanced information regarding the direction of the forthcoming force load was given 1000 ms before force load. Trials without the precue were inserted between the precued trials. A long latency stretch reflex was elicited by force load regardless of its direction, indicating that the long latency stretch reflex is elicited not only by muscle stretch afferents, but also by direction-insensitive sensations. Time preparation of motor response to either direction of force load enhanced the long latency stretch reflex, indicating that time preparation is not mediated by afferent discharge of muscle stretch. Direction preparation enhanced the long latency stretch reflex and increased corticospinal excitability 0–20 ms after force load when force load was given in the direction stretching the muscle. These enhancements must be induced by preset of the afferent pathway mediating segmental stretch reflex. Ó 2016 Elsevier B.V. All rights reserved.
1. Introduction In daily activities, external force load sometimes acts on the limb and interferes with ongoing movements. Humans quickly respond to the external force so as to minimize the unwanted deviation of ongoing movement trajectory. Force load over the arm induces two motor responses in the arm muscles (Hammond, 1955; see review by Matthews, 1991): (1) a short latency stretch response (SLSR) with 20–35 ms of latency; and (2) a long latency stretch reflex (LLSR) with 50–65 ms of latency (Lee & Tatton, 1982; Lewis, MacKinnon, & Perreault, 2006; Lewis, Polych, & Byblow, 2004; Manning, Tolhurst, & Bawa, 2012). Nevertheless, only the LLSR is elicited in the first dorsal interosseous (FDI) muscle when force load is given over the index finger (Johansson, Lemon, & Westling, 1994; Kourtis, Kwok, Roach, Wing, & Praamstra, 2008), in spite of one exceptional study, in which an SLSR was observed in 5 of 9 participants (Macefield, Rothwell, & Day, 1996). The neural mechanism underlying the SLSR and that underlying the LLSR must be different from that underlying voluntary motor response to an imperative cue, because the latency of the SLSR and that of the LLSR are shorter than the latency of voluntary motor response to an imperative cue (Brebner & Welford, 1980; Evarts, Teräväinen, & Calne, 1981; Manning et al., 2012). The SLSR has been thought to be of spinal origin, because the SLSR and motor evoked potential (MEP) elicited around ⇑ Corresponding author at: College of Health and Human Sciences, Osaka Prefecture University, 3-7-30 Habikino, Habikino City, Osaka 583-8555, Japan. E-mail address: [email protected] (K. Hiraoka). http://dx.doi.org/10.1016/j.humov.2016.01.016 0167-9457/Ó 2016 Elsevier B.V. All rights reserved.
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the period at which the SLSR appeared are not modulated by task instruction (MacKinnon, Verrier, & Tatton, 2000; Lewis et al., 2004, 2006). In contrast, the LLSR has been thought to be mediated by the transcortical pathways (Christensen, Petersen, Andersen, Sinkjaer, & Nielsen, 2000; Goodin, Aminoff, & Shih, 1990; Palmer & Ashby, 1992; see reviews by Bonnard, de Graaf, & Pailhous, 2004 and by Matthews, 1991), because long latency facilitation of motoneuron excitability induced by force load over the thumb is greater when the cortex is stimulated (Palmer & Ashby, 1992). Preparation of the LLSR is possible to be conditioned by prior instruction. Prior instruction to oppose force load enhanced the LLSR (Calancie & Bawa, 1985; Colebatch et al., 1979; Lee & Tatton, 1982; MacKinnon et al., 2000), activated the primary motor and sensory cortices (de Graaf et al., 2009), and increased corticospinal excitability around the period at which the LLSR appeared (Lewis et al., 2004, 2006). Moreover, prior instruction to oppose force load extending the wrist did not affect corticospinal excitability in the flexor carpi radialis muscle, but increased corticospinal excitability in the extensor carpi radialis muscle in the foreperiod (Meziane, Spieser, Pailhous, & Bonnard, 2009). According to these previous studies, preparation of the LLSR is under control of supraspinal cognitive process. Two aspects of preparation for motor response to force load have been investigated in previous studies. One concerns time preparation. A precue indicating the timing of the imperative cue affected corticospinal excitability when humans responded to an imperative cue (Davranche et al., 2007). Such time preparation was present even when humans responded to force load. The LLSR in the FDI muscle during a precision grip task was smaller when the timing of force load was predictable, and this was reflected in the amplitude of sensorimotor cortex potentials just preceding the LLSR (Kourtis et al., 2008). This finding indicates that time preparation modulates the excitability of the cortical sites which take part of the transcortical pathway mediating the LLSR. The other aspect concerns direction preparation. Corticospinal excitability in the foreperiod of voluntary motor response to a visual imperative cue was affected by a precue indicating direction of to-be-signaled motor response (van Elswijk, Schot, Stegeman, & Overeem, 2008). A previous study, investigating the effect of force load on jump of the visual target during goal directed movement, reported that motor response to force load depends on the direction of the visual target movement (Mutha, Boulinguez, & Sainburg, 2008). This finding indicates that visual information regarding the direction of ongoing movement affects motor response to force load. Moreover, direction preparation of motor response to force load has been investigated in monkeys (Evarts & Tanji, 1974; Tanji & Evarts, 1976). In these studies, monkeys were instructed ‘‘push” or ‘‘pull” against force load before onset of force load, and motor cortical activity was modulated according to the direction of motor response instructed in advance. The modulation occurred not only 200 ms after the instruction but also 20 ms after force load onset (Evarts & Tanji, 1974). According to these findings by Evarts and Tanji, the motor cortex processes direction preparation of motor response to force load both before and after force load. Preparation process of the LLSR has been thought to be achieved by presetting the excitability of the transcortical pathway. Gating the supraspinal sites of the transcortical pathway has been proposed to be mechanism underlying this process (see review by Bonnard et al., 2004). However, this mechanism is not reasonable when force load is given on the finger while intending to maintain the finger at the initial neutral position. Presetting supraspinal sites of the transcortical reflex must modulate motoneuron excitability causing small changes in force level of the finger. In this case, finger position deviates slightly even before force load, and this interferes with holding of the limb or finger at the initial position. We propose alternative hypothetical mechanism: Preparatory process of motor response to force load modulates the excitability of the afferent pathway mediating segmental stretch reflex while intending to maintain the finger at the initial neutral position. Force load in the direction opposite to the function of the target muscle stretches the muscle causing excitation of the afferent pathway mediating segmental stretch reflex. If preparation process of motor response to force load modulates the excitability of the afferent pathway mediating segmental stretch reflex, modulation of motoneuron excitability must be minor before discharge of the afferent pathway induced by force load, but preparation process affects motoneuron excitability immediately after force load stretching the tested muscle causing discharge of the afferent pathway. The present study tested this hypothesis. The corticospinal pathway and the transcortical pathway mediating the LLSR share the common neural pathways, according to a previous finding that MEP amplitude increases specifically around the onset of the LLSR (Day, Riescher, Struppler, Rothwell, & Marsden, 1991). Thus, MEP elicited before and after force load was the marker indicating neural mechanism underlying preparation of the LLSR in the present study. If preparation is processed through the afferent pathway mediating segmental stretch reflex, corticospinal excitability must not be modulated before force load but must be modulated after force load stretching the tested muscle, because afferent discharge does not occur before force load stretching the tested muscle but occurs during and shortly after force load. The findings in the present study must help us to understand how humans prepare for motor response to forthcoming force load for minimizing unwanted change in their ongoing movement induced by external force load while intending to maintain their finger at the initial neutral position. 2. Methods 2.1. Participants Participants were 10 healthy humans (9 males and 1 female), aged 20–34 years (26.3 ± 1.6). All participants were right handed according to the Edinburgh Handedness Inventory (Oldfield, 1971). The experimental design was approved by the ethics committee of Osaka Prefecture University.
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2.2. Apparatus Each participant sat on a chair with their right forearm and wrist fixed by metal frames. The right index finger tip was fixed over the attachment of the lever arm of the torque motor, as shown in Fig. 1A (FRL-2009, Uchida denshi, Tokyo). A laser pointer was attached over the lever arm. The surface recording electrodes were placed over the belly and tendon of the FDI muscle with a belly-tendon montage. The electromyographic (EMG) signal from the FDI muscle was band-pass filtered at 15 Hz to 3 kHz using an amplifier (MEG-5200, Nihon Kohden, Tokyo). Analogue signals of the motion of the lever arm and EMG were converted to digital signals at a sampling rate of 5 kHz using an A/D converter (UAS-108S, Unique Medical, Tokyo). 2.3. Transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) was delivered by a round coil (YM-133B, Nihon Kohden, Tokyo) connected to a magnetic stimulator (SMN-1200, Nihon Kohden, Tokyo). The outer diameter of the coil was 99 mm, and it had a maximum intensity of 0.67 T. The coil was placed over the vertex and moved little by little until a hotspot of the left primary motor cortex was located. The coil was then positioned over the hotspot, and TMS intensity was decreased trial by trial to find a resting motor threshold (RMT). The RMT was defined as the lowest stimulus intensity that produced an MEP larger than 50 lV in amplitude with 50% probability at rest. TMS intensity was then adjusted to be 1.2 times the resting motor threshold. 2.4. Procedure The lever arm of the torque motor constantly produced 0.4 N of downward force (i.e., in the direction of finger extension) throughout the trial before force load. The participants were instructed to keep the lever arm at a neutral position against the downward force of the lever arm with their index finger so that a laser pointer pointed a beam at a target point located at their midline on the wall 150 cm in front of them (Fig. 1A). This force was loaded so that participants exerted small constant force in the direction of flexion before change in force load to facilitate clear appearance of the SLSR (Manning et al., 2012). Participants were then asked to close their eyes (Fig. 1B). After that, one of three types of precue was given. A high-frequency tone (1 kHz) precue indicated that a force load in the direction of extension would be given to the finger 1000 ms after the precue, and a low-frequency tone (66.7 Hz) precue indicated that a force load in the direction of flexion would be given 1000 ms after the precue (Direction and time preparation condition; DT condition). A middle-range (143 Hz) precue did not indicate the direction of the forthcoming force load (Time preparation condition; T condition). Participants could process solely time preparation in this condition, because the precue was always given 1000 ms before force load onset. No precue
Fig. 1. Experimental setup (A) and experimental protocol (B).
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was given in the non-preparation condition (N condition). In the N condition, neither time nor direction preparation were processed. Force load of 1.6 N in the direction of either flexion or extension began 1000 ms after the precue and continued for 3000 ms. Force load extending the index finger was given in the stretch condition. In this condition, the FDI muscle was stretched by force load. Force load flexing the index finger was given in the non-stretch condition. In this condition, the FDI muscle was not stretched. The precue conditions (DT, T and N conditions) and the stretch conditions (stretch and non-stretch conditions) were randomly altered trial by trial. In the DT condition of the stretch condition, preparation of muscle stretch induced by force load was processed in addition to time preparation. In contrast, in the DT condition of the non-stretch condition, the participants did not prepare muscle stretch induced by force load, because force load flexing the index finger was predicted by the precue. Participants made an effort to maintain a neutral position with their index finger even when force load was given. After the force load was released, participants opened their eyes and returned the lever arm and index finger to the neutral position. The EMG response to force load and the angle of the lever arm were recorded 10 times for each precue condition without TMS. Trials with TMS were conducted in another experimental session. TMS was delivered 100 ms before force load onset (baseline period), or 0–20, 20–40, or 40–60 ms after force load onset. TMS timing was randomly altered each trial. Trials with EMG burst in the time window between TMS onset and force load onset were discarded. Trials with TMS were continued until 15 successful MEPs were elicited for each time period for each precue condition. Inter-trial interval was approximately 10 s. Before beginning the trials, participants performed practice tests to become familiar with the process. 2.5. Data analysis Time to peak and peak angle of the lever arm after force load onset, the latency of the EMG response to force load, and the amplitude of the rectified EMG response in the time window between 0 and 20 ms after the onset of the EMG response to force load were estimated each single trial without TMS (Fig. 1B). The EMG amplitude in the time window between 0 and 20 ms after the onset of the EMG response to force load roughly corresponds to EMG amplitude in the time window between the onset and around peak of the LLSR, because peak latency of the LLSR from the EMG onset in the FDI muscle is approximately 20 ms (Kourtis et al., 2008; Macefield et al., 1996). Averaging EMG traces following force load onset conducted in previous studies (Kourtis et al., 2008; Macefield et al., 1996) may cause greater involvement of the voluntary EMG response for the estimated amplitude due to averaging various latencies of EMG responses following the onset of force load. In contrast, estimating amplitude of EMG response each single trace in the present study allowed us to measure the amplitude of the early period of the LLSR with minimum involvement of the voluntary EMG response following the LLSR, because the end of the time window for this estimation was precisely 20 ms after EMG onset. MEP amplitude was estimated based on peak to peak. The peak latency of the MEP, defined as the duration between the time of TMS and the time of either the positive or negative peak of the MEP (whichever occurred later), was estimated. Background EMG (BEMG) level affects the MEP amplitude (Devanne, Lavoie, & Capaday, 1997; Hasegawa, Kasai, Tsuji, & Yahagi, 2001). Therefore, pre-stimulus BEMG amplitude in the time window between 12 and 2 ms before TMS was estimated from the rectified EMG trace in order to rule out the effect of EMG activity on MEP. BEMG amplitude in the time window between 0 and 1000 ms before force load was estimated each single trial without TMS to elucidate the preparatory process before force load. The amplitude of the MEP elicited 100 ms before force load and that of the pre-stimulus BEMG preceding the MEP elicited 100 ms before force load were compared across the precue conditions and between the stretch conditions to assure that the MEP and pre-stimulus BEMG amplitudes in the baseline period were similar across the experimental conditions. The amplitude of the MEP elicited after force load and that of the pre-stimulus BEMG preceding the MEP were averaged each 20 ms of the latency after force load (Kasai, Kawanishi, & Yahagi, 1998), in order to categorize elicited MEPs, distributing sequentially in the pre-response period, into one of the three time periods: 0–20, 20–40, and 40–60 ms after force load onset. The amplitude of the MEP elicited after force load was divided by amplitude of the MEP elicited 100 ms before force load averaged across the precue conditions, and the amplitude of the pre-stimulus BEMG preceding the MEP elicited after force load was divided by amplitude of the pre-stimulus BEMG amplitude preceding the MEP elicited 100 ms before force load averaged across the precue conditions. Dividing the amplitudes by amplitudes in the baseline period was to normalize the amplitudes across the participants. A paired t-test was conducted to examine the difference between two means. One-way repeat measures ANOVA was conducted for testing one main effect [3 (precues)]. Two-way repeated measure ANOVA was conducted for testing two main effects: [2 (stretch) * 3 (precues)] or [4 (time periods) * 3 (precues)]. When two-way repeated measures ANOVA revealed significant interaction between the two main effects, analysis of simple main effect followed by multiple comparisons was conducted. The statistical significance level was 0.05. Data was expressed as mean ± standard error of mean. 3. Results 3.1. Motion of the lever arm Time to peak of lever arm motion produced by force load across the precue conditions was 87.5 ± 2.6 ms in the stretch condition (Figs. 2A and 4a), and 84.6 ± 1.5 ms in the non-stretch condition (Figs. 2B and 4c). There was no significant differ-
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ence in time to peak of lever arm motion among the precue conditions in both the stretch [F(2,18) = 2.537, p = 0.107] and non-stretch conditions [F(2,18) = 0.324, p = 0.728]. Peak angle of the lever arm across the precue conditions was 9.5 ± 0.7 degrees in the stretch condition (Figs. 2A and 4b), and 15.6 ± 1.0 degrees in the non-stretch condition (Figs. 2B and 4d). There was no significant difference in peak angle among the precue conditions in both the stretch [F(2,18) = 0.044, p = 0.957] and non-stretch conditions [F(2,18) = 0.425, p = 0.660]. 3.2. EMG response to force load BEMG amplitude in the time window between 0 and 1000 ms before force load in the trials without TMS was not significantly different between the stretch conditions [F(1,9) = 1.017, p = 0.340] and among the precue conditions [F(2,18) = 0.853, p = 0.443] without significant interaction [F(2,18) = 0.410, p = 0.670] (Fig. 3). The EMG response was present in both the stretch and non-stretch conditions (Fig. 2). The latency of the EMG response to force load across the precue conditions was 74.9 ± 2.5 ms in the stretch condition (Figs. 2A and 5a), and 84.5 ± 2.0 ms in the non-stretch condition (Figs. 2B and 5c). There was no significant difference in the latency among the precue conditions in both the stretch [F(2,18) = 2.540, p = 0.107] and non-stretch conditions [F(2,18) = 0.039, p = 0.962]. The amplitude of the EMG response in the stretch condition was significantly different among the precue conditions as shown in Fig. 5b [F(2,18) = 24.104, p < 0.001]. Post-hoc test revealed that EMG amplitude in the DT condition was significantly larger than that in the other precue conditions: Meanwhile, EMG amplitude in the T condition was significantly larger than that in the N condition (P < 0.05). The amplitude of the EMG response in the non-stretch condition was significantly different among the precue conditions as shown in Fig. 5d [F(2,18) = 9.564, p = 0.002]. Post-hoc test revealed that the amplitude of the EMG response in the DT condition and that in the T conditions were significantly larger than that in the N condition (P < 0.05). 3.3. Pre-stimulus BEMG amplitude The amplitude of the pre-stimulus BEMG preceding the MEP elicited 100 ms before force load was not significantly different among the precue conditions [F(2,18) = 0.266, p = 0.770] and between the stretch conditions [F(1,9) = 0.000, p = 0.994] without significant interaction [F (2,18) = 0.552, p = 0.585]. Normalized pre-stimulus BEMG amplitudes before and after force load are shown in Figs. 6A and 7A. Pre-stimulus BEMG amplitude was not significantly different among the precue conditions [F(2,18) = 1.971, p = 0.168] or among the time periods [F(3,27) = 1.400, p = 0.264] in the stretch condition. There was no significant interaction between the two main effects [F(6,54) = 1.791, p = 0.118]. Pre-stimulus BEMG amplitude was not significantly different among the precue conditions [F(2,18) = 3.133, p = 0.068] or among the time periods [F(3,27) = 0.651, p = 0.589] in the non-stretch condition. There was no significant interaction between the two main effects [F(6,54) = 0.803, p = 0.572].
Fig. 2. Specimen record of the lever arm movement and rectified EMG response in trials without TMS. Filled triangles indicate the onset of lever arm movement. Open triangles indicate the onset of the EMG response.
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Fig. 3. Specimen record of the rectified BEMG in the time window between 0 and 1000 ms before force load (A) and averaged BEMG amplitude across the participants (B). Bars indicate means and error bars indicate standard error of mean (B).
Fig. 4. Time to peak (a, c) and peak angle (b, d) of the lever arm in the stretch and non-stretch conditions in trials without TMS. Bars indicate means and error bars indicate standard error of mean.
Fig. 5. The latency (a, c) and the amplitude of the EMG response (b, d) in the stretch and non-stretch conditions in trials without TMS. Bars indicate means and error bars indicate standard error of mean. Asterisks indicate significant difference (p < 0.05).
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Fig. 6. Normalized pre-stimulus BEMG and MEP amplitudes in the stretch condition. Data points indicate means and error bars indicate standard error of mean. Asterisks indicate the significant difference between the precue conditions, and daggers indicate the significant difference between the period 100 ms before force load and the other periods after force load.
Fig. 7. Normalized pre-stimulus BEMG and MEP amplitudes in the non-stretch condition. Data points indicate means and error bars indicate standard error of mean.
3.4. MEP The TMS threshold was 62.8 ± 3.9% of maximum stimulator output, and TMS intensity used in the experiment was 75.4 ± 4.6% of maximum stimulator output. The peak latency of the MEP was 27.7 ± 0.6 ms. The amplitude of the MEP elicited
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100 ms before force load was not significantly different among the precue conditions [F(2,18) = 0.030, p = 0.971] and between the stretch conditions [F(1,9) = 3.789, p = 0.083] without significant interaction [F(2,18) = 1.227, p = 0.317]. The averaged delay of TMS after force load was 10.7 ± 0.3 ms in the time period of 0–20 ms, 29.3 ± 0.4 ms in the time period of 20–40 ms, and 49.2 ± 0.3 ms in the time period of 40–60 ms after force load. ANOVA failed to reveal significant difference in the averaged delay among the precue conditions in all of the time periods. In the stretch condition, normalized amplitude of the MEP elicited after force load in the DT condition and that elicited 40–60 ms after force load in the T condition tended to be greater than that elicited 100 ms before force load (Fig. 6B). In contrast, such tendency was not observed in the N condition. Normalized MEP amplitude was significantly different among the precue conditions [F(2,18) = 5.195, p = 0.017] and among the time periods [F(3,27) = 20.165, p < 0.001] in the stretch condition. There was also a significant interaction between the two main effects [F(6,54) = 3.404, p = 0.006]. Simple main effect of the amplitude of the MEP elicited 40–60 ms after force load onset was significant for the precue conditions [F(2,70) = 14.003, p < 0.001]. Multiple comparisons revealed that the amplitude of the MEP elicited 40–60 ms after force load onset was significantly different among the precue conditions (p < 0.05). Simple main effect of MEP amplitude was significant among the time periods in the DT condition [F(3,80) = 20.617, p < 0.001] and in the T condition [F(3,80) = 7.870, p < 0.001], but not in the N condition [F(3,80) = 1.145, p = 0.336]. Multiple comparisons for the DT condition revealed that MEP amplitude was significantly different among all the time periods except between the period 0–20 ms after force load and the period 20–40 ms after force load (p < 0.05), while those for the T condition revealed that the amplitude of the MEP elicited 40–60 ms after force load onset was significantly larger than that in the other periods (p < 0.05). In the non-stretch condition, normalized amplitude of the MEP elicited after force load did not increase (Fig. 7B). MEP amplitude was similar across the precue conditions. MEP amplitude was not significantly different among the precue conditions [F(2,18) = 1.991, p = 0.166] or between the time periods [F(3,27) = 2.136, p = 0.119] in the non-stretch condition. There was no significant interaction between the two main effects [F(6,54) = 0.929, p = 0.482].
4. Discussion 4.1. Lever arm movement The index finger tip was kept touch with the end of the lever arm, and the participants attempted to maintain the initial neutral position of the finger against slight and constant force load exerted by the lever arm. Thus, lever arm motion reflects the difference between force exerted by the index finger tip and that exerted by the end of the lever arm. The lever arm moved immediately after force load, and this motion was followed by opposite motion back to the neural position shortly after the onset of the EMG response. The peak angle of the lever arm is the point at which external torque of force load over the lever arm and internal torque, which is the summation of passive and active torques of the metacarpophalangeal joint of the index finger, reach equivalent levels. Time to peak is the time to reach the equivalent levels. Thus, time to peak and the amplitude of the lever arm represent the ability of returning the index finger to the neutral position with a short period of time and with small amplitude of lever arm movement after external force load. In the present study, the time to peak and the amplitude of the lever arm motion were not significantly different among the precue conditions, indicating that neither time nor direction preparation of motor response to force load affects this ability. 4.2. EMG response In the present study, the latency of the EMG response was around 75–85 ms across the precue conditions, and was slightly longer than the latency of the LLSR in the FDI muscle (51–64 ms) observed in previous studies (Johansson et al., 1994; Kourtis et al., 2008). Accordingly, the EMG response observed in the present study was considered to be the LLSR. The SLSR was not observed in the present study. This finding was consistent with findings in previous studies which tested the FDI muscle (Johansson et al., 1994; Kourtis et al., 2008), but was inconsistent with another previous study in which the SLSR was observed in some participants (Macefield et al., 1996). The inconsistent findings among the studies indicate that the SLSR in the FDI muscle is observable only under certain circumstances. Plausible explanation for the absence of the SLSR in the present study is that force load was too weak to elicit the SLSR. Muscle stretch has been thought to be the cause of the EMG responses to force load (see review by Matthews, 1991). The FDI muscle was stretched in the stretch condition because the lever arm moved to extend the index finger in this condition, but that was not in the non-stretch condition because the lever arm moved to flex the index finger. In spite of that, the LLSR was observed no matter the direction of force load. This finding is reasonably explained by a view that the LLSR is elicited not only by muscle stretch afferents, but also by other sensations. Cutaneous sensation must have been produced by either direction of force load. It has been reported that the transcortical pathway mediating the LLSR in the FDI muscle is partially mediated by the cutaneous afferent pathways (Johansson et al., 1994). The LLSR in the FDI muscle is induced by cutaneous sensation (Macefield et al., 1996). Moreover, the LLSR was suppressed by local anesthesia eliminating cutaneous sensation (Loo & McCloskey, 1985). Therefore, not only muscle stretch afferents but also cutaneous sensation mediates the LLSR.
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4.3. The effect of preparation process on the EMG response The EMG response to force load was enhanced in the T condition of both the stretch and non-stretch conditions. In the T condition, the precue was constantly provided 1000 ms before force load. Thus, time prediction was possible, and time preparation of motor response to force load must have been processed in the T condition. Accordingly, the present finding means that time preparation enhances the LLSR when humans intend to maintain the finger at the initial neutral position. The enhancement must not be solely mediated by afferent discharge induced by muscle stretch, because the enhancement was present no matter force load stretched the muscle or not. There are two conflicting previous findings regarding the effect of time preparation on the LLSR. The amplitude of the LLSR in the abductor pollicis brevis muscle during a precision grip task was significantly smaller when the timing of force load was predictable, and similar insignificant tendency was found in the FDI muscle (Kourtis et al., 2008). In contrast, in a previous study by Yamamoto and Ohtsuki (1989), time preparation of motor response to force load enhanced the LLSR in the biceps muscle. In the previous study by Kourtis and colleagues, participants were instructed to hold an object with the index finger and the thumb without slipping off the object, but were not instructed to maintain the initial position of the object. Then, time preparation of motor response to force load increased BEMG amplitude before force load. In contrast, in the previous study by Yamamoto and Otsuki, participants intended to maintain the arm at the initial position, and BEMG amplitude before force load was not affected by time prediction. Accordingly, the conflicting findings between these studies must be originated from intention whether participants attempted to maintain the initial position of the fingers or the arm, causing different effect of time preparation on BEMG amplitude before force load. Task instruction and findings in our present study were consistent with the study by Yamamoto and Otsuki: The participants maintained the lever arm at the initial neutral position and BEMG amplitude before force load was same across the precue conditions before force load. Accordingly, rational explanation for the conflicting findings is that time preparation enhances the LLSR only when humans intend to maintain the finger at the initial position. The EMG response in the DT condition was larger than that in the T condition of the stretch condition. The muscle was stretched by force load in both the DT and T conditions of the stretch condition. In the DT condition, both time and direction preparation must have been processed, because advanced information regarding the direction of forthcoming force load was indicated by the precue constantly provided 1000 ms before force load. In contrast, only time preparation was processed in the T condition. Therefore, the difference between the DT and T conditions of the stretch condition is solely advanced information regarding force load direction. Given this, different amplitude of EMG response between the DT and T conditions in the stretch condition must be originated from the direction preparation of motor response to force load. Thus, the present finding means that preparation of motor response to muscle stretch enhances the LLSR to force load stretching the muscle. One possible event we have to note regarding enhancement of the EMG response to force load induced by the precue is superimposition of the proprioception-induced voluntary EMG response on the LLSR. When humans intend to oppose force load, voluntary EMG response to proprioceptive input occurs shortly after the onset of the LLSR (MacKinnon et al., 2000; Meziane et al., 2009). The choice reaction time of the proprioception-induced voluntary EMG response in the wrist flexor is around 100 ms (Manning et al., 2012). Similar reaction time of the proprioception-induced voluntary EMG response must have been produced in the present study, because proprioception was induced by force load and the task conducted was regarded as choice reaction time paradigm, in which the participants responded to two directions of force load of which the direction was altered randomly trial by trial. In the present study, the latency of the EMG response in the FDI muscle was around 75 ms in the stretch condition and 85 ms in the non-stretch condition. Given this, in the time window between 0 and 20 ms after force load, in which the amplitude of the EMG response was measured, superimposition of the proprioception-induced voluntary EMG response on the LLSR is minor. Thus, enhancement of the EMG response induced by time or direction preparation is mainly explained by enhancement of the LLSR. 4.4. The effect of preparation process on corticospinal excitability We must take account the superimposition of the MEP on the EMG response to force load as possible cause of the changes in MEP amplitude. The peak latency of the MEP elicited 40–60 ms after force load onset was approximately 70–90 ms after force load onset, because the peak latency of the MEP was approximately 28 ms. The latency of the EMG response to force load was around 75 ms in the stretch condition and 85 ms in the non-stretch condition. Given this, some MEPs elicited 40–60 ms after force load onset must have been superimposed on the EMG response to force load. As a result, we cannot rule out a possibility that enhancement of the MEP elicited 40–60 ms after force load onset is caused by superimposition of the MEP response on the EMG response to force load. Similar enhancement of the MEP elicited 40–60 ms after force load and the EMG response in the DT and T conditions of the stretch condition supports this view. Nevertheless, the MEP elicited 0–20 ms after force load must not have superimposed on the EMG response. The peak latency of the MEP elicited 0–20 ms after force load onset must have been approximately 30–50 ms after force load onset. Accordingly, the peak of the MEP elicited 0–20 ms after force load onset did not superimpose on the EMG response onset around 75–85 ms after force load. Thus, the amplitude of the MEP elicited 0–20 ms after force load solely represents corticospinal excitability. The amplitude of the MEP elicited 0–20 ms after force load in the DT condition of the stretch condition was larger than that elicited before force load in the same condition. The amplitude of the MEP elicited before force load was not significantly different among the precue conditions, indicating that direction preparation does not affect corticospinal excitability before force load. Major difference between before and after force load is afferent discharge: Afferent discharge
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induced by force load did not yet occur before force load but must have occurred during and shortly after force load. Thus, increases in the amplitude of the MEP elicited 0–20 ms after force load in the DT condition of the stretch condition must have been mediated by afferent discharge induced by force load. MEP amplitude depends on the excitability of the primary motor cortex. However, the increase in the excitability of the primary motor cortex must not be responsible for the increase in the amplitude of the MEP elicited 0–20 ms after force load, because the latency of the increase in the amplitude of the MEP after force load was too short to arrive the action potential of afferent discharge at the supraspinal sites. MEP amplitude is affected not only by change in the excitability of the primary motor cortex but also by that of motoneuron excitability. However, motoneuron excitability must not have been directly modulated by direction preparation, because BEMG amplitude was not increased by direction preparation before force load. Motoneuron excitability is affected by afferent discharge mediating segmental stretch reflex. The latency of the MEP in the FDI muscle is around 25 ms (Hiraoka et al., 2014; Iida et al., 2014). The latency of the SLSR, mediated by the segmental stretch reflex pathway (see review by Matthews, 1991), is around 34 ms in the FDI muscle (Macefield et al., 1996). Accordingly, action potentials of the muscle stretch afferents induced by force load and the descending volleys induced by TMS given 0–20 ms after force load must have arrived at the synaptic terminals on the motoneurons about the same time. Given this, most feasible explanation for the increase in MEP elicited 0–20 ms after force load in the DT condition of the stretch condition is greater motoneuron excitability immediately after force load due to greater afferent discharge of muscle stretch induced by preparation of motor response to muscle stretch. Taken together, increase in the amplitude of the MEP immediately after force load induced by preparation process of motor response to muscle stretch is reasonably explained by the following process. Preset of susceptibility of the afferent pathway mediating segmental stretch reflex occurs during preparation of motor response to muscle stretch. The preset of susceptibility of the afferent pathway does not affect corticospinal excitability before force load, because afferent discharge does not occur at this time. In contrast, the preset increases corticospinal excitability immediately after force load, because the afferent pathway discharges at this time. Finally, corticospinal excitability increases immediately after force load stretching the tested muscle when the participants prepare for motor response to muscle stretch. 4.5. Prediction of non-stretch of the muscle The amplitude of the EMG response and the amplitude of the MEP elicited 0–20 ms after force load were not significantly different between the DT and T conditions of the non-stretch condition. The participants predicted that the muscle would not be stretched in the DT condition of the non-stretch condition, although direction prediction was impossible in the T condition. Accordingly, the difference between the DT and T conditions of the non-stretch condition was whether prediction of non-stretch of the muscle was possible or not. Thus, the findings indicate that prediction of non-stretch of the muscle does not enhance motor response to force load, and does not increase corticospinal excitability immediately after force load. This is possibly explained by a view that direction preparation only processes to oppose muscle stretch. As mentioned above, increase in corticospinal excitability immediately after force load in the stretch condition is likely mediated by afferent discharge of segmental stretch reflex. Thus, another view to explain the finding is that motoneuron excitability, affecting corticospinal excitability, is not increased immediately after force load flexing the index finger due to absence of afferent discharge mediating preparation of motor response to muscle stretch. 5. Conclusion The LLSR is elicited not only by muscle stretch afferents but also by direction-insensitive sensations. Time preparation enhances the LLSR no matter the direction of force load while intending to maintain the finger at the initial neutral position. This enhancement is not mediated by afferent discharge of muscle stretch. Direction preparation enhances the LLSR and increases corticospinal excitability immediately after force load when force load is given in the direction stretching the tested muscle. These enhancements must be induced by the afferent pathway mediating segmental stretch reflex. Acknowledgements This work was supported by a grant from the Osaka Prefectural Government. References Bonnard, M., de Graaf, J., & Pailhous, J. (2004). Interactions between cognitive and sensorimotor functions in the motor cortex: Evidence from the preparatory motor sets anticipating a perturbation. Reviews in the Neurosciences, 15, 371–382. Brebner, J. T., & Welford, A. T. (1980). Introduction: An historical background sketch. In A. T. Welford (Ed.), Reaction times (pp. 1–23). New York: Academic Press. Calancie, B., & Bawa, P. (1985). Firing patterns of human flexor carpi radialis motor units during the stretch reflex. Journal of Neurophysiology, 53, 1179–1193. Christensen, L. O., Petersen, N., Andersen, J. B., Sinkjaer, T., & Nielsen, J. B. (2000). Evidence for transcortical reflex pathways in the lower limb of man. Progress in Neurobiology, 62, 251–272. Colebatch, J. G., Gandevia, S. C., McCloskey, D. I., & Potter, E. K. (1979). Subject instruction and long latency reflex responses to muscle stretch. Journal of Physiology, 292, 527–534.
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Davranche, K., Tandonnet, C., Burle, B., Meynier, C., Vidal, F., & Hasbroucq, T. (2007). The dual nature of time preparation: Neural activation and suppression revealed by transcranial magnetic stimulation of the motor cortex. European Journal of Neuroscience, 25, 3766–3774. Day, B. L., Riescher, H., Struppler, A., Rothwell, J. C., & Marsden, C. D. (1991). Changes in the response to magnetic and electrical stimulation of the motor cortex following muscle stretch in man. Journal of Physiology, 433, 41–57. de Graaf, J. B., Frolov, A., Fiocchi, M., Nazarian, B., Anton, J. L., Pailhous, J., & Bonnard, M. (2009). Preparing for a motor perturbation: Early implication of primary motor and somatosensory cortices. Human Brain Mapping, 30, 575–587. Devanne, H., Lavoie, B. A., & Capaday, C. (1997). Input-output properties and gain changes in the human corticospinal pathway. Experimental Brain Research, 114, 329–338. Evarts, E. V., Teräväinen, H., & Calne, D. B. (1981). Reaction time in Parkinson’s disease. Brain, 104(Pt 1), 167–186. Evarts, E. V., & Tanji, J. (1974). Gating of motor cortex reflexes by prior instruction. Brain Research, 71, 479–494. Goodin, D. S., Aminoff, M. J., & Shih, P. Y. (1990). Evidence that the long-latency stretch responses of the human wrist extensor muscle involve a transcerebral pathway. Brain, 113(Pt 4), 1075–1091. Hammond, P. H. (1955). Involuntary activity in biceps following the sudden application of velocity to the abducted forearm. Journal of Physiology, 127, 23P–25P. Hasegawa, Y., Kasai, T., Tsuji, T., & Yahagi, S. (2001). Further insight into the task-dependent excitability of motor evoked potentials in first dorsal interosseous muscle in humans. Experimental Brain Research, 140, 387–396. Hiraoka, K., Ae, M., Ogura, N., Komuratani, S., Sano, C., Shiomi, K., ... Yokoyama, H. (2014). Smooth pursuit eye movement preferentially facilitates motorevoked potential elicited by anterior-posterior current in the brain. NeuroReport, 25, 279–283. Iida, T., Komiyama, O., Obara, R., Baad-Hansen, L., Kawara, M., & Svensson, P. (2014). Repeated clenching causes plasticity in corticomotor control of jaw muscles. European Journal of Oral Sciences, 122, 42–48. Johansson, R. S., Lemon, R. N., & Westling, G. (1994). Time-varying enhancement of human cortical excitability mediated by cutaneous inputs during precision grip. Journal of Physiology, 481(Pt 3), 761–775. Kasai, T., Kawanishi, M., & Yahagi, S. (1998). Posture-dependent modulation of reciprocal inhibition upon initiation of ankle dorsiflexion in man. Brain Research, 792, 159–163. Kourtis, D., Kwok, H. F., Roach, N., Wing, A. M., & Praamstra, P. (2008). Maintaining grip: Anticipatory and reactive EEG responses to load perturbations. Journal of Neurophysiology, 99, 545–553. Lee, R. G., & Tatton, W. G. (1982). Long latency reflexes to imposed displacements of the human wrist: Dependence on duration of movement. Experimental Brain Research, 45, 207–216. Lewis, G. N., MacKinnon, C. D., & Perreault, E. J. (2006). The effect of task instruction on the excitability of spinal and supraspinal reflex pathways projecting to the biceps muscle. Experimental Brain Research, 174, 413–425. Lewis, G. N., Polych, M. A., & Byblow, W. D. (2004). Proposed cortical and sub-cortical contributions to the long-latency stretch reflex in the forearm. Experimental Brain Research, 156, 72–79. Loo, C. K., & McCloskey, D. I. (1985). Effects of prior instruction and anaesthesia on long-latency responses to stretch in the long flexor of the human thumb. Journal of Physiology, 365, 285–296. Macefield, V. G., Rothwell, J. C., & Day, B. L. (1996). The contribution of transcortical pathways to long-latency stretch and tactile reflexes in human hand muscles. Experimental Brain Research, 108, 147–154. MacKinnon, C. D., Verrier, M. C., & Tatton, W. G. (2000). Motor cortical potentials precede long-latency EMG activity evoked by imposed displacements of the human wrist. Experimental Brain Research, 131, 477–490. Manning, C. D., Tolhurst, S. A., & Bawa, P. (2012). Proprioceptive reaction times and long-latency reflexes in humans. Experimental Brain Research, 221, 155–166. Matthews, P. B. (1991). The human stretch reflex and the motor cortex. Trends in Neurosciences, 14, 87–91. Meziane, H. B., Spieser, L., Pailhous, J., & Bonnard, M. (2009). Corticospinal control of wrist muscles during expectation of a motor perturbation: A transcranial magnetic stimulation study. Behavioural Brain Research, 198, 459–465. Mutha, P. K., Boulinguez, P., & Sainburg, R. L. (2008). Visual modulation of proprioceptive reflexes during movement. Brain Research, 1246, 54–69. Oldfield, R. C. (1971). The assessment and analysis of handedness: The Edinburgh inventory. Neuropsychologia, 9, 97–113. Palmer, E., & Ashby, P. (1992). Evidence that a long latency stretch reflex in humans is transcortical. Journal of Physiology, 449, 429–440. Tanji, J., & Evarts, E. V. (1976). Anticipatory activity of motor cortex neurons in relation to direction of an intended movement. Journal of Neurophysiology, 39, 1062–1068. van Elswijk, G., Schot, W. D., Stegeman, D. F., & Overeem, S. (2008). Changes in corticospinal excitability and the direction of evoked movements during motor preparation: A TMS study. BMC Neuroscience, 9, 51. Yamamoto, C., & Ohtsuki, T. (1989). Modulation of stretch reflex by anticipation of the stimulus through visual information. Experimental Brain Research, 77, 12–22.
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Human Movement Science journal homepage: www.elsevier.com/locate/humov
Full Length Article
Time and direction preparation of the long latency stretch reflex Yasutaka Nikaido a, Ryota Hatanaka a, Yasutomo Jono a, Yoshifumi Nomura a, Keisuke Tani a, Yuta Chujo a, Koichi Hiraoka b,⇑ a b
Graduate School of Comprehensive Rehabilitation, Osaka Prefecture University, Japan College of Health and Human Sciences, Osaka Prefecture University, Japan
a r t i c l e
i n f o
Article history: Received 11 December 2013 Revised 18 September 2015 Accepted 31 January 2016
Keywords: Perturbation Force load Long latency stretch reflex First dorsal interosseous muscle Prediction
a b s t r a c t This study investigated time and direction preparation of motor response to force load while intending to maintain the finger at the initial neutral position. Force load extending or flexing the index finger was given while healthy humans intended to maintain the index finger at the initial neutral position. Electromyographic activity was recorded from the first dorsal interosseous muscle. A precue with or without advanced information regarding the direction of the forthcoming force load was given 1000 ms before force load. Trials without the precue were inserted between the precued trials. A long latency stretch reflex was elicited by force load regardless of its direction, indicating that the long latency stretch reflex is elicited not only by muscle stretch afferents, but also by direction-insensitive sensations. Time preparation of motor response to either direction of force load enhanced the long latency stretch reflex, indicating that time preparation is not mediated by afferent discharge of muscle stretch. Direction preparation enhanced the long latency stretch reflex and increased corticospinal excitability 0–20 ms after force load when force load was given in the direction stretching the muscle. These enhancements must be induced by preset of the afferent pathway mediating segmental stretch reflex. Ó 2016 Elsevier B.V. All rights reserved.
1. Introduction In daily activities, external force load sometimes acts on the limb and interferes with ongoing movements. Humans quickly respond to the external force so as to minimize the unwanted deviation of ongoing movement trajectory. Force load over the arm induces two motor responses in the arm muscles (Hammond, 1955; see review by Matthews, 1991): (1) a short latency stretch response (SLSR) with 20–35 ms of latency; and (2) a long latency stretch reflex (LLSR) with 50–65 ms of latency (Lee & Tatton, 1982; Lewis, MacKinnon, & Perreault, 2006; Lewis, Polych, & Byblow, 2004; Manning, Tolhurst, & Bawa, 2012). Nevertheless, only the LLSR is elicited in the first dorsal interosseous (FDI) muscle when force load is given over the index finger (Johansson, Lemon, & Westling, 1994; Kourtis, Kwok, Roach, Wing, & Praamstra, 2008), in spite of one exceptional study, in which an SLSR was observed in 5 of 9 participants (Macefield, Rothwell, & Day, 1996). The neural mechanism underlying the SLSR and that underlying the LLSR must be different from that underlying voluntary motor response to an imperative cue, because the latency of the SLSR and that of the LLSR are shorter than the latency of voluntary motor response to an imperative cue (Brebner & Welford, 1980; Evarts, Teräväinen, & Calne, 1981; Manning et al., 2012). The SLSR has been thought to be of spinal origin, because the SLSR and motor evoked potential (MEP) elicited around ⇑ Corresponding author at: College of Health and Human Sciences, Osaka Prefecture University, 3-7-30 Habikino, Habikino City, Osaka 583-8555, Japan. E-mail address: [email protected] (K. Hiraoka). http://dx.doi.org/10.1016/j.humov.2016.01.016 0167-9457/Ó 2016 Elsevier B.V. All rights reserved.
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the period at which the SLSR appeared are not modulated by task instruction (MacKinnon, Verrier, & Tatton, 2000; Lewis et al., 2004, 2006). In contrast, the LLSR has been thought to be mediated by the transcortical pathways (Christensen, Petersen, Andersen, Sinkjaer, & Nielsen, 2000; Goodin, Aminoff, & Shih, 1990; Palmer & Ashby, 1992; see reviews by Bonnard, de Graaf, & Pailhous, 2004 and by Matthews, 1991), because long latency facilitation of motoneuron excitability induced by force load over the thumb is greater when the cortex is stimulated (Palmer & Ashby, 1992). Preparation of the LLSR is possible to be conditioned by prior instruction. Prior instruction to oppose force load enhanced the LLSR (Calancie & Bawa, 1985; Colebatch et al., 1979; Lee & Tatton, 1982; MacKinnon et al., 2000), activated the primary motor and sensory cortices (de Graaf et al., 2009), and increased corticospinal excitability around the period at which the LLSR appeared (Lewis et al., 2004, 2006). Moreover, prior instruction to oppose force load extending the wrist did not affect corticospinal excitability in the flexor carpi radialis muscle, but increased corticospinal excitability in the extensor carpi radialis muscle in the foreperiod (Meziane, Spieser, Pailhous, & Bonnard, 2009). According to these previous studies, preparation of the LLSR is under control of supraspinal cognitive process. Two aspects of preparation for motor response to force load have been investigated in previous studies. One concerns time preparation. A precue indicating the timing of the imperative cue affected corticospinal excitability when humans responded to an imperative cue (Davranche et al., 2007). Such time preparation was present even when humans responded to force load. The LLSR in the FDI muscle during a precision grip task was smaller when the timing of force load was predictable, and this was reflected in the amplitude of sensorimotor cortex potentials just preceding the LLSR (Kourtis et al., 2008). This finding indicates that time preparation modulates the excitability of the cortical sites which take part of the transcortical pathway mediating the LLSR. The other aspect concerns direction preparation. Corticospinal excitability in the foreperiod of voluntary motor response to a visual imperative cue was affected by a precue indicating direction of to-be-signaled motor response (van Elswijk, Schot, Stegeman, & Overeem, 2008). A previous study, investigating the effect of force load on jump of the visual target during goal directed movement, reported that motor response to force load depends on the direction of the visual target movement (Mutha, Boulinguez, & Sainburg, 2008). This finding indicates that visual information regarding the direction of ongoing movement affects motor response to force load. Moreover, direction preparation of motor response to force load has been investigated in monkeys (Evarts & Tanji, 1974; Tanji & Evarts, 1976). In these studies, monkeys were instructed ‘‘push” or ‘‘pull” against force load before onset of force load, and motor cortical activity was modulated according to the direction of motor response instructed in advance. The modulation occurred not only 200 ms after the instruction but also 20 ms after force load onset (Evarts & Tanji, 1974). According to these findings by Evarts and Tanji, the motor cortex processes direction preparation of motor response to force load both before and after force load. Preparation process of the LLSR has been thought to be achieved by presetting the excitability of the transcortical pathway. Gating the supraspinal sites of the transcortical pathway has been proposed to be mechanism underlying this process (see review by Bonnard et al., 2004). However, this mechanism is not reasonable when force load is given on the finger while intending to maintain the finger at the initial neutral position. Presetting supraspinal sites of the transcortical reflex must modulate motoneuron excitability causing small changes in force level of the finger. In this case, finger position deviates slightly even before force load, and this interferes with holding of the limb or finger at the initial position. We propose alternative hypothetical mechanism: Preparatory process of motor response to force load modulates the excitability of the afferent pathway mediating segmental stretch reflex while intending to maintain the finger at the initial neutral position. Force load in the direction opposite to the function of the target muscle stretches the muscle causing excitation of the afferent pathway mediating segmental stretch reflex. If preparation process of motor response to force load modulates the excitability of the afferent pathway mediating segmental stretch reflex, modulation of motoneuron excitability must be minor before discharge of the afferent pathway induced by force load, but preparation process affects motoneuron excitability immediately after force load stretching the tested muscle causing discharge of the afferent pathway. The present study tested this hypothesis. The corticospinal pathway and the transcortical pathway mediating the LLSR share the common neural pathways, according to a previous finding that MEP amplitude increases specifically around the onset of the LLSR (Day, Riescher, Struppler, Rothwell, & Marsden, 1991). Thus, MEP elicited before and after force load was the marker indicating neural mechanism underlying preparation of the LLSR in the present study. If preparation is processed through the afferent pathway mediating segmental stretch reflex, corticospinal excitability must not be modulated before force load but must be modulated after force load stretching the tested muscle, because afferent discharge does not occur before force load stretching the tested muscle but occurs during and shortly after force load. The findings in the present study must help us to understand how humans prepare for motor response to forthcoming force load for minimizing unwanted change in their ongoing movement induced by external force load while intending to maintain their finger at the initial neutral position. 2. Methods 2.1. Participants Participants were 10 healthy humans (9 males and 1 female), aged 20–34 years (26.3 ± 1.6). All participants were right handed according to the Edinburgh Handedness Inventory (Oldfield, 1971). The experimental design was approved by the ethics committee of Osaka Prefecture University.
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2.2. Apparatus Each participant sat on a chair with their right forearm and wrist fixed by metal frames. The right index finger tip was fixed over the attachment of the lever arm of the torque motor, as shown in Fig. 1A (FRL-2009, Uchida denshi, Tokyo). A laser pointer was attached over the lever arm. The surface recording electrodes were placed over the belly and tendon of the FDI muscle with a belly-tendon montage. The electromyographic (EMG) signal from the FDI muscle was band-pass filtered at 15 Hz to 3 kHz using an amplifier (MEG-5200, Nihon Kohden, Tokyo). Analogue signals of the motion of the lever arm and EMG were converted to digital signals at a sampling rate of 5 kHz using an A/D converter (UAS-108S, Unique Medical, Tokyo). 2.3. Transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) was delivered by a round coil (YM-133B, Nihon Kohden, Tokyo) connected to a magnetic stimulator (SMN-1200, Nihon Kohden, Tokyo). The outer diameter of the coil was 99 mm, and it had a maximum intensity of 0.67 T. The coil was placed over the vertex and moved little by little until a hotspot of the left primary motor cortex was located. The coil was then positioned over the hotspot, and TMS intensity was decreased trial by trial to find a resting motor threshold (RMT). The RMT was defined as the lowest stimulus intensity that produced an MEP larger than 50 lV in amplitude with 50% probability at rest. TMS intensity was then adjusted to be 1.2 times the resting motor threshold. 2.4. Procedure The lever arm of the torque motor constantly produced 0.4 N of downward force (i.e., in the direction of finger extension) throughout the trial before force load. The participants were instructed to keep the lever arm at a neutral position against the downward force of the lever arm with their index finger so that a laser pointer pointed a beam at a target point located at their midline on the wall 150 cm in front of them (Fig. 1A). This force was loaded so that participants exerted small constant force in the direction of flexion before change in force load to facilitate clear appearance of the SLSR (Manning et al., 2012). Participants were then asked to close their eyes (Fig. 1B). After that, one of three types of precue was given. A high-frequency tone (1 kHz) precue indicated that a force load in the direction of extension would be given to the finger 1000 ms after the precue, and a low-frequency tone (66.7 Hz) precue indicated that a force load in the direction of flexion would be given 1000 ms after the precue (Direction and time preparation condition; DT condition). A middle-range (143 Hz) precue did not indicate the direction of the forthcoming force load (Time preparation condition; T condition). Participants could process solely time preparation in this condition, because the precue was always given 1000 ms before force load onset. No precue
Fig. 1. Experimental setup (A) and experimental protocol (B).
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was given in the non-preparation condition (N condition). In the N condition, neither time nor direction preparation were processed. Force load of 1.6 N in the direction of either flexion or extension began 1000 ms after the precue and continued for 3000 ms. Force load extending the index finger was given in the stretch condition. In this condition, the FDI muscle was stretched by force load. Force load flexing the index finger was given in the non-stretch condition. In this condition, the FDI muscle was not stretched. The precue conditions (DT, T and N conditions) and the stretch conditions (stretch and non-stretch conditions) were randomly altered trial by trial. In the DT condition of the stretch condition, preparation of muscle stretch induced by force load was processed in addition to time preparation. In contrast, in the DT condition of the non-stretch condition, the participants did not prepare muscle stretch induced by force load, because force load flexing the index finger was predicted by the precue. Participants made an effort to maintain a neutral position with their index finger even when force load was given. After the force load was released, participants opened their eyes and returned the lever arm and index finger to the neutral position. The EMG response to force load and the angle of the lever arm were recorded 10 times for each precue condition without TMS. Trials with TMS were conducted in another experimental session. TMS was delivered 100 ms before force load onset (baseline period), or 0–20, 20–40, or 40–60 ms after force load onset. TMS timing was randomly altered each trial. Trials with EMG burst in the time window between TMS onset and force load onset were discarded. Trials with TMS were continued until 15 successful MEPs were elicited for each time period for each precue condition. Inter-trial interval was approximately 10 s. Before beginning the trials, participants performed practice tests to become familiar with the process. 2.5. Data analysis Time to peak and peak angle of the lever arm after force load onset, the latency of the EMG response to force load, and the amplitude of the rectified EMG response in the time window between 0 and 20 ms after the onset of the EMG response to force load were estimated each single trial without TMS (Fig. 1B). The EMG amplitude in the time window between 0 and 20 ms after the onset of the EMG response to force load roughly corresponds to EMG amplitude in the time window between the onset and around peak of the LLSR, because peak latency of the LLSR from the EMG onset in the FDI muscle is approximately 20 ms (Kourtis et al., 2008; Macefield et al., 1996). Averaging EMG traces following force load onset conducted in previous studies (Kourtis et al., 2008; Macefield et al., 1996) may cause greater involvement of the voluntary EMG response for the estimated amplitude due to averaging various latencies of EMG responses following the onset of force load. In contrast, estimating amplitude of EMG response each single trace in the present study allowed us to measure the amplitude of the early period of the LLSR with minimum involvement of the voluntary EMG response following the LLSR, because the end of the time window for this estimation was precisely 20 ms after EMG onset. MEP amplitude was estimated based on peak to peak. The peak latency of the MEP, defined as the duration between the time of TMS and the time of either the positive or negative peak of the MEP (whichever occurred later), was estimated. Background EMG (BEMG) level affects the MEP amplitude (Devanne, Lavoie, & Capaday, 1997; Hasegawa, Kasai, Tsuji, & Yahagi, 2001). Therefore, pre-stimulus BEMG amplitude in the time window between 12 and 2 ms before TMS was estimated from the rectified EMG trace in order to rule out the effect of EMG activity on MEP. BEMG amplitude in the time window between 0 and 1000 ms before force load was estimated each single trial without TMS to elucidate the preparatory process before force load. The amplitude of the MEP elicited 100 ms before force load and that of the pre-stimulus BEMG preceding the MEP elicited 100 ms before force load were compared across the precue conditions and between the stretch conditions to assure that the MEP and pre-stimulus BEMG amplitudes in the baseline period were similar across the experimental conditions. The amplitude of the MEP elicited after force load and that of the pre-stimulus BEMG preceding the MEP were averaged each 20 ms of the latency after force load (Kasai, Kawanishi, & Yahagi, 1998), in order to categorize elicited MEPs, distributing sequentially in the pre-response period, into one of the three time periods: 0–20, 20–40, and 40–60 ms after force load onset. The amplitude of the MEP elicited after force load was divided by amplitude of the MEP elicited 100 ms before force load averaged across the precue conditions, and the amplitude of the pre-stimulus BEMG preceding the MEP elicited after force load was divided by amplitude of the pre-stimulus BEMG amplitude preceding the MEP elicited 100 ms before force load averaged across the precue conditions. Dividing the amplitudes by amplitudes in the baseline period was to normalize the amplitudes across the participants. A paired t-test was conducted to examine the difference between two means. One-way repeat measures ANOVA was conducted for testing one main effect [3 (precues)]. Two-way repeated measure ANOVA was conducted for testing two main effects: [2 (stretch) * 3 (precues)] or [4 (time periods) * 3 (precues)]. When two-way repeated measures ANOVA revealed significant interaction between the two main effects, analysis of simple main effect followed by multiple comparisons was conducted. The statistical significance level was 0.05. Data was expressed as mean ± standard error of mean. 3. Results 3.1. Motion of the lever arm Time to peak of lever arm motion produced by force load across the precue conditions was 87.5 ± 2.6 ms in the stretch condition (Figs. 2A and 4a), and 84.6 ± 1.5 ms in the non-stretch condition (Figs. 2B and 4c). There was no significant differ-
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ence in time to peak of lever arm motion among the precue conditions in both the stretch [F(2,18) = 2.537, p = 0.107] and non-stretch conditions [F(2,18) = 0.324, p = 0.728]. Peak angle of the lever arm across the precue conditions was 9.5 ± 0.7 degrees in the stretch condition (Figs. 2A and 4b), and 15.6 ± 1.0 degrees in the non-stretch condition (Figs. 2B and 4d). There was no significant difference in peak angle among the precue conditions in both the stretch [F(2,18) = 0.044, p = 0.957] and non-stretch conditions [F(2,18) = 0.425, p = 0.660]. 3.2. EMG response to force load BEMG amplitude in the time window between 0 and 1000 ms before force load in the trials without TMS was not significantly different between the stretch conditions [F(1,9) = 1.017, p = 0.340] and among the precue conditions [F(2,18) = 0.853, p = 0.443] without significant interaction [F(2,18) = 0.410, p = 0.670] (Fig. 3). The EMG response was present in both the stretch and non-stretch conditions (Fig. 2). The latency of the EMG response to force load across the precue conditions was 74.9 ± 2.5 ms in the stretch condition (Figs. 2A and 5a), and 84.5 ± 2.0 ms in the non-stretch condition (Figs. 2B and 5c). There was no significant difference in the latency among the precue conditions in both the stretch [F(2,18) = 2.540, p = 0.107] and non-stretch conditions [F(2,18) = 0.039, p = 0.962]. The amplitude of the EMG response in the stretch condition was significantly different among the precue conditions as shown in Fig. 5b [F(2,18) = 24.104, p < 0.001]. Post-hoc test revealed that EMG amplitude in the DT condition was significantly larger than that in the other precue conditions: Meanwhile, EMG amplitude in the T condition was significantly larger than that in the N condition (P < 0.05). The amplitude of the EMG response in the non-stretch condition was significantly different among the precue conditions as shown in Fig. 5d [F(2,18) = 9.564, p = 0.002]. Post-hoc test revealed that the amplitude of the EMG response in the DT condition and that in the T conditions were significantly larger than that in the N condition (P < 0.05). 3.3. Pre-stimulus BEMG amplitude The amplitude of the pre-stimulus BEMG preceding the MEP elicited 100 ms before force load was not significantly different among the precue conditions [F(2,18) = 0.266, p = 0.770] and between the stretch conditions [F(1,9) = 0.000, p = 0.994] without significant interaction [F (2,18) = 0.552, p = 0.585]. Normalized pre-stimulus BEMG amplitudes before and after force load are shown in Figs. 6A and 7A. Pre-stimulus BEMG amplitude was not significantly different among the precue conditions [F(2,18) = 1.971, p = 0.168] or among the time periods [F(3,27) = 1.400, p = 0.264] in the stretch condition. There was no significant interaction between the two main effects [F(6,54) = 1.791, p = 0.118]. Pre-stimulus BEMG amplitude was not significantly different among the precue conditions [F(2,18) = 3.133, p = 0.068] or among the time periods [F(3,27) = 0.651, p = 0.589] in the non-stretch condition. There was no significant interaction between the two main effects [F(6,54) = 0.803, p = 0.572].
Fig. 2. Specimen record of the lever arm movement and rectified EMG response in trials without TMS. Filled triangles indicate the onset of lever arm movement. Open triangles indicate the onset of the EMG response.
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Fig. 3. Specimen record of the rectified BEMG in the time window between 0 and 1000 ms before force load (A) and averaged BEMG amplitude across the participants (B). Bars indicate means and error bars indicate standard error of mean (B).
Fig. 4. Time to peak (a, c) and peak angle (b, d) of the lever arm in the stretch and non-stretch conditions in trials without TMS. Bars indicate means and error bars indicate standard error of mean.
Fig. 5. The latency (a, c) and the amplitude of the EMG response (b, d) in the stretch and non-stretch conditions in trials without TMS. Bars indicate means and error bars indicate standard error of mean. Asterisks indicate significant difference (p < 0.05).
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Fig. 6. Normalized pre-stimulus BEMG and MEP amplitudes in the stretch condition. Data points indicate means and error bars indicate standard error of mean. Asterisks indicate the significant difference between the precue conditions, and daggers indicate the significant difference between the period 100 ms before force load and the other periods after force load.
Fig. 7. Normalized pre-stimulus BEMG and MEP amplitudes in the non-stretch condition. Data points indicate means and error bars indicate standard error of mean.
3.4. MEP The TMS threshold was 62.8 ± 3.9% of maximum stimulator output, and TMS intensity used in the experiment was 75.4 ± 4.6% of maximum stimulator output. The peak latency of the MEP was 27.7 ± 0.6 ms. The amplitude of the MEP elicited
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100 ms before force load was not significantly different among the precue conditions [F(2,18) = 0.030, p = 0.971] and between the stretch conditions [F(1,9) = 3.789, p = 0.083] without significant interaction [F(2,18) = 1.227, p = 0.317]. The averaged delay of TMS after force load was 10.7 ± 0.3 ms in the time period of 0–20 ms, 29.3 ± 0.4 ms in the time period of 20–40 ms, and 49.2 ± 0.3 ms in the time period of 40–60 ms after force load. ANOVA failed to reveal significant difference in the averaged delay among the precue conditions in all of the time periods. In the stretch condition, normalized amplitude of the MEP elicited after force load in the DT condition and that elicited 40–60 ms after force load in the T condition tended to be greater than that elicited 100 ms before force load (Fig. 6B). In contrast, such tendency was not observed in the N condition. Normalized MEP amplitude was significantly different among the precue conditions [F(2,18) = 5.195, p = 0.017] and among the time periods [F(3,27) = 20.165, p < 0.001] in the stretch condition. There was also a significant interaction between the two main effects [F(6,54) = 3.404, p = 0.006]. Simple main effect of the amplitude of the MEP elicited 40–60 ms after force load onset was significant for the precue conditions [F(2,70) = 14.003, p < 0.001]. Multiple comparisons revealed that the amplitude of the MEP elicited 40–60 ms after force load onset was significantly different among the precue conditions (p < 0.05). Simple main effect of MEP amplitude was significant among the time periods in the DT condition [F(3,80) = 20.617, p < 0.001] and in the T condition [F(3,80) = 7.870, p < 0.001], but not in the N condition [F(3,80) = 1.145, p = 0.336]. Multiple comparisons for the DT condition revealed that MEP amplitude was significantly different among all the time periods except between the period 0–20 ms after force load and the period 20–40 ms after force load (p < 0.05), while those for the T condition revealed that the amplitude of the MEP elicited 40–60 ms after force load onset was significantly larger than that in the other periods (p < 0.05). In the non-stretch condition, normalized amplitude of the MEP elicited after force load did not increase (Fig. 7B). MEP amplitude was similar across the precue conditions. MEP amplitude was not significantly different among the precue conditions [F(2,18) = 1.991, p = 0.166] or between the time periods [F(3,27) = 2.136, p = 0.119] in the non-stretch condition. There was no significant interaction between the two main effects [F(6,54) = 0.929, p = 0.482].
4. Discussion 4.1. Lever arm movement The index finger tip was kept touch with the end of the lever arm, and the participants attempted to maintain the initial neutral position of the finger against slight and constant force load exerted by the lever arm. Thus, lever arm motion reflects the difference between force exerted by the index finger tip and that exerted by the end of the lever arm. The lever arm moved immediately after force load, and this motion was followed by opposite motion back to the neural position shortly after the onset of the EMG response. The peak angle of the lever arm is the point at which external torque of force load over the lever arm and internal torque, which is the summation of passive and active torques of the metacarpophalangeal joint of the index finger, reach equivalent levels. Time to peak is the time to reach the equivalent levels. Thus, time to peak and the amplitude of the lever arm represent the ability of returning the index finger to the neutral position with a short period of time and with small amplitude of lever arm movement after external force load. In the present study, the time to peak and the amplitude of the lever arm motion were not significantly different among the precue conditions, indicating that neither time nor direction preparation of motor response to force load affects this ability. 4.2. EMG response In the present study, the latency of the EMG response was around 75–85 ms across the precue conditions, and was slightly longer than the latency of the LLSR in the FDI muscle (51–64 ms) observed in previous studies (Johansson et al., 1994; Kourtis et al., 2008). Accordingly, the EMG response observed in the present study was considered to be the LLSR. The SLSR was not observed in the present study. This finding was consistent with findings in previous studies which tested the FDI muscle (Johansson et al., 1994; Kourtis et al., 2008), but was inconsistent with another previous study in which the SLSR was observed in some participants (Macefield et al., 1996). The inconsistent findings among the studies indicate that the SLSR in the FDI muscle is observable only under certain circumstances. Plausible explanation for the absence of the SLSR in the present study is that force load was too weak to elicit the SLSR. Muscle stretch has been thought to be the cause of the EMG responses to force load (see review by Matthews, 1991). The FDI muscle was stretched in the stretch condition because the lever arm moved to extend the index finger in this condition, but that was not in the non-stretch condition because the lever arm moved to flex the index finger. In spite of that, the LLSR was observed no matter the direction of force load. This finding is reasonably explained by a view that the LLSR is elicited not only by muscle stretch afferents, but also by other sensations. Cutaneous sensation must have been produced by either direction of force load. It has been reported that the transcortical pathway mediating the LLSR in the FDI muscle is partially mediated by the cutaneous afferent pathways (Johansson et al., 1994). The LLSR in the FDI muscle is induced by cutaneous sensation (Macefield et al., 1996). Moreover, the LLSR was suppressed by local anesthesia eliminating cutaneous sensation (Loo & McCloskey, 1985). Therefore, not only muscle stretch afferents but also cutaneous sensation mediates the LLSR.
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4.3. The effect of preparation process on the EMG response The EMG response to force load was enhanced in the T condition of both the stretch and non-stretch conditions. In the T condition, the precue was constantly provided 1000 ms before force load. Thus, time prediction was possible, and time preparation of motor response to force load must have been processed in the T condition. Accordingly, the present finding means that time preparation enhances the LLSR when humans intend to maintain the finger at the initial neutral position. The enhancement must not be solely mediated by afferent discharge induced by muscle stretch, because the enhancement was present no matter force load stretched the muscle or not. There are two conflicting previous findings regarding the effect of time preparation on the LLSR. The amplitude of the LLSR in the abductor pollicis brevis muscle during a precision grip task was significantly smaller when the timing of force load was predictable, and similar insignificant tendency was found in the FDI muscle (Kourtis et al., 2008). In contrast, in a previous study by Yamamoto and Ohtsuki (1989), time preparation of motor response to force load enhanced the LLSR in the biceps muscle. In the previous study by Kourtis and colleagues, participants were instructed to hold an object with the index finger and the thumb without slipping off the object, but were not instructed to maintain the initial position of the object. Then, time preparation of motor response to force load increased BEMG amplitude before force load. In contrast, in the previous study by Yamamoto and Otsuki, participants intended to maintain the arm at the initial position, and BEMG amplitude before force load was not affected by time prediction. Accordingly, the conflicting findings between these studies must be originated from intention whether participants attempted to maintain the initial position of the fingers or the arm, causing different effect of time preparation on BEMG amplitude before force load. Task instruction and findings in our present study were consistent with the study by Yamamoto and Otsuki: The participants maintained the lever arm at the initial neutral position and BEMG amplitude before force load was same across the precue conditions before force load. Accordingly, rational explanation for the conflicting findings is that time preparation enhances the LLSR only when humans intend to maintain the finger at the initial position. The EMG response in the DT condition was larger than that in the T condition of the stretch condition. The muscle was stretched by force load in both the DT and T conditions of the stretch condition. In the DT condition, both time and direction preparation must have been processed, because advanced information regarding the direction of forthcoming force load was indicated by the precue constantly provided 1000 ms before force load. In contrast, only time preparation was processed in the T condition. Therefore, the difference between the DT and T conditions of the stretch condition is solely advanced information regarding force load direction. Given this, different amplitude of EMG response between the DT and T conditions in the stretch condition must be originated from the direction preparation of motor response to force load. Thus, the present finding means that preparation of motor response to muscle stretch enhances the LLSR to force load stretching the muscle. One possible event we have to note regarding enhancement of the EMG response to force load induced by the precue is superimposition of the proprioception-induced voluntary EMG response on the LLSR. When humans intend to oppose force load, voluntary EMG response to proprioceptive input occurs shortly after the onset of the LLSR (MacKinnon et al., 2000; Meziane et al., 2009). The choice reaction time of the proprioception-induced voluntary EMG response in the wrist flexor is around 100 ms (Manning et al., 2012). Similar reaction time of the proprioception-induced voluntary EMG response must have been produced in the present study, because proprioception was induced by force load and the task conducted was regarded as choice reaction time paradigm, in which the participants responded to two directions of force load of which the direction was altered randomly trial by trial. In the present study, the latency of the EMG response in the FDI muscle was around 75 ms in the stretch condition and 85 ms in the non-stretch condition. Given this, in the time window between 0 and 20 ms after force load, in which the amplitude of the EMG response was measured, superimposition of the proprioception-induced voluntary EMG response on the LLSR is minor. Thus, enhancement of the EMG response induced by time or direction preparation is mainly explained by enhancement of the LLSR. 4.4. The effect of preparation process on corticospinal excitability We must take account the superimposition of the MEP on the EMG response to force load as possible cause of the changes in MEP amplitude. The peak latency of the MEP elicited 40–60 ms after force load onset was approximately 70–90 ms after force load onset, because the peak latency of the MEP was approximately 28 ms. The latency of the EMG response to force load was around 75 ms in the stretch condition and 85 ms in the non-stretch condition. Given this, some MEPs elicited 40–60 ms after force load onset must have been superimposed on the EMG response to force load. As a result, we cannot rule out a possibility that enhancement of the MEP elicited 40–60 ms after force load onset is caused by superimposition of the MEP response on the EMG response to force load. Similar enhancement of the MEP elicited 40–60 ms after force load and the EMG response in the DT and T conditions of the stretch condition supports this view. Nevertheless, the MEP elicited 0–20 ms after force load must not have superimposed on the EMG response. The peak latency of the MEP elicited 0–20 ms after force load onset must have been approximately 30–50 ms after force load onset. Accordingly, the peak of the MEP elicited 0–20 ms after force load onset did not superimpose on the EMG response onset around 75–85 ms after force load. Thus, the amplitude of the MEP elicited 0–20 ms after force load solely represents corticospinal excitability. The amplitude of the MEP elicited 0–20 ms after force load in the DT condition of the stretch condition was larger than that elicited before force load in the same condition. The amplitude of the MEP elicited before force load was not significantly different among the precue conditions, indicating that direction preparation does not affect corticospinal excitability before force load. Major difference between before and after force load is afferent discharge: Afferent discharge
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induced by force load did not yet occur before force load but must have occurred during and shortly after force load. Thus, increases in the amplitude of the MEP elicited 0–20 ms after force load in the DT condition of the stretch condition must have been mediated by afferent discharge induced by force load. MEP amplitude depends on the excitability of the primary motor cortex. However, the increase in the excitability of the primary motor cortex must not be responsible for the increase in the amplitude of the MEP elicited 0–20 ms after force load, because the latency of the increase in the amplitude of the MEP after force load was too short to arrive the action potential of afferent discharge at the supraspinal sites. MEP amplitude is affected not only by change in the excitability of the primary motor cortex but also by that of motoneuron excitability. However, motoneuron excitability must not have been directly modulated by direction preparation, because BEMG amplitude was not increased by direction preparation before force load. Motoneuron excitability is affected by afferent discharge mediating segmental stretch reflex. The latency of the MEP in the FDI muscle is around 25 ms (Hiraoka et al., 2014; Iida et al., 2014). The latency of the SLSR, mediated by the segmental stretch reflex pathway (see review by Matthews, 1991), is around 34 ms in the FDI muscle (Macefield et al., 1996). Accordingly, action potentials of the muscle stretch afferents induced by force load and the descending volleys induced by TMS given 0–20 ms after force load must have arrived at the synaptic terminals on the motoneurons about the same time. Given this, most feasible explanation for the increase in MEP elicited 0–20 ms after force load in the DT condition of the stretch condition is greater motoneuron excitability immediately after force load due to greater afferent discharge of muscle stretch induced by preparation of motor response to muscle stretch. Taken together, increase in the amplitude of the MEP immediately after force load induced by preparation process of motor response to muscle stretch is reasonably explained by the following process. Preset of susceptibility of the afferent pathway mediating segmental stretch reflex occurs during preparation of motor response to muscle stretch. The preset of susceptibility of the afferent pathway does not affect corticospinal excitability before force load, because afferent discharge does not occur at this time. In contrast, the preset increases corticospinal excitability immediately after force load, because the afferent pathway discharges at this time. Finally, corticospinal excitability increases immediately after force load stretching the tested muscle when the participants prepare for motor response to muscle stretch. 4.5. Prediction of non-stretch of the muscle The amplitude of the EMG response and the amplitude of the MEP elicited 0–20 ms after force load were not significantly different between the DT and T conditions of the non-stretch condition. The participants predicted that the muscle would not be stretched in the DT condition of the non-stretch condition, although direction prediction was impossible in the T condition. Accordingly, the difference between the DT and T conditions of the non-stretch condition was whether prediction of non-stretch of the muscle was possible or not. Thus, the findings indicate that prediction of non-stretch of the muscle does not enhance motor response to force load, and does not increase corticospinal excitability immediately after force load. This is possibly explained by a view that direction preparation only processes to oppose muscle stretch. As mentioned above, increase in corticospinal excitability immediately after force load in the stretch condition is likely mediated by afferent discharge of segmental stretch reflex. Thus, another view to explain the finding is that motoneuron excitability, affecting corticospinal excitability, is not increased immediately after force load flexing the index finger due to absence of afferent discharge mediating preparation of motor response to muscle stretch. 5. Conclusion The LLSR is elicited not only by muscle stretch afferents but also by direction-insensitive sensations. Time preparation enhances the LLSR no matter the direction of force load while intending to maintain the finger at the initial neutral position. This enhancement is not mediated by afferent discharge of muscle stretch. Direction preparation enhances the LLSR and increases corticospinal excitability immediately after force load when force load is given in the direction stretching the tested muscle. These enhancements must be induced by the afferent pathway mediating segmental stretch reflex. Acknowledgements This work was supported by a grant from the Osaka Prefectural Government. References Bonnard, M., de Graaf, J., & Pailhous, J. (2004). Interactions between cognitive and sensorimotor functions in the motor cortex: Evidence from the preparatory motor sets anticipating a perturbation. Reviews in the Neurosciences, 15, 371–382. Brebner, J. T., & Welford, A. T. (1980). Introduction: An historical background sketch. In A. T. Welford (Ed.), Reaction times (pp. 1–23). New York: Academic Press. Calancie, B., & Bawa, P. (1985). Firing patterns of human flexor carpi radialis motor units during the stretch reflex. Journal of Neurophysiology, 53, 1179–1193. Christensen, L. O., Petersen, N., Andersen, J. B., Sinkjaer, T., & Nielsen, J. B. (2000). Evidence for transcortical reflex pathways in the lower limb of man. Progress in Neurobiology, 62, 251–272. Colebatch, J. G., Gandevia, S. C., McCloskey, D. I., & Potter, E. K. (1979). Subject instruction and long latency reflex responses to muscle stretch. Journal of Physiology, 292, 527–534.
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Davranche, K., Tandonnet, C., Burle, B., Meynier, C., Vidal, F., & Hasbroucq, T. (2007). The dual nature of time preparation: Neural activation and suppression revealed by transcranial magnetic stimulation of the motor cortex. European Journal of Neuroscience, 25, 3766–3774. Day, B. L., Riescher, H., Struppler, A., Rothwell, J. C., & Marsden, C. D. (1991). Changes in the response to magnetic and electrical stimulation of the motor cortex following muscle stretch in man. Journal of Physiology, 433, 41–57. de Graaf, J. B., Frolov, A., Fiocchi, M., Nazarian, B., Anton, J. L., Pailhous, J., & Bonnard, M. (2009). Preparing for a motor perturbation: Early implication of primary motor and somatosensory cortices. Human Brain Mapping, 30, 575–587. Devanne, H., Lavoie, B. A., & Capaday, C. (1997). Input-output properties and gain changes in the human corticospinal pathway. Experimental Brain Research, 114, 329–338. Evarts, E. V., Teräväinen, H., & Calne, D. B. (1981). Reaction time in Parkinson’s disease. Brain, 104(Pt 1), 167–186. Evarts, E. V., & Tanji, J. (1974). Gating of motor cortex reflexes by prior instruction. Brain Research, 71, 479–494. Goodin, D. S., Aminoff, M. J., & Shih, P. Y. (1990). Evidence that the long-latency stretch responses of the human wrist extensor muscle involve a transcerebral pathway. Brain, 113(Pt 4), 1075–1091. Hammond, P. H. (1955). Involuntary activity in biceps following the sudden application of velocity to the abducted forearm. Journal of Physiology, 127, 23P–25P. Hasegawa, Y., Kasai, T., Tsuji, T., & Yahagi, S. (2001). Further insight into the task-dependent excitability of motor evoked potentials in first dorsal interosseous muscle in humans. Experimental Brain Research, 140, 387–396. Hiraoka, K., Ae, M., Ogura, N., Komuratani, S., Sano, C., Shiomi, K., ... Yokoyama, H. (2014). Smooth pursuit eye movement preferentially facilitates motorevoked potential elicited by anterior-posterior current in the brain. NeuroReport, 25, 279–283. Iida, T., Komiyama, O., Obara, R., Baad-Hansen, L., Kawara, M., & Svensson, P. (2014). Repeated clenching causes plasticity in corticomotor control of jaw muscles. European Journal of Oral Sciences, 122, 42–48. Johansson, R. S., Lemon, R. N., & Westling, G. (1994). Time-varying enhancement of human cortical excitability mediated by cutaneous inputs during precision grip. Journal of Physiology, 481(Pt 3), 761–775. Kasai, T., Kawanishi, M., & Yahagi, S. (1998). Posture-dependent modulation of reciprocal inhibition upon initiation of ankle dorsiflexion in man. Brain Research, 792, 159–163. Kourtis, D., Kwok, H. F., Roach, N., Wing, A. M., & Praamstra, P. (2008). Maintaining grip: Anticipatory and reactive EEG responses to load perturbations. Journal of Neurophysiology, 99, 545–553. Lee, R. G., & Tatton, W. G. (1982). Long latency reflexes to imposed displacements of the human wrist: Dependence on duration of movement. Experimental Brain Research, 45, 207–216. Lewis, G. N., MacKinnon, C. D., & Perreault, E. J. (2006). The effect of task instruction on the excitability of spinal and supraspinal reflex pathways projecting to the biceps muscle. Experimental Brain Research, 174, 413–425. Lewis, G. N., Polych, M. A., & Byblow, W. D. (2004). Proposed cortical and sub-cortical contributions to the long-latency stretch reflex in the forearm. Experimental Brain Research, 156, 72–79. Loo, C. K., & McCloskey, D. I. (1985). Effects of prior instruction and anaesthesia on long-latency responses to stretch in the long flexor of the human thumb. Journal of Physiology, 365, 285–296. Macefield, V. G., Rothwell, J. C., & Day, B. L. (1996). The contribution of transcortical pathways to long-latency stretch and tactile reflexes in human hand muscles. Experimental Brain Research, 108, 147–154. MacKinnon, C. D., Verrier, M. C., & Tatton, W. G. (2000). Motor cortical potentials precede long-latency EMG activity evoked by imposed displacements of the human wrist. Experimental Brain Research, 131, 477–490. Manning, C. D., Tolhurst, S. A., & Bawa, P. (2012). Proprioceptive reaction times and long-latency reflexes in humans. Experimental Brain Research, 221, 155–166. Matthews, P. B. (1991). The human stretch reflex and the motor cortex. Trends in Neurosciences, 14, 87–91. Meziane, H. B., Spieser, L., Pailhous, J., & Bonnard, M. (2009). Corticospinal control of wrist muscles during expectation of a motor perturbation: A transcranial magnetic stimulation study. Behavioural Brain Research, 198, 459–465. Mutha, P. K., Boulinguez, P., & Sainburg, R. L. (2008). Visual modulation of proprioceptive reflexes during movement. Brain Research, 1246, 54–69. Oldfield, R. C. (1971). The assessment and analysis of handedness: The Edinburgh inventory. Neuropsychologia, 9, 97–113. Palmer, E., & Ashby, P. (1992). Evidence that a long latency stretch reflex in humans is transcortical. Journal of Physiology, 449, 429–440. Tanji, J., & Evarts, E. V. (1976). Anticipatory activity of motor cortex neurons in relation to direction of an intended movement. Journal of Neurophysiology, 39, 1062–1068. van Elswijk, G., Schot, W. D., Stegeman, D. F., & Overeem, S. (2008). Changes in corticospinal excitability and the direction of evoked movements during motor preparation: A TMS study. BMC Neuroscience, 9, 51. Yamamoto, C., & Ohtsuki, T. (1989). Modulation of stretch reflex by anticipation of the stimulus through visual information. Experimental Brain Research, 77, 12–22.