Central and peripheral mediation of human force sensation following eccentric or concentric contractions

Transcription

1 Journal of Physiology (2002), 539.3, pp DOI: /jphysiol The Physiological Society Central and peripheral mediation of human force sensation following eccentric or concentric contractions Richard G. Carson, Stephan Riek and Nosratollah Shahbazpour Perception and Motor Systems Laboratory, The University of Queensland, Brisbane, Queensland 4072, Australia Fatigue was induced in the triceps brachii of the experimental arm by a regimen of either eccentric or concentric muscle actions. Estimates of force were assessed using a contralateral limb-matching procedure, in which target force levels (25 %, 50 % or 75 % of maximum) were defined by the unfatigued control arm. Maximum isometric force-generating capacity was reduced by 31 % immediately following eccentric contractions, and remained depressed at 24 (25 %) and 48 h (13 %) post-exercise. A less marked reduction (8.3 %) was observed immediately following concentric contractions. Those participants who performed prior eccentric contractions, consistently (at all force levels), and persistently (throughout the recovery period), overestimated the level of force applied by the experimental arm. In other words, they believed that they were generating more force than they actually achieved. When the forces applied by the experimental and the control arm, were each expressed as a proportion of the maximum force that could be attained at that time, the estimates matched extremely closely. This outcome is that which would be expected if the estimates of force were based on a sense of effort. Following eccentric exercise, the amplitude of the EMG activity recorded from the experimental arm was substantially greater than that recorded from the control arm. Cortically evoked potentials recorded from the triceps brachii (and extensor carpi radialis) of the experimental arm were also substantially larger than those elicited prior to exercise. The sense of effort was evidently not based upon a corollary of the central motor command. Rather, the relationship between the sense of effort and the motor command appears to have been altered as a result of the fatiguing eccentric contractions. It is proposed that the sense of effort is associated with activity in neural centres upstream of the motor cortex. (Resubmitted 8 October 2001; accepted after revision 18 December 2001) Corresponding author R. G. Carson: Perception and Motor Systems Laboratory, School of Human Movement Studies, The University of Queensland, Brisbane, Queensland 4072, Australia. richard@hms.uq.edu.au In most circumstances, we are both confident and capable of providing precise estimates of force and of weight. Yet the basis upon which such judgements are made remains a topic of discussion (e.g. McCloskey, 1981; Jones, 1986, 1995). The debate has focussed on the issue of whether the perception of force is mediated primarily by signals related to the central motor command, or by sensations originating in peripheral receptors. The classical view has been that the descending motor command is perceived, and forms the basis of the effort of will (Helmholtz, 1925) or sense of effort (McCloskey et al. 1974) associated with motor actions. The neural information that underlies this subjective awareness has variously been referred to as corollary discharge (Sperry, 1950) or efference copy (Holst, 1954). An alternative view (e.g. Sherrington, 1900) has been that a sensation of muscle force (Gandevia, 1987) is mediated by large diameter cutaneous, joint, or muscle afferents. In particular, it has been noted that Golgi tendon organs appear well suited to provide reliable information concerning muscle force (Gandevia & Burke, 1992; Jami, 1992). It has also been proposed that Ia muscle spindle afferents are capable of signalling intramuscular tension (Cafarelli, 1988). There is little doubt that, in certain circumstances, a sense of force or tension can be generated independently of a sense of effort. For example individuals are capable of perceiving intramuscular tension, when involuntary contractions are evoked via a tonic vibration reflex (McCloskey et al. 1974). The concept that sensory attributes are separable aspects of a stimulus that can be resolved into distinct percepts has a long history in experimental psychology (e.g. Boring, 1935). The foregoing considerations promote the view that effort and force are potentially separable sensory attributes that may represent different aspects of sensorimotor function. It is now well known that the ability of human subjects to make judgements of force deteriorates as a result of muscle fatigue (Gandevia & McCloskey, 1978). A variety of psychophysical methods have been employed in order to elucidate the basis of these changes (Jones, 1995). The most robust of these is the contralateral limb-matching method (McCloskey et al. 1974), in which participants are required to generate a specified level of force by contracting the muscles of the reference limb in the presence of

2 914 R. G. Carson, S. Riek and N. Shahbazpour J. Physiol external feedback, and to match the subjective magnitude of this force, using the muscles of the contralateral matching limb without the assistance of feedback. When individuals are required to reproduce the force applied during sustained fatiguing isometric contractions, by generating brief matching contractions using the contralateral limb, there is a monotonic increase in the perceived magnitude of the reference force (Gandevia & McCloskey, 1978; Jones & Hunter, 1983a,b; Cafarelli & Layton-Wood, 1986). The rate of change of the perceived force is contingent upon the intensity of the fatiguing contraction (Jones & Hunter, 1983a), and appears to reflect alterations in maximal force-generating capacity (Jones & Hunter, 1983b). Indeed, it has been proposed that neural systems underlying force estimation are calibrated continuously with reference to the capacity of the muscles to generate force (Cafarelli, 1988). If muscles are weakened by other means, for example by the local infusion of a neuromuscular blocking agent, the estimates of the weight supported by the paretic muscles are greater than those obtained prior to the blockade (Gandevia & McCloskey, 1977; cf. Roland & Ladegaard-Pedersen, 1977). When the maximum force-generating capacity of a muscle is decreased by an alteration in its length, the subject perceives that the intensity of the reference contraction has increased (Cafarelli & Bigland-Ritchie, 1979). These observations admit two possibilities in relation to the sensitivity of force estimation to alterations in maximal capacity during fatigue. In the first instance, it is possible that the state of the contractile apparatus is monitored via sensory signals arising in the muscle, and that force estimates are adjusted accordingly. Alternatively, force estimation may simply be sensitive to the motor outflow required to generate the reference contraction. Recordings of surface EMG have been employed as a measure of the level of neural drive directed to muscles during force estimation. There remains the caveat that segmental reflex pathways may also contribute appreciably to motoneuron firing and to force-generation (e.g. Gandevia et al. 1992). Nonetheless, it appears that, during fatiguing contractions, the force applied by the matching arm can be predicted quite accurately on the basis of the EMG recorded from the reference arm. Changes in EMG, due to either the magnitude of the target force or to progressive fatigue in the muscle, are represented faithfully in the force record of the contralateral arm (Jones & Hunter, 1983b). These data lend support to the hypothesis that alterations in force estimation during fatigue reflect changes in the descending voluntary command. It has been pointed out, however, that a role must be accorded to sensory input in providing a means of calibrating the perceived motor commands (e.g. Gandevia & Mahutte, 1982). In particular, in the absence of proprioceptive or visual cues that force has been applied, the descending voluntary command cannot be calibrated for events in the external world (Gandevia & McCloskey, 1978; Ross & Reschke, 1982). While such calibration need only be intermittent in circumstances in which the state of the contractile elements, and thus the relationship between the motor command and force output, remains relatively constant, it must necessarily become more frequent whenever there are rapid changes in the state of the muscle, such as those which occur during fatiguing contractions. In most studies that have employed the contralateral limb-matching method to examine force estimation during fatigue, extrinsic feedback of the force applied by the fatigued limb is available frequently (Gandevia & McCloskey, 1978) or continuously (e.g. Jones & Hunter, 1983a) throughout the experiment. In these circumstances, force matching during fatigue may be based primarily on a sensitivity to the descending voluntary commands (e.g. Cafarelli, 1988). In contrast, when external cues concerning the actual force that is being applied by the fatigued muscles are not available, individuals may utilise intrinsic feedback concerning the state of the contractile apparatus in order to generate estimates of force. The present study was designed to examine this possibility. We employed a contralateral limb-matching procedure. In an important variation, however, the experimental limb in which fatigue was induced served as the matching limb, and the unfatigued contralateral control limb served as the reference limb. During each force-matching trial visual feedback of the level of force applied by the reference limb was provided to the subject. At no stage during the experiment was the subject provided with extrinsic feedback concerning the level of force applied by the matching limb. In order to examine the process of force estimation in circumstances in which the force-generating capacity of the muscle was disrupted, separate groups of subjects performed eccentric and concentric fatiguing contractions. It is well known that strenuous, unaccustomed eccentric exercise induces greater damage to muscle fibres than concentric exercise, and is typically associated with a sensation of muscle weakness and reduced work capacity (e.g. Sargeant & Dolan, 1987). In order to investigate the impact of these time varying processes upon the accuracy of force estimation, subjects performed the contralateral limb-matching task at 20 min intervals during the 2 h immediately following exercise, and at 24 h and 48 h postexercise. The accuracy of force estimation was assessed at three levels of tension, expressed relative to the maximum force-generating capacity of the unexercised reference limb. In this and three subsequent experiments, the level of neural drive directed to muscles during force estimation was assessed on the basis of surface electromyography, or by examining the magnitude of motor potentials evoked by transcranial magnetic stimulation (TMS) of the motor cortex. In order to establish the generality of our findings,

3 J. Physiol Force sensation 915 in separate experiments we employed tasks that required the engagement of either the elbow extensor or the elbow flexor muscles. METHODS Participants Forty normal male volunteers (18 33 years) were studied. The procedures were performed in accordance with the guidelines contained in the Declaration of Helsinski, and were approved by the Medical Research Ethics Committee of the University of Queensland. Each person provided informed consent prior to his participation in the study. In the first experiment, 11 participants were assigned randomly to an eccentric exercise group, and 10 participants to a concentric exercise group. Two separate groups of six and a group of seven individuals participated in three subsequent experiments. Apparatus The participants lay in a supine position on a custom test bench. They were positioned with each forearm in a vertical position, flexed at an angle of 90 with respect to the upper arm. A webbing strap was placed around each wrist with its upper edge at the head of the ulna. Each strap was connected to a load cell (model , Scale Components Brisbane, Australia) that was calibrated prior to each experimental session. The participants were immobilised by shoulder restraints and by webbing straps placed around the chest and pelvis. Two digital LCD monitors, that provided visual feedback (two digits) of the force exerted by each arm, were placed above the subjects at eye level. In Expts 1, 2 and 4, surface EMG was recorded from the medial head of the triceps brachii of both arms, using bipolar surface electrodes placed parallel to the muscle fibres. In Expt 4, surface EMG was also recorded from extensor carpi radialis (ECR). In Expt 3, EMG recordings were obtained from the biceps brachii. The amplified EMG signals were bandpass (30 Hz 1kHz) filtered, and sampled at 2 khz. In Expts 2 and 3, single (200 ms duration) stimuli (Digitimer D7A) were delivered to the brachial plexus at Erb s point via surface electrodes. The cathode was located over the plexus and the anode over the acromion. The intensity of the stimulation was set to at least 120 % of the level necessary to obtain a maximal compound muscle action potential (m-wave) in the target muscle. In Expt 4, motor potentials were evoked by TMS delivered to the motor cortex by a Magstim 200 stimulator, using a figure-of-eight coil (outside diameter of each half-coil 55 mm). The orientation of the coil was such that the induced current flowed in an posterio-anterior direction. The coil was located at the optimal position to evoke a short-latency response (MEP) in triceps brachii. The stimulus intensity was approximately 110 % of that necessary to obtain a response of 100 mv at rest on three of five occasions. At these intensities, a potential was also evoked in ECR. As ECR was not activated during the force-matching task, these potentials provided a general index of motor cortex excitability. Experimental procedures In Expts 1, 2 and 4 the focal task required contraction of the elbow extensors. In Expt 3, the task required contraction of the elbow flexors. For simplicity, the procedures described are those that pertain to elbow extension. The one repetition maximum. This session was conducted 48 h prior to the experimental session, in order to determine a (concentric) one repetition maximum (1RM con ) for each individual. One half of the participants in each group performed the exercise with their non-dominant arm, the other half used their dominant arm. The participants first estimated the maximum amount of weight that they could lift (concentric extension of the elbow) through a full range of motion. The 1RM con was then determined from a series of three to five dumb bell lifts with the experimental arm, separated by 3 min intervals. This maximum value was used to establish the load of 85 % 1RM con that was applied during the subsequent bouts of eccentric or concentric exercise. Pre-exercise testing: Expt 1. Prior to the fatiguing exercise, a single isometric maximum voluntary contraction (IMVC) was recorded for each participant. The participants performed a maximal isometric elbow extension of 5 s duration, first with the experimental arm and then with the control arm. All the participants received strong verbal encouragement towards the end of the contraction. A single repetition was performed in order to minimise the resulting fatigue. Following 2 min rest, each participant was asked to exert a force equal to 25, 50, or 75 % IMVC with the control arm. During the course of this contraction, feedback of the level of force applied by the control arm was provided to the participant. The target level of force (expressed in the units of the digital display) was given to the participant immediately prior to each contraction. When he had reached the target level of force (typically within 1s), the participant then began to apply force with the experimental arm. No feedback was given to indicate the force applied by the experimental arm. When the participant was satisfied that he was applying, with the experimental arm, a level of force that matched that applied by the control arm, a verbal signal was given to the experimenter. A 5 s period of data collection was initiated at this point. The participant was told to relax (for 2 min) when the data collection interval had elapsed. The ordering of the different force level presentations was counterbalanced across subjects. The average force applied during the 5 s recording epoch was calculated subsequently. Pre-exercise testing: Expts 2, 3 and 4. Each participant performed six trials (each separated by 5 min) in which they were required to exert a force equal to 25 % IMVC with the control arm. During the course of the contraction, feedback of the level of force applied by the control arm was provided to the participant. They were asked to match this level of force with the experimental arm. As in the first experiment, there was no feedback of the level of force applied by the experimental arm. No contractions were performed at levels of force equal to 50 % and 75 % IMVC. In all other respects, the procedures were those employed previously. In Expts 2 and 3, Erb s point stimulation was used to elicit a maximal m-wave in the target muscle at the midpoint of the 5 min rest period between each contraction. In Expt 4, motor evoked potentials were elicited by TMS delivered to the contralateral motor cortex at a randomly determined time within a 3 s interval that commenced 1s following the onset of the contraction. The exercise regime. Following the pre-exercise testing, the participants performed a total of 50 repetitions in eight sets (6 w 7 and 2 w 4) of either eccentric or concentric elbow extension of the experimental arm, with a load equal to 85 % of 1RM con. The active phase of each repetition lasted approximately 3 s. There was a 1min rest between sets. In the eccentric condition, the experimenter raised the dumb bell (to full extension of the elbow) and the participants lowered the dumb bell. In the concentric condition, the participants raised the dumb bell and the experimenter lowered the dumb bell to the starting position (full

4 916 R. G. Carson, S. Riek and N. Shahbazpour J. Physiol flexion of the elbow). In Expts 2, 3 and 4, all participants performed eccentric exercise. Post-exercise testing. In Expt 1, the procedures undertaken preexercise were repeated immediately after exercise, and at 0.33, 0.67, 1, 1.33, 1.67, 2, 24 and 48 h post-exercise. In Expt 2, 3 and 4, the procedures undertaken prior to exercise were repeated immediately after exercise and then every 5 min until 12 postexercise trials had been performed. Serum creatine kinase. In order to assess the extent of the damage to the muscle fibres that occurred as a consequence of the bouts of eccentric and concentric exercise in Expt 1, we assessed serum levels of creatine kinase (CK). A 5 ml sample of venous blood was collected before exercise, immediately following exercise, and at 2, 24 and 48 h post-exercise. The blood was drawn using a venipuncture technique from the cubital fossa of the experimental arm, into a serum separation tube. The blood was allowed to clot at room temperature for 5 min. It was then centrifuged for 10 min to separate the serum, and stored at _20 C for subsequent analysis. Serum CK activity was measured using an enzymatic colorimetric kit (Randox, Perth, Australia) following Szasz et al. (1976). RESULTS Expt 1 Biochemical markers of muscle damage. There was a small but not statistically reliable (11.4 %) (F (1, 10) = 3.34, P = 0.1, f = 0.39) increase in serum creatine kinase activity in the 2 h immediately following eccentric exercise. By 24 h post-exercise, however, serum CK activity was markedly elevated (172.1 %) (F(1, 10) = 44.95, P <0.05, f = 1.429), and by 48 h post-exercise, the serum CK activity was more than double (235.7 %) that recorded prior to eccentric exercise (F(1, 10) = 58.35, P<0.05, f = 1.629). The corresponding values for the concentric exercise group were % (F(1, 9) < 1, P>0.20, f = 0.11) at 2 h post-exercise, % (F(1, 9) = 22.34, P<0.05, f = 1.057) at 24 h post-exercise, and % (F(1, 9) = 2.96, P=0.12, f = 0.383) at 48 h post-exercise, respectively. At the end of the 2 h period immediately following the fatiguing contractions, the degree of muscle soreness experienced by the group that had performed eccentric contractions was not different from that experienced by the group that performed concentric contractions. As such, there is no reason to believe that the pattern of results described below was influenced directly by muscle soreness. Consistent with previous reports, when similar estimates were obtained at 24 h and 48 h post-exercise, the level of muscle soreness reported by those who performed eccentric contractions was greater than that reported by the group that performed concentric contractions. Isometric maximum voluntary contractions (IMVC). Immediately following eccentric exercise, there was a 31% Figure 1. The levels of force applied during maximum isometric voluntary contractions (IMVC) prior to and up to 48 h following bouts of either eccentric or concentric exercise The levels of force applied by the control (unexercised) arm for the group that performed eccentric exercise (1, dotted lines) and the corresponding levels of force applied by the experimental (exercised) arm (ª, continuous lines) are shown. The levels of force applied by the control (unexercised) arm for the group that performed concentric exercise (3, dashed lines) and the corresponding levels of force applied by the experimental (exercised) arm (9, long dashed lines) are shown. Instances in which the post-exercise values were distinguished reliably (P <0.05) from the pre-exercise values are shown as filled symbols. The error bars correspond to 95 % confidence intervals.

5 J. Physiol Force sensation 917 reduction of maximum force-generating capacity. This decrement was expressed reliably during the first 2 h following exercise, and remained present at 24 (25 %) and 48 h (13 %) post-exercise (Fig. 1). The reduction in maximum force-generating capacity immediately following concentric exercise was much less marked (8.3 %), and sustained deficits were expressed reliably only at 1.67 and 2 h post-exercise. Force estimation. Sub-maximal forces (25, 50 and 75 % IMVC) were exerted by the un-exercised control arm in the presence of visual feedback of the level of applied force. The participants attempted to match this level of force using the experimental arm in the absence of visual feedback. Force matching was performed both before and after the fatiguing (eccentric or concentric) contractions performed by the experimental arm. All participants in both groups confirmed that they had attempted to estimate the targeted forces as accurately as possible, throughout the experimental procedure. The comparisons of primary interest were those between the level of force applied by the target control arm, and the force applied by the matching experimental arm. Preliminary inspection of the data obtained for the epoch commencing at the termination of the fatiguing contractions, and ending 2 h post-exercise, indicated that there were only minor changes in the level of applied force Figure 2. The target levels of force applied by the control arm (nominally 25 % (A), 50 % (B) and 75 % (C) IMVC) and the matching levels of force applied by the experimental arm, prior to and 0 2 h, 24 h and 48 h, following bouts of either eccentric (ECC) or concentric (CON) exercise The forces applied by each arm were normalised with respect to those applied during the respective preexercise IMVCs. Instances of a statistically reliable (P <0.05) difference between the normalised level of force applied by the experimental arm and that applied by the control arm are indicated by *. The error bars correspond to 95 % confidence intervals.

6 918 R. G. Carson, S. Riek and N. Shahbazpour J. Physiol during this period. In order to provide a more compact presentation of the data, therefore, we analysed the mean level of force (obtained by least squares estimates) applied during the 2 h immediately following exercise. Isometric force: normalised with respect to the preexercise IMVC. In the first instance, forces (25, 50 and 75 % IMVC) applied at each sample time were normalised with respect to the IMVC obtained prior to exercise (Fig. 2). The procedure was conducted separately for the control and the experimental arms. This measure provided an indication of the accuracy of force matching expressed in terms of the absolute maximum levels of force that could be applied by each arm. Planned comparisons of means were conducted, using a repeated measures analysis of variance design, to assess differences between the experimental and control arms, in each condition (i.e. at each level of target force). Similar analyses were conducted for the values obtained prior to exercise and at 24 h and 48 h post-exercise. Our results indicated that, at all target force levels (25 %, 50 % and 75 %), participants in the eccentric exercise group applied levels of force with the exercised arm that were markedly and consistently below those generated by the non-exercised control arm (Fig. 2). The persistent nature of this effect was emphasised by the observation that these differences were present not only during the 2 h immediately following the bout of eccentric exercise, but also during the following 2 days. A much less pronounced tendency to generate a level of force with the exercised arm below that applied by the control arm was exhibited by Figure 3. The R.M.S. EMG recorded from the control arm and the experimental arm, during the application of force (nominally 25 % (A), 50 % (B) and 75 % (C) IMVC), prior to and 0 2 h, 24 h and 48 h, following bouts of either eccentric (ECC) or concentric exercise The EMG amplitudes for each arm were normalised with respect to those recorded during the respective preexercise IMVCs. The error bars correspond to 95 % confidence intervals.

7 J. Physiol Force sensation 919 participants in the concentric exercise group only when the target level of force represented 50 % or 75 % of the pre-exercise IMVC. This effect was also less tenacious, being present only during the 2 h immediately following the concentric exercise. While the level of force applied by the arm that had been exercised eccentrically decreased, there was in every instance a marked increase in the EMG activity recorded from this arm during the matching contractions (Fig. 3). As such, there was a very pronounced change in the EMG force relationship. Following eccentric exercise, a much greater level of muscle activation was required to generate a given level of force than was required prior to exercise. When the levels of EMG recorded from the experimental arm and control arm in the 2 h post-exercise were expressed as a proportion of those recorded during the respective pre-exercise IMVCs, it was evident that the values did not match. The extent of the mismatch was: 80.4 % in the 25 % condition (F(1, 14) = 57.7, P<0.01, f = 1.90); 38.3 % in the 50 % condition (F(1, 14) = 36.9, P<0.01, f = 1.52); and 9.3 % in the 75 % condition (F(1, 14) = 2.54, P >0.10, f = 0.40). In every instance, the level of EMG recorded from the experimental arm was greater than that recorded from the control arm. Differences between the arms, in terms of the level of EMG, were not observed for the group that had performed concentric exercise, nor were there substantial changes in the EMG force relationship. Figure 4. The target levels of force applied by the control arm (nominally 25 % (A), 50 % (B) and 75 % (C) IMVC) and the matching levels of force applied by the experimental arm, prior to and 0 2 h, 24 h and 48 h, following bouts of either eccentric (ECC) or concentric (CON) exercise The forces applied by each arm were normalised with respect to those applied during the respective contiguous IMVCs (see text). The error bars correspond to 95 % confidence intervals.

8 920 R. G. Carson, S. Riek and N. Shahbazpour J. Physiol Isometric force: normalised with respect to the contiguous IMVC. In the preceding analyses, the target levels of force were, in all cases, expressed as a proportion of the preexercise isometric maximum voluntary contraction (IMVC). It was evident, however, that the magnitude of the IMVC was reduced markedly following bouts of fatiguing eccentric exercise. The possibility exists therefore, that the tendency of subjects in the eccentric exercise group to produce levels of force post-exercise that were below the target force defined by the control arm, was accounted for by an attempt on the part of subjects to produce a level of force expressed relative to the current Figure 5. Expt 2, 3 and 4 A, the forces applied by the experimental arm in either extension (Expts 2 and 4, mean of 13 participants) or flexion (Expt 3, mean of six participants) have been expressed relative to those applied by the control arm (E/C), during force matching conducted prior to (Pre) and following (Post) bouts of eccentric exercise. The forces are shown both when normalised to the respective pre-exercise IMVCs (%Pre-MVC), and when normalised with respect to the respective contiguous IMVCs (%Contiguous-MVC) (see text). B, the R.M.S. electromyogram recorded from the triceps brachii (Expts 2 and 4, mean of 13 participants) or biceps brachii (Expt 3, mean of six participants) of the experimental arm (Exp) and of the control arm (Control), prior to (Pre-exercise) and following (Post-exercise) eccentric contractions. The EMG is expressed as a percentage of that recorded prior to exercise during an IMVC. C, the mean amplitudes of the maximum m-waves elicited in the triceps brachii (Expt 2, mean of six participants) or biceps brachii (Expt 3, mean of six participants) of the experimental arm, by supramaximal electrical stimulation of the peripheral nerve. The values obtained prior to (Pre) and following (Post) bouts of eccentric exercise are presented. D, the mean amplitude of the potential evoked in triceps brachii and extensor carpi radialis (ECR) by transcranial magnetic stimulation of the contralateral motor cortex prior to (Pre) and following (Post) bouts of eccentric exercise (mean of seven participants). The individual values upon which the means are based were normalised with respect to background EMG (see text). In all panels, the error bars correspond to 95 % confidence intervals. In these experiments the target level of force was 25 % IMVC.

9 J. Physiol Force sensation 921 (post-exercise) maximum. In order to examine this in more detail, a further set of analyses was performed in which the force generated by the experimental arm was expressed in terms of the maximum force that could be generated by that arm at that time (the contiguous IMVC). In marked contrast to the outcomes outlined previously for the eccentric exercise group, when the level of force applied by each arm was expressed as a proportion of the respective contiguous IMVC, the resulting relative level of force applied by the exercised arm was not different from the relative level of force applied by the unexercised control arm. This pattern of results was obtained both immediately following the bout of fatiguing exercise and during the subsequent 2 days. In addition, the target level of force (25 %, 50 % and 75 %) did not influence appreciably the accuracy of relative force matching. An equivalent set of outcomes was obtained for the group that had performed prior concentric exercise (Fig. 4). These data indicate clearly that the participants in both experimental groups, applied a level of matching force, using fatigued muscles, that was scaled accurately in relation to the maximum level of force that could be generated at that time. The integrity of this scaling was preserved across very large changes in maximum levels of force such as those that resulted from prior eccentric exercise. Expts 2, 3 and 4 It is well established that unaccustomed eccentric exercise induces damage to muscle fibres and diminishes their capacity to generate force (Sargeant & Dolan, 1987). In order to achieve an equivalent level of tension, the activation of damaged muscle fibres must necessarily be greater than the activation of undamaged fibres. Similarly, a given level of activation will generate less tension in damaged fibres than in undamaged fibres. It is possible, therefore, that the lower levels of force applied by the eccentrically exercised muscles, observed in Expt 1, resulted from an attempt on the part of the participants to match the level of neural drive directed to the muscles of the target limb and the matching limb. In an attempt to examine this possibility, we employed surface EMG as a measure of muscle activation. Our results indicated that following eccentric exercise there was a pronounced mismatch between the level of EMG recorded from the experimental arm and the control arm. In our initial experiment, however, we were unable to ensure that the observed changes in EMG were not attributable to mechanisms post-synaptic to the motoneuron. In Expts 2 and 3, therefore, we also assessed the maximum electromyographic activity (m-wave) that could be generated by direct stimulation of the peripheral nerve. In Expt 4, we examined the magnitude of motor potentials evoked by TMS of the motor cortex, in order to assess the levels of voluntary activity in the corticospinal pathway (Gandevia et al. 1999). We first established that the pattern of results exhibited in terms of force matching, obtained in Expts 2, 3 and 4, was equivalent to that seen in Expt 1. (Fig. 5A). It was apparent that, as in Expt 1, the level of force applied by the matching limb, in both extension (F(1, 12) = 26.7, P<0.01, f = 1.01) and flexion (F(1, 5) = 14.9, P < 0.02, f = 5.72), declined dramatically following eccentric exercise. Once again, however, when the level of force applied by the experimental arm was expressed as a proportion of the contiguous IMVC, the matching force was not differentiated from the target force applied by the unexercised control arm (extension: (F(1, 12) < 1, P>0.20, f = 0.05); flexion ((F(1, 5) < 1, P >0.20, f = 0). Our findings relating to levels of EMG activity were equivalent to those obtained in 25 % IMVC condition in Expt 1. Prior to eccentric exercise, the levels of EMG recorded from the target (control) limb and the matching (exercised) limb were not distinguished reliably (triceps: (F(1, 12) = 1.86, P >0.15, f = 0.108); biceps: (F(1, 5) < 1, P > 0.20, f = 0.07)). Following eccentric exercise the root mean squared (R.M.S.) EMG recorded from the matching experimental arm was substantially greater than that recorded from the unexercised target control arm (triceps: (F(1, 12) = 8.84, P<0.02, f = 0.92); biceps (F(1, 5) = 10.83, P<0.05, f = 0.95)) (Fig. 5B). In marked contrast, the amplitude of the m-wave obtained by supramaximal stimulation of the peripheral nerve following exercise was statistically equivalent (P < 0.05) (Rogers et al. 1993) to that obtained prior to exercise, in 11 of the 12 participants (Fig. 5C). In the remaining participant, the m-wave obtained from triceps brachii following exercise was somewhat smaller than that recorded prior to the eccentric exercise. Differences in motoneuron firing rates, expressed in surface EMG, are not themselves indicative of variations in the descending input from supraspinal centres. During voluntary contractions, the firing behaviour of motoneurons can also be influenced by peripheral feedback from muscle afferents (Bigland-Ritchie et al. 1986). The observation that the level of EMG recorded from the target control limb and the matching exercised limb was distinct, therefore, does not rule out the possibility that the descending input was equivalent. In order to address this limitation, we used TMS to examine the excitability of the corticospinal pathway, during matching contractions performed following eccentric exercise. Following eccentric exercise the amplitudes of the motor potentials evoked in the triceps brachii of the matching limb were substantially greater than those recorded prior to the fatiguing contractions. Since the background EMG

10 922 R. G. Carson, S. Riek and N. Shahbazpour J. Physiol also changed, it was possible that this variation simply reflected changes in the excitability of the spinal motoneurons. To take account of this possibility, we normalised the amplitude of the TMS evoked potentials to the background EMG activity (Johansson et al. 1994). It was readily apparent (Fig. 5D) that the ratio of the amplitude of the motor evoked potential to the level of background EMG was greater following eccentric exercise than prior to the exercise (F(1, 6) = 5.98, P=0.05, f = 0.36). The result was exhibited by all of the seven participants tested. These data suggest that the increase in motoneuron firing rates observed during matching contractions, in the period following eccentric exercise, is not simply due to mechanisms operating at the segmental level. This conclusion is further supported by the pattern of results observed for ECR. This muscle was not subject to fatiguing contractions, nor was it engaged to any significant degree during the force matching task. The ratio of the amplitude of the motor evoked potential to the level of background EMG recorded from ECR was, however, elevated following eccentric contractions that engaged triceps brachii exercise (F(1, 6) = 6.27, P <0.05, f = 0.64) (Fig. 5D). DISCUSSION In the period immediately following the eccentric contractions, the level of force generated during a maximum isometric contraction was less than 75 % of that produced prior to the exercise. This reduction in forcegenerating capacity was sustained throughout the 24 h immediately following the eccentric contractions, and a residual deficit of 13 % was still evident 2 days later. Indirect evidence of exercise-induced muscle damage was provided by a substantial elevation in serum CK activity observed during this period. The decline in force-generating capacity in the 2 h period immediately following concentric exercise was much less severe, and the levels of force generated during maximum contractions had recovered completely by 24 h post-exercise. The accompanying changes in serum CK activity were also less marked than those that followed eccentric exercise. The accuracy of isometric force estimation was influenced profoundly by prior exposure to eccentric exercise. When the individuals who had performed eccentric contractions were subsequently required to reproduce a target level of force defined by the unexercised control arm, with a brief matching contraction of the exercised contralateral limb, the level of force applied was substantially lower than that required. In other words, the participants believed that they were generating more force than they actually achieved. This tendency to overassess the magnitude of the matching contraction was apparent at all levels of applied force, and persisted for 2 days following the eccentric exercise. Indeed, it is likely that the deficits endured well beyond the period of observation employed in the current study (Saxton et al. 1995). In contrast, overestimates of the absolute level of applied force resulting from prior concentric contractions were of smaller magnitude, dissipated during the 2 h following exercise, and were expressed only at higher levels of applied force. When expressed as a proportion of the maximum force that could be attained at that moment in time, the forces applied by the exercised arm and the control arm matched extremely closely. A similar result was obtained by Saxton et al. (1995), when the force applied following eccentric exercise was expressed as a proportion of the maximum force that could be generated on that day. The pattern of results is exactly that which would be expected if the participants were estimating levels of force on the basis of a sense of effort rather than relying upon a sense of tension (e.g. Thompson et al. 1990). It has generally been assumed that the sense of effort is informed by a perceivable central motor command that is directed to the muscles (e.g. Gandevia & McCloskey, 1977). In the present study, the EMG and MEPs recorded from the muscles that were exercised eccentrically increased in every instance, and the EMG was always greater than that recorded from the opposite limb. These observations imply that the sense of effort was not simply a corollary of the central motor command. Indeed, in circumstances in which the participants estimated the forces applied by both arms to be the same, the motor command was greater in the exercised arm than in the unexercised arm. Our results thus suggest that the relationship between the sense of effort and the motor command was altered as a result of the fatiguing eccentric contractions. It is likely that these changes were mediated by peripheral information concerning the state of the contractile apparatus. As a working hypothesis, we propose that alterations in afferent discharge arising from damage to the muscle fibres do not impinge directly upon the neural mechanisms that mediate the sense of effort. Instead, this information acts to regulate the gain of the relationship between the neural commands that form the basis of the sense of effort and the output of the motor centres. Thus, it is presumed to be the case that the sense of effort is associated with activity in neural centres upstream of the motor cortex. In the absence of altered afferent inflow, such as that generated by peripheral receptors following damage to muscle fibres, it is likely that there is a close relationship between activity in these centres and the output of the motor cortex. In normal circumstances, the motor command thus provides a reasonable representation of the sense of effort. When the disrupted state of the contractile apparatus is signalled by peripheral input, the gain of this pathway may be increased, such that a given level of effort results in greater excitability of the motor cortex and increased muscle activation. A contrast is thereby drawn with sustained

11 J. Physiol Force sensation 923 contractions to the point of voluntary fatigue, in which feedback of the force-generating capacity of the muscle and its biochemical status may impair the drive from neural centres upstream of the motor cortex (Gandevia, 2001). The system appears to be regulated in a fashion that preserves the relationship between the perceived sense of effort and the relative force-generating capacity of the contractile machinery. In the face of severe muscle damage, the relative rather than the absolute efficacy of volition is maintained. This form of adaptation may have considerable utility in the context of coordinated movements involving multiple muscles. It is the relative levels of tension contributed by the various muscles, from which a synergy is composed, which preserves the form of the resulting pattern of movement. What is the likely source of the afferent information that signals the altered state of the contractile apparatus? Inputs from Golgi tendon organs and small-diameter muscle afferents may be particularly important in this regard (Gandevia, 2001). It has been proposed previously (Brockett et al. 1997) that contractures in the muscle fibres damaged by eccentric contractions may result in changes in the sensitivity of Golgi tendon organs. Recent reports by this group (Gregory et al. 2002) have indicated, however, that while eccentric exercise alters resting tension in the passive muscle, it does not change the tension sensitivity of the tendon organs. Small diameter muscle afferents transmitting nocioceptive input are capable of reducing voluntary drive during sustained contractions (Gandevia et al. 1996), even though neither motoneurons nor motor cortical cells are subject to direct inhibition (Taylor et al. 2000). These findings suggest that group III and group IV afferents exert their effects upstream of the motor cortex. These afferents are known to be sensitive to several factors associated with both metabolic fatigue and muscle damage, and are responsive to deformation of the investing connective tissue (e.g. Kniffki et al. 1978). Studies involving acute animal preparations have revealed that the free nerve endings of group III and IV afferents are excited by a number of the products of muscle metabolism, including K +, H +, lactic acid and arachidonic acid (Rotto & Kaufman, 1988; Sinoway et al. 1993). It is clear that high intensity eccentric exercise, in particular, gives rise to an accumulation of metabolic products, and an inflammatory response resulting from damage to the muscle fibres (Avela et al. 1999). These changes in the metabolic milieu of the muscle fibres are likely to generate sustained alterations in the discharge rates of group III and group IV afferents. Alterations in the response characteristics of muscle spindle afferents can also not be discounted. Increases in the extracellular concentration of hydrogen ions following eccentric exercise may reduce the sensitivity of muscle spindles (Gollhofer et al. 1987). The intrafusal muscle fibres may themselves be subject to damage (Komi, 2000) or fatigue (Bongiovanni & Hagbarth, 1990). Modified fusimotor support to the muscle spindles may also be implicated (Macefield et al. 1991). In short, a number of peripheral afferents have the potential to provide information to the higher centres concerning the state of the contractile apparatus. It is also likely that the extent of their respective influences will vary in the period following exercise-induced muscle damage. One cannot entirely discount the possibility that the participants were attempting to match on the basis of a sense of force rather than upon a sense of effort. It is conceivable that the afferent pathways that give rise to force sensations may have been facilitated by the increased efferent activity that occurred following eccentric contractions. This might account for the finding that the actual level of force applied by the exercised arm was less than that generated by the control arm, even though the participants may have perceived the forces to be equal. In a related vein, it might be suggested that in circumstances of a mismatch between information provided by the sense of effort and the sense of tension, the motor command is adjusted upward. Nonetheless, such accounts leave unanswered the question of why, when the forces applied were expressed as a proportion of the maximum force that could be generated at that time, the match was extremely close in every instance. We prefer to raise the possibility that, in situations in which there is a large mismatch between the sense of force and the sense of effort, individuals place exclusive emphasis upon the sense of effort. Such circumstances are likely to arise when there is a substantial reduction in the force-generating capacity of the muscle, such as that which results from damaging, eccentric contractions. In the present study, the participants exhibited a strong sensitivity to the state of the musculature, in terms of its force-generating capacity. This sensitivity formed the basis of judgements of force that were scaled precisely with respect to the maximum level of force that could be generated at that time. The outcome is that which would be expected if the estimates of force were based on a sense of effort. Evidently, however, the sense of effort was not simply based upon a corollary of the central motor command. Rather, our results suggest that the relationship between the sense of effort and the motor command was altered as a result of the fatiguing eccentric contractions. The possibility that the sense of effort is associated with activity in neural centres upstream of the motor cortex is one that is worthy of further investigation.

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