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Evidence for a cardiovascular modulation of central neuronal activity in man
EXPERIMENTAL
NELIROLOGY
Evidence
141-149
51,
(1976)
for a Cardiovascular Neuronal Activity
Modulation in Man
of Central
A. FORSTER AND T. W. STONE 1 Departmeptt
of Physiology, Aberdeen
University AB9 lAS,
Received
November
of Aberdeen, Marischal Scotland, U.K.
College,
25, 1975
Finger tremor of human subjects has been recorded using a photoelectric technique. Directly recorded tremor was not related to the QRS spike of the electrocardiogram. Averaged records of tremor, triggered by the QRS complex, showed two waves. One component (B wave) was abolished immediately on inflating an arterial cuff, and was considered to be due to ballistic movements of the finger following the arrival of the cardiac pulse. The B-wave latency was the same as the latency of the directly measured fingertip pulse. The second component (N wave) was unaffected by arterial occlusion, but declined in amplitude after occlusion at the same rate as directly recorded tremor. It is suggested that the N wave reflects an effect of blood movement associated with the cardiac pulse on spinal cord excitability, possibly on gamma-motoneurons.
INTRODUCTION Normal skeletal muscles show a fine tremor at a frequency of about 8 to 12 Hz, superimposedon gross contractions. The tremor is often referred to as “physiological tremor.” There are two main schools of thought regarding the origin of physiological tremor. The generally accepted hypothesis is that it is due to oscillation in the stretch reflex servo-loop (7, 8, 12, 14, 15). The alternative argument has been advanced that tremor may be at least partly due to ballistic effects caused by movement of blood following each cardiac cycle. Brumlik (2), for example, noted a marked similarity between finger tremor and the ballistocardiogram. He also showed that neuromuscular blockade by succinylcholine did not abolish finger tremor, though the pattern of movement was altered. Marsden et al. (16) described a patient showing a normal 9.5-Hz tremor in the left (normal) 1 Reprint
requests
to T. W.
Stone. 141
Copyright 0 1976 by AcademicPress,ItIC. All rights of reproduction in any form reserved.
142
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arm and in the right arm, though this had been surgically deafferented. This observation seems to indicate that sensory information, and thus the stretch reflex arc, is not essential for limb tremor. Further evidence for a cardiovascular modulation of muscle movement was obtained by Yap and Boshes (21) who used the R wave of the electrocardiogram to trigger an averaging computer. A clear summation of the tremor recording was obtained from the unsupported limb, suggesting a close relationship with the ballistocardiogram. Lippold (13) interpreted the phenomenon as a synchronizing effect of the pulse wave on muscle spindle discharge. In view of the implications of these findings for the “textbook” explanation of physiological tremor, the present study was undertaken to reinvestigate the origin of the various components of physiological tremor in man. METHODS The subjects in these experiments were 39 persons of either sex age 17 to 22 years. Tremor of the index finger of the right hand was recorded by a method similar to that of Eagles et al. (5). Subjects were instructed to keep the index finger approximately horizontal in the path of a light beam directed onto a photodiode. The output from the photodiode was amplified in a Fenlow AD 55 amplifier and then passed to a Devices pen recorder. The output was also displayed on a Telequipment oscilloscope, and on a Biomac 1000 averaging computer. The electrocardiogram (ECG) was recorded using lead II to provide a large R wave. The ECG recordmg was fed into a pulse height analyser which produced a constant-size output pulse for each ECG R wave. These output pulses were then used to trigger the Biomac sweep. Direct recordings of tremor and ECG were obtained from the Devices pen recorder. Summated activity from the Biomac computer was usually stored on punched tape and representative records obtained on a Telsec pen recorder. For averaging the tremor records, the Biomac was usually programmed for 128 sweeps of 1.2%set duration, since (this allowed examination of a complete cardiac cycle in each sweep. During recording sessions the subjects were seated with the arm resting horizontally and in front of the body. The arm was supported to the metacarpals and was clamped firmly from the elbow to the wrist to reduce gross movements and ballistic effects on the arm. To eliminate ballistic effects in the recording of finger movement, tremor was recorded from several subjects following the inflation to 220 mm Hg of an arterial cuff around the upper arm. However, it has been found that tremor, recorded directly, begins to decline in amplitude after about 45
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set of arterial occlusion, probably due to the developing hypoxia of the excitable tissues and neuromuscular junctions (6, 17). Our averaged records were therefore taken only during the first 30 set of arterial occlusion, then the cuff was released and the arm allowed to recover for about 2 min. The procedure was repeated until the necessary 128 sweeps had been completed. In several subjects the effect of reactive hyperemia on the tremor was examined by inflating an arterial occlusive cuff around the upper arm to 220 mm Hg. Recordings of tremor were made on releasing the cuff after about 4 min. The arrival of the cardiac pulse at the fingertip was monitored in several subjects by means of a photoelectric pulse monitor, the MIE Mk IIB. The output of this monitor was fed into the Devices pen recorder, and recorded simultaneously with the ECG. RESULTS Direct Recordings. A direct pen recording of normal tremor is shown in Fig. 1A. Several relatively gross movements of the finger are seen but a clear underlying tremor at approximately 8.0 Hz is obvious. Figure 1B illustrates tremor in the same subject recorded within 30 set of arterial occlusion. The tremor is still apparent, indeed clarification of the basic tremor frequency was a common finding. As reported by Marsden et al. ( 17), arterial occlusion for more than about 45 set initiated a decline of tremor amplitude, tremor being almost completely absent after about 3 min of occlusion.
FIG. 1. Direct pen recordings of finger tremor. a. Normal tremor. b. Tremor recorded immediately after arterial occlusion of upper arm using a cuff inflated to 220 mm Hg. Note failure of such occlusion to abolish the tremor. The basic tremor at approximately 8 Hz is actually clarified. The amplitude of the tremor decreased slowly after occlusion and was virtually abolished after 3 min. Time: 1 sec.
144
FIG. 2. Simultaneous direct pen recordings of a, the electrocardiogram and b, finger movement taken immediately after 4 min arterial occlusion of the arm. Note large finger movements occurring about 300 msec after the QRS spike. Time: 1 sec.
No waves definitely and consistently related to the heart beat were seen in normal direct recordings, but when the arm was hyperemic after 4 min arterial occlusion, waves clearly related to the ECG did sometimes appear. One such example is illustrated in Fig. 2. Finger movements occurring about 290 msec after the QRS spikk are apparent. Covnpufer-Averaged Records. When the averaging computer was triggered by the QRS spike of the ECG, it was found that the basic S- to 12 Hz tremor did not consistently summate (Fig. 3A). Instead, the summatetl
a
FIG. 3. Computer-averaged recordings of tremor triggered by the QRS spike of the electrocardiogram. a. Normal finger. b. Finger movement during first 30 set of arterial occlusion. c. The electrocardiogram taken simultaneously with b, 128 sweeps were averaged for each trace. Note that the B wave seen in a disappeared on arterial occlusion but that a late wave (N) was revealed by this procedure. Time : 500 msec.
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FIG. 4. Simultaneous direct pen recordings of a, the electrocardiogram, and b, finger tremor. At the arrow arterial circulation to the arm was occluded by a cuff around the upper arm. Trace b clearly illustrates the progressive decline of tremor amplitude beginning about 45 set after occlusion and continuing to abolition of tremor after about 2.5 min. Time: 1 min.
records displayed a single large wave beginning about 200 msec (199.8 * 32.8 SD; n = 40) after the QRS spike and reaching a peak about 100 msec later (316.7 2 52.8 after QRS). Total duration of the wave was about 250 msec (Fig. 3A ; 5A). Arterial occlusion immediately abolished this wave (Fig. 3B) which we have therefore labeled the B wave (Fig. 3A) to indicate a presumed ballistic origin. Besides abolishing the B wave, arterial occlusion also resulted in the clarification of a later wave which has been labeled N as in Fig, 3B. The presence of this wave was only clearly revealed after arterial occlusion. The observed N waves had initial latencies of about 500 msec (497.1 * 68.5) and peak latencies of 600 msec (590.8 -t- 55.3) from the QRS spike. N wave duration was approximately 210 msec. If the arterial cuff was kept inflated for more than 45 set so that the amplitude of directly measured tremor decreased, then the size of the N wave also declined with a similar time course. Efect of Ischew& on Tremor. We were able to confirm that inflating a sphygmomanometer cuff on the upper arm to 220 mm Hg caused a gradual decline in the amplitude of tremor starting about 45 set after inflation and continuing until the tremor disappeared about 3 min after inflation (Fig. 4). Finger Pulse. By using the pulse monitor to detect the arrival of the systolic pulse at the tip of the index hger we obtained records such as that seen in Fig. 5. The initial latency of the fingertip pulse was recorded
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FIG. 5. Computer-averaged records triggered by the QRS spike of the electrocardiogram of a, finger movement; b, the arrival of the cardiac pulse (Pu) at the finger tip; c, the electrocardiogram. Inset: direct pen recordings of d, the finger tip pulse ; e, the electrocardiogram. Time : 500 msec.
as 230.1 * 25.7 msec after the QRS spike. Figure 5 demonstrates the coincidence in time of the B wave of the finger movement and the fingertip pulse. DISCUSSION The rhythmic S- to 12-Hz physiological tremor recorded here from the index finger does not seemto owe its origin to any effect of the circulatory system, because it does not normally summate when triggered by the ECG, and it persists apparently unchanged for some time after arterial occlusion of the upper arm. The decline of tremor amplitude after approximately 45 set of ischemia is probably due to the developing hypoxia of the excitable tissues of the arm (6, 17). The ECG-triggered summation of tremor recorded by Yap and Boshes (21) probably resulted from their experimenting on the unsupported arm, gross ballistic movements of which would almost certainly occur following the pulse wave. In the present experiments on the rigidly clamped arm, summation of S- to 12-Hz tremor was only rarely ‘seenand was then considered to be due to the tendency of regular wave forms to summate on averaging to a small extent, even with random triggering. Lippold (13) has also previously pointed out that such “random summation” can occasionally occur.
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The B wave which appeared on computer-averaged records was clearly related to the simultaneously averaged ECG. Since it disappeared completely on arterial occlusion, the B wave is presumed to result from the ballistic effects of blood movements in the limb. As gross movements of the limb were prevented by securely clamping the arm it is most likely that the B wave is the result of the transitory engorgement of the tissues of the finger resulting from the cardiac pulse. Such an engorgement of muscle tissues could also cause stretching and activation of muscle spindle receptors, so that a locally induced stretch reflex of the finger muscle might contribute to the B wave. This interpretation is supported by the observation that latency of the B wave is comparable with the latency of the directly recorded fingertip pulse. The N wave seen in compu’ter-averaged records persisted for some time after arterial occlusion. This indicates that the N wave cannot be due to any effect of the blood flow in the arm. Furthermore, since the amplitude of the N wave declined with approximately the same time course as directly recorded tremor after arterial occlusion, it would seem that the finger movement underlying the N wave is neurally mediated. The postocclusive decline would be attributable to developing hypoxia of the tissues as in the case of directly recorded tremor (6, 17). It would seem therefore that the relationship between the N wave and the ECG reflects an effect of the cardiac pulse on the central nervous system, presumably on the motoneuron pool in the spinal cord. If the alpha motoneuron pool were primarily affected the N wave would be expected to occur earlier than it does, having an initial latency from the QRS complex of about 500 msec. No figures are available for the latency of the cardiac pulse wave at the spinal cord in man, but the latency from the QRS complex to the beginning of blood movement at the posterior tibia1 artery in man is about 300 msec [G. R. Kelman, personal communication ; see (9)]. If, in the absence of more appropriate figures, this latency is considered comparable to that which might apply in the smaller arterioles of the spinal cord, and after allowing for muscle twitch time and assuming an alpha motoneuron conduction velocity of about 100 m/see-I, an N wave of alpha motoneuron origin should have an initial latency of the order of 325 msec. It is possible however that the primary effect of blood movement would be felt by the smaller gamma motoneurons and the consequent activation of intrafusal fibers would initiate a stretch reflex in the finger. The expected N wave latency would therefore be increased by gamma efferent conduction time, Ia afferent conduction time, and central reflex time. If central reflex time included the long-latency cerebral cortical loop which has been suggested as being involved in peripheral stretch reflexes (1,
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18, 19) then these various factors would increase the expected N wave latency by about 100 msec. Because this would make the expected N wave latency (400-500 msec) more nearly approximate to the observed value (497 msec) we favor this idea of a gamma-neuron origin Gf the N wave. How the cardiac pulse might affect central neurons is a matter for speculati&, but we would suggest the possibility that the rising phase of the systolic blood pressure curve might aIter neuronal excitability by a piezo-electric effect on the motoneuron membrane. A second possibility is that neuronal firing rate might change as a result of the changing microcirculatory. oxygen-carbon dioxide tensions during a cardiac cycle. The central nervous system’s avid appetite for oxygen is well known. Although several studies have shown that asphyxia does not usually produce a detectable change of neuronal membrane potential for several seconds, (3, 131, ZO), it should be remembered that those studies were carried out on deeply anesthetised or traumatized (by decerebration) animals. In conscious man both the level of neuronal excitability and the sensitivity of neurons to changing blood gas tensions is likely to be very much greater. A modulating effect of the cardiovascular system on activity in the central nervous system would explain a number of otherwise puzzling observations. For example it has been established that the ventilatory cycle begins at only certain preferred times during the cardiac cycle (4, 10). This may well reflect fluctuations of neuronal excitability during the cardiac cycle as we have proposed. REFERENCES 1. ADAM, J., C. D. MARSDEK, P. A. MERTON, and H. B. MORTON. 1975. The effect of lesions in the internal capsule and the sensory-motor cortex on servo action in human thumb. J. Physiol. (Lortdorr) 254 : 27-28 p. 2. BRUMLIK, J. 1962. On the nature of normal tremor. Nczc*oloyg (Mirzn.) 12: 159-179. 3. COLLEWIJN, H., and A. VAN HARREVELD. 1966. Intracellular recording from cat spinal motoneurones during acute asphyxia. J. Physiol. (Londm) 185: 1-14. 4. ENGEL, P., A. JAEGER, and G. HILDEBRANDT. 1972. Uber die Beinflussung de Frequenzund Phasenkoordination zwischen Herzschlag und Atmung durch verschiedene Narkotika. Arsneinz.-For&. 22 : 1460-1468. 5. EAGLES, J. B., A. M. HALLIDAY, and J. W. T. REDFEARN. 1953. Symposium on fatigue, p. 41. London, H. K. Lewis. The Ergonomics Research Society. 6. HALLIDAY, A. M., and J. W. T. REDFEARN. 1954. The effect of iscaemia on finger tremor. J. Physiol. (London) 123: 23-24P. 7. HALLIDAY, A. M., and J. W. T. REDFEAHN. 1956. An analysis of the frequencies of finger tremor in healthy subjects. J. Physiol. (London) 134: 600-611. 8. HALLIDAY, A. M., and J. W. T. REDFEARN. 1958. Finger tremor in tahetic patients and its bearing on the mechanism producing the rhythm of physiologi:al tremor. J. Nellvol. NCU~USUY~. Psychiut. 21 : 101-108.
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11.
12.
13. 14.
15.
16. 17.
18.
19. 20.
21.
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D. R., G. R. KELMAN, G. E. MAVOR, M. G. WALKER, and A. W. S. 1974. Time interval between ecg R wave and peak flow velocity in leg arteries of normal humans. J. Physiol. (Londo~z) 239: 21-22P. HILDEBRANDT, G., and F.-J. DAUMANN. 1965. Die Koordination von Puls und Atemrhythmus bei Arbeit. Int. 2. Angeeo. Physiol. Einschl. Arbeitsphysiol. 21: 27-48. KOLMODIN, G. M., and C. R. SKOGLUND. 1959. Influence of asphyxia on membrane potential level and action potentials of spinal motoand interneurones. Acta Physiol. Stand. 45: 1-18. LIPPOLD, 0. C. J. 1970. Oscillation in the stretch reflex arc and the origin of the rhythmical 8-12 Hz component of physiological tremor. J. Physiol. (Londort) 206: 359-382. LIPPOLD, 0. C. J. 1973. “The Origin of the Alpha Rhythm.” Churchill Livingstone, London. LIPPOLD, 0. C. J.. J. W. T. REDFEARN, and J. Vuco. 1957. The relation between the stretch reflex and the electrical and mechanical rhythmicity in human voluntary muscle. J. Physiol. (London) 138: 14-15P. LIPPOLD, 0. C. J., J. W. T. REDFEARN, and J. Vuco. 1957. The rhythmical activity of groups of motor units in the voluntary contraction of muscle. J. Physiol. (London) 137 : 473-487. MARSDEN, C. D., J. C. MEADOWS, G. W. LANGE, and R. S. WATSON. 1967. Effect of deafferentation on human physiological tremor. Lanret II: 700-702. MARSDEN, C. D., J. C. MEADOWS, G. W. LANGE, and R. S. WATSON. 1969. The role of the ballistocardiographic impulse in the genesis of physiological tremor. Brain 92: 647-662. MARSDEN, C. D., P. A. MERTON, and H. B. MORTON. 1973. Latency measurements compatible with a cortical pathway for the stretch reflex in man. J. Physiol. (London) 230 : 5859P. PHILLIPS, C. G. 1969. Motor apparatus of the baboon’s hand. Proc. Roy. Sot. B 173 : 141-174. VAN HARREVELD, A. 1946. Asphyxial depolarisation in the spinal cord. Am. J. Physiol. 147 : 669-684. YAP, C. B., and B. BOSHES. 1967. The frequency and pattern of normal tremor, Electroencephalogr. Clip Neurophysiol. 22 : 197-203, WATSON.
10.
PULSE
NELIROLOGY
Evidence
141-149
51,
(1976)
for a Cardiovascular Neuronal Activity
Modulation in Man
of Central
A. FORSTER AND T. W. STONE 1 Departmeptt
of Physiology, Aberdeen
University AB9 lAS,
Received
November
of Aberdeen, Marischal Scotland, U.K.
College,
25, 1975
Finger tremor of human subjects has been recorded using a photoelectric technique. Directly recorded tremor was not related to the QRS spike of the electrocardiogram. Averaged records of tremor, triggered by the QRS complex, showed two waves. One component (B wave) was abolished immediately on inflating an arterial cuff, and was considered to be due to ballistic movements of the finger following the arrival of the cardiac pulse. The B-wave latency was the same as the latency of the directly measured fingertip pulse. The second component (N wave) was unaffected by arterial occlusion, but declined in amplitude after occlusion at the same rate as directly recorded tremor. It is suggested that the N wave reflects an effect of blood movement associated with the cardiac pulse on spinal cord excitability, possibly on gamma-motoneurons.
INTRODUCTION Normal skeletal muscles show a fine tremor at a frequency of about 8 to 12 Hz, superimposedon gross contractions. The tremor is often referred to as “physiological tremor.” There are two main schools of thought regarding the origin of physiological tremor. The generally accepted hypothesis is that it is due to oscillation in the stretch reflex servo-loop (7, 8, 12, 14, 15). The alternative argument has been advanced that tremor may be at least partly due to ballistic effects caused by movement of blood following each cardiac cycle. Brumlik (2), for example, noted a marked similarity between finger tremor and the ballistocardiogram. He also showed that neuromuscular blockade by succinylcholine did not abolish finger tremor, though the pattern of movement was altered. Marsden et al. (16) described a patient showing a normal 9.5-Hz tremor in the left (normal) 1 Reprint
requests
to T. W.
Stone. 141
Copyright 0 1976 by AcademicPress,ItIC. All rights of reproduction in any form reserved.
142
FORSTER
AND
STONE
arm and in the right arm, though this had been surgically deafferented. This observation seems to indicate that sensory information, and thus the stretch reflex arc, is not essential for limb tremor. Further evidence for a cardiovascular modulation of muscle movement was obtained by Yap and Boshes (21) who used the R wave of the electrocardiogram to trigger an averaging computer. A clear summation of the tremor recording was obtained from the unsupported limb, suggesting a close relationship with the ballistocardiogram. Lippold (13) interpreted the phenomenon as a synchronizing effect of the pulse wave on muscle spindle discharge. In view of the implications of these findings for the “textbook” explanation of physiological tremor, the present study was undertaken to reinvestigate the origin of the various components of physiological tremor in man. METHODS The subjects in these experiments were 39 persons of either sex age 17 to 22 years. Tremor of the index finger of the right hand was recorded by a method similar to that of Eagles et al. (5). Subjects were instructed to keep the index finger approximately horizontal in the path of a light beam directed onto a photodiode. The output from the photodiode was amplified in a Fenlow AD 55 amplifier and then passed to a Devices pen recorder. The output was also displayed on a Telequipment oscilloscope, and on a Biomac 1000 averaging computer. The electrocardiogram (ECG) was recorded using lead II to provide a large R wave. The ECG recordmg was fed into a pulse height analyser which produced a constant-size output pulse for each ECG R wave. These output pulses were then used to trigger the Biomac sweep. Direct recordings of tremor and ECG were obtained from the Devices pen recorder. Summated activity from the Biomac computer was usually stored on punched tape and representative records obtained on a Telsec pen recorder. For averaging the tremor records, the Biomac was usually programmed for 128 sweeps of 1.2%set duration, since (this allowed examination of a complete cardiac cycle in each sweep. During recording sessions the subjects were seated with the arm resting horizontally and in front of the body. The arm was supported to the metacarpals and was clamped firmly from the elbow to the wrist to reduce gross movements and ballistic effects on the arm. To eliminate ballistic effects in the recording of finger movement, tremor was recorded from several subjects following the inflation to 220 mm Hg of an arterial cuff around the upper arm. However, it has been found that tremor, recorded directly, begins to decline in amplitude after about 45
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set of arterial occlusion, probably due to the developing hypoxia of the excitable tissues and neuromuscular junctions (6, 17). Our averaged records were therefore taken only during the first 30 set of arterial occlusion, then the cuff was released and the arm allowed to recover for about 2 min. The procedure was repeated until the necessary 128 sweeps had been completed. In several subjects the effect of reactive hyperemia on the tremor was examined by inflating an arterial occlusive cuff around the upper arm to 220 mm Hg. Recordings of tremor were made on releasing the cuff after about 4 min. The arrival of the cardiac pulse at the fingertip was monitored in several subjects by means of a photoelectric pulse monitor, the MIE Mk IIB. The output of this monitor was fed into the Devices pen recorder, and recorded simultaneously with the ECG. RESULTS Direct Recordings. A direct pen recording of normal tremor is shown in Fig. 1A. Several relatively gross movements of the finger are seen but a clear underlying tremor at approximately 8.0 Hz is obvious. Figure 1B illustrates tremor in the same subject recorded within 30 set of arterial occlusion. The tremor is still apparent, indeed clarification of the basic tremor frequency was a common finding. As reported by Marsden et al. ( 17), arterial occlusion for more than about 45 set initiated a decline of tremor amplitude, tremor being almost completely absent after about 3 min of occlusion.
FIG. 1. Direct pen recordings of finger tremor. a. Normal tremor. b. Tremor recorded immediately after arterial occlusion of upper arm using a cuff inflated to 220 mm Hg. Note failure of such occlusion to abolish the tremor. The basic tremor at approximately 8 Hz is actually clarified. The amplitude of the tremor decreased slowly after occlusion and was virtually abolished after 3 min. Time: 1 sec.
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FIG. 2. Simultaneous direct pen recordings of a, the electrocardiogram and b, finger movement taken immediately after 4 min arterial occlusion of the arm. Note large finger movements occurring about 300 msec after the QRS spike. Time: 1 sec.
No waves definitely and consistently related to the heart beat were seen in normal direct recordings, but when the arm was hyperemic after 4 min arterial occlusion, waves clearly related to the ECG did sometimes appear. One such example is illustrated in Fig. 2. Finger movements occurring about 290 msec after the QRS spikk are apparent. Covnpufer-Averaged Records. When the averaging computer was triggered by the QRS spike of the ECG, it was found that the basic S- to 12 Hz tremor did not consistently summate (Fig. 3A). Instead, the summatetl
a
FIG. 3. Computer-averaged recordings of tremor triggered by the QRS spike of the electrocardiogram. a. Normal finger. b. Finger movement during first 30 set of arterial occlusion. c. The electrocardiogram taken simultaneously with b, 128 sweeps were averaged for each trace. Note that the B wave seen in a disappeared on arterial occlusion but that a late wave (N) was revealed by this procedure. Time : 500 msec.
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FIG. 4. Simultaneous direct pen recordings of a, the electrocardiogram, and b, finger tremor. At the arrow arterial circulation to the arm was occluded by a cuff around the upper arm. Trace b clearly illustrates the progressive decline of tremor amplitude beginning about 45 set after occlusion and continuing to abolition of tremor after about 2.5 min. Time: 1 min.
records displayed a single large wave beginning about 200 msec (199.8 * 32.8 SD; n = 40) after the QRS spike and reaching a peak about 100 msec later (316.7 2 52.8 after QRS). Total duration of the wave was about 250 msec (Fig. 3A ; 5A). Arterial occlusion immediately abolished this wave (Fig. 3B) which we have therefore labeled the B wave (Fig. 3A) to indicate a presumed ballistic origin. Besides abolishing the B wave, arterial occlusion also resulted in the clarification of a later wave which has been labeled N as in Fig, 3B. The presence of this wave was only clearly revealed after arterial occlusion. The observed N waves had initial latencies of about 500 msec (497.1 * 68.5) and peak latencies of 600 msec (590.8 -t- 55.3) from the QRS spike. N wave duration was approximately 210 msec. If the arterial cuff was kept inflated for more than 45 set so that the amplitude of directly measured tremor decreased, then the size of the N wave also declined with a similar time course. Efect of Ischew& on Tremor. We were able to confirm that inflating a sphygmomanometer cuff on the upper arm to 220 mm Hg caused a gradual decline in the amplitude of tremor starting about 45 set after inflation and continuing until the tremor disappeared about 3 min after inflation (Fig. 4). Finger Pulse. By using the pulse monitor to detect the arrival of the systolic pulse at the tip of the index hger we obtained records such as that seen in Fig. 5. The initial latency of the fingertip pulse was recorded
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FIG. 5. Computer-averaged records triggered by the QRS spike of the electrocardiogram of a, finger movement; b, the arrival of the cardiac pulse (Pu) at the finger tip; c, the electrocardiogram. Inset: direct pen recordings of d, the finger tip pulse ; e, the electrocardiogram. Time : 500 msec.
as 230.1 * 25.7 msec after the QRS spike. Figure 5 demonstrates the coincidence in time of the B wave of the finger movement and the fingertip pulse. DISCUSSION The rhythmic S- to 12-Hz physiological tremor recorded here from the index finger does not seemto owe its origin to any effect of the circulatory system, because it does not normally summate when triggered by the ECG, and it persists apparently unchanged for some time after arterial occlusion of the upper arm. The decline of tremor amplitude after approximately 45 set of ischemia is probably due to the developing hypoxia of the excitable tissues of the arm (6, 17). The ECG-triggered summation of tremor recorded by Yap and Boshes (21) probably resulted from their experimenting on the unsupported arm, gross ballistic movements of which would almost certainly occur following the pulse wave. In the present experiments on the rigidly clamped arm, summation of S- to 12-Hz tremor was only rarely ‘seenand was then considered to be due to the tendency of regular wave forms to summate on averaging to a small extent, even with random triggering. Lippold (13) has also previously pointed out that such “random summation” can occasionally occur.
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The B wave which appeared on computer-averaged records was clearly related to the simultaneously averaged ECG. Since it disappeared completely on arterial occlusion, the B wave is presumed to result from the ballistic effects of blood movements in the limb. As gross movements of the limb were prevented by securely clamping the arm it is most likely that the B wave is the result of the transitory engorgement of the tissues of the finger resulting from the cardiac pulse. Such an engorgement of muscle tissues could also cause stretching and activation of muscle spindle receptors, so that a locally induced stretch reflex of the finger muscle might contribute to the B wave. This interpretation is supported by the observation that latency of the B wave is comparable with the latency of the directly recorded fingertip pulse. The N wave seen in compu’ter-averaged records persisted for some time after arterial occlusion. This indicates that the N wave cannot be due to any effect of the blood flow in the arm. Furthermore, since the amplitude of the N wave declined with approximately the same time course as directly recorded tremor after arterial occlusion, it would seem that the finger movement underlying the N wave is neurally mediated. The postocclusive decline would be attributable to developing hypoxia of the tissues as in the case of directly recorded tremor (6, 17). It would seem therefore that the relationship between the N wave and the ECG reflects an effect of the cardiac pulse on the central nervous system, presumably on the motoneuron pool in the spinal cord. If the alpha motoneuron pool were primarily affected the N wave would be expected to occur earlier than it does, having an initial latency from the QRS complex of about 500 msec. No figures are available for the latency of the cardiac pulse wave at the spinal cord in man, but the latency from the QRS complex to the beginning of blood movement at the posterior tibia1 artery in man is about 300 msec [G. R. Kelman, personal communication ; see (9)]. If, in the absence of more appropriate figures, this latency is considered comparable to that which might apply in the smaller arterioles of the spinal cord, and after allowing for muscle twitch time and assuming an alpha motoneuron conduction velocity of about 100 m/see-I, an N wave of alpha motoneuron origin should have an initial latency of the order of 325 msec. It is possible however that the primary effect of blood movement would be felt by the smaller gamma motoneurons and the consequent activation of intrafusal fibers would initiate a stretch reflex in the finger. The expected N wave latency would therefore be increased by gamma efferent conduction time, Ia afferent conduction time, and central reflex time. If central reflex time included the long-latency cerebral cortical loop which has been suggested as being involved in peripheral stretch reflexes (1,
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18, 19) then these various factors would increase the expected N wave latency by about 100 msec. Because this would make the expected N wave latency (400-500 msec) more nearly approximate to the observed value (497 msec) we favor this idea of a gamma-neuron origin Gf the N wave. How the cardiac pulse might affect central neurons is a matter for speculati&, but we would suggest the possibility that the rising phase of the systolic blood pressure curve might aIter neuronal excitability by a piezo-electric effect on the motoneuron membrane. A second possibility is that neuronal firing rate might change as a result of the changing microcirculatory. oxygen-carbon dioxide tensions during a cardiac cycle. The central nervous system’s avid appetite for oxygen is well known. Although several studies have shown that asphyxia does not usually produce a detectable change of neuronal membrane potential for several seconds, (3, 131, ZO), it should be remembered that those studies were carried out on deeply anesthetised or traumatized (by decerebration) animals. In conscious man both the level of neuronal excitability and the sensitivity of neurons to changing blood gas tensions is likely to be very much greater. A modulating effect of the cardiovascular system on activity in the central nervous system would explain a number of otherwise puzzling observations. For example it has been established that the ventilatory cycle begins at only certain preferred times during the cardiac cycle (4, 10). This may well reflect fluctuations of neuronal excitability during the cardiac cycle as we have proposed. REFERENCES 1. ADAM, J., C. D. MARSDEK, P. A. MERTON, and H. B. MORTON. 1975. The effect of lesions in the internal capsule and the sensory-motor cortex on servo action in human thumb. J. Physiol. (Lortdorr) 254 : 27-28 p. 2. BRUMLIK, J. 1962. On the nature of normal tremor. Nczc*oloyg (Mirzn.) 12: 159-179. 3. COLLEWIJN, H., and A. VAN HARREVELD. 1966. Intracellular recording from cat spinal motoneurones during acute asphyxia. J. Physiol. (Londm) 185: 1-14. 4. ENGEL, P., A. JAEGER, and G. HILDEBRANDT. 1972. Uber die Beinflussung de Frequenzund Phasenkoordination zwischen Herzschlag und Atmung durch verschiedene Narkotika. Arsneinz.-For&. 22 : 1460-1468. 5. EAGLES, J. B., A. M. HALLIDAY, and J. W. T. REDFEARN. 1953. Symposium on fatigue, p. 41. London, H. K. Lewis. The Ergonomics Research Society. 6. HALLIDAY, A. M., and J. W. T. REDFEARN. 1954. The effect of iscaemia on finger tremor. J. Physiol. (London) 123: 23-24P. 7. HALLIDAY, A. M., and J. W. T. REDFEAHN. 1956. An analysis of the frequencies of finger tremor in healthy subjects. J. Physiol. (London) 134: 600-611. 8. HALLIDAY, A. M., and J. W. T. REDFEARN. 1958. Finger tremor in tahetic patients and its bearing on the mechanism producing the rhythm of physiologi:al tremor. J. Nellvol. NCU~USUY~. Psychiut. 21 : 101-108.
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10.
PULSE