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A new instrument for the summation of evoked responses from the nervous system
T E C H N I C A L NOTES E d i t e d by H. S H I P T O N , A. M. B R [ T , I.R.E. and F. B U C H T H A L , M.D.
A NEW
INSTRUMENT FOR THE SUMMATION OF E V O K E D F R O M T H E N E R V O U S SYSTEM 1
RESPONSES
BtJRTON S. R o s s ~ a , Ph.D., Tgv~i-r ALL~SON, M.A., ELLIOT SWANSON, B.S.E.E. and WILLI~M R. GoeF, Ph.D.
West Haven Veterans Administration Hospital, West Haven, Yale University School of Medicine, N e w Haven, Connecticut and A m p e x Corporation, Montclair, New Jersey (Received for publication: Mt~rch 10, 1960) Algebraic s u m m a t i o n of successive neuroelectric responses evoked by external stimuli yields an average response f o r a given sample size. Successive summ a t i o n also u n m a s k s small evoked potentials hidden in the " n o i s e " of tile E E G ( B a r l o w 1957; Communication Biophysics Group and Siebert 1959; Daw-
tients. This p a p e r describes a new i n s t r u m e n t which automatically s u m m a t e s samples of up to 125 responses. The i n s t r u m e n t is designated E R A (Evoked Response A d d e r ) . F i g u r e 1 shows the block d i a g r a m of ERA. The c o m p u t e r essentially consists of commercial instru-
RI2
1
g~ WUP-
WLOP
A:~ ]2
.___V
(GRASS$40~}
="
TOFL.IP-~P B
i~V-n
(TEKTRONIX IGI)
i
•
P
f- ,N Fig.
1
Block diagram of ERA. 83 is non-locking; $6 has a neutral position. Relay F is Advance TS/¢;C/10~00: other relays are Advance TS/3C/10800. R4. R5, R10, and R12 are Borg Helipots. All resistors are + 1 per eent. son 1954). I n this way, one can electrophysiologically m e a s u r e sensory f u n c t i o n s in normal h u m a n s or pa1 This work was supported by Grant M-1530 from tho National Institute of Mental Heaitll.
ments, whicti greatly simi)lifies m:tintcn:/l~ec :lnd duplication. E R A presently has two independent d a t , channels; ttle f i g u r e shows j u s t one. An Ampex fourtrack FL-10O loop tape recorder provides memory
[ 745 ]
746
e.s.
t t O S N E R , T. A L L I S O N , E. S W A N S O N and W. R. G O F F
and repetitive t r i g g e r i n g . A P h i l b r i e k U P A - 2 a n a l o g a m p l i f i e r p e r f o r m s s u m m a t i o n . The c o m p n t e r acc o m m o d a t e s any s t i m u l a t i n g devices which accept an external t r i g g e r i n g pulse. To operate E R A , the FL-100 is placed in the " r e c o r d " mode. $9 is closed and all switches except $5 assmne the positions shown in the figure. The l)rc qmldifier , $5, and the m a i n amplifier determine the total gaill applied to each evoked response. M o m e n t a r y depression of s t a r t i n g switch $3 initiates vi:l waveform gener'~tor I a 50 V. positive t r i g g e r pulse from pulse g e n e r a t o r I. $2 is then closed. The t r i g g e r pulse t r i p s tile s t i m u l a t o r and waveform generator l l ; this pulse is silnultaneously directly recorded on tape a f t e r d r o p p i n g across R3 to 4 V. R3 prevents overh)ading of the direct record amplifier. Waveform generator I I operates gate relay G for a pre-set duration slightly longer t h a n t h a t of the ,euroelectri(- activity under study. The response evoked from the sut)jeet thus is amplified, p'lssed through the adder with no f u r t h e r change in gain~ :rod recorded t h r o u g h frequency modul:ltion on tape. The recorded t r i g g e r sigual and the first response then travel around the loop of tape to the reproduce heads. / ' p o n repro(luction, the t r i g g e r signal trips waveform Kelwrator l, initiating a new t r i g g e r pulse from lmlse generMor I. The f i r s t response is demodulated by the F M reproduce ~lml)lifier , which itwidentally del;lys it about 65 btsee, with rvspect to lhe rel,ro(hwed t r i g g e r sign:d. To a d j u s t f o r this iueid(qmd delay, the debly control on pulse g e n e r a t o r 1 is met so that the latter fires al)out 65 #see. a f t e r the s t a r t of the sawtooth o u t p u t f r o m w a v e f o r m ~,ener'~tor I. The reproduced response all(l the second ]Ji'W r e s ] l o l l s ( ' , t|leref()re~ reach the a(Ider ill exaetly the same tenlporal relatiollshi I) to the second t r i g g e r pulse and to the stimulus. The sum of two responses, :llong with the fresh t r i g g e r sigmd, is recorded on tape, reproduced. "aut added to the next r O S l ) O l l S e . This process c(mtimws until the desired samph' of r ( ' s l ) O l l S ( ' S h a s b e e n summated. The erase liP.ill (Ill the I:l,-l(}(I insures t h a t the record head always sees clean t:tpe. The length of tape between record and rei/,'oduce heuds may range from about 5 to 50 ft. This length (letermilles inter-stimulus time, which mqy vary between about I nna 10 see) T h r o u g h rela.v F, the flip-flop compensMes for the fact that the adder inverts the p o l a r i t y of any input. Opening of G pulses the flip-flop, which holds F operated on even-numbered trials. On these trials, F makes the negative input of the pre-amidifier ;a.tive. On odd mm, l)ered tri'ds, the positive input I We use S(.oteh No. 189 Instrumentation Tape, whieh requires a 27 ke. center carrier in the FM ehannels. Dr, J. S, Barlow kin/lly informed us about this mylar-sandwich tape, whi('h /'all withstand thousands of passes wiillout (leterioration.
is active. The s u m m a t e d responses at the o u t p u t of the adder thus reverse polarity on successive tritds. A f t e r ~t responses have been added, the tape recorder may be stopped. The s u m m a t e d Saml)le then may be reproduced as often as desired for (letailed study, e.g.. at d i f f e r e n t oscilloscopie speeds. Alternatively, the outlmt of the adder may be
Fig. 2 AI: into
OIItpllt l ' i of
o f a d d e r w h e n 50 Illset', fiffllre 1, Differentiation
pOS]~iVt! lille to
p u l s e is f e d 111' n e t w m ' k s
lu'eee(ling tape rerorder. A2: Same signal as in A I s~amped by random noise. A',I: ()tltpll[ Of adder after sllllllnation of 20 signals like that of A2. A4: Output of adder after summation of 40 su('h siKtlals. Naell nlajor (livisinn o n Jrr/Ith~lllc is 1 era. I'alibrations: 10 msec/em, for all tra(.es; A1 and A2, 0.5 mV/cm. : A3 and A4. 25 mV/em. BI: SuperimpositioIl o f 20 r e s p o n s e s r e c o r d e ( l b e t w e e n r i g h t s e a l p a n d r i g | i t eltl. flf [iHIna n s u b j e c t upon 5(1 u a l ' e - u III'(' e l e l * t F o e n l a n e o t l S stimulation of l e f t i n d e x f i n g e r . Positiviiy U l ) ~ a r d in t h i s illl(t a l l s u ( , c e e d i n ~ t r a c e s . Note barely detectable evoked a(.tivity. 112: ( ) u t l l u t o f a d d e r a f t e r s u m n l a t i ( m o f 20 s u c h resI)onses. I{:~ : o t l t p u | Of a ( h / e r a f t e r s t l n n l l a t i o n o f 40 r c sla)nses, B 4 : NaIIlO ilb; B~I ill fasteI" s w e e p r a t e to s h o w "classical" evoked lmtelltial, i ' M i b r a t i o n s : 1~1 t h r i ) u g h 113, 50 n l s c e / e l o . : B4, 10 m s e e , ' c n l . : P,1, 2.5 ]IV c,n. : 1/2 a l n l 113, 25 ¢ t V / c m . ; B 4 , 10 /~V.'em.
~t~lll. The total ~ain applied t'.) each response frmn the subject m u s t result in a response of :Ll,out 12 inV. peak going into the adder. This keeps tilt, data out of the noise of the FM system itself. Since the FM record amplifier begins over-h)a,ling fro' iJqmts
AUTOMATIC SUMMATION OF EVOKED RESPONSES g r e a t e r t h a n 1.4 V. peak, sanlple size caimot exceed about 125. T h e g a i n of the F M reproduce a m p l i f i e r is set at 0.5, which keeps the f r e q u e n c y response of t h e FL-100 f l a t b e y o n d 1 kc. E x c l u d i n g the T e k t r o n i x a m p l i f i e r s , the f r e q u e n c y response of E R A is f l a t f r o m DC to 5 kc. "~nd is down 3 db at 9 kc. C1 a n d C2 block DC d r i f t at the o u t p u t s of the T e k t r o n i x amplifiers. A n a s y m m e t r y in the F M f r e q u e n c y - d e v i a t i o n vs.-voltage curve n e c e s s i t a t e s the two v a r i a b l e r e s i s t o r s R4 a n d R5 before R7. The flip-flop reduces distortion due to this "tsymmetry. O t h e r n o n - l i n e a r i t i e s in the F M s y s t e m produce slight c h a n g e s in g a i n for i u c o m i n g s i g n a l s of d i f f e r e n t a m p l i t u d e s . These nonlinearities cause less t h ' u l 2 per cent error when R4, R5, a n d R10 are a d j u s t e d to yield u n i t y g a i n f o r a c ' d i b r a t i n g sine wave of ,).~i V. g o i n g into the "Mder.
747
$4 a n d $8 respectively i n t r o d u c e c a l i b r a t i n g s i g n a l s to the m a i n a m p l i f i e r a n d the F M record amplifier. R12 controls t h e a m p l i t u d e of these signals. $6 p e r m i t s choice of a n AC or DC signal, while $7 controls p o l a r i t y of the latter. DC c a l i b r a t i n g s i g n a l s :/re needed to ,qlign the F M record "unplifier. REFERENCI~;S
BARLOW, ,l. S. A n electronic m e t h o d for d e t e c t i n g evoked responses of the b r a i n a n d for rel)roducing their a v e r a g e w a v e f o r m . EEG Cliff. Neltrophysiol., 1957, 9: 340-34"L (~OMMUNICATIONS BIOPHYSICS GROUP alld SIEBERT, W . M . Processing Neuroeh+ctric Data. R e s e a r c h L a b o r a t o r y of Electronics, Mass. I n s t i t u t e of Technology, Technical R e p o r t 351. C a m b r i d g e , Technology P r e s s , 1959. DAWSON, G. D. A 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 Clin. Ne~trophysiol., 1954, 6: (;5-84.
Reference: ROSNER, B. S., ALLISOIq, T.~ SWANSON, E. a n d GOFF, W. R. A. new i n s t r u m e n t for t h e summ a t i o n of evoked responses f r o m tile n e r v o u s system. EEG Clin. Neurophysiol., 1960, 12: 745-747.
A NEW
INSTRUMENT FOR THE SUMMATION OF E V O K E D F R O M T H E N E R V O U S SYSTEM 1
RESPONSES
BtJRTON S. R o s s ~ a , Ph.D., Tgv~i-r ALL~SON, M.A., ELLIOT SWANSON, B.S.E.E. and WILLI~M R. GoeF, Ph.D.
West Haven Veterans Administration Hospital, West Haven, Yale University School of Medicine, N e w Haven, Connecticut and A m p e x Corporation, Montclair, New Jersey (Received for publication: Mt~rch 10, 1960) Algebraic s u m m a t i o n of successive neuroelectric responses evoked by external stimuli yields an average response f o r a given sample size. Successive summ a t i o n also u n m a s k s small evoked potentials hidden in the " n o i s e " of tile E E G ( B a r l o w 1957; Communication Biophysics Group and Siebert 1959; Daw-
tients. This p a p e r describes a new i n s t r u m e n t which automatically s u m m a t e s samples of up to 125 responses. The i n s t r u m e n t is designated E R A (Evoked Response A d d e r ) . F i g u r e 1 shows the block d i a g r a m of ERA. The c o m p u t e r essentially consists of commercial instru-
RI2
1
g~ WUP-
WLOP
A:~ ]2
.___V
(GRASS$40~}
="
TOFL.IP-~P B
i~V-n
(TEKTRONIX IGI)
i
•
P
f- ,N Fig.
1
Block diagram of ERA. 83 is non-locking; $6 has a neutral position. Relay F is Advance TS/¢;C/10~00: other relays are Advance TS/3C/10800. R4. R5, R10, and R12 are Borg Helipots. All resistors are + 1 per eent. son 1954). I n this way, one can electrophysiologically m e a s u r e sensory f u n c t i o n s in normal h u m a n s or pa1 This work was supported by Grant M-1530 from tho National Institute of Mental Heaitll.
ments, whicti greatly simi)lifies m:tintcn:/l~ec :lnd duplication. E R A presently has two independent d a t , channels; ttle f i g u r e shows j u s t one. An Ampex fourtrack FL-10O loop tape recorder provides memory
[ 745 ]
746
e.s.
t t O S N E R , T. A L L I S O N , E. S W A N S O N and W. R. G O F F
and repetitive t r i g g e r i n g . A P h i l b r i e k U P A - 2 a n a l o g a m p l i f i e r p e r f o r m s s u m m a t i o n . The c o m p n t e r acc o m m o d a t e s any s t i m u l a t i n g devices which accept an external t r i g g e r i n g pulse. To operate E R A , the FL-100 is placed in the " r e c o r d " mode. $9 is closed and all switches except $5 assmne the positions shown in the figure. The l)rc qmldifier , $5, and the m a i n amplifier determine the total gaill applied to each evoked response. M o m e n t a r y depression of s t a r t i n g switch $3 initiates vi:l waveform gener'~tor I a 50 V. positive t r i g g e r pulse from pulse g e n e r a t o r I. $2 is then closed. The t r i g g e r pulse t r i p s tile s t i m u l a t o r and waveform generator l l ; this pulse is silnultaneously directly recorded on tape a f t e r d r o p p i n g across R3 to 4 V. R3 prevents overh)ading of the direct record amplifier. Waveform generator I I operates gate relay G for a pre-set duration slightly longer t h a n t h a t of the ,euroelectri(- activity under study. The response evoked from the sut)jeet thus is amplified, p'lssed through the adder with no f u r t h e r change in gain~ :rod recorded t h r o u g h frequency modul:ltion on tape. The recorded t r i g g e r sigual and the first response then travel around the loop of tape to the reproduce heads. / ' p o n repro(luction, the t r i g g e r signal trips waveform Kelwrator l, initiating a new t r i g g e r pulse from lmlse generMor I. The f i r s t response is demodulated by the F M reproduce ~lml)lifier , which itwidentally del;lys it about 65 btsee, with rvspect to lhe rel,ro(hwed t r i g g e r sign:d. To a d j u s t f o r this iueid(qmd delay, the debly control on pulse g e n e r a t o r 1 is met so that the latter fires al)out 65 #see. a f t e r the s t a r t of the sawtooth o u t p u t f r o m w a v e f o r m ~,ener'~tor I. The reproduced response all(l the second ]Ji'W r e s ] l o l l s ( ' , t|leref()re~ reach the a(Ider ill exaetly the same tenlporal relatiollshi I) to the second t r i g g e r pulse and to the stimulus. The sum of two responses, :llong with the fresh t r i g g e r sigmd, is recorded on tape, reproduced. "aut added to the next r O S l ) O l l S e . This process c(mtimws until the desired samph' of r ( ' s l ) O l l S ( ' S h a s b e e n summated. The erase liP.ill (Ill the I:l,-l(}(I insures t h a t the record head always sees clean t:tpe. The length of tape between record and rei/,'oduce heuds may range from about 5 to 50 ft. This length (letermilles inter-stimulus time, which mqy vary between about I nna 10 see) T h r o u g h rela.v F, the flip-flop compensMes for the fact that the adder inverts the p o l a r i t y of any input. Opening of G pulses the flip-flop, which holds F operated on even-numbered trials. On these trials, F makes the negative input of the pre-amidifier ;a.tive. On odd mm, l)ered tri'ds, the positive input I We use S(.oteh No. 189 Instrumentation Tape, whieh requires a 27 ke. center carrier in the FM ehannels. Dr, J. S, Barlow kin/lly informed us about this mylar-sandwich tape, whi('h /'all withstand thousands of passes wiillout (leterioration.
is active. The s u m m a t e d responses at the o u t p u t of the adder thus reverse polarity on successive tritds. A f t e r ~t responses have been added, the tape recorder may be stopped. The s u m m a t e d Saml)le then may be reproduced as often as desired for (letailed study, e.g.. at d i f f e r e n t oscilloscopie speeds. Alternatively, the outlmt of the adder may be
Fig. 2 AI: into
OIItpllt l ' i of
o f a d d e r w h e n 50 Illset', fiffllre 1, Differentiation
pOS]~iVt! lille to
p u l s e is f e d 111' n e t w m ' k s
lu'eee(ling tape rerorder. A2: Same signal as in A I s~amped by random noise. A',I: ()tltpll[ Of adder after sllllllnation of 20 signals like that of A2. A4: Output of adder after summation of 40 su('h siKtlals. Naell nlajor (livisinn o n Jrr/Ith~lllc is 1 era. I'alibrations: 10 msec/em, for all tra(.es; A1 and A2, 0.5 mV/cm. : A3 and A4. 25 mV/em. BI: SuperimpositioIl o f 20 r e s p o n s e s r e c o r d e ( l b e t w e e n r i g h t s e a l p a n d r i g | i t eltl. flf [iHIna n s u b j e c t upon 5(1 u a l ' e - u III'(' e l e l * t F o e n l a n e o t l S stimulation of l e f t i n d e x f i n g e r . Positiviiy U l ) ~ a r d in t h i s illl(t a l l s u ( , c e e d i n ~ t r a c e s . Note barely detectable evoked a(.tivity. 112: ( ) u t l l u t o f a d d e r a f t e r s u m n l a t i ( m o f 20 s u c h resI)onses. I{:~ : o t l t p u | Of a ( h / e r a f t e r s t l n n l l a t i o n o f 40 r c sla)nses, B 4 : NaIIlO ilb; B~I ill fasteI" s w e e p r a t e to s h o w "classical" evoked lmtelltial, i ' M i b r a t i o n s : 1~1 t h r i ) u g h 113, 50 n l s c e / e l o . : B4, 10 m s e e , ' c n l . : P,1, 2.5 ]IV c,n. : 1/2 a l n l 113, 25 ¢ t V / c m . ; B 4 , 10 /~V.'em.
~t~lll. The total ~ain applied t'.) each response frmn the subject m u s t result in a response of :Ll,out 12 inV. peak going into the adder. This keeps tilt, data out of the noise of the FM system itself. Since the FM record amplifier begins over-h)a,ling fro' iJqmts
AUTOMATIC SUMMATION OF EVOKED RESPONSES g r e a t e r t h a n 1.4 V. peak, sanlple size caimot exceed about 125. T h e g a i n of the F M reproduce a m p l i f i e r is set at 0.5, which keeps the f r e q u e n c y response of t h e FL-100 f l a t b e y o n d 1 kc. E x c l u d i n g the T e k t r o n i x a m p l i f i e r s , the f r e q u e n c y response of E R A is f l a t f r o m DC to 5 kc. "~nd is down 3 db at 9 kc. C1 a n d C2 block DC d r i f t at the o u t p u t s of the T e k t r o n i x amplifiers. A n a s y m m e t r y in the F M f r e q u e n c y - d e v i a t i o n vs.-voltage curve n e c e s s i t a t e s the two v a r i a b l e r e s i s t o r s R4 a n d R5 before R7. The flip-flop reduces distortion due to this "tsymmetry. O t h e r n o n - l i n e a r i t i e s in the F M s y s t e m produce slight c h a n g e s in g a i n for i u c o m i n g s i g n a l s of d i f f e r e n t a m p l i t u d e s . These nonlinearities cause less t h ' u l 2 per cent error when R4, R5, a n d R10 are a d j u s t e d to yield u n i t y g a i n f o r a c ' d i b r a t i n g sine wave of ,).~i V. g o i n g into the "Mder.
747
$4 a n d $8 respectively i n t r o d u c e c a l i b r a t i n g s i g n a l s to the m a i n a m p l i f i e r a n d the F M record amplifier. R12 controls t h e a m p l i t u d e of these signals. $6 p e r m i t s choice of a n AC or DC signal, while $7 controls p o l a r i t y of the latter. DC c a l i b r a t i n g s i g n a l s :/re needed to ,qlign the F M record "unplifier. REFERENCI~;S
BARLOW, ,l. S. A n electronic m e t h o d for d e t e c t i n g evoked responses of the b r a i n a n d for rel)roducing their a v e r a g e w a v e f o r m . EEG Cliff. Neltrophysiol., 1957, 9: 340-34"L (~OMMUNICATIONS BIOPHYSICS GROUP alld SIEBERT, W . M . Processing Neuroeh+ctric Data. R e s e a r c h L a b o r a t o r y of Electronics, Mass. I n s t i t u t e of Technology, Technical R e p o r t 351. C a m b r i d g e , Technology P r e s s , 1959. DAWSON, G. D. A 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 Clin. Ne~trophysiol., 1954, 6: (;5-84.
Reference: ROSNER, B. S., ALLISOIq, T.~ SWANSON, E. a n d GOFF, W. R. A. new i n s t r u m e n t for t h e summ a t i o n of evoked responses f r o m tile n e r v o u s system. EEG Clin. Neurophysiol., 1960, 12: 745-747.