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Effect of electroconvulsive shock on the slow components of the brain stem auditory evoked potential
EXPERIMENTAL
NEUROLOGY
100,242-247
(1988)
RESEARCH
NOTE
Effect of Electroconvulsive Shock on the Slow Components of the Brain Stem Auditory Evoked Potential N. A.
SHAW’
Department OfPhysiology, School ofMedicine, University ofAuckland, Auckland, I, New Zealand Received July 2, 1987 The effects of electroconvulsive shock on the slow components of the brain stem auditory evoked potential were investigated in the rat during the ictal and the immediate postictal periods. Shock did not significantly alter any aspect of the slow positivenegative complex which underlies the high-frequency waves of the brain stem auditory evoked potential. However, a succeeding potential of probable cortical origin was markedly reduced in amplitude and its peak latency was temporarily increased.
0 1988 Academic
Press, Inc.
The brain stem auditory evoked potential (BAEP) consists of a series of high-frequency components which arise principally within the eighth nerve and pontine auditory pathways. The BAEP is a very stable potential and even an event as traumatic as the induction of tonic-clonic seizures by electroconvulsive shock (ECS) fails to alter its waveform. This has been shown for both man ( 13) and rat ( 10). However, the BAEP does not appear to be a homogeneous potential. Rather, the fast components are superimposed on a slow positivity (2). This slow wave underlying the BAEP can be revealed simply by restricting the higher frequency activity. In a recent report (1 I), the fast and slow components of the BAEP in the rat were separated by progressively raising the cutoff frequency of the low Abbreviations: ECS-electroconvulsive shock, BAEP-brain stem auditory evoked potentials, SP-slow positivity, SN-slow negativity. ’ This project was supported by the Medical Research Council of New Zealand.
242
0014-4886/88 $3.00 Copyright @ 1988 by Academic Press, Inc. AII right.5 of reproduction in any form reserved
EFFECT OF ECS ON SLOW BAEP
243
pass filter. When the high frequency cutoff was set relatively low (about 300 Hz), the waveform consisted primarily of a slow positive-negative complex. As the cutoff frequency of the low pass filter was raised, the fast components of the BAEP began to emerge and eventually dominated the waveform, largely masking the slow waves. Whether or not the slow activity ofthe BAEP is as invulnerable to the effects of ECS as is the fast activity remains unknown. Investigating this possibility was the purpose of the present study. Subjects were six adult male rats. Approximately 1 week prior to the experiment, each animal had a skull screw electrode inserted while under pentobarbital anesthesia. Electrodes were positioned about midway between the lambda and bregma, in the lateral aspect of the skull. On the experimental day, animals were initially curarized with an i.p. injection of d-tubocurarine chloride (4 mg/kg). When signs of neuromuscular paralysis became apparent, the rats were connected to a small animal respirator by means of a balloon mask stretched over the snout. Stroke rate and volume were adjusted to maintain a heart rate within the normal range. It was necessary to record evoked potentials from animals which were immobilized but awake in order to avoid the confounding effects of anesthesia. The ethical considerations when using this preparation were discussed elsewhere (7). The project was approved by the Auckland University Animal Ethical Committee. Slow BAEPs were recorded after unilateral stimulation of the ear contralateral to the site of the skull electrode. Stimuli were 0.1 -ms-duration rarefaction clicks delivered at 3/s. Stimulating conditions were otherwise identical to those described elsewhere (8, 11). The active (skull screw) electrode was referred to a needle inserted through the pinna of the stimulated ear. Evoked potentials were recorded using a Medelec MS6 with a bandpass of 3.2 to 320 Hz, an analysis time of 20 ms, and a sampling interval of 20 ps. Each BAEP was the average of 32 responses. Baseline BAEPs were recorded just prior to the administration of ECS. ECS (80 mA for 600 ms) was delivered transpinnately and was sufficient to cause tonic-clonic convulsions for an average of 1 min in noncurarized animals (7). The technique was essentially the same as that used previously (7,9, 10). The first slow BAEP was completed about 15 s after ECS, a second at about 45 s, a third at 90 s, and a fourth at 2 min. BAEPs were then recorded at 1-min intervals until 10 min. Animals were subsequently killed with an overdose of pentobarbital. In a previous report, the two principal components of the slow BAEP were labeled slow positivity 3 (SP3) and slow negativity 5 (SN5), respectively (11). The same nomenclature has been adopted here (see the baseline example in Fig. 1). This waveform was followed by a later positive potential whose morphology was much more unstable than that of the SP3-SN5 complex.
244
N. A. SHAW ( 2.83 SP3
) 2.84
BEFORE ECS
,&
6.85
2 MIN ( 4.50 ) 2.85
15
3 MIN
s
4.57
2.81 45
s
.A
7.05
,A
6
MIN
A
2.84
2.83 80
10 MIN
s .A
,/ky-
4.88
PIG. 1. An example of the effects of electroconvulsive shock (ECS) on the slow brain stem auditory evoked potential (BAEP) in the rat. The baseline (before ECS) recording was made just prior to the induction of seizure activity. Subsequent slow BAEPs were recorded at the times indicated after ECS. In the baseline example, the two principal components of the slow BAEP (SP3 and SN5) plus a later positivity (P8) are identified with their actual latencies (ms) shown in brackets. In the subsequent slow BAEPs, only the latency values are indicated. Amplitudes ofthe slow BAEP were measured by referring SP3 to the following negative trough (SN5). Latenties were calculated from the onset of the stimulus and about 0.5 ms of each can be accounted for by air conduction time. Note that slow BAEPs recorded at 4, 5, 7, 8, and 9 min are not illustrated.
Taking account of its mean latency, this potential was labeled P8. Embryonic forms of the fast BAEP waves were also detected on the upward and downward slopes of the slow BAEP. An example of the effects of ECSon the slow BAEP is shown in Fig. 1. It is apparent from the illustration that ECS had little or no effect on either its latencies or amplitude, even during the acute ictal phase. In contrast, there was a transient reduction in the amplitude of P8 although this potential was not completely lost. The peak latency of the attenuated response showed a temporary increase of almost 3 ms. Within 1 min, P8 had regained its normal configuration.
->57 =4-I w 2
32.
3s
1-
*
o-
BEFORE ECS
245
EFFECT OF ECS ON SLOW BAEP
SP3 - SN5
.25
.75
1.5
2
3 TIME
4 AFTER
5 ECS
6 (MIN
7
6
9
10
1
II-
I
10 S-
ypa 1’ I T
.
6-
:
7-
,” P if 3
5 4.
=
3-
9
1
1 T
SN5
2-
BEFORE ECS
.25
.75
*
SP3
T
1.5
2
3 TIME
4
5
AFTER
ECS
6 (MIN
7
6
9
10
)
FIG.2. Mean amplitudes and latencies (k 1 SD) of the slow BAEP components at the times indicated after ECS. Changes in the latency of the later P8 potential are also illustrated.
Group data are presented in Fig. 2 and confirm the generally representative nature of the example shown in Fig. 1. No overall change in the slow BAEP latencies could be discerned, nor was there any notable change in its amplitude. The slow BAEP was, however, a more intrinsically variable potential than the fast BAEP, which probably accounted for any minor fluctuations, especially of voltage. As in the example in Fig. 1, the mean increase in the latency of P8 was approximately 3 ms. Although P8 rapidly returned to a normal latency, this was followed by a small increase, a phenomenon observed in both Figs. 1 and 2 at 90 s. Such behavior suggests that P8 is an amalgam of activity from two or more generators. Because of its complex waveform and the difficulty in obtaining a reliable baseline, no attempt was made to quantify the amplitude changes of PS for the group as a whole. Nonetheless, a temporary reduction in the amplitude of P8 was seen in all six animals. The present set of results suggests that the slow BAEP is just as robust and resistant to ECS as is the fast BAEP, although the origins of the former are not as well established as those of the latter. In theory, the slow BAEP may be presumed to be generated primarily by synaptic activity. However, like
246
N. A. SHAW
the fast BAEP, it is possible that both axonal and synaptic events may contribute to its electrogenesis ( 12). The slow positivity (SP3) may represent an accumulation of activity from auditory brain stem nuclei (3). Alternatively, SP3 may reflect axonal and presynaptic activity from the more rostra1 portions of the lateral lemniscus (2, 6). The slow negativity (SN5) most likely arises within the inferior colliculus (2,6, 12). Contrary to orthodox interpretation, the inferior colliculus probably plays little or no role in the generation of any of the principal high frequency components of the BAEP ( 12). The origin of P8 is uncertain, although judging by its mean latency and considering the approximate location of the active electrode, it most likely arises in or near the auditory cortex. The peak latency of P8 seems to coincide with the earliest indication of cortical activity in the rat’s auditory system (1). If P8 is generated within the cortex, then this is the first report of the effects of ECS on a cortical auditory potential. In comparison, the acute effects of ECS on the cortical components of both somatosensory and visual evoked potentials have been well described (4, 5, 7). Characteristically, cortical responses are either reduced in amplitude or else abolished while their latencies are prolonged. Similar changes were also observed in the waveform of P8 following the administration of ECS. Overall, the present findings are consistent with the hypothesis that cortical potentials are especially vulnerable to ECS, whereas those arising from more caudal locations seem largely immune (7, 9, 10). Exactly what underlies this differential susceptibility is unclear. It could, for example, represent the cumulative impact of ECS on synaptic transmission within a sensory pathway. A more likely explanation is that the neuronal mechanisms that generate cortical potentials are particularly sensitive to disruption by ECS. Conceivably, these could involve some form of electrotonic processing. REFERENCES 1. HALL, R. D., AND A. A. BORBELY. 1970. Acoustically evoked potentials in the rat during sleep and waking. Exp. Brain Rex 11: 93- 110. 2. HASHIMOTO, I. 1982. Auditory evoked potentials from the human midbrain: slow brain stem responses. Electroencephalogr. Clin. Neurophysiol. 53: 652-657. 3. JEWTT, D. L. 1970. Volume-conducted potentials in response to auditory stimuli as detected by averaging in the cat. Electroencephalogr. Clin. Neurophysiol. 28: 609-6 18. 4. K~ISS, A., A. M. HALLIDAY, E. HALLIDAY, AND R. T. C. PRATT. 1980. Evoked potentials following unilateral ECT. I. The somatosensory evoked potential. Electroencephalogr. Clin. Neurophysiol. 48: 48 l-489. 5. KRISS,A.,A.M.HALLIDAY,E.HALLIDAY,AND R.T.C.PRATT. 1980.Evokedpotentials following unilateral ECT. II. The flash evoked potential. Electroencephalogr. Clin. Neurophysiol. 48: 490-501. 6. MOLLER, A. R., AND P. J. JANNETTA. 1982. Evoked potentials from the inferior colliculus in man. Electroencephalogr. Clin. Neurophysiol. 53: 6 12-620.
EFFECT
OF
ECS ON
SLOW
BAEP
247
7. SHAW, N. A. 1985. Effect of electroconvulsive shock on the somatosensory evoked potential in the rat. Exp. Neural. 90: 566-579. 8. SHAW, N. A. 1985. The effect of pentobarbital on the auditory evoked response in the brain stem of the rat. Neuropharmacology 25: 63-69. 9. SHAW, N. A. 1986. Effect of electroconvulsive shock on the cervical evoked potential in the rat. Exp. Neurol. 91: 646-649. 10. SHAW, N. A. 1986. The effect of electroconvulsive shock on the brain stem auditory evoked potential in the rat. Biol. Psychiatry 21: 1327- 133 1. 11. SHAW, N. A. 1987. Effects of low pass filtering on the brain stem auditory evoked potential in the rat. Exp. Brain Res. 65: 686-690. 12. SHAW, N. A. 1988. The auditory evoked potential in the rat-a review. Prog. Neurobiol., in press. 13. WEINER, R. D., C. W. ERWIN, AND B. A. WEBER. 1981. Acute effects of electroconvulsive therapy on brain stem auditory-evoked potentials. Electroencephalogr. Clin. Neurophysiol. 52: 202-204.
NEUROLOGY
100,242-247
(1988)
RESEARCH
NOTE
Effect of Electroconvulsive Shock on the Slow Components of the Brain Stem Auditory Evoked Potential N. A.
SHAW’
Department OfPhysiology, School ofMedicine, University ofAuckland, Auckland, I, New Zealand Received July 2, 1987 The effects of electroconvulsive shock on the slow components of the brain stem auditory evoked potential were investigated in the rat during the ictal and the immediate postictal periods. Shock did not significantly alter any aspect of the slow positivenegative complex which underlies the high-frequency waves of the brain stem auditory evoked potential. However, a succeeding potential of probable cortical origin was markedly reduced in amplitude and its peak latency was temporarily increased.
0 1988 Academic
Press, Inc.
The brain stem auditory evoked potential (BAEP) consists of a series of high-frequency components which arise principally within the eighth nerve and pontine auditory pathways. The BAEP is a very stable potential and even an event as traumatic as the induction of tonic-clonic seizures by electroconvulsive shock (ECS) fails to alter its waveform. This has been shown for both man ( 13) and rat ( 10). However, the BAEP does not appear to be a homogeneous potential. Rather, the fast components are superimposed on a slow positivity (2). This slow wave underlying the BAEP can be revealed simply by restricting the higher frequency activity. In a recent report (1 I), the fast and slow components of the BAEP in the rat were separated by progressively raising the cutoff frequency of the low Abbreviations: ECS-electroconvulsive shock, BAEP-brain stem auditory evoked potentials, SP-slow positivity, SN-slow negativity. ’ This project was supported by the Medical Research Council of New Zealand.
242
0014-4886/88 $3.00 Copyright @ 1988 by Academic Press, Inc. AII right.5 of reproduction in any form reserved
EFFECT OF ECS ON SLOW BAEP
243
pass filter. When the high frequency cutoff was set relatively low (about 300 Hz), the waveform consisted primarily of a slow positive-negative complex. As the cutoff frequency of the low pass filter was raised, the fast components of the BAEP began to emerge and eventually dominated the waveform, largely masking the slow waves. Whether or not the slow activity ofthe BAEP is as invulnerable to the effects of ECS as is the fast activity remains unknown. Investigating this possibility was the purpose of the present study. Subjects were six adult male rats. Approximately 1 week prior to the experiment, each animal had a skull screw electrode inserted while under pentobarbital anesthesia. Electrodes were positioned about midway between the lambda and bregma, in the lateral aspect of the skull. On the experimental day, animals were initially curarized with an i.p. injection of d-tubocurarine chloride (4 mg/kg). When signs of neuromuscular paralysis became apparent, the rats were connected to a small animal respirator by means of a balloon mask stretched over the snout. Stroke rate and volume were adjusted to maintain a heart rate within the normal range. It was necessary to record evoked potentials from animals which were immobilized but awake in order to avoid the confounding effects of anesthesia. The ethical considerations when using this preparation were discussed elsewhere (7). The project was approved by the Auckland University Animal Ethical Committee. Slow BAEPs were recorded after unilateral stimulation of the ear contralateral to the site of the skull electrode. Stimuli were 0.1 -ms-duration rarefaction clicks delivered at 3/s. Stimulating conditions were otherwise identical to those described elsewhere (8, 11). The active (skull screw) electrode was referred to a needle inserted through the pinna of the stimulated ear. Evoked potentials were recorded using a Medelec MS6 with a bandpass of 3.2 to 320 Hz, an analysis time of 20 ms, and a sampling interval of 20 ps. Each BAEP was the average of 32 responses. Baseline BAEPs were recorded just prior to the administration of ECS. ECS (80 mA for 600 ms) was delivered transpinnately and was sufficient to cause tonic-clonic convulsions for an average of 1 min in noncurarized animals (7). The technique was essentially the same as that used previously (7,9, 10). The first slow BAEP was completed about 15 s after ECS, a second at about 45 s, a third at 90 s, and a fourth at 2 min. BAEPs were then recorded at 1-min intervals until 10 min. Animals were subsequently killed with an overdose of pentobarbital. In a previous report, the two principal components of the slow BAEP were labeled slow positivity 3 (SP3) and slow negativity 5 (SN5), respectively (11). The same nomenclature has been adopted here (see the baseline example in Fig. 1). This waveform was followed by a later positive potential whose morphology was much more unstable than that of the SP3-SN5 complex.
244
N. A. SHAW ( 2.83 SP3
) 2.84
BEFORE ECS
,&
6.85
2 MIN ( 4.50 ) 2.85
15
3 MIN
s
4.57
2.81 45
s
.A
7.05
,A
6
MIN
A
2.84
2.83 80
10 MIN
s .A
,/ky-
4.88
PIG. 1. An example of the effects of electroconvulsive shock (ECS) on the slow brain stem auditory evoked potential (BAEP) in the rat. The baseline (before ECS) recording was made just prior to the induction of seizure activity. Subsequent slow BAEPs were recorded at the times indicated after ECS. In the baseline example, the two principal components of the slow BAEP (SP3 and SN5) plus a later positivity (P8) are identified with their actual latencies (ms) shown in brackets. In the subsequent slow BAEPs, only the latency values are indicated. Amplitudes ofthe slow BAEP were measured by referring SP3 to the following negative trough (SN5). Latenties were calculated from the onset of the stimulus and about 0.5 ms of each can be accounted for by air conduction time. Note that slow BAEPs recorded at 4, 5, 7, 8, and 9 min are not illustrated.
Taking account of its mean latency, this potential was labeled P8. Embryonic forms of the fast BAEP waves were also detected on the upward and downward slopes of the slow BAEP. An example of the effects of ECSon the slow BAEP is shown in Fig. 1. It is apparent from the illustration that ECS had little or no effect on either its latencies or amplitude, even during the acute ictal phase. In contrast, there was a transient reduction in the amplitude of P8 although this potential was not completely lost. The peak latency of the attenuated response showed a temporary increase of almost 3 ms. Within 1 min, P8 had regained its normal configuration.
->57 =4-I w 2
32.
3s
1-
*
o-
BEFORE ECS
245
EFFECT OF ECS ON SLOW BAEP
SP3 - SN5
.25
.75
1.5
2
3 TIME
4 AFTER
5 ECS
6 (MIN
7
6
9
10
1
II-
I
10 S-
ypa 1’ I T
.
6-
:
7-
,” P if 3
5 4.
=
3-
9
1
1 T
SN5
2-
BEFORE ECS
.25
.75
*
SP3
T
1.5
2
3 TIME
4
5
AFTER
ECS
6 (MIN
7
6
9
10
)
FIG.2. Mean amplitudes and latencies (k 1 SD) of the slow BAEP components at the times indicated after ECS. Changes in the latency of the later P8 potential are also illustrated.
Group data are presented in Fig. 2 and confirm the generally representative nature of the example shown in Fig. 1. No overall change in the slow BAEP latencies could be discerned, nor was there any notable change in its amplitude. The slow BAEP was, however, a more intrinsically variable potential than the fast BAEP, which probably accounted for any minor fluctuations, especially of voltage. As in the example in Fig. 1, the mean increase in the latency of P8 was approximately 3 ms. Although P8 rapidly returned to a normal latency, this was followed by a small increase, a phenomenon observed in both Figs. 1 and 2 at 90 s. Such behavior suggests that P8 is an amalgam of activity from two or more generators. Because of its complex waveform and the difficulty in obtaining a reliable baseline, no attempt was made to quantify the amplitude changes of PS for the group as a whole. Nonetheless, a temporary reduction in the amplitude of P8 was seen in all six animals. The present set of results suggests that the slow BAEP is just as robust and resistant to ECS as is the fast BAEP, although the origins of the former are not as well established as those of the latter. In theory, the slow BAEP may be presumed to be generated primarily by synaptic activity. However, like
246
N. A. SHAW
the fast BAEP, it is possible that both axonal and synaptic events may contribute to its electrogenesis ( 12). The slow positivity (SP3) may represent an accumulation of activity from auditory brain stem nuclei (3). Alternatively, SP3 may reflect axonal and presynaptic activity from the more rostra1 portions of the lateral lemniscus (2, 6). The slow negativity (SN5) most likely arises within the inferior colliculus (2,6, 12). Contrary to orthodox interpretation, the inferior colliculus probably plays little or no role in the generation of any of the principal high frequency components of the BAEP ( 12). The origin of P8 is uncertain, although judging by its mean latency and considering the approximate location of the active electrode, it most likely arises in or near the auditory cortex. The peak latency of P8 seems to coincide with the earliest indication of cortical activity in the rat’s auditory system (1). If P8 is generated within the cortex, then this is the first report of the effects of ECS on a cortical auditory potential. In comparison, the acute effects of ECS on the cortical components of both somatosensory and visual evoked potentials have been well described (4, 5, 7). Characteristically, cortical responses are either reduced in amplitude or else abolished while their latencies are prolonged. Similar changes were also observed in the waveform of P8 following the administration of ECS. Overall, the present findings are consistent with the hypothesis that cortical potentials are especially vulnerable to ECS, whereas those arising from more caudal locations seem largely immune (7, 9, 10). Exactly what underlies this differential susceptibility is unclear. It could, for example, represent the cumulative impact of ECS on synaptic transmission within a sensory pathway. A more likely explanation is that the neuronal mechanisms that generate cortical potentials are particularly sensitive to disruption by ECS. Conceivably, these could involve some form of electrotonic processing. REFERENCES 1. HALL, R. D., AND A. A. BORBELY. 1970. Acoustically evoked potentials in the rat during sleep and waking. Exp. Brain Rex 11: 93- 110. 2. HASHIMOTO, I. 1982. Auditory evoked potentials from the human midbrain: slow brain stem responses. Electroencephalogr. Clin. Neurophysiol. 53: 652-657. 3. JEWTT, D. L. 1970. Volume-conducted potentials in response to auditory stimuli as detected by averaging in the cat. Electroencephalogr. Clin. Neurophysiol. 28: 609-6 18. 4. K~ISS, A., A. M. HALLIDAY, E. HALLIDAY, AND R. T. C. PRATT. 1980. Evoked potentials following unilateral ECT. I. The somatosensory evoked potential. Electroencephalogr. Clin. Neurophysiol. 48: 48 l-489. 5. KRISS,A.,A.M.HALLIDAY,E.HALLIDAY,AND R.T.C.PRATT. 1980.Evokedpotentials following unilateral ECT. II. The flash evoked potential. Electroencephalogr. Clin. Neurophysiol. 48: 490-501. 6. MOLLER, A. R., AND P. J. JANNETTA. 1982. Evoked potentials from the inferior colliculus in man. Electroencephalogr. Clin. Neurophysiol. 53: 6 12-620.
EFFECT
OF
ECS ON
SLOW
BAEP
247
7. SHAW, N. A. 1985. Effect of electroconvulsive shock on the somatosensory evoked potential in the rat. Exp. Neural. 90: 566-579. 8. SHAW, N. A. 1985. The effect of pentobarbital on the auditory evoked response in the brain stem of the rat. Neuropharmacology 25: 63-69. 9. SHAW, N. A. 1986. Effect of electroconvulsive shock on the cervical evoked potential in the rat. Exp. Neurol. 91: 646-649. 10. SHAW, N. A. 1986. The effect of electroconvulsive shock on the brain stem auditory evoked potential in the rat. Biol. Psychiatry 21: 1327- 133 1. 11. SHAW, N. A. 1987. Effects of low pass filtering on the brain stem auditory evoked potential in the rat. Exp. Brain Res. 65: 686-690. 12. SHAW, N. A. 1988. The auditory evoked potential in the rat-a review. Prog. Neurobiol., in press. 13. WEINER, R. D., C. W. ERWIN, AND B. A. WEBER. 1981. Acute effects of electroconvulsive therapy on brain stem auditory-evoked potentials. Electroencephalogr. Clin. Neurophysiol. 52: 202-204.