Recording compound action potentials from the optic nerve in man and monkeys

Electroencephalography and clinical Neurophysiology, 1987, 67:549-555

549

Elsevier Scientific Publishers Ireland, Ltd. EEG03224

Recording compound action potentials from the optic nerve in man and monkeys Aage R. Moller, James E. Burgess 1 and Laligam N. Sckhar Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (U.S.A.) (Accepted for publication: 15 May, 1987)

Summary

Compound action potentials were recorded from the optic nerve in patients undergoing neurosurgical operations and in rhesus monkeys. The stimuli were short light flashes delivered by light-emitting diodes that were bonded to plastic contact lenses positioned on one or both eyes, and potentials were recorded simultaneously from electrodes placed on the scalp. Potentials recorded from the optic nerve in man have an initial small positive deflection, with a latency of about 45 msec, followed by a negativity with a latency of 60-70 msec. The wave form depends on the recording site on the optic nerve and, occasionally, oscillations with a frequency around 100 Hz were seen in the responses from the optic nerve. There was considerable individual variation in the shape and size of the recorded potentials, but most potentials recorded simultaneously from an electrode placed on Oz with a reference electrode on the forehead appeared as positive deflections with latencies of about 80 msec and, occasionally, with a small positivity with a latency of about 45 msec. Compound action potentials recorded from the optic nerve near the ocular globe in the rhesus monkey in response to similar light flashes appeared as negative deflections with latencies of about 17 msec. The potentials recorded at the chiasm appeared as initial positive deflections, with the latency of the earliest peak being about 35 msec, on which oscillations with frequencies of about 100-150 Hz occasionally could be seen. The recordings from electrodes placed on the scalp (Cz-Oz and Cz-shoulder) in the monkey showed a positive peak with a latency of about 65 msec. In some animals a small negative peak with a latency of 40 msec was seen. Key words: Compound action potentials; Optic nerve; (Man); (Monkey)

Visual evoked potentials (VEPs) are often used clinically and are considered to be important in the diagnosis of a variety of disorders affecting the v i s u a l n e r v o u s s y s t e m , as well as c e r t a i n c e n t r a l n e r v o u s s y s t e m d i s o r d e r s (see C h i a p p a 1 9 8 3 a ) . H o w e v e r , l i t t l e is k n o w n a b o u t t h e o r i g i n o f t h e s e potentials. VEPs are usually obtained in response to stimulation with a reversing checkerboard patt e r n (a p a t t e r n o f l i g h t a n d d a r k s q u a r e s t h a t r e v e r s e s p e r i o d i c a l l y ) ; t h e e f f e c t i v e s t i m u l u s is t h e reversal of the pattern.

1 Present address: Department of Neurosurgery, State University of New York at Buffalo, Buffalo, NY 14214, U.S.A.

Correspondence to: Dr. A.R. Moller, Dept. of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (U.S.A.).

H o w e v e r , p a t t e r n r e v e r s a l is o n l y a n e f f e c t i v e s t i m u l u s if t h e p a t i e n t c o o p e r a t e s b y k e e p i n g h i s or her attention fixed on the image. In patients w h o c a n n o t c o o p e r a t e (e.g., s m a l l c h i l d r e n a n d a n e s t h e t i z e d p a t i e n t s ) f l a s h s t i m u l i a r e u s e d , alt h o u g h s u c h s t i m u l i a r e n o t as e f f i c i e n t a s t h e r e v e r s i n g c h e c k e r b o a r d p a t t e r n i n e l i c i t i n g responses (Chiappa 1983b). T h e V E P s a r e u s u a l l y r e c o r d e d f r o m a n elect r o d e p l a c e d a t t h e i n i o n , O z o r Pz, w i t h t h e reference electrode placed on the earlobe or forehead. However, other electrode placements may b e u s e d , s u c h as O z o r Pz, u s i n g C z as t h e r e f e r ence. When recorded with the active electrode on Oz, t h e r e s p o n s e t o a f l a s h as well as t o a c h e c k e r b o a r d r e v e r s a l p a t t e r n is d o m i n a t e d b y a p o s i t i v e peak appearing about 100 msec after the onset of the flash (or the time of reversal of the checker-

0013-4649/87//$03.50 © 1987 Elsevier Scientific Publishers Ireland, Ltd.

550

board pattern), while the potential recorded at Cz has a negative deflection at the time of the normal appearance of P100. The P100 potential is assumed to be of cortical origin. While subcortical auditory and somatosensory evoked potentials have been studied extensively, only a few studies have focused on the early (subcortical) VEP in man. One was by Pratt et al. (1982), who studied the potentials that can be recorded from the scalp in response to flash stimuli in young adults. Recording from Cz, Fpz, and Oz with a non-cephalic reference, Pratt et al. (1982) recorded 6 well-defined potentials with latencies shorter than 100 msec. The earliest of these peaks, occurring at about 50 msec, was assumed to originate in the optic nerve or optic tract. When electrodes were placed on the infraorbital ridge, they recorded 4-5 initial components, followed by a broad negativity with a latency of about 45 msec. Kraut et al. (1985) assumed that P18 in the monkey corresponded to P40 in man, N40 to N70, P65 to P100, and N95 to N130, and hypothesized that the human P40 (monkey P18) might be of subcortical origin and that the human N70 is generated by the initial excitatory response within cortical lamina IV C. Further, they thought that P100 may reflect inhibitory processes within the cortical lamina, which receives input from the thalamus (this corresponds to P65 in the monkey). Doty et al. (1964), in recording from the optic tract in squirrel monkeys, found a latency of 10-12 msec in response to flash stimulation. The results of recording from the optic nerve and the optic tract in patients undergoing neurosurgical operations and in rhesus monkeys are presented in this paper. Results of recording VEPs simultaneously from electrodes placed on the scalp are shown.

Materials and methods

Responses from the optic nerve and nerve tract were recorded in 9 patients who were operated upon for tumors of the skull base involving the cavernous sinus (see Sekhar and Moiler 1986) and who were operated upon under endotracheal

A.R. M O L L E R ET AL.

anesthesia using intravenous pentobarbital for induction and isoflurane and nitrous oxide without the use of long-lasting muscle relaxants. The recording procedure was approved by the Biomedical Institutional Review Board of this institution, and informed consent was obtained from each patient before the procedure. The electrodes used to record from the optic nerve and optic tract in patients were identical to those used to record from the auditory nervous system (Moiler and Jannetta 1983). They consisted of fine, malleable, Teflon-coated silver wires with a small cotton wick sutured to the tip of each. The reference electrode was a 25-gauge hypodermic needle placed in the wound. Platinum needle electrodes were used to record VEP from the scalp, and electrodes were also placed subcutaneously, close to the eye that was stimulated, to record potentials generated in the eye. The reference electrode was placed on the lower face. The electrodes were connected to conventional AC amplifiers via probes that had current-limiting devices built in for the patient's safety. Filter settings were 0.3-300 Hz (6 dB/octave rolloff), and the recorded potentials were averaged (2 channels, 256 data points each), as they were being recorded, by an LSI 11/73 processor using a sampling interval of 640 /~sec to give a record length of 160 msec. The averaged recordings were stored on floppy disks and filtered off-line using digital filters. VEPs were recorded intraoperatively from electrodes placed on Cz and near the eye that was stimulated, and the potentials were amplified with amplifiers similar to those used to record intracranial potentials. Five rhesus monkeys were used in the present study. They had become unfit for further use in chronic studies on reproduction, but none of the animals had undergone any surgical procedure affecting the central nervous system, nor had they been treated with any drug that could permanently affect the visual system. Several other recordings were made from the same monkeys, mainly to study the neural generators of the brain-stem auditory evoked potentials (BAEPs) and somatosensory evoked potentials (SSEPs). The animals were anesthetized with Nembutal *, without the use of muscle relaxants, and access to

COMPOUND ACTION POTENTIALS FROM OPTIC NERVE

551 Results

Results from patients Fig. 2 shows a typical monopolar recording from the optic nerve in a patient undergoing an operation for removal of a cavernous sinus tumor. Also shown are the responses recorded simultaneously from electrodes placed on Oz (with the reference electrode placed on the forehead). In this recording, the earliest component from the VERTEX

Fig. 1. Light stimulator used in studies of both patients and monkeys. The contact lens is made of plastic (manufactured by Walter TiUman3). Four light-emitting diodes were bonded to the lens using cyanoacrylate adhesive (Superglue, Superglue Corporation, Hollis, New York).

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the optic nerve was gained through a bilateral frontal craniectomy. Using silver wire electrodes placed on the optic nerve and optic tract, both bipolar and monopolar recordings were made. Identical light stimuli were used to elicit responses from monkeys and patients: flashes of red or green light of different durations were delivered by 2 or 3 light-emitting diodes (Hewlett Packard, Type H L M P 3950 2) that were bonded to plastic haptic contact lenses, 20 mm in diameter (manufactured by Walter Tillman 3) (Fig. 1). The diodes were driven by rectangular current pulses totalling 100 mA (33 or 50 mA through each diode), and stimuli were presented at rates of 1, 2, 4, or 10 flashes/sec. Both patients and animals were adapted to the light used as the stimulus before the recordings were begun, and during the recording procedure no other light was presented to the eye being tested.

2 Hewlett Packard, Regional Headquarters, 5201 Tollview Drive, Rolling Meadows, IL 60008, U.S.A. 3 Walter Tiliman, 3520 Fifth Avenue, Suite 402, Pittsburgh, PA 15213, U.S.A.

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Fig. 2. A: recordings from the optic nerve (with the reference placed on the shoulder) in a patient undergoing operation for a tumor in the cavernous sinus. Upper curve: simultaneous recordings from the occipital scalp (Oz) with a reference on the forehead. B: preoperative recordings made after the patient had been anesthetized. Upper curves: recordings from Oz with a forehead reference. Lower curves: recordings from a location just lateral to the stimulated eye. The stimuli were red flashes of 1 msec duration presented at a rate of 2 pulses/sec. Negativity is shown as an upward deflection in all recordings.

552

A.R. MOLLER ET AL.

optic nerve is a negative peak that appears about 38 msec after the onset of the light flash. This peak is followed by a small positive peak and a long-lasting positivity, the peak of which has a latency of about 60 msec. The earliest discernible potentials in the recording from the scalp (Oz) show a positive peak with a latency of about 75 msec followed by a negative peak at about 90 msec. Recordings made from electrodes placed near the eye show a negative potential with a latency of about 65 msec, preceded by 3 small negative peaks, the earliest of which has a latency of about 20 msec. The negative peak with a latency of 65 msec coincides with the main negative peak in the recording from the optic nerve. Recordings from the scalp (Oz to forehead) obtained before the operation was begun show wave forms similar to those obtained during the operation. Fig. 3 shows monopolar recordings from the optic nerve similar to those shown in Fig. 2, but

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obtained in another patient who was operated upon for a pharyngioma. As was shown in Fig. 2, there is an initial positive peak in the response from the optic nerve with a latency of about 35 msec, which is followed by a small negative peak and then by a broad negative deflection, with a peak that has a latency of about 70 msec. The simultaneously obtained response from an electrode placed on the scalp (Oz) with a non-cephalic reference is a positive deflection with a latency of about 70 msec, which coincides with the negative peak seen in the intracranial recording. There is also a small positive peak with a latency of about 40 msec in this recording, which coincides with the small negative peak in the intracranial recording. Recordings made from a more distal location on the nerve, after portions of the tumor had been removed, show essentially a pattern of response similar to that recorded earlier in the operation from a more proximal location on the optic nerve, but the former recording shows a narrower negative peak with a latency of about 60 msec. In addition, there are oscillations at a frequency of about 100 Hz superimposed on the earliest 70 msec of the response.

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Fig. 3. Recordings similar to those in Fig. 2, but from another patient undergoing an operation for a craniopharyngioma. Upper curve: scalp recording Oz with reference on shoulder. Middle curve: optic nerve near chiasm. Lower curve: optic nerve near globe. Stimuli were green flashes of 1 msec duration presented at a rate of 2 pulses/sec.

The response from the optic nerve to brief flashes of light presented at a rate of 1 pulse/sec is a negative deflection preceded by a positive potential when recorded from the optic nerve near the ocular globe, but when recorded near the chiasm the potential is a positive deflection with a latency slightly longer than the negative deflection in the recording from the distal portion of the optic nerve (Fig. 4). The initial positive deflection in the response from the distal portion of the optic nerve most likely reflects processes in the eye itself (electroretinogram, ERG), whereas the two negative peaks that follow may be assumed to reflect neural processes in the optic nerve. Two positive peaks can be discerned in the response at the chiasm. The response from the optic nerve to light flashes of 1 msec duration presented at a rate of 1 pulse/sec has a latency of about 17 msec to the earliest discernible potential. The response recorded from electrodes placed on the scalp (Oz,

C O M P O U N D A C T I O N POTENTIALS FROM OPTIC N E R V E Oz

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Fig. 4. Recordings from the scalp (Oz) of a rhesus monkey with a reference on the shoulder, from the exposed optic nerve, and from the optic chiasm in response to stimulation with red flashes of 1 msec duration presented at a rate of 1 pulse/sec (upper row), 4 pulses/see (middle row), and 10 pulses/see (bottom row).

with a reference on the opposite side of the face) has a large positive peak with a latency of 65 msec followed by another positive peak at 90 msec.

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Fig. 5. Potentials recorded from the optic nerve in a monkey near the orbit (NII) and the optic chiasm using bipolar electrodes. The responses to light flashes of different durations are shown (0.1 msec, upper row; 1 msec, middle row; and 10 msec, bottom row). The stimuli were presented at a rate of 2 pulses/see.

554

stimulus presentation was increased to 4, the wave form of the potentials recorded from the optic nerve and the chiasm changed relatively little, whereas the wave form of the response from the scalp changed and the latency increased. At 10 pulses/sec little change was seen in the potentials recorded from the optic nerve and chiasm, but the amplitude of the response from the scalp became practically absent at that stimulus repetition rate. The effect of changing the duration of the light flashes is shown in Fig. 5, in which the responses from the optic nerve, recorded near the orbit, and at the chiasm of another animal are shown. In this case bipolar electrodes were used. It is seen that the wave form of the responses changes only to a small extent when the duration of the light flashes is increased, but the amplitude of the response is larger when flashes of 1 msec duration are used compared to when flashes of 0.1 msec duration are used. A series of oscillations is seen in the response from the distal optic nerve as well as from the chiasm. The oscillation has a frequency of about 100 Hz at the chiasm and a slightly higher frequency (about 150 Hz) when recorded from the distal portion of the optic nerve. The response lasted slightly longer when the duration of the stimulus was increased from 1 to 10 msec.

Discussion The potentials that can be recorded from the exposed optic nerve in man in response to short flashes of light are of low amplitude. The earliest component of the response from the optic nerve appeared with about the same latency as the P40 component of the human VEP (Pratt et al. 1982; Kraut et al. 1985). This supports the hypothesis that the optic nerve is the generator of the P40 component of the VEP. In the patients in whom we recorded intracranially we also made simultaneous surface recordings and noted early components in these surface recordings that corresponded to P40. However, placing the scalp electrode at Oz with a non-cephalic reference may not have been ideal for recording such early potentials (Pratt et al. 1982). Because the later and larger

A.R. M O L L E R ET AL.

components that were seen in the intracranial recordings with a latency of 60-70 msec correspond to the P70 component of the scalp response, the P70 component of the VEP most likely is not generated by the optic nerve but by more central structures. It is notable that in only 5 of the 9 patients studied was it possible to obtain reproducible responses from the optic nerve. This is in contrast to the results obtained in monkeys in which reproducible responses from the optic nerve were obtained in all 5 of the animals that were studied. Obtaining reproducible recordings from the exposed optic nerve could serve as a much-needed supplement to recording of VEP from scalp electrodes in operations involving the optic nerve for the purpose of preserving visual function. The low amplitude of the potentials from the exposed optic nerve, as well as the difficulties in obtaining reproducible recordings, may indicate that the stimuli used (light flashes) are not ideal for evoking this type of response. The pattern-reversal stimuli commonly used in the clinic would probably have been more suitable; however, no technique is yet available that can produce a focused image on the retina in patients undergoing neurosurgical operations. This makes light flashes the only practical stimulus to use intraoperatively. The difficulty in controlling the stimulus intensity during intraoperative monitoring is another source of variability in the responses obtained. It is generally not possible to dilate the patient's pupil with the use of atropine while recording intraoperatively, as can be done clinically, because the effects of atropine interfere with accurate neurological assessment of the patient immediately postoperatively. In addition, the level of adaptation to the stimulus is likely to change during a long operation, thus adding another source of variability to the results. To decrease variability in adaptation, we use green light instead of the more traditionally used red light, in an attempt to keep the stimulated eye light-adapted. If additional methods were developed to decrease variability in response, they would be of great value in monitoring patients undergoing operations in which muscle relaxants cannot be used, and also as an alternative to using traditional VEP for monitoring dur-

COMPOUND ACTION POTENTIALS FROM OPTIC NERVE

ing operations, such as those involving pituitary tumors. The results of recording from the optic nerve and the optic tract in the rhesus monkey are in agreement with the results of earlier studies in the cat and the squirrel monkey. References Chiappa, K.H. Press, New Chiappa, K.H. Baker and Lippincott,

Evoked Potentials in Clinical Medicine. Raven York, 1983a. Evoked potentials in clinical medicine. In: A.B. L.H. Baker (Eds.), Clinical Neurology, Vol. 1. Philadelphia, PA, 1983b: 1-55.

555 Doty, R.W., Kimura, D.S. and Mogenson, G.J. Photically and electrically elicited responses in the central visual system of the squirrel monkey. Exp. Neurol., 1964, 10: 19-51. Kraut, M.A., Arezzo, J.C. and Vaughan, Jr., H.G. Intracortical generators of the flash VEP in monkeys. Electroenceph. clin. Neurophysiol., 1985, 62: 300-312. Moiler, A.R. and Jannetta, P.J. Monitoring auditory functions during cranial nerve microvascular decompression operations by direct recording from the eighth nerve. J. Neurosurg., 1983, 59: 493-499. Pratt, H., Bleich, N. and Berliner, E. Short latency visual evoked potentials in man. Electroenceph. clin. Neurophysiol., 1982, 54: 55-62. Sekhar, L.N. and M~ller, A.R. Operative management of tumors involving the cavernous sinus. J. Neurosurg., 1986, 64: 879-889.