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Journal of Physiology (1990), 429, pp. 113-129 With 5 figures Printed in Great Britain

PERCEPTUAL RESPONSES TO MICROSTIMULATION OF SINGLE AFFERENTS INNERVATING JOINTS, MUSCLES AND SKIN OF THE HUMAN HAND

BY GARY MACEFIELD, SIMON C. GANDEVIA AND DAVID BURKE From the Department of Clinical Neurophysiology, Institute of Neurological Sciences, The Prince Henry and Prince of Wales Hospitals and School of Medicine, University of New South Wales, Sydney, Australia 2036

(Received 20 April 1990) SUMMARY

1. Microneurographic techniques were used to isolate single afferent axons within cutaneous and motor fascicles of the median and ulnar nerves at the wrist in thirteen subjects. Of the sixty-five identified afferents, eleven innervated the interphalangeal and metacarpophalangeal joints, sixteen innervated muscle spindles, three innervated Golgi tendon organs and thirty-five supplied the glabrous skin of the hand. 2. Intrafascicular stimulation through the recording microelectrode, using trains of constant-voltage positive pulses (0*3-48 V, 0-1-02 ms, 1-100 Hz) or constantcurrent biphasic pulses (0A4-13 0 ,uA, 0-2 ms, 1-100 Hz), evoked specific sensations from sites associated with some afferent species but not others. 3. Microstimulation of eight of the eleven joint afferent sites (73 %) evoked specific sensations. With four, subjects reported innocuous deep sensations referred to the relevant joint. With the other four, the subjects reported a sensation of joint displacement that partially reflected the responsiveness of the afferents to joint rotation. 4. Microstimulation of fourteen of the sixteen muscle spindle afferent sites (88 %) generated no perceptions when the stimuli did not produce overt movement. However, subjects could correctly detect the slight movements generated when the stimuli excited the motor axons to the parent muscle. 5. With seven of the nine rapidly adapting (type RA or FAI) cutaneous afferents (88 %) microstimulation evoked sensations of 'flutter-vibration', and with two of eight slowly adapting (type SAI) afferents (25%) it evoked sensations of 'sustained pressure'. Of the eighteen SAII afferents, which were classified as such by their responses to planar skin stretch, the majority (83 %) generated no perceptions, confirming previous work, but three evoked sensations of movements or pressure. 6. The present results suggest a relatively secure transmission of joint afferent traffic to perceptual levels, and it is concluded that the human brain may be able to synthesize meaningful information on joint displacement on the basis of impulses in a single joint afferent. This could partly compensate for the low responsiveness of individual joint afferents within the physiological range of joint displacements. Although single muscle spindle afferents can adequately encode joint position and 'MS 84

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movement, the results suggest that the brain needs the information from more than one muscle spindle afferent to perceive changes in joint angle. INTRODUCTION

Intrafascicular recording from tungsten microelectrodes inserted percutaneously into human peripheral nerves has allowed detailed study of the physiological properties of single afferents innervating low-threshold mechanoreceptors in the skin and within muscle (for reviews see Vallbo, Hagbarth, Torebj6rk & Wallin, 1979; Burke, 1981). Recently, the microneurographic technique has also been used to record from single afferents supplying the interphalangeal and metacarpophalangeal joints of the human hand (Burke, Gandevia & Macefield, 1988). Because microneurography is performed on conscious subjects it allows more than just the receptor properties to be characterized, lending itself to psychophysical studies on detection of stimuli. Johansson & Vallbo (1979) have calculated that subjects can detect a single impulse evoked by mechanical stimulation of a single rapidly adapting cutaneous afferent. A technique complimentary to microneurography, intraneural microstimulation, was introduced to address the issue of sensory specificity, i.e. whether the information carried by a single cutaneous afferent is sufficient to generate an elementary sensation of a particular tactile quality (Torebjork & Ochoa, 1980; Vallbo, 1981). The technique involves delivering low-level voltage or current pulses through the same microelectrode from which the activity of a single sensory axon can be recorded. The perceptual responses to microstimulation of rapidly adapting and slowly adapting cutaneous afferents are remarkably consistent: excitation of a single rapidly adapting afferent generally evokes a sensation of superficial flutter or vibration referred to the receptive field, whereas excitation of a slowly adapting afferent can evoke a sensation of sustained pressure (Torebjork & Ochoa, 1980; Vallbo, 1981; Ochoa & Torebjork, 1983; Schady & Torebjork, 1983; Schady, Torebj6rk & Ochoa, 1983a, b; Vallbo, Olsson, Westberg & Clark, 1984). In a previous study we compared the responses of single afferents originating in the digital joints, intrinsic muscles and glabrous skin of the human hand to passive joint rotation, and assessed the relative capacities of these three mechanoreceptor species to encode position and movement at a single joint (Burke et al. 1988). The present work details the perceptual responses to microstimulation of intrafascicular sites associated with single sensory axons supplying interphalangeal or metacarpophalangeal joints or intrinsic muscles. In addition, we have re-examined the perceptual responses to microstimulation of identified cutaneous afferents, with particular reference to the stretch-sensitive SAII afferents. We find that microstimulation of a single joint afferent site often evokes a specific sensation referred to the relevant joint, but that selective excitation of single muscle spindle afferents or cutaneous SAII afferents is not detected. METHODS

The observations are based on twenty-six experimental sessions performed on thirteen adult volunteers, including the authors and four other physiologists and six subjects who were completely unaware of the hypotheses being tested. All subjects were neurologically normal and

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each provided informed consent to the experimental procedures, which were conducted with the approval of the institutional ethics committee. Recording procedures The subject was seated comfortably with the left or right arm supported supine on a padded table. An insulated tungsten microelectrode (type 25-10-1, Frederick Haer) was inserted percutaneously into the median nerve (thirteen experiments) or ulnar nerve (thirteen experiments) 2-3 cm proximal to the wrist, and directed into a 'cutaneous' or 'motor' fascicle as described previously (Burke et al. 1988). An adjacent subdermal needle electrode served as the reference electrode. During the searching procedures pulses (1-10 V. 0-1-02 ms, 0-8 Hz) were delivered through the microelectrode from a constant-voltage stimulator (Grass S88), via an isolation unit (Grass SIU5). The median nerve was favoured for recording from cutaneous fascicles, which were defined as those from which radiating cutaneous paraesthesiae were evoked by intraneural stimulation and from which afferent activity could be evoked by superficial tactile stimulation of the fascicular innervation zone. The ulnar nerve was primarily employed for recording from motor fascicles, defined on the basis of the twitches evoked by intraneural stimulation and the afferent activity evoked by palpation or stretch of the intrinsic muscles. The microelectrode was manipulated until the activity of a single afferent could be recorded with a sufficiently high signal-to-noise ratio and minimal contamination from adjacent afferents. In four cases, pairs of identified, discriminable units were recorded and stimulated. Neural activity was amplified (2-5 x 104), filtered (03-30 kHz), and recorded with stimulus and voice signals on magnetic tape. During recording the unitary integrity of the action potentials was monitored by superimposing the spikes, triggered and delayed via a window discriminator (Bak Electronics), on a storage oscilloscope using a 2 ms time base. All recorded units were subsequently analysed offline and photographed from the oscilloscope and their instantaneous frequency profile (Ortec) displayed on an ink-jet recorder (Mingograf, Siemens-Elema).

Classification of afferents The classification procedures of single afferents from joints, muscle and skin of the hand have been detailed previously (Burke et al. 1988). Briefly, an afferent was classified as supplying a joint receptor if it satisfied the following criteria: (i) it did not respond to superficial cutaneous stimulation, (ii) it did not respond to pressure over adjacent muscles, and (iii) it did respond with a high mechanical threshold to maintained pressure applied directly over the joint capsule but not over adjacent non-articular bone. Additionally, all the joint afferents included in the present sample responded in one or more axes of rotation to passive displacements or stresses of a single interphalangeal or metacarpophalangeal joint. Single afferents were defined as originating in muscle on the basis of their low-threshold, slowly adapting responses to direct palpation of a muscle and to stretch of the muscle by rotation of one or more interphalangeal or metacarpophalangeal joints in one or more axes. Muscle afferents were classified as supplying muscle spindles or Golgi tendon organs according to their behaviour during the muscular twitch evoked by intrafascicular stimulation through the recording microelectrode (McKeon & Burke, 1980; Burke, Aniss & Gandevia, 1987; Burke et al. 1988). Spontaneously active muscle spindle afferents were silenced during the rising phase of the twitch contraction and those without a background discharge were recruited during its falling phase (> 80 ms post-stimulus). Conversely, Golgi tendon organ afferents were activated during the rising phase of the twitch (< 80 ms). Cutaneous afferents were classified as slowly or rapidly adapting on the basis of their response to a maintained indentation and further subdivided into FAI (RA), FAII (PC), SAI and SAII classes according to the criteria established by others (Knibestol & Vallbo, 1970; Knibest6l, 1973, 1975; Hulliger, Nordh, Thelin & Vallbo, 1979; Johansson & Vallbo, 1979; see also Burke et al. 1988). In brief, SAI afferents did not respond to remote planar skin stretch, whereas SAII afferents did. The receptive fields of the SAI and FAI afferents were generally small and those of the SAII and FAII afferents were large. Calibrated von Frey hairs (Semmes-Weinstein Aesthesiometer, Stoelting) were used to determine the mechanical threshold of the receptor. Stimulation procedures After identifying and characterizing a single afferent, the preamplifier was switched to allow stimuli to be delivered through the microelectrode. In twenty-one experiments positive, rectangular

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pulses (0-30-1-24 V, 0-1-02 ms) were delivered at 1-100 Hz from an isolated constant-voltage stimulator. Because the voltage relationship between the stimulator (Grass S88) and the isolator (Grass SIU5) is not linear, the absolute voltages delivered to the electrode were corrected from a calibration graph. In five experiments constant-current biphasic (positive-negative) pulses (0-40-13-00 1zA, 0-1-02 ms, 1-100 Hz) were used (Bak Electronics). Stimuli were given as single pulses or as trains lasting 0-5-2-0 s. The subject received no audiovisual feedback about the delivery of the stimuli, but was required to close his or her eyes and to concentrate when the experimenter indicated that stimulation was about to occur. The voltage or current pulses were slowly increased until the subject reported a sensation, and then carefully fractionated until the lowest threshold, consistent, elementary percept was reported. Subjects were provided with a set of standardized adjectives, expanded from the categories used by Ochoa & Torebjork (1983). The six levels of description were: (i) superficial or deep, (ii) stationary or migratory, (iii) natural or unnatural, (iv) intermittent or sustained, (v) non-painful or painful, (vi) tapping, flutter, tickle, tingle, vibration, buzzing, pressure, tension, torsion, movement or oscillation. Subjects were also encouraged to describe their sensations on tape. When movements were detected subjects were asked to nominate the perceived direction and estimate its extent. In some experiments a potentiometer was fixed over a relevant joint of the contralateral hand to allow the subject to indicate the perceived change in joint angle during microstimulation. After the perceptual responses had been characterized at different frequencies of stimulation, the preamplifier was switched back to the recording mode, the unitary integrity of the afferent was confirmed and its properties reassessed. RESULTS

Afferent sample and spike morphologies The experimental technique is represented schematically in Fig. 1. Unitary recordings were made from sixty-five identified afferents in the median and ulnar nerves at the wrist in thirteen subjects. Based on the criteria outlined in Methods, eleven of the single afferents were classified as joint afferents, nineteen as muscle afferents and thirty-five as cutaneous afferents. As noted previously (Burke et al. 1988), the spike amplitudes were similar between the three mechanoreceptor species. Representative morphologies of the recorded action potentials (0 3-30 kHz) are illustrated in Fig. 2. Based on the results of Vallbo (1976), the majority of the afferent

population (65%) had spike shapes characteristic of extra-axonal recordings. Of these, few had a biphasic shape, consisting of an initial positive phase and a subsequent negativity of approximately equal amplitude (Fig. 2A); most had triphasic negative spikes, consisting of an initial small positive deflection, a major negative spike and subsequent small positivity (Fig. 2B), which was occasionally succeeded by a broad negative phase (Fig. 2C). Such triphasic spike morphologies represent extra-axonal recordings from the nearest node of Ranvier (see Fig. 1). The remainder of the population had spike morphologies in which the major spike was positive, presumably reflecting impalement of the myelin sheath by the electrode tip (Vallbo, 1976). For 20% of these the recording was triphasic (Fig. 2D), indicating possible propagation block (Vallbo, 1976; see Calancie & Stein, 1988), which although limiting the transmission of naturally evoked discharges across the recording site would not prevent electrical excitation of the axon at that site. Fifteen per cent of the recorded spikes were polyphasic (Fig. 2E and F); the second spike of such a recording probably represents the action potential generated at the next node 'down-stream' from the microelectrode (Vallbo, 1976). The dominant spike morphologies of the afferent population were type B (i.e. as in Fig. 2B) for the joint

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Record U

Stim ulate

Intrafascicular recording site

Fig. 1. Experimental arrangement for recording and stimulating intrafascicular sites associated with single afferents originating in the skin, joint or muscle of the hand. As indicated in the exploded schematic view of a cutaneous fascicle of the median nerve, the tip of the microelectrode is manipulated until it is near a single axon. The behaviour of the afferent during natural stimulation of its receptive field can be recorded and the amplifier then switched to allow microstimulation of the recording site. The highimpedance microelectrode records and stimulates preferentially in the vicinity of the nearest node of Ranvier.

afferents, type C for the muscle afferents, and types B and D for the cutaneous afferents. Thus, it was only the cutaneous afferent sample that included a large proportion of recordings suggestive of impalement of the myelin sheath and possible propagation block (but not stimulation block); the joint and muscle afferent recordings were each made primarily in the vicinity of a single axonal node. As illustrated in Fig. 3, the voltage levels used during microstimulation were in the same range for intrafascicular sites associated with single joint, muscle and

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cutaneous afferents (mean + S.D., 044 + 020 V), indicating that for each type of afferent the proximity of the microelectrode tip to the axon was probably similar. The range was similar to that employed by Schady et al. (1983 a). In the five experiments in which constant-current biphasic pulses were used to stimulate twelve cutaneous sites and one joint afferent site the mean level was 5-47 ,uA (S.D. 4 23). Extra-axonal recording

Myelin sheath impaled

I

0.5 ms

I L,

1

0.5 ms

Fig. 2. Representative morphologies of the recorded unitary action potentials, and their relative contributions to the unit sample. Each panel consists of 15 superimposed spikes recorded from a single afferent. Those recordings in the left column were the most common, having major negative spikes and reflecting voltage differences in the immediate vicinity of a node of Ranvier. Those in the right column had major positive spikes, presumably reflecting potential differences in the internodal region, the microelectrode tip having impaled the myelin sheath. Sources of the records: A, cutaneous FAI afferent; B, joint afferent; C, cutaneous SAII afferent; D, muscle spindle afferent; E and F, cutaneous SAII afferent. -

Joint afferents Responses to natural stimulation Of the eleven identified single joint afferents, three innervated the metacarpophalangeal joint of digits I, II and IV, four the interphalangeal joint of digit I, three the proximal interphalangeal joint of digits II and V, and one the distal interphalangeal joint of digit III. The majority (8) were recorded from cutaneous fascicles of the median nerve. Two afferents were recorded from cutaneous fascicles of the ulnar nerve and one from a motor fascicle. The responses of human joint afferents to passive joint movement have been

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Joint afferents

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Cutaneous afferents n 6-

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0-75

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Fig. 3. Range of voltages used to microstimulate intrafascicular sites associated with a single afferent originating in a digital joint, intrinsic muscle or in glabrous skin of the hand. The columns represent the number of sites at which a stimulus evoked a specific sensation. For the muscle afferents, the indicated stimulus levels caused a visible contraction of the receptor-bearing muscle, due to excitation of motor axons adjacent to the recorded muscle spindle afferent. TABLE 1. Responses of joint afferents to natural and electrical stimulation Bidirectional Multiaxial Perceptual Resting response response Units response Digit discharge 5 2 4 5 I 5 1 0 1 1 1 1 0 2 2 2 III 0 1 1 1 1 IV 1 2 0 1 2 v 8 10 11 4 (36%) 9 (82%) Total (91 %) (73 %) Behaviour of single joint afferents originating in the metacarpophalangeal and interphalangeal joints of the hand during passive joint rotation, and the sensations evoked by microstimulation of the intrafascicular recording site that were referred to the relevant joint. The majority of the joint afferents responded in both directions of angular excursion and in two or three axes of joint rotation. Microstimulation evoked specific percepts for the majority of afferent sites.

detailed previously (Burke et al. 1988); the present sample includes seven of the afferents whose behaviour has been described in the earlier paper. In addition to responding to firm pressure over the joint capsule, all responded with a slowly adapting discharge to extreme angular displacements in one or more axes of joint rotation. None responded to passive joint movement across the physiological range.

G. MACEFIELD, S. C. GANDEVIA AND D. BURKE Table 1 summarizes the behaviour of the present sample of joint afferents during passive joint movements. Four of the afferents were tonically active when their joints were in the position of rest, and the majority responded in both directions of joint rotation and in two or three axes of rotation. 120

Joint afferent Digit I interphalangeal

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Fig. 4. A, behaviour of a single joint afferent associated with the interphalangeal joint of the thumb. Upper trace, instantaneous frequency; lower trace, schematic representation of changes in joint angle during passive movement. In the position of rest, with the thumb flexed 90 deg, the afferent was silent, but responded with a slowly adapting discharge when sustained pressure was applied directly over the joint capsule. The afferent also responded when the joint was flexed by 45 deg, accelerating towards hyperflexion, and when held extended (180 deg) maintained a regular discharge, accelerating towards the limits of extension. B, superimposed spikes recorded from the joint afferent before and after microstimulation, indicating that the morphology of the action potential (and hence the recording site) remained constant.

Figure 4A illustrates the behaviour of an afferent originating in the interphalangeal joint of the thumb. In the rest position of the hand the afferent was silent, but could be recruited by deep pressure over the joint. It was also activated by passive rotation of the joint towards the limits of both flexion and extension, and could maintain a regular discharge frequency when held at angles near the limits of rotation. In addition, the afferent responded to longitudinal rotation of the interphalangeal joint towards the index finger (intorsion), but its maximal response was always to flexion or deep pressure. The behaviour of another unit innervating the same joint is

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illustrated in Fig. 5A. This afferent was unidirectionally responsive in all three axes of rotation, maintaining a highly regular discharge at each of the angular extremes. Responses to electrical stimulation Microstimulation of eight of the joint afferent sites generated perceptions; the remaining three afferent sites that were microstimulated gave no definite perceptions A Joint afferent Digit interphalangeal

Pressure

B

Perceptual responses

Abduction

Abduction

__JEUEEhUL_ Maintained flexion Extorsion Extorsion

Extorsion

, 5s

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Fig. 5. A, responses of a single joint afferent associated with the interphalangeal joint of the thumb to sustained pressure and passive joint movements in each of the three axes of rotation: abduction (lateral stress applied to distal phalanx), full flexion and extorsion (longitudinal rotations of the distal phalanx). The behaviour of this unit has been described previously (Fig. 5 in Burke et al. 1988). B, perceptual matching during microstimulation of the same joint afferent. The subject recorded the perceived movements by flexing the interphalangeal joint of the contralateral thumb; changes in joint angle were registered by a potentiometer fixed over the axis of rotation (upper trace in both panels). The spikes in the lower traces represent the voltage pulses (0-35 V, 0.1 Ims, 20 Hz trains) delivered to the intrafascicular recording site. In both examples the response latency to the stimulus is 350 ms.

referred to the relevant joint (Table 1). Single pulses were perceived as deep punctate sensations referred to the joint capsule. Trains of stimuli (20-50 Hz, 0-5-2-0 s) were delivered to six sites. For four of these, subjects perceived a simple or complex movement of the relevant joint during the train; for two sites only a deep sensation was felt across the joint. Of the four afferent sites that generated perceptions of movement one was located in the metacarpophalangeal joint of the thumb, two in its interphalangeal joint, and one in the proximal interphalangeal joint of the index finger. Microstimulation of the joint afferent site in Fig. 4 resulted in a perception of interphalangeal flexion. The extent of the perceived rotation was dependent on the frequency of stimulation. At 10 Hz the subject did not feel any displacement. Between 20 and 40 Hz the subject perceived a slight flexion, of approximately 2-4 deg. Trains of stimuli at 80 Hz were felt as slightly greater movements, estimated at 7 deg. Note that flexion was the direction in which the afferent was

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maximally responsive, but it only discharged at 20 Hz at the limit of flexion. Figure 4B indicates that the spike morphology of the afferent had not changed when its properties were reassessed following microstimulation. Figure 5B illustrates an experiment in which a potentiometer was fixed over the interphalangeal joint of the contralateral thumb and the subject indicated the perceived movement that occurred during microstimulation. The afferent responded to sustained pressure over the joint and also responded unidirectionally in all three axes of rotation. During microstimulation, the subject reported a complex movement which contained each of the elements of the afferent's responses to natural stimulation - the subject felt as if the distal phalanx of the thumb was being bent laterally at the same time as being flexed and twisted outwards about its longitudinal axis. The subject matched the perceived complex angular displacement by flexing the interphalangeal joint of the contralateral thumb. The latency between delivery of the stimulus train and the matching response was identical in the two examples shown (350 ms). With each of the four afferents for which microstimulation evoked perceptions of movement the reported displacements were only small, not at the limits of joint rotation at which they were maximally responsive. None of the subjects considered the sensations uncomfortable.

Muscle afferents Responses to natural stimulation Nineteen single muscle afferents were recorded from and microstimulated. On the basis of the twitch test (see Methods), sixteen were classified as innervating muscle spindles and three as innervating Golgi tendon organs. Six muscle spindle afferents were recorded from motor fascicles of the median nerve, four supplying abductor pollicis brevis and two supplying opponens pollicis. The remainder were recorded from the ulnar nerve: two supplied adductor pollicis, one each the first and third dorsal interossei, two the fourth palmar interosseous, one the fourth lumbrical and three abductor digiti minimi. All of the muscle spindle afferents were activated by direct palpation, stretch of the parent muscle in one or more axes of joint rotation, or weak voluntary contraction of the parent muscle. Four were spontaneously active in the position of rest (Table 2). No formal subdivision of the afferent sample into spindle primaries and secondaries was undertaken, although the regular discharge frequencies of the spontaneously active afferents would suggest that they originated in secondary endings. The Golgi tendon organs were in opponens pollicis and the first and third dorsal interossei, and were recruited during the muscular twitches evoked by intrafascicular stimulation. One was responsive to muscle stretch and could be voluntarily activated.

Responses to electrical stimulation Only for two muscle spindle afferent sites did microstimulation produce a perception below the electrical threshold for an overt contraction of the parent muscle (Table 2). One subject perceived abduction of the thumb, i.e. stretch of the receptor-bearing muscle (adductor pollicis), for 10% of the stimulus trains The other a (0-56 V, 30 Hz). subject reported 'tightness' in the receptor-bearing -

PERCEPTION OF INFORMATION FROM THE HAND 123 muscle (abductor pollicis brevis); although the stimuli were below movement threshold, local skin dimpling was apparent, indicating that some motor units were activated by the stimulus trains (0-48 V, 100 Hz). Two other subjects also detected fasciculations in the muscle at stimulus levels immediately below those required to cause a movement. All subjects could perceive the slight movements (- 5 deg) TABLE 2. Responses of muscle spindle afferents to natural and electrical stimulation Resting Bidirectional Multiaxial Perceptual Digit Units discharge response response response I .0 8 0 0 1 II 1 1 0 0 0 III 1 1 0 0 0 IV 0 V 2 1 6 3 0 (0%) 4 (25%) Total 16 3 (19%) 2 (13%) Behaviour of single muscle spindle afferents originating in the intrinsic muscles of the hand during passive joint rotation, and the sensations evoked by microstimulation of the intrafascicular recording site that were perceived as stretch of the receptor-bearing muscle. All muscle spindle afferents responded in only one direction of joint rotation, that which stretched the parent muscle, and few responded to rotations in two or more axes. Microstimulation of the majority did not evoke sensations of joint movements that would produce muscle lengthening. When the stimulus trains were at or just above threshold for evoking an overt contraction of the parent muscle all subjects reported movements that would shorten the muscle.

generated by excitation of adjacent motor axons innervating the muscle under study, but with the exception of the subject referred to above, no sensations of stretch of the parent muscle were reported. Subjects could correctly detect the direction of the movement evoked by 20-50 Hz trains of stimuli at motor threshold. Occasionally, subjects reported the evoked movements in terms of cutaneous sensations. For example, one subject described flexion of the metacarpophalangeal joint as 'stretch of the skin on the back of the hand'; another described adduction at the joint as 'contact between the finger tips'. One subject, on seeing the stimulusevoked movement, noted that the perceived movement was greater than the actual movement. Of the three Golgi tendon organ afferents recorded and stimulated only one, originating in opponens pollicis, generated a perception below motor threshold (0-72 V). Microstimulation of the afferent site (0-41 V, 30 Hz) was felt as 'a pulling at the base of the thumb' into abduction, i.e. as a lengthening of opponens pollicis. However, because of the small sample little can be said on the perception of information from single Golgi tendon organs.

Cutaneous afferents Responses to natural stimulation Twenty-six single afferents, innervating low-threshold mechanoreceptors in the glabrous skin of the hand, were identified in cutaneous fascicles of the median nerve and nine in cutaneous fascicles of the ulnar nerve. Nine adapted rapidly to a sustained indentation and had discrete receptive fields (type FAI), but none

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possessed the extensive receptive fields characteristic of Pacinian (FAII) endings. The remainder were slowly adapting: eight did not respond to planar skin stretch and were classified as SAI; eighteen that did respond to skin stretch and had wider receptive fields were classified as SAII. The greater representation of SAII afferents in the sample can be attributed to the fact that our searching procedures were biased TABLE 3. Responses of cutaneous SAII afferents to natural and electrical stimulation Multiaxial Perceptual Resting Bidirectional Units response response Digit discharge response 1 I 0 8 0 3 II 1 2 0 0 0 1 2 III 2 0 3 2 1 1 1 IV 0 V 3 0 0 0 0 3 (17%) 3 (17%) Total 18 1 (6%) 6 (33%) Behaviour of single cutaneous SAII afferents originating in the glabrous skin of the hand during passive joint rotation, and the sensations evoked by microstimulation of the intrafascicular recording site that were perceived as movement or pressure. The majority of the SAII afferents responded unidirectionally in one axis of rotation, and microstimulation did not evoke a percept referred to the receptive field.

towards recording from these afferents, in order to determine whether excitation of these stretch-sensitive afferents would yield a sensation of joint movement or skin stretch (Table 3). With the exception of one SAII afferent associated with the distal interphalangeal joint of the middle finger, all SA units were silent in the rest position of the hand. The majority were associated with joints or were located near the nails. The responses of cutaneous afferents from the human hand to active and passive joint movements have been characterized previously (Hulliger et al. 1979; Burke et al. 1988).

Responses to electrical stimulation The present observations on the perceptual responses to stimulation of intrafascicular sites associated with single cutaneous afferents (0-30-0-72 V or 0-40-13-00 4A) largely confirm the findings of the original microstimulation studies (Ochoa & Torebjork, 1983; Schady & Torebjork, 1983; Schady et al. 1983 a, b; Vallbo et al. 1984; Torebjork, Vallbo & Ochoa, 1987), which dealt exclusively with cutaneous afferents. With seven of the nine RA afferent sites (88 %) microstimulation generated sensations of superficial 'flutter', 'vibration' or 'tingling' when trains of stimuli were delivered at 20-100 Hz. Low-frequency stimulation was perceived as superficial 'tapping', which developed into 'flutter' as the stimulation frequency increased to - 20 Hz. For two of the afferent sites the perceptions were not referred to the receptive field. With only two of the eight SAI afferent sites (25 %), however, did perceptions of 'sustained pressure' occur, the subjective intensity increasing with stimulation frequency (10-80 Hz). For three others microstimulation evoked no sensations referred to the receptive field, two evoked a sensation of 'fluttervibration-tickle' and another evoked a sensation of 'tingling' in response to trains of 10-100 Hz. Following stimulation of the latter three sites a search of the fascicular

PERCEPTION OF INFORMATION FROM THE HAND 125 innervation zone in the vicinity of the percept failed to identify rapidly adapting afferents. As noted by Schady et al. (1983 a), intermittent sensations can be detected more readily than sustained sensations, so evoked signals of pressure may not have been noticed by some subjects. None of our subjects received any cues on the type of stimulus (single pulses or trains of differing frequency) they were about to receive or had just received. With fifteen of the eighteen SAII afferent sites (83%), microstimulation (10-100 Hz) consistently produced no specific sensations referred to the receptive field or adjacent skin (Table 3). The first sensations evoked as stimulus intensity was increased were usually tactile sensations, referred to areas (and digits) remote from the receptive field, or mildly painful sensations. One subject reported a feeling of 'swelling through the finger... like when you come into a warm room from the cold ... nothing definite' during stimulation of an SAII site. However, stimulation of two SAII afferent sites, located near nailbeds and responding to movements of the distal joint, evoked sensations of movement corresponding to their responsiveness to passive movements. The other afferent site, located at the web space between the thumb and index finger, evoked a sensation of sustained pressure. This unit was unusual in that, although it responded to longitudinal skin stretch and had a large receptive field, it possessed a high dynamic sensitivity and irregular discharge features of the SAI afferents (Knibest6l, 1975). DISCUSSION

Using similar techniques, the present study has confirmed earlier reports on the perception of afferent signals conducted by single cutaneous axons: rapidly adapting mechanoreceptors with discrete receptive fields (type FAI or RA) generally evoke tactile sensations of cyclic events (flutter-vibration), and some slowly adapting mechanoreceptors with discrete receptive fields (type SAI) convey information on non-cyclic events (pressure), but stimulation of SAII afferents, which are responsive to planar skin stretch and have relatively large receptive fields, generally evoke no specific tactile percept (Ochoa & Torebj6rk, 1983; Schady & Torebjork, 1983; Schady, Torebj6rk & Ochoa, 1983a, b; Vallbo et al. 1984). The novel findings of this study, however, lie in characterization of the perceptual responses to microstimulation of intrafascicular sites at which single, identified mechanoreceptor afferents innervating the joints and intrinsic muscles of the hand are located. We conclude that activation of a single joint afferent can evoke a specific and meaningful sensation referred to the relevant joint, but that a single muscle spindle afferent cannot provide perceptual information on muscle length. Intraneural stimulation of single axons Wall & McMahon (1985) have criticized the technique of intraneural microstimulation, claiming that the voltage or current pulses delivered through the recording microelectrode could not possibly excite a single axon in isolation. The objections raised by these authors were largely theoretical, based on assumptions that have been refuted by Torebjork et al. (1987). When a single cutaneous afferent is recorded and subsequently stimulated (or vice versa), subjects may perceive one

G. MACEFIELD, S. C. GANDEVIA AND D. BURKE 126 or more sensations referred to one or more circumscribed fields. That these evoked sensations are quantal in nature, each generating a simple tactile percept that can be discriminated and projected to a corresponding receptive field by the subject, and that an axon of the lowest electrical threshold will evoke a unitary sensation suggests that activation of a single identified cutaneous afferent can be perceived as a stimulus with a specific tactile quality (Ochoa & Torebjork, 1983; Schady & Torebj6rk, 1983; Schady, Torebjork & Ochoa, 1983a, b; Vallbo et al. 1984; present results). In the present study the majority of the recorded action potentials were triphasic, with the dominant spike being negative. This morphology, together with the uniformly high signal-to-noise ratio of the selected axons, indicates that the tip of the microelectrode was located outside the axon but close to a node of Ranvier, rather than intra-axonally (cf. Schady & Torebj6rk, 1983). The close correlation between the receptive and projected fields of cutaneous axons (Ochoa & Torebjork, 1983; Schady & Torebj6rk, 1983; Schady et al. 1983b; Vallbo et al. 1984) indicates that the same sensory axon that can be recorded in isolation can also be stimulated in isolation. The probability of recording from and stimulating a single axon has been discussed on the grounds of the number of myelinated fibres in a fascicle, their diameters and hence electrical threshold, and the number of nodes of Ranvier (the sites of axonal excitation) in the vicinity of the electrode tip (Schady et al. 1983a). In the present study, microstimulation of muscle spindle afferents and cutaneous SAII afferents consistently produced no sensations referred to the receptive field, but adjacent motor or cutaneous axons in the fascicle could be excited when stimulus levels were increased, resulting in contraction of the relevant muscle or quantal sensations referred remotely or diffusely. The voltage or current levels used were in the same range as those with which single joint and cutaneous SAI and FAI afferents evoked sensations, and were comparable to those employed by Schady et al. (1983 a) and Vallbo et al. (1984) in their studies of cutaneous axons.

Implications for kinaesthesia of the hand A recent microneurographic study documents the responses during passive movement of the three mechanoreceptor species that have been proposed to provide sensations of joint position and movement in the hand and elsewhere: afferents from the joint capsule, the muscle spindle and skin (Burke et al. 1988). The conclusions of this study were that none of the afferent species can unambiguously encode movement of a single joint in a single axis of rotation, but that muscle spindle afferents provide the most relevant kinaesthetic information because they respond unidirectionally across the physiological range of movement. Only a few joint afferents respond across the physiological range, the majority responding towards extreme angular excursions in more than one axis of rotation (Burke et al. 1988). Cutaneous afferents also respond at the limits of joint rotation, and their role in kinaesthesia must therefore be limited (Hulliger et al. 1979; Burke et al. 1988). In the present study microstimulation of only two cutaneous afferent sites, classified as SAII, evoked perceptions of joint movement. However, subjects occasionally relied on cues from the skin when describing the actual movements evoked when the stimulation was sufficient to excite motor axons. This latter observation, together with the observation that subjects occasionally detected fasciculations in the muscle (resulting

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in deformation of the overlying skin) at stimulus levels below those required to evoke an overt movement, suggests that cutaneous afferents can provide important directional information about small movements. Despite the capacity of individual spindle afferents from human finger flexors to encode passive position of the metacarpophalangeal joint (Vallbo, 1974; Hulliger, Nordh & Vallbo, 1982), the absence of a perceptual response to stimulation of single spindle afferents from muscles acting on the same and associated joints needs to be reconciled with psychophysical observations that attribute an important role to spindle afferents in position and movement sense (Goodwin, McCloskey & Matthews, 1972; Gandevia & McCloskey, 1976; McCloskey, 1978; Matthews, 1982; McCloskey, Macefield, Gandevia & Burke, 1987). Stimulation of low-threshold muscle afferents from the hand evokes a short-latency cortical potential (Gandevia, Burke & McKeon, 1984) and, below motor threshold, even a single stimulus can evoke illusions of muscle stretch (Gandevia, 1985). However, these studies involved stimulation of a population of muscle afferents, rather than of single afferents as in the present investigation. More than one muscle spindle afferent is activated during passive movement and presumably the brain can obtain information on muscle length and hence joint position from the ensemble pattern of spindle activity. Spatial summation from many muscle spindle afferents must be required to ensure synaptic transmission to perceptual levels. The same may be true for the majority of the cutaneous SAII afferents. It should be stressed that a normal joint movement will activate many mechanoreceptors. The heightened activity in a single-afferent channel would need to be interpreted on the basis of unchanged activity in other channels. Presumably, the brain resolves this conflict by ignoring the discrepant single channel. Conversely, the brain can probably obtain meaningful information from the afferent traffic of a single joint afferent, despite the limited capacity of these afferents to encode position and movement. Microstimulation of the majority of joint afferent sites evoked a sensation related to the relevant joint. For four of these sites, movement was perceived. The perceived change in joint position was judged to be small, a paradox because the relevant afferents were activated physiologically towards the limits of joint rotation. Presumably, the brain can abstract only partial information on the basis of activity in a single joint afferent, requiring co-activation of other afferents in muscle, skin and joint to synthesize an appropriate picture of extreme joint position. It is likely that in these experiments the subjects were presented with conflicting sensory cues, one which suggested an extreme joint position and others which denied any change in joint angle, and that they chose to resolve this conflict by some form of perceptual compromise. This work was supported by the National Health and Medical Research Council of Australia. We are most grateful to Professors K.-E. Hagbarth and E. Torebjork for their constructive criticism of this study.

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