Department of Physiology and Biophysics and Regional Primate Research Center, University of Washington, Seattle, Washington 98195
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ABSTRACT |
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Maier, Marc A., Steve I. Perlmutter, and Eberhard E. Fetz. Response patterns and force relations of monkey spinal interneurons during active wrist movement. J. Neurophysiol. 80: 2495-2513, 1998. The activity of C6-T1 spinal cord neurons was recorded in three macaques while they generated isometric wrist flexion and extension torques in visually guided step-tracking tasks. Electromyographic activity (EMG) was recorded in 12 independent forearm muscles. Spike-triggered averages (STAs) of rectified and unrectified EMG were used to classify neurons into four groups. Motoneurons (MNs) had a clear postspike motor unit signature in the unrectified STA of one muscle. Premotor interneurons (PreM-INs) had postspike effects in at least one muscle, with onset latencies of
3.5 ms from the trigger. Synchrony interneurons (Sy-INs) were non-PreM-Ins that had spike-related features with latencies <3.5 ms in at least one muscle. Unidentified interneurons (U-INs) showed no features in any of the STAs. A total of 572 task-related spinal neurons were studied; 29 cells were MNs, 97 PreM-INs, 32 Sy-INs, and 414 U-INs. MNs were activated predominantly in a tonic fashion during the ramp-and-hold torques and were active in one direction only. The most common response pattern for interneurons, irrespective of their class, was phasic-tonic activity, followed by purely tonic and purely phasic activity. Most interneurons (77%) were bidirectionally active in both flexion and extension. For all classes of interneurons, units with phasic response components tended to be activated first, before torque onset, followed by tonic units. The onset times of PreM-INs relative to onsets of their target muscles were distributed broadly, with a mean of
25 ± 128 (SD) ms. For most neurons with tonic response components (all MNs, 71% of PreM-INs, 67% of Sy-INs, and 84% of U-INs), activity during the hold period was correlated significantly with the magnitude of static torque exerted by the monkey. The rate-torque regressions generally had positive slopes with higher mean slopes for extension than for flexion. The phasic response components were correlated significantly with rate of change of torque for a smaller percentage of tested PreM-Ins (50%), Sy-INs (83%), and U-INs (77%). In contrast to other premotor neurons [corticomotoneuronal (CM), rubromotoneuronal (RM), and dorsal root ganglion (DRG) afferents] previously characterized under similar conditions, a larger proportion of the spinal PreM-INs were activated after onset of their target muscles, probably reflecting a larger proportion of PreM-INs driven by peripheral input. The rate-torque slopes of PreM-INs tended to be less steep than those of CM and RM cells. Unlike the CM and DRG PreM afferents, which were activated unidirectionally, most spinal PreM-INs showed bidirectional activity, like RM cells.
A quantitative picture of the neural inputs driving primate forearm motoneurons during voluntary movement must include synaptic inputs from several groups of last-order neurons. In behaving animals, such premotor cells can be identified by postspike effects (PSEs) in spike-triggered averages (STAs) of muscle activity. This technique has elucidated the projections and response properties of premotor cells in primary motor cortex [corticomotoneuronal (CM) cells (Fetz and Cheney 1980 In three male macaques (2 Macaca nemestrina and 1 M. mulatta), we recorded the activity of single C6-T1 interneurons extracellularly with glass-coated tungsten microelectrodes. The surgery for implanting the recording chamber, the experimental setup, the behavioral paradigm, and the procedures for recording electromyographic activity (EMG) and for identifying PreM-INs are described in the companion paper (Perlmutter et al. 1998 Behavioral paradigm
The monkeys were trained to produce isometric ramp-and-hold flexion or extension torques of the wrist after step changes in a visual target. One animal, monkey W, was trained in the center-out task and the other two monkeys, B and R, in the alternating task (Perlmutter et al. 1998 Unit identification
Units were grouped into four classes according to features in their STAs (cf. Perlmutter et al. 1998 Response patterns
To identify the response patterns of spinal neurons during the ramp-and-hold task, we compiled averages separately for flexion and extension trials. In the center-out task, trials were aligned at onset of the torque ramps; in the alternating task, trials were aligned on the point of torque reversal (i.e., 0 torque at the transition from flexion to extension or vice versa). Unit histograms and torque trajectories were averaged separately for each of the six target levels for the center-out task and also across all flexion or extension trials. Response averages were compiled off-line with a binwidth of 80 ms per channel. Figures show torque in the flexion and extension directions as positive and negative deflections, respectively.
Onset estimation
Criteria for defining the onset of activity in response averages were formulated empirically on representative data and then applied consistently to all trials. In the center-out task, torque onset for each successful trial was calculated as the first bin in which the rate of change of torque was >0.8 Nm/s (smaller values were in the noise level during steady torque production) and torque rose continuously afterwards.
Relation to movement parameters
The relation between neuronal firing rate and torque was assessed from trial-by-trial data. For units with a tonic response component (i.e., a constant firing rate during the static hold), mean instantaneous firing rate (spikes/s) and mean torque (Nm) were calculated in the last second of the hold period of each trial (Fig. 1). A scatter plot of tonic firing rate versus static torque was displayed for all trials and linear Pearson correlation coefficients were calculated separately for flexion and extension. Torque sensitivity was measured by the rate-torque slope, i.e., the slope of the linear regression line in spikes/s/Nm. Rate-torque slopes were calculated for neurons that were recorded in
Database
Data were collected for 572 task-related spinal neurons: 409 from monkey W, 141 from monkey B, and 22 from monkey R. STAs of at least three flexor and three extensor muscles were obtained for these units.
Identification of neurons
The 572 task-related neurons identified on the basis of STA features comprised 29 MNs, 97 PreM-INs, 32 Sy-INs, and 414 U-INs. Typical examples are shown in Figs. 2-5, which illustrate the criteria used to classify the spinal neurons. Eighteen of the PreM-INs were classified as last-order interneurons (see METHODS). The properties of these last-order interneurons were not significantly different from those of other PreM-INs for all neuronal characteristics described in this report. Therefore, last-order interneurons are not considered separately for the remainder of this paper.
Response patterns
For the center-out task, spinal neurons were classified according to the modulation of their firing rates during flexion and extension with respect to any activity in the center hold position. The direction that corresponded to the strongest increase in firing rate was called the unit's preferred direction. Spinal neurons showed a variety of response patterns in relation to the ramp-and-hold torques. The proportion of the response patterns seen in the preferred direction for each cell type is summarized in Table 1 and Fig. 13. Patterns of increased activity were classified as tonic (t+, e.g., Figs. 2 and 3), phasic (p+, Figs. 9 and 11), phasic-tonic (p + t+, Fig. 10), decrementing (decr, Fig. 8 of Perlmutter et al. 1998
Directionality
The activity of neurons in their nonpreferred direction further differentiates their directional tuning (Table 2). For each unit, the activity in the nonpreferred direction was classified as being absent, unmodulated relative to baseline activity, or "similar" to or the "inverse" of the activity in the preferred direction. Units were classified as "similar" if they showed increased activity with both flexion and extension and "inverse" if their activity increased in one direction and decreased in the other.
Onset latency
Onset time indicates the possible source of a neuron's initial activation
Relation to static torque
To quantify the firing rate of interneurons and MNs as a function of torque, we required monkey W to generate three different levels of static torque in each direction in the center-out task. The relation between tonic firing rate and static torque was tested for 13 MNs, 50 PreM-INs, 15 Sy-INs, and 182 U-INs in monkey W that had a tonic component in their firing pattern. In addition, nine PreM-INs and six U-INs were tested at different static torque levels in the alternating task. Scatter plots of tonic firing rate versus static torque are illustrated for a MN, an excitatory, and an inhibitory PreM-IN and a U-IN in Figs. 2-5. The points in the scatter plots represent the mean static activity during a 1-s period of steady torque in single trials, and the plots combine values for extension, center position, and flexion. A regression line and associated statistics are included in the expanded scatter plots for active torque of either flexion or extension (excluding the center hold).
Relation to dynamic torque
Many spinal neurons also showed phasic activity associated with the dynamic transition to new levels of active torque. The peak rate of change of torque during individual trials varied as the monkeys produced different levels of static torque; higher static levels were acquired with higher rates of change (Fig. 1). The relation between peak firing rate and peak dT/dt was investigated in monkey W for 34 PreM-INs, 6 Sy-INs, and 65 U-INs with a phasic response component. A phasic-tonic PreM-IN that facilitated a single flexor muscle, flexor digitorum superficialis (FDS), is shown in Fig. 10A. The scatter plot of peak firing rate versus peak dT/dt indicates a significant covariation of the phasic response component with dT/dt, with a slope of 228 (spikes/s)/(Nm/s) (Fig. 10B, left). In addition, the tonic firing rate of this PreM-IN was well correlated with static flexion torque (Fig. 10B, right). A purely phasic, bidirectional response of a U-IN is shown in Fig. 11. Peak firing rate was related to the rate of torque change in both extension and flexion, with similar slopes of 249 and 289 (spikes/s)/(Nm/s) (Fig. 11B).
Relation between PSEs and static torque correlation
Figure 12 tabulates all the spinal neurons in terms of the parametric relation between tonic firing rate and static torque, in both their preferred and nonpreferred directions, represented as a continuum on a single axis (as done implicitly in the abscissa of the rate-torque figures). Neurons are classified by the slopes (positive, negative, or flat) of these relations (diagrams on left of figure) rather than by response pattern. For example, group 8 of Fig. 12 includes neurons that had increased, tonic activity for one direction of torque, but for which firing rate was independent of the magnitude of the torque.
Identification of spinal neurons
Ideally, it would be desirable to identify the spinal interneurons described here in terms of the "classical" cell types characterized in acute experiments. Determining such correspondence is complicated by the different identification criteria used in chronic and acute experiments. Spike-triggered averaging of EMG permits the classification of spinal neurons into MNs, PreM-INs with PSEs in forearm muscles, Sy-INs associated with early, "synchrony" effects in muscles, and U-INs with no spike-related modulation of muscle activity. This classification is based strictly on the output effects associated with the recorded neuron. In contrast, the classical identification of spinal interneurons in anesthetized animals (e.g., Ia-inhibitory interneuron) is based largely on the profile of synaptic input activating the interneurons. In addition, we could characterize the response patterns and force relations of neurons during normal voluntary activity. This basic difference in criteria represents a fundamental dichotomy between the classification schemes used classically and in the present study.
Response patterns
The units' response patterns during ramp-and-hold torque trajectories consist of two major components: the phasic activity that occurs during dynamic changes in torque and the sustained discharge during maintained static torque. The sustained activity was tonic in most cases but also could be increasing or decrementing. The firing patterns in the preferred direction for different cell groups, including other PreM populations, are shown in Fig. 13. This tabulation combines our MNs with motor units recorded in forearm muscles under similar conditions (Palmer and Fetz 1985 Relation to static torque and rate of change of torque
The PreM cells, which have output effects on their target muscles, contribute causally to generating active force in proportion to their activity. For this reason, their firing rate as a function of active torque is a salient issue. Earlier studies in monkeys have investigated force coding of neurons in motor cortex (reviewed by Evarts 1981 Output effects versus torque relation
To understand the contribution of PreM-INs to movement, we must interpret their response patterns in the context of their output projections. In the companion paper we described the various relations between the PSEs and activity patterns of PreM-INs (Perlmutter et al. 1998 Comparison with supraspinal and afferent PreM cells
It is interesting to compare the properties of spinal PreM-INs with those of other populations of neurons previously tested under similar conditions, i.e., in the alternating task. The majority of response patterns of PreM-INs also have been seen in supraspinal and afferent premotor cells (Fig. 13). The most prominent among those were phasic-tonic, followed by tonic and phasic patterns, which also were common in the CM, RM, and DRG populations (Cheney and Fetz 1980 Functional conclusions
These results suggest that spinal interneurons and CM cells differ from each other in their relations to alternating flexion-extension wrist movements. Whereas almost all CM cells fired unidirectionally, with either flexion or extension, but not both, most of the INs were bidirectionally active. This reflects a sharper representation of opposing movement direction in the premotor cortical output neurons than the broader, overlapping representation in spinal neurons. Indeed, some spinal neurons increased their activity with torque in both directions, a property never seen in any supraspinal CM or RM cells. The bidirectional activity of excitatory PreM-INs has a counterproductive component
INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References
; Lemon et al. 1986
)], red nucleus [rubromotoneuronal (RM) cells (Cheney et al. 1988
; Mewes and Cheney 1991
)], and peripheral afferents in dorsal root ganglia (DRG cells) (Flament et al. 1992
). Segmental spinal interneurons provide another major source of direct input to motoneurons. Specifically, spinal premotor interneurons (PreM-INs), i.e., those producing PSEs on motoneurons, play a major role in shaping motoneuron discharge. These neurons receive convergent projections from various descending tract neurons, including cortico-, rubro- and reticulo-spinal fibers, as well as from cutaneous and proprioceptive afferent fibers. In the companion paper (Perlmutter et al. 1998
), we described the output properties of PreM-INs identified by STAs of forearm muscle activity. In this paper, we quantify the task-related responses of PreM-INs and other intraspinal neurons during voluntary wrist movement.
; Jankowska 1992
). Identified interneurons such as Ia-inhibitory interneurons, Ib interneurons, Renshaw cells, flexor reflex afferent interneurons, and others have been characterized during segmental reflexes and fictive locomotion, from which their roles in voluntary movement have been inferred indirectly. For example, Ia-inhibitory interneurons may be responsible primarily for inhibiting motoneurons in reciprocal movements. The Ib-interneurons, with a broader pattern of divergence, may be responsible for wider motor synergies across muscles acting at different joints. Recurrent inhibition via Renshaw cells may have a role in coactivating antagonist muscles. These hypotheses emphasize the need for direct physiological evidence regarding the role of spinal interneurons during voluntary limb movements.
) and Renshaw cells (Horner et al. 1991
) to motoneurons may be organized differently in the forelimb segments than in hindlimb segments in the cat (Hamm et al. 1987
; Thomas and Wilson 1967
). This also seems to be the case in monkeys (Flament et al. 1992
) and humans (Aymard et al. 1995
; Chalmers and Bawa 1997
; Day et al. 1984
; Pierrot-Deseilligny 1989
).
,b
; Kitazawa et al. 1993
). The rhythmic activity of last-order interneurons controlling the activity of elbow motoneurons during fictive locomotion also has been described (Ichikawa et al. 1991
; Terakado and Yamaguchi 1990
). Less is known about PreM-INs in monkeys. Earlier accounts of cervical interneuronal activity during voluntary movement are relatively anecdotal and do not identify PreM-INs (Bromberg and Fetz 1977
; Courtney and Fetz 1973
).
), most spinal interneurons exhibit a significant level of activation with both flexion and extension. By analyzing whether and how this activity covaries with muscle force, we could further resolve the parametric relation between firing rate and torque and the functional relations between interneurons and voluntary movements.
METHODS
Abstract
Introduction
Methods
Results
Discussion
References
). Briefly, a unilateral laminectomy of vertebrae C5-T1 was performed with the animals under halothane or isoflurane anesthesia and a recording chamber was implanted. The implant remained securely fixed to the vertebrae for
6 mo. During recording, the monkey was seated in a primate chair with its head and upper back restrained. Unit activity and EMG from wrist and digit flexor and extensor muscles (see Perlmutter et al. 1998
for muscle abbreviations) were recorded and interneurons were classified on the basis of STAs of rectified EMG as described below.
). In the center-out task, a trial always began from a relaxed wrist position (center position) and required sustained active flexion or extension at one of three different torque levels
0.04, 0.07, or 0.1 Newton-meters (Nm), ±0.02 Nm
followed by a release back to the center position. Hold times varied randomly between 1.5 and 2.0 s for flexion and extension targets and between 1.0 and 4.0 s for the center position. In the alternating task, used previously in studies of wrist-related CM cells (Fetz and Cheney 1980
), RM cells (Mewes and Cheney 1991
), and peripheral afferents (Flament et al. 1992
), the monkeys switched from active extension directly to active flexion without an intervening neutral hold. For this task, we occasionally tested the monkeys with different torque levels. Although the center-out and alternating tasks are identical under steady-state conditions, the center-out task offers the advantage of a clearer comparison between active and passive states, is more sensitive for detecting bidirectionally modulated activity, and can identify transient OFF responses at the release of active torque.
). Motoneurons (MNs) had a large "motor unit" signature in the STA of unrectified EMG in a single muscle. Premotor interneurons (PreM-INs) had a PSE with an onset latency of
3.5 ms in the STA of rectified EMG for at least one muscle. PreM-INs with at least one PSE with a latency of <4.5 ms were classified as last-order interneurons. STA features with onsets earlier than 3.5 ms after the trigger spike were classified as early spike-related effects that could not be due to a synaptic connection from the trigger cell to MNs. Interneurons with STAs that exhibited an early effect but no PSEs were classified as synchrony interneurons (Sy-INs). Unidentified interneurons (U-INs) showed no spike-related modulations of EMG in any of the sampled muscles. Neurons were classified as PreM-INs, Sy-INs, and U-INs only if
2,000 triggers were available to compute STAs.
10 trials. Averages of correlation coefficients (using Fisher's z transformation) and slopes were calculated for different neuronal groups.
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FIG. 1.
Recordings of 3 trials of the step-tracking task. Top to bottom: 1: target position. Shown are 2 extension trials of different amplitudes followed by a flexion trial. 2: isometric wrist torque. Monkey followed the target and produced 2 static extension torques of different amplitudes followed by a flexion torque. 3: rate of torque change (dT/dt). Monkey usually scaled its torque change according to the target torque required. 4: unit activity of a spinal interneuron processed by a frequency meter that provided a continuous signal proportional to the instantaneous frequency. 5: electromyogram (EMG) of a representative wrist extensor muscle (extensor carpi ulnaris). 6: EMG of a representative wrist flexor muscle (flexor digitorum superficialis). For parametric analysis: static torque and tonic firing rate were averaged trial-by-trial in the last second of the hold period (arrows). Peak firing rate and peak dT/dt are indicated by circles.
RESULTS
Abstract
Introduction
Methods
Results
Discussion
References
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FIG. 2.
Properties of a putative FCR motoneuron. A: spike-triggered averages (STAs) of, from top, triggering action potential and EMG for coactive flexor muscles. FCR shows a clear "motor-unit" action potential in the unrectified STA. Stippled vertical line at time 0: onset of trigger spike. Number of trigger spikes for STAs is given below top trace. B: response histogram of the motoneuron (MN), showing tonic flexor-related activity, isometric torque, and rectified EMG of coactive muscles. Number of averaged trials given below torque trace. Positive torques indicate flexion. Stippled line at time 0: torque onset. C: scatter diagrams for tonic firing rate vs. static torque. Left: "whole-task" plot showing the static activity in extension (E), center position (near-zero torque) and flexion (F). Right: scatter plot for the flexion direction with regression line. s, rate-torque slope of the regression; r, correlation coefficient; n, number of data points, i.e., trials, used for the regression. This FCR MN is shut off in extension and center position and has a threshold of ~0.04 Nm flexion torque.
3.5 ms (Perlmutter et al. 1998
). The PreM-IN shown in Fig. 3 produced postspike facilitations in extensor digitorum-4,5 (ED-4,5) and extensor carpi ulnaris (ECU) at onset latencies of 8-9 ms. This excitatory PreM-IN had a high tonic firing rate during extension and a slow resting discharge during the center hold (both properties distinguished this neuron from a MN).
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FIG. 3.
A: STA of an excitatory premotor interneuron (PreM-IN) recorded in C7. This unit produced postspike facilitation in 2 extensor muscles (*) with onset latencies of 8.9 and 8.4 ms. B: response average of neuron and muscles. Negative torque indicates extension. Unit was activated tonically during extension (onset at 72 ms), had resting activity in the center position, and shut off in flexion (not shown). C: activity in extension (right) is correlated highly with torque (plot inverted around the vertical axis).
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FIG. 4.
STA and response average of an inhibitory PreM-IN recorded in caudal C6. A: STA shows postspike suppression in FCR; no effects were seen in other simultaneously recorded, independent muscles (5 other flexors and 6 extensors). B: response average of neuron and muscles during flexion and extension responses. C: rate-torque relations.
). U-INs showed no spike-related features in any of the tested muscles in STAs of
2,000 sweeps. Figure 5 illustrates an U-IN that had a resting discharge in the center position and increased its activity in both the flexion and extension directions. The STAs of flexor and extensor muscles (not shown) exhibited no spike-related fluctuation.
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FIG. 7.
Mean onset latencies of extensor and flexor EMGs with respect to torque onset for the center-out task and with respect to torque reversal for the alternating task. Negative latencies indicate onset before torque onset or torque reversal. Error bars are standard deviations. Muscles ordered according to increasing mean onset latency. Muscles with primary action of wrist or digit flexion or extension were activated earlier and had smaller variations than other muscles. Onset latencies of extensor and flexor PreM-INs and U-INs shown to right of muscle onsets. Larger variations for the alternating task are due to the alignment of response averages on torque reversal, which was more variable than torque onset from trial to trial. Mean onset times for the center-out task (with similar values in flexion and extension) were 28 ms for U-INs and
38 ms for PreM-INs (SD ~ 130 ms). The mean onset time of MNs was
27 for extensor and
5 ms for flexor MNs (SD ~ 43 ms). For the alternating task, mean latencies were
190 ms for U-INs and
230 ms for PreM-INs (SD ~ 250 ms) with little difference between flexion and extension.
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FIG. 8.
Histograms of onset times of activity for PreM-INs relative to target muscle onset. Response types of PreM-INs are indicated separately by shading. , mean ± SE of onset times for PreM-INs separated into groups by response pattern. Decrementing and ramp patterns included in t+. A: PreM-INs sampled in the center-out task. Mean onset time is
11 ms (n = 83 cell-muscle pairs). B: PreM-INs sampled in the alternating task. Mean onset time is
46 ms (n = 58 cell-muscle pairs).
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FIG. 5.
A and B: response averages of a bidirectionally and tonically activated unidentified interneuron (U-IN) recorded in C7. Onset latency was 0 ms for both extension and flexion. This unit had no postspike effects (PSEs) in any of the recorded EMGs after 2,000 trigger spikes. C: static flexion and extension activity show high correlations to torque with similar slopes.
), ramp (monotonically increasing activity during static torque), and phasic-ramp (p + ramp). For the center-out task, it was also possible to identify a decrease of activity relative to any resting discharge in the center position; thus in this task inhibitory response patterns could be classified as tonic (t
, Fig. 9B), phasic (p
), and phasic-tonic (p
t
). These inhibitory patterns usually occurred in the nonpreferred direction. A few "mixed" units had an increasing and decreasing component in a single direction. For the alternating task, the cell's increased activity was judged relative to that in the opposite direction, which precluded identification of tonic suppressed activity (t
). Thus in the alternating task, the only inhibitory response pattern that could be classified was phasic (p
). A few neurons exhibited only inhibitory response patterns, and no preferred direction was assigned (Table 1).
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TABLE 1.
Type and numbers of response patterns in alternating and center-out tasks in the preferred direction
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FIG. 13.
Summary of response patterns in the preferred direction for different populations of neurons during generation of flexion and extension torques at the wrist. Examples of each pattern are illustrated on left. Proportions are given for corticomotoneuronal (CM) (Fetz et al. 1989 ) and rubromotoneuronal cells (RM) (Fetz et al. 1989
), premotor afferents in dorsal root ganglia (DRG) (Flament et al. 1992
), spinal premotor interneurons (PreM-IN), spinal unidentified interneurons (U-IN), spinal interneurons with synchrony effects (Sy-IN), and motoneurons (MU). Latter combines motor unit data from Palmer and Fetz (1985)
with putative motoneurons from present study. In contrast to Table 1, which includes inhibitory patterns identifiable only in the center-out task, this figure summarizes patterns identifiable in the alternating task used in previous studies. Unmodulated U-INs are not included because they were not studied systematically and their proportion could be made arbitrarily large.
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FIG. 9.
STAs and responses of a PreM-IN recorded in C6. A: STAs show a facilitation of 2 flexor muscles [palmaris longus (PL), flexor carpi ulnaris (FCU); *] and synchronous facilitation in FCR. Response average shows a phasic task modulation during flexion (onset: 88 ms). B: responses for extension averaged separately for (top to bottom) low, medium, high, and combined torque levels; neuron becomes silent at higher torque levels. C: whole-task scatter plot shows decreasing activity during extension and unmodulated tonic activity during flexion. Significant negative correlation and slope between firing rate and extension torque shown in the bottom scatter plot.
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FIG. 11.
U-IN with bidirectional phasic activity recorded in C6. No significant PSEs were detected in 11 independent, simultaneously recorded muscles. A: response averages show onset at 0 ms for flexion and extension. B: scatter plots show clear correlations of peak firing rate to rate of change in torque for both extension and flexion.
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FIG. 10.
Spinal PreM-IN with phasic response component. A: STA and response averages show facilitation of a single flexor muscle [flexor digitorum superficialis (FDS); *] and phasic-tonic activity during flexion. B: scatter plot of peak firing rate vs. peak dT/dt in flexion. C: scatter plot of tonic firing rate vs. static torque in flexion.
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TABLE 2.
Directionality (response in nonpreferred direction) and release activity
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FIG. 6.
Response averages of an interneuron with release activity. Traces are, from top, unit histogram, averaged torque, averaged EMGs of agonist, and antagonist muscles. Responses are shown for active extension (A), active flexion (B), release from extension (C), and release from flexion (D).
central versus peripheral. Figure 7 summarizes the onset times of muscle and interneuronal activity with respect to torque onset for the center-out task and with respect to torque reversal for the alternating task. Muscles with primary action of wrist or digit flexion or extension (i.e., carpi and digitorum muscles) were activated earlier and exhibited smaller variations than muscles without primary actions [brachioradialis (BR), abductor pollicis longus (APL), palmaris longus (PL), pronator teres (PT)]. Similar tendencies were found in the alternating task, although the precise order of onsets was different. Muscle onsets appeared to be earlier in the alternating task than in the center-out task, but this is largely attributable to the different reference points for the measurements. Although the absolute values of the onset latencies for the two tasks cannot be compared, their relative orders are directly comparable.
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TABLE 3.
Mean onset latency in milliseconds with respect to torque onset (center-out task) and torque reversal (alternating task)
25 ± 128 ms (86 PreM-INs). For most of the PreM-IN-target muscle pairs (86/141 = 61%) the PreM-IN began firing before its target muscle. The rank order of onset times relative to target muscle onset for PreM-IN with different response patterns was similar to that relative to torque. In the center-out task, units with phasic components had an earlier onset than those with tonic components. Interestingly, the excitatory PreM-INs had significantly earlier onset times (
34 ± 119 ms; 74 cells) relative to their facilitated target muscles than the inhibitory PreM-INs relative to their suppressed target muscles (+51 ± 156 ms; 12 cells; difference P < 0.02).
600 spikes/s/Nm), indicating the gradual decrease of activity with increases in extension torque until the unit was silenced at the highest torques. Given the relatively high resting discharge of this flexor PreM-IN, it makes functional sense to suppress its activity during extension. Interestingly, its activity dropped in a graded manner. Seven PreM-INs of this type were recorded and five had the same pattern: negative correlation with torque produced by the antagonists of the facilitated muscles. Only one of these also had a significant positive correlation to torque produced by the facilitated muscles.
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TABLE 4.
Mean correlations and slopes between tonic firing rate and static torque
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TABLE 5.
Mean correlations and slopes between peak firing rate and torque change
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FIG. 12.
Rate-torque relationships in preferred and nonpreferred directions for different groups of spinal neurons. PreM-INs are tabulated separately according to their PSEs on agonist and antagonist muscles. Preferred direction was defined on the basis of highest phasic as well as tonic activity, so some neurons could show parametric increases of static firing rates in the nonpreferred direction (e.g., group 2). For this figure only, neurons for which the only task-related modulation was a decrease in activity for 1 direction of torque ("no preferred dir" in Table 1) were assigned a preferred direction opposite that in which the firing rate decreased. Slope of parametric rate-torque relation is schematically indicated on left. Note that these slopes do not indicate response patterns; for example, 0 slope could represent unmodulated activity during the static hold period, modulated activity with no significant relation to static torque level, or no activity at all. For groups 2 and 3, continuity at 0 torque level shown in diagrams is schematic only (firing rate-torque relationships for 7/14 of these neurons were not continuous at transition between flexion and extension torques). Squares represent matched properties between PSE and static torque relation (see text for details), circles and triangles represent mixed and incongruent relations, respectively.
), Fig. 12 shows the correspondence between the static rate-torque slopes and the PSEs. Combining these two properties provides a functional description of how PreM-INs control the graded activity of wrist muscles during ramp-and-hold movements. Most of the PreM-INs tested (42/59 = 71%) had firing rates that were correlated significantly with static torque. Three kinds of PreM-INs can be distinguished. Those with "matched" relations between parametric properties and PSEs were consistent with reciprocal control of the flexion/extension continuum. Indeed, 40% of the PreM-INs tested (24/59) had a matched relation. They all were modulated monotonically over the extended torque continuum and had a variety of functionally consistent PSEs. Among those, five different patterns could be distinguished (indicated by squares in Fig. 12). For the most common pattern, firing rate increased in proportion to torque in the ON direction of facilitated muscles and was uncorrelated with opposite torques (group 1, Fac agonist). Cells with "mixed" relations had parametric behavior that was only partially consistent with reciprocal activation of agonist and antagonist muscles (numbers shown in circles). These cells included neurons that had positive rate-torque slopes in the ON direction of facilitated muscles but also were correlated with torque in the opposite direction, when these muscles were silent. A few PreM-INs had purely counterintuitive or "incongruent" relations (numbers shown in triangles); for example, the firing rates of six neurons increased parametrically with torques for which facilitated target muscles were inhibited.
DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References
). The previous motor unit sample included a larger proportion of decrementing patterns, probably due to the higher torque levels examined in that study.
). This indicates that although muscles are activated reciprocally during flexion-extension movements, spinal neurons involved in these movements are not strictly partitioned into separate flexion and extension groups. The flexion-extension dimension may be represented centrally as a movement continuum, with interneurons having overlapping domains of activity in these two opposing directions.
; Hepp-Reymond 1988
), cerebellum (Smith and Bourbonnais 1981
; Thach 1978
), basal ganglia (Allum et al. 1983
; Mink and Thach 1991a
,b
), and thalamus (Anner-Baratti et al. 1986
). Similar analyses have been done for CM cells (Cheney and Fetz 1980
; Maier et al. 1993
) and RM cells (Cheney et al. 1988
; Mewes and Cheney 1994
). In this study, we found that most PreM-INs with tonic response components showed a significant parametric relation to static torque. The mean rate-torque slope (i.e., the sensitivity, or gain, of this relation) tended to be higher for PreM-INs, Sy-INs, and U-INs than for MNs. Generally, mean extension slopes were higher than flexion slopes.
found mean values of 260 and 410 spikes/s/Nm, respectively, for extension and flexion motor units. Mean values were similar for our extension MNs but not for the flexion MNs. This discrepancy is probably due to the restricted samples in both studies.
). In the present study, we extended this analysis to the parametric change in firing rate with static torque in the context of both torque directions. We observed a variety of parametric rate changes (Fig. 12), consisting of different combinations of increasing, decreasing, or unchanged activity with torques in the preferred and nonpreferred directions. In considering the flexion-extension axis as a continuum, we broaden the concept of the "strict" reciprocal organization and suggest that the cells' relation to increasing torque in the preferred direction could be seen as a continuation of its relation to decreasing torque in the nonpreferred direction.
). The behavior of most monotonic interneurons can be viewed as components of a similar sigmoidal behavior, with the nonlinear transitions occurring at different points of the extended torque range. Most (n = 26) of the PreM-INs with monotonic increases toward the preferred direction produced functionally consistent PSEs, i.e., facilitation of agonist muscles and/or suppression of antagonists (squares in Fig. 12). Because the increase of firing rate with torque produces a proportional facilitation or suppression of target muscles, PreM-INs with these properties can be regarded as being causally involved in generating and regulating active force.
; Flament et al. 1992
; Mewes and Cheney 1994
).
; Mewes and Cheney 1994
). Rate-torque slopes tended to be higher for extension than for flexion in all three PreM populations. However, PreM-INs seem to be less sensitive than CM cells but more sensitive than RM cells (e.g., extension mean slopes: CM, 480 spikes/s/Nm; PreM-IN, 342 spikes/s/Nm; RM, 160 spikes/s/Nm; MN, 253 spikes/s/Nm).
showed that some motor cortical neurons exhibit parametrically decreasing activity in the nonpreferred direction. Some spinal PreM-INs displayed significant negative correlations to static torque, usually to static torque produced by antagonists of their facilitated muscles. These units thus shut off their facilitation when torque was generated in the nonfacilitated direction and did so in a linearly graded fashion. In contrast, some CM cells had negative correlations to force produced in the precision grip and facilitated force-producing muscles (Maier et al. 1993
).
). Among CM and RM cells a larger proportion was activated before target onset (71 and 94%), indicating that more of the supraspinal PreM units may be involved in movement initiation (Cheney and Fetz 1980
; Mewes and Cheney 1994
). This trend also is reflected in the mean lead onset times relative to target muscles. The average onsets of segmental neurons in the alternating task [46 ms for PreM-INs and 51 ms for PreM DRG afferents (Flament et al. 1992
)] were later than the mean onset of supraspinal CM and RM cells [82 and 88 ms, respectively (Cheney and Fetz 1980
; Mewes and Cheney 1994
)].
). The mean onset times suggest a successive recruitment order, with supraspinal PreM cells tending to be activated first, followed by afferent PreM cells, and, finally, spinal PreM-INs. However, the large dispersion in each of these distributions produces considerable overlap of onset times; this could be interpreted as a network of PreM units primarily activated in parallel, with some units preceding and others following muscle onset.
i.e., the activity that occurs when their facilitated target muscles must be inactivated. Clearly these inappropriate excitatory effects are gated out or overridden by simultaneous inhibition from inhibitory interneurons. This coactivation of excitatory and inhibitory PreM-INs in the spinal cord differs from the reciprocal activation of excitatory CM cells in the cortex.
). The more specific projections of spinal INs, combined with their broader activation, indicate that spinal circuits tend to operate more in terms of separate but simultaneously activated excitatory and inhibitory influences, whereas cortical output cells are organized more in terms of muscle synergies generating movement.
, 1988
; Kalaska et al. 1989
) and like many muscles acting at the wrist (Hoffman and Strick 1986
). In this case, the bidirectional interneurons might be seen as having a sufficiently broad activation range to generate a component in the "nonpreferred" flexion-extension direction. In this context, the CM cells would appear to be relatively sharply tuned in their preferred direction, exhibiting no activity in the nonpreferred direction. It seems possible that non-CM cortical neurons with wrist-related activity may show more broadly tuned behavior, like shoulder-related cells; in fact some of these may be pyramidal tract neurons driving spinal interneurons. This issue can be elucidated by documenting the activity of cortical and spinal neurons and the action of their target muscles in relation to two-dimensional wrist movements.
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ACKNOWLEDGEMENTS |
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We thank J. Garlid and L. Shupe for expert technical assistance and K. Elias for editorial help.
This study was supported by National Institutes of Health Grants RO1-NS-12542, F32-NS-9189, and RR-00166; American Paralysis Association Grants PB1-9402-1 and PBR2-9502; and a Swiss National Science Foundation fellowship (M. A. Maier).
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FOOTNOTES |
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Present address of M. A. Maier: Sobell Dept. of Neurophysiology, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Address for reprint requests: S. I. Perlmutter, Dept. of Physiology and Biophysics, Box 357330, University of Washington, Seattle, WA 98195-7330.
Received 2 December 1997; accepted in final form 28 July 1998.
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REFERENCES |
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