- Email: [email protected]
An evoked response detector
AN EVOKED RESPONSE DETECTOR ROBERT R. COX AND EDWARD V. EVARTS
Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Betkesda, Md. (U.S.A.) (Received for publication:September 15, 1960)
Within recent years a number of techniques has been developed for detecting evoked cerebral potentials in recordings from the scalp in man. The techniques of Dawson (1954) and Brazier and Barlow (Barlow 1957) have shown that such responses may be easily demonstrated when a series of responses to the stimulus is averaged. The averaging process leads to an increase in the ratio of signal (evoked response) to noise (spontaneous electrical activity of the brain). The increase in this ratio is a function of the square root of the number of responses averaged. The
present report describes a technique which allows such averaging. In principle, the method to be described is similar to that of Dawson (1954), involving the successive charging of the elements of a bank of condensers, such that each condenser is charged at a fixed time with respect to the occurrence of a stimulus. The method involves a new switching technique which provides a high degree of reliability and flexibility, and which can average responses either directly from the subject or indirectly, from tape recordings. CIRCUIT DESIGN AND OPERATION
M
G ~
+450VDC
B
• -
300K~
+
>12o VDC
H --
d
--
+450voc '
300K ~.,
",/N/k/~ 15K
_ >-20 VDC
15K
59,0,
.
One hundred 0.33 mfd polystyrene dielectric (1% Iol) capacitors (Fig. 1, A, B) are successively connected in fixed sequence across an operational amplifier (Fig. 1, K), from summing point to output. After each individual capacitor is transferred, a high speed relay (Fig. I, C) in series with a potentiometer (Fig. I, D) connected between the summing point of the operational amplifier and the circuit input closes. Amplified EEG voltage is applied to the circuit input. The individual capacitor charges in linear relationship to the current flowing in the series potentiometer, the direction of charge depending on the polarity of the current (Johnson 1956). If there is no current flow, the charge on the capacitor remains the same. The high speed relay now opens, the capacitor is switched out and the next capacitor is switched in. This continues until each of the 100 capacitors has had its turn across the operational amplifier. The rate of the transfer X 100 determines the epoch duration. In the system being described, the shortest epoch is 250 msec, the longest in excess of 15 min. Output in the form of a histograph is obtained between output of the operational amplifier and ground. The output is continuously displayed on an oscilloscope without deterioration of the stored information. A synchronizing pulse is provided to start the oscilloscope sweep at the beginning of the epoch. Suitable blanking of the Z axis at the 1/100 epoch rate transforms the bar histograph to a dotted graph. To keep the operational amplifier quiescent between epochs, the final capacitor in the sequence is replaced by a resistor (Fig. 1, E), transforming the circuit from a bidirectional integrator to an amplifier of near zero gain. This resistor remains connected between summing point and output of the operational amplifier between epochs. A small capacitor (Fig. 1, F) between summing point and ground minimizes switching transients. Each storage capacitor is in series with a separate relay (Fig. 1, G) which consists of a glass reed switch
-20 VDC
d • q
.
1
Fig. 1. A,B. 0.33 mfd 1% tol polystyrene dielectric capacitor (Plastic Capacitor Corp.) C. Sigma 72AOZ-160TS-TCP Relay D. One M~,2 potentiometer connected as rheostat (Ohmite) E,L. 10K-~ lW carbon resistor F. 0.006 mfd paper capacitor G. Relay, made of Revere Corp. glass reed switch inserted in Guardian coil assembly No. 200-115a (with core removed) H. 6BY6 tube J. GSI0D Dekatron (Baird-Atomic) K. UPA 2 operational amplifier (Philbrick) M. Push button switch, normally open 478
EVOKED RESPONSE DETECTOR inserted in a solenoid. The relays are useable at d u r a t i o n s as short as 2 I / 2 msec, have very high open circuit resistance (greater t h a n 5 >~. 10 l~ ~)), a n d are comparatively economical. T h e solenoid o f each of the relays is in the plate circuit o f a separate 6BY6 tube (Fig. 1, H). T h e 6BY6 tube has two control grids, either one o f which can c u t off the tube a n d open its associated glass reed relay. T w o D e k a t r o n selector tubes (Fig. 1, J) (Baird-Atomic 1960) connected as a scale of 100 c o u n t e r provide a matrix control voltage to the 6BY6 grids. Each D e k a t r o n selector has 10 cathodes. T h e " u n i t s " D e k a t r o n is externally triggered at the 1/100 epoch rate a n d provides a repeating (~9 c o u n t activating each c a t h o d e in turn. F o r each 10 "'units" c o u n t s completed the " t e n s " D e k a t r o n advances one "10 s`, count. C r o s s b a r s connect the D e k a t r o n cathodes to the proper "'units" a n d " t e n s " grids o f the 6BY6 tubes, thus activating each tube in turn in the sequence 00 t h r o u g h 99; a circuit is provided to interrupt the trigger pulses a n d cause the D e k a t r o n s to stop at 00. 00 is the circuit provided with the s h u n t i n g resistor previously mentioned. Each time that the tenth 6BY6 tube is activated, a s t i m u l u s trigger occurs, thus fixing the time of occurrence of the s t i m u l u s in the epoch. This provides a short interval in the epoch before the stimulus, a n d gives a rough indication o f signal to noise ratio. Since each storage capacitor is charged in fixed sequence, c o m p o n e n t s of the input waveforms that have a fixed temporal relationship to the epoch s u m linearly. R a n d o m c o m p o n e n t s will also s u m , but only as the function of the square root of the n u m b e r o f epochs s u m m e d . Care should be taken to insure that no artifact locked to the epoch be introduced, as it will also s u m linearly. The circuit is convenient in operation in that the potentials on the storage capacitors m a y be viewed with each new epoch. T h e experimenter will observe early in an individual experiment if e n h a n c e m e n t is being obtained. If the input is disconnected the information stored will be retained a n d m a y be displayed m a n y h u n d r e d s of times without significant deterioration. If the D e k a t r o n s are not cycled the charge on the capacitors will be held for several h o u r s with less t h a n I per cent loss of charge. T h e epoch duration m a y be readily c h a n g e d a n d the epoch repetition rate can also be c h a n g e d or even randomized by an external trigger. Since the epoch m a y be initiated by a n external trigger, it is possible to average responses which have been tape recorded. At the conclusion of a given experiment the storage capacitors are discharged to zero by connecting a resistor (Fig. I, L) between the s u m m i n g point a n d the o u t p u t terminal o f the operational amplifier and allowing the Dekatrons to cycle several epochs. This discharging resistor is provided with a p u s h b u t t o n switch (Fig. 1, M). Sixty cycle artifact can be troublesome, particularly when the signal to noise ratio is u n u s u a l l y low. It has been f o u n d a d v a n t a g e o u s to initiate the triggering of each succeeding epoch at the nearest alternate 180 ° phase of the 60 cycle line. T h u s , the epoch repetition rate is the selected repetition rate plus the short delay necessary to trigger at the proper phase. This has proven to be quite an effective solution, suppressing both internal circuit 60 cycle pickup a n d the 60 cycle artifact s o m e t i m e s contained
479
in the EEG. However, the action is unlike that of a low pass filter since inherent 60 cycle c o m p o n e n t s o f the c o m plex E E G w a v e f o r m s are not attenuated. Fig. 2 shows the average o f 400 responses to a flash, recorded from scalp in m a n at an epoch repetition rate of 2 sec. T h e lower graph d e m o n s t r a t e s the response as
Fig. 2 Average o f 400 responses to photic stimulation, recorded between scalp electrodes in man. The curves were: obtained successively in the s a m e subject. The points are separated by 5 msec in the upper curve a n d 2.5 msec in the lower curve.
depicted by points 2.5 msec apart; in the upper graph a longer segment of the response is shown, the individual points being 5 msec apart. In cases requiring points to be separated by less than 2.5 msec, the responses m a y be tape recorded at high speed, with s u b s e q u e n t analysis of the tape record at low speed. The evoked response detector has been in operational use for several m o n t h s a n d has been reliable, requiring the replacement of one 6BY6 tube during this period. T h e use of the hermetically sealed glass reed switches entirely eliminates the need for cleaning of the switching mechanism. At the currents passed in the present application, the switch life is rated by the m a n u f a c t u r e r in billions of operations. T h e assembly of the detector is simplified by the fact that the m a j o r critical electronic c o m p o n e n l , the operational amplifier, can be purchased. F r o m the econ o m i c viewpoint, the c o m p o n e n t cost of the evoked response detector is s o m e w h a t less t h a n that of a s t a n d a r d E E G recorder or frequency analyzer. T h e detector., less auxiliary triggering circuits, can be housed in one 6-foot high, 19-inch wide s t a n d a r d relay rack. T h e a u t h o r s wish to express their appreciation to Drs Karl F r a n k a n d W a d e Marshall for their helpful suggestions during the course of development of the in-
480
R.R. COX AND E. V. EVARTS
strument, and also to Mrs. Edith Kessler for her assistance in obtaining recordings. REFERENCES BAmD-A'roMIC, Inc. Handbook of counting tubes. Cambridge, Mass., 1960. BARLOW, J. S. An electronic method for detecting evoked
responses of the brain and for reproducing their average waveforms. Electroenceph. clin. Neurophysiol., 1957, 9: 340-343. DAWSON, G. D. A summation technique for the detection of small evoked potentials. Electroenceph. clin. Neurophysiol., 1954, 6:65 84. JOHNSON, C. L. Analog computer techniques. McGrawHill, New York, 1956, p. 11.
Reference: Cox, R. R. and EVARTS,E. V. An evoked response detector. Electroenceph. c/in. Neurophysiol., 1961, 13: 478-48O.
Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Betkesda, Md. (U.S.A.) (Received for publication:September 15, 1960)
Within recent years a number of techniques has been developed for detecting evoked cerebral potentials in recordings from the scalp in man. The techniques of Dawson (1954) and Brazier and Barlow (Barlow 1957) have shown that such responses may be easily demonstrated when a series of responses to the stimulus is averaged. The averaging process leads to an increase in the ratio of signal (evoked response) to noise (spontaneous electrical activity of the brain). The increase in this ratio is a function of the square root of the number of responses averaged. The
present report describes a technique which allows such averaging. In principle, the method to be described is similar to that of Dawson (1954), involving the successive charging of the elements of a bank of condensers, such that each condenser is charged at a fixed time with respect to the occurrence of a stimulus. The method involves a new switching technique which provides a high degree of reliability and flexibility, and which can average responses either directly from the subject or indirectly, from tape recordings. CIRCUIT DESIGN AND OPERATION
M
G ~
+450VDC
B
• -
300K~
+
>12o VDC
H --
d
--
+450voc '
300K ~.,
",/N/k/~ 15K
_ >-20 VDC
15K
59,0,
.
One hundred 0.33 mfd polystyrene dielectric (1% Iol) capacitors (Fig. 1, A, B) are successively connected in fixed sequence across an operational amplifier (Fig. 1, K), from summing point to output. After each individual capacitor is transferred, a high speed relay (Fig. I, C) in series with a potentiometer (Fig. I, D) connected between the summing point of the operational amplifier and the circuit input closes. Amplified EEG voltage is applied to the circuit input. The individual capacitor charges in linear relationship to the current flowing in the series potentiometer, the direction of charge depending on the polarity of the current (Johnson 1956). If there is no current flow, the charge on the capacitor remains the same. The high speed relay now opens, the capacitor is switched out and the next capacitor is switched in. This continues until each of the 100 capacitors has had its turn across the operational amplifier. The rate of the transfer X 100 determines the epoch duration. In the system being described, the shortest epoch is 250 msec, the longest in excess of 15 min. Output in the form of a histograph is obtained between output of the operational amplifier and ground. The output is continuously displayed on an oscilloscope without deterioration of the stored information. A synchronizing pulse is provided to start the oscilloscope sweep at the beginning of the epoch. Suitable blanking of the Z axis at the 1/100 epoch rate transforms the bar histograph to a dotted graph. To keep the operational amplifier quiescent between epochs, the final capacitor in the sequence is replaced by a resistor (Fig. 1, E), transforming the circuit from a bidirectional integrator to an amplifier of near zero gain. This resistor remains connected between summing point and output of the operational amplifier between epochs. A small capacitor (Fig. 1, F) between summing point and ground minimizes switching transients. Each storage capacitor is in series with a separate relay (Fig. 1, G) which consists of a glass reed switch
-20 VDC
d • q
.
1
Fig. 1. A,B. 0.33 mfd 1% tol polystyrene dielectric capacitor (Plastic Capacitor Corp.) C. Sigma 72AOZ-160TS-TCP Relay D. One M~,2 potentiometer connected as rheostat (Ohmite) E,L. 10K-~ lW carbon resistor F. 0.006 mfd paper capacitor G. Relay, made of Revere Corp. glass reed switch inserted in Guardian coil assembly No. 200-115a (with core removed) H. 6BY6 tube J. GSI0D Dekatron (Baird-Atomic) K. UPA 2 operational amplifier (Philbrick) M. Push button switch, normally open 478
EVOKED RESPONSE DETECTOR inserted in a solenoid. The relays are useable at d u r a t i o n s as short as 2 I / 2 msec, have very high open circuit resistance (greater t h a n 5 >~. 10 l~ ~)), a n d are comparatively economical. T h e solenoid o f each of the relays is in the plate circuit o f a separate 6BY6 tube (Fig. 1, H). T h e 6BY6 tube has two control grids, either one o f which can c u t off the tube a n d open its associated glass reed relay. T w o D e k a t r o n selector tubes (Fig. 1, J) (Baird-Atomic 1960) connected as a scale of 100 c o u n t e r provide a matrix control voltage to the 6BY6 grids. Each D e k a t r o n selector has 10 cathodes. T h e " u n i t s " D e k a t r o n is externally triggered at the 1/100 epoch rate a n d provides a repeating (~9 c o u n t activating each c a t h o d e in turn. F o r each 10 "'units" c o u n t s completed the " t e n s " D e k a t r o n advances one "10 s`, count. C r o s s b a r s connect the D e k a t r o n cathodes to the proper "'units" a n d " t e n s " grids o f the 6BY6 tubes, thus activating each tube in turn in the sequence 00 t h r o u g h 99; a circuit is provided to interrupt the trigger pulses a n d cause the D e k a t r o n s to stop at 00. 00 is the circuit provided with the s h u n t i n g resistor previously mentioned. Each time that the tenth 6BY6 tube is activated, a s t i m u l u s trigger occurs, thus fixing the time of occurrence of the s t i m u l u s in the epoch. This provides a short interval in the epoch before the stimulus, a n d gives a rough indication o f signal to noise ratio. Since each storage capacitor is charged in fixed sequence, c o m p o n e n t s of the input waveforms that have a fixed temporal relationship to the epoch s u m linearly. R a n d o m c o m p o n e n t s will also s u m , but only as the function of the square root of the n u m b e r o f epochs s u m m e d . Care should be taken to insure that no artifact locked to the epoch be introduced, as it will also s u m linearly. The circuit is convenient in operation in that the potentials on the storage capacitors m a y be viewed with each new epoch. T h e experimenter will observe early in an individual experiment if e n h a n c e m e n t is being obtained. If the input is disconnected the information stored will be retained a n d m a y be displayed m a n y h u n d r e d s of times without significant deterioration. If the D e k a t r o n s are not cycled the charge on the capacitors will be held for several h o u r s with less t h a n I per cent loss of charge. T h e epoch duration m a y be readily c h a n g e d a n d the epoch repetition rate can also be c h a n g e d or even randomized by an external trigger. Since the epoch m a y be initiated by a n external trigger, it is possible to average responses which have been tape recorded. At the conclusion of a given experiment the storage capacitors are discharged to zero by connecting a resistor (Fig. I, L) between the s u m m i n g point a n d the o u t p u t terminal o f the operational amplifier and allowing the Dekatrons to cycle several epochs. This discharging resistor is provided with a p u s h b u t t o n switch (Fig. 1, M). Sixty cycle artifact can be troublesome, particularly when the signal to noise ratio is u n u s u a l l y low. It has been f o u n d a d v a n t a g e o u s to initiate the triggering of each succeeding epoch at the nearest alternate 180 ° phase of the 60 cycle line. T h u s , the epoch repetition rate is the selected repetition rate plus the short delay necessary to trigger at the proper phase. This has proven to be quite an effective solution, suppressing both internal circuit 60 cycle pickup a n d the 60 cycle artifact s o m e t i m e s contained
479
in the EEG. However, the action is unlike that of a low pass filter since inherent 60 cycle c o m p o n e n t s o f the c o m plex E E G w a v e f o r m s are not attenuated. Fig. 2 shows the average o f 400 responses to a flash, recorded from scalp in m a n at an epoch repetition rate of 2 sec. T h e lower graph d e m o n s t r a t e s the response as
Fig. 2 Average o f 400 responses to photic stimulation, recorded between scalp electrodes in man. The curves were: obtained successively in the s a m e subject. The points are separated by 5 msec in the upper curve a n d 2.5 msec in the lower curve.
depicted by points 2.5 msec apart; in the upper graph a longer segment of the response is shown, the individual points being 5 msec apart. In cases requiring points to be separated by less than 2.5 msec, the responses m a y be tape recorded at high speed, with s u b s e q u e n t analysis of the tape record at low speed. The evoked response detector has been in operational use for several m o n t h s a n d has been reliable, requiring the replacement of one 6BY6 tube during this period. T h e use of the hermetically sealed glass reed switches entirely eliminates the need for cleaning of the switching mechanism. At the currents passed in the present application, the switch life is rated by the m a n u f a c t u r e r in billions of operations. T h e assembly of the detector is simplified by the fact that the m a j o r critical electronic c o m p o n e n l , the operational amplifier, can be purchased. F r o m the econ o m i c viewpoint, the c o m p o n e n t cost of the evoked response detector is s o m e w h a t less t h a n that of a s t a n d a r d E E G recorder or frequency analyzer. T h e detector., less auxiliary triggering circuits, can be housed in one 6-foot high, 19-inch wide s t a n d a r d relay rack. T h e a u t h o r s wish to express their appreciation to Drs Karl F r a n k a n d W a d e Marshall for their helpful suggestions during the course of development of the in-
480
R.R. COX AND E. V. EVARTS
strument, and also to Mrs. Edith Kessler for her assistance in obtaining recordings. REFERENCES BAmD-A'roMIC, Inc. Handbook of counting tubes. Cambridge, Mass., 1960. BARLOW, J. S. An electronic method for detecting evoked
responses of the brain and for reproducing their average waveforms. Electroenceph. clin. Neurophysiol., 1957, 9: 340-343. DAWSON, G. D. A summation technique for the detection of small evoked potentials. Electroenceph. clin. Neurophysiol., 1954, 6:65 84. JOHNSON, C. L. Analog computer techniques. McGrawHill, New York, 1956, p. 11.
Reference: Cox, R. R. and EVARTS,E. V. An evoked response detector. Electroenceph. c/in. Neurophysiol., 1961, 13: 478-48O.