Proprioceptive illusions induced by muscle vibration: contribution by muscle spindles to perception?

When vibration of 100 hertz was applied to the tendon of the biceps or the triceps muscle, the subject made a systematic misjudgment of the angle at the elbow. During contraction the error could be as much as 40 degrees. The subject thought that the elbow was in the position that it would have assumed if the vibrated muscle had been stretched.

Kinaesthetic signals and muscle contraction.

Signals generated both peripherally and centrally contribute to the group of sensations termed kinaesthesia. Many experiments report sensations of position and movement under passive relaxed conditions without muscle contraction. However, kinaesthetic acuity is probably of greater functional value when subjects are active rather than passive and, accordingly, movement detection is markedly improved by muscular contraction. One mechanism contributing to this enhancement is likely to involve muscle spindle volleys. When identical microstimulation techniques are applied to skin, joint and muscle spindle endings innervating the hand, some cutaneous afferents and some joint afferents elicit a sensation, but activation of certain other cutaneous afferents and muscle spindle afferents rarely does. Activity in more than one muscle spindle afferent may be required for kinaesthetic sensations, whereas some single cutaneous and joint afferents may have a more 'secure' central projection.

Muscular reflex and baroreflex influences on heart rate during isometric contractions.

Isometric hindlimb contractions were induced in anaesthetised dogs by stimulation of appropriate spinal ventral roots. During such contractions there were appreciable reflex systemic pressor responses accompanied by small increases in heart rate. The heart rate responses during contractions were small because the primary cardioacceleratory reflexes from muscle were partly masked during contractions by opposing baroreceptor-cardiodepressor reflexes.

Effects of blood pressure on force production in cat and human muscle.

In anesthetized cats reducing local arterial pressure from 125 to 75 Torr decreased blood flow (53 +/- 5%) and force production (57 +/- 7%) in soleus and medial gastrocnemius. Force was produced in these muscles by aerobic, slowly fatiguing fibers. Similar reductions in arterial pressure did not affect force production in caudofemoralis, which contains mainly fast-fatiguing fibers. In human subjects the electromyogram produced by the ankle extensors during rhythmic constant-force contractions increased as the contracting muscles were raised above the heart during legs-up tilt. This suggests that force production of active muscle fibers at a given level of activation fell with muscle perfusion pressure, thus requiring augmentation of muscle activity to sustain the standard contractions. Because aerobic fibers contributed to these contractions, it appears that force production of human muscle fibers is sensitive to small changes in perfusion pressure and, presumably, blood flow. The critical dependence of developed muscular force on blood pressure is of importance to motor control and may also play a significant role in cardiovascular control during exercise.

Effects of systemic arterial blood pressure on the contractile force of a human hand muscle.

The effect of physiological changes in systemic blood pressure on the force output of working abductor pollicis (AP) muscle was studied in six normal subjects. Supramaximal tetanic stimulation at the ulnar nerve produced repeated isometric contractions at 1-s intervals. Force output declined gradually with time. During the train of contractions, subjects voluntarily contracted the knee extensors for 1 min; this raised systemic blood pressure by 29%. Force output from AP rose in parallel with blood pressure so that 18% of the contraction force lost through fatigue was recovered for each 10% increase in blood pressure. When blood pressure in the hand was kept constant despite the increased systemic pressure, force output did not rise. The results show that muscle performance is strongly affected by physiological changes in central blood pressure and suggest that sensory input concerning the adequacy of muscle performance exerts a feedback control over the increase in systemic blood pressure during muscular activity.

Effects of muscle perfusion pressure on fatigue and systemic arterial pressure in human subjects.

The effects of changes in arterial perfusion across the physiological range on the fatigue of a working human hand muscle were studied in seven normal subjects. With the hand above heart level, subjects made repeated isometric contractions of the adductor pollicis muscle at 50% of maximal voluntary contraction in a 6-s on, 4-s off cycle. To assess fatigue, a maximal isometric twitch was elicited in each "off" period by electrical stimulation of the ulnar nerve. The experiment was repeated at least 2 days later with the hand at heart level. Five subjects showed faster fatigue with the arm elevated, and two subjects showed little difference in fatigue for the two conditions. Central blood pressure rose in proportion to fatigue for the subjects overall and returned quickly to its initial level afterwards. We conclude that human muscle fatigue can be increased by physiological reductions in perfusion pressure. Central blood pressure increases as the muscle fatigues, a response that may partially offset declining muscle performance.

Peptide YY reduces effects of sympathetic nerves and neuropeptide Y on cardiac vagal action.

In anesthetized dogs intravenous injection of neuropeptide Y (NPY) or stimulation of the cardiac sympathetic nerve is followed by a period of attenuation of vagal action at the heart lasting from many minutes to over an hour. Peptide YY (PYY), a related peptide (but one not reported to occur in the heart or its autonomic innervation), also inhibits cardiac vagal action but is more powerful and has a longer duration action. In 5 of 9 dogs, cardiac sympathetic nerve stimulation inhibited vagal action on the heart in control conditions, but relieved preexisting inhibition when repeated in the presence of PYY. In 3 dogs, exogenous NPY inhibited cardiac vagal action in control conditions, but failed to augment preexisting inhibition in the presence of PYY. An explanation offered for these results is that when PYY is occupying receptors on vagal nerve terminals, nerve-released NPY or exogenous NPY is either unable to produce an effect, because it cannot gain access to the receptors, or displaces PYY from at least some receptors and, being less powerful than PYY in its inhibitory action, lessens the preexisting vagal attenuation. The results reported are consistent with the proposal that the factor released from the sympathetic nerves following their stimulation and which is responsible for cardiac vagal inhibition is NPY.

Neuropeptide Y and control of vascular resistance in skeletal muscle.

The effect of neuropeptide Y (NPY) on the increase in skeletal muscle vascular resistance caused by exogenous noradrenaline and by sympathetic stimulation was examined in gracilis muscles of anaesthetised dogs. NPY potentiated the increases in resistance caused by both of these to similar degrees. Although NPY itself often caused an elevation in the basal resistance, correlation coefficients for the percentage increase in basal resistance due to NPY and the percentage increase in the evoked sympathetic and noradrenergic responses in the presence of NPY indicated that it was the NPY itself (rather than the increase in basal resistance per se) which was responsible for the potentiation. The potentiation was apparently biphasic, with an initial peak in response during the first 20 min following administration of NPY followed by a secondary peak between 30 and 60 min. Radioimmunoassay for plasma levels of NPY indicated that the secondary increase of vascular resistance was not associated with a secondary peak in the plasma level of NPY.

Neuromodulation of the cardiac vagus: comparison of neuropeptide Y and related peptides.

Neuropeptide Y (NPY), a putative co-transmitter in noradrenergic sympathetic nerves of the cardiovascular system, inhibits the negative chronotropic action of the cardiac vagus. In the present study, peptides related to NPY were tested for potency in producing this effect. In bilaterally vagotomized, anaesthetised dogs, the increase in pulse interval caused by electrical stimulation of the peripheral stump of the right vagus was measured before and after intravenous administration of peptide. The effects of doses of NPY were compared with those of equimolar doses of peptide YY (PYY), and of avian and human pancreatic polypeptides (APP and HPP). PYY inhibited the vagal action more effectively than did NPY. APP and HPP, however, caused no change in strength of vagal action at the doses used. The response to a second injection of NPY, given soon after the injection of APP or HPP, was not significantly different from the original. Thus no evidence was obtained for a competitive inhibition of the action of NPY by either pancreatic polypeptide. A C-terminal hexapeptide fragment of human pancreatic polypeptide was also tested. Like APP and HPP, it neither inhibited the cardiac vagus nor blocked the action of NPY. The order of potency obtained here (PYY greater than NPY much greater than APP, HPP, CFPP) can be expected to be of use in efforts to distinguish the active site(s) of the NPY molecule, and to characterise the receptors involved in these modulatory effects.

Functional effects of a family of galanin antagonists on the cardiovascular system in anaesthetised cats.

Previous studies have shown that injection of galanin (GAL: 6.2 nmol/kg) causes prolonged inhibition of cardiac vagal action in anaesthetised cats. Stimulation of the cardiac sympathetic nerve (16 Hz for 5 min) also produces inhibition of cardiac vagal action, an effect which has been proposed to be due to the release of endogenous GAL from sympathetic nerves. In a previous study we tested galantide (M15) and in this study we compared galantide with two other GAL antagonists for their GAL antagonist activity in our experimental model. Each of these incorporate the N-terminal fragment GAL 1-13 and a C-terminal portion of another bioactive peptide and all are C-terminally amidated. GAL 1-13 Substance P 5-11 amide (galantide: M15: 62 nmol/kg and 156 nmol/kg), GAL 1-13 Spantide amide (C7: 156 nmol/kg) and GAL 1-13 NPY 24-36 amide (M32a: 62 nmol/kg) all significantly reduced the cardiac vagal inhibitory effect of exogenous GAL and also reduced the effect of sympathetic stimulation on subsequent cardiac vagal slowing, giving strong support to our hypothesis that GAL is involved in this phenomenon. No antagonist reduced the depressor effect of GAL. This study demonstrates the GAL antagonist properties of these agents on autonomic neuroeffector functions making them useful tools in elucidating further functions of endogenous GAL.

The effects of galanin and galanin fragments on cardiac-vagal action and blood pressure in the anaesthetised cat.

Galanin (GAL), 29 amino acid peptide, has previously been shown to inhibit cardiac vagal action, and to cause a fall in systemic blood pressure in anaesthetised cats, at a dose of 6.2 nmol/kg. Here, the biological activity of exogenous GAL fragments was assessed in anaesthetised cats. GAL 1-16 at a dose equimolar with the full GAL 1-29 peptide (6.2 nmol/kg) and at a dose five times the molar dose of GAL 1-29 (31 nmol/kg), was found to be biologically active although the effects were less than that of the full peptide. GAL 1-15 at doses up to 10-times the molar dose of GAL 1-29, however, was not active, suggesting that amino acid 16, isoleucine, is critical for activity. In addition, GAL 15-29 and 21-29 showed no biological activity at doses up to 10-times the molar dose of GAL 1-29. These results suggest that the N-terminal rather than the C-terminal end of the GAL molecule is the one responsible for most of GAL's biological activity in this preparation.

Pre- and postjunctional actions of neuropeptide Y and related peptides.

The effects of neuropeptide Y (NPY) and related peptide fragments on blood pressure and vagal action at the heart were compared in the anaesthetized rat. A change in vagal action was taken as a measure of presynaptic activity and a change in blood pressure was taken as a measure of postsynaptic activity. NPY, NPY-(13-36), PYY-(13-36), des-Ser22-NPY-(13-36) and a stabilized 13-36 analogue of NPY (ANA NPY) all exerted pressor actions and attenuated vagal action at the heart. The maximum vagal inhibitory or presynaptic action in order of potency was NPY, ANA-NPY, PYY-(13-36) significantly greater than NPY-(13-36), des-Ser22-NPY-(13-36). The order of potency for the half time of this effect was NPY, ANA-NPY significantly longer than PYY-(13-36) and NPY-(13-36), which were significantly longer than des Ser22-NPY-(13-36). For the pressor or postsynaptic effects, NPY increased blood pressure significantly more and for a longer duration than all the 13-36 fragments, which were not demonstrably different in this respect. These results are consistent with the proposal that there are two populations of NPY receptors. The C-terminal flanking peptide of NPY (CPON) and desamido-NPY had no effect on either vagal action at the heart or on blood pressure.

Pointing.

The roles of vision and proprioception in the task of pointing at a distant object were investigated. When guided solely by proprioception, subjects pointed from the shoulder through the finger to the object, down the long axis of the arm. When vision was present, it dominated proprioception and subjects pointed with the fingertip close to a sight line from the eyes to the object.

Effects of externally imposed elastic loads on the ability to estimate position and force.

Normal adult subjects attempted, with vision excluded, to match the position of the left index finger by pointing to it with the right one, using only flexion-extension movements at the right elbow. An elastic load applied at the right wrist was altered from trial to trial. When instructed to align the fingers, subjects were found to select the position of the right forearm by taking into account both a position signal and some measure of the force exerted by the elbow flexors. When instructed to match a target force, instead of position, the subjects were able to give greater weighting to signals of force than in the position matching task.

Proprioceptive contributions to tactile identification of figures: dependence on figure size.

Studies on the recognition of objects or shapes explored by a hand or finger have concentrated on the relative merits of different methods of exploration--in particular, whether the exploring hand or finger is moved by the subject himself (active), is guided by an assistant (passive), or remains stationary with the shape being moved by an assistant (tactile). These factors, together with another variable--the size of the explored shape--were investigated in twelve normal adults whose task, without the aid of vision, was to explore and identify various shapes with the tip of the extended right index finger. Two series of shapes were used, a large (15 cm) and small (3 cm) series, both of which consisted of twelve shapes each being a variant of the letter 'S'. The shapes were outlined as rows of Braille-like dots on a flat surface. Exploration was also tested in the proprioceptive mode, in which the exploring hand was guided by an assistant around a shape which was simply drawn on the surface so as to give a minimum of tactile information. For neither large nor small shapes could we demonstrate differences between active, passive and proprioceptive exploration. For the small shapes, the active, passive and proprioceptive modes gave no advantage over purely tactile assessment. However, for the larger shapes, active, passive and proprioceptive modes allowed better identification than movement of the shape. Thus, purely cutaneous signals appear sufficient for optimal discrimination of small figures but proprioceptive signals, generated by movement, are needed for optimal discrimination of larger figures.

Postural stability of the head in response to slowly imposed, small elastic loads.

To examine postural stability of the head, slow, undetectable rotations of small amplitude were imposed about a vertical axis while human subjects maintained a stationary body. Six normal subjects were used. The rotations were imposed through an elastic linkage, and lasted 4 s. The amplitude of head rotation was small, approximately 0.002 rad. The imposed perturbations commenced from an unloaded resting position with the head facing forward, under four conditions (1) relaxed, eyes closed; (2) relaxed, eyes open; (3) still, eyes closed; and (4) still, eyes open. The terms "relaxed' and "still' refer to the prior instructions given to the subjects regarding how they were to hold their head. There was a near linear relationship between average torque and average head angle. The effective stiffness of the head on the neck was notably low, approximately 10 Nm rad-1. Two-way analysis of variance (ANOVA) demonstrated ability to increase mean stiffness between "relaxed' and "still' conditions by 51% (P < 0.02). Visual input did not change mean stiffness significantly. Therefore, for the rotations to have been imperceptible, either the visual shifts involved must have been imperceptible, or the eyes must have counterrotated.

Comparison of the inhibitory roles of neuropeptide Y and galanin on cardiac vagal action in the dog.

Prolonged attenuation of cardiac vagal action occurs following cardiac sympathetic nerve stimulation or intravenous neuropeptide Y (NPY) injections in anaesthetised dogs. Equimolar intravenous injections of galanin (GAL) had no effect on cardiac vagal action in this species. Immunohistochemical analysis of dog stellate ganglia and cardiac muscle showed that most nerve cell bodies showing tyrosine hydroxylase immunoreactivity (TH-IR) also showed immunoreactivity to both NPY and GAL. The results are consistent with the proposal that NPY released from cardiac sympathetic nerves is responsible for the prolonged inhibition of cardiac vagal action known to be caused by such stimulation. A role for GAL, shown here to exist in cardiac sympathetic nerves in the dog, has yet to be determined.

Effects of human, rat and porcine galanins on cardiac vagal action and blood pressure in the anaesthetised cat.

Galanin (GAL) is distributed in sympathetic nerves in the cat, and exogenous GAL inhibits cardiac vagal action and lowers blood pressure in this species. This study on anaesthetised cats compares the effects on cardiac vagal action and blood pressure of human, rat and porcine GAL. Human GAL has only recently been sequenced. It is of particular interest as it is not C-terminally amidated, unlike porcine and rat GAL. Many regulatory peptides require a C-terminal amide group for their action. However, human GAL showed similar biological activity to the other (amidated) GALs here. Omission of a single amino acid (Ser6) from rat GAL significantly attenuated both cardiovascular actions studied here.