Electroencephalography and Clinical Neurophysiology, 1977, 43 : 837--845 © Elsevier/North-Holland Scientific Publishers, Ltd.

837

CHANGES IN VISUAL EVOKED POTENTIALS OF SCHIZOPHRENICS AFTER ADDITION TEST IWAO KADOBAYASHI,MICHIHIKO NAKAMURA and NOBUKATSU KATO Department of Psychiatry, Kyoto Prefectural University of Medicine, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto (Japan)

(Accepted for publication: May 3, 1977)

In recent years, evoked potential studies have come to receive attention in psychiatry. Several findings using the evoked potential method in schizophrenic disorders have been reported. The mean amplitude of evoked potentials in some schizophrenic groups is smaller than in a healthy control group (Rodin et al. 1964; Rodin et al. 1968; Shirakawa 1970; Saletu et al. 1971; Roth and Cannon 1972; Levit et al. 1973; Rappaport et al. 1975; Landau et al. 1975). Schizophrenics have greater variability in the evoked potential than normals (Speck et al. 1966; Liftshitz 1969; Callaway et al. 1970; Rappaport et al. 1975). When paired stimuli axe applied, the amplitude of the second response is smaller in schizophrenics than in healthy controls (Shagass and Schwartz 1963; Speck et al. 1966; Floris et al. 1968). In chronic schizophrenic patients, the amplitude of the visual evoked potential (VEP) is reduced in the presence of increased electromyographic activity associated with verbal hallucinations (Inouye and Shimizu 1972). TABLE I Age and sex of subject groups

Group

Schizophrenics Neurotics Affective disorders

N

Sex

Age (yrs)

M

F

M e a n Range

30

19

26

14

11 12

25 25

12

8

4

49

13--36 18--45 29--74

We have observed reduction in amplitude of VEPs after the Kraepelin performance test (addition test) in schizophrenics, in contrast to no change in normals and neurotics (Kadobayashi et al. 1973; Kadobayashi et al. 1975). In this report, a more systematic study of changes in VEPs of schizophrenic patients after the addition test was undertaken.

Methods Subjects The schizophrenic group was composed of 23 new outpatients who had never been treated with psychotropic drugs, 3 outpatients who visited our clinic again because of their recurrence of the illness w i t h o u t medication for more than 3 months and 4 inpatients who, for 14 days prior to the testing, were given as a placebo, digestive ferment (Festal, Hochst). Classification of schizophrenics was as follows: paranoid, 5; simple, 9; hebephrenic, 16 (typical, 7: atypical, 9). According to Bleuler, hebephrenia includes some cases t h a t do not fit into one type, so we called those cases atypical hebephrenia. All of the three authors could agree on the clinical picture. No case had a history of organic brain disease. Those who had been treated with electrical convulsive therapy and those whose electroencephalograms (EEGs) showed paroxysms and/or high voltage alpha activity were excluded. The neurotic group consisted of 26 new outpatients whose EEGs showed regular

838 alpha activity, with n o h i s t o r y o f m e d i c a t i o n . The affective disorders g r o u p was c o m p o s e d o f 5 manic-depressives (2 in h y p o m a n i c states; 3 in depressive states), 4 depressives, I m a n i c and 2 cases o f involutional melancholia. Five had no h i s t o r y o f m e d i c a t i o n and the o t h e r s were given the placebo for 2 weeks b e f o r e the test. No case had been t r e a t e d with convulsive t h e r a p y (Table I).

Experimental situation When subjects e n t e r e d the test r o o m , the p u r p o s e and c o n d i t i o n s o f the e x p e r i m e n t were briefly explained. T h e y were asked t o lie back in an easy-chair with closed eyes in the semi-dark r o o m and were i n s t r u c t e d to relax as m u c h as possible. H e a d p h o n e s o f a taper e c o r d e r were fixed o n t h e subject's ears, a n d a x e n o n flash lamp was placed 40 c m in f r o n t o f his eyes. The subject was told n o t to p a y a t t e n t i o n to flash stimuli w h i c h w o u l d occur. He was also told t o answer as s o o n as possible the p r o b l e m s (addition o f t w o digits, such as t h r e e plus eight) t h a t he heard in the headp h o n e s while keeping his eyes closed.

Data recording and data processing The E E G was r e c o r d e d with a 9-channel EEG m a c h i n e with a time c o n s t a n t o f 0.3 sec. The r e c o r d i n g e l e c t r o d e was l o c a t e d in t h e midline 3 c m above the inion, with reference t o t h e left ear. 70 successive flashes at an interval o f 1 sec were presented f r o m the flash lamp, and E E G responses were r e c o r d e d on a d a t a recorder. S i m u l t a n e o u s l y an inked E E G r e c o r d was m o n i t o r e d t h r o u g h o u t the recording session. A f t e r d a t a recording, a b o u t 60 responses o f 70, e x c l u d i n g t h o s e w h e n artifacts o r high voltage basic activity a p p e a r e d , were averaged b y a signal-averaging c o m p u t e r . The VEP was p h o t o g r a p h e d and w r i t t e n o u t o n an X-Y plotter. Initially 3 VEPs were r e c o r d e d . T h e n the a d d i t i o n test was p e r f o r m e d for 20 sec, 1 min after the end o f the test flashes started, and a VEP was o b t a i n e d . A f t e r m o r e t h a n 3 min rest, one m o r e V E P (B) was r e c o r d e d a n d

[. KUDOBAYASHI ET AL.

~IVvi

A1

A31 A5 A7

_J

Fig. 1. VEPs of a neurotic patient (26-year-old female). The numbers on the curve classify the various positive and negative peaks according to the nomenclature of Cigdnek. B: the VEP before the test for 15 min. AI: the VEP that flashes started 1 min after the end of the test for 15 min. Thereafter series of VEPs (A3, A5, A7) at an interval of 2 rain were recorded. Negativity at the occipital electrode results in upward deflection. Calibration: 10 pV, 100 msec.

the a d d i t i o n test for 15 min was p e r f o r m e d * Flashes started 1 min a f t e r the end o f the perf o r m a n c e , and t h e VEP (A1) was o b t a i n e d . T h e r e a f t e r a series o f VEPs at an interval o f 2 min were r e c o r d e d (A3, A5, etc.) (Fig. 1). A m p l i t u d e o f each VEP was m e a s u r e d f r o m peak I I I to peak IV ( a c c o r d i n g t o the n o m e n clature o f Cig~inek). M e a s u r e m e n t s were also made o f l a t e n c y t o peak IV. Statistical treatm e n t o f t h e d a t a was carried o u t o n schizo~ phrenic, n e u r o t i c , and affective disorders group.

Results

Amplitude of VEPs A m p l i t u d e o f VEPs of s c h i z o p h r e n i c s was reduced a f t e r the a d d i t i o n test for 15 min (Fig. 2, Table II), while t h a t o f n e u r o t i c s and

* For the purpose of finding changes in VEPs during the addition test, 60 flashes every 1 sec started 1 min after and 14 min after the beginning of the test, and single flashes were given simultaneously with presentation of every addition problem for 10 rain from 3 rain after the beginning of the test. These findings will be described in another paper.

VEP IN SCHIZOPHRENIA

839

TABLE II Mean amplitudes (in pV) of the wave IV of the VEP before and after the addition test for 15 rain Group Subgroup

N

B

A1

A3

A5

A7

Neurotics

26

M SD

9.95 3.10

9.97 3.13

10.18 2.94

10.13 3.23

9.81 3.07

Affective disorders

12

M SD

8.11 2.81

8.24 3.27

8.08 3.06

8.57 3.18

8.32 3.26

Schizophrenics

30

M SD

9.92 3.93

6.87 3.39

5.68 2.89

6.40 2.84

5 paranoid schizophrenics

M SD

9.65 2.69

5.10 1.57

6.01 1.62

atypical hebephrenics

9

M SD

9.83 2.94

5.36 1.31

typical hebephrenics

7

M 10.29 SD 4.89 M SD

9 simple schizophrenics

9.88 4.47

A9

All

F *

df

P

0.92

4/100

>0.25

NS

8.56 3.22

0.75

5/55

>0.25

NS

7.39 3.35

8.48 3.59

22.25

5/145

0.25). In schizophrenics, 4 types of changes in amplitude of VEPs after the test for 15 min

could be seen. Namely, marked reduction occurred in A1 (A1 type), in A3 with fast recovery (A3f type), in A 3 with slow recovery (A3s type), and in A5 (A5 type).

100

80

B

60

40

i

2G

0

Fig. 2. VEPs of a paranoid schizophrenic patient (34-year-old, male) showing the A1 type change. Calibration: 10 pV, 100 msec.

A1

A3

A5

A7

A9

ACt

Fig. 3. Recovery curves of VEPs for schizophrenics who showed the A1 type change. Abscissa: A1, A3, A5, etc. Ordinate: amplitude of the wave IV after the test as percentage of that of B. A g e a n d s e x are indicated on the left of the curve. (e) represents the recurred case.

840

I KbDOBAYASHIETAL.

A 1 type Amplitude was reduced most markedly in A1, with recovery to the pre-test level later. Fig. 2 shows an example of this type. This case was a 34-year-old paranoid schizophrenic. His illness began with primary delusions and sleeplessness about 2 years ago. He improved with chlorpromazine treatment. As his delusions recurred, he visited our clinic again. He was examined, with no medicatiom for those 15 months. Fig. 3 shows recovery curves of A1 type. Age and sex of the case is indicated on the left of the curve. The asterisk represents the recurred case, and no mark is indicated for the new untreated patient. Most of the cases (5 o u t o f 7) who showed the A1 t ype change had typical s y m p t o m s of paranoid schizophrenia. The remaining two were atypical hebephrenics who had a delusional mood.

A3[ type Amplitude was reduced most prominently in A3 with fast recovery (Fig. 4). Clinical picture of one of these cases is as follows: A case came to our clinic with auditory hallucinations, delusions and thought-blocking at the age of 34. He had received no t r e a t m e n t with psychotropic drugs, but the beginning of his Y~ 100 i

/~'-

6ol

~

.

40 ~

201

/

J 01

AI

A3

A5

A7

A3s type Amplitude was reduced most markedly ill A3 with slow recovery (Fig. 5). Clinical picture of one of these cases is as follows: A 13-year-old girl lost her drive and volition, and was autistic, Derealization and outbt "sts of terror were her manifestations. She had no hallucinations. Her expression was flat. She was o f asthenic physique. Her clinical picture was typical as hebephrenia. All who showed the A3s t ype change had typical s y m p t o m s of hebephrenia and were o f asthenic constitution. In the figures the sign: indicates the case whose t r e a t m e n t with psychotropic drugs was stopped and who was given the placebo for 2 weeks before the testing.

j

S!//- ~/ ""

80

illness was presumed to have started about the age of 20, becuase of his severe sleeplessness and abnormal findings in psychological tests. He was of pyknic constitution. His clinical picture was rather atypical as hebephrenia. All of those who showed the A3f t y p e change had clinical features of atypical hebephrenia. All had t hought disorder, and most of them (5 out of 6) had hallucinations mid delusions. A 15-year-old boy, an early ease. remained in a delusional mood. Most of then, (5 out of 6) were of pyknic physique.

A9

All

Fig. 4. Recovery curves of VEPs for schizophrenics who showed the A3f type change.

A 5 type The most marked reduction in amplitude appeared in A5 (Fig. 6). Clinical picture of one of these cases is as follows: A 29-yearold man had an experience of feeling he was becoming mad at the age of 20. He had spent about nine years without florid symptoms. He visited our clinic because of a delusional mood, and was diagnosed as simple schizophrenia becuase of his shallowness of emotional response, personality change, etc. Most of those (9 out of 10) who showed the A5 t ype change had the clinical picture of simple schizophrenia. The remaining one was diagnosed as atypical hebephrenia because of his auditory hallucinations.

9 7 9

atypical hebephrenics

typical hebephrenics

simple schizophrenics

* Analysis of variance.

5

30

Schizophrenics

paranoid schizophrenics

12

Affective disorders

N 26

Sub~oup

Neurotics

Group

M SD

M SD

M SD

M SD

M SD

M SD

M SD

114.3 3.7

113.4 9.0

115.0 8.0

110.3 7.2

113.7 7.3

117.1 11.0

115.5 8.9

B

116.3 5.5

115.0 8.9

116.7 7.5

114.5 7.4

115.8 7.4

116.9 11.0

115.6 8.3

A1

117.4 4.7

117.0 9.4

117.7 9.4

113.1 8.8

116.7 8.2

118.2 12.5

116.7 8.9

A3

117.9 4.6

116.7 8.9

117.4 8.9

113.3 8.5

116.7 8.0

118.2 13.0

116.3 9.4

A5

1 i 6 .9 6.5

116.4 9.5

117.5 9.7

112.5 8.2

116.3 8.5

116.7 11.6

115.9 9.5

A7

116.8 5.7

116.2 9.5

116.8 7.6

113.1 9.8

116.0 8.2

115.5 11.4

A9

116.5 6.8

All

Mean latencies (in msec) to the peak of the wave IV of the VEP before and after the addition test for 15 min

TABLE III

df

4/100 5/55 5/145

F *

0.84 0.90 14.01

0.25

>0.25

P

NS

NS

O0

>

t~

O *o

< t~

I. K U D O B A Y A S H I ET AL.

842

the three groups in the mean latency of B (F = 0.70, dr= 2/65, P~> 0.25).

1OO , , ,

Discussion

~-0

0

A1

A3

A5

A7

A9

All

Fig. 5. R e c o v e r y curves o f VEPs for s c h i z o p h r e n i c s w h o s h o w e d the A3s t y p e c h a n g e . (~) r e p r e s e n t s t h e case w h o s e t r e a t m e n t w i t h p s y c h o t r o p i c drugs was s t o p p e d a n d w h o w a s given t h e p l a c e b o for 14 d a y s before the testing.

Latency of VEPs Latency of VEPs of schizophrenics was prolonged after the test for 15 min, whereas that of neurotics and affective disorders showed no significant change (Table III). There was no significant difference between

Y;

/ 40

2O

ol~

Aa

A5

A'7

A9

A~

Fig. 6. R e c o v e r y curves o f VEPs for s c h i z o p h r e n i c s w h o s h o w e d t h e A5 t y p e c h a n g e .

We have previously demonstrated that amplitude of VEPs of schizophrenics reduces after the Kraepelin performance test (addition test) for 15 min whereas that of normals and neurotics shows no change (Kadobayashi et al. 1973; Kadobayashi et al. 1975). In this study, too, reduction in amplitude was observed in VEPs of schizophrenics after the addition test for 15 rain, in contrast to no change in those of neurotics and in those of patients with affective disorders. Reduced amplitude of VEPs in schizophrenics was observed at the presence of an increased electromyographic activity of speech muscles associated with verbal hallucinations (Inouye and Shimizu 1972). In normal subjects, many studies bearing on the relationship between amplitude of evoked potentials and levels of consciousness and attention have been made (Williams et al. 1962; Domino et al. 1963; Davis 1964; Guerrero=Figueroa and Heath 1964; Haider et al. 1964; Satterfield 1965; Spong et al. 1965; Ciganek 1967; Corletto et al. 1967; Donchin and Cohen 1967; Groves 1969; Koppet et al. 1969; Ritter and Vaughan 1969; Tecce 1970; Schwent and Hillyard 1975). Among them, of interest is that responses evoked by signals which a subject fails to detect during an experiment are reduced in amplitude as compared with those evoked by an equal number of signals which are correctly detected (Haider et al. 1964). So schizophrenic patients may become more inattentive when reduced amplitude of VEPs is observed after the addition test. It has been reported that schizophrenics have greater variability of VEPs (Speck et al. 1966; Liftshitz 1969) and auditory evoked potentials (Callaway et al. 1970; Rappaport et al. 1975) than normal but that more psychotic, less depressed schizophrenic patients have greater wave stability in the first 100 msec of the somatosensory evoked potential

V E P IN S C H I Z O P H R E N I A

(Shagass et al. 1974). As the wave IV is the most reliable in the VEPs of man (Creel et al. 1974), we measured the wave IV in this study. We added responses to flashes, excluding those when there were artifacts or high voltage basic activity, which might be one of the causes of variability. R e d u c e d amplitude of VEPs of schizophrenics after the addition test recovered to the pre-test level later. Therefore, it can be said that the reduction in amplitude we observed in this study is n o t due to variability, b u t caused b y performing the test for 15 min. Schizophrenic patients show a longer latency of a wave of the somatosensory evoked potential than normals (Shagass 1968), and those with thought process disorders have shorter latencies of the auditory evoked potential (Saletu et al. 1971). In patients in good health and free of neurologic or psychiatric disorders, light surgical anesthesia produces prolongation of latencies of VEPs (Domino et al. 1963). So, prolongation of latency of VEPs in schizophrenics after the addition test may reflect a change in the brain of the patients after performing the test. Amplitude of the auditory evoked potential is smaller in schizophrenics than in normals (Roth and Cannon 1972), especially in those with thought process disorders (Saletu et al. 1971). Schizophrenics have smaller amplitudes of VEPs when compared to normals (Rodin et al. 1964; Rodin et al. 1968; Levit et al. 1973; Landau et al. 1975; Rappaport et al. 1975). Most of those who show lower amplitudes of VEPs have typical clinical features of hebephrenia, such as autism, loss of volition, etc. (Shirakawa 1970). On the other hand, the more psychotic, less depressed schizophrenic patients have higher amplitudes in the first 100 msec of the somatosensory evoked potential (Shagass et al. 1974). As there is interindividual variability n o t only in normals b u t also in psychotic patients, we attempted to find out whether some changes in the VEPs would occur after the addition test. As a result, 4 types of changes could be seen in schizophrenic patients: namely, A1,

843

A3f, A3s, and A5 types. Of particular interest is that each type was related closely to the clinical picture. Paranoid schizophrenics showed the A1 t y p e change, and simple schizophrenics the A5 type. Those who showed the A3s t y p e change had the typical clinical picture of hebephrenia, b u t those who showed the A3f t y p e change had the atypical one. Classification of schizophrenia b y this method using more cases will be described in detail in another paper. When paired stimuli are applied, the amplitude of the second response at some interstimulus intervals is smaller in schizophrenics than in normal subjects (Shagass and Schwartz 1963; Speck et al. 1966; Floris et al. 1968). Schizophrenic patients showed smaller amplitude increases with increasing light intensity than either normals or bipolar affective disorders for the negative component (120--140 msec latency) of the VEP (Landau et al. 1975). These findings and our data support the idea that brain functions are deviant in schizophrenics. In any case, further studies are necessary to explain the underlying mechanisms of the VEP changes after the addition test. Summary

Visual evoked potentials were obtained for schizophrenics, neurotics and patients with affective disorders, and comparison between those before and after an addition test for 15 min was made. Reduction in amplitude and prolongation of latency of the potential were observed in schizophrenics after the test, while there was no change after that in neurotics and patients with affective psychosis. In schizophrenics, 4 types of changes in amplitude of the potential could be seen after the test. Namely, marked reduction occurred in A1 (A1 type), in A3 with fast recovery (A3f type), in A3 with slow recovery (A3s type), and in A5 (A5 type). (A1, A3, A5: Averaged potentials evoked b y 1 c/sec flashes

844

which started 1 min, 3 min and 5 min after the end of the test.) Each type closely corresponded to paranoid schizophrenia, atypical hebephrenia, typical hebephrenia and simple schizophrenia, respectively.

g6sum6

Modifications des potentiels dvoquds visuels chez les schizophrdnes aprds test d'addition Les potentiels 6voqu6s visuels ont 6t6 obtenus chez des malades schizophr6nes, n6vrotiques, et avec psychose affective; il a 6t6 proc4d6 ~ une comparaison entre les potentiels obtenus avant et apr6s test d'addition de 15 min. Une diminution d'amplitude et une augmentation de latence des potentiels a 6t6 observ6e chez les schizophr~nes apr6s le test, alors qu'il n'y avait aucune modification chez les malades n6vrotiques et les malades avec psychoses affectives. Chez les schizophr6nes, quatre types de modifications d'amplitude des potentiels peuvent s'observer apr~s le test: r6duction marqube en A1 (type A1), en A3 avec r6cup6ration rapide (type A3f), en A3 avec r6cup6ration lente (type A3s), et en A5 (type A5). Pour A1, A3, A5, les r6ponses 6voqu6es moyenn6es sont cons6cutives ~ des 6clairs de 1 c/see qui d6butent 1 min, 3 min, et 5 min apr6s la fin du test). Chaque type correspond approximativement aux classifications suivantes: schizophr6nie parano'/de, heb6phr6nie atypique, heb6phr6nie typique et schizophr6nie simple respectivement.

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Changes in visual evoked potentials of schizophrenics after addition test.

Electroencephalography and Clinical Neurophysiology, 1977, 43 : 837--845 © Elsevier/North-Holland Scientific Publishers, Ltd. 837 CHANGES IN VISUAL...
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