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1Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico; and 2Neuroscience Program and Biomedical Engineering Laboratory, Escola Politécnica, University of São Paulo, São Paulo, Brazil
Submitted 13 May 2005; accepted in final form 6 July 2005
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ABSTRACT |
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INTRODUCTION |
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The observation that stretch reflexes are highly variable was first reported by Sherrington (1906)
. Further work demonstrated that ipsilateral spinal monosynaptic reflexes (MSRs) produced by constant afferent stimuli exhibit considerable variations in size (Hunt 1955; Lloyd and McIntyre 1955; Somjen and Heath 1966). Rall and Hunt (1956) differentiated a linearly correlated from an uncorrelated component of this variability, showing that the firing probability of individual motoneurons within a population during MSR was only partly correlated with the population response amplitude. These authors suggested that postsynaptic background drive was the main source of both the correlated and uncorrelated fluctuations that they observed. In other studies, the origin of this variability has been attributed to excitability fluctuations within the motor pool, which are introduced either pre- and/or postsynaptically (Chang et al. 1994; Gossard et al. 1994; Rudomin and Dutton 1967, 1969a,b; Rudomin and Madrid 1972; Rudomin et al. 1969). Recently, Manjarrez et al. (2000) demonstrated that in cats there is a high correlation between amplitude fluctuations of ipsilateral MSRs and amplitude fluctuations of ipsilateral negative spontaneous cord dorsum potentials (nSCDPs), thus suggesting that the main cause for the ipsilateral MSR fluctuations was the variable activity of ipsilateral dorsal horn neurons. All of these investigations using conditioning by spontaneous potentials or by afferent volleys into the spinal cord have been restricted to ipsilateral actions. Furthermore, there is an absence of information about the possible interconnection between bilateral dorsal horn spinal neurons with spontaneous activity and their common influence on the amplitude of bilateral MSRs elicited by simultaneous trains of stimuli applied on ipsilateral and contralateral Ia muscle afferents. Some recent studies (Butt and Kiehn 2003; Edgley et al. 2003), about the functional identification of neurons responsible for left–right coordination of hindlimbs or the crossed reflexes from group II afferents, support this possibility.
The idea that bilateral spinal mechanisms can regulate movements was first introduced by Sherrington (1910), and the existence of a bilateral coordination in man is well documented (Swinnen and Duysens 2004). For example, during stance, unilateral displacements of one leg produce a bilateral response with similar latencies on both sides (Dietz et al. 1989). In other studies, alternate leg movement amplifies locomotor-like muscle activity in spinal cord–injured persons (Kawashima et al. 2005).
The present work is a counterpart of experiments done in awake humans by Mezzarane and Kohn (2002). They studied the correlation between H-reflex amplitudes recorded bilaterally to simultaneous stimulation of the right and left tibial nerves. The experiments showed that for 50% of the subjects there was a statistically significant correlation between the H-reflex amplitudes recorded bilaterally. This finding indicates that, in 50% of the cases, H-reflex–amplitude variations tend to fluctuate synchronously in both legs. Mezzarane and Kohn (2002) also reported the case in which a subject changed from a nonflat (synchronous fluctuations) to a flat (absence of synchronous fluctuations) cross-covariance between bilateral H-reflexes on the second day of recording. However, because experiments in humans offer certain limitations, no experimental evidence was provided about the sources modulating the synchronous fluctuations of such bilateral H-reflexes.
The purpose of the present research was to extend the study of Mezzarane and Kohn (2002) to examine the correlation between the amplitude of the bilaterally synchronous nSCDPs and the amplitude of the bilateral MSRs in cats. Analysis of this correlation, before and after spinal sections, could be important to identify the sources contributing to this synchrony. Mechanisms that correlate random fluctuations in the activity of spinal neurons may prove to be significant to our understanding of the organization of spinal circuits and of motor control (Newell and Corcos 1993). The present study also could be important to uncover the sources of the high variability of MSRs, which usually affect the performance of intraoperative monitoring during selective partial dorsal rhizotomy (Barolat 1991; Rivera et al. 1994; Weiss and Schiff 1993).
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METHODS |
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Experiments were carried out around noon in 17 adult cats (weight range, 2.4–3.8 kg) initially anesthetized with pentobarbitone (35 mg/kg of weight, intraperitoneally). The blood pressure was monitored through the carotid artery. The left radial vein was also cannulated to administer additional doses (10 mg/kg, intravenously) of pentobarbital to maintain (after induction) the animals in deep anesthesia. At the end of the experiment each animal was killed with an overdose of pentobarbital. Guidelines contained in National Institutes of Health Guide for the Care and Use of Laboratory Animals (85–23, revised in 1985) were strictly followed.
The lumbosacral and low thoracic spinal segments were exposed and the dura mater was removed. After the surgical procedures, the animal was mounted in a stereotaxic apparatus using spinal and pelvic clamps. The left and right ventral roots L5–S2 were dissected and sectioned. Pools were formed with the skin around the exposed tissues, filled with mineral oil (after placement of the electrodes) and maintained at a constant temperature (37°C). Adequacy of anesthesia was assessed by verifying that the pupils were constricted, and that blood pressure was stable (usually between 100 and 120 mmHg). The animals were paralyzed with pancuronium bromide (Pavulon, Organon) and artificially ventilated.
Stimulation
Left and right gastrocnemius plus soleus (GS) or posterior biceps and semitendinosus (PBSt) nerves were stimulated with single pulses of approximately 1.2–1.4 times the threshold level (xT) of the afferent volleys recorded on the surface of the spinal cord. The frequency of stimulation was adjusted to 0.5 Hz. We used TTL (transistor–transistor logic) pulses and a Master-8 system to produce simultaneous pulses of stimulation as illustrated in Fig. 1G. The stimulus intensity was adjusted to evoke MSRs that were between 20 and 30% of the maximal ventral root discharge because it is known that the susceptibility of the reflex to facilitation and to inhibition depends on its size (Crone et al. 1990). We adjusted the intensity of the stimulus as necessary to keep equivalent mean MSR sizes after different spinal sections. We excluded experiments in which the spinalization abolished the bilateral MSRs.
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We recorded bilateral monosynaptic reflexes simultaneously from the central ends of the sectioned L7 (or L6) ventral roots (Fig. 1. G—I and J–K). We observed that when the stimulus was applied on only one nerve no monosynaptic reflexes were evoked on the contralateral ventral root (Fig. 1, A–F). These observations imply that muscle spindle afferents do not activate contralateral motoneurons (Harrison and Zytnicki 1984), thus indicating that there are no crossed reflexes. In our experiments, we simultaneously applied the electrical stimuli (see Fig. 1G) to avoid bilateral interactions. We observed that the afferent volleys from the two sides arrived at the cord simultaneously. We verified that MSRs on each side of the spinal cord were evoked simultaneously (i.e., the time interval between left and right MSRs was 0 ms). The MSR size was expressed as a percentage of the maximal ventral root discharge. The size of the MSR was continually monitored during the course of an experiment to assess stability of stimulation and recording conditions.
Bilateral evoked afferent volleys were recorded at lumbar segment L6 by means of two silver ball electrodes placed on the cord dorsum against an indifferent electrode inserted in the back muscles. Low-noise, high-gain differential amplifiers (Grass model P511) were used to amplify the potentials.
In other series of experiments, nSCDPs were monopolarly recorded on a Synamps electroencephalographic (EEG) amplifier (NeuroScan, Sterling, VA) using a system of 30 Ag–AgCl electrodes (diameter 200 µm) positioned on the surface of the lumbar L5–L7 spinal cord (Fig. 5A) against an indifferent electrode placed on the paravertebral muscles. The distance between electrodes was 5 mm along the rostrocaudal axis and 1.5 mm along the mediolateral direction. Topographic maps were created using Scan 4.2 Software from NeuroScan. We simultaneously recorded nSCDPs (band-pass 0.15–70 Hz) and bilateral monosynaptic reflexes (Fig. 5A) with a sampling rate of 10 kHz.
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We used a window discriminator to select nSCDPs from electrode 12, or electrode 20, from the system of multielectrodes illustrated in Fig. 5A. Channel 12 was located on the left side of the spinal cord, whereas channel 20 was positioned on the right side of the spinal cord (Fig. 5). We selected these electrodes (12 and 20) because in the regions in which they are positioned we have observed the largest bilateral nSCDPs (Manjarrez et al. 2002, 2003). The trigger output pulses from the window discriminator were used to produce single trigger pulses only when the maximum amplitude of the left or right nSCDPs occurred. These trigger pulses were used to apply simultaneous stimulation to the left and right GS nerves. The trigger output pulses also were used to synchronize the averaging of the evoked bilateral MSRs, as is illustrated in Fig. 1, G–I and J–K.
Figure 5 shows bilateral GS monosynaptic reflexes preceded at a fixed time interval by nSCDPs (black arrow). The red arrow in Fig. 5A illustrates the time at which the stimuli to the left and right GS (1.4 x T) nerves were applied. Note that these stimuli were applied 2 ms after the occurrence of one nSCDP recorded by channel 12 of the multielectrode system. With this protocol, we examined the interaction between negative nSCDPs and bilateral GS-evoked MSRs ("nSCDP + MSR"). We demonstrated that the spontaneous potentials (the nSCDPs) were not a single event detected (by volume conduction) on both sides of the spinal cord (see maps in Fig. 6, E and G).
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We measured peak amplitudes of the nSCDPs using Neuroscan software and the peak amplitudes of the monosynaptic reflexes using Axoscope software (Axon Instruments). The procedure used in the cross-covariance (CCV) analysis of bilateral reflexes was similar to that used in Mezzarane and Kohn (2002) and is briefly described here.
The CCV measures the correlation between a sample of the first signal and a sample of the other signal occurring with a lag K away from the first. If both signals were generated independently, then the CCV will be zero for all K lag values. If the two signals have a common source of variability, then there will be a peak in the CCV at lag K = 0. If one signal is a delayed version of the other, the CCV will have a peak at a lag equal to the delay. Each time series of MSR amplitudes was detrended by subtraction of the best straight line fit.
Before computing the CCV sequence each MSR time series was whitened by an inverse filtering. This whitening is necessary because spurious peaks may appear in a cross-covariance even if the two signals are independent (Brockwell and Davis 1991). After the two signals were whitened a confidence interval (CI) was used to evaluate the significance of any peak in the CCV of the whitened signals (Brockwell and Davis 1991). A 95% CI given by ±1.96/N1/2, where N is the number of reflex responses, was used in the lag range between –100 and +100 s. The whitening was achieved by passing each signal through an inverse filter whose coefficients were obtained from an autoregressive model fitted to the signal (Rangayyan 2002). CCV samples out of the CI would suggest a correlation between the two series of monosynaptic-reflex amplitudes at the corresponding lags. The same algorithms described above were used to compute the CCV between continuous recordings of bilateral nSCDPs (Fig. 1, L–M).
In the series of experiments illustrated in Fig. 6, we normalized the data as in a previous study (Manjarrez et al. 2000). Data in the horizontal axis were normalized with respect to the amplitude of the largest averaged nSCDPs in each particular series. The MSR amplitudes in the vertical axis were expressed as a percentage of control (100%). Then the Spearman's rank correlation method was used to test for significant correlations [P < 0.001, 22 degrees of freedom (df)]. Every point in Fig. 6, B, D, F, and H was obtained from the averaging of 32 samples.
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RESULTS |
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The results presented in this section were derived from 12 cats in which a peak at zero lag in the cross-covariance between bilateral MSRs was observed. In 10 animals the bilateral MSRs were evoked by stimulation to the GS nerves, and in two others the MSRs were evoked by stimulation to the PBSt nerves. Figure 2 illustrates the results obtained from one experiment. We simultaneously applied 2,000 successive stimuli (1.2 x T) of 100 µs with time intervals of 2 s (0.5 Hz) to the left and right PBSt nerves. The duration of continuous recordings of bilateral MSRs was 1.11 h. Figure 1K shows three successive pairs of bilateral L7-MSRs. Figure 2A shows the time course (from 3,000 to 4,000 s) of the bilateral MSR fluctuations obtained from the same experiment. Figure 2B represents a zoom of the graph 2A from 3,800 to 4,000 s of recording. The dots represent the amplitudes of successive bilateral MSRs. It is clear that left and right MSR amplitudes have a high tendency to fluctuate in a synchronized form. Figure 2C shows a graph for the left versus right MSR amplitudes. We obtained a correlation coefficient of 0.8, which also suggests that the MSRs evoked in the left and right ventral roots have a high degree of correlation in their fluctuations.
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Is there a link between MSR size and CCV peak? Figure 2E shows a graph of the MSR amplitude versus CCV peak for 12 different experiments. We did not observe evidence of a linear relation between the MSR size and the CCV peak at zero lag obtained from bilateral MSR (correlation coefficient = 0.1).
Analysis of cross-correlation from long-time series of bilateral monosynaptic reflexes
The results presented in this section were derived from four cats in which long-duration recordings (
8 h) of bilateral MSRs (evoked by stimulation to the left and right GS nerves) were obtained. Figure 3 shows sets of four graphs (MSR amplitude, MSR–CCV peak at zero lag vs. time, nSCDP amplitude, and nSCDP–CCV peak at zero lag vs. time) for each one of the cats. Each symbol represents the corresponding measurements computed from time series of 500 bilateral MSRs. To avoid fatigue after every sequence of 500 MSRs the stimulus train was not applied during a time interval of 5 min.
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5 h). In contrast, the MSR–CCV tends to remain for shorter time intervals (<1 h, or <30 min) inside the confidence interval. Figure 3, I–L shows the corresponding changes in amplitude of the nSCDPs. These bilateral nSCDPs exhibited CCV peaks at zero lag >0.4 (Fig. 3, M–P). No transitory changes in the nSCDP–CCV were observed as in the MSR–CCV. Effects of spinalization and longitudinal bisection on the amplitude and synchrony of bilateral monosynaptic reflexes and bilateral negative spontaneous cord dorsum potentials
In five other cats, we simultaneously recorded bilateral MSRs and bilateral nSCDPs. We analyzed the changes in: the peak amplitude of the CCV between bilateral MSRs, the peak amplitude of the CCV between bilateral nSCDPs, and the amplitude of the MSRs and nSCDPs after spinalization (at L1) and longitudinal bisection (from L1 to S2 segments). Theintegrity of the spinal cord caudal to the transection (L1) was monitored (on the basis of the size of MSRs and nSCDPs). We have included experiments in which the amplitudes of the MSRs were depressed <40% with respect to control and exhibited a clear stability in their fluctuations. In cases where the MSR amplitude was depressed after spinalization the stimulus intensity was adjusted to evoke an equivalent MSR response to that of the control MSR.
Figure 4, A, D, and G illustrates MSR–CCV graphs obtained from one cat. Note that the peak amplitude of the MSR–CCV peak was not significantly altered after the spinalization (Fig. 4D). However, the MSR–CCV peak was abolished after a subsequent longitudinal bisection from the L1 to S2 segments (Fig. 4G). Similar results were obtained in four other cats (control, spinalization, and subsequent longitudinal bisection). Figure 4, B, E, and H shows the mean amplitude of the bilateral MSR for the five cats in the conditions indicated above. Figure 4, C, F, and I shows the mean changes in the corresponding MSR–CCV peaks for the same five animals. After the spinalization the mean MSR–CCV peaks for bilateral MSRs weresimilar in both conditions (control and spinalization) (Fig. 4, C and F). However, after a subsequent longitudinal bisection the mean MSR–CCV peak was abolished (Fig. 4I).
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Correlation between the amplitude of bilateral nSCDPs and the amplitude of nSCDP-conditioned bilateral MSRs
We obtained simultaneous recordings of the nSCDPs and of the bilateral GS–MSRs. Figure 5A shows the recordings of the nSCDPs (electrodes 1 to 30) and of the left and right MSRs (electrodes 31 and 32, respectively). With the method of conditioned stimulation shown in Fig. 5 (see details in METHODS), we examined the effects of different bilateral nSCDP amplitudes (five different amplitudes) on bilateral MSRs. Figure 6 shows the results obtained from four cats in three different conditions (control, spinalization, and longitudinal bisection) and in two different types of nSCDP-triggered averaging (left nSCDP or right nSCDP).
Figure 6A shows averages from n = 32 samples of the nSCDP-conditioned bilateral nSCDPs (top traces) and of the corresponding nSCDP-conditioned bilateral MSRs (bottom traces), obtained from one animal in control conditions. The white circle on the map of Fig. 6A indicates the electrode from which the left nSCDPs were recorded and used to trigger the averaging of the bilateral nSCDPs and MSRs. Bilateral MSRs were produced by stimulation to the GS nerve 2 ms after the peak of the left nSCDPs, as described in Fig. 5. The map in Fig. 6A illustrates the topographic distribution of the averaged nSCDPs. Figure 6B (left) shows superimposed graphs of amplitude of the nSCDP-conditioned left MSRs versus the amplitude of the left nSCDPs [Spearman's rank correlation coefficient (rs), rs = 0.9, P < 0.001, t = 9.7 with 22 df] in control conditions for four animals. Note that the larger the left nSCDP amplitude, the larger was the nSCDP-conditioned left MSR amplitude (i.e., the corresponding time-locked MSR). Figure 6B (right), shows superimposed graphs of amplitude of the nSCDP-conditioned right MSRs versus the amplitude of the left nSCDPs (rs = 0.7, P < 0.001, t = 5.4 with 22 df) in control conditions for the same four animals. Similar correlations were found after spinalization [rs = 0.9, P < 0.001, t = 16.4 and rs = 0.9, P < 0.001, t = 9.9, with 22 df; Fig. 6, D (left) and D (right), respectively]. However, after the complete longitudinal bisection (from L1 to S2 segments) the larger the left nSCDP amplitude, the larger was the nSCDP-conditioned left MSR amplitude, but not the nSCDP-conditioned right MSR amplitude [rs = 0.8, P < 0.001, t = 9.4 and rs = –0.2, P = 0.3, t = –1.0, with 22 df; Fig. 6, F (left) and F (right), respectively]. In contrast, when the right nSCDPs were used to trigger the averaging we observed the opposite effect [rs = –0.1, P = 0.4, t = –0.7 and rs = 0.8, P < 0.001, t = 9.2, with 22 df; Fig. 6, H (left) and H (right), respectively]. Figure 6, F and H, suggests that after the longitudinal bisection the dorsal horn neurons producing nSCDPs were separated on both sides of the spinal cord to act independently on left and right monosynaptic reflex pathways. These observations were consistent for the same four animals and indicate that in control conditions bilateral fluctuations of nSCDPs are correlated with the fluctuations of bilateral MSRs.
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DISCUSSION |
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the studies about the origin of variability of monosynaptic reflexes have been restricted to ipsilateral actions. Here we show that such studies should consider the bilateral actions from spinal sources. Synchronous fluctuations of bilateral MSRs in humans and cats
The present work is a counterpart of previous experiments done in awake humans (Mezzarane and Kohn 2002). The approach was to study the correlation between H-reflex amplitudes recorded bilaterally to simultaneous stimulation of the right and left tibial nerves.
In the present study, we observed that bilateral MSRs exhibit "spontaneous" transient changes in the amplitude of the MSR–CCV peak at zero lag. Figure 3, E–H shows this phenomenon: the MSR amplitudes on the two sides covary during long periods, but in shorter intervals the MSR amplitudes from the two sides seem to vary independently of each other.
The results illustrated in Fig. 3, E–H are consistent with the observations of Mezzarane and Kohn (2002), who reported the case in which a subject changed from a nonflat (synchronous fluctuations) to a flat cross-covariance on the second day of experiment. Further work in cats and humans will be necessary to understand the mechanisms involved in the activation or deactivation of the sources producing the synchronous fluctuations of bilateral MSRs.
Because all the experiments started at noon, the potential effects of circadian rhythms on the degree of synchrony between bilateral MSRs were minimized (Chen et al. 2002).
Spinal sources contributing to the synchronous fluctuations of bilateral MSRs
It has been established that there is a strong functional link between sensory neural circuits on the two sides of the spinal cord. Recently Petko et al. (2004) provided a morphological confirmation of this functional phenomenon, presenting evidence for the presence of a direct commissural connection between the lateral aspects of the dorsal horn on the two sides of the lumbar spinal cord of the rat. These authors found that the cells of origin of commissural fibers in the lateral aspect of the dorsal horn were confined to laminae III–IV and projected to the corresponding area of the contralateral gray matter. Most of the commissural axon terminals established synaptic contacts with dendrites. They demonstrated that there is a substantial reciprocal commissural synaptic interaction between the lateral aspects of laminae III–IV on the two sides of the lumbar spinal cord and that this pathway may transmit both inhibitory and excitatory signals to their postsynaptic targets. Because dorsal horn neurons producing the nSCDPs are located within laminae III–VI of the lumbar spinal cord (Manjarrez et al. 2000), we suggest that the neurons described by Petko et al. (2004) are probably a subset of the neurons responsible for the production of nSCDPs.
The results obtained in Garcia et al. (2004) suggest the existence of a system of spontaneously active dorsal horn neurons that is bilaterally distributed along the lumbosacral segments (Manjarrez et al. 2002, 2003; Vazquez et al. 2004) that affects, in a synchronized manner, impulse transmission in the spinal cord. However, in the study performed in Garcia et al. (2004) no evidence was provided about the influence of bilateral dorsal horn neurons producing nSCDPs on bilateral MSRs. Here we show (Fig. 6) that MSRs recorded on either side of the spinal cord are correlated with left nSCDPs until a longitudinal bisection is made.
Figure 6, E–H extends the findings of Manjarrez et al. (2000) by showing that after spinalization and longitudinal bisection separated groups of neurons on both sides of the spinal cord can exert an independent modulation in the amplitude of MSRs.
Based on the evidence that MSR fluctuations at a given ventral root are generated in part by the spontaneous activity of lamina III–VI ipsilateral dorsal horn neurons (Manjarrez et al. 2000), and on the results of our spinalization and longitudinal bisection experiments (Fig. 4), we suggest that bilaterally interconnected dorsal horn neurons contribute in part to the synchrony of the bilateral fluctuations of MSRs. This is what should be expected on the basis of early anatomical observations of Ramon y Cajal (1909), who found that in the dog spinal cord there are posterior commissural neurons located in bilateral zones of the dorsal horn.
The results illustrated in Fig. 6 also provide support to the hypothesis that dorsal horn neurons producing nSCDPs are involved in the synchronous fluctuations of bilateral MSRs. We suggest that if bilaterally situated dorsal horn neurons (lamina III–VI) mutually excite or inhibit each other by crossing axons, then this could be a source contributing to the bilateral reflex covariance in cats and humans. However, based on the evidence that there are also anterior commissural neurons (Jankowska et al. 2003) in the spinal cord, these could also contribute to the correlated fluctuations of bilateral MSRs.
The idea that other possible unilateral sources could contribute to the fluctuations of the corresponding ipsilateral MSRs but not to the correlation between bilateral MSRs is justified by the evidence that there is a spontaneous activation of groups of neurons in different zones of the spinal cord (Vazquez et al. 2004); however, it is not as frequent (or as potent) as the synchronous nSCDPs occurring in bilateral zones of the spinal cord. We suggest that such unilateral spontaneous activation of dorsal horn neurons in different zones of the spinal cord contribute to the fluctuations of MSRs but not to the correlations of bilateral MSRs.
Other possible sources of common random inputs to both sides of the spinal cord in the intact animal and in humans are the supraspinal centers and the long propriospinal systems above the L1 segment. These possibilities also merit a discussion in this paper.
Propriospinal centers could contribute to the synchronous fluctuations of bilateral MSRs
The propriospinal interneuron system with its cells in the gray matter and its axons in the white matter of the spinal cord conduct activity between different spinal cord segments. This system—together with mono- and oligosynaptic reflex arcs and polysynaptic pathways—participates continuously in the generation of spinal cord reflex output activating muscles. There is some evidence that suggests that a long propriospinal system could act on lumbosacral neurons (Jankowska et al. 1974), which could then contribute to the synchronous fluctuations of bilateral MSRs. Bolton et al. (1991) identified commissural neurons projecting to the contralateral ventral horn of the cat upper cervical spinal cord. Furthermore, Jankowska et al. (1983) demonstrated that propriospinal neurons originating in the forelimb segments have direct excitatory connections with interneurons of Ib reflex pathways to hindlimb motoneurons. Recently Krutki and Mrowczynski (2004) showed a bilateral projection of cervical propriospinal neurons to sacral segments of the cat spinal cord. They suggested that cervical neurons transmit information to motor centers controlling hindlimb muscles, forming a part of the system contributing to the process of coordination of movements of forelimbs and hindlimbs. This putative link could cause correlations between forelimb and hindlimb MSRs as well as between forelimb MSRs. It is tempting to suggest that in some motor tasks bilateral MSRs of hindlimbs may be synchronized with bilateral MSRs of forelimbs, with the participation of propriospinal systems and of dorsal horn neurons that produce bilateral nSCDPs.
In humans there are corticospinal projections to lower limb motoneurons (Brouwer and Ashby 1992). Additionally, there are also indirect corticospinal connections by propriospinal neuronal circuits (Dietz 2004; Pierrot-Deseilligny 1996). For example, the interlimb coordination during stance and gait is mediated by propriospinal neurons, which themselves are under supraspinal control (Dietz 2004).
At present, limited information is available regarding the anatomy of the propriospinal system in humans (Nathan et al. 1996). However, there are several electrophysiological studies suggesting the existence of propriospinal neurons in humans (Baldissera et al. 1998; Delwayde et al. 1977; Dimitrijevic et al. 2005; Faganel and Dimitrijevic 1982; Hiraoka and Nagata 1999; Meinck and Piesiur-Strehlow 1981; Zehr et al. 2001). Some of these studies have suggested that propriospinal neurons provide a linkage between cervical and lumbar neuronal circuits of the spinal cord that act in the interlimb coordination of leg and arm movements during human locomotor activities (Dietz 2004; for review see Swinnen and Duysens 2004). On the basis of these studies we suggest that a propriospinal system could also constitute another important source for the bilateral MSR fluctuations.
Supraspinal centers could contribute to the synchronous fluctuations of bilateral MSRs
We suggest that either there are common bilateral inputs originating from some nucleus, such as pontine reticular system (Matsuyama et al. 1999), or there is a correlation between bilaterally descending drives; or still, a specific descending drive acts on spinal interneurons that bilaterally influence the homonymous motoneuron pools. These possibilities receive some support from reports of reflex depression modulation by raphe nuclei stimulation in frogs (Cardona and Rudomin 1983). In this context, recently, Jankowska et al. (2003) demonstrated that although direct actions of reticulospinal fibers are much more potent on ipsilateral motoneurons, interneuronally mediated actions are as potent contralaterally as ipsilaterally, and midlumbar commissural neurons are likely to contribute to them. Such interneurons mediating crossed actions evoked from the reticular formation have been found in Rexed's lamina VIII. According to Jankowska et al. (2003), these are interneurons that are powerfully monosynaptically excited by stimuli on the reticular formation and project to contralateral motor nuclei through the anterior commissure. Therefore posterior and anterior commissural neurons could be potential spinal sources for the correlated variations of bilateral MSRs.
In humans, a report on spinal cord–injured subjects (Nozaki et al. 1996) showed a desynchronization between the H-reflex time series on the two sides, with the suggestion of a supraspinal origin for the correlation between two-sided H-reflexes in normal subjects. It is not clear whether their method (coherence analysis) was sensitive enough to detect spinally generated two-sided correlation, as we found in cats, or in spinal cord–injured humans some mechanism inhibits or decreases the effects of such spinally originated bilateral reflex variabilities.
It has been reported (Ellaway et al. 1998) that bilateral transcranial magnetic stimulation causes correlated variation in the bilaterally recorded upper limb muscle responses. These authors suggested the corticospinal pathways as possible sites for the fluctuations. However, Figs. 4 and 6 also suggest that the spinal cord is itself another important putative source of bilateral correlations. Further work will be necessary to determine the relative contributions of lumbar and propiospinal/supraspinal systems to these correlations.
Sensory inputs could affect correlations between bilateral MSRs
In humans and animals the afferent input plays a major role in shaping the interlimb coordination (for review see Dietz 2004; Duysens et al. 2004; Swinnen and Duysens 2004; Zehr and Duysens 2004). For example, during gait the interlimb coordination depends on sensory input, mainly from Ib afferents (Duysens et al. 2004).
Delwayde et al. (1977) reported that stretch reflexes in the lower limbs of humans can be affected by alterations in arm postures, thus suggesting that there may be "interlimb reflex" modulation with movement. In this context, Zehr et al. (2001) investigated directly the existence of "interlimb reflexes" in neurologically intact humans. Zehr et al. (2001) showed that electrical stimulation of a cutaneous nerve in the hand evoked large bilateral reflexes in the legs and contralateral arm. Their study supports the idea that interlimb reflex pathways connecting distant cutaneous receptive fields could be important to access relevant exteroceptive information for the reflex coordination of movement. We suggest that bilateral MSRs, in humans and cats, also could be modulated by the activation of such interlimb reflex pathways. In this context, it is tempting to propose that the CCV between bilateral MSRs in lower limbs could be affected by the simultaneous activation of a cutaneous receptive field on the upper limb of neurologically intact humans. A study of this kind in spinal cord–injured humans could be important to assess the degree of lesion of the proprioceptive system mediating the modulation of interlimb reflexes. Nevertheless, the extent to which the CCV between bilateral MSRs can be affected by the activation of a cutaneous receptive field of an upper limb in humans (and forelimb in cats) remains to be demonstrated in future research. This possibility is supported by recent studies (Frigon et al. 2004; Zehr et al. 2004) showing that there is an influence of cutaneous nerve stimulation from the upper limb on transmission through the soleus H-reflex pathway in the leg during static contractions and during rhythmic arm movements.
Another issue that may be important to examine is the analysis of the CCV and autocovariance of the amplitudes of bilateral interlimb reflexes elicited by cutaneous stimulation of an upper limb. It is probable that in such bilateral interlimb reflexes the dorsal horn spinal neurons (producing the nSCDPs) also contribute to the bilateral correlations.
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GRANTS |
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FOOTNOTES |
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Address for reprint requests and other correspondence: E. Manjarrez, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla., 14 sur 6301, Col. San Manuel, Apartado Postal 406, C.P. 72570, Puebla, Pue., México (E-mail: emanjar{at}siu.buap.mx)
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REFERENCES |
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Barolat G. Dorsal selective rhizotomy through a limited exposure of the cauda equina at L-1. J Neurosurg 75: 804–807, 1991.[Web of Science][Medline]
Bolton PS, Goto T, and Wilson VJ. Commissural neurons in the cat upper cervical spinal cord. Neuroreport 2: 743–746, 1991.[Web of Science][Medline]
Brockwell PJ and Davis RA. Time Series: Theory and Models. New York: Springer-Verlag, 1991.
Brouwer B and Ashby P. Corticospinal projections to lower limb motoneurons in man. Exp Brain Res 89: 649–654, 1992.[Web of Science][Medline]
Butt SJ and Kiehn O. Functional identification of interneurons responsible for the left-rght coordination of hindlimbs in mammals. Neuron 38: 953–963, 2003.[CrossRef][Web of Science][Medline]
Cardona A and Rudomin P. Activation of brainstem serotoninergic pathways decreases homosynaptic depression of monosynaptic responses of frog spinal motoneurones. Brain Res 280: 373–378, 1983.[CrossRef][Web of Science][Medline]
Chang T, Schiff SJ, Sauer T, Gossard JP, and Burke RE. Stochastic versus deterministic variability in simple neuronal circuits: I. Monosynaptic spinal cord reflexes. Biophys J 67: 671–683, 1994.[Web of Science][Medline]
Chen XY, Chen L, Wolpaw JR, and Jakeman LB. Corticospinal tract transection reduces H-reflex circadian rhythm in rats. Brain Res 942: 101–108, 2002.[CrossRef][Web of Science][Medline]
Crone C, Hultborn H, Mazieres L, Morin C, Nielsen J, and Pierrot-Deseilligny E. Sensitivity of monosynaptic test reflexes to facilitation and inhibition as a function of the test reflex size: a study in man and the cat. Exp Brain Res 81: 35–45, 1990.[Web of Science][Medline]
Delwayde PJ, Figiel C, and Richelle C. Effects of postural changes of the upper limb on reflex transmission in the lower limb. Cervicolumbar reflex interactions in man. J Neurol Neurosurg Psychiatry 40: 616–621, 1977.
Dietz V. Spinal networks involved in interlimb co-ordination and reflex regulation of locomotion. In: Neuro-Behavioral Determinants of Interlimb Coordination. A Multidisciplinary Approach, edited by Swinnen SP and Duysens J. Norwell, MA: Kluwer Academic, 2004, p. 92–108.
Dietz V, Horstmann GA, and Berger W. Interlimb coordination of leg-muscle activation during perturbation of stance in humans. J Neurophysiol 62: 680–693, 1989.
Dimitrijevic MR, Persy I, Forstner C, Kern H, and Dimitrijevic MM. Motor control in the human spinal cord. Artif Organs 29: 216–219, 2005.[CrossRef][Web of Science][Medline]
Duysens J, Donker S, Verscueren SMP, Smits-Engelsman BCM, and Swinnen SP. Sensory influences on interlimb coordination during gait. In: Neuro-Behavioral Determinants of Interlimb Coordination. A Multidisciplinary Approach, edited by Swinnen SP and Duysens J. Norwell, MA: Kluwer Academic, 2004, p. 3–33.
Edgley SA, Jankowska E, Krutki P, and Hammar I. Both dorsal horn and lamina VIII interneurones contribute to crossed reflexes from feline group II muscle afferents. J Physiol 552: 961–974, 2003.
Ellaway PH, Davey NJ, Maskill DW, Rawlinson SR, Lewis HS, and Anissimova NP. Variability in the amplitude of skeletal muscle responses to magnetic stimulation of the motor cortex in man. Electroencephalogr Clin Neurophysiol 109: 104–113, 1998.[CrossRef][Medline]
Faganel J and Dimitrijevic MR. Study of propriospinal interneuron system in man. Cutaneous exteroceptive conditioning of stretch reflexes. J Neurol Sci 56: 155–172, 1982.[CrossRef][Web of Science][Medline]
Frigon A, Collins DF, and Zehr EP. Effect of rhythmic arm movement on reflexes in the legs: modulation of soleus H-reflexes and somatosensory conditioning. J Neurophysiol 91: 1516–1523, 2004.
Garcia CA, Chavez D, Jimenez I, and Rudomin P. Effects of spinal and peripheral nerve lesions on the intersegmental synchronization of the spontaneous activity of dorsal horn neurons in the cat lumbosacral spinal cord. Neurosci Lett 361: 102–105, 2004.[CrossRef][Web of Science][Medline]
Gossard JP, Floeter MK, Kawai Y, Burke RE, Chang T, and Schiff SJ. Fluctuations of excitability in the monosynaptic reflex pathway to lumbar motoneurons in the cat. J Neurophysiol 72: 1227–1239, 1994.
Harrison PJ and Zytnicki D. Crossed actions of group I muscle afferents in the cat. J Physiol 356: 263–273, 1984.
Hiraoka K and Nagata A. Modulation of the soleus H reflex with different velocities of passive movement of the arm. Electromyogr Clin Neurophysiol 39: 21–26, 1999.[Medline]
Hunt CC. Temporal fluctuation in excitability of spinal motoneurons and its influence on monosynaptic reflex response. J Gen Physiol 38: 801–811, 1955.
Jankowska E, Hammar I, Slawinska U, Maleszak K, and Edgley SA. Neuronal basis of crossed actions from the reticular formation on feline hidlimb motoneurons. J Neurosci 23: 1867–1878, 2003.
Jankowska E, Lundberg A, Roberts WJ, and Stuart D. A long propriospinal system with direct effect on motoneurones and on interneurones in the cat lumbosacral cord. Exp Brain Res 21: 169–194, 1974.[Web of Science][Medline]
Jankowska E, Lundberg A, and Stuart D. Propriospinal control of interneurons in spinal reflex pathways from tendon organs in the cat. Brain Res 261: 317–320, 1983.[CrossRef][Web of Science][Medline]
Kawashima N, Nozaki D, Abe MO, Akai M, and Nakazawa K. Alternate leg movement amplifies locomotor-like muscle activity in spinal cord injured persons. J Neurophysiol 93: 777–785, 2005.
Krutki P and Mrowczynski W. Convergence of forelimb afferent actions on C7-Th1 propriospinal neurones bilaterally projecting to sacral segments of the cat spinal cord. Arch Ital Biol 142: 47–58, 2004.[Web of Science][Medline]
Lloyd DPC and McIntyre AK. Monosynaptic reflex responses of individual motoneurons. J Gen Physiol 38: 771–787, 1955.
Manjarrez E, Jimenez I, and Rudomin P. Intersegmental synchronization of spontaneous activity of dorsal horn neurons in the cat spinal cord. Exp Brain Res 148: 401–413, 2003.[Web of Science][Medline]
Manjarrez E, Perez H, Rojas-Piloni G, Velez D, Martinez L, and Flores A. Absence of coherence between cervical and lumbar spinal cord dorsal surface potentials in the anaesthetized cat. Neurosci Lett 328: 37–40, 2002.[CrossRef][Web of Science][Medline]
Manjarrez E, Rojas-Piloni G, Jimenez I, and Rudomin P. Modulation of synaptic transmission from segmental afferents by spontaneous activity of dorsal horn spinal neurones in the cat. J Physiol \?\529. 2: 445–460, 2000.
Matsuyama K, Mori F, Kuze B, and Mori S. Morphology of single pontine reticulospinal axons in the lumbar enlargement of the cat: a study using the anterograde tracer PHA-L. J Comp Neurol 410: 413–430, 1999.[CrossRef][Web of Science][Medline]
Meinck HM and Piesiur-Strehlow B. Reflexes evoked in leg muscles from arm afferents: a propriospinal pathway in man? Exp Brain Res 43: 78–86, 1981.[Web of Science][Medline]
Mezzarane RA and Kohn AF. Bilateral soleus H-reflexes in humans elicited by simultaneous trains of stimuli: symmetry, variability, and covariance. J Neurophysiol 87: 2074–2083, 2002.
Nathan PW, Smith M, and Deacon P. Vestibulospinal, reticulospinal and descending propriospinal nerve fibres in man. Brain 119: 1809–1833, 1996.
Newell KM and Corcos DM. Issues in variability and motor control. In: Variability and Motor Control, edited by Newell KM and Corcos DM. Champaign, IL: Human Kinetics, 1993.
Nozaki D, Nakazawa K, and Yamamoto Y. Supraspinal effects on the fractal correlation in human H-reflex. Exp Brain Res 112: 112–118, 1996.[Web of Science][Medline]
Petko M, Veress G, Vereb G, Storm-Mathisen J, and Antal M. Commissural propriospinal connections between the lateral aspects of laminae III–IV in the lumbar spinal cord of rats. J Comp Neurol 480: 364–377, 2004.[CrossRef][Web of Science][Medline]
Pierrot-Deseilligny E. Transmission of the cortical command for human voluntary movement through cervical propriospinal premotoneurones. Prog Neurobiol 48: 489–517, 1996.[CrossRef][Web of Science][Medline]
Rall W and Hunt CC. Analysis of reflex variability in terms of partially correlated excitability fluctuations in a population of motoneurons. J Gen Physiol 39: 397–422, 1956.
Ramon y Cajal S. Histologie du systeme nerveux de l'homme et des vertébrés. Paris: Maloine, 1909.
Rangayyan RM. Biomedical Signal Analysis. New York: IEEE Press–Wiley, 2002.
Rivera AD, Burke T, Schiff SJ, and Weiss IP. An experimental study of reflex variability in selective dorsal rhizotomy. J Neurosurg 81: 885–894, 1994.[Web of Science][Medline]
Rudomin P and Dutton H. Effects of presynaptic and postsynaptic inhibition on the variability of the monosynaptic reflex. Nature 216: 292–293, 1967.[CrossRef][Medline]
Rudomin P and Dutton H. Effects of conditioning afferent volleys on variability of monosynaptic responses of extensor motoneurons. J Neurophysiol 32: 140–157, 1969a.
Rudomin P and Dutton H. Effects of muscle and cutaneous afferent nerve volleys on excitability fluctuations of Ia terminals. J Neurophysiol 32: 158–169, 1969b.
Rudomin P, Dutton H, and Muñoz-Martinez J. Changes in correlation between monosynaptic reflexes produced by conditioning afferents volleys. J Neurophysiol 32: 759–772, 1969.
Rudomin P and Madrid J. Changes in correlation between monosynaptic responses of single motoneurons and information transmission produced by conditioning volleys to cutaneous nerves. J Neurophysiol 35: 44–64, 1972.
Sherrington C. The Integrative Action of the Nervous System. New York: Scribner's, 1906.
Sherrington C. Flexion reflex of the limb, crossed extension reflex and reflex stepping and standing. J Physiol 40: 28–121, 1910.
Somjen GG and Heath CJ. Covariation of monosynaptic reflexes in spinal and decerebrate cats. Exp Brain Res 15: 79–99, 1966.
Swinnen SP and Duysens J. Neuro-Behavioral Determinants of Interlimb Coordination. A Multidisciplinary Approach. Norwell, MA: Kluwer Academic, 2004.
Vazquez D, Rojas-Piloni G, Martinez L, Hernández-Paxtián Z, and Manjarrez E. Two-dimensional mapping of background neuronal activity in the cat spinal cord. Soc Neurosci Abstr 639: 14, 2004.
Walmsley B and Tracey DJ. The effect of transection and cold block of the spinal cord on synaptic transmission between Ia afferents and motoneurons. Neuroscience 9: 445–451, 1983.[CrossRef][Web of Science][Medline]
Weiss IP and Schiff SJ. Reflex variability in selective dorsal rhizotomy. J Neurosurg 79: 346–353, 1993.[Web of Science][Medline]
Zehr EP, Collins DF, and Chua R. Human interlimb reflexes evoked by electrical stimulation of cutaneous nerves innervating the hand and foot. Exp Brain Res 140: 495–504, 2001.[CrossRef][Web of Science][Medline]
Zehr EP and Duysens J. Regulation of arm and leg movement during human locomotion. Neuroscientist 10: 347–361, 2004.
Zehr EP, Frigon A, Hoogenboom N, and Collins DF. Facilitation of soleus H-reflex amplitude evoked by cutaneous nerve stimulation at the wrist is not suppressed by rhythmic arm movement. Exp Brain Res 159: 382–388, 2004.[CrossRef][Web of Science][Medline]
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