Increased gravitational force reveals the mechanical, resonant nature of physiological tremor.

KEY POINTS: Physiological hand tremor has a clear peak between 6 and 12 Hz, which has been attributed to both neural and resonant causes. A reduction in tremor frequency produced by adding an inertial mass to the limb has usually been taken as a method to identify the resonant component. However, adding mass to a limb also inevitably increases the muscular force required to maintain the limb's position against gravity, so ambiguous results have been reported. Here we measure hand tremor at different levels of gravitational field strength using a human centrifuge, thereby increasing the required muscular force to preserve limb position without changing the limb's inertia. By comparing the effect of added mass (inertia + force) versus solely added force upon hand acceleration, we conclude that tremor frequency can be almost completely explained by a resonant mechanical system. ABSTRACT: Human physiological hand tremor has a resonant component. Proof of this is that its frequency can be modified by adding mass. However, adding mass also increases the load which must be supported. The necessary force requires muscular contraction which will change motor output and is likely to increase limb stiffness. The increased stiffness will partly offset the effect of the increased mass and this can lead to the erroneous conclusion that factors other than resonance are involved in determining tremor frequency. Using a human centrifuge to increase head-to-foot gravitational field strength, we were able to control for the increased effort by increasing force without changing mass. This revealed that the peak frequency of human hand tremor is 99% predictable on the basis of a resonant mechanism. We ask what, if anything, the peak frequency of physiological tremor can reveal about the operation of the nervous system.

Is postural tremor size controlled by interstitial potassium concentration in muscle?

OBJECTIVES: To determine whether factors associated with postural tremor operate by altering muscle interstitial K(+). METHODS: An experimental approach was used to investigate the effects of procedures designed to increase or decrease interstitial K(+). Postural physiological tremor was measured by conventional means. Brief periods of ischaemic muscle activity were used to increase muscle interstitial K(+). Infusion of the beta(2) agonist terbutaline was used to decrease plasma (and interstitial) K(+). Blood samples were taken for the determination of plasma K(+). RESULTS: Ischaemia rapidly reduced tremor size, but only when the muscle was active. The beta(2) agonist produced a slow and progressive rise in tremor size that was almost exactly mirrored by a slow and progressive decrease in plasma K(+). CONCLUSIONS: Ischaemic reduction of postural tremor has been attributed to effects on muscle spindles or an unexplained effect on muscle. This study showed that ischaemia did not reduce tremor size unless there was accompanying muscular activity. An accumulation of K(+) in the interstitium of the ischaemic active muscle may blunt the response of the muscle and reduce its fusion frequency, so that the force output becomes less pulsatile and tremor size decreases. When a beta(2) agonist is infused, the rise in tremor mirrors the resultant decrease in plasma K(+). Decreased plasma K(+) reduces interstitial K(+) concentration and may produce greater muscular force fluctuation (more tremor). Many other factors that affect postural tremor size may exert their effect by altering plasma K(+) concentration, thereby changing the concentration of K(+) in the interstitial fluid.

Human balancing of an inverted pendulum: is sway size controlled by ankle impedance?

Using the ankle musculature, subjects balanced a large inverted pendulum. The equilibrium of the pendulum is unstable and quasi-regular sway was observed like that in quiet standing. Two main questions were addressed. Can subjects systematically change sway size in response to instruction and availability of visual feedback? If so, do subjects decrease sway size by increasing ankle impedance or by some alternative mechanism? The position of the pendulum, the torque generated at each ankle and the soleus and tibialis anterior EMG were recorded. Results showed that subjects could significantly reduce the mean sway size of the pendulum by giving full attention to that goal. With visual feedback sway size could be minimised significantly more than without visual feedback. In changing sway size, the frequency of the sways was not changed. Results also revealed that ankle impedance and muscle co-contraction were not significantly changed when the sway size was decreased. As the ankle impedance and sway frequency do not change when the sway size is decreased, this implies no change in ankle stiffness or viscosity. Increasing ankle impedance, stiffness or viscosity are not the only methods by which sway size could be reduced. A reduction in torque noise or torque inaccuracy via a predictive process which provides active damping could reduce sway size without changing ankle impedance and is plausible given the data. Such a strategy involving motion recognition and generation of an accurate motor response may require higher levels of control than changing ankle impedance by altering reflex or feedforward gain.

There is no simple temporal relationship between the initiation of rapid reactive hand movements and the phase of an enhanced physiological tremor in man.

1. A postural hand tremor of enhanced size was induced in eleven subjects. There was rhythmic activity in the posturally active extensor muscles synchronised to the tremor oscillation, which implied an oscillatory modulation of motor neurones. 2. The subjects executed single rapid wrist flexion movements in response to a flash of light. The light flash was presented at an instant when the wrist was spontaneously moving in the flexion direction, extension direction or at random. The time taken to generate a movement was not significantly different or more consistent in any of the conditions. 3. Inspection of individual and averaged acceleration and EMG records strongly suggests that the movement is made at a time that is independent of the tremor cycle at the time of stimulus presentation or at the moment of movement initiation. 4. These observations suggest that the central or spinal mechanism generating tremor does not gate the central mechanism that produces voluntary movement.

Tremulousness--the perception of tremor in man.

The thresholds for detection of a tremor-like movement are described. Detection is poorest at frequencies which correspond to natural tremor. The results are in accord with the failure of persons often to notice that their hands are tremulous.

The phase of postural hand tremor is not influenced by repetitive photic brain stimulation.

Powerful photic stimulation was employed to produce driving of the EEG rhythm recorded from occipital cortex. The resulting quasi-sinusoidal signal was considerably larger than the spontaneous alpha rhythm, and Fourier analysis showed it to be sharply tuned to the frequency of the stimulation which ranged from 7-11 Hz. Physiological postural hand tremor was recorded bilaterally during the period of stimulation. Signal averaging was used to investigate the relationship of the EEG and tremor waveform to the light flashes. The EEG was clearly phasically related to the repetitive stimulus, but the waveform of the tremor was not. We conclude that this external stimulus fails to produce a detectable entrainment of motor output.

A cross-bridge mechanism can explain the thixotropic short-range elastic component of relaxed frog skeletal muscle.

1. The passive tension and sarcomere length of relaxed frog skeletal muscle fibres were measured in response to imposed length stretches. The tension response to a constant-velocity stretch exhibited a clear discontinuity. Tension rose more rapidly during the initial approximately 0.4 % L0 of the stretch than during the latter stages (where L0 is the resting length of the fibre). This initial tension response is attributed to the short-range elastic component (SREC). 2. The use of paired triangular stretches revealed that the maximum tension produced during the SREC response of the second stretch was significantly reduced by the first stretch. This history-dependent behaviour of the SREC reflects thixotropic stiffness changes that have been previously described in relaxed muscle. 3. The biphasic nature of the SREC tension response to movement was most apparent during the first imposed length change after a period at a fixed length, irrespective of the direction of movement. 4. If a relaxed muscle was subjected to an imposed triangular length change so that the muscle was initially stretched and subsequently shortened back to its original fibre length, the resting tension at the end of the stretch was reduced relative to its initial pre-stretch value. Following the end of the stretch, tension slowly increased towards its initial value but the tension recovery was not accompanied by a contemporaneous increase in sarcomere length. This finding suggests that the resting tension of a relaxed muscle fibre is not entirely due to passive elasticity. The results are compatible with the suggestion that a portion of the resting tension - the filamentary resting tension (FRT) - is produced by a low level of active force generation. 5. If a second identical stretch was imposed on the muscle at a time when the resting tension was reduced by the previous stretch, the maximal tension produced during the second stretch was the same as that produced during the first, despite the second stretch commencing from a lower initial resting tension. 6. In experiments using paired triangular length changes, an inter-stretch interval of zero did not produce a substantially greater thixotropic reduction in the second stretch elastic limit force than an inter-stretch interval in the range 0.5-1 s. 7. A theoretical model was developed in which the SREC and FRT arise as manifestations of a small number of slowly cycling cross-bridges linking the actin and myosin filaments of a relaxed skeletal muscle. The predictions of the model are compatible with many of the experimental observations. If the SREC and FRT are indeed due to cross-bridge activity, the model suggests that the cross-bridge attachment rate must increase during interfilamentary movement. A mechanism (based on misregistration between the actin binding sites and the myosin cross-bridges) by which this might arise is presented.

Shooting performance is related to forearm temperature and hand tremor size.

The changes in postural tremor of the hand and the subsequent effect on shooting performance produced by moderate cooling and heating of the forearm were studied in six subjects. Cooling produced a large decrease in tremor size of the ipsilateral hand, whereas warming the limb produced an increase in tremor size. Cooling or warming the forearm did not change the peak frequency of tremor significantly, which was quite stable for each subject. The improvement in shooting performance after cooling the forearm, as measured by grouping pattern of the shots, reached statistical significance and warming caused a significant worsening. This measure of performance was shown to correlate (r = 0.776) inversely with tremor size. The causes and implications of these changes are discussed. It is suggested that local cooling may be useful for people who wish temporarily to reduce tremor in order to improve dexterity for shooting and for other purposes.

The effect of alcohol on physiological tremor.

Ethanol reduces the size of essential tremor. We here show that, contrary to a recent report, ethanol also causes a large decrease in the size of physiological tremor. As in the case of essential tremor, the frequency is not changed. The reduction in tremor probably explains the well-known link between certain types of skilled activity and alcohol consumption.

Limb temperature and human tremors.

The changes in postural tremor of the hand produced by moderate cooling of the muscles of one forearm have been investigated in 16 normal subjects and in 16 patients with essential tremor. In both groups, cooling produced a profound long lasting decrease in tremor level of the ipsilateral hand. In normal subjects, although cooling reduced the tremor size, the EMG of the active muscle clearly increased. Warming the limb in normal subjects produced an increase in tremor level and decrease in EMG. Cooling or warming the limb did not, however, significantly change the peak frequency which was quite stable for each subject. The results of cooling were compared with a brief period of ischaemia, which also reduces tremor size. Local cooling may be a useful manoeuvre for patients with essential tremor, and for others who wish to reduce their tremor temporarily in order to improve dexterity.

A study of the early signs of drug induced parkinsonism.

Postural tremor was recorded from psychiatric patients who had been treated with phenothiazine or butyrophenone neuroleptic drugs. None of the patients had previously been diagnosed as having extrapyramidal dysfunction. A significant number of these patients had abnormally low tremor frequencies. Low frequency tremors are often associated with Parkinson's disease (PD) so that some of these patients may have early signs of drug induced Parkinsonism (DIP). The results indicate that DIP is not necessarily characterised by a bilateral slow frequency tremor, but may initially be similar to idiopathic PD, even though its cause and prognosis are different.

Effect of stereotactic thalamic lesion on essential tremor.

The cause of essential (low-frequency) tremor is unknown and its relation to physiological (high-frequency) tremor is unclear. We assessed essential tremor in one patient before and after a stereotactic thalamic lesion. The procedure changed the size of the tremor in the right hand but not in the left. Persistence of a low-frequency component suggested that essential tremor was an additional feature superimposed on physiological tremor in this patient. The focus of essential tremor seems to be an autonomous central generator that is independent of physiological tremor mechanisms.

Tremor and the anti-obesity drug BRL 26830A.

The thermogenic beta 3-adrenoceptor agonist BRL 26830A has been shown to increase weight loss in dieting subjects but tremor was a frequent adverse effect. We have investigated the magnitude and nature of this tremor after a single oral dose in 18 subjects. Two complementary techniques were used to attach the recording apparatus to the subjects to give both isotonic and isometric measures of tremor. Increases of 84% and 40% respectively were found due to exaggeration of physiological tremor presumably mediated through concomitant beta 2-adrenoceptor stimulation. The use of beta 3-adrenoceptor agonist drugs in the treatment of obesity may increase but the development of an agent without tremor inducing properties would be an obvious advantage.

Thixotropy in frog single muscle fibres.

The thixotropic properties of single muscle fibres have been investigated. The effect is larger than in whole muscle and although the time course of stiffness recovery is generally similar, there is an indication that two phases may be involved. Rigor, induced chemically, eliminates thixotropic behaviour.

Finger tremor in Parkinson's disease.

Finger tremor was investigated in 20 patients (age range 54-88 yr) diagnosed as suffering from idiopathic Parkinson's disease and six controls of a similar age and no known neurological abnormality. In nine of the patients tremor was not clinically obvious. When the tremor of these patients was recorded immediately after voluntary movement and subjected to instrumental analysis there were consistently observable differences from the controls. Such analysis may have diagnostic potential when there is clinical uncertainty. Surface EMG recordings were obtained from four patients. One patient had a large resting tremor with obvious reciprocating activity in flexors and extensors; in the others who had no symptomatic tremor there was reciprocating activity only after movement, and this died away in a few seconds as the induced tremor disappeared.

Biodynamics of the wrist in rheumatoid arthritis--the enigma of stiffness.

The wrist has been moved rhythmically in the horizontal plane by sinusoidal torques provided by a printed motor. Measurements have been made on normal subjects and subjects with rheumatoid arthritis. Both groups exhibited a resonance, the oscillations being greatest when the applied torque was of certain frequency. In both groups the resonant frequency fell to approximately the same constant value when the torque was raised. While the main relationships were similar a somewhat lower torque resulted in the lowering of resonant frequency in the patients. The relationship between applied torque and peak velocity at resonance was also studied. For a given torque the motion was greater in the patients. No objective signs of increased viscous or elastic stiffness were demonstrable at the wrist in patients with rheumatoid arthritis.

Thixotropy: the effect of stimulation in frog muscle.

Recent reports have shown that the stiffness of relaxed frog muscle is not a fixed property, but is dependent on the previous history of movement (Lakie & Robson, 1988a). Passive movement decreases stiffness; when the muscle is subsequently allowed to rest it returns at a progressively declining rate to a level of stiffness that is close to its original value (Lakie & Robson, 1988b). We now report that the stiffness of relaxed muscle is also affected by prior tetanic electrical stimulation under isometric conditions. The effect of electrical stimulation is similar to passive movement in that both produce a temporary decrease in stiffness.

Thixotropic changes in human muscle stiffness and the effects of fatigue.

Two methods have been used to study the stiffness of the relaxed finger musculature after movement followed by various times at rest. The muscles stiffen considerably as the time at rest increases. The time course of this change has been plotted; it continues at a declining rate for at least 30 min. The increased stiffness after resting can be immediately reduced by active or passive movements but not by isometric efforts. These changes characterize a thixotropic system and suggest a long-term molecular rearrangement in relaxed muscle. Extensive eccentric exercise of the muscles under investigation reduces the overall stiffness and there is a concomitant increase in tremor on movement.

Thixotropy: stiffness recovery rate in relaxed frog muscle.

The stiffness of relaxed frog muscle is affected by its previous history of movement. The extent of this thixotropic effect is dependent on the size of the applied force (Lakie & Robson, 1988). The stiffness recovery following movement has now been studied at two temperatures, and has been shown to proceed at a logarithmically declining rate.

Thixotropy: the effect of stretch size in relaxed frog muscle.

Small forces were applied to isolated frog muscle; the resulting displacements were used to calculate muscle stiffness (elastic modulus, E). Stiffness is much greater for small forces within the range of the Short Range Elastic Component (SREC; Hill, 1968). 'Stirring' the muscle greatly reduces the stiffness, but only when the applied force is small. Stiffness subsequently returns to its original level. This strongly suggests that muscle thixotropy (Lakie, Walsh & Wright, 1984) is a property of the SREC.