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Transcutaneous electrical stimulation with repetitive bursts of a kilohertz carrier frequency is thought to be less painful than conventional pulsed currents by reducing the sensitivity of pain receptors. However, no purported benefit has been shown unequivocally. We compared the effects of carrier-frequency stimulation and conventional stimulation on pain tolerance and the thresholds for sensory and motor axons in twelve participants. The ulnar nerve was stimulated transcutaneously with a conventional single pulse and 5 and 10 kHz carrier-frequency waveforms that had 5 and 10 pulses, respectively, when delivered in bursts of ∼1 ms duration. Phase durations were adjusted across waveform types to match the total charge for a given current amplitude. Single bursts of stimulation were delivered from 1 mA up until no longer tolerable. This was repeated with repetitive bursts of stimulation at 20 Hz for 1 s. Participants tolerated higher current amplitudes with both carrier-frequency waveforms than conventional stimulation, with repetitive bursts more painful than single bursts. However, compared to conventional stimulation, carrier-frequency waveforms required more current to produce sensory and motor-threshold responses and to obtain a maximal motor response (M max ). When the current at pain tolerance was normalised to the current at M max , participants tolerated lower stimulus intensities with carrier-frequency waveforms than conventional stimulation. These findings indicate that there is little to no benefit in using carrier-frequency waveforms to minimise the discomfort from electrical stimulation as the increase in stimulus intensity at pain tolerance is more than offset by reduced effectiveness in the activation of sensory and motor axons. KEY POINTS: Transcutaneous electrical stimulation with repetitive bursts of a kilohertz carrier-frequency waveform is thought to be less painful than conventional pulsed currents. For ulnar nerve stimulation, when stimulus waveforms were matched for total phase charge, participants tolerated higher current amplitudes with carrier-frequency stimulation than conventional stimulation. However, compared to conventional stimulation, carrier-frequency waveforms required more current to produce a threshold response in both sensory and motor axons and to produce a maximal motor response (M max ). When current at pain tolerance was normalised to current at M max , participants tolerated lower stimulus intensities with carrier-frequency waveforms than conventional stimulation. Carrier-frequency waveforms provide little to no benefit in minimising the discomfort from transcutaneous electrical stimulation as the increase in stimulus intensity at pain tolerance is more than offset by reduced effectiveness in activating sensory and motor axons., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Key Points: In the adult turtle spinal cord, action potential generation in motoneurones is inhibited by spillover of serotonin to extrasynaptic serotonin 1A (5-HT 1A ) receptors at the axon initial segment. We explored whether ingestion of the 5-HT 1A receptor partial agonist, buspirone, decreases motoneurone excitability in humans. Following ingestion of buspirone, two tests of motoneurone excitability showed decreases. F-wave areas and persistence in an intrinsic muscle of the hand were reduced, as was the area of cervicomedullary motor evoked potentials in biceps brachii. Our findings suggest that activation of 5-HT 1A receptors depresses human motoneurone excitability. Such a depression could contribute to decreased motoneurone output during fatiguing exercise if there is high serotonergic drive to the motoneurones., Abstract: Intense serotonergic drive in the turtle spinal cord results in serotonin spillover to the axon initial segment of the motoneurones where it activates serotonin 1A (5-HT 1A ) receptors and inhibits generation of action potentials. We examined whether activation of 5-HT 1A receptors decreases motoneurone excitability in humans by determining the effects of a 5-HT 1A receptor partial agonist, buspirone, on F waves and cervicomedullary motor evoked potentials (CMEPs). In a placebo-controlled double-blind study, 10 participants were tested on two occasions where either placebo or 20 mg of buspirone was administered orally. The ulnar nerve was stimulated supramaximally to evoke F waves in abductor digiti minimi (ADM). CMEPs and the maximal M wave were elicited in biceps brachii by cervicomedullary stimulation and brachial plexus stimulation, respectively. Following buspirone intake, F-wave area and persistence, as well as CMEP area, were significantly decreased. The mean post-pill difference in normalized F-wave areas and persistence between buspirone and placebo days was -27% (-42, -12; 95% confidence interval) and -9% (-16, -2), respectively. The mean post-pill difference in normalized CMEP area between buspirone and placebo days showed greater variation and was -31% (-60, -2). In conclusion, buspirone reduces motoneurone excitability in humans probably via activation of 5-HT 1A receptors at the axon initial segment. This has implications for motor output during high drive to the motoneurones when serotonin may spill over to these inhibitory receptors and consequently inhibit motoneurone output. Such a mechanism could potentially contribute to fatigue with exercise., (© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.)

Key Points: The output of human motoneurone pools decreases with fatiguing exercise, but the mechanisms involved are uncertain. We explored depression of recurrent motoneurone discharges (F-waves) after sustained maximal voluntary contractions (MVCs). MVC depressed the size and frequency of F-waves in a hand muscle but a submaximal contraction (at 50% MVC) did not. Surprisingly, activation of the motoneurones antidromically by stimulation of the ulnar nerve (at 20 or 40 Hz) did not depress F-wave area or persistence. Furthermore, a sustained (3 min) MVC of a hand muscle depressed F-waves in its antagonist but not in a remote hand muscle. Our findings suggest that depression of F-waves after voluntary contractions is not simply due to repetitive activation of the motoneurones but requires descending voluntary drive.  Furthermore, this effect may depress nearby, but not distant, spinal motoneurone pools., Abstract: There are major spinal changes induced by repetitive activity and fatigue that could contribute to 'central' fatigue but the mechanisms involved are poorly understood in humans. Here we confirmed that the recurrent motoneuronal discharge (F-wave) is reduced during relaxation immediately after a sustained maximal voluntary contraction (MVC) of an intrinsic hand muscle (abductor digiti minimi, ADM) and explored the relationship between motoneurone firing and the depression of F-waves in three ways. First, the depression (in both F-wave area and F-wave persistence) was present after a 10 s MVC (initial decrease 36.4 ± 19.1%; mean ± SD) but not after a submaximal voluntary contraction at 50% maximum. Second, to evoke motoneurone discharge without volitional effort, 10 s tetanic contractions were produced by supramaximal ulnar nerve stimulation at the elbow at physiological frequencies of 25 and 40 Hz. Surprisingly, neither produced depression of F-waves in ADM to test supramaximal stimulation of the ulnar nerve at the wrist. Finally, a sustained MVC (3 min) of the antagonist to ADM (4th palmar interosseous) depressed F-waves in the anatomically close ADM (20 ± 18.2%) but not in the more remote first dorsal interosseous on the radial side of the hand. We argue that depression of F-waves after voluntary contractions may not be due to repetitive activation of the motoneurones but requires descending voluntary drive. Furthermore, this effect may depress nearby, but not distant, spinal motoneurone pools and it reveals potentially novel mechanisms controlling the output of human motoneurones., (© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.)

The assessment of voluntary activation of human muscles usually depends on measurement of the size of the twitch produced by an interpolated nerve or cortical stimulus. In many forms of fatiguing exercise the superimposed twitch increases and thus voluntary activation appears to decline. This is termed 'central' fatigue. Recent studies on isolated mouse muscle suggest that a peripheral mechanism related to intracellular calcium sensitivity increases interpolated twitches. To test whether this problem developed with human voluntary contractions we delivered maximal tetanic stimulation to the ulnar nerve (≥60 s at physiological motoneuronal frequencies, 30 and 15 Hz). During the tetani (at 30 Hz) in which the force declined by 42%, the absolute size of the twitches evoked by interpolated stimuli (delivered regularly or only in the last second of the tetanus) diminished progressively to less than 1%. With stimulation at 30 Hz, there was also a marked reduction in size and area of the interpolated compound muscle action potential (M wave). With a 15 Hz tetanus, a progressive decline in the interpolated twitch force also occurred (to ∼10%) but did so before the area of the interpolated M wave diminished. These results indicate that the increase in interpolated twitch size predicted from the mouse studies does not occur. Diminution in superimposed twitches occurred whether or not the M wave indicated marked impairment at sarcolemmal/t-tubular levels. Consequently, the increase in superimposed twitch, which is used to denote central fatigue in human fatiguing exercise, is likely to reflect low volitional drive to high-threshold motor units, which stop firing or are discharging at low frequencies.

Despite maximal voluntary effort, the output of human motoneurone pools diminishes during fatigue. To assess motoneurone behaviour, we measured recurrent discharges evoked antidromically by supramaximal nerve stimulation after isometric maximal voluntary contractions (MVCs).They were measured as F-waves in the electromyographic activity (EMG). Supramaximal stimuli to the common peroneal and ulnar nerves evoked F-waves at rest before and after MVCs in tibialis anterior (TA) and abductor digit minimi (ADM), respectively. F-waves were depressed immediately after a sustained MVC. For TA, the size and time course of depression of the F-wave area (26 ± 13%; mean ± SD; P =0.007) and persistence (∼20%) were similar after a 10-s or 1-min MVC. For ADM, the decline in F-wave area (39.8 ± 19.6%; P <0.01) was similar after the two contractions but the decline in persistence (probability of occurrence) of the F-wave differed (14.6 ± 10.5% and 32.5 ± 17.1% after 10-s and 1-min MVCs respectively). Comparison of a very long (2-min) with a very short (2-s)MVC in ADM showed that the depression of F-wave area, as well as persistence, was greater after the longer contraction. This suggests, at least for ADM, that the depression is related to the duration of voluntary activity and that the decrease in F-waves could contribute to central fatigue. To examine whether changes in motor axon excitability caused the depression, we measured compound muscle action potentials (M-waves) to submaximal stimulation of the ulnar nerve after a 2-s and 2-min MVC. Submaximal M-waves were not depressed after a 2-s MVC. They were depressed by a 2-min MVC, but the time course of depression of the F- and M-waves differed. Thus, depression of F-waves does not simply reflect reduced excitability of peripheral motor axons.Hence, we propose that activity-dependent changes at the soma or the initial segment depress the recurrent discharge of human motoneurones and that this may contribute to central fatigue.

The present study explores the threshold behaviour of human axons and the mechanisms contributing to this behaviour. The changes in excitability of cutaneous afferents in the median nerve at the wrist were recorded to a long-lasting subthreshold conditioning stimulus, with a waveform designed to maximize the contribution of currents active in the just-subthreshold region. The conditioning stimulus produced a decrease in threshold that developed over 3-5 ms following the end of the depolarization and then decayed slowly, in a pattern similar to the recovery of axonal excitability following a discharge. To ensure that the conditioning stimulus did not activate low-threshold axons, similar recordings were then made from single motor axons in the ulnar nerve at the elbow. The findings were comparable, and behaviour with the same pattern and time course could be reproduced by subthreshold stimuli in a model of the human axon. In motor axons, subthreshold depolarizing stimuli, 1 ms long, produced a similar increase in excitability, but the late hyperpolarizing deflection was less prominent. This behaviour was again reproduced by the model axon and could be explained by the passive properties of the nodal membrane and conventional Na+ and K+ currents. The modelling studies emphasized the importance of leak current through the Barrett-Barrett resistance, even in the subthreshold region, and suggested a significant contribution of K+ currents to the threshold behaviour of axons. While the gating of slow K+ channels is slow, the resultant current may not be slow if there are substantial changes in membrane potential. By extrapolation, we suggest that, when human axons discharge, nodal slow K+ currents will be activated sufficiently early to contribute to the early changes in excitability following the action potential.

The muscles that control wrist posture receive large inputs from reflexes driven by hand afferents. In several studies, we have investigated these reflexes by electrical stimulation of cutaneous (median nerve) and proprioceptive (ulnar nerve) afferents from the hand. Median stimulation produced short latency inhibition in all motor nuclei investigated, possibly through inhibitory propriospinal-like interneurones. Ulnar stimulation produced similar inhibition but only in wrist extensors. In the other motor nuclei, ulnar stimulation produced short latency excitation mediated by group I motoneuronal drive through both monosynaptic and non-monosynaptic pathways involving excitatory propriospinal-like interneurones. This was followed by late excitations mediated through spinal group II and trans-cortical group I pathways. These results show that these pathways are concerned with the integration of afferent inputs, proprioceptive and cutaneous, to control of wrist posture during hand movements. Patients with focal hand dystonia exhibit abnormal postures. To investigate whether these spinal pathways contribute to these conditions, the effects of ulnar stimulation on wrist muscle activity during voluntary tonic contraction were examined in patients who suffer writer's cramp. Ulnar-induced inhibition of the wrist extensors was reduced on the dystonic side of patients compared with their normal side and controls. In patients who exhibited abnormal wrist posture, group II excitation of the wrist flexors was also modified on the dystonic side. Cutaneous stimuli, by contrast, increased wrist flexor EMG on both sides and only in patients who exhibited normal posture. We conclude that spinal interneurones have a significant role in integrating afferent inputs from the hand to control wrist posture during hand movements and that altered function in these spinal networks is associated with the complex pathophysiology of writer's cramp.

This study addresses whether there is excitation from human hand muscles to flexor carpi radialis (FCR) motoneurones mediated through propriospinal circuits and, if so, whether it is used in specific motor tasks. Electrical stimuli to the ulnar nerve at wrist level produced an excitation in FCR motoneurones with characteristics typical of a propriospinally mediated effect: low threshold (0.6 x motor threshold (MT)), a group I effect that was not reproduced by purely cutaneous stimuli, long central delay (4.1 +/- 0.4 ms in single units), suppression when the stimulus intensity was increased, and facilitation of the corticospinal excitation at the premotoneuronal level. Ulnar-induced propriospinally mediated excitation was compared during selective voluntary contractions of the FCR and, at equivalent level of FCR EMG, during tasks in which the FCR was activated automatically in postural contractions rather than voluntarily (grip, pinching and pointing). The excitation was significantly greater during grip (and pinching) than during voluntary FCR contractions and pointing, whether measured in single motor units or tonic EMG activity, or whether the response to motor cortex stimulation was assessed as the compound motor-evoked potential or the corticospinal peak in single units. The discrepancy between the tasks appeared with ulnar intensities above 0.8 x MT and was then present across a wide range of stimulus intensities. This suggests a reduction in the corticospinal control of 'feedback inhibitory interneurones' mediating peripheral inhibition to propriospinal neurones during grip and pinching. The resulting more effective background excitation of propriospinal neurones by the peripheral input from hand muscles could contribute to stabilizing the wrist during grip.

The efficacy of sensory input to the spinal cord can be modulated presynaptically during voluntary movement by mechanisms that depolarize afferent terminals and reduce transmitter release. It remains unclear whether similar influences are exerted on the terminals of descending fibres in the corticospinal pathway of Old World primates and man. We investigated two signatures of presynaptic inhibition of the macaque corticospinal pathway following stimulation of the peripheral nerves of the arm (median, radial and ulnar) and the pyramidal tract: (1) increased excitability of corticospinal axon terminals as revealed by changes in antidromically evoked cortical potentials, and (2) changes in the size of the corticospinal monosynaptic field potential in the spinal cord. Conditioning stimulation of the pyramidal tract increased both the terminal excitability and monosynaptic fields with similar time courses. Excitability was maximal between 7.5 and 10 ms following stimulation and returned to baseline within 40 ms. Conditioning stimulation of peripheral nerves produced no statistically significant effect in either measure. We conclude that peripheral afferents do not exert a presynaptic influence on the corticospinal pathway, and that descending volleys may produce autogenic terminal depolarization that is correlated with enhanced transmitter release. Presynaptic inhibition of afferent terminals by descending pathways and the absence of a reciprocal influence of peripheral input on corticospinal efficacy would help to preserve the fidelity of motor commands during centrally initiated movement.

This study addresses the question of the origin of the long-latency responses evoked in flexors in the forearm by afferents from human hand muscles. The effects of electrical stimuli to the ulnar nerve at wrist level were assessed in healthy subjects using post-stimulus time histograms for flexor digitorum superficialis and flexor carpi radialis (FCR) single motor units (eight subjects) and the modulation of the ongoing rectified FCR EMG (19 subjects). Ulnar stimulation evoked four successive peaks of heteronymous excitation that were not produced by purely cutaneous stimuli: a monosynaptic Ia excitation, a second group I excitation attributable to a propriospinally mediated effect, and two late peaks. The first long-latency excitation occurred 8-13 ms after monosynaptic latency and had a high-threshold (1.2-1.5 x motor threshold). When the conditioning stimulation was applied at a more distal site and when the ulnar nerve was cooled, the latency of this late excitation increased more than the latency of monosynaptic Ia excitation. This late response was not evoked in the contralateral FCR of one patient with bilateral corticospinal projections to FCR motoneurones. Finally, oral tizanidine suppressed the long-latency high-threshold excitation but not the early low-threshold group I responses. These results suggest that the late high-threshold response is mediated through a spinal pathway fed by muscle spindle group II afferents. The second long-latency excitation, less frequently observed (but probably underestimated), occurred 16-18 ms after monosynaptic latency, had a low threshold indicating a group I effect, and was not suppressed by tizanidine. It is suggested that this latest excitation involves a transcortical pathway.

Although cathodal transcranial direct current stimulation (tDCS) decreases cortical excitability, the mechanisms underlying DC-induced changes remain largely unclear. In this study we investigated the effect of cathodal DC stimulation on spontaneous neural activity and on motor responses evoked by stimulation of the central and peripheral nervous system. We studied 17 healthy volunteers. Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) of the motor area were used to study the effects of cathodal tDCS (1.5 mA, 10 min) on resting motor threshold and motor evoked potentials (MEPs) recorded from the contralateral first dorsal interosseous muscle (FDI). The electroencephalographic (EEG) activity in response to cathodal tDCS was analysed by power spectral density (PSD). Motor axonal excitability changes in response to transcutaneous DC stimulation of the ulnar nerve (0.3 mA, 10 min) were assessed by testing changes in the size of the compound muscle action potential (CMAP) elicited by submaximal nerve stimulation. Cathodal tDCS over the motor area for 10 min increased the motor threshold and decreased the size of MEPs evoked by TMS for at least 60 min after current offset (t(0) 71.7 +/- 5%, t(20) 50.8 +/- 11%, t(40) 47.7 +/- 7.7%, and t(60) 39.7 +/- 6.4%, P < 0.01). The tDCS also significantly decreased the size of MEPs elicited by TES (t(0) 64 +/- 16.4%, P = 0.09; t(20) 67.6 +/- 10.8%, P = 0.06; and t(40) 58.3 +/- 9.9%, P < 0.05). At the same time in the EEG the power of delta (2-4 Hz) and theta (4-7 Hz) rhythms increased (delta 181.1 +/- 40.2, P < 0.05; and theta 138.7 +/- 27.6, P = 0.07). At the peripheral level cathodal DC stimulation increased the size of the ulnar nerve CMAP (175 +/- 34.3%, P < 0.05). Our findings demonstrate that the after-effects of tDCS have a non-synaptic mechanism of action based upon changes in neural membrane function. These changes apart from reflecting local changes in ionic concentrations, could arise from alterations in transmembrane proteins and from electrolysis-related changes in [H(+)] induced by exposure to constant electric field.

Repetitive transcranial magnetic stimulation (rTMS) has long lasting effects on cortical excitability at the site of stimulation, on interconnected sites at a distance and on the connections between them. In the present experiments we have used the technique of transcallosal inhibition between the motor cortices to examine all three effects in the same protocol. Ten healthy subjects received 900 rTMS stimuli at 1 Hz from a figure of eight coil over the left motor hand area. The intensity of rTMS was above the threshold for inducing short latency interhemispherical inhibition with a single stimulus (equivalent to 115-120 % resting motor threshold). Before and after the rTMS we evaluated: (1) in the left hemisphere, the amplitude of motor-evoked potentials (MEPs), and contralateral and ipsilateral cortical silent periods (CSP, ISP); (2) in the right hemisphere, MEP, CSP, ISP and short-interval intracortical inhibition and intracortical facilitation (SICI/ICF), and (3) interhemispherical inhibition (IHI) from the left-to-right hemisphere using a paired-pulse method. There were two main effects after rTMS to the left hemisphere: first, the amplitude of MEPs from the right hemisphere increased; second, there was a reduction in the IHI from the left-to-right hemisphere at interstimulus intervals of 7 and 10 ms but not at longer intervals (15-75 ms). Control experiments showed that these effects were not due to afferent inputs produced by the muscle twitches induced during the rTMS. The data are compatible with the notion that rTMS to the left hemisphere leads to reduced interhemispherical inhibition of the right hemisphere and a consequent increase in corticospinal excitability in that hemisphere.

During a sustained maximal effort a progressive decline in the ability to drive motoneurones (MNs) develops. We used the recently developed triple stimulation technique (TST) to study corticospinal conduction after fatiguing exercise in healthy subjects. This method employs a collision technique to estimate the proportion of motor units activated by a transcranial magnetic stimulus. Following a sustained contraction of the abductor digiti minimi muscle at 50 % maximal force maintained to exhaustion there was an immediate reduction of the TST response from > 95 % to about 60 %. This effect recovered to control levels within 1 min and implies that a decreased number of spinal MNs were excited. Additional TST experiments after maximal and submaximal efforts showed that the decrease in size of the TST response was related to duration and strength of exercise. Motor evoked potentials (MEPs) after conventional transcranial magnetic stimulation (TMS) and responses to peripheral nerve stimulation were recorded following the same fatigue protocol. The size of both the MEPs and the peripheral responses increased after the contraction and were in direct contrast to the decrease in size of the TST response. This points to increased probability of repetitive spinal MN activation during fatigue even if some MNs in the pool failed to discharge. Silent period duration following cortical stimulation lengthened by an average of 55 ms after the contraction and recovered within a time course similar to that of the TST response depression. Overall, the results suggest that the outflow from the motor cortex could become insufficient to drive all spinal MNs to discharge when the muscle is fatigued and that complex interactions between failure of activation and compensatory mechanisms to maintain motor unit activation occur during sustained voluntary activity. When inability to maintain force occurs during submaximal effort, failure of activation of motor units is predominant.

We tested the effect of repetitive transcranial magnetic stimulation (rTMS) over the motor cortex on the size of transcortical stretch and mixed nerve reflexes. Fourteen healthy subjects were investigated using either 25 min of 1 Hz rTMS or 30 min of 0.1 Hz rTMS paired with electrical stimulation of the motor point of the first dorsal interosseous muscle (FDI). Following treatment, we measured the effect on the size of: (1) EMG responses evoked in FDI by transcranial magnetic stimulation (MEPs), (2) somatosensory evoked potentials (SEPs) evoked by ulnar nerve stimulation, and (3) transcortical stretch or electrically elicited reflexes. rTMS at 1 Hz reduced the amplitude of both MEPs and long latency reflexes by 20-30 % for about 10 min after the end of stimulation. Short latency reflexes were unaffected. SEPs were not studied, as it has been shown previously that they are also suppressed. rTMS at 0.1 Hz paired with motor point stimulation (interstimulus interval of 25 ms) increased the amplitude of the MEP and the cortical components of the SEP (N20/P25 and later peaks) for up to 10 min. Long latency reflexes were facilitated with the same time course. We conclude that rTMS over the motor cortex either alone or in conjunction with peripheral inputs can decrease or increase the excitability of the sensory and motor cortex for short periods after the end of stimulation. These changes affect not only MEPs and SEPs but also EMG responses to more 'natural' inputs involved in transcortical stretch reflexes.

1. The organization and pattern of cutaneous reflex modulation during rhythmic cyclical movements of the human upper limbs has received much less attention than that afforded the lower limb. Our working hypothesis is that control mechanisms underlying the modulation of cutaneous reflex amplitude during rhythmic arm movement are similar to those that control reflex modulation in the leg. Thus, we hypothesized that cutaneous reflexes would show task dependency and nerve specificity in the upper limb during rhythmic cyclical arm movement as has been demonstrated in the human lower limb. 2. EMG was recorded from 10 muscles crossing the human shoulder, elbow and wrist joints while bilateral whole arm rhythmic cyclical movements were performed on a custom-made, hydraulic apparatus. 3. Cutaneous reflexes were evoked with trains (5 x 1.0 ms pulses at 300 Hz) of electrical stimulation delivered at non-noxious intensities (approximately 2 x threshold for radiating parasthesia) to the superficial radial, median and ulnar nerves innervating the hand. 4. Cutaneous reflexes were typically modulated with the movement cycle (i.e. phase dependency was observed). There was evidence for nerve specificity of cutaneous reflexes during rhythmic movement of the upper limbs. Task-dependent modulation was also seen as cutaneous reflexes were of larger amplitude or inhibitory (reflex reversal) during arm cycling as compared to static contraction. 5. While there are some differences in the patterns of cutaneous reflex modulation seen between the arms and legs, it is concluded that cutaneous reflexes are modulated similarly in the upper and lower limbs implicating similar motor control mechanisms.

1. Blockade of uptake carriers of gamma-aminobutyric acid (GABA) has been shown to modulate inhibition in cortical slices of experimental animals, although little is known about this mechanism in vivo and, in particular, in humans. 2. The effects of blockade of GABA uptake were studied using transcranial magnetic stimulation (TMS) in humans. In eight healthy volunteers several measures of cortical excitation and inhibition were obtained before and approximately 2 h after ingestion of 5-15 mg of tiagabine (TGB). 3. After TGB ingestion, the duration of the TMS-induced silent period observable in the electromyogram of the voluntarily contracted target muscle was prolonged. Similarly, paired-pulse inhibition of the motor-evoked potential (MEP), as tested by delivering two magnetic shocks of equal suprathreshold intensities at 160 ms interstimulus interval (ISI), was more pronounced. In apparent contradistinction, paired-pulse inhibition of the MEPs produced by a subthreshold conditioning stimulus delivered 3 ms prior to a suprathreshold stimulus was reduced. Paired-pulse facilitation elicited by the same double-shock protocol at an ISI of 10 ms was increased. 4. The prolongation of the GABAB receptor-mediated component of the inhibitory postsynaptic potential observed with TGB in in vitro studies probably underlies the increase in cortical silent period duration. The reduction of the paired-pulse inhibition at 3 ms, in turn, probably reflects inhibition of GABAA receptor-mediated inhibition via presynaptic GABAB receptors. 5. These data provide in vivo evidence of differential modulation of cortical inhibition by blockade of GABA uptake. Presynaptic GABA autoreceptors may be involved in modulating cortical inhibition in the human motor cortex.

1. The time constants of motor and sensory nerve fibres were studied in normal human ulnar nerves by the method of latent addition, using threshold tracking to follow the recovery of excitability after brief conditioning current pulses. The 60 microseconds test and conditioning stimuli were applied at the wrist, and the conditioning stimuli were set to 90, 60, 30, -30, -60 and -90% of the control threshold current. Compound muscle action potentials were recorded from abductor digiti minimi, and sensory nerve action potentials from the little finger. 2. Recovery from depolarizing conditioning pulses was slower than recovery from hyperpolarizing pulses and strongly dependent on conditioning pulse amplitude. The voltage dependence of latent addition was attributed to subthreshold activation of sodium channels (local response). 3. Motor and sensory nerve excitability generally recovered from -90% hyperpolarizing pulses as the sum of two exponential components, although the slow component was negligible in some motor nerves. The fast component (time constant 43.3 +/- 2.0 microseconds, mean +/- S.E.M., n = 9) was similar between motor and sensory fibres in the same subject. It showed no consistent voltage dependence, and was attributed to a passive input time constant of the fibres. The slow component of recovery from hyperpolarizing pulses was greater in sensory than in motor fibres and was voltage dependent: it could be greatly increased in motor and sensory fibres by steady depolarization. It was attributed to a regenerative membrane current, active at the resting potential in sensory and at least some motor nerves. 4. The latent addition responses were compared with the computed responses of four theoretical models. Both motor and sensory responses were well fitted by a model in which a fraction of the sodium channels (less in motor than in sensory fibres) were activated at potentials 20 mV more negative than normal and at half the normal rate, and did not inactivate. 5. It is concluded that the differences in latent addition between motor and sensory fibres are primarily due to differences in non-classical, voltage-dependent ion channels, active close to the resting potential. These "threshold channels' may help to account for the longer strength-duration time constant of sensory fibres, for their lower rheobase, and for their greater tendency to fire repetitively.

1. The possibility of eliciting H reflexes in relaxed hand muscles using a collision between the orthodromic impulses generated by magnetic cortical stimulation and the antidromic motor volley due to a supramaximal (SM) peripheral nerve stimulus was investigated in seven subjects. 2. Magnetic stimuli, applied through a circular coil (outer diameter, 13 cm) centred at the vertex, evoking EMG responses of 3-5 mV amplitude in the relaxed abductor digit minimi (ADM) muscle, and SM test stimuli to the ulnar nerve at the wrist producing a direct maximal motor response (Mmax) in the ADM muscle, were given either alone or combined. 3. In all subjects, combined cortical and SM ulnar stimulation produced a response after the Mmax with the latency of an H reflex evoked by the ulnar stimulus. This response occurred only within interstimulus intervals (1-20 ms) compatible with collision in the motor axons. The response behaved like an H reflex being time-locked to the SM ulnar stimulus, facilitated by voluntary activation of ADM muscle, depressed by vibration (4 s, 100 Hz) of ADM tendon and by a submotor-threshold ulnar nerve stimulus applied 50 and 80 ms before the combined stimulation, respectively. 4. In some subjects, it was also possible to distinguish an earlier response preceding the H reflex by 3 ms. Evidence is given that this response is probably of cortical origin. 5. Varying the intensity of magnetic stimulation resulted in a non-linear relationship between the H reflex size and the size of the cortical response. When the latter was between 5-25% of Mmax, H reflexes were small (2.5-7.5% of Mmax); with cortical responses between 25-50% of Mmax, there was a steep increase in H reflex amplitude (10-30% of Mmax). We suggest that this behaviour is due to an uneven distribution of Ia effects within the motoneurone pool.

1. The possibility that stimulation of the motor cortex facilitates transmission in the pathway mediating non-monosynaptic ('propriospinal') excitation from low-threshold afferents to upper limb motoneurones was investigated. 2. Convergence between peripheral afferent volleys (from the ulnar or musculo-cutaneous nerve) and corticospinal volleys (evoked by magnetic stimulation of the motor cortex) was investigated using the spatial facilitation technique. Thus the effects of these volleys on the flexor carpi radialis H reflex were compared when applied separately and together. When cortical stimulation was optimal for the muscle from which the conditioning volley originated the facilitation of the reflex on combined stimulation was significantly larger than the algebraic sum of the effects of separate stimuli. 3. The extra facilitation on combined stimulation had all the characteristics of 'propriospinal' excitation (low threshold, long central delay, brief duration and depression when the afferent input was increased), and it is suggested that this reflects corticospinal excitation of 'propriospinal' neurones. 4. When varying the time interval between cortical and test stimulations, it was shown that extra facilitation on combined stimulation began 1 ms later than the onset of the control reflex facilitation. Assuming that the latter onset reflects the arrival of the monosynaptic corticospinal volley at the motoneurone pool, this 1 ms delay suggests a disynaptic pathway for the cortical excitation of motoneurones through 'propriospinal' neurones. 5. As at the onset of voluntary movement, the pattern of the cortical excitation of 'propriospinal' neurones was quite specific: extra facilitation of the reflex on combined stimulation only occurred when the cortical volley was preferentially directed to motoneurones supplying the muscle from which the afferents used for the peripheral volley originated. 6. It is concluded that corticospinal axons activate human 'propriospinal' neurones and thereby produce disynaptic excitation of the motoneurone pool. Given temporal summation with the monosynaptic excitation, this 'propriospinally mediated' disynaptic excitation might make a significant contribution to the evoked EMG potential.

1. The silent period evoked in the first dorsal interosseous (FDI) muscle after electrical and magnetic transcranial stimulation (TCS), electrical stimulation of the cervicomedullary junction and ulnar nerve stimulation was studied in ten healthy subjects. 2. With maximum-intensity shocks, the average duration of the silent period was 200 ms after electrical TCS, 300 ms after magnetic TCS, 43 ms after stimulation at the cervicomedullary junction and 100 ms after peripheral nerve stimulation. 3. The duration of the silent period, the amplitude of the motor-evoked potential, and the twitch force produced in the muscle were compared at increasing intensities of magnetic TCS. When the stimulus strength was increased from 30 to 70% of the stimulator output, the duration of the silent period lengthened as the amplitude of the motor potential and force of the muscle twitch increased. At 70 to 100% of the output, the amplitude of the motor potential and force of the muscle twitch saturated, whereas the duration of the silent period continued to increase. 4. Proximal arm muscle twitches induced by direct electrical stimulation of the biceps and extensor wrist muscles produced no inhibition of voluntary activity in the contracting FDI muscle. 5. The level of background activation had no effect on the duration of the silent period recorded in the FDI muscle after magnetic TCS. 6. Corticomotoneurone excitability after TCS was studied by means of a single magnetic conditioning shock and a test stimulus consisting either of one single magnetic shock or single and double electrical shocks (interstimulus interval 1.8 ms) in the relaxed muscle. A conditioning magnetic shock completely suppressed the response evoked by a second magnetic shock, reduced the size of the response evoked by a single electrical shock but did not affect the response evoked by double electrical shocks. Inhibition of the test magnetic shock was also present during muscle contraction. 7. Our findings indicate that the first 50 ms of the silent period after TCS are produced mainly by spinal mechanisms such as after-hyperpolarization and recurrent inhibition of the spinal motoneurones. If descending inhibitory fibres contribute, their contribution is small. Changes in proprioceptive input probably have a minor influence. From 50 ms onwards the silent period is produced mainly by cortical inhibitory mechanisms.

1. The patterns of excitation and convergence by peripheral afferents on propriospinal-like neurones projecting to forearm flexor carpi radialis (FCR) motoneurones in human subjects were determined at rest and during various voluntary contractions, using H reflex testing. 2. At rest, the FCR H reflex could be facilitated by mixed nerve (ulnar, musculocutaneous) and cutaneous (afferents from both sides of the hand) inputs. The characteristics of this facilitation (low threshold, long central latency, short duration) were compatible with those of the propriospinal-like system. Quantitatively this facilitation was rare and weak. 3. Voluntary contraction increased the extent of the propriospinal-like facilitation of the FCR H reflex. It is shown in the companion paper (Burke, Gracies, Meunier & Pierrot-Deseilligny, 1992) that this increase results not from a decrease in presynaptic inhibition of afferents to propriospinal-like neurones, but from increased excitation of these neurones. It is argued that at the onset of contraction this excitation is purely descending in origin, whereas the contraction-induced afferent discharge is probably the major factor during weak tonic contraction. 4. The distribution of the increased facilitation of the FCR H reflex depended on the muscles involved in the contraction: ulnar nerve-evoked facilitation was increased much more at the onset of voluntary wrist flexion than voluntary elbow flexion, and vice versa for the musculo-cutaneous-induced facilitation. This finding is consistent with the view that there are subsets of propriospinal-like neurones, specialized with regard to afferent input, and indicates that descending excitation is directed preferentially to the subset of neurones which receives excitatory feedback from the contracting muscle. 5. To investigate the convergence of different afferent inputs onto common neurones the spatial facilitation technique was used. When present the convergence had a threshold and time course compatible with those of the propriospinal-like system. Convergence was found between the different mixed nerves and between ulnar and superficial radial nerves. 6. The wide convergence found between different inputs onto common neurones and the finding that, during contraction of a given muscle, descending excitation reaches subsets of neurones projecting to motor nuclei of muscles operating at other joints suggest that the propriospinal-like system would be operative during complex multi-joint movements.

1. Neural recordings were made from motor fascicles of the ulnar or radial nerves while the motor cortex was stimulated percutaneously using high-voltage electrical stimuli or transient magnetic pulses to determine whether human muscle spindle endings could be activated by such stimuli and, if so, whether this occurred before the recruitment of alpha-motoneurones. 2. In relaxed subjects, no evidence of muscle spindle activation could be detected in nine recordings of multiunit neural activity and four recordings from single spindle afferents using stimulus levels up to 600 V and 1.5 T. These levels produced a prominent twitch contraction of the intrinsic muscles of the hand and of forearm muscles. Passive stretch of the contracting muscle did not reveal a fusimotor action too weak to be detected under isometric circumstances. 3. With twenty-six single spindle afferents, the stimuli were delivered during a voluntary contraction of the receptor-bearing muscle. This served to 'focus' the effects of the stimulus on the relevant motoneurone pools and increased the probability that fusimotor neurones innervating the endings were active. 4. None of the twenty-six spindle afferents could be activated by stimuli subthreshold for alpha-motoneurones, even when the stimuli were delivered during passive stretch of the contracting muscle. With eighteen afferents, stimuli above threshold for alpha-motoneurones were delivered: twelve remained unaffected but the discharge of six altered. 5. Three afferents were activated at latencies of 35, 39 and 40 ms, respectively 16, 20 and 20 ms after the onset of the EMG potentials in the receptor-bearing muscles. This latency difference is too short to be attributable to activation of gamma-motoneurones: arguments are presented that the increase in spindle discharge could result from activation of beta-motoneurones. 6. The discharge of three afferents increased at latencies of 70, 75 and 85 ms, too early to be due to stretch on the falling phase of the twitch contraction of the receptor-bearing muscle. Responses at these latencies could involve activation of gamma- or beta-motoneurones. 7. These findings in human subjects suggest that transient stimulation of the motor cortex may effectively access fusimotor neurones.

1. The possibility that activation of low-threshold afferents in the median and ulnar nerves in man evokes an interneuronally mediated excitation of wrist flexor motoneurones was investigated. Two independent techniques were used: (i) the indirect technique of spatial and temporal facilitation of the flexor carpi radialis H reflex; (ii) the post-stimulus time histogram (PSTH) method for measurement of the firing probability of voluntarily activated motor units following different stimuli. 2. Conditioning volleys were evoked by weak electrical stimuli (to the median nerve, the ulnar nerve, the skin and cutaneous nerve branches) and by a tap to the tendon of the flexor carpi radialis muscle. 3. In the H reflex experiments the comparison was drawn between the effects of two conditioning stimuli applied separately or together. In some experimental conditions the facilitation of the reflex evoked when combining two conditioning stimuli was larger than the algebraic sum of the effects from separate stimuli. The central latency of this additional facilitation, which is denoted 'extra facilitation', was 3 ms. It is argued that the extra facilitation reflects summation at a premotoneuronal level. 4. PSTHs of voluntarily activated flexor carpi radialis and flexor carpi ulnaris motor units were computed following stimulation of the median or the ulnar nerve. In 60% of the recordings the afferent volley evoked a peak of increased firing probability with a latency which was 3-6 ms longer than the monosynaptic Ia latency. 5. Both the extra facilitation of the reflex and the late peak in the PSTH were evoked from very low-threshold afferents. A contribution from Ia afferents was demonstrated in reflex experiments. Group I afferents alone are responsible for the onset of the non-monosynaptic excitation but it is probable that cutaneous afferents give a later contribution. 6. On the basis of the characteristics of the non-monosynaptic excitation studied with the two methods (same very low-threshold, comparable central latencies), it is argued that both the extra facilitation of the H reflex on combined stimulation and the late peak in the PSTHs from individual motor units are mediated through the same pre-motoneuronal pathway. 7. The possibility that the non-monosynaptic excitation may be mediated through propriospinal neurones is discussed.

1. Single unit impluses were recorded from the ulnar and median nerves of awake human subjects with tungsten electrodes inserted percutaneously in the upper arm. 2. One hundred and one slowly adapting receptors with receptive fields in the glabrous skin area were studied. The units were classified as type SA-I and type SA-II largely on the basis of their responses to lateral stretching of the skin. Eighty-eight receptors did not respond to this type of stimulus (type SA-I), whereas thirteen receptors readily responded to stretching (type SA-II), AND OFTEN EXHIBITED DIRECTIONAL SENSITIVITY. 3. The SA-I receptors showed no spontaneous discharge, and the discharge pattern was mostly rather irregular, whereas most of the SA-II receptors had a spontaneous discharge, and a very regular discharge pattern. 4. The conduction velocities of the afferent were all in a A alpha range. The mean value for the SA-I receptors was 58-7 plus or minus 2-3m/sec, and for the SA-II receptors 45.3 plus or minus 3.6 m/sec. 5. The neural response to stimuli of varying skin indentation amplitudes was analyzed. The threshold for a dynamic response ranged for the SA-I receptors from 0.15 to 1.35 mm and for the SA-II receptors from 0.25 to 0.95 mm. The threshold for a static discharge ranged for the SA-I receptors from 0.25 to more than 2.0 mm and for the SA-II receptors from 0.55 to 1.65 mm. 6. The stimulus-response functions were analysed for 25 SA-I receptors and 2 SA-II receptors. A hyperbolic log tangent function was the best description when the neural response was defined as the total number of impluses evoked by a stimulus of 1 sec duration. When only the static part of this type of plot was analyzed, a power function was a very good description for many units, but other functions (linear, logarithmic exponential, log tanh) were equally good or better for many units. This was also the dase when the mean impulse frequency of the sustained discharge was defined as a measure of the neural response. These two latter types of plots were clearly negatively accelerating, the exponent of the power function being 0.66 (mean).

1. The possibility was investigated that the transmission of the interneuronally mediated Ia excitation to wrist flexor motoneurones described in the companion paper is inhibited by stimulation of afferent fibres. Two techniques were used: (i) the post-stimulus time histogram (PSTH) method for studying changes in firing probability of individual voluntarily activated wrist flexor motor units following various peripheral stimulations; and (ii) the indirect technique of spatial facilitation of the H reflex. 2. In those individual units where stimulation of the median and/or the ulnar nerve evoked a non-monosynaptic excitation, this excitation was reduced when the afferent input was increased. This reduction of the non-monosynaptic Ia excitation was found in 80% of the motor unit recordings, whether the afferent input was increased by increasing the stimulus intensity to one nerve or by using combined stimulation of two nerves. 3. Both group I muscle and low-threshold cutaneous afferents were shown to be able to reduce the non-monosynaptic Ia excitation. 4. The onset of the depression of the excitation was always found within the same 1 ms bin as that of the excitation. 5. Whatever the amount of afferent input (stimulus intensity increased up to motor threshold, spatial and temporal summation, summation of inhibitory effects from different origins), the depression could at the very most suppress the non-monosynaptic Ia excitation: i.e. a trough in the PSTH, reflecting an inhibition at the motoneuronal level, never appeared. In those units in which there was not non-monosynaptic excitation, peripheral stimulation did not evoke any inhibition appearing as a trough in the PSTH either. Hence, inhibition only appeared when there was a non-monosynaptic excitation, and then as a depression of it. 6. On the basis of these findings it is argued that the inhibition is not exerted directly onto motoneurones but acts at a pre-motoneuronal level on the interneurones mediating the non-monosynaptic Ia excitation to motoneurones. 7. Similarly, the homonymous non-monosynaptic Ia facilitation of the flexor carpi radialis H reflex was shown to be reduced by a preceding stimulation applied to the ulnar nerve. It is argued that this result is also compatible with an inhibition of transmission in interneuronal excitatory pathways to motoneurones. 8. It is suggested that the non-monosynaptic excitation of wrist flexor motoneurones in man and the inhibition of this excitation, both evoked by stimulation of low-threshold afferents, could be mediated through a system of cervical propriospinal neurones. Some aspects of the possible role of this system during movement are discussed.

1. It was the aim of the present study to isolate and identify the components underlying the human sensory compound action potential and to study their axonal conduction velocities and refractory periods. For this purpose the technique of percutaneous microneurography was combined with intradermal electrical stimulation of nerve fibre terminals. Sixty-four median and ulnar nerve afferents innervating the glabrous skin of the digits were isolated and type identified. 2. The range of axonal conduction velocities was wide (20-60 m/s), but similar for each afferent category (20-60 m/s). Most afferents conducted slower than expected from the intrafascicularly recorded compound potential (50-60 m/s) and their conduction velocities generally decreased from the base to the tip of the digits. 3. The duration of the absolute axonal refractory periods of all types of afferents ranged from 0.7 to 3.5 ms. The duration of the total refractory periods ranged from 3 to 9 ms. Both absolute and total axonal refractory periods were inversely correlated (r = -0.70 and r = -0.67) with their axonal conduction velocities. 4. The size of individual action potentials was significantly correlated with axonal conduction velocities, although the correlation coefficient was relatively low (r = 0.43), even after correction for variability due to electrode resistance (partial correlation r = 0.44). 5. The results showed that different types of cutaneous afferents cannot be separated on the basis of their axonal conduction properties. The data demonstrate features of neural impulse conduction along the entire axonal tree and which are inaccessible to routine electrodiagnostic procedures. The present approach provides a sensitive means for assessing, in health and disease, nerve conduction in terminal axons.

Climbing fibre responses were recorded in the cerebellar anterior lobe on stimulation of the cerebral cortex. A zonal pattern was demonstrated in the cortical projection, which was related to the cerebellar sagittal zones, as identified from peripheral climbing fibre input. In all zones, except c2, a co-variation of the responses evoked on peripheral nerve stimulation and on stimulation of the corresponding part of the sensorimotor cortex was found. There was a bilateral projection to the a, b, c2 and d1 zones which also, to a varying extent, receive a bilateral peripheral input. The x, c1 and c3 zones, receiving an ipsilateral peripheral input, were activated exclusively from the contralateral cortex. Stimulation of the posterior sigmoid gyrus (p.s.g.) evoked responses in all the zones. These responses had, in all zones except d1, lower thresholds and shorter latencies than the responses from other cortical areas. Two separate p.s.g. areas were shown to project to the pars intermedia zones (c1, c2, c3 and d1), the lateral area to the caudal parts and the medial area to the rostral parts of the zones. In contrast, the b zone received a projection from only one p.s.g. area, centred between, but overlapping, the two areas projecting to the pars intermedia zones. Stimulation of the anterior sigmoid gyrus evoked short-latency responses in the d1 zone and long-latency responses in all other zones. Stimulation of the first and second somatosensory areas (SI and SII) was generally less effective in evoking climbing fibre responses than was stimulation of the p.s.g. The only exception was the c2 zone, in which responses were evoked from the SII with nearly as low thresholds and short latencies as on p.s.g. stimulation. From the parietal cortex, long-latency responses were regularly evoked in the d1 zone and less frequently in the a, b and c2 zones.

1. Neurones in the Group I projection area of the first sensori-motor cortex were investigated with extra- and intracellular technique.2. The majority of the neurones influenced by volleys in Group I afferents of contralateral forelimb nerves received exclusively excitation, but some received exclusively inhibition, and some mixed excitation and inhibition.3. The Group I influenced cells were usually found 500-1500 mu beneath the cortical surface.4. The EPSPs and IPSPs evoked from Group I afferents had a steep rising phase and a slow, approximately exponential decay. The duration was sometimes more than 50 msec. The EPSP evoked by a maximal Group I volley was often formed by a small number of large unitary EPSPs.5. Latency measurements indicate that the majority of the Group I activated neurones were monosynaptically excited from the thalamic fibres, and hence constitute the fourth-order neurones in the Group I projection system. The latencies of the IPSPs suggest a disynaptic linkage with thalamic fibres. Hence, the exclusively inhibited cells would constitute fifth-order neurones. It is suggested that most or all of the fourth-order neurones are inhibitory.6. The convergence of excitation and/or inhibition to individual cells was usually extensive and included effects not only from muscle groups working at different joints but also effects from antagonistic groups at the same joint. In addition cutaneous afferents contributed synaptic actions which had a longer latency than the synaptic actions from Group I afferents.7. The neurones influenced from Group I afferents were not antidromically activated on stimulation of the pyramidal tract.

1. Median and ulnar nerves of anaesthetized Soay sheep have been investigated in vivo.2. The compound action potentials of these nerves indicate that the most rapidly conducting fibres had mean velocities of 87 m/sec in the median nerve and 57 m/sec in the ulnar nerve. The mean conduction velocities of the axons responsible for the Group A gammadelta wave in the median nerve were 23-30 m/sec and those responsible for the Group A delta wave in the ulnar nerve conducted at 23-26 m/sec.3. Single myelinated afferents were isolated by microdissection of median and ulnar nerves in the metacarpal region, and action potentials were recorded from hair follicle units, cutaneous mechanoreceptors, deeply situated proprioceptors, and from units of unknown function which were spontaneously active.4. The hair follicle units fell into two categories: ;diffuse' units which innervated many hairs in an area of about 1-3 cm(2) anywhere on the hairy skin above the hoof, and ;localized' units which innervated a few hairs within small areas of the skin adjacent to the hoof. The ;diffuse' units generally resembled the ordinary hair follicle units of other animals except that in the sheep the afferents had higher conduction velocities. The ;localized' units also had large myelinated axons, but their physiological properties differed in several aspects from the guard hair, tylotrich and carpal hair units which have been studied in other animals.

1. The corticospinal connexions that are responsible for the firing of fusimotor impulses at short latency in response to brief, high-frequency stimulation of the baboon's motor cortex have been investigated by micro-electrode recording from antidromically identified fusimotor neurones of the forearm and hand.2. Of nineteen fusimotor neurones investigated by intracellular recording, six showed EPSPs at monosynaptic latency.3. In extracellular records, the latency of firing of an early fusimotor impulse was always too long to be explained by monosynaptic excitation by the corticospinal D volley, but could be explained by monosynaptic excitation from an I volley.4. Four of the nineteen intracellularly recorded fusimotor neurones showed short-latency (?disynaptic) IPSPs in response to brief high frequency cortical bursts.

1. Single unit impulses were recorded from the ulnar and median nerves of awake human subjects with tungsten electrodes inserted percutaneously in the upper arm.2. Forty-nine rapidly adapting mechanoreceptors with receptive fields in the glabrous skin area were studied. Thirty-nine units had small receptive fields with distinct borders (RA-receptors) while ten units had large fields with indistinct borders (PC-receptors).3. The afferent response to stimuli of varying indentation amplitude and velocity of indentation, was analysed.4. Amplitude thresholds varied from 0.05 to 1.65 mm for the RA-receptors. For the PC-receptors amplitude thresholds ranged from less than 0.05 to 1.95 mm.5. Velocity thresholds varied for the RA-receptors from 0.4 to 39.3 mm/sec, and for the PC-receptors from 0.5 to 19.6 mm/sec.6. The conduction velocities of the afferents were all in the A alpha-beta range. For the RA-receptors the conduction velocities ranged from 26 to 91 m/sec (mean = 55.3 +/- 3.4), and for PC-receptors the range was from 34 to 61 m/sec (mean = 46.9 +/- 3.6).7. The nerve impulse frequency as a function of indentation velocity was analysed for nineteen RA-receptors and four PC-receptors. A hyperbolic log tangent function of the type first introduced by Naka & Rushton (1966) in studies on S-potentials in the fish retina was found to be the best description of the stimulus-response function for sixteen RA-receptors and two PC-receptors. For the remaining units a pure logarithmic function was the best description. However, the logarithmic function may be, as found in the present study, a special case of the more general log tanh function.

1. The discharge of impulses in afferent fibres dissected from the infraorbital and ulnar nerves of anaesthetized cats was recorded during controlled movements of the maxillary and carpal sinus hairs.2. Four main types of afferent units were identified. Two had slowly adapting responses characteristic of the epidermal type I, and dermal type II mechanoreceptors of the hairy skin. Two rapidly adapting responses to movement of the sinus hairs were found, one with a high velocity threshold and another with a low velocity threshold.3. The slowly adapting units showed a power relationship between the degree of displacement of the hair and the mean interspike interval of the response. Slowly adapting units also exhibited a power relationship between the velocity of displacement of a hair and the mean interspike interval of the response.4. The conduction velocities of all types of afferent units were measured and fell in the range of the Aalpha, fast myelinated fibres.5. Movements of the carpal sinus hairs yielded both types of slowly adapting response recorded in fibres of the ulnar nerve directly innervating the carpal sinus hair follicles, and rapidly adapting responses from Pacinian corpuscles, found in close association with, but external to, these follicles.6. On the basis of the findings in this study and the results of anatomical investigations of the receptor structures in the sinus hair follicle a correlation between the distinguishable afferent responses and the morphologically identifiable nerve endings has been proposed.

1. The precentral and postcentral banks of the Rolandic fissure of the arm area of the baboon's cortex have been probed to their depths with extracellular micro-electrodes under nitrous oxide and oxygen anaesthesia, supplemented by minimal intravenous pentobarbitone or chloralose.2. Afferent volleys were sent in from the deep (motor) radial nerve and the deep palmar (motor) branch of the ulnar nerve. Their entry into the central nervous system was timed at the dorsal root entry zone. The nerves were stimulated in continuity and the effects of stimuli below threshold for the motor axons were investigated.3. Area 3a, in the depths of the postcentral bank, which is cytoarchitectonically transitional between areas 3 and 4, is the receiving area for afferent impulses from muscle.4. Evoked potential waves and unitary discharges began 4 msec, and the majority of units discharged between 5 and 10 msec, after the afferent volley reached the dorsal root entry zone.5. Similar responses were elicited by a brief pull (70 mu in 1 msec) or brief vibration (50 mu at 250-400 Hz) applied to the tendons of m. extensor digitorum communis.6. No potential waves were evoked in area 4, even in the depths adjacent to area 3a, by muscle afferent volleys.