124
Electroencephalography and Clinical Neurophysiology, 1 9 7 6 , 41 : 1 2 4 - - 1 3 6 ~) Elsevier Scientific P u b l i s h i n g C o m p a n y , A m s t e r d a m -- P r i n t e d in T h e N e t h e r l a n d s
INFLUENCE OF COLOR ON THE PHOTOCONVULSIVE RESPONSE
T. T A K A H A S H I and Y. T S U K A H A R A
Department of Neuropsychiatry and Department of Physiology, Tohoku University School of Medicine, Sendai (Japan) ( A c c e p t e d for p u b l i c a t i o n : J a n u a r y 15, 1 9 7 6 )
The wavelength of intermittent photic stimulation (IPS) is considered to be one of the most important parameters influencing the appearance of the photoconvulsive response (Bickford et al. 1952). Conclusions concerning this problem, however, have not been consistent. Since Carterette and Symmes (1952) first reported that red-flicker evoked more significant activating effects in provoking the photoconvulsive response (PCR), reports supporting this finding have followed (Buskirk et al. 1952; R~mond 1952; Bickford et al. 1953; Marshall et al. 1953; Bickford 1954; Courjon 1955; Pantelakis et al. 1962; Kojima et al. 1963; Brausch and Ferguson 1965; Harley et al. 1967; Takahashi and Tsukahara 1972a,b, 1973). Contrary to these reports, however, it has also been reported that red-flicker is less effective than that of other wavelengths in provoking PCRs (Rao and Prichard 1955; Arima et al. 1960; Kanaya et al. 1961; Tan et al. 1963; Origuchi and Nonaka 1972). In one report (Brazier 1953), there was no apparent difference in the effectiveness at the same intensity regardless of wavelength. Watanabe et al. (1969) reported that the sensitivity to different wavelengths varied on successive days. Meanwhile, Carterette and Symmes (1952) suggested that red-minus eyeglasses or contact lenses (Brausch and Ferguson 1965) might be of therapeutic importance to photosensitive patients. Following this report, similar views
have appeared (Buskirk et al. 1952; Marshall et al. 1953; Bickford 1954; Otawara et al. 1961; Asano and Umezaki 1965; Maruyama and Maruyama 1968; Takahashi and Tsukahara 1972b, 1974a). However, we cannot disregard the opinion that the observed improvement is due more to a reduction in intensity than to any specific effect of wavelength (Bickford et al. 1953; Rao and Prichard 1955; Pantelakis et al. 1962). Further, Rao and Prichard (1955) and Harley et al. (1967) reported that red eyeglasses afforded clinical relief to patients with photogenic epilepsy. Carterette and Symmes (1952) also reported that photosensitive patients vary in their sensitivity to different parts of the wavelength. Consequently, it has been recommended that suitable eyeglasses should be determined by an EEG examination, using white and colored IPS (Rao and Prichard 1955; Arima et al. 1960; Kojima et al. 1963; Troupin 1966). Troupin (1966) mentioned that proper eyeglasses to reduce the incident light intensity could also be prescribed to photosensitive patients. On the other hand, it is a well-known fact that IPS provokes more PCRs when the eyes are closed, especially immediately after their closure (Panayiotopoulos 1974), than when they are open. Under such a condition of eyeclosure, several phenomena promote the appearance of PCRs. Examples include a reduction in visual pattern input (Davidson and Watson 1956; Bickford and Klass 1969), a
INFLUENCE OF COLOR ON THE PCR more diffuse effect (Davidson and Watson 1956; Pantelakis et al. 1962; Brausch and Ferguson 1965; Bickford and Klass 1969; Takahashi 1973b), a red filter effect of the eyelids (Carterette and Symmes 1952; Marshall et al. 1953; Pantelakis et al. 1962; Brausch and Ferguson 1965; Troupin 1966; Takahashi 1973b; Takahashi and Tsukahara 1973), and movement of the eyelids and eyes in the act of closing eyes (Robinson 1939; Gastaut and Tassinari 1966; Green 1968; Lewis 1972; Tieber 1972; Takahashi 1973a,b, 1975; Takahashi and Tsukahara 1975a). In addition, it has been known that the difference in intensity between the stimulus light and the ambient light is of great significance (Carterette and Symmes 1962; Gastaut et al. 1961; Takahashi 1973b). As one of the important endogenous factors, a probable activation effect of PCRs by fatigue due to insomnia cannot be overlooked (Scollo-Lavizzari and ScolloLavizzari 1974). Since various factors as mentioned above and some probable additional factors are related to the IPS activation, experiments designed to determine color effects on PCRs should be carried out under controlled conditions excluding as many extraneous factors as possible. Most of the work concerning color effect on PCRs, however, has n o t paid careful attention to the nature of the experimental conditions. That is, we consider the light source itself to be one of the most important factors that might produce such a variety of results. The intensity of the stroboscopic light used by other authors is far above what we consider to be appropriate. Using the previously introduced visual stimulator (Tsukahara and Takahashi 1972), we reported that paroxysmal discharges were provoked in some of the photosensitive patients b y diffuse red light of 40 cd/m 2 and that the paroxysmal discharges were markedly enhanced when the stimulus changed into redflicker with the same patients. In another preliminary study (Takahashi and Tsukahara 1975b), we also showed that among the redflicker stimuli of 5, 10, 15, 20, 25 and 30 c/sec
125 frequencies with the 3 levels of brightness of 40, 25 and 4 cd/m 2, that of 15 c/sec frequency revealed the strongest activating effect on PCRs at every level of brightness. These findings agree with the result given by Walter and Walter (1949), Carterette and Symmes (1952), and others, that the maximal EEG response was evoked b y stroboscopic light of 15 c/sec frequency. An intensity of 20 cd/m 2 was concluded to be the lowest brightness that has a sufficiently p o t e n t activating effect on PCRs. Furthermore, we found that the activating effect of a red-flicker of 15 c/sec and 20 cd/m 2 was superior to that of stroboscopic light, and that the studies using such red-flicker brought much information of clinical importance (Takahashi and Tsukahara 1974a,b, 1975a). Using the '~¢isual simulator" (Tsukahara and Takahashi 1973), we carried out our experiments for the purpose of determining the color effect on PCRs, and reproducibly found that red light of 20 cd/m 2 had an excitatory effect on the PCR, and that PCRs provoked b y red-flicker of 20 cd/m 2 and 15 c/sec were inhibited by blue light of 1.9 cd/m 2.
Subjects and methods As seen in Table I, the subjects were 11 epileptics, 1 patient with atypical psychosis, 1 patient with pubertas praecox, and 1 patient with mental retardation. Of these 11 epileptics, 5 had photosensitivity, clinically as well as electroencephalographically, and 6 had photosensitivity only electroencephalographically. Ages ranged from 9 to 27 years, with a mean age of 14.9 years. Of these 14 cases, 10 were female and 4 male. There were no cases having abnormalities of color sensation, which was confirmed by Ishihara's test. In all 14 cases generalized PCRs (sharp-and-wave complex, spike-and-wave complex) were observed to be provoked b y the red-flicker during the routine examination with visuo-sensory activation (Takahashi and Tsukahara 1974a,b, 1975a). Gold electrodes for EEG recording were
126
T. TAKAHASHI, Y. TSUKAHARA
TABLE I The PCRs provoked by red-flicker in 14 patients. In this table are shown the latency of appearance of the PCRs in response to the red-flicker (Appearance latency), the duration of the PCRs until stopping the red-flicker (Duration), and the duration of the PCRs after stopping the red-flicker ("Duration"). Case
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Age
9 11 11 11 12 13 14 14 15 17 18 18 19 27
Sex
F F M M F F F F M F F M F F
Clinical diagnosis
Photosensitive epilepsy Photosensitive epilepsy Photosensitive epilepsy Photosensitive epilepsy Photosensitive epilepsy Photosensitive epilepsy Photosensitive epilepsy Atypical psychosis Pubertas praecox Photosensitive epilepsy Mental retardation Photosensitive epilepsy Photosensitive epilepsy Photosensitive epilepsy
Red-flicker
* * ** ** ** * * * ** ** **
Appearance latency (sec)
Duration (sec)
"Duration" (sec)
1.5 0.6 1.9 0.8 2.4 0.6 1,0 1.2 3.4 1.0 1.6 2.0 3.8 0.4
1.0 1.0 1.0 l. 3 1.4 1.3 1.0 1.2 1.0 1.1 1.4 1.6 1.2 ]. 2
0.7 0.4 0.3 0.9 0.8 0.7 0.5 0.6 0.7 0.9 0.8 0.4 0.4 0.4
* Clinically as well as electroencephalographically photosensitive. ** Only electroencephalographically photosensitive.
a t t a c h e d to the scalp with paste, placed a c c o r d ing t o the I n t e r n a t i o n a l 1 0 - - 2 0 system. The E E G was r e c o r d e d b y m e a n s o f a 1 3 - c h a n n e l e l e c t r o e n c e p h a l o g r a p h f r o m the left a n d rightfrontal-pole, frontal, central, parietal, occipital, and p o s t e r i o r - - t e m p o r a l regions; m o n o p o l a r derivation with ipsilateral ear lobe reference was used.
1. Flicker stimuli with different colored lights F o r the flicker stimuli with d i f f e r e n t c o l o r e d lights, channel I o f the visual s t i m u l a t o r was used. This a p p a r a t u s gave an a p p r o x i m a t e l y sine-wave o u t p u t o f light. The subject, after 2--3 rain d a r k - a d a p t a t i o n , l o o k e d t h r o u g h a small w i n d o w at a screen f r o m a 25 c m distance, and the stimuli as m e n t i o n e d b e l o w were p r o j e c t e d o n the c e n t e r o f the screen (12 X 18 cm). A neutral d e n s i t y filter for
w h i t e light and glass filters for red, yellow, green and blue light (Toshiba V - R 6 1 , S-G1, V G - 5 0 and V-V42, respectively) were used. The transmission s p e c t r u m o f the filters is s h o w n in Fig. 1. Keeping the brightness o f each o f these 5 c o l o r e d lights on the screen at 20 c d / m 2 b y direct m e a s u r e m e n t , 15 c/sec c o l o r e d flicker stimuli were given t o the subject in the following o r d e r : flicker stimuli o f : (1) w h i t e light; (2) red light; ( 3 ) y e l l o w light; (4) green light; and (5) blue light. First we gave (1) f o r 10 sec. A f t e r keeping the subject q u i e t u n d e r the same c o n d i t i o n o f eyes o p e n f o r 30 sec, we carried o u t s t i m u l a t i o n (2). T h e n we c o n t i n u e d t o give stimuli in the o r d e r f r o m (3) t o (5), and if a P C R was p r o v o k e d b y a n y o f t h e m , especially b y the red-flicker, we i m m e d i a t e l y s t o p p e d the stimulation. A f t e r the P C R disappeared, we r e c o r d e d t h e E E G , eyes o p e n , f o r 30 sec, and t h e n c o n t i n u e d w i t h the n e x t p r o c e d u r e .
IN F LU E NC E OF COLOR ON THE PCR
127
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EEG studies were repeated in 7 patients as shown in Table III. The interval of the repeated EEG studies varied from 3 to 12 months. First, we confirmed the appearance of a PCR provoked b y the red-flicker. After keeping the subject quiet, eyes open, for 30 sec, we gave blue light of 1.9 cd/m 2 simultaneously with the red-flicker from the start for 7 sec. After 30 sec, we gave red light of 1.9 cd/m 2 again simultaneously with the red-flicker from the start, If a PCR was provoked by this stimulus, we immediately stopped giving the stimulation.
Results
Fig. l . Transmi~ion spectrum of colored ~assfilters.
1. Flicker stimuli with different colored lights 2. Effects o f dim background lights on the PCRs provoked by the red-flicker Blue light The following examination was then carried out. Using channel II of the visual stimulator, we projected steady illumination b y blue light of 1.9 cd/m 2 on the screen immediately after confirming the appearance of a PCR provoked b y the red-flicker. As soon as the PCR disappeared as a result of the illumination of blue light, b o t h the red-flicker and the blue light were continuously given for 7 sec. Again, after keeping the subject quiet under the same condition, eyes open, for 30 sec, we gave the blue light simultaneously with the red-flicker from the start. If no PCRs were provoked, this was continued for 7 sec. Following this procedure, the entire examination was repeated using blue light of 1 cd/m 2. At the time of EEG recording, 10 epileptics had ceased taking anticonvulsants for 18 h; 1 patient with photosensitive epilepsy (Case 6), 1 patient with pubertas praecox and 1 patient with mental retardation were n o t given any anticonvulsant; 1 patient with atypical psychosis was taking a tranquilizer.
Fig. 2 is an example of the findings recorded on a case of photosensitive epilepsy of a 12year-old female (Case 5, see Table I). In all subjects, PCRs were provoked by the redflicker alone, with EEGs similar to Fig. 2. In this series of experiments (see Table I), the latency of appearance of the PCRs in response to the red-flicker ranged from 0.4 to 3.8 sec, with a mean of 1.6 sec. The duration of the PCRs until stopping the red-flicker ranged from 1.0 to 1.6 sec, with a mean of 1.2 sec. The duration of the PCRs after stopping the red-flicker ranged from 0.3 to 0.9 sec, with a mean of 0.6 sec.
2. Effects of dim background lights on the PCRs provoked by the red-flicker Blue light of 1.9 cd/m: As shown in Fig. 3, when blue light of 1.9 cd/m 2 was given (arrow at trace A) after the appearance of a PCR provoked by the redflicker, the PCR completely disappeared. This p h e n o m e n o n was observed in all the subjects. As shown in Table II, the latency of appearance of the PCRs in response to the red-flicker ranged from 0.4 to 4.2 sec with a mean of 1.5 sec. The duration of the PCRs until the blue
128
T. T A K A H A S H I , Y. T S U K A H A R A
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Fig. 2. E E G s o f a 12-year-old female patient with p h o t o s e n s i t i v e epilepsy (Case 5). Only the red-flicker o f 15 c/sec and 20 c d / m 2 was e f f e c t i v e in p r o v o k i n g a p h o t o c o n v u l s i v e response (PCR). Other flicker stimuli o f white, y e l l o w , green and blue light at 15 c/sec and 20 c d / m 2 were all ineffective. The l a t e n c y o f appearance o f the PCR in response to the red-flicker was 2.4 sec. For this E E G activation, the visual stimulator was used. Unipolar derivation with ipsilateral ear lobe reference.
light was given ranged from 0.6 to 1.6 sec, with a mean of 0.9 sec. The latency of disappearance of the PCRs in response to the blue light ranged from 0.2 to 3.2 sec, with a mean of 0.9 sec. As shown in Fig. 5, the latency of appearance of the PCRs in response to the red-flicker showed an inverse relation to the latency of disappearance of the PCRs in response to the blue light. Simultaneous stimuli of both the red-flicker and the blue light from the start brought a continuous suppression in all the subjects (for example see trace B of Fig. 3). Blue light o f I cd/m 2 As shown in Table II, the latency of appear-
ance of the PCRs in response to the red-flicker ranged from 0.5 to 4.2 sec, with a mean of 1.4 sec. The duration of the PCRs until the blue light was given ranged from 0.6 to 2.0 sec, with a mean of 1.2 sec. As shown in Fig. 4 (arrow at trace A), when the blue light of 1 cd/m 2 was given after the appearance of the PCRs provoked by the red-flicker, the PCRs tended to persist without being much influenced by the blue light. Such a sustained appearance of the PCRs was seen in 10 cases; continuous (2 cases) or transient suppression (2 cases) in 4 cases. The latency of disappearance of the PCRs in response to the blue light in these 4 cases was 1.7, 0.6, 0.8 and 1.4 sec. Of these 4 cases, 2 showed continuous sup-
INFLUENCE OF COLOR ON THE PCR
129
TABLE II The effect of the blue light of 1.9 and 1 cd/m 2 upon the PCRs provoked by red-flicker in 14 patients. In this table are shown the latency of appearance of the PCRs in response to the red-flicker (Appearance latency), the duration of the PCRs until giving blue light (Duration), the latency of disappearance of the PCRs in response to the blue light (Disappearance latency), and the suppression of the PCRs with simultaneous stimuli of both the redflicker and the blue light from the start (Suppression from start). Case
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Blue light of 1.9 cd/m 2
Blue light of 1 cd/m 2
Appearance latency (sec)
Duration (sec)
Disappearance latency (sec)
Suppression from start
Appearance latency (sec)
Duration (sec)
Disappearance latency (sec)
Suppression from start
2.3 0.8 1.7 0.5 1.2 0.4 0.7 0.7 2.6 0.8 1.8 2.4 4.2 0.4
0.8 0.8 1.1 0.7 1.0 0.6 0.6 0.9 0.6 1.0 1.6 1.2 1.0 0.8
0.6 0.6 0.5 1.1 1.4 1.9 0.4 0.7 0.2 0.2 0.6 0.4 0.4 3.2
(+) (+) (+) (+) (+) (+) (+) (+) (+) (+) (+) (+) (+) (+)
1.5 0.8 1.6 0.5 1.4 0.5 0.8 0.8 1.8 0.7 1.3 2.6 4.2 0.5
1.2 1.2 1.4 1.8 1.1 0.8 0.6 1.0 1.2 0.9 2.0 1.8 1.2 1.2
(--) * (--) (--) (--) 1.7 (--) (--) (--) 0.6--1.0 *** (--) (--) 0.8 1.4--0.6 (--)
(--) (--) (--) (--) (+) (--) (--) (--) (--) (--) (--) (--) (--) (--)
1.4 ** 0.7 1.5 1.6 0.5 0.6 0.5 5.2 1.2 1.6 4.2 1.6 0.4
* A sustained appearance of the PCRs, not suppressed by blue light. ** A latency of appearance (sec) of the PCRs provoked by the simultaneous stimuli of both the red-flicker and the blue light. *** PCR transiently suppressed only for time interval shown.
TABLE III The effect of the red light of 1.9 cd/m 2 upon the PCRs provoked by the red-flicker in 7 patients. In this table are shown the latency of appearance of the PCRs in response to the red-flicker (Appearance latency), suppression of the PCRs with simultaneous stimuli of both the red-flicker and the blue light of 1.9 cd/m 2 from the start (Suppression from start), and the suppression of the PCRs with simultaneous stimuli of both the red-flicker and the red light of 1.9 cd/m 2 from the start (Suppression from start by red light). Case
Appearance latency (sec)
Suppression from start
Suppression from start by red light
2 4 5 6 7 10 13
0.8 1.0 2.2 0.6 0.9 0.6 3.6
(+) (+) (+) (+) (+) (÷) (+)
(--) (--) (--) (--) (--) (--) (--)
2.0 * 0.6 2.0 0.7 0.7 0.8 3.8
* A latency of appearance (see) of the PCRs provoked by the simultaneous stimuli of both the red-flicker and the red light.
130
T. T A K A H A S H I , Y. T S U K A H A R A
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Fig. 3. EEG of an 11-year-old female patient with photosensitive epilepsy (Case 2). The PCR p r o v o k e d by the red-flicker was inhibited by adding blue light of 1.9 c d / m 2 (arrow at trace A). Simultaneous stimuli of the redflicker and the blue light from the start did not provoke a PCR (trace B).
pression (Cases 5, 12), and 2 showed a transient suppression, which lasted for 1 sec (Case 9) and 0.6 sec {Case 13). Simultaneous stimuli o f b oth red-flicker and blue light from the start brought a continuous suppression o f the PCR in 1 case alone. The remaining 13 cases showed a continuous appearance of PCRs (see trace B o f Fig. 4); the latency of appearance o f the PCRs ranged from 0.4 to 5.2 sec, with a mean of 1.6 sec.
Red light As shown in Table III, the latency of appearance of the PCRs in response to the redflicker ranged from 0.6 to 3.6 sec, with a
mean of 1.4 sec. Simultaneous stimuli of the red-flicker and the blue light of 1.9 cd/m 2 from the start brought a cont i nuous suppression of the PCRs in all the 7 cases. On the contrary, simultaneous stimuli o f the redflicker and the red light of 1.9 cd/m 2 from the start showed no such suppression but the activation effect of the PCR as provoked by the red-flicker alone (see trace C of Fig. 6); the latency of appearance o f the PCRs in response to the red-flicker plus the dim red background light o f 1.9 cd/ m 2 ranged from 0.6 to 3.8 sec, with a mean of 1.5 sec, which was similar to those obtained by the red-flicker alone.
INFLUENCE OF COLOR ON THE PCR
131
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Fig. 4. EEG of the same patient of Fig. 3. The PCR provoked by the red-flicker was not inhibited by adding blue light of 1 cd/m2 (arrow at trace A ). Simultaneous stimuli of the red-flicker and blue light of 1 cd/m2 from the start also provoked a PCR (trace B).
Discussion
The main results obtained in this study may be summarized as follows: (1) PCI%s were provoked by the red-flicker alone at 15 c/sec and 20 cd/m 2. (2) The PCRs provoked by the red-flicker were completely suppressed by the blue light of 1.9 cd/m 2. These findings of (1) and (2) will hereafter be called the excitatory effect on the PCR by red light and the inhibitory effect on the PCR by blue light, respectively.
1. Excitatory effect on the PCR by red light The results of our experiments provide direct and unequivocal evidence that red light
has an excitatory effect on the PCR. Since our experiments were carried o u t during a short period of dark-adaptation (between about 2 to 10 min after dark-adaptation), the retina is presumed to have remained in a photopic condition. It is suggested that when the red-flicker of 20 cd/m 2 is given in such a condition, the cones, especially the red cones might, perhaps, respond more predominantly than the rods. The electrical discharge in potential produced in the red cones as a result of the red-flicker would then be transmitted to the brain, finally to the visual cortex. Fukada and Saito (1971) reported that abnormally enhanced repetitive firing could be recorded from the cat optic nerve during and after flicker stimulation. Their finding
132
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Fig. 5. Relationship between the latency of appearance of the PCRs in response to the red-flicker and the latency of disappearance of the PCRs in response to the blue light of 1.9 cd/m 2 obtained from the 14 patients. The abscissa is plotted on a logarithmic scale for convenience.
appears to have some characteristics that suggest "paroxysmal discharges" in the epileptic brain. Therefore, there is a possibility that the red-flicker may give rise to "paroxysmal discharges" even in the retina of the photosensitive patients. Thus, the p o t e n t activating effect on PCRs by red light should not be explained w i t h o u t considering the whole neuronal mechanisms from the retinal level to the visual cortex. Takahashi and Tsukahara (1975a) suggested that the nonspecific thalamo-cortical system is chiefly concerned with the appearance of PCRs of generalized type provoked by red-flicker, though n o t by pattern stimuli nor by eye movements.
Additionally, it has been suggested that photosensitivity may be a familial trait (Davidson and Watson 1956; Daly et al. 1959; Doose et al. 1969). Doose et al. (1969) reported that PCRs were regarded as a s y m p t o m of susceptibility to convulsions of the centrencephalic type. In addition to this, other biological factors, such as maturational and sexual differences, are presumed to play other important roles in lowering the threshold of sensitivity to the IPS by stroboscopic light, since Doose et al. (1969) clearly demonstrated that photosensitive epilepsy was most commonly seen between the ages of 6 and 15 years, and that female patients were more c o m m o n than male. For more precise clinical-EEG correlates, reaffirmation of these findings by using the method of red-flicker remains to be done. In contrast, when studying photosensitive epilepsy in the Papio papio, Serbanescu et al. (1973) reported that the most effective were the colors blue-green and dark-green, and the least effective were green and red.
2. Inhibitory effect on the PCR by blue light A question may arise whether the inhibitory effect on the PCR by blue light is due to the decrease of light and dark ratio of the flickering light by giving the dim blue background light of 1.9 cd/m 2 on the red-flicker. However, the controlled experiments with the red-flicker, by adding the dim red background light of the same brightness as the blue light, showed a similar excitatory effect to that obtained by the red-flicker alone. Although there have been reports in which an inhibitory effect on the PCR by short wavelengths was demonstrated electroencephalographically (Carterette and Symmes 1952; Marshall et al. 1953; Bickford 1954; Asano and Umezaki 1965; Takahashi and Tsukahara 1972b, 1974a), exact quantitative data have not yet appeared. As a preliminary report, Takahashi and Tsukahara (1972b) reported t h a t the PCRs provoked by red-flicker of 15 c/sec and 40 cd/m 2 was inhibited bv blue light
I N F L U E N C E O F C O L O R ON T H E PCR
133
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Fig. 6. E E G o f a 14-year-old female patient with photosensitive epilepsy (Case 7 ). The PCR p r o v o k e d by the redflicker (trace A ) was n o t seen by simultaneous stimuli o f the red-flicker and blue light of 1.9 c d / m 2 f r o m the start (trace B). However, simultaneous stimuli of the red-flicker and red light of 1.9 c d / m 2 f r o m the start p r o v o k e d a similar P C R to the PCR shown in trace A.
of 0.7 cd/m 2. This study, however, was carried out only when giving blue light simultaneously with red-flicker. In the current investigation, the effect of blue light on the PCRs provoked by red-flicker was studied in different ways as already described. The direct action of blue light having an inhibitory effect m a y act either at the peripheral level, i.e., the pupil and the retina, or at the brain level, i.e., the geniculate body and the visual cortex. However, the influence of the pupil, presumably the constriction of the pupil, is probably not of great importance. The immediate inhibition of the PCRs by the blue light of 1.9 c d / m 2, as if the red-flicker was stopped, is especially suggestive of an important role of the retina in such a mecha-
nism. As already mentioned, since our experiments were carried out in a photopic condition, it is presumed that the inhibitory effect by blue light was produced by the blue cones in the retina. From a therapeutic viewpoint, the finding of an inverse relation between the latencies of appearance and disappearance of PCR (as shown in Fig. 5) can be important. Based on this finding, we adjusted the dosage of anticonvulsants for photosensitive epileptics; for the patients who showed long latency of appearance of PCR in response to the redflicker, we prescribed a minimal a m o u n t of anti-convulsants, and vice versa. In addition, we have tried letting them use blue eyeglasses, and apparent clinical improvements have been
134 confirmed in all of them. Here, we must mention the difference observed in a patient with photosensitive epilepsy associated with color blindness (Takahashi and Tsukahara 1974b). The PCRs provoked by the IPS of stroboscopic light was in fact provoked by the flickering pattern itself, not by red-flicker. Furthermore, the generalized paroxysmal discharges were not inhibited by blue light. In this case, smoked eyeglasses, regardless of color, were found to give improvement. Excepting such cases of color blindness, blue-colored eyeglasses other than simply redminus eyeglasses as suggested by Bickford (1954) are recommended to the photosensitive epileptics. Finally, after this series of experiments, we have repeated the same experiment on some other photosensitive patients, giving the stimuli b u t not in a constant order. Even in this experiment, similar results to those described were obtained. We have also tested some other photosensitive epileptics in whom sustained generalized paroxysmal discharges provoked by the red-flicker (even by that of 5 cd/m z) were not suppressed by blue light of 1.9 cd/m 2. However, reexamination after giving proper anticonvulsants revealed the same inhibitory effect of blue light. Again these findings support evidence of inhibitory effect of blue light. As to whether the rods of retina are also concerned with the mechanism of the excitatory and inhibitory effects, the same experiments on photosensitive patients after sufficient dark-adaptation or on the same subjects associated with nyctalopia remain to be done. In order to know whether green light shows the similar inhibitory effect to that obtained by blue light on the PCR, another experiment should also be made using a proper filter for green light.
Summary Using the visual stimulator, the effect of color on the photoconvulsive response (PCR)
T. TAKAHASHI, Y. TSUKAHARA was studied in 14 photosensitive patients. When stimuli of 15 c/sec flickers of white, red, yellow, green and blue light of 20 cd/m 2 were given to the subjects, generalized PCRs were provoked only by the red-flicker. These PCRs were all inhibited by blue light of 1.9 cd/m 2 when given either after the appearance of the PCRs or simultaneously with the red-flicker from the start. When blue light was given after the appearance of the PCRs, the latency of appearance of the PCRs in response to the red-flicker showed an inverse relation to the disappearance latency of the PCR in response to the blue light. With blue light of 1 cd/m 2, however, inhibition of the PCRs was seen in only 2 cases when it was given after the appearance of the PCR, and in only 1 case when the blue light was simultaneously given with the red-flicker from the start. These results clearly disclosed the following findings: (1) among various colored lights, an excitatory effect on generalized PCR was always seen only with red light at 15 c/sec and 20 cd/m2; (2) the PCRs provoked by the red-flicker were inhibited by blue light of 1.9 cd/m 2, but not by blue light of 1 cd/m 2.
1
J
Resume
Influence de la couleur sur la rdponse photoconvulsive
Les effets de la couleur sur la r~ponse photoconvulsive (RPC) ont ~t~ ~tudi~s, ~ l'aide du stimulateur visuel, sur 14 malades photosensibles. Quand on soumet les sujets ~ une oscillation lumineuse de 15 c/sec et de 20 cd/m 2, successivement blanche, rouge, jaune, verte, et bleue, seule la rouge provoque des RPC g~n&alis~s. Ces RPC sont toutes neutralis~es par une tumi~re bteue de 1,9 cd/m 2, quand celle-ci est ~mise, soit apr~s l'apparition des RPC, soit d~s le d~but, simultan~ment avec le trait rouge. Quand la lumiSre bleue est ~mise aprSs l'apparition des RPC, la latence de l'apparition des RPC en r~ponse au trait rouge apparalt en relation inverse de la latence de
INFLUENCE OF COLOR ON THE PCR
disparition des RPC en rdponse ~ la lumi~re bleue. Avec une lumi~re bleue de I cd/m 2, cependant, la suppression des RPC n'est notde que deux fois quand elle est dmise apr~s l'apparition des RPC et ne l'est qu'une fois quand la lumi~re bleue est dmise d~s le ddbut, simultandment avec le trait rouge. Ces rdsultats m o n t r e n t clairement les fairs suivants: (1) parmi des lumi~res de diffdrentes couleurs, on peut seulement constater un effet d'excitation sur la RPC gdndralisd avec une lumi~re rouge de 15 c/sec et de 20 cd/m2; (2) les RPC provoqudes par le trait rouge sont neutralis~es par une lumi~re bleue de 1,9 cd/m 2, mais non par une lumi~re de 1 cd/m 2. Our thanks to Prof. Teruo Okuma for a critical reading of the manuscript; to Dr. Makoto Tamai for his discussions on the manuscript; to Mr. Masaichi Sasaki for his help in recording EEGs.
References Arima, M., Maruyama, H., Fukuyama, Y. and Sato, H. [Photogenic epilepsy -- A review of its physiological mechanism and report of a case with self-precipitation of attacks.] (in Japanese). Brain Nerve, 1960, 12: 31--39. Asano, T. and Umezaki, H. [Photogenic e p i l e p s y - Presentation of case.] (in Japanese). Clin. Neurol., 1965, 5: 519--523. Bickford, R.G. Sensory precipitation o f seizures. J. Mich. med. Soc., 1954, 53: 1018--1020. Bickford, R.G. and Klass, D.W. Sensory precipitation and reflex mechanisms. In H.H. Jasper et al. (Eds.), Basic mechanisms of the epilepsies. Little, Brown, Boston, Mass., 1969 : 543--564. Bickford, R.G., Daly, D. and Keith, H.M. Convulsive effects of light stimulation in children. Amer. J. Dis. Child., 1953, 86: 170--183. Bickford, R.G., Sem-Jacobsen, C.W., White, P.T. and Daly, D. Some observations on the mechanism of photic and photo-metrazol activation. Electroenceph, clin. Neurophysiol., 1952, 4: 275--282. Brausch, C.C. and Ferguson, J.H. Color as factor in light-sensitive epilepsy. Neurology (Minneap.), 1965, 15: 154--164. Brazier, M.A.B. A review of physiological mechanisms of the visual system in relation t o activating techniques in electroencephalography. Electroenceph. clin. Neurophysiol., 1953, Suppl. 4: 93--107. Buskirk, C.V., Casby, J.U., Passouant, P. and Schwab,
135 R.S. The effect of different modalities of light on the activation of the EEG. Electroenceph. clin. Neurophysiol., 1952, 4: 244--245. Carterette, E.C. and Symmes, D. Color as an experimental variable in photic stimulation. Electroenceph, clin. Neurophysiol., 1952, 4: 289--296. Courjon, J. La protection des dpileptiques photog~niques par des verres filtrant la partie rouge du spectre. Rev. Oto-neuro-opthal., 1955, 27: 462-463. Daly, D., Siekert, R.G. and Burke, E.C. A variety of familial light sensitive epilepsy. Electroenceph. clin. Neurophysiol., 1959, 11: 141--145. Davidson, S. and Watson, C.W. Hereditary light sensitive epilepsy. Neurology (Minneap.), 1956, 6: 235--261. Doose, H., Gerken, H., Hien-VSlpel, K.F. and VSlzke, E. Genetics of photosensitive epilepsy. Neurop~diatrie, 1969, 1: 56--73. Fukada, Y. and Saito, H. The relationship between response characteristics to flicker stimulation a n d receptive field organization in the cat's optic nerve fibers. Vision Res., 1971, 11: 227--240. Gastaut, H. and Tassinari, C.A. Triggering mechanisms in epilepsy. The electroclinical point of view. Epilepsia (Amst.), 1966, 7: 85--138. Gastaut, H., Regis, H., Bostem, J. et Beaussart, M. A propos des crises survenant au cours des spectacles tdl~vis~s et de leur mdcanisme. Presse m4d., 1961, 69: 1581--1583. Green, J.B. Seizures on closing the eyes. Neurology (Minneap.), 1968, 18: 391--396. Harley, R.D., Baird, H.W. and Freeman, R.D. Selfinduced photogenic epilepsy. Report of four cases. Arch. Ophthal. (Chic.), 1967, 78: 730--737. Kanaya, H., Onodera, H. and Motegi, H. [A case of photogenic epilepsy with self-induced attacks by waving hand.] (in Japanese). Brain Nerve, 1961, 13 : 445--455. Kojima, K., Suguro, T., Miyamoto, K., Inazumi, H. and Sakaya, S. [Photogenic epilepsy. I. Television epilepsy.] (in Japanese). J. Pediat. Pract., 1963, 26: 1377--1381. Lewis, J.A. Eye closure as a m o t o r trigger for seizures. Neurology (Minneap.), 1972, 22: 1145--1150. Marshall, C., Walker, A.E. and Livingston, S. Photogenic epilepsy: parameters of activation. Arch. Neurol. Psychiat. (Chic.), 1953, 69: 760--765. Maruyama, K. and Maruyama, H. [Light sensitive epilepsy. Clinical and eleetroencephalographic studies on 75 cases, especially on EEG activation by television.] (in Japanese). Advanc. neurol. Sci., 1968, 12: 537--553. Origuchi, Y. and Nonaka, M. [A case of self-induced photogenic epilepsy.] (in Japanese). J. Pediat. Pract., 1972, 35: 851--856. Otawara, S., Kajiya, T. and Fujimoto, S. [Three cases
136 of photogenic epilepsy.] (in Japanese). J. Pediat. Pract., 1961, 24: 1384--1390. Panayiotopoulos, C.P. Effectiveness of photic stimulation on various eye-states in photosensitive epilepsy. J. neurol. Sci., 1974, 23: 165--173. Pantelakis, S.N., Bower, B.B. and Jones, H.D. Convulsions and television viewing. Brit. reed. J., 1962, 2 : 633--638. Rao, K.S. and Prichard, J.S. Photogenic epilepsy. J. Pediat., 1955, 47: 619--623. R~mond, A. Photo-Metrazol activation. Electroenceph, clin. Neurophysiol., 1952, 4: 265--270. Robinson, L.J. Induction of seizures by closing of the eyes, or by ocular pressure, in a patient with epilepsy. J. nerve, ment. Dis., 1939, 90: 333--336. Scollo-Lavizzari, G. and Scollo-Lavizzari, G.R. Sleep, sleep deprivation, photosensitivity and epilepsy. Europ. Neurol., 1974, 11 : 1--21. Serbanescu, T., Naquet, R. and Menini, C. Various physical parameters which influence photosensitive epilepsy in the Papio papio. Brain Res., 1973, 52: 145--158. Takahashi, T. [Study of visual epilepsy. 1. On--Off activation and clinical--EEG findings.] (in Japanese). Clin. Neurol., 1973a, 13: 156--165. Takahashi, T. [Study of visual epilepsy. 2. Off--PS activation and clinieat--EEG findings.] (in Japanese). Clin. Neurol., 1973b, 13: 689--696. Takahashi, T. [Three cases of ophthalmic epilepsy of oculomotor type.] (in Japanese). Brain Nerve, 1975, 27 : 219--224. Takahashi, T. and Tsukahara, Y. [EEG activation by red color.] (in Japanese). Igaku No Ayumi, 1972a, 83 : 25--26. Takahashi, T. and Tsukahara, Y. [Inhibitory effect of blue color on seizure discharges.] (in Japanese). Igaku No Ayumi, 1972b, 83: 81--82. Takahashi, T. and Tsukahara, Y. [Study of visual epilepsy. 3. Red-flicker activation and clinical--EEG
T. TAKAHASHI, Y. TSUKAHARA findings.[ (in Japanese). Clin. Neurol., 1973, 13: 697--704. Takahashi, T. and Tsukahara, Y. [EEG activation by elemental visual s t i m u l a t i o n - With special reference to visual epilepsy.[ (in Japanese). Clin. Psychiat., 1974a, 16: 133--143. Takahashi, T. and Tsukahara, Y. [Ophthalmic epilepsy.] (in Japanese). Igaku No Ayumi, 1974b, 91: 231--242. Takahashi, T. and Tsukahara, Y. Generalized paroxysmal discharges induced by visual stimuli and eye movements. Tohoku J. exp. Med., 1975a, 115: 1--10. Takahashi, T. and Tsukahara, Y. [Reconsideration of EEG activation method by flicker stimulation.[ (in Japanese). Jap. J. EEG EMG, 1975b, 3: 12--18. Tan, M., Sato, H., Naito, S., Sakaoka, U., Kirikae, T. and Nakagawa, H. [A case of photogenic epilepsy seen in an identical twin.[ (in Japanese). Psychiat. Neurol. Jap., 1963, 65: 184--192. Tieber, E. Anfallmuster bei Augenschluss. Bericht tiber drei F~/lle in einer Familie. Neurop~/diatrie, 1972, 3: 305--312. Troupin, A.S. Photic activation and experimental data concerning colored stimuli. Neurology (Minneap.), 1966, 16: 269--276. Tsukahara, Y. and Takahashi, T. [Visual stimulator for EEG activation.] (in Japanese). Igaku No Ayumi, 1972, 81: 818--819. Tsukahara, Y. and Takahashi, T. Visual stimulator for EEG activation. Electroenceph. clin. Neurophysiol., 1973, 35: 333--335. Walter, V.J. and Walter, W.G. The central effects of rhythmic sensory stimulation. Electroenceph. clin. Neurophysiol., 1949, 1 : 56--86. Watanabe, K., Sato, I., Kato, T. and Iwase, K. [A case of self-induced photogenic epilepsy. ] (in Japanese). Clin. EEG, 1969, 11: 112--118.
Electroencephalography and Clinical Neurophysiology, 1 9 7 6 , 41 : 1 2 4 - - 1 3 6 ~) Elsevier Scientific P u b l i s h i n g C o m p a n y , A m s t e r d a m -- P r i n t e d in T h e N e t h e r l a n d s
INFLUENCE OF COLOR ON THE PHOTOCONVULSIVE RESPONSE
T. T A K A H A S H I and Y. T S U K A H A R A
Department of Neuropsychiatry and Department of Physiology, Tohoku University School of Medicine, Sendai (Japan) ( A c c e p t e d for p u b l i c a t i o n : J a n u a r y 15, 1 9 7 6 )
The wavelength of intermittent photic stimulation (IPS) is considered to be one of the most important parameters influencing the appearance of the photoconvulsive response (Bickford et al. 1952). Conclusions concerning this problem, however, have not been consistent. Since Carterette and Symmes (1952) first reported that red-flicker evoked more significant activating effects in provoking the photoconvulsive response (PCR), reports supporting this finding have followed (Buskirk et al. 1952; R~mond 1952; Bickford et al. 1953; Marshall et al. 1953; Bickford 1954; Courjon 1955; Pantelakis et al. 1962; Kojima et al. 1963; Brausch and Ferguson 1965; Harley et al. 1967; Takahashi and Tsukahara 1972a,b, 1973). Contrary to these reports, however, it has also been reported that red-flicker is less effective than that of other wavelengths in provoking PCRs (Rao and Prichard 1955; Arima et al. 1960; Kanaya et al. 1961; Tan et al. 1963; Origuchi and Nonaka 1972). In one report (Brazier 1953), there was no apparent difference in the effectiveness at the same intensity regardless of wavelength. Watanabe et al. (1969) reported that the sensitivity to different wavelengths varied on successive days. Meanwhile, Carterette and Symmes (1952) suggested that red-minus eyeglasses or contact lenses (Brausch and Ferguson 1965) might be of therapeutic importance to photosensitive patients. Following this report, similar views
have appeared (Buskirk et al. 1952; Marshall et al. 1953; Bickford 1954; Otawara et al. 1961; Asano and Umezaki 1965; Maruyama and Maruyama 1968; Takahashi and Tsukahara 1972b, 1974a). However, we cannot disregard the opinion that the observed improvement is due more to a reduction in intensity than to any specific effect of wavelength (Bickford et al. 1953; Rao and Prichard 1955; Pantelakis et al. 1962). Further, Rao and Prichard (1955) and Harley et al. (1967) reported that red eyeglasses afforded clinical relief to patients with photogenic epilepsy. Carterette and Symmes (1952) also reported that photosensitive patients vary in their sensitivity to different parts of the wavelength. Consequently, it has been recommended that suitable eyeglasses should be determined by an EEG examination, using white and colored IPS (Rao and Prichard 1955; Arima et al. 1960; Kojima et al. 1963; Troupin 1966). Troupin (1966) mentioned that proper eyeglasses to reduce the incident light intensity could also be prescribed to photosensitive patients. On the other hand, it is a well-known fact that IPS provokes more PCRs when the eyes are closed, especially immediately after their closure (Panayiotopoulos 1974), than when they are open. Under such a condition of eyeclosure, several phenomena promote the appearance of PCRs. Examples include a reduction in visual pattern input (Davidson and Watson 1956; Bickford and Klass 1969), a
INFLUENCE OF COLOR ON THE PCR more diffuse effect (Davidson and Watson 1956; Pantelakis et al. 1962; Brausch and Ferguson 1965; Bickford and Klass 1969; Takahashi 1973b), a red filter effect of the eyelids (Carterette and Symmes 1952; Marshall et al. 1953; Pantelakis et al. 1962; Brausch and Ferguson 1965; Troupin 1966; Takahashi 1973b; Takahashi and Tsukahara 1973), and movement of the eyelids and eyes in the act of closing eyes (Robinson 1939; Gastaut and Tassinari 1966; Green 1968; Lewis 1972; Tieber 1972; Takahashi 1973a,b, 1975; Takahashi and Tsukahara 1975a). In addition, it has been known that the difference in intensity between the stimulus light and the ambient light is of great significance (Carterette and Symmes 1962; Gastaut et al. 1961; Takahashi 1973b). As one of the important endogenous factors, a probable activation effect of PCRs by fatigue due to insomnia cannot be overlooked (Scollo-Lavizzari and ScolloLavizzari 1974). Since various factors as mentioned above and some probable additional factors are related to the IPS activation, experiments designed to determine color effects on PCRs should be carried out under controlled conditions excluding as many extraneous factors as possible. Most of the work concerning color effect on PCRs, however, has n o t paid careful attention to the nature of the experimental conditions. That is, we consider the light source itself to be one of the most important factors that might produce such a variety of results. The intensity of the stroboscopic light used by other authors is far above what we consider to be appropriate. Using the previously introduced visual stimulator (Tsukahara and Takahashi 1972), we reported that paroxysmal discharges were provoked in some of the photosensitive patients b y diffuse red light of 40 cd/m 2 and that the paroxysmal discharges were markedly enhanced when the stimulus changed into redflicker with the same patients. In another preliminary study (Takahashi and Tsukahara 1975b), we also showed that among the redflicker stimuli of 5, 10, 15, 20, 25 and 30 c/sec
125 frequencies with the 3 levels of brightness of 40, 25 and 4 cd/m 2, that of 15 c/sec frequency revealed the strongest activating effect on PCRs at every level of brightness. These findings agree with the result given by Walter and Walter (1949), Carterette and Symmes (1952), and others, that the maximal EEG response was evoked b y stroboscopic light of 15 c/sec frequency. An intensity of 20 cd/m 2 was concluded to be the lowest brightness that has a sufficiently p o t e n t activating effect on PCRs. Furthermore, we found that the activating effect of a red-flicker of 15 c/sec and 20 cd/m 2 was superior to that of stroboscopic light, and that the studies using such red-flicker brought much information of clinical importance (Takahashi and Tsukahara 1974a,b, 1975a). Using the '~¢isual simulator" (Tsukahara and Takahashi 1973), we carried out our experiments for the purpose of determining the color effect on PCRs, and reproducibly found that red light of 20 cd/m 2 had an excitatory effect on the PCR, and that PCRs provoked b y red-flicker of 20 cd/m 2 and 15 c/sec were inhibited by blue light of 1.9 cd/m 2.
Subjects and methods As seen in Table I, the subjects were 11 epileptics, 1 patient with atypical psychosis, 1 patient with pubertas praecox, and 1 patient with mental retardation. Of these 11 epileptics, 5 had photosensitivity, clinically as well as electroencephalographically, and 6 had photosensitivity only electroencephalographically. Ages ranged from 9 to 27 years, with a mean age of 14.9 years. Of these 14 cases, 10 were female and 4 male. There were no cases having abnormalities of color sensation, which was confirmed by Ishihara's test. In all 14 cases generalized PCRs (sharp-and-wave complex, spike-and-wave complex) were observed to be provoked b y the red-flicker during the routine examination with visuo-sensory activation (Takahashi and Tsukahara 1974a,b, 1975a). Gold electrodes for EEG recording were
126
T. TAKAHASHI, Y. TSUKAHARA
TABLE I The PCRs provoked by red-flicker in 14 patients. In this table are shown the latency of appearance of the PCRs in response to the red-flicker (Appearance latency), the duration of the PCRs until stopping the red-flicker (Duration), and the duration of the PCRs after stopping the red-flicker ("Duration"). Case
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Age
9 11 11 11 12 13 14 14 15 17 18 18 19 27
Sex
F F M M F F F F M F F M F F
Clinical diagnosis
Photosensitive epilepsy Photosensitive epilepsy Photosensitive epilepsy Photosensitive epilepsy Photosensitive epilepsy Photosensitive epilepsy Photosensitive epilepsy Atypical psychosis Pubertas praecox Photosensitive epilepsy Mental retardation Photosensitive epilepsy Photosensitive epilepsy Photosensitive epilepsy
Red-flicker
* * ** ** ** * * * ** ** **
Appearance latency (sec)
Duration (sec)
"Duration" (sec)
1.5 0.6 1.9 0.8 2.4 0.6 1,0 1.2 3.4 1.0 1.6 2.0 3.8 0.4
1.0 1.0 1.0 l. 3 1.4 1.3 1.0 1.2 1.0 1.1 1.4 1.6 1.2 ]. 2
0.7 0.4 0.3 0.9 0.8 0.7 0.5 0.6 0.7 0.9 0.8 0.4 0.4 0.4
* Clinically as well as electroencephalographically photosensitive. ** Only electroencephalographically photosensitive.
a t t a c h e d to the scalp with paste, placed a c c o r d ing t o the I n t e r n a t i o n a l 1 0 - - 2 0 system. The E E G was r e c o r d e d b y m e a n s o f a 1 3 - c h a n n e l e l e c t r o e n c e p h a l o g r a p h f r o m the left a n d rightfrontal-pole, frontal, central, parietal, occipital, and p o s t e r i o r - - t e m p o r a l regions; m o n o p o l a r derivation with ipsilateral ear lobe reference was used.
1. Flicker stimuli with different colored lights F o r the flicker stimuli with d i f f e r e n t c o l o r e d lights, channel I o f the visual s t i m u l a t o r was used. This a p p a r a t u s gave an a p p r o x i m a t e l y sine-wave o u t p u t o f light. The subject, after 2--3 rain d a r k - a d a p t a t i o n , l o o k e d t h r o u g h a small w i n d o w at a screen f r o m a 25 c m distance, and the stimuli as m e n t i o n e d b e l o w were p r o j e c t e d o n the c e n t e r o f the screen (12 X 18 cm). A neutral d e n s i t y filter for
w h i t e light and glass filters for red, yellow, green and blue light (Toshiba V - R 6 1 , S-G1, V G - 5 0 and V-V42, respectively) were used. The transmission s p e c t r u m o f the filters is s h o w n in Fig. 1. Keeping the brightness o f each o f these 5 c o l o r e d lights on the screen at 20 c d / m 2 b y direct m e a s u r e m e n t , 15 c/sec c o l o r e d flicker stimuli were given t o the subject in the following o r d e r : flicker stimuli o f : (1) w h i t e light; (2) red light; ( 3 ) y e l l o w light; (4) green light; and (5) blue light. First we gave (1) f o r 10 sec. A f t e r keeping the subject q u i e t u n d e r the same c o n d i t i o n o f eyes o p e n f o r 30 sec, we carried o u t s t i m u l a t i o n (2). T h e n we c o n t i n u e d t o give stimuli in the o r d e r f r o m (3) t o (5), and if a P C R was p r o v o k e d b y a n y o f t h e m , especially b y the red-flicker, we i m m e d i a t e l y s t o p p e d the stimulation. A f t e r the P C R disappeared, we r e c o r d e d t h e E E G , eyes o p e n , f o r 30 sec, and t h e n c o n t i n u e d w i t h the n e x t p r o c e d u r e .
IN F LU E NC E OF COLOR ON THE PCR
127
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EEG studies were repeated in 7 patients as shown in Table III. The interval of the repeated EEG studies varied from 3 to 12 months. First, we confirmed the appearance of a PCR provoked b y the red-flicker. After keeping the subject quiet, eyes open, for 30 sec, we gave blue light of 1.9 cd/m 2 simultaneously with the red-flicker from the start for 7 sec. After 30 sec, we gave red light of 1.9 cd/m 2 again simultaneously with the red-flicker from the start, If a PCR was provoked by this stimulus, we immediately stopped giving the stimulation.
Results
Fig. l . Transmi~ion spectrum of colored ~assfilters.
1. Flicker stimuli with different colored lights 2. Effects o f dim background lights on the PCRs provoked by the red-flicker Blue light The following examination was then carried out. Using channel II of the visual stimulator, we projected steady illumination b y blue light of 1.9 cd/m 2 on the screen immediately after confirming the appearance of a PCR provoked b y the red-flicker. As soon as the PCR disappeared as a result of the illumination of blue light, b o t h the red-flicker and the blue light were continuously given for 7 sec. Again, after keeping the subject quiet under the same condition, eyes open, for 30 sec, we gave the blue light simultaneously with the red-flicker from the start. If no PCRs were provoked, this was continued for 7 sec. Following this procedure, the entire examination was repeated using blue light of 1 cd/m 2. At the time of EEG recording, 10 epileptics had ceased taking anticonvulsants for 18 h; 1 patient with photosensitive epilepsy (Case 6), 1 patient with pubertas praecox and 1 patient with mental retardation were n o t given any anticonvulsant; 1 patient with atypical psychosis was taking a tranquilizer.
Fig. 2 is an example of the findings recorded on a case of photosensitive epilepsy of a 12year-old female (Case 5, see Table I). In all subjects, PCRs were provoked by the redflicker alone, with EEGs similar to Fig. 2. In this series of experiments (see Table I), the latency of appearance of the PCRs in response to the red-flicker ranged from 0.4 to 3.8 sec, with a mean of 1.6 sec. The duration of the PCRs until stopping the red-flicker ranged from 1.0 to 1.6 sec, with a mean of 1.2 sec. The duration of the PCRs after stopping the red-flicker ranged from 0.3 to 0.9 sec, with a mean of 0.6 sec.
2. Effects of dim background lights on the PCRs provoked by the red-flicker Blue light of 1.9 cd/m: As shown in Fig. 3, when blue light of 1.9 cd/m 2 was given (arrow at trace A) after the appearance of a PCR provoked by the redflicker, the PCR completely disappeared. This p h e n o m e n o n was observed in all the subjects. As shown in Table II, the latency of appearance of the PCRs in response to the red-flicker ranged from 0.4 to 4.2 sec with a mean of 1.5 sec. The duration of the PCRs until the blue
128
T. T A K A H A S H I , Y. T S U K A H A R A
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~
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Fig. 2. E E G s o f a 12-year-old female patient with p h o t o s e n s i t i v e epilepsy (Case 5). Only the red-flicker o f 15 c/sec and 20 c d / m 2 was e f f e c t i v e in p r o v o k i n g a p h o t o c o n v u l s i v e response (PCR). Other flicker stimuli o f white, y e l l o w , green and blue light at 15 c/sec and 20 c d / m 2 were all ineffective. The l a t e n c y o f appearance o f the PCR in response to the red-flicker was 2.4 sec. For this E E G activation, the visual stimulator was used. Unipolar derivation with ipsilateral ear lobe reference.
light was given ranged from 0.6 to 1.6 sec, with a mean of 0.9 sec. The latency of disappearance of the PCRs in response to the blue light ranged from 0.2 to 3.2 sec, with a mean of 0.9 sec. As shown in Fig. 5, the latency of appearance of the PCRs in response to the red-flicker showed an inverse relation to the latency of disappearance of the PCRs in response to the blue light. Simultaneous stimuli of both the red-flicker and the blue light from the start brought a continuous suppression in all the subjects (for example see trace B of Fig. 3). Blue light o f I cd/m 2 As shown in Table II, the latency of appear-
ance of the PCRs in response to the red-flicker ranged from 0.5 to 4.2 sec, with a mean of 1.4 sec. The duration of the PCRs until the blue light was given ranged from 0.6 to 2.0 sec, with a mean of 1.2 sec. As shown in Fig. 4 (arrow at trace A), when the blue light of 1 cd/m 2 was given after the appearance of the PCRs provoked by the red-flicker, the PCRs tended to persist without being much influenced by the blue light. Such a sustained appearance of the PCRs was seen in 10 cases; continuous (2 cases) or transient suppression (2 cases) in 4 cases. The latency of disappearance of the PCRs in response to the blue light in these 4 cases was 1.7, 0.6, 0.8 and 1.4 sec. Of these 4 cases, 2 showed continuous sup-
INFLUENCE OF COLOR ON THE PCR
129
TABLE II The effect of the blue light of 1.9 and 1 cd/m 2 upon the PCRs provoked by red-flicker in 14 patients. In this table are shown the latency of appearance of the PCRs in response to the red-flicker (Appearance latency), the duration of the PCRs until giving blue light (Duration), the latency of disappearance of the PCRs in response to the blue light (Disappearance latency), and the suppression of the PCRs with simultaneous stimuli of both the redflicker and the blue light from the start (Suppression from start). Case
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Blue light of 1.9 cd/m 2
Blue light of 1 cd/m 2
Appearance latency (sec)
Duration (sec)
Disappearance latency (sec)
Suppression from start
Appearance latency (sec)
Duration (sec)
Disappearance latency (sec)
Suppression from start
2.3 0.8 1.7 0.5 1.2 0.4 0.7 0.7 2.6 0.8 1.8 2.4 4.2 0.4
0.8 0.8 1.1 0.7 1.0 0.6 0.6 0.9 0.6 1.0 1.6 1.2 1.0 0.8
0.6 0.6 0.5 1.1 1.4 1.9 0.4 0.7 0.2 0.2 0.6 0.4 0.4 3.2
(+) (+) (+) (+) (+) (+) (+) (+) (+) (+) (+) (+) (+) (+)
1.5 0.8 1.6 0.5 1.4 0.5 0.8 0.8 1.8 0.7 1.3 2.6 4.2 0.5
1.2 1.2 1.4 1.8 1.1 0.8 0.6 1.0 1.2 0.9 2.0 1.8 1.2 1.2
(--) * (--) (--) (--) 1.7 (--) (--) (--) 0.6--1.0 *** (--) (--) 0.8 1.4--0.6 (--)
(--) (--) (--) (--) (+) (--) (--) (--) (--) (--) (--) (--) (--) (--)
1.4 ** 0.7 1.5 1.6 0.5 0.6 0.5 5.2 1.2 1.6 4.2 1.6 0.4
* A sustained appearance of the PCRs, not suppressed by blue light. ** A latency of appearance (sec) of the PCRs provoked by the simultaneous stimuli of both the red-flicker and the blue light. *** PCR transiently suppressed only for time interval shown.
TABLE III The effect of the red light of 1.9 cd/m 2 upon the PCRs provoked by the red-flicker in 7 patients. In this table are shown the latency of appearance of the PCRs in response to the red-flicker (Appearance latency), suppression of the PCRs with simultaneous stimuli of both the red-flicker and the blue light of 1.9 cd/m 2 from the start (Suppression from start), and the suppression of the PCRs with simultaneous stimuli of both the red-flicker and the red light of 1.9 cd/m 2 from the start (Suppression from start by red light). Case
Appearance latency (sec)
Suppression from start
Suppression from start by red light
2 4 5 6 7 10 13
0.8 1.0 2.2 0.6 0.9 0.6 3.6
(+) (+) (+) (+) (+) (÷) (+)
(--) (--) (--) (--) (--) (--) (--)
2.0 * 0.6 2.0 0.7 0.7 0.8 3.8
* A latency of appearance (see) of the PCRs provoked by the simultaneous stimuli of both the red-flicker and the red light.
130
T. T A K A H A S H I , Y. T S U K A H A R A
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Fig. 3. EEG of an 11-year-old female patient with photosensitive epilepsy (Case 2). The PCR p r o v o k e d by the red-flicker was inhibited by adding blue light of 1.9 c d / m 2 (arrow at trace A). Simultaneous stimuli of the redflicker and the blue light from the start did not provoke a PCR (trace B).
pression (Cases 5, 12), and 2 showed a transient suppression, which lasted for 1 sec (Case 9) and 0.6 sec {Case 13). Simultaneous stimuli o f b oth red-flicker and blue light from the start brought a continuous suppression o f the PCR in 1 case alone. The remaining 13 cases showed a continuous appearance of PCRs (see trace B o f Fig. 4); the latency of appearance o f the PCRs ranged from 0.4 to 5.2 sec, with a mean of 1.6 sec.
Red light As shown in Table III, the latency of appearance of the PCRs in response to the redflicker ranged from 0.6 to 3.6 sec, with a
mean of 1.4 sec. Simultaneous stimuli of the red-flicker and the blue light of 1.9 cd/m 2 from the start brought a cont i nuous suppression of the PCRs in all the 7 cases. On the contrary, simultaneous stimuli o f the redflicker and the red light of 1.9 cd/m 2 from the start showed no such suppression but the activation effect of the PCR as provoked by the red-flicker alone (see trace C of Fig. 6); the latency of appearance o f the PCRs in response to the red-flicker plus the dim red background light o f 1.9 cd/ m 2 ranged from 0.6 to 3.8 sec, with a mean of 1.5 sec, which was similar to those obtained by the red-flicker alone.
INFLUENCE OF COLOR ON THE PCR
131
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Fig. 4. EEG of the same patient of Fig. 3. The PCR provoked by the red-flicker was not inhibited by adding blue light of 1 cd/m2 (arrow at trace A ). Simultaneous stimuli of the red-flicker and blue light of 1 cd/m2 from the start also provoked a PCR (trace B).
Discussion
The main results obtained in this study may be summarized as follows: (1) PCI%s were provoked by the red-flicker alone at 15 c/sec and 20 cd/m 2. (2) The PCRs provoked by the red-flicker were completely suppressed by the blue light of 1.9 cd/m 2. These findings of (1) and (2) will hereafter be called the excitatory effect on the PCR by red light and the inhibitory effect on the PCR by blue light, respectively.
1. Excitatory effect on the PCR by red light The results of our experiments provide direct and unequivocal evidence that red light
has an excitatory effect on the PCR. Since our experiments were carried o u t during a short period of dark-adaptation (between about 2 to 10 min after dark-adaptation), the retina is presumed to have remained in a photopic condition. It is suggested that when the red-flicker of 20 cd/m 2 is given in such a condition, the cones, especially the red cones might, perhaps, respond more predominantly than the rods. The electrical discharge in potential produced in the red cones as a result of the red-flicker would then be transmitted to the brain, finally to the visual cortex. Fukada and Saito (1971) reported that abnormally enhanced repetitive firing could be recorded from the cat optic nerve during and after flicker stimulation. Their finding
132
T. TAKAHASHI, Y. TSUKAHARA
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of
PCR
Fig. 5. Relationship between the latency of appearance of the PCRs in response to the red-flicker and the latency of disappearance of the PCRs in response to the blue light of 1.9 cd/m 2 obtained from the 14 patients. The abscissa is plotted on a logarithmic scale for convenience.
appears to have some characteristics that suggest "paroxysmal discharges" in the epileptic brain. Therefore, there is a possibility that the red-flicker may give rise to "paroxysmal discharges" even in the retina of the photosensitive patients. Thus, the p o t e n t activating effect on PCRs by red light should not be explained w i t h o u t considering the whole neuronal mechanisms from the retinal level to the visual cortex. Takahashi and Tsukahara (1975a) suggested that the nonspecific thalamo-cortical system is chiefly concerned with the appearance of PCRs of generalized type provoked by red-flicker, though n o t by pattern stimuli nor by eye movements.
Additionally, it has been suggested that photosensitivity may be a familial trait (Davidson and Watson 1956; Daly et al. 1959; Doose et al. 1969). Doose et al. (1969) reported that PCRs were regarded as a s y m p t o m of susceptibility to convulsions of the centrencephalic type. In addition to this, other biological factors, such as maturational and sexual differences, are presumed to play other important roles in lowering the threshold of sensitivity to the IPS by stroboscopic light, since Doose et al. (1969) clearly demonstrated that photosensitive epilepsy was most commonly seen between the ages of 6 and 15 years, and that female patients were more c o m m o n than male. For more precise clinical-EEG correlates, reaffirmation of these findings by using the method of red-flicker remains to be done. In contrast, when studying photosensitive epilepsy in the Papio papio, Serbanescu et al. (1973) reported that the most effective were the colors blue-green and dark-green, and the least effective were green and red.
2. Inhibitory effect on the PCR by blue light A question may arise whether the inhibitory effect on the PCR by blue light is due to the decrease of light and dark ratio of the flickering light by giving the dim blue background light of 1.9 cd/m 2 on the red-flicker. However, the controlled experiments with the red-flicker, by adding the dim red background light of the same brightness as the blue light, showed a similar excitatory effect to that obtained by the red-flicker alone. Although there have been reports in which an inhibitory effect on the PCR by short wavelengths was demonstrated electroencephalographically (Carterette and Symmes 1952; Marshall et al. 1953; Bickford 1954; Asano and Umezaki 1965; Takahashi and Tsukahara 1972b, 1974a), exact quantitative data have not yet appeared. As a preliminary report, Takahashi and Tsukahara (1972b) reported t h a t the PCRs provoked by red-flicker of 15 c/sec and 40 cd/m 2 was inhibited bv blue light
I N F L U E N C E O F C O L O R ON T H E PCR
133
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B
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Fig. 6. E E G o f a 14-year-old female patient with photosensitive epilepsy (Case 7 ). The PCR p r o v o k e d by the redflicker (trace A ) was n o t seen by simultaneous stimuli o f the red-flicker and blue light of 1.9 c d / m 2 f r o m the start (trace B). However, simultaneous stimuli of the red-flicker and red light of 1.9 c d / m 2 f r o m the start p r o v o k e d a similar P C R to the PCR shown in trace A.
of 0.7 cd/m 2. This study, however, was carried out only when giving blue light simultaneously with red-flicker. In the current investigation, the effect of blue light on the PCRs provoked by red-flicker was studied in different ways as already described. The direct action of blue light having an inhibitory effect m a y act either at the peripheral level, i.e., the pupil and the retina, or at the brain level, i.e., the geniculate body and the visual cortex. However, the influence of the pupil, presumably the constriction of the pupil, is probably not of great importance. The immediate inhibition of the PCRs by the blue light of 1.9 c d / m 2, as if the red-flicker was stopped, is especially suggestive of an important role of the retina in such a mecha-
nism. As already mentioned, since our experiments were carried out in a photopic condition, it is presumed that the inhibitory effect by blue light was produced by the blue cones in the retina. From a therapeutic viewpoint, the finding of an inverse relation between the latencies of appearance and disappearance of PCR (as shown in Fig. 5) can be important. Based on this finding, we adjusted the dosage of anticonvulsants for photosensitive epileptics; for the patients who showed long latency of appearance of PCR in response to the redflicker, we prescribed a minimal a m o u n t of anti-convulsants, and vice versa. In addition, we have tried letting them use blue eyeglasses, and apparent clinical improvements have been
134 confirmed in all of them. Here, we must mention the difference observed in a patient with photosensitive epilepsy associated with color blindness (Takahashi and Tsukahara 1974b). The PCRs provoked by the IPS of stroboscopic light was in fact provoked by the flickering pattern itself, not by red-flicker. Furthermore, the generalized paroxysmal discharges were not inhibited by blue light. In this case, smoked eyeglasses, regardless of color, were found to give improvement. Excepting such cases of color blindness, blue-colored eyeglasses other than simply redminus eyeglasses as suggested by Bickford (1954) are recommended to the photosensitive epileptics. Finally, after this series of experiments, we have repeated the same experiment on some other photosensitive patients, giving the stimuli b u t not in a constant order. Even in this experiment, similar results to those described were obtained. We have also tested some other photosensitive epileptics in whom sustained generalized paroxysmal discharges provoked by the red-flicker (even by that of 5 cd/m z) were not suppressed by blue light of 1.9 cd/m 2. However, reexamination after giving proper anticonvulsants revealed the same inhibitory effect of blue light. Again these findings support evidence of inhibitory effect of blue light. As to whether the rods of retina are also concerned with the mechanism of the excitatory and inhibitory effects, the same experiments on photosensitive patients after sufficient dark-adaptation or on the same subjects associated with nyctalopia remain to be done. In order to know whether green light shows the similar inhibitory effect to that obtained by blue light on the PCR, another experiment should also be made using a proper filter for green light.
Summary Using the visual stimulator, the effect of color on the photoconvulsive response (PCR)
T. TAKAHASHI, Y. TSUKAHARA was studied in 14 photosensitive patients. When stimuli of 15 c/sec flickers of white, red, yellow, green and blue light of 20 cd/m 2 were given to the subjects, generalized PCRs were provoked only by the red-flicker. These PCRs were all inhibited by blue light of 1.9 cd/m 2 when given either after the appearance of the PCRs or simultaneously with the red-flicker from the start. When blue light was given after the appearance of the PCRs, the latency of appearance of the PCRs in response to the red-flicker showed an inverse relation to the disappearance latency of the PCR in response to the blue light. With blue light of 1 cd/m 2, however, inhibition of the PCRs was seen in only 2 cases when it was given after the appearance of the PCR, and in only 1 case when the blue light was simultaneously given with the red-flicker from the start. These results clearly disclosed the following findings: (1) among various colored lights, an excitatory effect on generalized PCR was always seen only with red light at 15 c/sec and 20 cd/m2; (2) the PCRs provoked by the red-flicker were inhibited by blue light of 1.9 cd/m 2, but not by blue light of 1 cd/m 2.
1
J
Resume
Influence de la couleur sur la rdponse photoconvulsive
Les effets de la couleur sur la r~ponse photoconvulsive (RPC) ont ~t~ ~tudi~s, ~ l'aide du stimulateur visuel, sur 14 malades photosensibles. Quand on soumet les sujets ~ une oscillation lumineuse de 15 c/sec et de 20 cd/m 2, successivement blanche, rouge, jaune, verte, et bleue, seule la rouge provoque des RPC g~n&alis~s. Ces RPC sont toutes neutralis~es par une tumi~re bteue de 1,9 cd/m 2, quand celle-ci est ~mise, soit apr~s l'apparition des RPC, soit d~s le d~but, simultan~ment avec le trait rouge. Quand la lumiSre bleue est ~mise aprSs l'apparition des RPC, la latence de l'apparition des RPC en r~ponse au trait rouge apparalt en relation inverse de la latence de
INFLUENCE OF COLOR ON THE PCR
disparition des RPC en rdponse ~ la lumi~re bleue. Avec une lumi~re bleue de I cd/m 2, cependant, la suppression des RPC n'est notde que deux fois quand elle est dmise apr~s l'apparition des RPC et ne l'est qu'une fois quand la lumi~re bleue est dmise d~s le ddbut, simultandment avec le trait rouge. Ces rdsultats m o n t r e n t clairement les fairs suivants: (1) parmi des lumi~res de diffdrentes couleurs, on peut seulement constater un effet d'excitation sur la RPC gdndralisd avec une lumi~re rouge de 15 c/sec et de 20 cd/m2; (2) les RPC provoqudes par le trait rouge sont neutralis~es par une lumi~re bleue de 1,9 cd/m 2, mais non par une lumi~re de 1 cd/m 2. Our thanks to Prof. Teruo Okuma for a critical reading of the manuscript; to Dr. Makoto Tamai for his discussions on the manuscript; to Mr. Masaichi Sasaki for his help in recording EEGs.
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