Frequency spectrum of optokinetic nystagmus in the normal monkey

VisionRcs.Vol. 13,pp. 2361-2368.PergamonPress1973.Printedin Great Britain.

FREQUENCY

SPECTRUM OF OFTOKINETIC IN THE NORMAL MONKEY’

NYSTAGMUS

Jo& A. VALCIUKXS*, PEDRO PAZJK and TAU~A PASIK Department of Neurology, Mount Sinai School of Medicine of The City University of New York, New York, N.Y. 10029, U.S.A. (Received 9 Febramy 1973)

INTRODUCTION SUCCESSIVEtargets moving across the visual field elicit oculomotor responses consisting of jerky repetitive movements designated as optokinetic nystagmus (O.K.N.). This pattern of eye movements involves an alternation of slow smooth deviations in the direction of the moving stimuli and of fast movements in the opposite direction. It is tempting to equate the fast and slow phases of nystagmus to the two types of eye movements which occur in the primate in response to visual stimuli, namely the saccade and the smooth pursuit movement (RASHBASS, 1961). While the saccade is a response to the change in target position, presumably for bringing the object of regard to the fovea, the smooth pursuit is a response to the velocity of the retinal image, apparently to keep the object of regard on the fovea. However some investigators (BENDER, 1969) have considered it more appropriate to interpret O.K.N. as comprising two interrelated phases forming a unit, the nystagmic beat, which cannot be split into independent components. The direction of O.K.N. is given by the direction of the fast phase. This viewpoint has a physiologic basis given by the results of ablation experiments in monkeys and clinicopathological correlations in man. It has been found that any lesion of the central nervous system affecting conjugate gaze in one particular direction interferes with all kinds of eye movements in that direction, namely smooth pursuit, saccades and O.K.N. (PASIK and PASIK, 1964; BENDERand SHANZER,1964). For instance, a left cerebral hemid~o~i~tion will affect smooth pursuit movement and saccades to the right as well as O.K.N. with the quick phase to the right (PASIK, PASIK and BENDER,1960). It should be emphasized that the slow phase to the left is also defective whereas smooth pursuit movements to the left are not. Studies on O.K.N. have followed two main lines of research. One was directed to tid out the various brain structures concerned with the phenomenon, utilizing basically the ablation technique (TER BRAAK, 1936; PASIK and PASIK, 1964; BENDERand SEANZER, 1964). A common problem with these studies has been their limitation to qualitative descriptions. A second approach has been the study of stimulus-response relationships, which in turn would help to a better understanding of how the visuo-oculomotor system encodes and processes visual information. Initial investigations in man have offered a series of free-hand curves 1 Aided in part by U.S.P.H.S. Grants No. MH-02261 and K3-Ey-16,865. We are tha~u1 to DR. PETER writing the computer program used for data analysis. 2 Present address: Laboratorio de Investigaciones Sensoriales. Facultad de Mcdicina, Univmidad de Buenos Aires, Cbrdoba 2351, Buenos Aires, Argentina. Request reprints to Mount Sinai School of Medicine address. 2361 YJI.13112~M SCHILDERfor

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Josi A. VALCIUIW, PEDRO PWK ANDI”NB~ P.UIK

describing some of these relationships (GRUTTNER, 1939). More recently, attempts were made to quantify the phenomenon in the monkey and the results were given in graphical displays of data for selected animals (K~M~TSUZAK~, HARRIS, ALPERTand COHEN, 1969). Finally, upper and lower optokinetic frequency thresholds have been obtained for the same experimenta animal (VIILCIUKAS,1972). In the latter study the absolute luminance threshold for optokinetic responses was also estimated. The present investigation represents our first attempt to determine suprathreshold stimulus-response relationships in the O.K.N. of a group of normal monkeys in terms of the influence of stimulus temporal frequency and Iuminance upon the nystagmus frequency. The selection of the latter as the dependent variabte was made because it is a response characteristic that applies to the concept of considering the nystagmic beat as the response unit. The peak-to-peak amplitude of the beat, which also satisfies this criterion, has the obvious disadvantages of requiring involved calibration techniques in animal subjects. In addition, the use of the response frequency allows the evaluation of the entire spectrum of the phenomenon and the further analysis of the data in terms of a so-called “efficiency” function which has been defined as the ratio between response and stimulus frequencies (BERMANN, CHAIMOVITZ, GUTMANand ZELIG, 1963).

MATERIALS AND METHODS Six monkeys (Macace mulattu), 2-5 kg of body weight, were used and selected on the basis of a not-ma1 neurologic status and the absence of spontaneous nystagmus in darkness as revealed by electrooculography. It was found that 10-20 per cent of animals obtained from an importer exhibited this abnormality. Testing sitaatlon Stimulatiofl techniques were similar to those described in a previous publi~tjon (VALCW, 1972). In short, the monkey sat partially restrained in a primate chair behind a 106 x IO6 cm rear-projection screen located at 25 cm in front of the animal’s face. The head was held relatively Sxed with a molded, rubberpadded holder. A specially designed 35 mm film-loop projector with a regulated d.c. power supply was used to produce the stimuli on the screen. The stimulus unit consisted of a vertical luminous stripe and a dark band with a total width of 30 cm (64” of visual angle at the center of the screen). The light-dark ratio was 1:9. The mean luminance of the luminous stripes was O-56 log ft-L as measured with a Macbeth Illuminometer. Another luminance level was obtained by fitting a 4 log calibrated neutral density filter in front of the projection lens. The stimuli could be moved at constant speed to the right or to the left by means of a scrvomotor coupled to the film transport mechanism. In four of the monkeys, five velocities were utilized resulting in stimulus frequencies of 05, l-0,2*0,4*0 and 8.0 I%. Therefore, they covered a I.2 log unit range in 0.3 log steps. In the other two animals a wider range, covering 3.0 log units from O-03 to 32 Hz, was used in order to test the validity of a prediction based on the results from the previous four monkeys. Binocular stimulation was used throughout. Each monkey was given an intramuscular dose of 1 mg/kg of body weight of amphetamine sulfate, 30 min before the session in order to attain a reproducible level of aitertness during the experimental session without affecting the oculomotor response (COHEN, ALPERT, KOMATSUZAKIand HYAMS,1969; VALWJIC.G, 1972). Eye movements in the horizontal plane were recorded by conventional RC-coupled a.c. electrooculography with a 0.1 set time-constant through sharp platinum needles inserted subcutaneously at the outer canthi. These electrodes are commonly used for electroencephalography in man without causing major discomfort. Procedures for collection and analysis af data Each of the initial four monkeys was tested in six daily sessions utilizing either the 4.56 log ft-L (low) or the O-56 log ft-L (high) luminance level on alternating days. In each session a block of six trials at each of the five stimulus frequency values was given in a random order. The trial duration was 20 set and in each block, half the trials were to the right and half to the left in a random sequence. Since for the purpose of analysis, the results of trials to the right and to the left were combined, this program of stimulus presentations resulted in a total of 18 determinations (trials) at each luminance and stimulus frequency (F,) examined. In the other two animals, 11 stimulus frequencies were tested at each of the two luminance levels.

Frequency Spectrum of Optokinetic

Nystagmus

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The total number of rapid eye movements to the right and to the left were counted automatically by means of a specially programmed PDP-g/I digital computer. The auxiliary output of the polygraph was matched to the input of an analog-to-digital converter. Analog-to-digital conversions were taken every 50 msec and stored in a 400 location table, thus providing the timing of 20 set trials. At the completion of these conversions the number of each was substracted from the one that followed it. The resulting differences and their sign were then stored in a 399 location table. These numbers were analyzed via a series of short programs which compared them to a limit value selected empirically so that the number of eye movements counted by the computer matched the eye movements counted visually in the electrooculograms. These programs performed the following operations: (1) Any difference below the limit value was rejected; (2) The 6rst difference greater than the limit value was counted as an eye movement and then assigned a direction according to the sign, to the right if positive and to the left if negative; (3) Subsequent differences were ignored until one fell below the limit value. The correlation coefficient between the computer and visual counting was checked periodically and maintained at least at 0.99. The program also calculated the frequency of response (F,) as the result of (R-L)/?, where R was the total number of nystagmic beats to the expected side, L the beats to the opposite side and t the duration of the trial which was constant and equal to 20 sec. This procedure was necessary because the response frequency could vary within a trial and rapid eye movements in the direction opposite to the nystagmus were present occasionally.

RESULTS

Influence of stimulus frequency (FJ and luminance (B)

A similar pattern was present in each of the initial four experimental animals: F, increased with the log of F, up to a peak, after which F, started to decline. In each case, a higher peak response was always associated with a shift in its location towards higher values of F,. Figure 1 (top) illustrates in graphical form the group data in terms of means and standard deviations for every value explored. Mean F, indeed increased linearly with the logarithm of F,. The mean peak response was higher at the higher luminance condition, the values being 2.3 and 1.3 nystagmic beats per second respectively. The locus of the peak also occurred at different F, values, namely 4 and 2 Hz respectively. The degree of variability of the data was greater at the low luminance level. Although the initial increase in F, appeared to be slower at low luminance, no significant difference in the slopes were found, possibly due to the small number of points determined. In order to evaluate the influence of B upon F,, t-tests for matched pairs were performed. The difference between the means of F, at both luminances were compared for each F, value and found to be statistically significant (p c 0.025) except at 0.5 Hz. “Eficiency” function

Figure 1 (bottom) depicts the same data as illustrated in Fig. 1 (top), but replotted in terms of the “efficiency” ratio (E) defined as the number of nystagmic beats per stimulus unit (BERGMANNetaf., 1963). Means and standard deviations are displayed, and it is apparent that the means at each luminance level fall on remarkably straight lines. It should be noted that similar functions were found in individual animals. These findings allowed to relate E and log F, by a logarithmic function of the type: E = a + b log F,.

The values of the constants a and b were calculated by the method of least squares and the equations of the “efficiency” ratio for the two luminance levels were found to be: EC4.56, = 0.964 -

I.033 log F,

E C0.56j= I.236 -

1.073 log F,

where the subscript of E indicates the level of B in log ft-L.

Josf A. VALCWKAS, PEDROPurr AYD TAUBA PMK

2364

1

E'0.964-1.033 loq Fs *0.044-0.161 lop VI

O

Ell.236-1.07310qFs ~0.050-0.166

lop V,

I

f

L

0.5

1.0

2.0

4.0

6.0

0.S

1.0

2.0

4.0

6.0

F,

32

64

126

256

512

32

64

I26

256

512

v,

FIG. 1. Influence of stimulus frequency (F,) and luminance (B) upon O.K.N. frequency (F,). The abscissa is a logarithmic scale with values given in bands/xc (F,) and equivalent degrees/ set at center of screen ( V,). Solid circies correspond to B = 4.56 log ft-L; open circles, B = 0.56 log ft-L. Each point represents the group mean (n = 4) which is based on 18 determinations for each monkey. Vertical segments indicate the standard deviations. At the top, the ordinate is in nystagmic beats/xc. Note the increase of F, with log F,. and the magnitude and location of the peak F, which are higher at higher luminance levels. At the bottom, the ordinate is in nystagmic beats/stimulus unit defined as “efficiency” (E = F./F,). The straight lines represent the lines of best fit for the sample data as determined by the method of least squares. Equations are given in terms of both F, and V,.

These equations indicate that the slopes of the functions for these levels of luminance are practically parallel as revealed by the similarity of the regression coefficients (1.033 and 1.073). In addition, the difference between the Y intercepts for both functions is approx. 0.25. In other words, a 4 log increase in B results in an increase of l/4 of nystagmic beat per stimulus unit at each F, tested. It is also evident from these curves that the 1: 1 relationship between F, and Fp is represented by a single point in each curve which is different for the low and the high luminance level (O-92and 1.70 respectively). Optokinetic frequency function

The equation described above allowed the computation of F, values which covered the entire theoretical range of O.K.N. by a simple algebraic manipulation. Since E = F,/F,, then F; = F, (a + b log F,) and therefore, F rCa.56j= F, (0.964 - I.033 log F,) F rC,,.56j= F, (I.236 -

2.073 log FJ

Frequency Spectrum of Optokinetic Nystagmus

2

4

6

I6

32

64

I26

256

512

2365

1024 2046 V,

FIG. 2. Theoretical and empirical O.K.N. frequency spectra at two luminance levels. Notations as in Fig. 1. Curve-srepresent the functions at both luminance levels predicted from data of the initial four monkeys. Circles indicate mean values of empirical determinations in two additional animals. Note that in the middle range there is agreement with the findings illustrated in Fig. 1, top. It is clear that there is a most effective stimulus with a decay of the response above and below this value. The left and right tails of the functions represent the regions where lower and upper Iimens are expected. Extremely low F, can not be effectively discriminated from spontaneous activity and consequently the empirical data at both tails are probably the expression of the latter. As previously demonstrated, luminance does not affect the lower thresholds whereas it influences significantly the upper thresholds (VALCIUKAS, 1972).

Figure 2 depicts the two theoretical curves (solid lines) representing the latter equations, covering the entire range of stimulus frequency at both luminance levels. It is apparent that these curves have in common an initial slow acceleration, and, after a peak response, a rapid deceleration. The differences in the magnitude of the peak response and its location in the F, axis are similar to those obtained from the empirical data. Moreover, these curves also

predict that luminance would influence the upper frequency thresholds, since there is a considerable separation of the functions at the highest F,, whereas the effect on the lower thresholds would be negligible because the curves converge toward an asymptote in the region of low F,. Empirical test of predicted functions

The last two monkeys served to test the validity of the predicted optokinetic frequency function for the two luminances explored. Figure 2 shows that the means obtained at 11 values of F, match closely the theoretical curves. In fact the values of the constants a and b were 1G48 and - 1.073 at low luminance, and 1.339 and -1.183 at high luminance.The proposed equations therefore appear to describe satisfactorily the relationship between stimulus and response frequencies in O.K.N. DISCUSSION

The present findings showed that the frequency of O.K.N. is related to the temporal frequency of the stimulus in a complex manner which is predictable by an equation of

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Jo& A. VAUZUKAS. PEDRO PAQK AYDTAUBA

PASIK

logarithmic nature. In addition, this function is also affected by the stimulus luminance. It should be emphasized that the spatial frequency was held constant in these experiments and therefore no conclusions can be drawn as to its effects. In any event, no such influence could be demonstrated in the cat (HOMCUBIA,Scorr and WARD, 1967). Since spatial frequency was not varied, temporal frequency was linearly related to velocity, and consequently the results apply also to the effect of this latter stimulus parameter. The only change in the proposed equations would be reflected in the value of the constants (see Fig. 1, bottom). A curve resembling that described in the present study has been reported for the relationship between stimulus and response frequencies in another type of visually evoked nystagmus, namely the response to monocular flicker stimulation (PASIK,PASIKand VALCIUECAS, 1970). It is also noteworthy that a similar function has been offered for the relationship between the frequency of moving light-dark patterns and the frequency of discharge of visual cortex neurons in the cat (GR~;‘ssER,GRATER-CORNETS and HAMASAKI,1970). It is tempting to speculate that the general shape of the O.K.N. frequency spectrum is the expression of the response of a population of visual units which are more or less optimally fired at different stimulus frequency values. Similarly to the response of other sensory systems, the spectrum of ocular movements elicited by moving patterned light occurs only within a portion of the stimulus range. Such spectrum can be considered as the resuit of limiting factors imposed by the visual and oculomotor systems at the input and output ends, as we11as the interaction between the stimulus movement and the additional movement of the retinal image produced by the ocular deviations (TER BRAAK,1936). Purely oculomotor factors can be safely excluded as being responsible for the influence of luminance. When this parameter increases, it affects at least three components of the optokinetic frequency function. There is an increase in the magnitude of the peak response and in the stimulus value at which it occurs, as well as a widening of the range of effective stimuli. The latter effect results mainly from the shift in the upper frequency thresholds (VALCIUKAS, 1972). The present data do not allow a full description of the influence of Iuminance since only two values were utilized. However, earlier results ~ALCIUKAS,1972) suggest the presence of scotopic and photopic components within the Iuminance effect. Only preliminary attempts have been made to study the influence of luminance on O&N. in man (GR~~TIXER,1936). It was noted that “wide” changes in this parameter did not affect the response and that only at very “low” luminances a progressive decline of frequency, amplitude and slow phase velocity was apparent. It is possible that the initial range where no variations were found was in fact too narrow (less than 2 log units} to detect the changes. The contribution of oculomotor factors to the shape of the O.K.N. frequency spectrum can not be ascertained from our findings. It is apparent, however, that the peak response, within the restrictions of the experimental conditions, was not limited by the monkey’s motor capacity. In the latter case, a plateau would be expected instead of a peak. Moreover, it is known that nystagmus of higher frequency can be elicited by vestibular stimulation and that . occasionally even O.K.N. frequencies have been observed in the 3-4 beatslsec range (KOMATSUZAKI et al., 1969). The limitations set by the oculomotor system may be expected to determine the maximum value of the peak response which would occur at luminances above the highest utilized in the present study. This possibility is suggested by the fact that the latter value was only 6 log units above the absolute threshold (VALCIUIC~S, 1972) and therefore a further influence of luminance is conceivable for other 5-6 log units. The interaction between visual and oculomotor factors in the final outcome of the

Frequency Spectrum of Optokinetic

Nystagmus

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phenomenon may also be reflected to some extent in the equation derived from our data. It has been recently demonstrated in the monkey that when the interaction is eliminated by monocular stimulation of an opthalmoplegic eye, the O.K.N. frequency of the contralateral normal eye increases significantly when low stimulus velocities are used (KOERNERand SCHILLER,1972). It is difficult to compare the present results to findings by other investigators who explored rather narrow stimulus ranges and usually without specifications as to the luminance level. A possible exception is a study in the rabbit (BERG~U~ et al., 1963) where a curve similar to ours was given. The fragments of the spectrum reported by other investigations for man (GRUTTNER,1936), monkey (KO~~ATSUZAKI et al., 1969) and cat (HO&~RUBIA et al., 1967) included only the ascending portion of our function reaching usually the peak response. When these data were re-analyzed in terms of “efficiency” functions, straight lines were also obtained and therefore a reconstruction of the entire spectrum was possible and found to be of similar nature as the one reported here. The values of the constants, however, were different and this may be attributed to variations in other stimulus parameters from which luminance could be the most significant one. Other studies in man have failed to show a significant influence of the temporal frequency or velocity of the stimulus upon the frequency of the response (MACKENSEN,1954). This apparent discrepancy may be due to the fact that this investigator explored a very narrow range, roughly equivalent to 4-8 Hz at the high luminance level, where our curve exhibits also a small plateau around the peak response.

REFERENCES BENDER, M. B. (1969). Disorders of eye movements. In Hun&ok of Clinica Neurology (edited by P. J. VINKEN and G. W. BRWN) Vol. I, pp. 574-630. North Holland. Amsterdam. BENDER, M. B. and SHANZER\ S. (1964). Gculomotor pathways defined by electrical stimulation and lesions

in the brainstem of monkey. In T!re Oculomotor System (edited by M. B. BENDE@,pp. 81-140. Harper and Row, New York. BERGMANN, F., CHAIMOVITZ, M., GUTMAN, J. and ZELIG, S. (1963). Optokinetic nystagmus and its interaction with central nystagmus. J. PhysioL,Lond. 168,318-331. COHEN, B., ALPERT, J., KOMAT~UZAKI.A. and HYAMS,L. (1969). Effects of light and amphetamine on horizontal saccadic eye movements of the rhesus monkey. Neurology, 19, 316-317. GROSSER,O.-J., GR~&ER-CORNEHLS.U. and HAMASAKI, D. I. (1970). Cited in: Grtisser, O.-J. and GrtisserComehls, U. Neuronal mechanisms of visual movement perception and some psychophysical and behavioral correlations. In Handbook of SensoryPhysiology (edited by R. JUNG), Vol. VII (In press). GR~JTTNER,R. (1939). Experimentelle Untersuchungen iiber den optokinetischen Nystagmus. 2. Sinnesphysiol. 68, l-48. HONRUBIA,V., SCOTT, B. J. and WARD, P. H. (1967). Experimental studies on optokinetic nystagmus. I. Normal cats. Actu oto-lur. 64,388-402. KOERNER,F. and SCHILLER(1972). The optokinetic response under open and closed loop conditions in the monkey. Exp. Bruin Res. 14, 318-330. KOMATSUZAKI, A., HARRIS, H. E., ALPERT, J. and COHEX, B. (1969). Horizontal nystagmus of rhesus monkeys. Actu oto-lur. 67,535~551. MACKENSEN, G. (1954). Untersuchungen zur Physiologie des optokinetischen Nystagmus. Afbrecht V. Gruefes Arch. Opthul. lSS,284-313. PASIK, P. and PASIK, T. (1964). Gculomotor function in monkeys with lesions of the cerebrum and the superior colliculi. In 7he Ocuiomofor System (edited by BENDER,M. B.), pp. 40-80. Harper and Row, New York. PASIK, P., PASIK, T. and BENDER,M. B. (1960). Oculomotor functions following cerebral hemidecortication in the monkey. Archs. Neural. 3,298-305. PASIK, T., PASIK, P. and VALCIUK~S,J. A. (1970). Nystagmus induced by stationary repetitive light flashes in monkeys. Bruin Res. 19,313-317. RASHBASS.C. (1961). The relationshio between saccadic and smooth trackina eve movements. J. Phvsiol.. Lond. iS9, j26-_j38.

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BRAAK, J. W. G. (1936). Untersuchungen iiher optokinetischen Nystagmus. Arch. n&4. Physiol. 21, 309-376. VALCIUKAS, J. A. (1972). Optokinetic thresholds in the normal monkey. Vision Res. 12, 1397-1407.

TER

Abstract-The frequency of optokinetic nystagmus was determined in four monkeys at two luminance levels utilizing middle ranges of stimulus temporal frequency. Results conformed to an equation of logarithmic nature which allowed the prediction of the entire spectrum. Empirical testing in two additional monkeys contirmed the properties of such a function. Nystagmus frequency increased linearly with the logarithm of stimulus frequency to a peak and declined thereafter. An increase in luminance resulted in increases of the peak response magnitude and location, and in the widening of the effective stimulus range. The relative contribution of visual and oculomotor factors as well as the interaction between them is discussed.

R&&--On determine la frequence du nystagmus optocinttique sur quatre singes B deux niveaux de luminance et en utilisant les domaines moyens de frequence temporelle du stimulus. Les rCsultats obeissent B une equation de nature Iogarithmique qui permet la prediction du spectre entier. Des essais empiriques sur 2 autres singes confirment les propri&Cs d’une telle fonction. La frkquence du nystagmus augmente r&uIi&rement avec le logarithme de la fr& quence du simulus jusqu’g un maximum et diminue ensuite. En augmentant la luminance, on augmente l’amplitude et la position du maximum de rhponse et on elargit le domaine du stimulus effectif. On discute la contribution relative des facteurs visuels et oculomoteurs et de I’interaction entre eux.

Zusammenfassuog-Die

Frequenz des optokinetischen Nystagmus wurde bei 4 Men fiir zwei Leuchtdichteniveaus unter Benutzung eines mittleren Zeitfrequenzbereichs fur den Reiz bestimmt. Die Resultate passten zu einer Gleichung von logarithmischer Natur, die die Vorhersage des gesamten Spektrums gestattete. Ein empirischer Test bei zwei zusltzlichen Atfen be&it&e die Eigenschaften einer solchen Funktion. Die Nystagmusfrequenz stieg linear mit dem Logarithmus der Reizfrequenz zu einem Gipfel an und fiel nachher wieder ab. Ein Vergriissem der Leuchtdichte fiihrte zu einem Anheben der Antwortgriisse beim Gipfel und der Lage des Gipfels und zu einer Verbreiterung des effektiven Reizbereiches. Die relativen Anteile von visuellen und okulomotrischen Funktionen am Effekt als such ihre Wechselwirkung werden diskutiert.

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