A summation technique for the detection of small evoked potentials

A summation technique for the detection of small evoked potentials

A S U M M A T I O N T E C H N I Q U E F O R T H E D E T E C T I O N OF SMALL EVOKED POTENTIALS G. D. DAWSON, M.B., M.Sc. The N a t i o n a l Hospital,...

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A S U M M A T I O N T E C H N I Q U E F O R T H E D E T E C T I O N OF SMALL EVOKED POTENTIALS G. D. DAWSON, M.B., M.Sc. The N a t i o n a l Hospital,

Neurological Research Unit, Medical Research Council,

Queen Square, L o n d o n

(Received for publication: July 10, t953) A certain Dr. Brown~ on being rebuked because he had failed to acknowledge some previous work on

the subject of his writings, replied: I ¢nade no claim to originality for I have long since f o u n d that to eonsider oneself original one ~nust read nothing at all. All I have done is to describe those ~nethods which I have found to suit ~ne best in practice.

INTRODUCTION Cerebral action potentials evoked by stimulation of somatic nerves may be detected on the scalp in man by superimposing a large number of records (Dawson 1947, 1950). In a majority of healthy subjects the form of these sensory responses is still obscured by the relatively large spontaneous brain potentials; those people showing responses large enough to be useful for experimental purposes are so few that they may not be taken as typical. It was suggested by Dr. J. N. Hunt that the discrimination against irregular deflections, in favour of those waves regularly evoked by the stimuli, would be greatly increased if the records could in some way be added instead of being superimposed. This suggestion has been followed successfully (Dawson 1951), and the purpose of this paper is to consider briefly some of the methods available for earrying out such an addition, and to describe fully the particular technique which has been adopted. The detail of the method may become obsolete, but it nevertheless seems worth description as it is relatively simple. It is giving useful experimental results and it illustrates a principle which has probably not received the attention it deserves in physiological recording, although long known and well tried in other fields.

Averaging has long been applied to the detection of systematic fluctuations amongst larger irregular ones. For example Laplace, in the eighteenth century, predicted that by averaging enough data it should be possible to demonstrate a lunar tide in the atmospheric pressure. The achievement of this in the tropics by Lefroy is described by Sabine (1847) but even the averaging of 180,000 hourly observations by Airy (1878) failed to detect the tide in higher latitudes where the irregular variations are much larger. Chapman (1918) demonstrated a lunar tide in the pressure at Greenwich of the order of 0.01 mm. of mercury. Wilkes (1949) reviewing this work said: " T h e amplitude of the tide is less than the error of reading of the photographic barometer from which the data were obtained and it is an interesting illustration of the theory of random errors that it should be possible to determine a systematic variation of this magnitude." The present problem is essentially similar to this example but fortunately the ratios of systematic to irregular deflections in the records are more favourable, though in a series of experiments the number of measurements to be averaged may be larger. The example of the lunar atmospheric tide also emphasises one very important point. Wherever possible any large variations, either irregular or systematic, which are not related to the function being studied, should be removed from the data before averaging is carried out. Until he had removed from t h e data the larger irregular fluctuations and also the very large, but regular variations d u e to the heat of the sun, Chapman was unable to demonstrate the variation of pressure of 65 ]

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lunar origin, i n the electroencephalogram any variations such as those due to spontaneous brain potentials or instrumental causes must likewise be reduced to a mininlum. The value of repeating on a cathode ray tube signals masked by an irregular background was recognised early in the history of radar. The production of special cathode ray tubes with an improved integrating effect for this purpose was proposed in 1938 (WatsonW a t t 1946). Baldoek and Walter (1946) have described an averaging device, using a mechanical distributor with storage and summation in capacitors, for showing alterations in the pattern of a frequency analysis too small to be significant in a single set of observations. Another approach to the problem of detecting evoked responses too small to be seen in a simple E E G record is that of Brazier and Casby (1952) who have used both reconstruction from resonator analyses and the crosscorrelation method described by Lee (1950). Autocorrelation can bc used to extract a periodic variation from amongst irregular fluctuations, but it is not apt for studying waveform since information about phase is lost. Crosscorrelation between the record containing the periodic variable plus noise, and a series of harmonically related sinusoidal reference waveforms will extract the harmonic components of the periodic waveform. Since this method retains information about phase the periodic variable can be reconstructed from the components and its waveform studied, but the process is time consuming. Lee (loc. cit.) makes use of a special case of crosscorrelation in which he correlates between the record containing the periodic function and noise, and a " u n i t impulse funct i o n " of the same period as the variable to be examined. As he points out this amounts to a regular sampling procedure. The apparatus to be described is therefore identical in principle with Lee's method. He uses an electronic method to carry out the sampling whilst this apparatus uses a mechanical one. His analysis of the gain in signal-noise ratio also applies to this method.

At this point it may 5e noted that any gain in signal-noise ratio brought about by a change in the recording method must be paid for. If the band of frequencies which the recording device will pass is narrowed, the improvement in signal-noise ratio which may result is obtained at the expense of speed of response or "signalling speed". That a certain product of bandwidth and time is necessary for a given amount of information to be passed without loss was shown by Hartley (1928). If the range of rates of change iu the signals to be recorded cannot be reduced, as is the case with the evoked responses in the E E G , then any attempt to improve signal-noise ratio by reducing the bandwidth below certain limits, which are set by the time course of the signal, must result in its distortion and loss of information. The improvement obtained by repeating the stimuli, for averaging or integrating the responses, also involves a reduction in signalling speed, since it takes correspondingly longer to obtain the results than if one response alone was large enough for it to be seen clearly above the background. The gain in accuracy to be expected from averaging a series of observations which are disturbed by random errors is proportional to the square root of the number of observations added (see e.g. Yule 1932, chap. X V I I , section 10). Though precise quantitative in.. formation about the power spectrum of the E E G is lacking it is clearly far from random. F o r this reason it seemed worthwhile to test what could be gained from adding a number of records. The brain potentials evoked by an electric shock, applied once a second to the ulnar nerve, were recorded from the scalp of the opposite side. T w e n t y of these records, photographed separately, are shown in figure la. In the subject chosen the responses were unusually large and they may be seen clearly in the separate traces, although considerable differences occur between them. In each of the 20 records the heights of 40 ordinates above an a r b i t r a r y baseline were measured and the corresponding ordinates from all the re(~or(ls were added and averaged. When the

DETECTION OF SMALL EVOKED POTENTIALS

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2b shows a ~vaveform not obvious in the original traces. W h e n 20 more records were added to the average, the waves shown in figure 2e had the same shape but were smoother. This suggests that they were not due to a chance summation of irregular deflections. I n the same experiment a set of control records was made with no stimulus applied to the nerve, and a sample of 5 records

average values were plotted the curve of figure l c was obtained; it shows none of the irregularities of the original records and several significant phases of the response m a y be seen. The averaging of even 5 records, figure lb, shows a considerable improvement over any single trace. The same process of measurement was next carried out on sets of records in which

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@ Fig. 1 Separate records of the brain's responses to a series of 20 electric shocks, applied once a second to a nerve in the left arm, are shown in a. The pick up leads on the right scalp were connected so that positivity of the electrode connected to the broken line gave an upward deflection. The stimuli were released at the times indicated by the black dots above the traces. The calibration in a shows the deflection produced by a p.d. of 20 /~V. at the input of the amplifier. The duration of the sweeps m a is 120 msec. In b and c are shown the average of the first 5 and all 20 of the records in a. the sensory responses were completely obscured b y spontaneous activity. A sample of 5 records f r o m a set of 40 is shown in figure 2a. The stimulus was applied shortly after the start of the record at the time shown b y the black dot, but no response is evident. A n average of the first 20 records in figure

from this set of 40 is shown in figure 2d. I n the corresponding average curves in figure 2e and f, no significant response appeared, but the same decrease of irregularity eccured as more records were added. I n test records where a calibration pulse of 0.1 to 0.25 ~V was added to the r a n d o m noise from an

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amplifier it was found that, with an amplifier pass band from 2 c/sec, to 200 c/sec., the addition of 50 to 200 records would give useful outlines of the pulses. One point of importance was immediately emphasised by these manual averages. The records in figure la showed little sign of the

start which was shown to be due to the:~, operation of the circuit used to define the starting level of the trace. It is clear that any artefacts in the records which are systematically related to the sweep will add up i~ an average just as will the wanted signals. Therefore any unwanted deflections such as

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Fig. 2 A sample of 5 records from a set of 40 taken under the same conditions as those in figure 1, but with the ~imulus applied to the right arm and the record from the left sealp~ is shown in a. In these records the ruponsee are not dear amoni~t the spontammus activity. The averages of 20 and 40 records are shown in b and c. Control records in d, with no stimulus applied, show a v e r a i ~ like e and f. The stimuli were applied at the times of the dots below the traces and the marks on the lowest trace in a show an interval of 20 reset. The calibration to the right of e shows the defleatien due to 10/~V.

steady fall which was clear in the average r e c o r d o f figure lc. This fall was due to the slope of the baseline in the records resulting f r o m the continuous movement of the recording paper in these experiments in a direction perpendicular to that of the sweep. The average curves from both the test and control sets of records in figure 2 had a rise at the

those due to spread of the stimulating current, or interference arising from the recording apparatus and related regularly to the sweep, must be reduced below what would be acceptable in a single record, at lower amplification. Plots such as those shown in figures 1 and 2 demonstrate the gain to be obtained by averaging; but the graphical method is o f

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DETECTION OF SMALL E V O K E D P O T E N T I A L S

little value in physiological experiments because of the time taken to obtain the results. For this reason the available instrumental methods for carrying out the same processes were considered. Digital computing methods offer speed and accuracy, but at the expense of considerable bulk; while magnetic storage and addition appears to need considerable development for this application. A method was tried in which the trace on a cathode ray tube was intensity modulated by the signal and the integration of the sweeps was carried Sla -Cs, =

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cords of the events in the first 100 msee. following the stimulus would give valuable information, and that the form of the responses in this period would be usefully outlined by anything more than 50 ordinates. The method to be described is relatively inflexible but meets these requirements and is ~dequate for the present investigations. METHOD

The method uses a rotating switch to sample the signal voltages at regular intervals Ix112511127

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out photographically. This method is relatively simple and it may be made accurate, but in general photographic methods do not give results sufficiently quickly. The results shown in figures 1 and 2, suggested that re-

after each stimulus. Charges corresponding to the value of these samples are stored in capacitors and added there to the charges acquired following preceeding stimuli. The charges stored in these capacitors can be

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examined continuously on a cathode ray tube and photographic records may be made of the average they represent.

General Arrangement A schema of the apparatus used to carry out the addition of signals within the limits outlined above is shown in figure 3. The distributing switch which rotates 10 times a second has two banks, Sl a and Slb, each with 124 contacts. The storage capacitors Csl to Cs62 are connected to alternate contacts of both banks. On the same spindle as the distributor a single rotating contact K1 is arranged to close when the rotor of the distributor reaches contact ] 24. Geared down from this is

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trips the main sweep and the signal being fed into the store is displayed on the oscillograph CRT 2. The main sweep also times the stimuli which may be applied at any part of this revolution of the distributor or during subsequent revolutions. During those revolutions of the distributor when charging of the store is not taking place the contents of the storage capacitors are presented continuously as a waveform on oscillograph CRT 1, the sweep for which is released 10/sec. by K1. Immediately after the last charging cycle the average of the signals fed in is available for inspection or photographic recording on CRT ]. i f the rate of rotation of the switch is

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Fig. 4 The records compare waves of different shapes and durations recorded through the averager and directly. The upper traces are the averaged records. I n this and all following figures the time scales show intervals of 1, 5 and 20 msee.

a second contact K2 which selects, through the gate unit, every tenth pulse from the closing of K1. Either the 10/sec. pulses from K1 or the 1/sec. pulses from K2 are taken from the gate unit to a counter which may be set to give an output after from 1 to 8 input pulses. The rate of output from the counter is therefore variable between 1 pulse in 8 sec. and 10 pulses per sec. The output from the counter initiates a square wave, lasting for one rotation of the distributor, which will be referred to as the charging pulse. During this one revolution of the distributor the input signal is fed by the charging unit to the storage capacitors, which acquire charges corresponding to the values of 62 ordinates of the signal voltage. At the same time the charging pulse

slowed down to one or two revolutions a second after storage is finished, the stored waveform may be recorded on an inkwriting oscillograph or any convenient low frequency oscillograph. The second bank of the distributor, Slb, may carry out a charging cycle at the same time as the first bank, Sla, or later by a multiple of 100 msec., in which case its charging pulse is tripped through a delay unit. The second storage system may therefore be used either to record events simultaneous with those being stored by the first, but from different places, or it may record later samples of the same series of events, the earlier part of which is being stored by Sla. Full details of the apparatus are given in the appendix.

D E T E C T I O N OF S M A L L E V O K E D P O T E N T I A L S RESULTS

1. Performance on test signals In considering the use of a technique for recording waveforms not visible in a simple oscillogram, particular care must be taken to assess the errors of the method and their variability. Corrections may be made for large but stable inaccuracies by calibration and they are therefore of less importance than smaller but variable errors. A major limita-

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Fig. 5 The records in a are of 220 test pulses of 25 /~V. averaged in the upper trace, superimposed ill the lower trace. They show the frequency response of the amplifier used for b and c. I n b the lower trace shows superimposed 220 records of a 0.25 ~V. pulse a t 100x the gain used in a. I n the upper trace in b 5 averages, each of 220 of the lower sweeps are superimposed and show little scatter. I n e the lower trace shows a single sweep containing a 0.1 ~V. pulse a t 200x the gain used in a. The upper trace shows 5 superimposed averages each of 220 sweeps such as the lower trace, and outlines the 0.1 pV. pulse well. I n d, e and f, a pulse has been mixed with noise having a smaller high frequency content t h a n in b and e. I n d, 1, is shown the pulse alone, in d, 2, the pulse plus noise. I n e is an average of 220 sweeps of noise alone and in f an average of 220 sweeps of pulse plus noise.

tion of the apparatus lies in the relatively small number of ordinates used. The upper traces in figure 4 a, b, and c, show records of waves of different shapes made with the averager; the lower traces show for comparison the same waveforms recorded directly. From figure 4c it may be seen that waves with a duration of 10 reset, or longer are

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well outlined. The causes of the irregularities in the records and of other sources of inaccuracy arc considered in the appendix. To indicate the frequency response of the signal amplifier used in the following tests a record of a square pulse of 25 ~V. is shown in figure 5a, trace 2. Trace 1, above it, shows an average of 220 of these sweeps; the whole trace lasts 100 msec. and the pulse duration is 25 msec. In figure 5b the size of the pulse has been reduced to 0.25 pV. and the voltage gain of the amplifier increased 100 times. In the lower trace, where 220 sweeps have been superimposed the position of the 0.25 ~V. signal may be seen. In the upper trace 5 averages, each of 220 sweeps, are superimposed and show little scatter, giving as good a record of the 0.25 ~V. pulse as that of the 25 ~V. pulse in figure 5a. In figure 5c trace 2 shows, at twice the gain used in 5b, a single sweep of the noise from the amplifier containing a pulse of 0.1 ~V. In the upper trace, 1, are superimposed five averages, each of 220 sweeps such as that in the lower record, and again the agreement is good although the scatter between the averages is greater than for the records in figure 5b. A comparison of a number of averages in this way, is used to decide whether or not a sufficient number of records is being added for the prevailing levels of unwanted and wanted signals in any particular experiment. The records in figure 5a, b and c, may give too favourable an impression of the improvement to be gained from averaging a number of records. This is due to the fact that the noise with which the signal is mixed contains a relatively large amount of high frequencies which are recorded in the lower traces in 5b and c. In the average records the signal to noise ratio is also improved because of the effective reduction of the high frequency response of the system by the limited number of ordinates used. To make a fair comparison between the superimposed and averaged records the high frequency response of the amplifier should have been matched to that of the averager. None of the available high frequency filters in the amplifier were suitable for this purpose. For

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this r e a s o n the r e c o r d s in f i g u r e 5d, e a n d f, were made. H e r e t h e high f r e q u e n c y c o n t e n t of the noise has been r e d u c e d a n d a l a r g e p u l s e a d d e d to i t a t a l a t e r stage. A single r e c o r d of t h e p u l s e alone is silown in 5d, t r a c e 1, a n d t h e noise alone is show~ in t r a c e 2. I n f i g u r e 5e a r e s u p e r i m p o s e d 220 sweeps of the noise w i t h t h e h i g h f r e q u e n c i e s r e d u c e d , a n d in the u p p e r t r a c e the a v e r a g e of them. I n f i g u r e 5f t h e noise a n d the t e s t p u l s e h a v e been a d d e d . T h e u p p e r r e c o r d shows t h e i m p r o v e m e n t f r o m a v e r a g i n g 220 r e c o r d s in these c i r c u m s t a n c e s . T h e r e c o r d s show t h a t a

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se(~o~d p r o d u c e s a l a r g e d e f l e c t i o n in t h e u p p e r trace, f r o m the r i g h t side, b u t l i t t l e defh,~.tion of s i g n i f i c a n c e f r o m the l e f t side. l ~ 6b the same r e f e r e n c e e l e c t r o d e on t h e f o r e h e a d was used b u t b o t h t r a c e s a r e f r o m e l e c t r o d e s over the r i g h t s e n s o r y a r e a , ~he lower one c o m i n g f r o m 3 em. b e h i n d t h e upp¢,r one. I n both e x a m p l e s the p o l a r i t y of the c o n n e c t i o n s was such t h a t a n u p w a r d def l e c t i o n i n d i c a t e s t h a t the e l e c t r o d e s o v e r t h e selisory a r e a h a d become p o s i t i v e w i t h r e s p e c t to the r e f e r e n c e . The t i m e scale shows i n t e r v a l s of 1, 5, a n d 20 reset. The s t i m u l u s

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Fig. 6 The records show cerebral responses in a normal person to electrical stimulation of the left ulnar nerve at the wrist. In a the upper trace is from electrodes on the right side of the head and the lower trace from the left side. The stimulus was apphed 6 msec. after the start of the sweep. In b both amplifiers were connected to the right side of the head, that for the upper trace as nearly as possible over the sensory area and that for the lower 3 era. behind it. In c are control records with no stimulus applied. In all cases 220 sweeps were averaged. A calibration pulse of 2%/~V. is shown in d. u s e f u l o u t l i n e of a p u l s e m a y be o b t a i n e d f r o m 220 r e p e t i t i o n s w h e n i t is less t h a n one q u a r t e r of t h e size of t h e noise.

2. Records of physiological events Two e x a m p l e s of t h e use of t h e m e t h o d to r e c o r d t h e e l e c t r i c a l r e s p o n s e s of t h e b r a i n to s e n s o r y s t i m u l i a r e s h o w n in f i g u r e s 6 a n d 7. I n f i g u r e 6 a r e shown r e c o r d s f r o m a h e a l t h y p e r s o n in w h i c h t h e two a v e r a g i n g c h a n n e l s a r e u s e d to c o m p a r e s i m u l t a n e o u s e v e n t s a t two d i f f e r e n t p l a c e s on t h e head. T h e r e c o r d s in 6a c o m p a r e t h e d i f f e r e n c e s of p o t e n t i a l b e t w e e n e l e c t r o d e s over t h e r i g h t a n d l e f t s e n s o r y areas, 6 cm. l a t e r a l to t h e midline, and a common electrode over the m i d l i n e on t h e f o r e h e a d . A s t i m u l u s a p p l i e d to the l e f t u l n a r n e r v e at the w r i s t once a

was a p p l i e d 6 msec. a f t e r t h e s t a r t of t h e trace. I n t h e u p p e r t r a c e s of f i g u r e 6a a n d b the f i r s t d e f l e c t i o n i n d i c a t i n g t h e a r r i v a l of the s e n s o r y i m p u l s e s a t t h e s e n s o r y a r e a of t h e b r a i n occurs 20 msec. a f t e r the s t i m u l u s . A t t h i s t i m e the s e n s o r y a r e a becomes p o s i t i v e w i t h r e s p e c t to t h e r e f e r e n c e e l e c t r o d e on t h e f o r e h e a d , b u t a t the e l e c t r o d e f u r t h e r b a c k on t h e r i g h t side, in the l o w e r r e c o r d in 6b, an i n i t i a l n e g a t i v e d e f l e c t i o n occurs a n d t h e f i r s t p o s i t i v e p e a k is s e v e r a l m i l l i s e c o n d s l a t e r . I n f i g u r e 6c is a c o n t r o l r e c o r d in which the same n u m b e r of sweeps was a v e r a g e d (220) as in the p r e c e d i n g r e c o r d s b u t no s t i m u l u s was a p p l i e d . The a v e r a g i n g o u t of t h e s p o n t a n e o u s b r a i n a c t i v i t y , w h i c h was so l a r g e t h a t no sign of the r e s p o n s e s could

DETECTION OF SMALL EVOKED POTENTIALS be seen in single records, is practically complete. The second example of the use of the method shows records of different p a r t s of t h e same response. The subject of the investigation was unusual in t h a t stimulation produced v e r y large responses, often recognisable in a single trace. However the size of the responses varied greatly f r o m one stimulus to the next and the average was used to allow assessment of the r a p i d i t y with which the sensory system recovered a f t e r a response. The records in figure 7 were made f r o m a single p a i r of electrodes, the first 7 cm. to the right of the midline over the sensory area and

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first positive phase is immediately followed by an equally large negative deflection. I n the records in figure 7b the stimulus was applied at the same site on the ulnar nerve but 15 msec. before the s t a r t of the lower trace. This produced a response essentially similar to that in the preceding records. W h e n the two stimuli were applied separated by an interval of 160 msec. the resulting records (fig. 7c) show that the initial positive potential follows the second stimulus of the p a i r without a n y diminution of amplitude, but the negative potential fails to occur. I n single records where spontaneous variations in the sizes of the responses occur little significance can be

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Fig. 7 The records show an unusually large response to stimulation of a nerve. Upper and lower traces are from the same pair of electrodes on the head, but the lower trace starts 100 msee. after the finish of the upper one. In a a single stimulus was applied once a second. In b a single stimulus was applied 15 msee. before the start of the lower trace. In e the pair of stimuli, separated by 160 msec., were applied at 1 see. interval. Eleven responses were averaged in each record. The calibration lines at the right of e indicate the deflection due to 50 pV.

the second 6 cm. in f r o n t of it. The connections of t h e e l e c t r o d e s w e r e such t h a t an u p w a r d d e f l e c t i o n o e e u r e d i n t h e record when t h e back electrode became positive with respect to the f r o n t one. The s t a r t of the lower trace began 100 msec. a f t e r t h e end of the u p p e r one and both traces record the potential changes f r o m the same p a i r of leads. I n figure 7a a single stimulus was applied to the u l n a r nerve 25 msec. a f t e r the s t a r t of the top trace. T w e n t y msec. later the initial positive potential occured at the electrode over t h e sensory area, but in this record, unlike t h a t f r o m the healthy person (fig. 6a), the

attached to an alteration of the kind shown in 7c, but in the records in t h a t figure, each of which is the average of 11 responses, the change is almost certainly important. DISCUSSION The method which has been described, f o r measuring and a v e r a g i n g a n u m b e r of successive signals as they occur, is being applied to a s t u d y of the responses in the h u m a n brain to stimulation of sensory nerves. Although some inaccuracies in the technique remain considerable, its convenience and r a p i d i t y have so f a r outweighed its disadvantages, and

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G. D. DAWSON

useful records are obtainable of the f o r m of cerebral evoked potentials which were too small to be observed by other methods. F r o m these records it is possible to make an analysis of the components of the responses and to s t u d y the time course of recovery of some of the processes involved. I n addition to its use for- detecting small signals, the method has been found valuable in studying the causes of variability in the size or form of large signals. W h e n a mean form has been obtained the effects of variables, tried one at a time, on its shape and size can be examined. The most serious limitation of the method lies in the shortness and inflexibility of the time scale that is available. A f t e r a stimulus to a nerve, systematic changes of potential occur in the a p p r o p r i a t e sensory area of the brain for half a second, or possible longer (Larsson 1953), and it would be an a d v a n t a g e to be able to extend the recording time to cover this period. W i t h the present system this could be done only at the expense of slowing down the distributor and losing resolution of the more r a p i d l y occurring events, or by diverting the second channel to sampling later p a r t s of the responses. A need for a faster time scale also arises when the cerebral responses are being related to the character of the volley of impulses in the nerve being stimulated. I n this case the nerve action potentials are usually recorded by superimposition (Dawson and Scott 1949), and when the potential recorded from the nerve has fallen below the biological and i n s t r u m e n t a l noise level a cerebral response, and a sensation, may still sometimes be detected. The nerve action potentials have a time course of a few milliseconds and it seems unlikely t h a t a n y speeded up version of the present method would be able to outline them usefully. No a t t e m p t has so f a r been made to increase the rate of rotation of the distributor, but no sign of failure has a p p e a r e d at the rate used and some increase should be possible. In addition to the lack of longer a n d shorter time scales the present method also imposes the limitation t h a t the stimuli must be released at intervals t h a t are multiples of 100 msec. This means that the stimuli cannot be related to n a t u r a l l y occurring events, or

made altogether non rhythmic, which is a necessary condition for some investigations. This limitation is not inherent in the averaging method but is solely due to the use of a rotating mechanical distributor. A purely electronic method of sampling a n d storage would overcome all these limitations and for this reason the possibilities of using storage tube techniques are at present being investigated. SUMMARY

1. It has been shown t h a t small responses to stimulation m a y be detected amongst large spontaneous activity in the electroencephalogram b y averaging measurements made f r o m a n u m b e r of single oscillograms. 2. An i n s t r u m e n t a l method is described for automatically and r a p i d l y making and averaging such measurements; the details of the method are presented in the following appendix. 3. Sources of error in the method are considered and records of test signals and of sensory evoked potentials are presented. 4. The limitations of the method a n d the lines along which development would be desirable are discussed. 1 ACKNOWLEDGMENTS I would like to thank Mr. J. P i t m a n who constructed the a p p a r a t u s and was responsible for m a n y of the details of the design, Messrs Muirhead and Co. for the loan of the contact discs around which the distributors were built and Dr. Richardson for the photographs of the apparatus. The work w a s carried out with the encouragement of Dr. E. A. Carmichael and benefitted at all stages from discussion with friends too numerous to mention.

APPENDIX For detailed description the apparatus falls into four sections; the first contains the distributor~, storage capacitors, tuning contacts, gearboxes and motor; the second the t u n i n g circuits and the third the circuits for charging and r e a d i n g the store. The cathode ray tube displays for e x a m i n i n g the input and average signals, together with their tune bases and circuits for tuning the stimuli applied to the subject will not be considered in detail since there are m a n y published arrangements which should be 1 Since this account was written an article has appeared (Beard and Skomal 1953) deleribing a commutator memory for improving signal-noise ratio in geophysical experiment, which is in many respects identical with that described here. Details of differences are considered in the Appendix;

D E T E C T I O N OF SMALL E V O K E D P O T E N T I A L S perfectly satisfactory for these purposes. The fourth section is concerned with assessment of the causes of inaccuracy.

1. Distributor and Storage U,it. A general view of the storage unit is shown in figure 8. The 50 c/see, synchronous motor M, with a spindle speed of 25 rev./see., is connected through gear boxes G1 and G2 to the spindle carrying the rotors of the two distributors A and B. These gears give a reduction ratio of 2.5 x 1127/1125 to 1, so that the rotor spindle revolves at approximately 10 rev./sce. The factor of 1127/1125 in the gear ration produces a d r i f t between the 50 c/sec, mains and the distributor such t h a t 50 c/see, interference will be spread almost evenly over any period which is a multiple of 11 see. Normally unimportant ripple

75

G3 drives the spindle carrying K2 which closes every tenth revolution of the distributor spindle. The contacts K1 and K2 are between a fixed brass stud and a brass wiper. The processes started by K1 and K2 must begin at the same time and to avoid difficulties in lining them up, which may be considerable on account of the difference in their angular velocities, K2 is used to gate K1, closing before it and opening after it. Uncertainties in the contact of K1 have been made less important in the same gating circuit. The contact discs of the distributors are of the type used in the contivuous rotation Muirhead switch B-709-A/100, and one of them is shown before wiring and modification in figure 10a. The arrangement of the distributors is shown in figure 9. The spindle C, of insulating material, is mounted in ball bearings in the end plates, P. The two distributor units A and B

Fig. 8

General view of the storage unit. A and B are the two distributors, Csl - Cs62 one bank of storage capacitors, G1, G2 and G3 the reduction gears, K1 and K2 the timing contacts initiating the stimuli, the charging of the store and the starting of the display sweeps. M is the 50 c/see, synchronous driving motor. f r o m power supplies, which would become objectionable if it was summated in a number of records, therefore does not appear in the average waveform. The distributor will be in the same phase with the mains only every 45 see. the 50 c/see, waves being interlaced during successive intervals. Although this arrangement excludes 50 e/see, interference a waveform with a 50 e/see, component which is initiated by the stimulus will be correctly recorded. The gears used have 90 and 92 teeth in G1, 40 and 70, and 50 and 70 teeth in G2. Gear ratios giving a d r i f t of one complete cycle in 10 scc. would have been more convenient in use but the ratio of 500/499 is not simply obtained by mechanical means. On the same spindle as the distributor rotors is the contact K1 which closes every revolution. A final 10 to 1 reduction gear in

are separated by an earthed screen E and are screened from it by the screens D and F. The stray capacities between the rotating contacts and the earthed screen E are reduced by the reading unit which maintains D at the same potential as the rotating contact on A, and F at the same potential as the contact on B. Further screens connected in the same way are fixed to each contact disc in the way shown in figure 10b, S. Without this screening the stray capacities from the rotors to earth sample the charge in each storage capacitor and transfer the sample to the next in the series; .this causes the stored waveferm to lose its shape rapidly. The contact making connection with the condenser studs on each rotor is a brass disc, K~ figure 10c, which is slightly larger than one stud in diameter. A steel wire spring resting in a conical

76

G. i). D A W S O N

depression holds the disc a g a i n s t the c o n t a c t studs, allowing it to rotate freely when the d i s t r i b u t o r rotor is revolving. S p u r i o u s spikes i~ the f i n a l record are m u c h reduced if the open (,ir{mit period b e t w e e n adj a c e n t c a p a c i t o r s is minimal. Ii! a simple w i p i n g c o n t a c t is used s l i g h t wear t e n d s t(, produce a tail on the t r a i l i n g e,lge; the el'feetive c o n t a c t l e n g t h t h e n increases until a d j a c e n t (':~t,n('itors are s h o r t e d t o g e t h e r nnd severe d~stortion o~.(,urs. ]3y r o t a t i n g a n d w e a r i n g evenly all rou,,d th(, disc f o r m oi: c(mt a c t averts this f a u l t a n d it n m y ,!:isily be repb~ceO. Occasion:~l lubric~*tion with :, 1t} }),.," cent solution of medicinal p a r a f f i n oil i~ tohwm. ~xil[ allow qcv(rt'a{ h o u r s of c o n t i n u o u s runlfil~g b¢~tw~,,'~ cle'inings. The

c a p a c i t o r s t h a n equality of size, since a b a t c h m a y easily be g r a d e d in order of size to avoid i r r e g u l a r i t y .

'2. (;sting Unit and Charging Pulse Generator. lu the following d e s c r i p t i o n s t h e circuit d i a g r a m s are d r a w n a c c o r d i n g to the c o n v e n t i o n t h a t j u n c t i o n s ;~re indicated only by a " T e e " am1 two lines crossi n g never show a connection. F o r simplicity t h e 470 o h m resistors on the g r i d p i n s of the valves, which have been used t h r o u g h o u t , a n d the capacitors, u s u a l l y of ]0 to 20 pf., across the top ends of DC c o u p l i n g s are not shown. All power supplies are f r o m sources with an o u t p u t i m p e d a n c e not exceedi n g 5 o h m s between l)(? a n d apl)roximately 10 kes.

-"f:

B ~i ~

Fig. 9 V i e w of the distributor unit. Tile i n s u l a t i n g s p i n d l e C, r e v o l v e s in b a l l b e a r i n g s in the e n d p l a t e s P a n d c a r r i e s t h e r o t a t i n g c o n t a c t s of the t w o distributors A a n d B. E is an e a r t h e d s c r e e n s e p a r a t i n g t h e u n i t s a n d s c r e e n s D a n d F are m a i n t a i n e d at the sarae p o t e n t i a l as the rotors in A a n d B to r e d u c e c a p a c i t y from t h e rotors to E.

steel wire s p r i n g h o l d i n g t h e c o n t a c t is n m u n t e d on a n i n s u l a t i n g b u s h on t h e rotor a r m a n d is connected to it t h r o u g h a 3 9 K o h m q u a r t e r w a t t resistor, R in f i g u r e 10c, whose f u n c t i o n is considered in t h e t h i r d section describing t h e r e a d i n g circuits. T h e other e n d of t h e rotor a r m b e a r s a b r a s s s p r i n g wiper which m a k e s c o n t a c t with a b r a s s disc D, in f i g u r e 10b, in t h e centre of the cathode screen S, which is connected to t h e i n p u t of t h e r e a d i n g circuit. T h e s t o r a g e c a p a c i t o r s Csl to Cs62, f i g s . 3 a n d 9, are each of 0.1 ~fd. a n d r a t e d f o r a w o r k i n g v o l t a g e of 600 P C . Good a n d equal i n s u l a t i o n resistanee a n d low dielectric a b s o r p t i o n are more i m p o r t a n t in t h e s e

Once the f u n c t i o n s of the v a r i o u s circuits have been g r a s p e d it will be clear t h a t , with few exceptions, t h e s a m e r e s u l t s could be achieved in a n u m b e r of ways. The p a r t i c u l a r circuits chosen have u s u a l l y been t h o s e a l r e a d y in use in the l a b o r a t o r y for other p u r p o s e s a n d therefore familiar. The c o n t a c t K 1 , f i g u r e s 3 a n d 8, works on a r a d i u s of 4 cm. a n d gives a s u f f i c i e n t l y precise t i m i n g of the f i r s t make. A n y t e n d e n c y to bounce or b r e a k p r e m a t u r e l y i n t e r f e r e s with t h e f l y b a e k of the 10 see. sweep which d i s p l a y s the c o n t e n t s of t h e store a n d is t r i p p e d f r o m t h i s contact. To avoid t h i s t h e g a t e circuit shown in f i g u r e l l is used. T h e p e n t o d e

DETECTION OF SMALL E V O K E D P O T E N T I A L S V2, a type V R l l 6 , has a short suppressor base and when the contacts K1 and K2 are open the grid and suppressor are both biassed beyond cutoff. The cathode, grid and screen of V2, and the triode V3a, together form a monostable multivibrator which is tripped into the unstable state when K1 closes. The circuit relaxes into the stable state after an interval timed by the .005 ~fd. condenser and the 1.2~ ohm

77

contact K2 closes before and opens a f t e r every tenth contact of K1. A negative going pulse then appears at the anode of V2 as well as at the screen, and the leading edges of the two pulses coincide and their durations are the same. This makes unnecessary any great precision in lining up the contacts K1 and K2. The coupling capacitor and the diode V1 in the input from K2 were found to give more reliable operation

Fig. I0 A Contact disc before modification is shown in a. Each disc has 124 contacts, alternately free and connected to a storage capacitor. The disc in b has added to It a screen S, maintained at the same potential as the rotor, and a contact ring D, picking up the potentials from the rotor by a brass wiper. In c is an enlarged view of the rotor. K is a disc contact big enough to leave minimum open time between alternate studs. K is connected to the rotor arm through R, a quarter watt 39K ohm resistor.

resistor coupling the screen of V2 to the grid of V3a. duration of the unstable state is made slightly longer than the contact of K1 so that the negative going 10/see. pulse which appears at the screen of V2 has a duration unaffected by variations in the time for which K1 remains closed. As the suppressor of V2 remains beyond cutoff no pulse appears at the anode of V2 during the first nine contacts of K1. Rotating with one tenth the angular velocity the The

than a direct connection, but the values used would need modification if the rate of rotation of the distributor is slowed much from 10 rev./sec. The chokes L1 and L2 were necessary to prevent interference due to the sudden discharge of the co~xi~l cables connecting the contacts to the gate unit. T h e size of the chokes is not critical and those used were made by winding 20 turns of 28 SWG wire round a 1 megohm ~ watt resistor. In early records m a d e

78

G . D . DAWSON

with the apparatus interference of this order of frequency and size caused severe disturbances when a large number of sweeps were added. A double triode trigger, which was otherwise operating normally, was found to be causing a similar pulse of high frequency oscillation during the transition phase. The steel cases of the units were relatively ineffective in screening this pulse and it produced serious deflections in the integrated records. ]Per this reason resistors of 470 ohms have been included at the grid pins of valves throughout the circuits~ even where no tendency to oscillation was obvious. In initial experiments the charging cycle was always timed directly from the anode of ¥2 and stimulation was therefore limited to 1/see. To allow some variation outside this rate a counter was added con-

it is also taken directly to the charging pulse generator for the first storage unit Sla. I n addition it is taken either directly or through the delay unit to the charging pulse generator for the second storage unit Slb. When the storage units are being used to record synchronous events the main sweep is usually set to a duration of 100 msec., but when the delay is in use and later stimuli are required, it may be set to any period which is shorter than the interval between two charging cycles. The two charging pulse generators are identical and only the direct one is shown in figure 11. I t consists of a bistable trigger formed by V4 and V5 and an ouput cathode follower V3b, which is only n e cessary if the circuits to be controlled are in separate units with long interconnecting leads. The trigger

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~ CHARGING I:~I..SE GENEI~A'tQR I

Fig. 11 Circuit of the gating and charging pulse unit. The contacts K1 and K2 in figures 3 and 8 are connected to the inputs of V2. The output pulse from V3b is connected to the input of V16a in figure 14. sisting of 3 se.~le of 2 circuits which may be selected by a switch to give an output a f t e r every 2, 4 or 8 input pulses. The same switch will add feedback loops so that outputs will occur after 3, 5 or 7 input pulses. As the eirouit is a counter rather than a divider, the pulses may be fed in at any rate and either the 1/see. or the 10/zee. output frofia V2 may he used. Also the rate of rotation o f the distributor may be altered without upzetting the ratio between the input and output p u l ~ s given by the counter. Stimulus rates between f l / s e e , one charging cycle every alternate rotation of the distributor, and 1 in 8 sec. are t h e r e f o r e available. T h ~ type of eouuter has been dealt with elsewhere (Woodbury and Holdam 1949) and it will not be described. The output pulse from the counter is used to trip the main sweep and

rests with VSa cut off and the plate of V5b at 80 volts negative to the earth llne. The 10/sce. negative pulses from the screen of V2 to the grid of VSa do not affect this state. The first ouput pulse from the counter cuts o f f VSb, the anode of which rises to -~-175 V. and remains there until the end of the revolution of the distributor when K1 closes again and the resulting pulse from the screen of V2 is able to trip the trigger back to the initial state. The charging pulse will therefore last for one revolution of S1 and the eireuit~ like that of the counter~ will operate independently of the rate of rotation of the distributor. A pulse from - - 4 0 to q - 2 0 V. with respect to earth is sufficient to operate the chargin8 circuits; the extra size available is used for: con. trolling the brilliance of the recording cathode ray

D E T E C T I O N OF SMALL EVOKED P O T E N T I A L S tubes and for pulsing the time scale generator. This last is necessary because the drift of the distributor rotation in relation to 50 e/see, would also cause it to drift relative to a continuously running time marker generator which gave any of the usual convenient intervals. The marker pips would therefore not be available for timing precisely the release of stimuli and the time scales on the observation tubes would drift continuously. Several systems have been described to meet this situation using pulsed oscillators (Gamertsfelder and Holdam 1949; Laws 1946; Mynall 1946) or a storage tube method, (Bell, Forbes and MaeNiehol 1949), but for the present application a 100 ke/see, crystal oscillator, which was already available, is gated and the dividers to which it is fed arc reset and released by the charging

79

cathode of V8a which results keeps it conducting after the input pulse has finished. L e f t to itself the circuit would relax into the stable state after a time determined by the size of the capacitors C2 to C5, the resistors from the grid of VSb to the positive rail and the setting of the potentiometer P4 controlling the grid volts of V8a. The relaxation time with C2 is set by P4 to be just longer than one revolution of the distributor, at present 100 reset., and the circuit will then be reset to the stable state by the next negative going 10/see. pulse on the grid of VSa through the diode V7b. The 1.5 megohm resistor from the anode of VTb controls the amplitude of the 10/see. pulses at the grid of VSa so that they do not reset the circuit until shortly before it would relax on its own. With the capacitors C2 to C5 of 0.12, 0.25, 0.35 and

-+250

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33Ok

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V76H6

Coun'=,r 820k

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-I,~22k

~tp4 4O A. *-250

DELAY UNIT 12 Ctrcuit of the uutt for delaying the charging cycle of the second distributor.

Fig.

pulses. This may give rise to an uncertainty in the time markers of up to 5 i,sec., which is unimportant in this work. The delay circuit for sampling events after the charging revolution of S l a is shown in figure 12. I t has the function of producing a negative going pulse, delayed after the leading edge of the main charging pulse by multiples of 100 mace., to trip the second charging pulse generator. A monostable cathode coupled multivibrator is used and because, unlike the counter and charging pulse circuits, it has a natural period of relaxation it is not suitable if the rate of rotation of the distributor is to be made variable. In that case a counter type of circuit would be necessary here also, but the arrangement shown is simple and has so far been satisfactory. In operation VSa is normally cut off and V8b conducting. The output from the counter, a negative going pulse, is clipped and inverted by V6 the positive going pulse from the anode of which makes V8a conduct. The fall at the anode o f ' V S a cuts off V8b and the drop at the

0.5 ~,fd the circuit will then be tripped back after the first, second, third or fourth 100 msee. period or revolution of the distributor. The negative going output pulse from the anode of V8b then trips the second charging pulse generator for S l b and events up to 500 resets, later than those stored by S l a may be recorded. In the undelayed position the switch S4b selects the output from the counter directly and S4a makes the multivibrator inoperative. 3. 8torage a~d Reading Circuits. For storing the signals and reading the stored waveform two identical systems were used; a scheme of one of them is shown in figure 13 and the circuit in figure 14. The first section is a cathode follower with a high input impedance; this follows the potential, Vc, to which the storage capacitors Cs are charged without significantly discharging them. The output from this cathode follower is taken to the store display, CRT1 in figure 3, and also to the second section which inverts it without change of

80

G. D. DAWSON

amplitude. During the charging cycles, when the relay contacts Rkl and Rk2 are closed, the third stage adds the input signal, .... Vs, to the output of the second stage, - - V c , and inverts the sum of them to give an output Vs + AVe, where A is the total gain of all three sections. This output voltage is taken to the charging resistance R3 and with a loop gain, A, of 1 the potential difference across R3 would always be Vs and the rate of change of Vc, the potential to which the storage condensers Cs are charged, would be proportional to the signal voltage, irrespective of the level of the charge in the store. Normally A is set to 0.99 to avoid regeneration "~nd the heavy negative feedback in each stage will 1)re~ vent it from rising above ] even if the characteristics of the valves change by a n amount which would double their gain in the "~bsenc,. of feedback. A h)op gain of 0.99 gives :~ linearity of charging to 1 per cent when the signal, Vs, is equ:Jl to the potential of the charge, Ve, in the storage capacitors. The CRO used to display Vc gives a full scale deflection with an input of 20 V. pp., so that a maximum level of wanted signal of 20 volts is s u f ficient. I f the wanted signal is obscured by noise of

t).5 volt RMS AC signal as Vs, with Rkl and Rk2 closed and the distributor on a blank stud. The output of the second inverter and adder is then set t~, 49.5 volts . This rise of voltage on free studs at the input to the cathode follower causes large spikes ou the display during the charging cycles, but they do not affect the functioning of the circuit. [ f desired the display CRO may be blanked during the charging cycles or disconnected by a third pair of relay contacts opening during the charging periods. No trouble has been experienced from slow drifts in the level of the output from the second inverter. ][f such a drift occurs it will cause a charge to ac ~ cumulate in the storage capacitors and to prevent this the inverter valves are rml under relatively low c~rr(mt conditions where drift is reduced (Jacobsen :~,~d ltohlam 1948). In addition all heater supplies for this and other units are obtained from a source r~,gu[ated to 0.5 per cent against slow line fluetua tio~s of up to 10 per cent. A~ well as reading the charges in the storage c:q>a
Rk2

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,7" Fig. 13 Scheme of the c h a r g i n g and reading circuits.

four times this size, i.e. 80 V. pp., the output stage of the signal amplifiers will not have to handle more than 100 V. pp. With a simple resistor charging circuit the same degree of linearity in charging would demand 100 times this voltage handling capacity in the signal amplifiers. Initially this difficulty was reduced by allowing a much smaller maximum charge in the storage capacitors, but this introduced other difficulties and the arrangement shown has been found more satisfactory, I f a signal is applied to the input with Rkl and Rk2 closed, but with the distributor S1 on a blank stud between two capacitors the potential at the top end of R3 is fed into the cathode follower unattenuated and, as the feedback is positive the ouput from the inverter and adder, A 3 in figure 13, rises to Vs( ). With A _~ 0.99 1 --AB and fl ~ 1 the gain in this state, from the signal input to the output of the third stage, is 99. The loop gain may conveniently be set by applying a

if these strays are not minimised they degrade the form of the stored waveform by passing on samples of the stored potentials from one capacitor to the next. To reduce this effect screens around the rotor and the wiring connected to it were taken to the cathode of the input cathode follower and they followed the potential of the rotor closely. I ~ a ! l y the circuit used by Nastuk and IIodgkin (1950) for this purpose was tried. However, as these authors point out, a relatively large capacity connected across the output of a simple cathode follower will cause it to give an oscillatory response to a step input. As the capacities from eathode to earth~ due to the cables and switch screens used totalled 900 pf, this effect became serious and the oscillatory overshoots which resulted when the distributor contact passed from one contact to another at a different p o t e n t i a l caused spurious charges to accumulate in the store. The magnitude of this effect in a circuit similar to that of figure 14, but with the valve V l l replaced by a resi~t~r connected to the negative rail, is shown

D E T E C T I O N OF S M A L L E V O K E D P O T E N T I A L S in figure ~[5. I n figure 15c, where the test pulse was applied directly to the deflection amplifiers, the record shows the waveform of the pulse and the response to it of the recording system. I n figure 15d and e this waveform was applied to the grid of the cathode follower through 47k ohms and 100k ohms respectively, and the outputs recorded from the cathode. The amplitude of the pulse was 10 volts and ".he time scale is 100 kcs. per second. Any attempt to reduce the cathode resistor to lessen the tendency to oscillatory overshoots caused trouble, since it reduced the gain of the circuit a n d allowed the gridcathode potential to depart more from the optimum for minimum grid current. The circuit finally developed is t h a t of V10, V l l and V12 in figure 14. I t was later found to have been described by White (1944) and is a special case of the class of circuits

+ill{

81

39k ohm resistor shown on the rotor in figures 10c, R, and figure 14, completely prevents this tendency to oscillation. The charging characteristics of the circuit are not significantly affected by this resistor and i t does not unduly prolong the discharge time of the store. The input cable and the switch screens put a capacity of 225 pf from grid to cathode of V10, and 900 pf from cathode to earth. With these capacities the circuit of V10 and V l l reduces the effective capacity applied to the rotor of the distributor to 3 pf. This was measured by applying a step input to the rotor through a resistance of 20M ohms with the feedback loop open and the rotor contact on a blank stud. The added capacity needed to halve the rate of change at the cathode of V10 was then found. The part of the input capacity due to capacity from

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Fig. 14

Circuit of the charging, storgge and reading circuits. The signal input is through the RC coupling and Rkl ; the averaged output from the cathode of V15b.

analysed by Cooper (1951). The responses of this cirenit to the waveform of figure 15c are shown in fig. 15a, where it was applied through 47k ohms, and in fig. 15b, where i t was applied through 100k ohms. By comparison with the simple cathode follower in 15d and 15e, the responses a t the cathode have a faster rise time and the overshoot is reduced in amplitude and duration. The test pulse used had a rise time to 90 per cent of less t h a n 2 /zsec.; no faster rising test pulses than this have been used but the circuit is satisfactory in use with the distributor. W i t h a resistance of 4k ohms from either the grid end or distributor end of the input cable to earth, the circuit has a tendency to o~i]]~te a t about 800 kcs. With the grid either earthed or connected to earth through not less t h a n 10k ohms at the distributor end the circuit is stable, and the

screen to grid of V10 is also reduced in the manner described by Nastuk and Hodgkin (/oo. c/t.) by making the screen of V10 follow its cathode. Instead of using a battery for this purpose it was found more convenient to connect V12 to produce at the screen of V10, a t a convenient level, a replica of changes at its cathode. F o r V10 a n EF37 was chosen because of the antimichrophonic characteristics and low grid current of this type. Whether this valve is a t all critical is not clear as no others have been tried in this position. The grid-cathode potential of V10 is set by altering its screen v o l t a g e until there is minimum change of cathode potential when the free grid is earthed and vice versa. The resistance of the circuit, cables and distributors to earth, with the rotor on a blank stud, is not less t h a n 5000M ohms, as measured f r o m t h e ratio of the

b2

G . D . DAWSON

outputs when applying a fixed potential directly to the rotor or through 1000M ohms. With the grid-cathode potential of V10 set to the optimum the cimnge in cathode potential on open circuiting the grid is less than 0.1 volts, corresponding to a grid current of not more than 2 x 10-5 ~amp., which is satisfactory in this application. The setting of the screen voltage on V10 is carried out by the potentiometer P1 on the grid of V12a; P2. b~tween the cathodes of V12a

a

d

b

C

Fig. 15 The records in a and b show the responses of the cathode follower of figure 14 to a test pulse of the form shown in c. In a the pulse was delivered through a resistance of 47K ohms and in grid to cathode was For comparison d inputs but with a

b of 100K ohms. The loading from the 200 pf. and from cathode to earth 900 pf. and e s h o w the responses to similar resistor as cathode load instead of V l l .

Pulse amplitude 10 V., time scale 100 kc/sec. and V12b is first set for unity gain between cathode and screen of V10. The setting of P2 is not critical and after the initial setting up it has been replaced by a fixed resistor of 33k ohms in this apparatus. While reading with no charges in the storage capacitors, grid current flowing in V10 will appear on the display as a series of spikes occurring when the rotor passes over the blank studs. P1 may also be set to minimise these spikes and in use readjustment has only been found necessary at long intervals. After the levels in Vl0 have been adjusted the zero level of the two inverters is adjusted by P3. For this the rotor is earthed and P3 set to give zero output on the meter V, connected temporarily to the cathode of V15a. This control also has needed little adjustment in use and no automatic correction for drift in V13 and V14 has been considered necessary. The output from the cathode of V10 is taken to the buffer V15b and thence to the display. I t also goes to the feedback inverter VI3, whose gain is defined at about unity by the input and output resistors in the grid circuit. These grid resistors should be of 1 per cent t o l e r a n c e a n d high stability. In the second feedback stage, Comprising V14 and Vl5a, the input signal, coming through the double RC coupling from the main signal a m p l i f i e r s a n d through the r e l a y Rkl which is closed during the charging cycle, is added to the output from V13 and the inverted sum

of tile two appears at the cathode of V15a. In this stage also the input and output grid resistors should be of high stability. The gain from the grid of V10 to the cathode of V15a is set to 0.99 in the manner described above by altering the resistor r, shown on the output side of the grid of V14 in figure 14. This resistance is placed on either the input or output side of V14, depending on whether the tolerances of the 1M ohm grid resistors make necessary an increase or decrease of gain to reach the correct figure. The double RC coupling in the signal input to V14 reduces any potentials across the coupling resistor due to capacitor leakage which, although very small, may otherwise produce a base!ine shift in an integrated record of many sweeps. The output from V15a is taken to the charging resistor R3 and from there is applied to the distributor rotor every charging cycle when Rk2 closes. The charging resistor R3 is switched in steps with the ratios 1, 2, 5, 10 and 20, with a minimum value of 100k ohms. The values of the resistors are such t h a t with an input signal of 10 V. peak the storage capacitors will charge to approximately 10 V. in 11, 22, 55. 110 and 220 charging cycles respectively. The minimum figure of 11 charging cycles is based on a rate of 1 c/see, and then gives good cancellation of 50 cycle and related interference. I f more than one charging cycle per second is used, for example 2 or 5, storage must still be carried out over a minimum period of 11 seconds or a multiple of this, i.e. for 22 or 55 cycles if the cancellation of interference is to be as good as at the slower rate. The charging cycle takes place when the charging pulse from VS, figure 11, turns on V16a and the switch S2b is in the ~ ' c h a r g e " position allowing the relay coil Rc to be energised and the contacts RK1 and RK2 to be closed. In the " c h a r g e " and " r e a d " positions the switch S2a leaves the distributor roter free and iJl the " d i s c h a r g e " position shorts it to earth.

4. Asscss~nent of Accuracy. The irregularities which appear in the average records, which may be seen in figures 4a and 16, may be caused by inequalities in either size or leakage of the storage capacitors, or by inequalities in the resistances or durations of the distributor contacts. Differences in the sizes of the capacitors are made unimportant by grading them in order, so that the differences between adjacent ordinates are minimal. The effects of capacitor leakage would be small under the conditions of recording in figure 4 and they will be considered later. Variations of resistance in the distributor contacts have not been found to be important since, with the charging circuit used, the effective resistance through which the capacitors are being charged is 10M ohms, even when using the smallest charging resistor of 100k ohms. When the contact resistance does rise it may prolong the discharge time of the store and for this reason it. may become necessary to clean the contacts after 2 to 3 hours running. Variation of the duration of contact at the different studs, possibly due to surface irregularities or slight differences in the spacing of the distributor studs, appears to be rosponsible for most of the irregularities in the records. The size of these irregularities is proportional to the a m p l i t u d e of the stored voltages and the relation is shown in figure t6a, b, and c. I n these records a s i ~ of 5 V. was applied to the input during 11, 22 and

DETECTION OF SMALL E V O K E D P O T E N T I A L S 44 charging cycles, in e a c h c a s e with the same charging resistor. This source of inaccuracy is the largest one remaining, but its size is not sufficient to warrant the added complication necessary to overcome it. I f greater accuracy is needed the irregularities a r e sufficiently constant during one experiment to be allowed for by calibration. I n the records considered so f a r the charges were fed into the storage capacitors at 1 see. intervals over a period of 11 see., with the exception of those records in figure 16b and c, where the charging

b

ia ) _

ii

Ij

I

"

--i

_~ll

il

c HIJL

/[

II

HH

"

Fig,

-

i

-

Iltll

It

i

I

IJI

........

16

The records in a, b and c show the addition of 11, 22 and 44 sweeps respectively, with the same value of charging resistor in each case.

periods were 22 and 44 sec. Under these conditions the •effects of leakage or dielectric absorption in the storage capacitors, or of ~'earry o v e r " of charge from one capacitor to the next by the stray capacities of the rotor and reading circuits, will be small. If, however, 220 or more traces are to be averaged, charging may have to be carried out over 3 to 5 rain. and errors due to leakage or carry over will be greater. The loss of amplitude of the stored signals due to capacitor leakage and absorption, and any leakage in the reading circuits is shown in figure 17. Here 11 charging cycles at 1 see. intervals

8

~

b

O

i

~

~ammlmm

Fig. 17 records show the loss of amplitude of a stored waveform. A set of 11 sweeps was stored, giving the average in a. This store was then read continuously, its state at 2 min. is shown in b and at 5 min. in c. The

completed the store, which was then read continuously. The state of the store immediately a f t e r completion is recorded in figure 17a and its state when it has been read for 2 and 5 rain. is shown in figure 17b and e. The amplitude of the stored pulse has fallen by 10 per cent over the 5 rain. from 17a to 17c. This means that if the charges, instead of

83

being fed in at the start, had been evenly spread out over the 5 rain. period, those stored f i r s t would have decayed by 10 per cent and the average would be weighted by those stored last. This effect also accounts for some loss of accuracy in the averaging. For a fixed size of signal input the same result should be given by 11 charging cycles with a charging resistor of 100K ohms and by 220 charging cycles with a resistance of 2M ohms. But since the 220 charging cycles will usually have been spread out over a longer time than the 11 cycles the earlier charges will have decayed to some extent and the final integrated signal will be smaller. The discrepancy between the average of 11 and 220 charging cycles, both at 1 sec. intervals, with the appropriate resistors is 6 per cent. Both this error and the weighting of the average by the later signals could, if they were sufficiently serious, be overcome by setting the gain of the signal amplifier high at the start and then reducing it progressively throughout the charging period. This fall in the amplitude of the stored signals was found to be in small part due to capacitor leakage but largely due to dielectric absorption in the storage capacitors (Gray 1948). Tile input resistance of the reading circuits does not cause any serious loss as it is more than 5000 M ohms and it is connected across each capacitor for only one sixtieth of the total time. The amount of the dielectric absorption may be assessed if the capacitors are left charged to a known voltage for 5 rain.; at the end of this period the capacitors are discharged for 5 sec. This reduces the charges to a level not visible on the display, but as reading is continued a reduced replica of the original signal waveform appears and its amplitude may reach 80 per cent of the loss between the records in figure 17a and c. I f the capacitors have held a charge for 5 rain., a discharge period of 1 rain., through the 39K resistor on the rotor, is sufficient to reduce any remaining charge which may soak out to such a level that it will not affect significantly any subsequent records. This residual charge will be lessened correspondingly when shorter storage times have been used. Capacitors with polystyrene dielectric overcome this error from absorption and they are being fitted to later models of this apparatus. The distortion of the stored waveform due to large stray capacities from the rotor to earth was severe in early experiments• The carrying over of part of the charge of one capacitor to the next, produces an effect which could be seen clearly on the leading and trailing edges of square waves, which become rounded off after continuous reading. With the circuits described the distortions due to this cause are slight compared with the loss of amplitude on storage; the change in shape over a 5 min. storage period can be assessed from the records in figure 17a and c. The effectiveness of the charging circuit in keeping the relation linear between the input signal and the rate of charge of the capacitors is shown in figure 16. Here an input pulse of 5 volts was applied with a charging resistor appropriate to 22 charging cycles, which should give a 5 volt charge in the store with that number of charging cycles. In figure 16a this pulse was applied for 11 cycles, in figure 16b for 22 cycles and in figure 16c for 44 cycles. The charges acquired by the capacitors should then have been in the ratio 1, 2, and 4. This relation is obtained to better than 5 per cent, or

84

G.D.

less than the irregularities in the records, even though the input signal in figure 16e was only half as large as the stored signal., Beard and Skomal (1953) give no account of difficulty with stray capacities or with dielectric absorption in the storage capacitors. The first difficulty may have been overcome because they used larger storage capacitors than were used in the apparatus described, and for their purposes it may not have been necessary to store or read over such long periods as arc needed in biological work. The larger size of the storage capacitors used by them (1 ~fd. instead of 0.1 ~fd.) would probably make the cost of polystyrene dielectric capacitors prohibitive, but it seems t h a t they are necessary for biological work where rapid and complete clearance of the store for a further recording is often essential. REFERENCES AIRY, G. B. Greenwich Meteorological Reductions, Barometer. 1854-1873 pp. 10, 14 and 30, H. M. Stationery Office, London, 1878. BALDOCK, G. R. and WALTER, W. G. A new electronic analyser. Electron. Eng., 1946, 18: 339-342. BEARD, C. I. and SY:0:~AL, E. N. RC Memory Commutator for signal to noise improvement. Rev. Sci. Instr., 1 9 5 , ~4: 276-280. BELL, P. R., FORBES, G. D. and MAcNICHOL, E. F. Storage tubes, p. 707 in " W a v e f o r m s " , Radiation Laboratory Series No. 19, New York, Me Graw-Hill, 1949. BRAZIER, M. A. B. and CASBY, J. U. Crosscorrelation and autocorrelation studies of electroencephalographic potentials. EEG Clin. Neurophysiol., 1952, 4: 201-211. CHAPMAN, S. The lunar atmospheric tide at Greenwich. Quart. J. Roy. Meteor. Soy., 1918, 44: 271-280. COOPER, V. J. Shunt regulated amplifiers. .Wireless Eng., 1951, ~8: 132-145. DAWSON, G. D. Cerebral responses to electrical stimulation of peripheral nerve in man. J. Neurol. Neurosurg. Psychiat., 1947, 10: 134-140. DAWSON, G. D. Cerebral responses to nerve stimulation in man. Brit. reed. Bull., 1950, 6: 326329. DAWS0N, G. D. A summation technique for detecting small signals in a large irregular background. J. Physiol., 1951, 115: 2.

DAWSON DAWSON, G. D. and SCOTT, J. W. The recording of nerve action potentials through skin in man. J. Neurol. Neurosurg. Psychiat., 1949, 12: 259267. GAMERTSFELDER, G. R. and HOLDA~, J. V. Sinusoidal waveform generators, p. 140 in " W a v e f o r m s " , Radiation Laboratory Series No. 19, New York, McGraw-Hill, 1949. GRAY, J. W. Calculus, p. 68 in " E l e c t r o n i c Instrum e n t s " , Radiation Laboratory Series No. 21, New York, McGraw-Hill, 1948. HARTLEY, R. V. L. The transmission of information. Bell Syst. Teeh. J., 1928, 7: 535-563. JACOSSEN, A. and HOLDAM, J. V. Regulator elements, p. 513 in " E l e c t r o n i c I n s t r u m e n t s " , Radiation Lab. Series No. 21, New York, McGraw-Hill, 1948. LARSSON, L. E. Electroencephalographic responses to peripheral nerve stimulation m man. EEG Clin. Neurophysiol., 1958, 5: 377-384. LAws, C. A. A precision ranging equipment using a crystal oscillator as a timing standard. J. Inst. Elect. Eng., 1946, 93: P a r t I I I A 423-440. LEE, Y. W. Application of statistical methods to communication problems. Technical Report No. 181, Massachusetts Institute of Technology, 1950. MYNALL, D. J. A pulsed crystal oscillator circuit for radar ranging. J. Inst. Elect. Eng. 1946, 93: P a r t I I I A 1207-]214. NASTUK, W. L. and HODGKIN, A. L. The electrical activity of single muscle fibres. J. Cell. Comp. Physiol. 1950, 35: 39-74. SASINE, E. On the lunar atmospheric tide at St. Helena. Philos. Trans. roy. 8oe., 1847, [37: 4550. WATSON-WAT% R. The evolution of radiolocation, J. Inst. Elec. Eng., 1948, 93: P a r t I I I A 11-19. WroTE, E. L. C. British P a t e n t Specification, 1944, No. 564250. WILKES, M. V. Oscillations of the e a r t h ' s atmosphere. ' ' Monographs on Physics ' ', London, Cambridge University Press, 1949. WOODSUaY, R. B. and HOLVAM, J. Y. Counting, p. 611 in " W a v e f o r m s , " Radiation Laboratory Series, No. 19, New York, McGraw-Hill, 1949. YULE, G. U. An introduction to the theory of statistics. Griffin, London ( l l t h ed. 1957).

Reference: DAWSON, G. D. A summation technique for the detection of small evoked potentials. BEG Glin, Neurophysiol., 1954, 6: 65-84.