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An electronic device for continuous counting of chemically induced epileptic discharges
Electroencephalography and Clinical Neurophysiology, 1974, 37:191-193 ' Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
TECHNICAL
191
CONTRIBUTION
A N E L E C T R O N I C DEVICE F O R C O N T I N U O U S C O U N T I N G OF C H E M I C A L L Y I N D U C E D EPILEPTIC D I S C H A R G E S ST. ZSCHOCKE
Neurolooische Uni~,ersitdtsklinik Eppendorf, 2 Hambur O 20 ( W. Germany) (Accepted for publication: February 18, 1974)
Experimental investigations of epilepsy sometimes require continuous electronic counting of epileptic interictal "'spike" discharges. Generally an amplitude discriminator will be used for this purpose. With this method, however, the accuracy of discrimination depends upon the wave-form of the seizure potentials as well as upon the amplitude ratio of seizure activity to background EEG. Thus complex or polyphasic wave-forms may lead to false multiple detection of single seizure discharges if each individual component exceeds the discriminator threshold. Moreover, if the amplitude of the epileptic potentials does not exceed that of the non-epileptic ones, discrimination will become quite impossible. In the latter case, a differentiator would enable a selective amplification of epileptic discharges with respect to their slope (Carrie 1972). The efficiency of this technique~ however, may be limited by the first, above mentioned, source of error: polyphasic components of seizure discharges may be enhanced, and even small splittings within the seizure potential would thus be amplified and give rise to spurious pulses at the discriminator output causing erroneous counting. The aim of this paper is to describe an electronic device which prevents the undesired counting of these spurious pulses. METHODS The block diagram of the electronic equipment is shown in Fig. 1. Between pre-amplifier (isolation unity-gain ampli-
tier model 273 A, Analog Devices, Inc., followed by an operational amplifier with gain of 1000) and power amplifier an active (low pass) filter unit is inserted. Branching off from this filter unit, the EEG will be routed to the differentiator (1). The derivative will then be led to the amplitude discriminator (2); the output of the discriminator is connected to a pulse rejection stage (3) which eliminates spurious pulses 1. The result of the continuous counting will finally be displayed or printed out~ under control of a timer, as counts per time unit (e.9., per minute). Before differentiation suppression of noise is essentially obtained by adjusting the upper cut-off frequency of the filter unit. This bandwidth limitation, however, should not diminish the slope of seizure potentials, since their steepness is the basis for spike detection by differentiation. From our experience, 100 Hz is optimal provided that a pre-amplifier with sufficient signal-to-noise ratio is employed. The time constant of the differentiator should be adjustable from 1 to 50 msec. The pulse rejection stage (3), which prevents the undesired counting of extra pulses, consists essentially of a single-shot multivibrator whose pulse duration (energization time) is adjustable. If a given pulse from the amplitude discriminator energizes the monostable circuit, additional pulses appearing within the limits of the chosen energization time will be ineffective, and thus rejected. This time is, in our device. adjustable from 1 to 500 msec. RESULTS Fig. 2 shows short sections of an electrocorticogram (ECoG) recorded in the rat, showing spikes induced by continuous i.p. injection of pentylenetetrazol (150-250 mg/kg/h, following an initial dose of about 100 mg/kg) which maintains an approximately constant sequence of "spikes" and avoids fits as much as possible. The output of the pulse rejection stage is shown in trace C. Section 1 gives an example-of the initial development of seizure activity
Fig. 1. Block diagram of the whole equipment for continuous counting of seizure discharges. See text for description. A, B and C denote sources of records in corresponding traces of Fig. 2 and 3.
1 Specified circuit diagram of (1) to (3) are available on request.
1
2
3
frl
f
4
5
EGG
A
I
I
I[f -
I
l see Fig. 2. Short sections of a rat's ECoG showing spikes induced by pentylenetetrazol. Explanations of sections 1 5 in text. A: Derivative of ECoG. B: Amplitude discriminator output. C: Output of pulse rejection stage, pulse duration 200 msec (overshoots of the square-wave pulses in C are due to the inertia of the mechanical writing system). Notice rejection of spurious pulses in section 5 (trace C in comparison with trace B). In all traces positive deflexions downwards.
1
2
3
4
5
6
EGG I
A B
C
I
I
1 sec Fig. 3. Short sections of rat ECoGs showing pentylenetetrazol spikes of various forms giving rise to incorrect discrimination and causing spurious pulses at the discriminator output (trace B). These are rejected by the pulse reiection stage (trace C). Calibration for ECoG in section 1-3 : 2 mV (marked beside section 3), in section 4-6 : 500 #V. Pulse duration in trace C, 200 msec (section 1) and 250 msec (section 2 6). In all traces positive deflections downwards.
CONTINUOUS COUNTING OF EPILEPTIC DISCHARGES
193
after thc first administration of pentylenetetrazol. Sections 3 5 were obtained after a transient asphyxia which had suppressed the E C o G for a short time. In sections 1, 3 and 4 there are tiny spikes which can only be detected if differentiation is introduced (trace A). Section 5 shows the inherent disadvantage of differentiation (artificial polyphasia in trace A. with spurious pulses in trace B), but this can be eliminated by the pulse rejection stage, as illustrated in trace C Fig. 3 shows examples of various forms of pentylenetetrazol spikes recorded in the rat which would lead to detection difficulties if based only on amplitude discrimination. Some seizure potentials are originally polyphasic (sections 1, 3 and 6). Some potentials differ with regard to the direction of the main deflexion; this could lead to faults in detection if the amplitude discriminator only permitted the adjustment of one threshold level, either in the positive or negative range. In this case, the artificial polyphasic derivatives in trace A permit better detection, regardless of the adjusted polarity of the discriminator threshold. In sections 4 and 5 of Fig. 3, finally, the epileptic character of the potentials, obtained from hypoxic damaged cortex, is not quite clear. It only becomes apparent after disclosing the residual steeply rising phases by differentiation. These improvements of detection possibilities, however, can only be used if the inevitable spurious pulses at the discriminator output (trace B) can be eliminated. This can be achieved by the pulse rejection stage, as shown in trace C of Fig. 3.
The device is also useful for the continuous counting of spikes followed by after-discharges, such as those induced by penicillin and other agents (rid. G r i m m el al. 1973). Here the after-discharges may cause multiple counts. They' must be denoted as spurious if only detection and counting of the initial spike is desired, both initial spike and after-discharges being interpreted as a single epileptic event. The undesired counting of pulses generated by these after-discharges can easily be avoided by suitably adapting the rejection time to the period of after-activity; however, in this case the pulse rejection time should be extensible to the range of seconds.
DISCUSSION The advantage of this device is that the discriminating power can be considerably increased by better utilization of the differentiation technique, without errors in the counting of detected seizure potentials. The accuracy of the pulse rejection depends simply upon correct adjustment of the rejection time (i.e., the pulse duration of the single-shot multivibrator, as described above). It must be adapted to the actual observed duration of recorded seizure discharges ; ,an adjustment range from 1 to 500 msec may be sufficient. Repeated controls of the rejection power are advisable, because the respective durations of the seizure discharges and of their derivatives can change in the course of an experiment, especially if procedures are used which alter cortical function (e.g., hypoxic damage; see Fig. 3). Such controls are facilitated by use of a storage oscilloscope. A rejection time too short in comparison with the duration of the epileptic event would lead to incomplete rejection of spurious pulses. On the other hand, if the rejection time is set too long, "fusion" of two square-wave pulses at the rejection stage output m a y occur, leading to a loss of counts. Such an error can arise from abrupt development of fits. In this case, correct and fast readjustment may not be possible. In counting long-lasting pre-ictal and interictal discharges, however, for which the device was primarily developed, the necessary accuracy in counting detected seizure potentials can be achieved.
SUMMARY The amplitude discriminating power for detection of epileptic interictal "spikes" can be increased by a preceding differentiation of the EEG, which enables a selective amplification of the seizure potentials with respect to their slope. An unavoidable disadvantage of such a method is that polyphasic components of single seizure potentials will also be enhanced, causing spurious pulses at the discriminator output and thus disturbing the automatic counting of these epileptic discharges. This paper describes a device which rejects such spurious pulses, using a monostable multivibrator. RESUME DISPOSITIF CONTINU INDUITES
ELECTRONIQUE POUR COMPTAGE DES DECHARGES EPILEPTIQUES
Dans la d6tection des "pointes'" 6pileptiques interictales le pouvoir de discrimination &litude peut 6tre accru en proc6dant ~ la diff6renciation du signal EEG, ce qui permet une amplification s61ective de ces pointes, en fonction de leur pente d'btablissement. Toutefois, cette m6thode a un d6savantage +vident en ce sens que les composantes successives d'une seule pointe paroxystique polyphasique seront toutes amplifi6es, ce qui introduit une erreur '5. la sortie du discriminateur et par cons6quent dans un comptage automatique de ces pointes. Le pr6sent travail d6crit un montage permettant a l'aide d'une bascule monostable d'6viter ces erreurs de comptage.
REFERENCES
CARRIE,J. R. G. A hybrid computer technique for detection of sharp EEG transients. Electroenceph. clin. Neurophysiol., 1972, 33 : 336. GRIMM, R. J.. FRAZEE, J. G. and OZBAY, S. After-discharge bursts in cobalt and penicillin foci in primate cortex. Electroenceph. olin. Neurophysiol.. 1973, 34 : 28 I.
TECHNICAL
191
CONTRIBUTION
A N E L E C T R O N I C DEVICE F O R C O N T I N U O U S C O U N T I N G OF C H E M I C A L L Y I N D U C E D EPILEPTIC D I S C H A R G E S ST. ZSCHOCKE
Neurolooische Uni~,ersitdtsklinik Eppendorf, 2 Hambur O 20 ( W. Germany) (Accepted for publication: February 18, 1974)
Experimental investigations of epilepsy sometimes require continuous electronic counting of epileptic interictal "'spike" discharges. Generally an amplitude discriminator will be used for this purpose. With this method, however, the accuracy of discrimination depends upon the wave-form of the seizure potentials as well as upon the amplitude ratio of seizure activity to background EEG. Thus complex or polyphasic wave-forms may lead to false multiple detection of single seizure discharges if each individual component exceeds the discriminator threshold. Moreover, if the amplitude of the epileptic potentials does not exceed that of the non-epileptic ones, discrimination will become quite impossible. In the latter case, a differentiator would enable a selective amplification of epileptic discharges with respect to their slope (Carrie 1972). The efficiency of this technique~ however, may be limited by the first, above mentioned, source of error: polyphasic components of seizure discharges may be enhanced, and even small splittings within the seizure potential would thus be amplified and give rise to spurious pulses at the discriminator output causing erroneous counting. The aim of this paper is to describe an electronic device which prevents the undesired counting of these spurious pulses. METHODS The block diagram of the electronic equipment is shown in Fig. 1. Between pre-amplifier (isolation unity-gain ampli-
tier model 273 A, Analog Devices, Inc., followed by an operational amplifier with gain of 1000) and power amplifier an active (low pass) filter unit is inserted. Branching off from this filter unit, the EEG will be routed to the differentiator (1). The derivative will then be led to the amplitude discriminator (2); the output of the discriminator is connected to a pulse rejection stage (3) which eliminates spurious pulses 1. The result of the continuous counting will finally be displayed or printed out~ under control of a timer, as counts per time unit (e.9., per minute). Before differentiation suppression of noise is essentially obtained by adjusting the upper cut-off frequency of the filter unit. This bandwidth limitation, however, should not diminish the slope of seizure potentials, since their steepness is the basis for spike detection by differentiation. From our experience, 100 Hz is optimal provided that a pre-amplifier with sufficient signal-to-noise ratio is employed. The time constant of the differentiator should be adjustable from 1 to 50 msec. The pulse rejection stage (3), which prevents the undesired counting of extra pulses, consists essentially of a single-shot multivibrator whose pulse duration (energization time) is adjustable. If a given pulse from the amplitude discriminator energizes the monostable circuit, additional pulses appearing within the limits of the chosen energization time will be ineffective, and thus rejected. This time is, in our device. adjustable from 1 to 500 msec. RESULTS Fig. 2 shows short sections of an electrocorticogram (ECoG) recorded in the rat, showing spikes induced by continuous i.p. injection of pentylenetetrazol (150-250 mg/kg/h, following an initial dose of about 100 mg/kg) which maintains an approximately constant sequence of "spikes" and avoids fits as much as possible. The output of the pulse rejection stage is shown in trace C. Section 1 gives an example-of the initial development of seizure activity
Fig. 1. Block diagram of the whole equipment for continuous counting of seizure discharges. See text for description. A, B and C denote sources of records in corresponding traces of Fig. 2 and 3.
1 Specified circuit diagram of (1) to (3) are available on request.
1
2
3
frl
f
4
5
EGG
A
I
I
I[f -
I
l see Fig. 2. Short sections of a rat's ECoG showing spikes induced by pentylenetetrazol. Explanations of sections 1 5 in text. A: Derivative of ECoG. B: Amplitude discriminator output. C: Output of pulse rejection stage, pulse duration 200 msec (overshoots of the square-wave pulses in C are due to the inertia of the mechanical writing system). Notice rejection of spurious pulses in section 5 (trace C in comparison with trace B). In all traces positive deflexions downwards.
1
2
3
4
5
6
EGG I
A B
C
I
I
1 sec Fig. 3. Short sections of rat ECoGs showing pentylenetetrazol spikes of various forms giving rise to incorrect discrimination and causing spurious pulses at the discriminator output (trace B). These are rejected by the pulse reiection stage (trace C). Calibration for ECoG in section 1-3 : 2 mV (marked beside section 3), in section 4-6 : 500 #V. Pulse duration in trace C, 200 msec (section 1) and 250 msec (section 2 6). In all traces positive deflections downwards.
CONTINUOUS COUNTING OF EPILEPTIC DISCHARGES
193
after thc first administration of pentylenetetrazol. Sections 3 5 were obtained after a transient asphyxia which had suppressed the E C o G for a short time. In sections 1, 3 and 4 there are tiny spikes which can only be detected if differentiation is introduced (trace A). Section 5 shows the inherent disadvantage of differentiation (artificial polyphasia in trace A. with spurious pulses in trace B), but this can be eliminated by the pulse rejection stage, as illustrated in trace C Fig. 3 shows examples of various forms of pentylenetetrazol spikes recorded in the rat which would lead to detection difficulties if based only on amplitude discrimination. Some seizure potentials are originally polyphasic (sections 1, 3 and 6). Some potentials differ with regard to the direction of the main deflexion; this could lead to faults in detection if the amplitude discriminator only permitted the adjustment of one threshold level, either in the positive or negative range. In this case, the artificial polyphasic derivatives in trace A permit better detection, regardless of the adjusted polarity of the discriminator threshold. In sections 4 and 5 of Fig. 3, finally, the epileptic character of the potentials, obtained from hypoxic damaged cortex, is not quite clear. It only becomes apparent after disclosing the residual steeply rising phases by differentiation. These improvements of detection possibilities, however, can only be used if the inevitable spurious pulses at the discriminator output (trace B) can be eliminated. This can be achieved by the pulse rejection stage, as shown in trace C of Fig. 3.
The device is also useful for the continuous counting of spikes followed by after-discharges, such as those induced by penicillin and other agents (rid. G r i m m el al. 1973). Here the after-discharges may cause multiple counts. They' must be denoted as spurious if only detection and counting of the initial spike is desired, both initial spike and after-discharges being interpreted as a single epileptic event. The undesired counting of pulses generated by these after-discharges can easily be avoided by suitably adapting the rejection time to the period of after-activity; however, in this case the pulse rejection time should be extensible to the range of seconds.
DISCUSSION The advantage of this device is that the discriminating power can be considerably increased by better utilization of the differentiation technique, without errors in the counting of detected seizure potentials. The accuracy of the pulse rejection depends simply upon correct adjustment of the rejection time (i.e., the pulse duration of the single-shot multivibrator, as described above). It must be adapted to the actual observed duration of recorded seizure discharges ; ,an adjustment range from 1 to 500 msec may be sufficient. Repeated controls of the rejection power are advisable, because the respective durations of the seizure discharges and of their derivatives can change in the course of an experiment, especially if procedures are used which alter cortical function (e.g., hypoxic damage; see Fig. 3). Such controls are facilitated by use of a storage oscilloscope. A rejection time too short in comparison with the duration of the epileptic event would lead to incomplete rejection of spurious pulses. On the other hand, if the rejection time is set too long, "fusion" of two square-wave pulses at the rejection stage output m a y occur, leading to a loss of counts. Such an error can arise from abrupt development of fits. In this case, correct and fast readjustment may not be possible. In counting long-lasting pre-ictal and interictal discharges, however, for which the device was primarily developed, the necessary accuracy in counting detected seizure potentials can be achieved.
SUMMARY The amplitude discriminating power for detection of epileptic interictal "spikes" can be increased by a preceding differentiation of the EEG, which enables a selective amplification of the seizure potentials with respect to their slope. An unavoidable disadvantage of such a method is that polyphasic components of single seizure potentials will also be enhanced, causing spurious pulses at the discriminator output and thus disturbing the automatic counting of these epileptic discharges. This paper describes a device which rejects such spurious pulses, using a monostable multivibrator. RESUME DISPOSITIF CONTINU INDUITES
ELECTRONIQUE POUR COMPTAGE DES DECHARGES EPILEPTIQUES
Dans la d6tection des "pointes'" 6pileptiques interictales le pouvoir de discrimination &litude peut 6tre accru en proc6dant ~ la diff6renciation du signal EEG, ce qui permet une amplification s61ective de ces pointes, en fonction de leur pente d'btablissement. Toutefois, cette m6thode a un d6savantage +vident en ce sens que les composantes successives d'une seule pointe paroxystique polyphasique seront toutes amplifi6es, ce qui introduit une erreur '5. la sortie du discriminateur et par cons6quent dans un comptage automatique de ces pointes. Le pr6sent travail d6crit un montage permettant a l'aide d'une bascule monostable d'6viter ces erreurs de comptage.
REFERENCES
CARRIE,J. R. G. A hybrid computer technique for detection of sharp EEG transients. Electroenceph. clin. Neurophysiol., 1972, 33 : 336. GRIMM, R. J.. FRAZEE, J. G. and OZBAY, S. After-discharge bursts in cobalt and penicillin foci in primate cortex. Electroenceph. olin. Neurophysiol.. 1973, 34 : 28 I.