Search

There is evidence in experimental animals that, in addition to receiving fusimotor drive, muscle spindles are subject to modulation by the sympathetic nervous system. We examined the validity of this idea in human subjects by recording from muscle spindles in the relaxed ankle and toe extensor muscles during a strong and sustained physiological activation of muscle sympathetic outflow. Unitary recordings were made from 20 primary and 17 secondary muscle spindle afferents via a tungsten microelectrode inserted percutaneously into the peroneal nerve in 10 awake, healthy subjects seated with the legs supported in the extended position. ECG, blood pressure, respiration and calf circumference were also recorded. The majority of the muscle spindles were spontaneously active at rest; a background discharge was induced in four silent spindles by vibrating the tendon. A sustained increase in muscle vasoconstrictor activity, an increase in calf volume and a fall in pulse pressure were produced by subjects performing a 30‐40 s maximal inspiratory breath‐hold. Despite this strong increase in muscle sympathetic outflow no significant changes occurred in the discharge of either primary or secondary muscle spindle afferents, measured as a change in mean frequency and variability over sequential 5 s epochs and compared with the preceding period of rest. Strong chemoreceptor‐driven sympathetic bursts during sustained expiratory breath‐holds also failed to modulate the firing of 14 spindle endings. We conclude that a sustained, physiological increase in muscle sympathetic activity causes no detectable change in muscle spindle firing, lending no support to the concept that the sympathetic nervous system can influence the sensitivity of human muscle spindles directly.

We report unusual muscle sympathetic nerve activity (MSNA) in patients with Cheyne-Stokes respiration (CSR), one suffering congestive heart failure (CHF) and three with obstructive sleep apnea syndrome (OSAS). MSNA was recorded via a tungsten microelectrode in the peroneal nerve. Our index patient had severe CHF (LVEF 15 %) and showed typical MSNA for this condition, with large sympathetic bursts occurring with every heart beat. However, superimposed on this pattern appeared broad surges of increased MSNA which lasted for 6–8 cardiac intervals. Although the cardiac rhythmicity of MSNA was preserved during these surges, the baroreceptor-mediated inhibition was never complete, resulting in an increase in baseline neural activity during the surge. Because their occurrence can be explained by the periodicity of the CSR and the estimated circulation time from the lung to the carotid bodies, we suggest that these surges in MSNA reflect a chemoreceptor-mediated increase in muscle vasoconstrictor drive.

1While it is known that the average firing rate of a population of motoneurones declines with time during a maximal voluntary contraction, at least for many muscles, it is not known how the firing patterns of individual motoneurones adapt with fatigue. To address this issue we used tungsten microelectrodes to record spike trains (mean ±s.e.m., 183 ± 27 spikes per train; range, 100–782 spikes) from 26 single motor units in extensor hallucis longus during sustained (60–180 s) maximal dorsiflexions of the big toe in seven human subjects.2Long spike trains were recorded from 13 units during the first 30 s of a maximal voluntary contraction (mean train duration, 9.6 ± 1.2 s; range, 3.6–21.9 s) and from 13 units after 30 s (mean train duration, 16.6 ± 3.7 s; range, 7.1–58.1 s). Maximal isometric force generated by the big toe declined to 78.3 ± 6.3 % of its control level by 60–90 s and to 39.5 ± 1.4 % of control by 120–150 s. Despite this substantial fatigue, mean firing rates did not change significantly over time, declining only slightly from 15.8 ± 0.7 Hz in the first 30 s to 14.0 ± 0.5 Hz by 60–90 s and 13.6 ± 0.3 Hz by 120–150 s.3To assess fatigue‐related adaptation in discharge frequency and variability of individual motor units, each spike train was divided into 2–15 equal segments containing at least 50 interspike intervals. Discharge variability was measured from the coefficient of variation (s.d./mean) in the interspike intervals, with the s.d.being calculated using a floating mean of 19 consecutive intervals. Adaptation was computed as the average change in firing rate or variability that would occur for each 1 s of activity. There were no systematic changes in either firing rate or variability with time.4We conclude that single motoneurones supplying the extensor hallucis longus, a muscle comprised primarily of slow twitch muscle units, show little adaptation in firing with fatigue, suggesting that a progressive reduction in firing rate is not an invariable consequence of the fatigue associated with sustained maximal voluntary contractions.

1The firing of single sympathetic neurones was recorded via tungsten microelectrodes in cutaneous fascicles of the peroneal nerve in awake humans. Studies were made of 17 vasoconstrictor neurones during cold‐induced cutaneous vasoconstriction and eight sudomotor neurones during heat‐induced sweating. Oligounitary recordings were obtained from 8 cutaneous vasconstrictor and 10 sudomotor sites. Skin blood flow was measured by laser Doppler flowmetry, and sweating by changes in skin electrical resistance within the innervation territory on the dorsum of the foot.2Perispike time histograms revealed respiratory modulation in 11 (65 %) vasoconstrictor and 4 (50 %) sudomotor neurones. After correcting for estimated conduction delays, the firing probability was higher in inspiration for both classes of neurone. Measured from the oligounitary recordings, the respiratory modulation indices were 67.7 ± 3.9 % for vasoconstrictor and 73.5 ± 5.7 % for sudomotor neurones (means ± s.e.m.). As previously found for sudomotor neurones, cardiac rhythmicity was expressed by 7 (41 %) vasoconstrictor neurones, 5 of which showed no significant coupling to respiration. Measured from the oligounitary records, the cardiac modulation of cutaneous vasoconstrictor activity was 58.6 ± 4.9 %, compared with 74.4 ± 6.4 % for sudomotor activity.3Both vasoconstrictor and sudomotor neurones displayed low average firing rates (0.53 and 0.62 Hz, respectively). The percentage of cardiac intervals in which units fired was 38 % and 35 %, respectively. Moreover, when considering only those cardiac intervals when a unit fired, vasoconstrictor and sudomotor neurones generated a single spike 66 % and 67 % of the time. Rarely were more than four spikes generated by a single neurone.4We conclude that human cutaneous vasoconstrictor and sudomotor neurones share several properties: both classes contain subpopulations that are modulated by respiration and/or the cardiac cycle. The data suggest that the intensity of a multi‐unit burst of vasoconstrictor or sudomotor impulses is probabably governed primarily by firing incidence and the recruitment of additional neurones, rather than by an increase in the number of spikes each unit contributes to a burst.

1Single‐unit recordings were made from 19 postganglionic muscle vasoconstrictor axons via tungsten microelectrodes in the peroneal nerve in seven healthy subjects with many multi‐unit sympathetic discharges at rest (‘high group’, 75 ± 5 multi‐unit bursts per 100 heart beats, mean ± s.e.m.). The results were compared with previous data from 14 units in subjects with 21 ± 2 multi‐unit bursts per 100 heart beats (‘low group’).2In the ‘high group’ the units fired spontaneously in 35 ± 4 % of all cardiac intervals. One unit only ever fired once per cardiac interval, 14 units (74 %) generated maximally two to three spikes, and four units (21 %) up to four to five spikes. Of those cardiac intervals in which a unit fired, a single spike occurred in 78 %, two spikes in 18 %, three spikes in 4 % and four spikes in less than 1 % of cardiac intervals. Measured as the inverse of all interspike intervals, the mean rate was 0.33 ± 0.04 Hz and the mean intraburst frequency 22.2 ± 1.6 Hz. Most results were similar to those in the ‘low group’, but in the ‘low group’ heart rate was higher (64.5 vs.50.4 beats min−1) and mean firing frequency was higher (0.49 ± 0.06 Hz).3During increases of multi‐unit burst activity evoked by sustained inspiratory‐capacity apnoea the firing probability of nine units in the ‘high group’ increased from 33 ± 6 to 56 ± 3 % of the cardiac intervals. Simultaneously, the incidence of single spikes decreased and the incidence of multiple spikes per cardiac interval increased, resulting in an increase of mean firing frequency from 0.23 ± 0.04 Hz at rest to 1.04 ± 0.14 Hz during the apnoea.4We conclude that single muscle vasoconstrictor neurones usually fire only a solitary spike during sympathetic bursts both in subjects with a high and in subjects with a low number of bursts at rest. Presumably, differences in the numbers of bursts are due mainly to differences in firing probability and recruitment of sympathetic fibres. During acuteincreases of multi‐unit activity, both increases in discharge frequency and recruitment of additional neurones contribute to the increased intensity of an individual sympathetic burst.

Force-frequency and fatigue properties of motor units in muscles that control digits of the human hand. Modulation of motor unit activation rate is a fundamental process by which the mammalian nervous system encodes muscle force. To identify how rate coding of force may change as a consequence of fatigue, intraneural microstimulation of motor axons was used to elicit twitch and force-frequency responses before and after 2 min of intermittent stimulation (40-Hz train for 330 ms, 1 train/s) in single motor units of human long finger flexor muscles and intrinsic hand muscles. Before fatigue, two groups of units could be distinguished based on the stimulus frequency needed to elicit half-maximal force; group 1 (n= 8) required 9.1 ± 0.5 Hz (means ± SD), and group 2 (n= 5) required 15.5 ± 1.1 Hz. Twitch contraction times were significantly different between these two groups (group 1 = 66. 5 ms; group 2 = 45.9 ms). Overall 18% of the units were fatigue resistant [fatigue index (FI) > 0.75], 64% had intermediate fatigue sensitivity (0.25 ≤ FI ≤ 0.75), and 18% were fatigable (FI < 0.25). However, fatigability and tetanic force were not significantly different among groups. Therefore unlike findings in some other mammals, fast-contracting motor units were neither stronger nor more susceptible to fatigue than slowly contracting units. Fatigue, however, was found to be greatest in those units that initially exerted the largest forces. Despite significant slowing of contractile responses, fatigue caused the force-frequency relation to become displaced toward higher frequencies (44 ± 41% increase in frequency for half-maximal force). Moreover, the greatest shift in the force-frequency relation occurred among those units exhibiting the largest force loss. A selective deficit in force at low frequencies of stimulation persisted for several minutes after the fatigue task. Overall, these findings suggest that with fatigue higher activation rates must be delivered to motor units to maintain the same relative level of force. Questions regarding classification of motor units and possible mechanisms by which fatigue-related slowing might coexist with a shift in the force-frequency curve toward higher frequencies are discussed.

A quantitative assessment was made of the firing characteristics of repetitive axonal discharges encountered during microneurographic recordings from human peripheral nerves. Spontaneous activity was recorded from 16 single axons using tungsten microelectrodes inserted percutaneously into fascicles of the median or peroneal nerves in normal subjects. These discharges typically consisted of brief bursts of 2–5 spikes occurring at a frequency of 7–10 Hz. Peak instantaneous frequencies usually exceeded 300 Hz. Based on their similarity with spontaneous high‐frequency discharges recorded from single axons following nerve damage, ischemia, prolonged electrical stimulation, or hyperventilation, it is concluded that they are generated ectopically at the site of a previous impalement of a nerve fiber. It is suggested that short‐term damage to the nerve fiber caused by the microelectrode may allow accumulation of K+underneath the myelin, triggering an inward flow of K+and regenerative depolarizations. Alternatively, internodal channels may be exposed following damage to the myelin, resulting in the generation of spontaneous pacemaker potentials and repetitive discharges. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:461–468, 1998.

Evoked potentials were recorded in 10 subjects to assess cortical involvement in automatic control of grip force during restraint of a manipulandum held between finger and thumb. Brisk pulling loads elicited an increase in first dorsal interosseous EMG after 60.6 ± 2.4 ms. Preceding this response were several time-locked scalp potentials, the most significant being a widespread negativity that appeared first over the frontal cortex and peaked 19.5 ± 1.8 ms before the EMG peak, and a positivity that followed the EMG by 24.3 ± 5.4 ms. The slope of the negativity and the amplitude of the posititivy were greater than during passive conditions, suggesting that these potentials reflect cortical processes associated with automatic regulation.

A quantitative assessment was made of the firing characteristics of repetitive axonal discharges encountered during microneurographic recordings from human peripheral nerves. Spontaneous activity was recorded from 16 single axons using tungsten microelectrodes inserted percutaneously into fascicles of the median or peroneal nerves in normal subjects. These discharges typically consisted of brief bursts of 2–5 spikes occurring at a frequency of 7–10 Hz. Peak instantaneous frequencies usually exceeded 300 Hz. Based on their similarity with spontaneous high-frequency discharges recorded from single axons following nerve damage, ischemia, prolonged electrical stimulation, or hyperventilation, it is concluded that they are generated ectopically at the site of a previous impalement of a nerve fiber. It is suggested that short-term damage to the nerve fiber caused by the microelectrode may allow accumulation of K⁺ underneath the myelin, triggering an inward flow of K⁺ and regenerative depolarizations. Alternatively, internodal channels may be exposed following damage to the myelin, resulting in the generation of spontaneous pacemaker potentials and repetitive discharges. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:461–468, 1998.

Unexpected pulling and pushing loads exerted by an object held with a precision grip evoke automatic and graded increases in the grip force (normal to the grip surfaces) that prevent escape of the object; unloading elicits a decrease in grip force. Anesthesia of the digital nerves has shown that these grip reactions depend on sensory signals from the digits. In the present study we assessed the capacity of tactile afferents from the digits to trigger and scale the evoked grip responses. Using tungsten microelectrodes inserted percutaneously into the median nerve of awake human subjects, unitary recordings were made from ten FA I and 13 FA II rapidly adapting afferents, and 12 SA I and 18 SA II slowly adapting afferents. While the subject held a manipulandum between a finger and the thumb, tangential load forces were applied to the receptor-bearing digit (index, middle, or ring finger or thumb) as trapezoidal load-force profiles with a plateau amplitude of 0.5 – 2.0 N and rates of loading and unloading at 2 – 8 N/s, or as “step-loads” of 0.5 N delivered at 32 N/s. Such load trials were delivered in both the distal (pulling) and proximal (pushing) direction. FA I afferents responded consistently to the load forces, being recruited during the loading and unloading phases. During the loading ramp the ensemble discharge of the FA I afferents reflected the first time-derivative of the load force (i.e., the load-force rate). These afferents were relatively insensitive to the subject's grip force responses. However, high static finger forces appeared to suppress excitation of these afferents during the unloading phase. The FA II afferents were largely insensitive to the load trials: only with the step-loads did some afferents respond. Both classes of SA afferents were sensitive to load force and grip force, and discharge rates were graded by the rate of loading. The firing of the SA I afferents appeared to be relatively more influenced by the subject's grip-force response than the discharge of the SA II afferents, which were more influenced by the load-force stimulus. The direction in which the tangential load force was applied to the skin influenced the firing of most afferents and in particular the SA II afferents. Individual afferents within each class (except for the FA IIs) responded to the loading ramp before the onset of the subject's grip response and may thus be responsible for initiating the automatic increase in grip force. However, nearly half of the FA I afferents recruited by the load trials responded to the loading phase early enough to trigger the subject's gripforce response, whereas only ca. one-fifth of the SA Is and SA IIs did so. These observations, together with the high density of FA I receptors in the digits, might place the FA I afferents in a unique position to convey the information required to initiate and scale the reactive gripforce responses to the imposed load forces.

Long-latency electromyographic (EMG) responses can be evoked in the first dorsal interosseous muscle (FDI) by unexpected slips of an object (skin stretch) held between the index and thumb, or by forcible adduction of the metacarpophalangeal joint (muscle stretch). The former type of response is due to stimulation of tactile afferents in the skin of the digits, whereas the latter also activates muscle receptors. Previous studies have provided good evidence that long-latency reflex responses to stretch of distal muscles involve activity in a transcortical reflex pathway. The present experiments examined whether cutaneous reflexes also utilise a transcortical route. Transcranial magnetic or electrical stimuli were given over the motor cortex to evoke EMG activity during the period of the long-latency reflex response. When evoked by muscle stretch the responses to magnetic stimulation were facilitated more than those to electric stimulation. In contrast, facilitation was equal during the long-latency reflex elicited by cutaneous stimulation. Because of the different ways in which electrical and magnetic stimuli are believed to activate the motor cortex, we interpret these results to mean that the long-latency response to skin stretch is not mediated by a transcortical mechanism in the majority of subjects, whereas that following muscle stretch is. However, these are average data. In a few individual subjects, the opposite results were obtained. We suggest that there may be differences between subjects in the transcortical contribution to long-latency reflex responses. The implication is that, under normal circumstances, several pathways may contribute to these responses. If so, the relative roles of the pathways may change during different tasks, and in pathological states lesions in one system may well be accompanied by compensatory changes in other systems.

Pulling or pushing forces applied to an object gripped between finger and thumb excite tactile afferents in the digits in a manner awarding these afferents probable roles in triggering the reactive increases in grip force and in scaling the changes in grip force to the changes in applied load-force. In the present study we assessed the possible contributions from slowly adapting afferents supplying muscles involved in the generation of grip forces and from digital joint afferents. Impulses were recorded from single afferents via tungsten microelectrodes inserted percutaneously into the median or ulnar nerves of awake human subjects. The subject held a manipulandum with a precision grip between the receptor-related digit (index finger, middle finger, ring finger or thumb) and an opposing digit (thumb or index finger). Ramp-and-hold load forces of various amplitudes (0.5–2.0 N) and ramp rates (2–32 N/s) were delivered tangential to the parallel grip surfaces in both the distal (pulling) and the proximal (pushing) directions. Afferents from the long flexors of the digits (n=19), regardless of their muscle-spindle or tendon-organ origin, did not respond to the load forces before the onset of the automatic grip response, even with the fastest ramp rates. Their peak discharge closely followed the peak rate of increase in grip force. During the hold phase of the load stimulus, the afferents sustained a tonic discharge. The discharge rates were significantly lower with proximally directed loads despite the mean grip-force being similar in the two directions. This disparity could be explained by the differing contributions of these muscles to the finger-tip forces necessary to restrain the manipulandum in the two directions. Most afferents from the short flexors of the digits (n=17), including the lumbricals, dorsal interossei, opponens pollicis, and flexor pollicis brevis, did not respond at all, even with the fastest ramps. Furthermore, the ensemble pattern from the joint afferents (n=6) revealed no significant encoding of changes in finger-tip forces before the onset of the increase in grip force. We conclude that mechanoreceptors in the flexors of the digits and in the interphalangeal joints cannot be awarded a significant role in triggering the automatic changes in grip force. Rather, their responses appeared to reflect the reactive forces generated by the muscles to restrain the object. Hence, it appears that tactile afferents of the skin in contact with the object are the only species of receptor in the hand capable of triggering and initially scaling an appropriate change in grip force in response to an imposed change in load force, but that muscle and joint afferents may provide information related to the reactive forces produced by the subject.

The somatosensory nervous system is subserved by specialised mechanoreceptors in muscles, joints and skin. We now know that joint receptors primarily act as limit detectors of joint rotation, and that both cutaneous afferents and muscle spindle afferents can encode joint movements. Moreover, studies in individuals lacking muscle spindles emphasise the importance of these receptors in sensorimotor control, but also point to the redundancy in the system that allows cutaneous afferents to take over.