Hemodynamic determinants of aortic dissection propagation by 2D computational modeling: implications for endovascular stent-grafting.

AIM: Aortic dissection is a life-threatening aortic catastrophe where layers of the aortic wall are separated allowing blood flow within the layers. Propagation of aortic dissection is strongly linked to the rate of rise of pressure (dp/dt) experienced by the aortic wall but the hemodynamics is poorly understood. The purpose of this study was to perform computational fluid dynamics (CFD) simulations to determine the relationship between dissection propagation in the distal longitudinal direction (the tearing force) and dp/dt. METHODS: Five computational models of aortic dissection in a 2D pipe were constructed. Initiation of dissection and propagation were represented in 4 single entry tear models, 3 of which investigated the role of length of dissection and antegrade propagation, 1 of which investigated retrograde propagation. The 5th model included a distal re-entry tear. Impact of pressure field distribution on tearing force was determined. RESULTS: Tearing force in the longitudinal direction for dissections with a single entry tear was approximately proportional to dp/dt and L2 where L is the length of dissection. Tearing force was much lower under steady flow than pulsatile flow conditions. Introduction of a second tear distally along the dissection away from the primary entry tear significantly reduced tearing force. CONCLUSION: The hemodynamic mechanism for dissection propagation demonstrated in these models support the use of ß-blockers in medical management. Endovascular stent-graft treatment of dissection should ideally cover both entry and re-entry tears to reduce risk of retrograde propagation of aortic dissection.

The effect of firing on the excitability of a model motoneurone and its implications for cortical stimulation.

1. To help clarify the use of measurements of 'excitability', a simple model motoneurone receiving noisy tonic background excitation was tested with brief stimuli. Its response was determined from its PSTH (post-stimulus time histogram). The tonic background was varied from well below to well above the threshold for tonic firing. The conclusions should apply to many other neurones. 2. The response of the model to a stimulus depended upon a number of factors, including stimulus strength, synaptic membrane noise and especially whether or not the background drive elicited tonic firing. With the onset of firing, the shape of the stimulus-response curve changed drastically and the model then responded to the smallest stimulus without a threshold. When the drive was subthreshold, increasing the background excitation always increased the response to a given stimulus. However, what happened when the tonic drive exceeded the threshold for tonic firing depended upon the stimulus strength. With weak stimuli, the response increased with the drive to reach a plateau level where it was independent of the background firing rate; this occurred for stimuli comparable in size to the synaptic noise. With stronger stimuli, the response rose to a maximum for very low firing rates, but then decreased by up to 50 % to a plateau for high firing rates. Increasing the membrane noise reduced or abolished the maximum. 3. The model was also used to simulate a monosynaptic conditioning-testing paradigm. The effect of a given conditioning stimulus was then found to change with the onset of firing, including when the strength of the testing stimulus was adjusted to make the size of the test response the same in the presence and absence of firing. 4. The behaviour of real motoneurones can be expected to be at least as complex with the transition from silence to firing, so H reflex and other tests of 'excitability' must then be treated with caution. In particular, as has been observed experimentally, the response of a unit may decrease with increasing background excitation, as well as with inhibition. 5. Transferring the findings to corticospinal neurones makes it unlikely that the magnitude of the descending volley elicited by a given cortical stimulus ('excitability') will always increase with the initial level of cortical activity. In addition, the appreciable threshold for transcranial magnetic stimulation during voluntary contraction suggests that it first excites axons rather than the neural pacemakers.

Properties of human motoneurones and their synaptic noise deduced from motor unit recordings with the aid of computer modelling.

This paper reviews two new facets of the behaviour of human motoneurones; these were demonstrated by modelling combined with analysis of long periods of low-frequency tonic motor unit firing (sub-primary range). 1) A novel transformation of the interval histogram has shown that the effective part of the membrane's post-spike voltage trajectory is a segment of an exponential (rather than linear), with most spikes being triggered by synaptic noise before the mean potential reaches threshold. The curvature of the motoneurone's trajectory affects virtually all measures of its behaviour and response to stimulation. The 'trajectory' is measured from threshold, and so includes any changes in threshold during the interspike interval. 2) A novel rhythmic stimulus (amplitude-modulated pulsed vibration) has been used to show that the motoneurone produces appreciable phase-advance during sinusoidal excitation. At low frequencies, the advance increases with rising stimulus frequency but then, slightly below the motoneurones mean firing rate, it suddenly becomes smaller. The gain has a maximum for stimuli at the mean firing rate (the 'carrier'). Such behaviour is functionally important since it affects the motoneurone's response to any rhythmic input, whether generated peripherally by the receptors (as in tremor) or by the CNS (as with cortical oscillations). Low mean firing rates favour tremor, since the high gain and reduced phase advance at the 'carrier' reduce the stability of the stretch reflex.

Spindle and motoneuronal contributions to the phase advance of the human stretch reflex and the reduction of tremor.

1. The human stretch reflex is known to produce a phase advance in the EMG reflexly evoked by sinusoidal stretching, after allowing for the phase lag introduced by simple conduction. Such phase advance counteracts the tendency to tremor introduced by the combined effect of the conduction delay and the slowness of muscle contraction. The present experiments confirm that the EMG advance cannot be attributed solely to the phase advance introduced by the muscle spindles, and show that a major additional contribution is provided by the dynamic properties of individual motoneurones. 2. The surface EMG was recorded from biceps brachii when two different types of sinusoidally varying mechanical stimuli were applied to its tendon at 2-40 Hz. The first was conventional sinusoidal displacement ('stretch'); the spindle discharge would then have been phase advanced. The second was a series of weak taps at 103 Hz, with their amplitude modulated sinusoidally ('modulated vibration'). The overall spindle discharge should then have been in phase with the modulating signal, since the probability of any individual 1 a fibre responding to a tap would increase with its amplitude. The findings with this new stimulus apply to motoneurone excitation by any rhythmic input, whether generated centrally or peripherally. 3. The sinusoidal variation of the EMG elicited by the modulated vibration still showed a delay-adjusted phase advance, but the value was less than that for simple stretching. At 10 Hz the difference was 70-80 deg. This was taken to be the phase advance introduced by the spindles, very slightly underestimated because of the lags produced by tendon compliance in transmitting sinusoidal stretch to the muscle proper. The adjusted phase advance with modulated vibration was taken to represent that introduced by the reflex centres, undistorted by tendon compliance. At 10 Hz the reflex centres produced about the same amount of phase advance as the muscle spindles. 4. At modulation frequencies above 10 Hz the adjusted central phase advance remained approximately constant. However, when the frequency was reduced to below 6 Hz the central phase advance decreased. The depth of EMG modulation (reflex gain) also fell rapidly, starting from a slightly higher frequency. Thus the central phase advance mechanisms behave like a high-pass filter. 5. A simple model of the motoneurone, incorporating synaptic noise and an after-hyperpolarization, was tested with sinusoidal inputs and gave a phase advance over a wide range of frequencies. The effect was tightly linked to two particular facets of the motor discharge; these were the ratio between the stimulus frequency and the mean firing rate (the 'carrier frequency' of the unit), and the coefficient of variation of the interspike interval distribution. The gain rose to a maximum at the carrier frequency, while the phase advance showed a maximum at 0.8 of the carrier. The more regular the discharge, the greater were these effects. The phase advance might increase to above 90 deg, showing that the motoneurone potentially provides a major contribution to the phase advance of the stretch reflex. Related effects have already been observed in other neuronal models and for the discharge of the muscle spindle, without their significance for the motoneurone being appreciated. In essence, a rhythmically firing neurone is particularly affected by a rhythmic stimulus when the two frequencies approximately coincide. 6. Recording from single human motor units confirmed the role of the 'carrier frequency' in determining the phase advance with sinusoidal inputs. In particular, for both stretching and modulated vibration, the phase advance of the response elicited by a fixed sinusoidal stimulus changed appropriately when the firing rate of the unit varied 'spontaneously' over a long recording period. 7. Thus a combination of modelling and experiment has shown that the motoneurones themselves produce a significant phase advance.

Relationship of firing intervals of human motor units to the trajectory of post-spike after-hyperpolarization and synaptic noise.

1. Interspike interval distributions from human motor units of a variety of muscles were analysed to assess the role of synaptic noise in excitation. The time course of the underlying post-spike after-hyperpolarization (AHP) was deduced by applying a specially developed transform to the interval data. Different firing rates were studied both by varying the firing voluntarily, and by selecting subpopulations of spikes for a given firing rate from long recordings with slight variations in frequency. 2. At low firing rates the interval histograms had an exponential tail. Thus at long intervals, the motoneurone was randomly excited by noise and its post-spike AHP was complete. This contrasts with the firing produced by intracellular current injection in the cat, when the membrane potential increases linearly until threshold is reached. The interval histogram was therefore analysed with the aid of a model of synaptic excitation to deduce the mean 'trajectory' of membrane voltage in the last part of the interspike interval. 3. The computer model, described in the Appendix, was used to determine the effect of the mean level of membrane potential on the probability of a spike being excited, per unit time, during an on-going interspike interval. All variables were treated as voltages, with synaptic noise simulated by time-smoothed Gaussian noise. This enabled an interval distribution to be transformed into a segment of the underlying trajectory of the membrane potential; the potential was expressed in terms of the noise amplitude and the spike threshold. 4. At low firing rates, the equilibrium value of the membrane voltage trajectory lay well below threshold; the deviation typically corresponded to the standard deviation of the noise or more. The noise standard deviation was estimated to be about 2 mV. 5. With increasing mean firing rate, the near-threshold portion of the trajectory obtainable from the histogram occurred earlier, was steeper and rose to a higher level. Trajectories for different firing rates fell on the same curve after shifting them vertically by varying amounts. The curve was taken to represent the AHP of the motoneurone and was closely exponential. The shift of the trajectory gave its mean synaptic drive. The duration of the AHP varied between units and was longer than average for units from soleus muscle. 6. Further modelling showed that summation of noise with the AHP can explain the well-known changes in discharge variability that occur as firing rate increases. 7. It is concluded that synaptic noise plays a major role in the excitation of tonically firing human motoneurones and that the noiseless motoneurone with a linear trajectory provides an inadequate model for the conscious human. This is of interest in relation to various standard measures of human motor unit activity such as short-term synchronization.

The simple frequency response of human stretch reflexes in which either short- or long-latency components predominate.

1. The stretch reflexes of the human abductor digiti minimi (ADM) and biceps brachii muscles were compared using small-amplitude sinusoidal stretching at 10-50 Hz and recording the surface EMG. The stimulus was applied either to the relevant proximal phalanx or to the biceps tendon while the muscle studied was contracting; the same amplitude was used for all frequencies (range 0.5-2 mm for ADM, 0.1-1 mm for biceps). 2. As the frequency increased, the response of ADM decreased while that of biceps increased. Neither muscle showed a minimum at 20-25 Hz, as previously found for wrist muscles and attributed to an interaction between short- and long-latency components of the reflex. 3. For both muscles, the phase of the response lagged behind the stimulus by an amount which increased approximately linearly with frequency, without the gross inflexion found for wrist muscles. Such linearity would be found for a system dominated by a fixed time delay; its value sets the slope. The slope for biceps was half that for ADM. The values of reflex delay calculated from the slope of the phase plots agreed reasonably with the absolute latencies of the responses evoked by tap or ramp stimulation. Part of the difference between the muscles was due to differences in peripheral conduction time, since ADM lies more distally. Most of it, however, was due to different reflexes being involved, with biceps being predominantly controlled by short-latency pathways and ADM by long-latency pathways. 4. For both muscles, the phase lag at any given frequency was less than that expected from the reflex latency, determined from the slope of the phase plot. Thus, sensory transduction and central transmission had produced a phase advance in the reflex. The 'neural phase advance' of biceps was appreciably larger than that of ADM, and more than would be expected from the behaviour of its spindle afferents. The excess is suggested to be due to the action of Renshaw inhibition, which ADM may lack. 5. The results were substantiated by recording from single motor units in biceps. Stretching at the present amplitudes had rather little effect on the overall rhythmic behaviour, as shown by interspike interval histograms. However, cycle histograms showed that the discharge was modulated reasonably sinusoidally by the stretching, whatever its frequency (i.e. the probability of the occurrence of a spike varied over the cycle). Cyclic changes were also found in autocorrelograms and amplitude spectra of the spike trains.(ABSTRACT TRUNCATED AT 400 WORDS)

Texture perception and afferent coding distorted by cooling the human ulnar nerve.

The roughness of standardized surfaces (embossed dot arrays or gratings) was compared by scanning them with the little finger of either hand while the ulnar nerve was cooled unilaterally at the elbow; both hands remained warm. Across-hand comparison of roughness showed that a given surface felt smoother on the cooled side. When the surfaces were adjusted to feel equally rough, that on the cooled side would normally have felt appreciably rougher. The effect of the nerve cooling on axonal conduction was monitored during the psychophysical experiments by stimulating the ulnar nerve above the cooled region and recording the EMG of an ulnar-innervated hand muscle. During cooling, large myelinated axons remained unblocked, but prolongation of their absolute refractory period to 5-10 msec left them unable to transmit trains of impulses at high frequencies (Wedensky inhibition). By varying the length of nerve cooled and the cooling temperature, it was shown that the perceptual effects were not due to an increase in the normal temporal dispersion of impulses transmitted by different-sized afferents. The effect of increasing the absolute refractory period on the signals from the various types of cutaneous afferent was modeled mathematically, using earlier human single-fiber responses to dot arrays. It is concluded that the reduction of perceived roughness with nerve cooling is due to Wedensky inhibition, and that the percept of roughness is related to the local contrast in the afferent spatiotemporal image.

Interaction between short- and long-latency components of the human stretch reflex during sinusoidal stretching.

1. Using wrist muscles, the subdivision of the human stretch reflex into separate components was examined with small amplitude sinusoidal stretching of relatively high frequency (10-40 Hz). The reflex was evoked by angular rotation of the wrist (below 1 deg amplitude), applied via the hand during maintained voluntary contraction of the muscle studied; both flexors and extensors were tested. 2. The reflex response was recorded electromyographically rather than mechanically. For each condition, the surface EMG was rectified and averaged to give a cycle average showing the mean response evoked by a cycle of stretching. The cycle average was fitted with a sinusoid, the amplitude and phase of which were used to assess the reflex; their value reflects the combined action of its various sub-components. Fourier analysis gave similar results (the EMG was then rectified but not averaged). 3. The amplitude of the reflex response typically fell to a minimum in the region of 20-25 Hz. The phase lag of the response in relation to the stimulus increased approximately linearly with frequency, except in the region of the amplitude minimum. Here the lag tended to remain constant, or to decrease slightly; this created a discontinuity between the upper and lower limbs of the phase plot. 4. Such effects are attributed to an interaction between two components of the reflex that differ in latency by 20-25 ms. These would progressively change their relative phase as the frequency increased. At first they would come to interfere with each other, but then the more delayed reflex produced by a given cycle of stretching would begin to sum with the shorter latency reflex evoked by the next stretch. 5. At high and low frequencies the cycle averages were normally well fitted by a single sinusoid. Around 20-25 Hz, however, they typically showed appreciable harmonic distortion, with the second harmonic larger than the fundamental. The cycle average then showed two separate responses per cycle of stretching. These were considered to represent the uncancelled non-linear residua of separate components of the reflex response. Their relative timing shifted appropriately with change of frequency. 6. These 'double responses' are unlikely to be due to mechanical resonance. First, the relative sizes of the two components could be altered by the reflex action of cutaneous afferents. Second, the same pattern of behaviour was found when the mechanical stimuli were applied directly to the tendon of flexor carpi radialis while the hand remained fixed.(ABSTRACT TRUNCATED AT 400 WORDS)

The human stretch reflex and the motor cortex.

The spinal stretch reflex, exemplified by the tendon jerk, appears to be less important in humans than a delayed 'long-latency' response. This is easily observed when muscles of the hand are stretched while they are already contracting voluntarily. On limited evidence, many have long held that the delayed response is a transcortical reflex and have tended to neglect alternative possibilities, particularly that it might be a spinal reflex dependent upon slow afferents. New experiments have now eliminated the alternatives, leaving the transcortical hypothesis in command of the field.

On the localization of the stretch reflex of intrinsic hand muscles in a patient with mirror movements.

1. The patient studied showed the typical mirror movements of the Klippel-Feil syndrome. Earlier intensive electrophysiological analysis suggests that many of her corticospinal axons branch abnormally to supply motoneurones on both sides of the spinal cord. Thus, in her, a long-latency reflex utilizing the motor cortex should manifest itself bilaterally. 2. EMG recordings were made simultaneously from the first dorsal interosseous (FDI) muscles of both hands while they were being voluntarily activated by the subject. The FDI of one hand was then briefly stretched by forcibly adducting the index finger. Similar but more limited studies were made using flexor pollicis brevis. 3. The reflex response of the stretched muscle consisted of a typical mixture of early (M1) and late (M2) components, with mean latencies of 32 and 49 ms respectively. 4. Unlike normal controls, the contralateral muscle responded on stretch of the ipsilateral muscle. However, its response consisted solely of a long-latency reflex. This was comparable in size, latency and waveform to the ipsilateral late component. (Mean size, 84% of the ipsilateral M2 response; mean latency 46 ms, or 3 ms less than the ipsilateral response due to the absence of M1). 5. The short-latency response did not spread to the homologous contralateral muscle even when it was large ipsilaterally. The long-latency response elicited from FDI did not spread to the abductor digiti minimi muscle of either hand. 6. Reducing the duration of the stretch reduced the duration of the crossed response by an equivalent amount. Unloading the ipsilateral muscle produced a delayed reduction of EMG activity contralaterally. Thus her long-latency pathway can act tonically as well as phasically. 7. These findings strongly support the hypothesis that delayed components of the human stretch reflex are relayed via the motor cortex and the corticospinal tract.

The 1989 James A. F. Stevenson memorial lecture. The knee jerk: still an enigma?

This is a wide-ranging review of muscle proprioceptors, intended primarily for the nonspecialist. It emphasizes how much more they are concerned with, than just the production of the knee jerk; it concentrates on principle rather than documenting detail and cites selectively. The main topics covered are the effect of deafferentation, position sense, the proprioceptors themselves, the control of the muscle spindle by the CNS, and spinal and long-latency "stretch" reflexes. The emphasis is on human work. The knee jerk itself is seen as a "physiological artefact," resulting from a mode of stimulation that does not occur in life, with the normal function of its underlying circuitry still under debate.

Observations on the reflex effects seen in Parkinson's disease on terminating a period of tendon vibration.

Vibration was applied to the tendon of flexor carpi radialis while recording the EMG of the wrist flexors in 29 Parkinsonian patients. Cessation of the vibration led to a small short-latency (approximately 25 ms) reduction in the level of activity which did not differ in magnitude from the normal. Moreover, there was no sign of any subsequent long-latency reduction of activity. Thus the maintained tonic activity of Parkinsonian muscles seems unlikely to be due to an enhancement of the tonic reflex actions of the Ia afferents, especially via the short-latency pathway. In addition, the findings argue against reduction of either Ia or Ib firing being responsible for the delayed excitatory "Westphal" (or "shortening") response that may occur in parkinsonism on allowing a muscle to shorten; this was never found on terminating vibration, even when present on muscle release.

Long-latency stretch reflexes of two intrinsic muscles of the human hand analysed by cooling the arm.

1. The arm was cooled to examine the effect of slowing nervous conduction on the latency of various reflex responses of the abductor digiti minimi (ADM) and the first dorsal interosseus (FDI) muscles. A reflex dependent upon slow afferents acting with a short central delay should be slowed by more than one of comparable initial latency, but dependent upon fast afferents acting with a long central delay. The F wave seen in the EMG on stimulating the ulnar nerve was used to assess the effect of cooling in slowing fast fibres. 2. Cooling showed that the prominent long-latency excitation evoked on stretching one or other muscle by displacing the appropriate finger is medicated by fast afferent fibres. 3. Both fast cutaneous and group I muscles afferents were found to be capable of contributing to the long-latency responses. The muscle afferent contribution was consistently dominant for slow 'stretches', while a cutaneous afferent contribution was sometimes recognizable for finger taps. 4. The distinction proved possible because the cutaneous afferents from the relevant finger run in the median nerve for FDI and the ulnar nerve for ADM. The cooling produced much greater slowing of conduction for the ulnar nerve. 5. The prior suggestion that spindle group II afferents are responsible for the major part of the long-latency component of the human stretch reflex thus fails to stand; however, some contribution has not been finally excluded.

Analysis of human long-latency reflexes by cooling the peripheral conduction pathway; which afferents are involved?

This chapter first outlines current views on the afferents of origin of human "long-latency stretch reflexes", and especially whether they are fast or slow. Attention is concentrated on methodology; other approaches can be found elsewhere with appropriate bibliography (Marsden et al., 1983; Matthews, 1985, 1986a; Wiesendanger, 1986). Recent experiments involving cooling of the human arm are then described. They were performed on the abductor digiti minimi and first dorsal interosseus muscles. The arm was cooled from wrist to axilla by circulating cold water through a tube wrapped round it. Cooling slows conduction by a constant proportion, hence the conduction delay introduced by cooling a segment of nerve is greater for small slow axons than for large fast ones. On this basis it was concluded that group I muscle afferents (presumably Ia) can elicit a long-latency reflex with a long central delay, as also can fast cutaneous afferents. No evidence was found for a long-latency reflex with the delay introduced peripherally by conduction along slow axons (i.e. spindle group II afferents). However, the co-existence of such a mechanism has yet to be excluded.

On the long-latency reflex responses of the human flexor digitorum profundus.

1. Electromyography (surface and intramuscular) has been used to study the reflex responses of the human flexor digitorum profundus (FDP) to angular rotation of the distal interphalangeal joint of the 4th finger. This has been done with the hand in three separate positions which, owing to the arrangement of the various tendons, allow the movement to be transmitted to (a) both the flexor and extensor muscles, (b) FDP alone (extensors disengaged) and (c) neither flexor nor extensor muscles (all muscles disengaged, but cutaneous and joint receptors still potentially activated). The stimuli were applied while the subject was voluntarily contracting FDP to produce a constant level of EMG activity; this remained possible when the muscle was disengaged from the joint. 2. With all muscles connected, FDP behaved similarly to the analogous long flexor of the thumb. 'Stretch' elicited a prolonged complex response starting with a short-latency component corresponding to the tendon jerk. Unloading of the contracting muscle caused a pronounced reduction of its on-going EMG activity. The latency of this latter effect was approximately 20 ms greater than that of the initial stretch-evoked response, thereby demonstrating that it was not due to a disfacilitation via the short-latency pathway (on reduction of the tonic spindle afferent firing from FDP as it shortened). 3. With all muscles disengaged, movement of the joint in either direction evoked simply a weak, variable excitatory response, with a latency somewhat greater than that of the normal unloading response. This was attributed to the activation of cutaneous and/or joint receptors. The effectiveness of the disengagement of the flexor was demonstrated by the abolition of its normal stretch-evoked short-latency response. 4. With the flexor engaged and the extensors disengaged both stretch and release evoked their normal types of response. In control experiments, surface EMG recordings from the interosseus muscles confirmed that the procedure used for extensor disconnection was effective. These findings exclude the possibility that the reduction of EMG activity of the unloading response of FDP might be attributable to an inhibition evoked by the concomitant stretch of its antagonists. 5. The long-latency unloading response (whether with the extensors engaged or disengaged) remained when the sensory receptors in the finger itself were inactivated, confirming that these were not responsible.(ABSTRACT TRUNCATED AT 400 WORDS)

Proprioceptors and their contribution to somatosensory mapping: complex messages require complex processing.

This review of other people's work concentrates on two matters. First, which of the various receptors are chiefly involved in creating the central representations or maps of the body that both underlie the conscious perception of our body image and are needed to control our motor performance. Second, how are these relatively well-charted signals used in sensorimotor mapping, with particular attention paid to various human psychophysical observations and illusions that throw light on the central integrative mechanisms involved. Detailed citation is largely restricted to developments since earlier reviews.

Observations on the automatic compensation of reflex gain on varying the pre-existing level of motor discharge in man.

The human stretch reflex is well known to show 'automatic gain compensation'; in other words, the electromyographic (e.m.g.) response evoked by a given disturbance increases progressively with the level of pre-existing voluntary activity, and so remains an approximately constant proportion of the background. Such behaviour has now been observed using vibration as the stimulus to Ia action and recording the reflexly developed force, in addition to the e.m.g. Inhibition was studied as well as excitation by vibrating the antagonist as well as the agonist, and found to be similarly regulated. The experiments were performed on the elbow flexors while they were contracting isometrically under voluntary drive. The vibration was either square-wave modulated at 5 Hz or delivered in bursts of one to five pulses. The latency of the e.m.g. responses produced by the latter was sufficiently short to show that gain compensation was a feature of spinal reflex action. In the Discussion, it is concluded that in principle 'automatic gain compensation' can be readily attributed to the known organization of the motoneurone pool. As the background force increases so does the number of active motoneurones available to be frequency-modulated by a given input, and the larger and stronger will be those motor units which are on the verge of recruitment or de-recruitment.

Observations on the genesis of the stretch reflex in Parkinson's disease.

Using surface electromyography the reflex response of flexor carpi radialis elicited by forcibly dorsiflexing the wrist was compared with that elicited by applying vibration percutaneously to its tendon. This was done both in patients with Parkinson's disease and in normal subjects. The reflexes were elicited on top of a pre-existing voluntary contraction of the muscle of about 20 per cent maximum. The responses in parkinsonism were qualitatively similar to the normal, but differed quantitatively in certain respects. The response to 'stretch' of the muscle by wrist dorsiflexion normally continued at a high level up to at least 80 ms from the beginning of the movement, commonly with an apparent separation into 'short' and 'long' latency responses. On average, the later components of the response were enhanced in parkinsonian patients in comparison with the normals, confirming other workers' findings; they were also prolonged. The short-latency responses were unchanged. Vibration, in contrast, elicited solely a short-latency response with the initial reflexly-evoked augmentation of EMG activity coming to an end 40 to 50 ms from the beginning of the stimulation, even though the vibration was continuing. Such an absence of the later components that were so prominent with stretch was found whatever the size of the initial short-latency response evoked by vibration, including when it was comparable to that evoked by stretch in the same subject. This purely short-latency vibration response was on average unchanged in parkinsonism. The findings support the hypothesis, already advanced for the long flexor of the thumb, that the long-latency components of response are largely attributable to a spinal excitatory action of the spindle group II afferents with the delay arising from the slowness of their conduction. They are not readily compatible with either of the two major alternative hypotheses, namely the 'long-loop' (or transcortical) hypothesis and the 'resonance' hypothesis, both of which attribute the late response, as well as the initial response, to the spindle Ia afferents. The enhancement of the later components of response in parkinsonism thus now seems likely to be due to an increase in the postulated spindle group II excitatory action, possibly related to a reduction in opposing inhibition, rather than to any change in the reflex excitability of the higher centres on Ia activation. However, the rigidity of parkinsonism cannot be uniquely ascribed to an enhancement of group II action, because over the population as a whole clinically similar degrees of rigidity could be accompanied by quite different long-latency responses, and vice versa.

Observations on the time course of the electromyographic response reflexly elicited by muscle vibration in man.

Surface electromyography has been used to study the initial reflex response of various muscles to vibration, applied to their tendons, when the subject was already contracting them voluntarily. The response at the onset of vibration was of a latency appropriate for Ia monosynaptic action and was always highly phasic with an initial wave rising far above any maintained increase in electromyogram (e.m.g.) activity; its duration was typically well below 20 ms in the rectified average. Thus, there is nothing peculiar, in this respect, about flexor pollicis longus for which such behaviour has already been described, and used to draw certain wide-ranging conclusions about the stretch reflex. Theoretical considerations, developed in an Appendix, show that quite apart from the operation of any inhibitory mechanisms such a phasic response is to be expected from a population of tonically discharging motoneurones when there is a step increase in the level of their excitatory drive.