VERTICAL OPTOKINETIC NYSTAGMUS AND OPTOKINETIC AFTERNYSTAGMUS IN HUMANS. A. Bohmer and R. W. Baloh

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1 Journal of Vestibular Research, Vol. 1, pp , 1990/91 Printed in the USA. All rights reserved /91 $ Copyright 1991 Pergamon Press pic VERTICAL OPTOKINETIC NYSTAGMUS AND OPTOKINETIC AFTERNYSTAGMUS IN HUMANS A. Bohmer and R. W. Baloh UCLA School of Medicine, Los Angeles, California Reprint address: Dr. R. W. Baloh, Department of Neurology, UCLA School of Medicine, Los Angeles, CA o Abstract-Vertical optokinetic nystagmus (OKN) and optokinetic afternystagmus (OKAN) were recorded in 6 normal subjects using the magnetic scleral search coil technique in order to reevaluate the up-down symmetry of these responses. The effects of body position relative to gravity were investigated by comparing OKN and OKAN elicited with the subjects in an erect and in a lateral side position. No consistent up-down asymmetry in vertical OKN was found but OKAN was asymmetric (up slow phase velocity> down slow phase velocity). Most subjects had an immediate reversal in OKAN slow phase velocity after dow"nward stimuli. No significant effects of static head position (upright versus lateral position) on vertical OKN and OKAN were found. These features of human OKAN can be explained by the summation of two oppositely directed velocity storage mechanisms. o Keywords - vertical eye movements; optokinetic nystagmus; optokinetic afternystagmus; velocity storage. Introduction Moving the visual field around a stationary observer induces reflexive conjugate eye movements, consisting of alternating slow trackmg phases in the direction of the moving surround and fast resets in the opposite direction in anticipation of the next tracking phase. This optokinetic nystagmus, OKN, is believed to supplement the vestibulo-ocular reflex in Dr. Bohmer's current address is Otolaryngological Clinic, University Hospital, Ramistr. 100, 8091 Zurich, Switzerland. gaze stabilization during head movements and several features demonstrate a close interaction of the vestibular and the optokinetic systems. On cessation of optokinetic stimulation, OKN does not immediately stop, but decays gradually (optokinetic afternystagmus, OKAN) and may be followed by a nystagmus in the opposite direction (OKAN II or OKAAN). OKAN and OKAAN,are thought to be related to an eye velocity storage mechanism in the vestibular system. The gain of OKN, ie, slow phase eye velocity divided by stimulus velocity, depends on stimulus velocity and also on stimulus direction. While there is general agreement that horizontal OKN and OKAN are right-left symmetrical in normal subjects (1), data on vertical OKN and OKAN in humans are inconsistent. Some studies report higher OKN gains for slow phase up than for slow phase down (2-5); others found no consistent asymmetries (6,7). Only the two most recent studies of vertical OKN have used a search coil technique for eye movement recording (4,5). All others have used electro-oculography, and asymmetries in these studies might have resulted from the vvell-known EOG lid artifact (8), Furthermore, vertical OKN and OKAN are influenced by static vestibular inputs. In Rhesus monkeys vertical OKN and OKAN are markedly asymmetric (slow phase up velocity > slow phase down velocity) when the animals are tested in a lateral head and body position, while these asymmetries diminished in an upright, sitting position (9). In squirrel monkeys OKAN is asymmetric even when the RECEIVED 16 January 1991; REVISION RECEIVED 19 March 1991; ACCEPTED 21 March

2 310 animals are tested in an upright position (10). In humans, vertical OKAN is less prominent than in monkeys (3,5,7). Furthermore, only slow phase up OKAN was found in humans; following downward stimulation there was either no OKAN or there was OKAN in the 'wrong' direction. Baloh and colleagues (7) considered this slow phase up nystagmus following downward stimulation as OKAN II (without OKAN I), while LeLiever and Correia (3) called it an "inappropriately directed OKAN". The present study reevaluates the effects of body position relative to gravity on human vertical OKN and OKAN using the precise scleral search coil technique for recording eye movements. Method Eye Movement Recording Vertical eye movements were recorded in 6 healthy volunteers (age 23 to 39 years) using a magnetic search coil technique (11,12). The search coil, embedded in a soft contact lens (Skalar Medical, Delft, The Netherlands), was placed on one eye after topical anesthesia. The contact lens stayed on the eye for approximately 30 minutes. The subject was seated with the eye in the center of a 90- x 90-cm cube containing the induction coils. Eye position was calculated from the magnetically induced signal with a quadrature system and simultaneously plotted on paper and stored on magnetic tape for later digital computer analysis. Eye position was calibrated by asking the subject to fixate on small visual targets 10 above and below the center of gaze. Eye velocity was obtained from analog differentiation of the eye position signals by means of operational amplifiers and was plotted on-line on paper together with the eye position signal. Optokinetic Stimulation The front wall of the cube containing the induction coils consisted of a transparent screen (90 x 90 cm). The sides between the A. Bohmer and R. W. Baloh screen and the subjects head were covered with black cloths and the experimental room was kept completely dark. A pattern of stripes was generated with a Macintosh II computer running VIDEOWORKS II and Hypercard and projected from behind onto the transparent screen using a Sony multi-scan video projector (VPH 1031 Q). The stripes, 3 X 90, rather than being uniformly bright, consisted of two columns of small bright dots; this prevented the subject from seeing any irregularities on the stationary screen. Although only 90 X 90 of the visual field was stimulated, the subject could not see any stationary targets (except the black borders of the screen). Subjects were instructed to look straight ahead at the stripes directly in front of them. To demonstrate that our projected optokinetic stimulus was an effective stimulus for generating OKN and OKAN, we induced horizontal OKN and OKAN in 3 subjects with a 30 0 /s constant velocity stimulus for 1 min in each direction. All 3 subjects exhibited symmetrical horizontal OKN and OKAN. Two sets of experiments were performed: 1. Up-down symmetry of OKN was evaluated in 3 subjects with the head in an upright position at 4 different stimulation velocities (15, 30, 45, and 60 0 /s). The stripes were oriented earth horizontal and ran in randomized order for 60 sec either up or down. Subjects were given a 1 min rest period between trials. 2. Vertical OKAN and the influence of head position relative to gravity on OKN and OKAN was evaluated in 5 SUbjects. The subjects were seated first with their heads in a lateral position on a support. In this paradigm the stripes were oriented earth vertical and moved earth horizontally (vertical relative to the subject's head). After 90 seconds of constant velocity optokinetic stimulation (45 /s) the lights were turned off and the subjects were asked to keep their eyes open and look straight ahead. The next trial began after OKAN completely disappeared. Order of up and down stimulation was randomized. Immediately afterward, the subjects and stripes

3 Vertical OKN and OKAN in Humans were arranged as in experiment 1 and the stimulations were repeated. Data Analysis Complete details of the digital computer analysis techniques are reported elsewhere (13). In brief, the eye position signal was digitized at a rate of 200 samples/s and then differentiated to yield instantaneous eye velocity. Fast components (saccades) were identified and removed based on their direction and velocity profile. Conventionally, OKN is quantified by a gain measurement. Since vertical OKN slow phase velocity fluctuated with time (see Figure 1), any method of calculating OKN gain depended on the selection of a "representa- 311 tive" sample of the response. We chose to measure the average slow phase velocity for the first 30 seconds:. average slow phase velocity (30 s) gain =.' stimulus velocity For OKAN, we measured the average slow phase velocity of single nystagmus beats at specific time intervals (2, 10, and 20 s) after lights out. VerticalOKN Results Nystagmus pattern. At the onset of vertical optokinetic stimulation, nystagmus slow Subject 3,I~i-I II i.ile~~~iymwi~amr~l'i'nr(ffi(..{}r~~!riirlil{f'(' ]]..... '.j.... ~ ~...: , r~,.. 5 sec....j.. U..n.....~~~fWVw.r~. JJI.IW,.}IJ\J,)Ii), 1111 L I ~ I 25 /s.~......i~,m,~11'~~,~~i~frlitl~'~,iiwiitlffmii,rlmtil'fjm t 45 0/s Jl I '" I I ~1M~Jrr.n'w~~J~1 '1--'N~JJ~~J~I~~~IJJJ~V~W~lkJJ;\W~~~~~V~!,l~ ;il~hv~~;~~~~wrl;;\~ Figure 1. Slow phase velocity profiles of vertical OKN in two subjects (upright head position). Zero velocity is indicated by the level at which fast phases were clipped. Upper traces = slow phase up OKN, lower traces = slow phase down OKN. Vertical bars indicate onset of stimulus. Note irregular pattern, especially at higher velocities, slow phase velocity peaks during the first few nystagmus beats and opposite up-down asymmetries in the two subjects.

4 312 phase velocity increased to a peak level within the first second. After the first 3 to 5 nystagmus beats, slow phase velocity decreased to a slightly lower level and then fluctuated around a steady state value over the stimulation period (Figure 1). Slow phase velocities depended strongly on vigilance; asking the subjects to concentrate on the stripes immediately increased slow phase velocity. Fluctuations of slow phase velocity were greater at higher stimulus velocities (particularly downgoing) 'out [here was considerable iiner-individual variability. Gain and influence of posture. OKN gain values for different stimulus velocities and head positions are given in Table 1. There were no consistent up-down asymmetries. Furthermore, gain was not reliably altered by position (head onside versus head upright). Vertical OKAN Nystagmus pattern. Optokinetic stimulation at 45 /s for 90 s elicited OKAN jn all 5 subjects (Figure 2). The strongest and most consistent OKAN was obtained with the subject's head onside after upward optokinetic stimulation (relative to the head). Even in this op- A. Bohmer and R. W. Baloh timal condition, OKAN was much weaker and had a different time course than vertical OKAN reported in monkeys. The slow phase velocity dropped from approximately 30 / s at the end of OKN stimulation to about 5 /s in less than 1 s and then further declined slowly with some fluctuations. No reversal of OKAN was observed following upward optokinetic stimulation. By contrast, nystagmus following downward stimulation reversed direction almost immediately after the lights were turned off. one SUbject developed OKAN in the appropriate direction after downward stimulation and this only occurred in the onside position. Gain and influence of posture. Following upward stimulation, mean upward slow phase velocity was higher in the lateral than in the upright position but 2 of 5 subjects had slightly greater upward slow phase velocity in erect position (Table 2). The decay in OKAN slow phase velocity following upward stimulation was approximately linear degrees per second per second based on mean values in Table 2 (0.25 and 0.20 per second per second between 2 and 10 and 10 and 20 seconds, respectively). The magnitude of OKAN II following downward stimulation was too low to measure a rate of decay in either position. Table 1. Vertical OKN Gain (Slow Phase Eye Velocity/Drum Velocity) for Individual Subjects at Different Stimulus Velocities ( /s) and Head Positions (Stimulus Velocity 45 /5) At different stimulus velocities 15 /s 30 0 /s 45 /s 60 0 /s Subject Up Down Up Down Up Down Up Down At different head positions Upright On side Subject Up Down Up Down

5 Vertical OKN and OKAN in Humans 313 Subject 1 t{) 4 ~! ~ i Stimulus -::;: ~~ (re subject) vi~~~~~~~~ t. 1 ~~j~~1 Subject 5 ~-~ rnidjwj~~ + '1Jrl""Wl\.JJ\OI\,/llylr.. lljlwih,mfir-th~~t~i'1~~f"~~!i~, I Figure 2. Eye position (top) and eye velocity (bottom) curves of OKN/OKAN elicited with 45 0 Is vertical optokinetic stimulation in head onside (left) and upright position (right) in two subjects. Vertical bars indicate "lights off." Discussion We found no consistent asymmetry of vertical OKN in normal human subjects tested in the erect or onside positions using the scleral search coil technique. This contrasts with prior studies in humans, which reported higher gains for slow phase up than for slow phase down OKN (2-5). However, the asymmetries were also inconsistent in these studies. Takahashi et al (2) found the asymmetry only at stimulus velocities> 60 0 /s, while LeLiever and Correia (3) observed it at 50 0 /s, but not at higher or lower velocities. Furthermore, some subjects showed a reverse asymmetry (down slow phase velocity> up slow phase velocity) (3,7). With the search coil technique, OKN gains in response to upward stimulus motion were higher in 6 of 7 subjects in the study of Van den Berg and Collewijn (4) and in 7 of 10 subjects reported by Murasugi and Howard (5), while in another study of the latter group only 3 of 5 subjects had higher upward gains (14). Another source for inconsistencies might be the way OKN gain is measured. As shown in this study (Figure 1),

6 314 Table 2. Slow Phase Velocity (Degrees/Second) of OKAN at Discrete Time Intervals (2, 10, and 20 s) after the End of Optokinetic Stimulation with Subject Onside and Upright. Negative Values Indicate Slow Phases in Opposite Direction to Optokinetic Stimulation Slow phase up OKAN Slow phase down OKAN Subject 2 s 10 s 20 s 2 s 10 s 20 s Onside X SO Upright X SO vertical OKN is irregular, especially at higher stimulus velocities, and any method that determines one gain value is somewhat arbitrary. In monkeys tested onside, upward optokinetic stimulation (re the animal's head) induces more regular nystagmus with a higher slow phase velocity than does downward stimulus movement (9). There is a gradual buildup in upward slow phase velocity after stimulus onset. When tested in the upright position, these differences between up and down slow phases diminish (ie, upward slow phase velocity decreases to approach that of downward slow phase velocity). Presumably otolith signals generated in the onside position selectively enhance upward slow phase velocity via the velocity storage mechanism (9). In humans, the effect of static head position on vertical OKN gains has been studied before only with EOG techniques, and an elimination or decrease of OKN asymmetry was found in the lateral and head-hanging position in some subjects and even reversal of asymmetry occurred in other subjects. In the present study, vertical OKN was not affected by a change of position. From our findings A. Bohmer and R. W. Balah and other reported data (5,14) we conclude that asymmetries in human vertical OKN are inconsistent with a tendency to higher slow phase up than slow phase down gains, especially at higher stimulus velocities. In contrast to vertical OKN, OKAN is consistently asymmetric in human subjects. Slow phase up OKAN was poor in the erect and onside positions; slow phase velocity dropped immediately to about of the OKN velocitv and then declined slowly. Following optokinetic downward stimulation, nystagmus reversed direction and then slowly decayed. Similar findings in humans studied with EOG have been reported by Baloh et al (7) and LeLiever and Correia (3). By contrast, monkeys have OKAN in the appropriate direction after upward and downward optokinetic stimulation. When tested in the onside position the initial velocity of upward slow phases is about 800,10 of the steady state OKN veloc- : ity (9). OKAN then exponentially declines I with a time constant around 15 s, occasionally followed by OKAN II. In the upright position, slow phase up OKAN has a lower velocity and a more rapid decay than in the onside position, but is still easily elicited. Slow phase down OKAN occurs in the monkey, but it has a lower velocity than slow phase up OKAN in the upright and onside positions. Thus, human vertical OKAN differs from monkey vertical OKAN in that the former decays at a different rate and has an immediate reversal of nystagmus direction following downward stimulation. Immediate reversal of nystagmus direction following horizontal optokinetic stimulation, ie, horizontal OKAN II without OKAN I, has been observed in bilateral labyrinthinedefective humans (15), in bilateral labyrinthectomized monkeys (16), and in monkeys following bilateral section of the lateral semicircular canal nerves (17). Reversed OKAN in these circumstances occurs in both directions. From these data it was concluded that OKAN I is related to a velocity storage mechanism that disappears after loss of peripheral vestibular input, while OKANII results from another mechanism that persists after loss of vestibular input (18). These two mechanisms differ in other respects: prolonged optokinetic

7 Vertical OKN and OKAN in Humans stimulation diminishes OKAN I, but increases the intensity and duration of OKAN II (10,16); OKAN I but not OKAN II is sensitive to amphetamine (19). Brandt and colleagues (19) postulated that these two systems produce antagonistic nystagmus, both discharging simultaneously after cessation of the optokinetic stimulation. The final outcome is the sum of the two. Our data suggest that vertical OKAN in humans can also be described as the of two directed storage mechanisms, a shorter time constant system in the direction of the prior OKN (system A), and a longer time constant system in the reverse direction (system B). Upward optokinetic stimulation (particularly in the onside position) results in greater velocity storage in system A than in system B so that OKAN is in the direction of the optokinetic stimulus. Downward optokinetic stimulation activates system B more than resulting in a reversed OKAN. Models of the vestibulo-ocular and optokinetic aptation element ferent OKAN that include a central adl) can predict these difa different time constant for uri and down stimulation. Acknmv/edgl11enrs- Dr. Bohmer \\'as supported the Scbweiz Stiftung fuer medizinisch-biologische Forschung and Dr. Baloh by NIH Grant DC The authors thank IVls. K. Jacobson and Mr. K. Beykirch for their technical assistance. REFERENCES 1. Jell RM, Ireland DJ, Lafortune S. Human optokinetic afternystagmus. Slow phase characteristics and analysis of the decay of slow phase velocity. Acta Otolaryngol (Stockh). 1984;98: Takahashi M, Sakurai S, Kanzaki J. Horizontal and vertical optokinetic nystagmus in man. ORL J Otorhinolaryngol Relat Spec. 1978;40: LeLiever WC, Correia MJ. Further observations on the effects of head position on vertical OKN and OKAN in normal subjects. Otolaryngol Head Neck Surg. 1987;97: Van den Berg AV, CoIlewijn H. Directional asymmetries of human optokinetic nystagmus. Exp Brain Res. 1988;70: iviurasugi CM, Howard IP. Up-down asymmetry in human vertical optokinetic nystagmus and afternystagmus: contributions of the central and peripheral retinae. Exp Brain Res. 1989;77: J Collins WE, Schroeder DJ, Rice N, Mertens RA, Kranz Some characteristics of optokinetic eyemovement patterns: a comparative study. Aerospace Med. 970:41' j 251 clvnanilc> mal! /;.. Melvill.lone'.. I nflucncc oj' c\'clid move melli upon elecllc' onllograrhic recording or vertical mo\emcnt:. i\erospac~' Md. i l}6sj6:~ l\tlatsuc; V Cohen B. Vertical optc)kinclic nystagmus and vest ibula! nystagmus the mon key: up-down asymmetry and effects or gravity. Ex!, Brain Re~. 1984;53: Himi T, Igarashi M, Kulecz WB, Kalaura A. Asymmetry of vertical optokinetic afternystagmus in squirrel monkeys. Act.a Otolaryngol. J988;105: Robinson DA. A method of measuring eye movements using a scleral search coil in a magnetic field. IEEE Trans Biomed Elect. 1963; 10: CoIlewijn H, Martins AJ, Steinman RM. Compensatory eye movements during active and passive head movements: fast adaptation to changes in visual magnification. J Physio! ;340: Baloh RW, Langhofer L, Honrubia V, Yee RD. Online analysis of eye movements using a digital computer. Aviat Space Environ Med. 1980;51: Howard IP, Simpson WA. Human optokinetic nystagmus is linked to the stereoscopic system. Exp Brain Res. 1989; Zee DS, Yee RD, Robinson DA. Optokinetic responses in labyrinthine-defective human beings. Brain Res. 1976;113: J 6. Igarashi M, lsago H, Alford BR. Effects of pro longed optokinetic stimulation on oculomotor and locomotor balance functions. Acta Otolaryngol (Stock). 1983;95: Cohen B, Suzuki.11. Raphan 1'. Role of the otolith organs in generation of horizontal nystagmus: ecrccl', of selective lalwrinthinc lesions. Brain Res Ui.ltlon: inverted SC1!1l)()li(ll l'crccpllon and onluiinet]\. altcl -nnu.li2111u: Brair' j: 19. igarashi,himi!\syml1lcij'\ verticalo[llokinetic n)'stagmm aild aflernystagnlu';. nrl. 1%~:;SO: 21 :W. Leigh I<.. i Robinson hypothetical explanation for periodic alternating nystagmus: instability in the optokinetic-vestibular system. Ann NY Acacl Sci. 1981;374: Furman JivlR, Hain TC, Paige GD. Central adaptation models of the vestibulo-ocular and optokinetic systems. Bioi Cybern. 1989;61 :