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An electronic method for detecting evoked responses of the brain and for reproducing their average waveforms
TECHNICAL NOTES Editor for Western Hemisphere and Far East, J. KNOTT, Iowa City, Iowa, U.S.A. Editor for Europe and Middle East, tI. SHIPTON, Bristol, England AN ELECTRONIC OF T H E B R A I N A N D
M E T H O D FOR D E T E C T I N G E V O K E D R E S P O N S E S FOR R E P R O D U C I N G THEIR A V E R A G E W A V E F O R M S I JOHN S. BARLOW, M . D .
Neurophysiological Laboratory o[ the Neurological Service, Massachusetts General Hospital, Boston, and Research Laboratory of Electronics, 2 Massachusetts Institute o~ Technology, Cambridge, Mass. (Received f o r p u b l i c a t i o n : October 15, 1956) The detection b y v i s u a l m e a n s of cortical pot e n t i a l s evoked by s e n s o r y s t i m u l i is f r e q u e n t l y difficult in tile presence of E E G a c t i v i t y of equal or h i g h e r a m p l i t u d e in a n i m a l s if t h e a n e s t h e s i a level is light, a n d even more d i f f i c u l t in t h e h u m a n subject. T e c h n i q u e s b a s e d on the a v e r a g i n g of m a n y responses (such as D a w s o n ' s e l e c t r o m e c h a n i c a l a v e r a g e r (1953, 1954)) rely on the E E G w a v e s b e i n g unrelated to the s t i m u l u s a n d t h u s t e n d i n g to a v e r a g e out, w h e r e a s t h e p o t e n t i a l s of t h e specific response (following, as t h e y do, at a c o n s t a n t l a t e n c y ) will be a c c e n t u a t e d by t h e a v e r a g i n g process. The p r e s e n t note describes a n electronic m e t h o d for d e t e c t i n g such r e s p o n s e s a n d for r e p r o d u c i n g t h e i r a v e r a g e w a v e f o r m . T h e m a t h e m a t i c a l equivalence of a v e r a g i n g to t h e process of crosscorrelation of a s i g n a l with a repetitive b r i e f pulse h a s been shown by Lee (1950). A m e t h o d for erosseorrelation
l,til T0"" T§
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Fig. 1 Schema of gating of brain potentials with stimuli at successively larger delays (r) after the incidence of the stimuli (~-o), of b r a i n potenti'/ls Ires been described in t h i s J o u r n a l (B'lrlow a n d B r a z i e r 1954) ; a m o r e complete description of this i n s t r u m e n t a t i o n h a s since a p p e a r e d ( B a r low a n d B r o w n 1955). T h e electronic e q u i p m e n t employed for the p r e s e n t p u r p o s e utilizes the m a g n e t i c delay d r u m , i n t e g r a t o r , a n d t i m e r ( a u t o m a t i c recycling device) of the abovc correlator, b u t a g a t i n g a n d 1 Aided by a grant, No. B369 P h y s i o l ( 1 ) , from the V. S. P u b l i c H e a l t h S e r v i c e to Dr. M. A. B. B r a z i e r at the M a s s a chusetts General Hospital. 2 The work of this Laboratory ls supported in p a r t by the U.S. A ir F orce (Office of Scientific Research, Air Research and Development Command), the U.S. Army (Signal Corps), and the U.S. N a v y (Office of N a v a l R e s e a r c h ) .
s t o r a g e circuit is used i n s t e a d of the multiplier of t h a t instrmnent. S t i m u l i a n d b r a i n p o t e n t i M s are recorded simult a n e a u s l y on n m g n e t i e t a p e f r o m a e o n w m t i o n a l elect r o e n c e p h a l o g r a p h , and the aw,rages of evoked re sponses are obt'fined as the t a p e s are played back repeqtedly. By m e a n s of the m a g n e t i c d r m n , the s t i m u l u s a r t e f a c t s cnn be delayed in time ( r ) with respect to the b r a i n potentials, as i n d i c a t e d in f i g u r e 1. P e r a given s e t t i n g of the m a g n e t i c d r u m , i.e., •l given displqcement of stimuli in time, t h e ins t a n t a n e o u s voltage of the b r a i n 1)otentials correspondi n g tO each of the stimuli is not(,& A n a v e r a g e of all such s a m p l e s is o b t a i n e d by the Miller i n t e g r a t o r , a n d the result w r i t t e n out on "in E s t e r l i n e - A n g u s gr:,phic nfilliammeter. T h e s e t t i n g of tile m a g n e t i c d r u m is t h e n a n t o n m t i c a l l y c h a n g e d to a new delay, the tape played t h r o u g h a g a i n , '~ new "~verage ol)tained, a n d so on. The r e s u l t i n g ph)t of a v e r a g e s a g a i n s t tile delay r t h e n gives the a v e r a g e d evoke,1 response for the p a r t i c u l a r mmfl)er of stimuli chosen. A schematic "rod w a v e f o r m s of t h e g a t i n g a n d s t o r a g e u n i t ai)l)e:lr in f i g u r e 2. U t i l i z i n g ~he (lelayed stimuli as a t i m i n g signal, the g:ltillg a n d s t o r a g e unit s a m p l e s the b r a i n p o t e n t i a l s :it tile incidence of each delayed s t i m u l u s , a n d stores the samlde o b t a i n e d until t h e incidence of the n e x t delayed s t i n m l u s , at which time a new smni)le is taken, stored, a m l so on. Tile o u t p u t of the u n i t is t h u s in the f o r m of a s t e p - f u n c t i o n , the :lw'rage of which is o b t a i n e d by the Miller i n t e g r M o r . The g a t i n g , or s a m p l i n g , is accomplished by the diodes V7 a n d VS, a n d tile st'.)rage is accomplished by the condensers CI a n d (?2, in the following n m n n e r . T h e delayed s t i m u l u s pulse, a f t e r a m p l i f i c a t i o n (V1) t r i g g e r s a u n i v i b r a t o r ( V 2 ) , folh)wing which both positive a n d n e g a t i v e g a t i n g pulses of v e r y s h o r t d u r a t i o n are available at low i m p e d a n c e by m e a n s of a p h a s e i n v e r t e r (V3) a n d cathode followers ( V 6 A and V6B). Similarly, t h e b r a i n p o t e n t i a l s , a f t e r
[ 340 ]
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341
RESPONSES
e f f e c t of V6 (via VT) t h u s removed, t h e p o t e n t i a l s at A1 a n d A2 (fig. 2) become t h e s a m e ; V8 now acts as a shunt~ c o n n e c t i n g t h e c a t h o d e of V5 (via t h e 2 2 K r e s i s t o r s ) to t h e s t o r a g e condensers C1 a n d C2: VSA c o n d u c t s for n e g a t i v e c h a n g e s of t h e i)otential at the cathode of V5, a n d VSB conducts for llositive c h a n g e s of this potential. A t the end of tile g a t i n g pulse, the previous conditions are resumed, a n d the s t o r a g e circuit r e t a i n s t h e i n s t a n t a n e o u s voltage at the c'~thodc of V5 ~t the end of the last g a t i n g pulse u n t i l the incidence of the n e x t one. A t this time, tile new i n s t a n t a n e o u s v o l t a g e is stored, a n d so on. F r o m the f o r e g o i n g , it is seen t h a t V7 a n d V8 serve as a switch, c o n n e c t i n g tile cathode of V5 with
suitable a m p l i f i c a t i o n (V4) are available at low imp e d a n c e front a cathode follower ( V 5 ) . D u r i n g t h e i n t e r v a l s b e t w e e n g a t i n g pulses, the relative p o t e n t i a l s at the c a t h o d e s of V5 a n d V6 are such t h a t p o i n t s A1 a n d A2 ( f i g . 2) are e f f e c t i v e l y tied to t h e catho(les of VfiA a n d V6B, via the c o n d u c t i n g diodes VTA a n d V7B, respectively. The f l u c t u a t i n g v o l t a g e s at tile c;/tho(le of V5A "rod V5B a c c o r d i n g l y a p p e a r :dmost entirely "tcross the 2 2 K series resistors, R1 a n d R2, respectively. A t tile s a m e time, t h e p o t e n t i a l s at the electrodes of VSA a n d V8B are such t h a t tim t u b e is n o n c o n d u c t i n g : t h e cathode of V8B, b e i n g conn e t t e d to the relatively h i g h p o t e n t i a l a t t h e cathode of VTB, is at a h i g h e r p o t e n t i a l t h a n the plate of VSB; :lml the ldate of V8A, being connected to t h e
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relatively low p o t e n t i a l at t h e plate of V7A, is at a lower p o t e n t i a l t h a n the cathode of V8A. The s t o r a g e c o n d e n s e r s (C1 a n d C2) are t h u s isolated f r o m the f l u c t u a t i n g p o t e n t i a l s at the cathode of V5. A t the a p p e a r a n c e of a g a t i n g (i.e., delayed s t i m u l u s ) pulse, the p o t e n t i a l s a t t h e c a t h o d e s of V f A a n d V6B are reversed, so t h a t diodes V 7 A a n d V7B are no longer c o n d u c t i n g : t h e plate of V 7 B is now at a lower p o t e n t i a l t h a n t h e c a t h o d e of V7B, a n d the cathode of V 7 A is at a h i g h e r p o t e n t i a l t h a n the plate of V7A, (thc m a x i m u m s i g n a l o u t of V5 d u r i n g t h e g a t i n g pulse n o t b e i n g l a r g e e n o u g h to s t a r t c o n d u c t i o n in either s e c t i o n ) . W i t h t h e s h u n t i n g
the s t o r a g e circuit at the incidence of g a t i n g pulses, a n d i s o l a t i n g the s t o r a g e circuit f r o m the cathode of V5 in the absence of g a t i n g pulses. Tile s t o r a g e condensers C1 a n d C2 are a r r a n g e d so t h a t f e e d b a c k o b t a i n e d f r o m t h e i r c e n t e r - t a p to the cathode of V 9 A c o m p e n s a t e s , w i t h i n limits, f o r leakage of tlle stored p o t e n t i a l ( C h a n c e 1949). T h e o u t p u t s t e p - f u n c t i o n available at low i m p e d a m t e f r o m the cathode follower V9B, is f e d to tile Miller int e g r a t o r for o b t a i n i n g the a v e r a g e at tim p a r t i c u l a r delay f o r t h e series of stimuli. T h e result is recorded on a n E s t e r l i n e - A n g u s g r a p h i c m i l l i a m m e t e r (1 millia m p e r e full scale).
342
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J O H N S. BARLOW The clarification obtained by averaging a number m o c k responses of c o n s t a n t a m p l i t u d e a m i d an
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Fig. 3 Detection of a simulated evoked response by electronic averaging. Single responses are shown oll the left, averaged responses on the right. The simulated response is a single cycle of a 100 c/see, sine wave with a repetition rate of 5 per sec. The background activity consists of randomly fluctuating potentials of frequency range 20-400 c/see.
AI
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em Fig. 4 Responses from the lateral gyrus of a cat under light Nembutal anesthesia to stroboscopic stimulation at a rate of 1 per sec. (A) Average of 200 responses. Delay after the stimulus in milliseconds (steps of delay 0.5 mscc). (B) Sample of inked Irace, showing four individual responses. Calibration 200 #V.
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ELECTRONIC
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343
f i n a l l y t h e b a c k g r o u n d a c t i v i t y alone. On t h e r i g h t in the f i g u r e are s h o w n tile a v e r a g e of 180 m o c k responses of the sine wave alone, a n d of t h e sine wave m i x e d with t h e b a c k g r o u n d noise activity. The a v e r a g e of 180 r e s p o n s e s w i t h noise shows t h e sine wave m u c h more clearly t h a n it c a n be seen in the i n d i v i d u a l responses, in which the sine wave is a l m o s t comph'te/y obscured by the noise. The t h e a r e t i c a l g a i n in the signal to noise ratio, given by the S/luare root of the n u m b e r of responses a v e r a g e d (Lee 1950), is alq)r(:xinlately 13 (i.e.~/180) in the e x a m p l e given fll~ove.
tape. Details of these modifications will appear elsewhere.
The a v e r a g e of 210 responses to stroboscopic s t i m u l q t i o n at a rate of one per second, recorded f r o m the lateral g y r u s of "t eat u n d e r l i g h t N e m b u t a l anesth(,si'l, is shown in f i g u r e 4. I n this example, the steps of' delqy are 0.5 msee. F r o m tile f i g u r e , t h e l a t e n c y of onset of s u r f a c e i)ositivity is seen to be 17 rose:'., the peak of s u r f a c e l)ositivity occurs "it '22 reset, a n d the peak of s u r f a c e n e g a t i v i t y at 36 n/see. .\ b r i e f s:mq)Ie of t h e c o r r e s p o n d i n g ink-rec o r d i n g is also shown. Tlle clarity of t h e a v e r a g e d rosponse as c o m p a r e d with sin~'le resl)onses is evident t'von, the figure. Exanq)les of some results o b t a i n e d in clinical cases have previously been i)ublislled ( B r a zier :~ml B:trlow 1956).
BARLOW, J. S. a n d BRow~% R. M. A n a n a l o g correlator s y s t e m for b r a i n potentials. T e c h n i c a l Report 300, R e s e a r c h L a b o r a t o r y of Electronics. M a s s a c h u s e t t s I n s t i t u t e of Technology, 1955. BARLOV(, J. S. a n d I~RAZIEg, M. :~.. B. A note on a correlator for e l e e t r o e n e e p h a l o g r a p h i e work. EE(; Cli~t. Neurophysiol., 1984, 6: 321-325. BRAZIER, M. A. t~. a n d ][~ARLO'~V, J. S. Sonic applications of correlation a n a l y s i s to clinical p r o b l e m s in electroencephalogr'~phv. EEG Clin. Ncurophysiol., 1956, 8: 325-331. CHANCE, B. Ed. Wavcforms, Vol. 19, M I T Radiati.~n L a b o r a t o r y Seriec~, M c G r a w - H i l l Book Comp a n y , Inc., New York. 1949. DAWSOX, G. D. A u t o c o r r e l a t i o n a n d a u t o n m t i c integration. EEG Clin. Neurophysiol., Supp. No. 4, 26-37, 1953. I)AV¢SON, G. I). i s u m m a t i o n t e c h n i q u e for the detection of small evoked potentials. EEG Clb~. Ne~lrophysiol., 1954, 6: 65-84. LEF, Y. W. A p p l i c a t i o n of s t a t i s t i c a l m e t h o d s to e e m m u n i c a t i o n problems. T e c h n i c a l R e p o r t 181, R e s e a r c h L a b o r a t o r y of Electronics, M a s s a c h u s e t t s I n s t i t u t e of T e c h n o l a g y . 1950.
In the f u t u r e , it is p l a n n e d to s u b s t i t u t e a p h ' / n t a s t r o l l type of delay (Chance 1919) for the n m g n e t i c d r u m f o r d e l a y i n g the stimuli, a n d to use an endless loop of m a g n e t i c t a p e as all a l t e r n a t e to the iw(,sent p r o c e d u r e of repeated r e w i n d i n g of ~he
Reft:rcnee: I~ARLO\V, .]. S.
The a u t h o r is i n d e b t e d to Dr. l~Iary A. B. B r a z i e r of the M a s s a c h u s e t t s General H o s p i t a l , a n d to P r o f . W a l t e r A. R o s e n b l i t h of t h e M a s s a c h u s e t t s I n s t i t u t e of Technology, for their c o n t i n u i n g i n t e r e s t a n d encouragelnent. Ill the completion of the s y s t e m f o r correlation a n a l y s i s of b r a i n potentials, of which t h e e q u i p m e n t described here is a p a r t , t h e a u t h o r h a s enj o y e d close collaboration with Mr. Robert M. Brown, of the R e s e a r c h L a b ~ i ' a t o r y of Electronics, M. I. T. REFERENCES
A n electronic m e t h o d fo~" d e t e c t i n g evoked responses of the b r a i n a n d for reprod u e i n g t h e i r a v e r a g e wavefornls. EEG Clim Ne'urophy,wol., 1957, 9: 340-343.
M E T H O D FOR D E T E C T I N G E V O K E D R E S P O N S E S FOR R E P R O D U C I N G THEIR A V E R A G E W A V E F O R M S I JOHN S. BARLOW, M . D .
Neurophysiological Laboratory o[ the Neurological Service, Massachusetts General Hospital, Boston, and Research Laboratory of Electronics, 2 Massachusetts Institute o~ Technology, Cambridge, Mass. (Received f o r p u b l i c a t i o n : October 15, 1956) The detection b y v i s u a l m e a n s of cortical pot e n t i a l s evoked by s e n s o r y s t i m u l i is f r e q u e n t l y difficult in tile presence of E E G a c t i v i t y of equal or h i g h e r a m p l i t u d e in a n i m a l s if t h e a n e s t h e s i a level is light, a n d even more d i f f i c u l t in t h e h u m a n subject. T e c h n i q u e s b a s e d on the a v e r a g i n g of m a n y responses (such as D a w s o n ' s e l e c t r o m e c h a n i c a l a v e r a g e r (1953, 1954)) rely on the E E G w a v e s b e i n g unrelated to the s t i m u l u s a n d t h u s t e n d i n g to a v e r a g e out, w h e r e a s t h e p o t e n t i a l s of t h e specific response (following, as t h e y do, at a c o n s t a n t l a t e n c y ) will be a c c e n t u a t e d by t h e a v e r a g i n g process. The p r e s e n t note describes a n electronic m e t h o d for d e t e c t i n g such r e s p o n s e s a n d for r e p r o d u c i n g t h e i r a v e r a g e w a v e f o r m . T h e m a t h e m a t i c a l equivalence of a v e r a g i n g to t h e process of crosscorrelation of a s i g n a l with a repetitive b r i e f pulse h a s been shown by Lee (1950). A m e t h o d for erosseorrelation
l,til T0"" T§
lilis TO"" T 5
lllll TO'" T §
~',,', L T 0 "-" T t
Fig. 1 Schema of gating of brain potentials with stimuli at successively larger delays (r) after the incidence of the stimuli (~-o), of b r a i n potenti'/ls Ires been described in t h i s J o u r n a l (B'lrlow a n d B r a z i e r 1954) ; a m o r e complete description of this i n s t r u m e n t a t i o n h a s since a p p e a r e d ( B a r low a n d B r o w n 1955). T h e electronic e q u i p m e n t employed for the p r e s e n t p u r p o s e utilizes the m a g n e t i c delay d r u m , i n t e g r a t o r , a n d t i m e r ( a u t o m a t i c recycling device) of the abovc correlator, b u t a g a t i n g a n d 1 Aided by a grant, No. B369 P h y s i o l ( 1 ) , from the V. S. P u b l i c H e a l t h S e r v i c e to Dr. M. A. B. B r a z i e r at the M a s s a chusetts General Hospital. 2 The work of this Laboratory ls supported in p a r t by the U.S. A ir F orce (Office of Scientific Research, Air Research and Development Command), the U.S. Army (Signal Corps), and the U.S. N a v y (Office of N a v a l R e s e a r c h ) .
s t o r a g e circuit is used i n s t e a d of the multiplier of t h a t instrmnent. S t i m u l i a n d b r a i n p o t e n t i M s are recorded simult a n e a u s l y on n m g n e t i e t a p e f r o m a e o n w m t i o n a l elect r o e n c e p h a l o g r a p h , and the aw,rages of evoked re sponses are obt'fined as the t a p e s are played back repeqtedly. By m e a n s of the m a g n e t i c d r m n , the s t i m u l u s a r t e f a c t s cnn be delayed in time ( r ) with respect to the b r a i n potentials, as i n d i c a t e d in f i g u r e 1. P e r a given s e t t i n g of the m a g n e t i c d r u m , i.e., •l given displqcement of stimuli in time, t h e ins t a n t a n e o u s voltage of the b r a i n 1)otentials correspondi n g tO each of the stimuli is not(,& A n a v e r a g e of all such s a m p l e s is o b t a i n e d by the Miller i n t e g r a t o r , a n d the result w r i t t e n out on "in E s t e r l i n e - A n g u s gr:,phic nfilliammeter. T h e s e t t i n g of tile m a g n e t i c d r u m is t h e n a n t o n m t i c a l l y c h a n g e d to a new delay, the tape played t h r o u g h a g a i n , '~ new "~verage ol)tained, a n d so on. The r e s u l t i n g ph)t of a v e r a g e s a g a i n s t tile delay r t h e n gives the a v e r a g e d evoke,1 response for the p a r t i c u l a r mmfl)er of stimuli chosen. A schematic "rod w a v e f o r m s of t h e g a t i n g a n d s t o r a g e u n i t ai)l)e:lr in f i g u r e 2. U t i l i z i n g ~he (lelayed stimuli as a t i m i n g signal, the g:ltillg a n d s t o r a g e unit s a m p l e s the b r a i n p o t e n t i a l s :it tile incidence of each delayed s t i m u l u s , a n d stores the samlde o b t a i n e d until t h e incidence of the n e x t delayed s t i n m l u s , at which time a new smni)le is taken, stored, a m l so on. Tile o u t p u t of the u n i t is t h u s in the f o r m of a s t e p - f u n c t i o n , the :lw'rage of which is o b t a i n e d by the Miller i n t e g r M o r . The g a t i n g , or s a m p l i n g , is accomplished by the diodes V7 a n d VS, a n d tile st'.)rage is accomplished by the condensers CI a n d (?2, in the following n m n n e r . T h e delayed s t i m u l u s pulse, a f t e r a m p l i f i c a t i o n (V1) t r i g g e r s a u n i v i b r a t o r ( V 2 ) , folh)wing which both positive a n d n e g a t i v e g a t i n g pulses of v e r y s h o r t d u r a t i o n are available at low i m p e d a n c e by m e a n s of a p h a s e i n v e r t e r (V3) a n d cathode followers ( V 6 A and V6B). Similarly, t h e b r a i n p o t e n t i a l s , a f t e r
[ 340 ]
ELECTRONIC
AVERAGING
OF EVOKED
341
RESPONSES
e f f e c t of V6 (via VT) t h u s removed, t h e p o t e n t i a l s at A1 a n d A2 (fig. 2) become t h e s a m e ; V8 now acts as a shunt~ c o n n e c t i n g t h e c a t h o d e of V5 (via t h e 2 2 K r e s i s t o r s ) to t h e s t o r a g e condensers C1 a n d C2: VSA c o n d u c t s for n e g a t i v e c h a n g e s of t h e i)otential at the cathode of V5, a n d VSB conducts for llositive c h a n g e s of this potential. A t the end of tile g a t i n g pulse, the previous conditions are resumed, a n d the s t o r a g e circuit r e t a i n s t h e i n s t a n t a n e o u s voltage at the c'~thodc of V5 ~t the end of the last g a t i n g pulse u n t i l the incidence of the n e x t one. A t this time, tile new i n s t a n t a n e o u s v o l t a g e is stored, a n d so on. F r o m the f o r e g o i n g , it is seen t h a t V7 a n d V8 serve as a switch, c o n n e c t i n g tile cathode of V5 with
suitable a m p l i f i c a t i o n (V4) are available at low imp e d a n c e front a cathode follower ( V 5 ) . D u r i n g t h e i n t e r v a l s b e t w e e n g a t i n g pulses, the relative p o t e n t i a l s at the c a t h o d e s of V5 a n d V6 are such t h a t p o i n t s A1 a n d A2 ( f i g . 2) are e f f e c t i v e l y tied to t h e catho(les of VfiA a n d V6B, via the c o n d u c t i n g diodes VTA a n d V7B, respectively. The f l u c t u a t i n g v o l t a g e s at tile c;/tho(le of V5A "rod V5B a c c o r d i n g l y a p p e a r :dmost entirely "tcross the 2 2 K series resistors, R1 a n d R2, respectively. A t tile s a m e time, t h e p o t e n t i a l s at the electrodes of VSA a n d V8B are such t h a t tim t u b e is n o n c o n d u c t i n g : t h e cathode of V8B, b e i n g conn e t t e d to the relatively h i g h p o t e n t i a l a t t h e cathode of VTB, is at a h i g h e r p o t e n t i a l t h a n the plate of VSB; :lml the ldate of V8A, being connected to t h e
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relatively low p o t e n t i a l at t h e plate of V7A, is at a lower p o t e n t i a l t h a n the cathode of V8A. The s t o r a g e c o n d e n s e r s (C1 a n d C2) are t h u s isolated f r o m the f l u c t u a t i n g p o t e n t i a l s at the cathode of V5. A t the a p p e a r a n c e of a g a t i n g (i.e., delayed s t i m u l u s ) pulse, the p o t e n t i a l s a t t h e c a t h o d e s of V f A a n d V6B are reversed, so t h a t diodes V 7 A a n d V7B are no longer c o n d u c t i n g : t h e plate of V 7 B is now at a lower p o t e n t i a l t h a n t h e c a t h o d e of V7B, a n d the cathode of V 7 A is at a h i g h e r p o t e n t i a l t h a n the plate of V7A, (thc m a x i m u m s i g n a l o u t of V5 d u r i n g t h e g a t i n g pulse n o t b e i n g l a r g e e n o u g h to s t a r t c o n d u c t i o n in either s e c t i o n ) . W i t h t h e s h u n t i n g
the s t o r a g e circuit at the incidence of g a t i n g pulses, a n d i s o l a t i n g the s t o r a g e circuit f r o m the cathode of V5 in the absence of g a t i n g pulses. Tile s t o r a g e condensers C1 a n d C2 are a r r a n g e d so t h a t f e e d b a c k o b t a i n e d f r o m t h e i r c e n t e r - t a p to the cathode of V 9 A c o m p e n s a t e s , w i t h i n limits, f o r leakage of tlle stored p o t e n t i a l ( C h a n c e 1949). T h e o u t p u t s t e p - f u n c t i o n available at low i m p e d a m t e f r o m the cathode follower V9B, is f e d to tile Miller int e g r a t o r for o b t a i n i n g the a v e r a g e at tim p a r t i c u l a r delay f o r t h e series of stimuli. T h e result is recorded on a n E s t e r l i n e - A n g u s g r a p h i c m i l l i a m m e t e r (1 millia m p e r e full scale).
342
of
J O H N S. BARLOW The clarification obtained by averaging a number m o c k responses of c o n s t a n t a m p l i t u d e a m i d an
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Fig. 3 Detection of a simulated evoked response by electronic averaging. Single responses are shown oll the left, averaged responses on the right. The simulated response is a single cycle of a 100 c/see, sine wave with a repetition rate of 5 per sec. The background activity consists of randomly fluctuating potentials of frequency range 20-400 c/see.
AI
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em Fig. 4 Responses from the lateral gyrus of a cat under light Nembutal anesthesia to stroboscopic stimulation at a rate of 1 per sec. (A) Average of 200 responses. Delay after the stimulus in milliseconds (steps of delay 0.5 mscc). (B) Sample of inked Irace, showing four individual responses. Calibration 200 #V.
and
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ELECTRONIC
AVERAGING
OF E V O K E D
RESPONSES
343
f i n a l l y t h e b a c k g r o u n d a c t i v i t y alone. On t h e r i g h t in the f i g u r e are s h o w n tile a v e r a g e of 180 m o c k responses of the sine wave alone, a n d of t h e sine wave m i x e d with t h e b a c k g r o u n d noise activity. The a v e r a g e of 180 r e s p o n s e s w i t h noise shows t h e sine wave m u c h more clearly t h a n it c a n be seen in the i n d i v i d u a l responses, in which the sine wave is a l m o s t comph'te/y obscured by the noise. The t h e a r e t i c a l g a i n in the signal to noise ratio, given by the S/luare root of the n u m b e r of responses a v e r a g e d (Lee 1950), is alq)r(:xinlately 13 (i.e.~/180) in the e x a m p l e given fll~ove.
tape. Details of these modifications will appear elsewhere.
The a v e r a g e of 210 responses to stroboscopic s t i m u l q t i o n at a rate of one per second, recorded f r o m the lateral g y r u s of "t eat u n d e r l i g h t N e m b u t a l anesth(,si'l, is shown in f i g u r e 4. I n this example, the steps of' delqy are 0.5 msee. F r o m tile f i g u r e , t h e l a t e n c y of onset of s u r f a c e i)ositivity is seen to be 17 rose:'., the peak of s u r f a c e l)ositivity occurs "it '22 reset, a n d the peak of s u r f a c e n e g a t i v i t y at 36 n/see. .\ b r i e f s:mq)Ie of t h e c o r r e s p o n d i n g ink-rec o r d i n g is also shown. Tlle clarity of t h e a v e r a g e d rosponse as c o m p a r e d with sin~'le resl)onses is evident t'von, the figure. Exanq)les of some results o b t a i n e d in clinical cases have previously been i)ublislled ( B r a zier :~ml B:trlow 1956).
BARLOW, J. S. a n d BRow~% R. M. A n a n a l o g correlator s y s t e m for b r a i n potentials. T e c h n i c a l Report 300, R e s e a r c h L a b o r a t o r y of Electronics. M a s s a c h u s e t t s I n s t i t u t e of Technology, 1955. BARLOV(, J. S. a n d I~RAZIEg, M. :~.. B. A note on a correlator for e l e e t r o e n e e p h a l o g r a p h i e work. EE(; Cli~t. Neurophysiol., 1984, 6: 321-325. BRAZIER, M. A. t~. a n d ][~ARLO'~V, J. S. Sonic applications of correlation a n a l y s i s to clinical p r o b l e m s in electroencephalogr'~phv. EEG Clin. Ncurophysiol., 1956, 8: 325-331. CHANCE, B. Ed. Wavcforms, Vol. 19, M I T Radiati.~n L a b o r a t o r y Seriec~, M c G r a w - H i l l Book Comp a n y , Inc., New York. 1949. DAWSOX, G. D. A u t o c o r r e l a t i o n a n d a u t o n m t i c integration. EEG Clin. Neurophysiol., Supp. No. 4, 26-37, 1953. I)AV¢SON, G. I). i s u m m a t i o n t e c h n i q u e for the detection of small evoked potentials. EEG Clb~. Ne~lrophysiol., 1954, 6: 65-84. LEF, Y. W. A p p l i c a t i o n of s t a t i s t i c a l m e t h o d s to e e m m u n i c a t i o n problems. T e c h n i c a l R e p o r t 181, R e s e a r c h L a b o r a t o r y of Electronics, M a s s a c h u s e t t s I n s t i t u t e of T e c h n o l a g y . 1950.
In the f u t u r e , it is p l a n n e d to s u b s t i t u t e a p h ' / n t a s t r o l l type of delay (Chance 1919) for the n m g n e t i c d r u m f o r d e l a y i n g the stimuli, a n d to use an endless loop of m a g n e t i c t a p e as all a l t e r n a t e to the iw(,sent p r o c e d u r e of repeated r e w i n d i n g of ~he
Reft:rcnee: I~ARLO\V, .]. S.
The a u t h o r is i n d e b t e d to Dr. l~Iary A. B. B r a z i e r of the M a s s a c h u s e t t s General H o s p i t a l , a n d to P r o f . W a l t e r A. R o s e n b l i t h of t h e M a s s a c h u s e t t s I n s t i t u t e of Technology, for their c o n t i n u i n g i n t e r e s t a n d encouragelnent. Ill the completion of the s y s t e m f o r correlation a n a l y s i s of b r a i n potentials, of which t h e e q u i p m e n t described here is a p a r t , t h e a u t h o r h a s enj o y e d close collaboration with Mr. Robert M. Brown, of the R e s e a r c h L a b ~ i ' a t o r y of Electronics, M. I. T. REFERENCES
A n electronic m e t h o d fo~" d e t e c t i n g evoked responses of the b r a i n a n d for reprod u e i n g t h e i r a v e r a g e wavefornls. EEG Clim Ne'urophy,wol., 1957, 9: 340-343.