Vi&m Res. Vol. 12,pp.487-493. Pergamon Press 1972. Printed in Great Britain
INTERMITTENCY, THE VISUALLY
PUPILLARY DIAMETER, EVOKED POTENTIAL
DONOVANI?. FLEMING,’CHARLJSE. WILSONand H. KENT MERRILL Veterans Administration Hospital, Phoenix, Arizona, U.S.A. (Received 15 April 1971; in revisedform 21 July, 1971)
A CONS~~RABLE amount of interest has been generated relative to the correlations between visually evoked response (VER) parameters and psychophysical functions (e.g. VON LOFWENICH and FINKENZELLER,1967; MACKAY, 1969). For the most part single photic pulses have been used as stimuli, although a number of studies have been reported wherein photic in~~it~ncy has been utilized. For example, consistent with a light adaptive process, ARMINGTON (1964) noted a diminution in amplitude of certain VER components following exposures to brief photic pulse trains. However, definitive results were not obtained when the photic pulses were distributed repetitively over 5-min exposure intervals. The absence of definitive results was attributed by Armington to the “inherent variability” of cortical VERs. That the presentation of intermittent photic pulses to the eye results in a light adaptive process is well known (e.g. BROWN and WATANABE,1965; FLEMINGand MERRILL, 1970). Tbe question remains, however, whether an adaptive process initiated by presenting intermittent photic stimulation to the retina can be definitively demonstrated with the cortical VER. Because the variability of the VER occluded the effects of prolonged intermittent stimulation in Armington’s study, a methodological approach to this question other than that utilized by Armington was indicated. One such approach was to utilize photic intermittency as background adapting stimulation and to sum responses evoked by single photic pulses presented against this background. It was hypothesized that the background stimuli would reduce fluctuations or “drive” intrinsic cortical rhythms (BARTLEY,1941) to the extent that a single photic pulse would evoke a relatively stabIe VER. This VER should show an overall amplitude modulation in relation to the frequency of intermittent stimulation. Intermittent stimulation of varying frequencies of presentation also has a differential effect on pupillary motility (HARVEY,1970). In most studies, however, modified pupillary diameter is effectively removed as an experimental variable by pupil fixation (e.g. HARVEY, 1970) or by the use of optical systems (e.g. ~NGTON, 1964; BARTLEYand NELSON,1961). Because there is a direct relationship between pupillary size and VER amplitude (BERGAMINI, BERGAMASCO and MOMBELLI,1966) it was reasoned that with the unfixed pupil, a decrease in VER amplitude would accompany an increase in rate of intermittency. Such a decrease in amplitude would presumably covary with the adapting effects of the background stimuli. Therefore, if the fixed eye were used, the direct effects of the adapting stimuli on VER 1 Presentaddress: Department of Psychology, Brigham Young University, Provo, Utah 84601. 487
DONOVAN E. FLEMING.CHARLESE. WILSON AND H. I(EM MERRILL
could be measured; examined using VER amplitude Accordingly the present study was to investigate conditions,
dependent variable. pupillary
subjects of this investigation subjects demonstrated re5ecting hemisphere into which light pulses could be delivered occipital scalp 4 cm above the inion on the The electrode grounding the Brain responses amplified by a Grass Model 7 Polygraph using capacitancecoupled preamplifiers (O-3Hz-3 kHz frequency response; coupling time constant 024 set) and were recorded on magnetic tape. For analysis, responses were summed on a Model 4OOBComputer of Average Transients using a I-see analysis time and were plotted on 25 x 38 cm graph paper. The data were co&ted in the following marmer. A subject was fitted with recording electrodes and then allowed to dark adapt for 5 min. At the conch&on of the dark adapting interval the re5ecting hemisphere was illuminated by intermittent stimulation of a fixed frequency. A series of 5, 10, 15,20, 30 and 100 IIz was used. A “no background”’ (control) condition was also used. The ilhnninan~ of the hemisphere with intermittent stimulation was one ft-c. Illuminance values were obtained with a General Electric Type DW58 photometer by illuminating the hemisphere with intermittent stimulation at 100 Hz. In order to determine whether the light output of the stimulator varied with changes in frequency of intermlttency, values in successive steps of 10 Hz from 0 to 90 Hz were compared with the 100 Hx value. It was determined that the light output was stable throughout the intermittency range studied. In order of appearance of each intermittent condition was randomized for each subject. One min. following the onset of ~te~t~t stimulation, the hemisphere was ~~~ by 100five f&c. single photic pulses separated by a 2-3 set interval. The single pulse stimulus was presented randomly with respect to the phase cycle of the intermittent stimuli. Cortical responses evoked by the 100 pulses were recorded and summed for analysis. The procedure was repeated until 100 photic pulses had been presented against the control and each intermittent background. A S-min dark adaptation period was hterposed between each experimental condition. The procedure was repeated twice for each subject; one run with mobile pupils, a second run with pupils dilated with a 10 per cent neosynephrine solution. The procedures were carried out on different days. At the conclusion of the experiment pupil size for each condition of photic intermlttency was determined for each subject by photographing the left eye while the subject faced the re5ecting hemispherein the standard raoordlng conditions and by measnring the horizontal diameter of the pupils. The diameter of the fixed pupils was aIso measured for each subject. RESULTS
For both pupillary conditions eight regularly appearing wave components of the VER, arbitrarily labelled u-h, were identified and peak delay and peak-to-trough amplitude values were determined for each component. Mean peak delay and amplitude values for mobile and mydriatic control conditions (no intermittent background stimulation) are presented in Table 1. A prelimin~y examina~on with a Wilcoxon Matched-Pairs Signs-Ranks test (SIEGAL, 1956) based on these data revealed that systematic peak delay differences did not exist under the two pupillary conditions (r = 12, p > 0~10). On the other hand, systematic amplitude differences between mobile and mydriatic pupil conditions were observed for control responses (T = 5, p < 0.05). Six of the eight waves were larger under mydriatic than under mobile pupil conditions. To obtain a unitary measure encompassing each of the eight wave components which could be utilized for the statistical comparison of the experimental treatments (pupiliary condition and frequency of background intermittent stimulation over subjects) a measure of total excnrsian was obtained by running a map reading wheel over the VER plots obtained for each procedure. The measure of total excursion represented the first 300 msec of I-set VER plot. These values were submitted to a threedimensional analysis of variance procedure.
Pupillary Diameter, and the Visually Evoked Potential
AMFUTUDEVALUESOF VER COMPONENTS UNDERCONTROL TABLR~.MEANPRAKDRLAYAND (NO INTERhtITlENCY)CONDITIONS FOR MOBILE AND MYDRIATIC PUPaS
Mobile pupils Wave component
Mean peak delay (ms-1
Mean amplitude fr;V)
Mean peak delay (m=G
Mean amplitude (c;v)
416 63.6 81.0 133-6 157.8 201.2 263-S 290.1
261 3.72 4.66 11*01 4.72 5.53 6.69 2.14
38.1 64.4 84.2 121.0 155.2 193.3 263.5 301-l
4.75 6.79 7.23 9.97 4.79 5.19 10.99 3-88
Tutid excursion aimlysis
The comparison of the two pupillary conditions indicated that under mydriasis total excursion was reliably greater than when the pupil was mobile (F = 14-29, df = l/3, p c 0.05).The data in Table 2 show that at every frequency of background examined, total excursion for the mydriatic condition was greater than those for the mobile pupil condition. This is also apparent with inspection of Fig. 1. MOBILE
FIG. 1. VERs of subject CW recorded with mobile and mydriatic pupils under conditions of varied background photic intermittency. In this and the following illustration, surface negativity is indicated by an upward deflection.
E. FLEMING,CHARLESE. WILSON AND H. KENT MERRILL
TABLE~.MEANTOTALEXCURSION (INcm) DJSPLAYEDINTERMSOFPUPILLARYCONDITIONANDFREQUBNCYOP BACKOROUNDINTERMllTENCY Frequency of background
Pupil condition --___ Mobile Mydriatic B
Control 5 _______.~ 40.2 55.0 47.6
33.8 49.2 41.5
10 34.2 47.2 40.7
15 20 ..- -__-_-~___.-~__..________ 35.0 43.2 39.1
29.8 41.8 35.8
33.5 38.5 36.0
29.5 35.5 32.5
It was also noted that frequency of background stimulation had a reliable effect on total excursion (F = 3.23, df = 6/l& p < O-025). As frequency of background was increased, there was a general decrease in total excursion as illustrated in Fig. 1 and displayed in Table 2. In magnitude of total excursion the greatest decrease in excursion was noted between the condition of no intermittency and 5 Hz background stimulation. However, a NewmanKeuls (WINER, 1967) test based on the analysis of variance indicated that the major portion of variance was partitioned between the control condition and those frequencies at and beyond 15 Hz. MOBILE
Photic Intermittency, Pupillary Diameter, and the VisuallyEvoked Potential
An examination of the statistical interaction between the experimental treatments and between the trea~ents and subjects of this investigation indicated that there was no interaction between pupillary condition and frequency of intermittent background stimulation. However, while the subjects responded generally alike with respect to the pupillary and frequency conditions, there were apparent individual differences among subjects in response to the procedures carried out with them. Both the pupil by subject (F = 5.04, df = 3/8, p < 0.01) and frequency by subject (F = 2.73, df = 18/18, p c 0.025) interactions were statistically reliable. Individual differences in response to the treatment conditions can be observed by comparing Fig. 2 with Fig. 1. With mobile pupils, the rank-order correlation between total excursion and frequency of intermittency was -0.82 indicating an inverse relationship between excursion and frequency. On the other hand, the correlation between mobile pupil and frequency of intermittency was 0.99 indicating a direct relationship between diameter and frequency. To remove statistically the effects of pupillary constriction in order to examine the role of light adaptation, a Kendall partial correlation coefficient (SIEGAL, 1956) was computed using frequencies of intermittency and the corresponding total excursions and pupillary diameters as variables. A -0.34 value was obtained. This value suggests that at least 34 per cent of the total excursion changes observed with mobile pupils at the various frequencies of background stimulation were associated with light adaptive processes. With mydriatic pupils (average dilation 9 mm) the correlation between total excursion and frequency of background intermittency was - 1.00 indicating that the diminution in total excursion as frequency of intermittency was increased can be related directly to the operation of light adaptive processes.
Changes in frequency of background intermittent stimulation did not reliably affect wave component peak delay values obtained under mobile or mydriatic pupil conditions. However, peak-to-trough amplitudes of certain waves were reliably affected by changes in background intermittency. For example, with mobile pupils a and d wave amplitudes were both reliably decreased as frequency of background intermittency was increased (F = 4.07, df = 6/18, p < O-025 for a wave; f; = 3.15, df = 6/18, p < O*OSfor d wave). On the other hand with mydriasis, amplitudes of waves Q, e and f were reliably decreased as frequency of background stimulation was increased (F = 15.60, df = 6118, p < O%lOlfor a wave; F = 2.83, df = 6/18, p < 0.05 for e wave; F = 3.45, df = 6118, p < 0.05 for f wave). As these data suggest, there was a generally negative relationship between component amplitude and frequency of background stimulation. The mean correlation between wave component and frequency of background stimulation was -0.32 for the mobile pupil conditions. For the mydriasis condition the mean correlation was -0*50.
DISCUSSION That mydriasis resulted in the recording of VERs of greater amplitude than those obtained with mobile pupils is an observation consistent with the report of BERGAMINI et al. (1966). There had been some question concerning whether evoked cortical potential amplitude was modifiable when pupillary diameter was modified (e.g. FWNANDEZGUARDIOLA, H=ow and ROLDIN, 1964; NAQUET, AEGIS, FISCHW-WILLIAMSand F~A~Ez-Gu~Io~, 1959). It seems well established that cortical response amplitudes
E. FL~MIN~*~KARLES E.
in both human and animal preparations
FLEMING, 1969). It is also apparent that VER
amplitude can be reduced systematically by experimentally reducing the diameter of the pupil. By stimulating the visual system with an intermittent background, varied parametrically, discrete decreases in pupillary diameter can be obtained. Such decreases in diameter are associated with decreases in VER excursion. However, with mobile pupils, not all of the VER diminution could be related to the process of constriction. A component of diminution, as suggested by statistical analysis, was produced by light adaptation. With the fixed pupil, a clear diminution in VER excursion was observed as frequency of background intermittency was increased. These results suggest that the use of background intermittency was an effective means of producing an adaptation to light which was not occluded by the variability intrinsic to the VER. Other sources of variability related to the procedures are apparent, however. Individual differences among subjects in response to the experimental situation were evidenced with the treatments by subjects’ statistical interactions. While there was a general consistency in cortical response produced by the experimental treatments, there were variable shifts in response among the subjects. Presumably, intra-organismic factors modulated the VER patterns elicited by the photic stimuli. These response shifts might be associated with attentional shift, boredom or fatigue. HAIDER, SPONG and LINDSLEY (1964) and SPONG, HAIDER and LINDSLEY(1965) have demonstrated
that such variables have a profound
cortical evoked response amplitudes. Whether or not a control procedure to stabilize attentional shift and boredom would reduce the interactions between subjects and the treatments is problematical. Additional experimentation is needed to examine these factors. Fatigue factors should have been eliminated by the randomization procedure utilized in the experimental design. Notwithstanding these sources of variability, it has been demonstrated that modulations in pupillary diameter and adaptive state of the visual system are reflected in the amplitude parameters of the VER. ~ck~u~le~e~e~f~ur
appreciation is tendered to Mr. DONALDSHEARER for his technical assistancein ali
phases of this study.
REFERENCES ARMINOTON, J. C. (1964).Adaptational changes in the human electroretinogram and occipital response. Vision Res. 4, 179-192. BART~Y, S. H. (1941). Vision: A Sfudy ofifs Basis. Van Nostrand, New Jersey. BARTLEY,S. H. and NELSON,T. M. (1961). A further study of pulse-to-cycle fraction and critical flickerfrequency. A decisive theoretical test. J. oppl.Sot. Am. 51,41X% BERGAM~NI, L., BERG-O, B. and MOTELS, A. M. (1966). V~iations du potent% evoque chez I’homme provoquees par Ies modifications du diametre pupillaire et de l’etat d’activation eorticale, avec reference particuliere aux phonomenes d’habituation, d’attention et de distraction. J. Pkytiol, (P&is) 5% 6rl1-685. BROWN,K. T. and WATANABB, K. (1965). Neural stage of adaptation between the receptors and inner nuclear layer of monkey retina. Science, N. Y. 148,1113-l1IS. Modulations of visuaf input by pupillary Elecfroenceph. 16,259-268. FLEMINQ,D. E. (1969). Modified pupiIIary diameter and evoked potential component variation in waking cats. Eiecfroencepk.
Pupillary Diameter, and the Visually Evoked Potential
MACKAY,D. M. (1969). Evoked brain potentials as indicators of sensory information processing. Neurosci. Res. Prog. Bull. 7, 181-276. NAQUET, R., REGIS, H., FISCHER-WILLIAMS,M. and FERNANDEZ-GUARDIOLA, A. (1959). Variations des responses evoquees par la lumiere de long de la voie specitique. Cr. Sot. Biol. (Paris) 153, 809412. S~EGAL,S. (1956). ~onpar~etric Statistics. McGraw-Hill, New York. SPONG, P., HAIDER, M. and LINIXLEY, D. B. (196.5). Seiective attentiveness and cortical evoked responses to visual and auditory stimuli. Science, N. Y. 148, 395-397. VON LOEWENICX,V. and FINKENZELLER, P. (1967). Reizstarkenabhangigkeit und Stevenssche Potenzfunktion beim optisch evozierten Potential des Menschen. Ppiigers Arch. ges Physiol. 293,2%-2X WINER, B. J. (1962). Statisfical Principles in Experimental Design. McGraw-Hill, New York.
A~~aet-Photi~ly evoked cortical potentials (VERs) were recorded from four subjects under conditions of systematically varied background intermittent stimulation. Cortical responses recorded when the subjects’ pupils were mobile were compared with those obtained with pupillary mydriasis. VER amplitude was reliably greater when responses were recorded with mydriatic pupils than with mobile pupils. Under either condition, response amplitude was reliably diminished by increasing the frequency of background intermittent stimulation. With mobile pupils, VER diminution was partitioned between the results of pupillary constriction and light adaptation produced by the intermittent stimulation. Under conditions of mydriasis, VER diminution was related singularly to light adaptive processes in the visual system. R&am&--On enregistre sur quatre sujets les potentiels corticaux evoques par la lumi&re (VER) dans des conditions de stimulation intermittente du fond qui varient systematiquement. On compare les rtponses corticales quand les pupilles des sujets sont naturelles et quand il y a mydriase. L’amplitude VER est systematiquement plus grande avec mydriase. Dans les deux conditions la reponse diminue syst~matiquement quand on augmente la frequence de la stimulation intermittente du fond. Avec les pupilles naturelles, la diminution VER est partiellement due a la constriction pupillaire et a l’adaptation lumineuse produite par la stimulation intermittente. En cas de mydriase, la diminution VER ne provient que des processus ~adaptation a la lumiere du systeme visuel.
Zusammenfassunt-An vier Versuchspersonen wurden durch Licht erzeugte cortikale Potentiale (VER) gemessen, wobei der inte~ittie~nde H~ter~nds~iz systematisch variiert wurde. Die Signale des Cortex wurden aufgenommen, wlhrend die Pupillen der Versuchspersonen beweglich waren, und mit solchen verglichen, die mit mydriatisierten Pupillen erhalten wurden, Im letzteren Fall waren die Reizantworten signifikant gri%er. Unter beiden Bedingungen verringerte sich die Si~aIamplitude signifikant mit steigender Frequeaz des intermittierenden Hintergrundreizes. Bei beweglichen Pupillen war die VER-Verringerung sowohl auf die Pupillenverengung als such auf die Adaptation auf den intermittierenden Reiz zurtickzufiihren, hei My~~tisierung nur auf den adaptiven ProzeS des visuellen Systems.
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3Ha~T~bHO ~e~m~~b rrpu: ysenwfemu YacroTbI RpepbIBucroZt cr5ibsyJuIww.ITpsiIIoABHmHbIx spawax yMeHbmeHwe VER~~~TI~YH~~~B~~~JI~OTB~ ~1cymerrw13pa~oB,a~ac~o0~cBeToBofiaAan~a~~, II~OI~~BOAKMO~E npepbIBKcToii CT~J?BIWieiL B YCJIOBEBX Mnnpaasa yMeubmenne VER 0npe~eJuumcb e~craemio ~o~rbrcoripo~~ecco~CBCT~BO~~ aAaIrraqmf B 3prrreJIbrrotL wcTeMe.