Habituation of the orienting reaction in patients with epileptogenic cerebral tumours

65

Biological Psychology 16 (1983) 65-84 North-Holland Publishing Company

HABITUATION OF THE ORIENTING REACTION EPILEPTOGENIC CEREBRAL TUMOURS

Radu

ROGOZEA

Department

IN PATIENTS

WITH

* and Viorica FLOREA-CIOCOIU

of Behavioural

Sciences, Institute

of Neurology and Psychiatry,

Bucharest, Romania

and Alexandru

CONSTANTINOVICI

Clinic of Neurosurgery, Accepted

for publication

Bucharest, Romania 25 October

1982

A polygraphic study on resistance to habituation of the somatic, autonomic and EEG components of the orienting reaction elicited by a repetitive auditory stimulus was performed in 41 patients with epileptogenic cerebral tumours and in 128 matched subjects in three control groups. The study evidenced a significantly higher resistance to habituation of the orienting reaction in patients with epileptogenic cerebral tumours than in control subjects. The degree of habituation disturbances depended on the tumour site and size as well as on the electro-clinical form and frequency of seizures.

1. Introduction

The orienting reaction, an innate adaptive response elicited by any new environmental stimulus, is a complex psychophysiological reaction consisting in man of somatic, autonomic, EEG, emotional and verbal components (Gastaut, Jus, Morrell, Storm van Leeuwen, Dongier, Naquet, Regis, Roger, Bekkering, Kamp and Werre, 1957; Magoun, 1958; Sokolov, 1958). Its repeated elicitation by the same unchanged stimulus determines progressive response decrement, i.e. its habituation (Roger, Voronin and Sokolov, 1958; Sokolov, 1959, 1963 a, 1963 b; Jus and Jus, 1960; Gastaut and Bert, 196 1). Previous studies showed that in some diseases of the cerebral nervous system disturbances occur in the habituation process which can be detected by testing the electrographic components of the orienting reaction (Venables, 1960; Rogozea and Florea-Ciocoiu, 1973, 1979; Siddle, Nicol and Foggitt, * Address for correspondence: C.P. 6180, R-75622, Bucharest,

Dr. R. Rogozea, Romania.

030 l-05 11/83/0000-0000/$03.00

Institute

of Neurology

0 1983 North-Holland

and Psychiatry,

O.P. 61,

66

R. Rogorea et al. / Habituation

in epileptogenic cerebral turnours

1973; Saarma, 1974; Lader, 1975; Raskin, 1975; Chattopadhyay, Cooke, Toone and Lader, 1980). In this work we set ourselves the task to study by this electrophysiologic method the habituation process of the orienting reaction in patients with epileptogenic cerebral tumours (ECT) and to compare it with habituation in three appropriate control groups. This study set out from the supposition that a tumoural expanding process may induce, besides epileptic seizures, also psychophysiologic disturbances that may be expressed by alterations in the orienting reaction habituation. We supposed that the presence of hemispheric cerebral tumours may determine psychophysiologic disturbances differentiated according to the tumours size and topography as well as to the epileptic seizures presence and to their features. Consequently, to estimate and interprete the results most judiciously, we set ourselves the task of comparing the data obtained in the ECT group with the similar data obtained both in a group of healthy subjects and, especially, in groups of patients with differentiated central nervous system diseases and, hence, with differentiated symptoms (with cerebral tumours but without seizures, or with seizures but without tumours).

2. Material and methods 2. I. Subjects The study was performed on 169 subjects: 41 patients with ECT, 43 normals (control group I), 36 patients with non-epileptogenic cerebral tumours (NCT) (control group II) and 49 patients with partial or/and generalized seizures of unknown etiology (SUE) (control group III). The patients were selected from the neurological and neurosurgical departments of the ‘Gh. Marinescu’ hospital of Bucharest. The ECT group included exclusively subjects presenting hemispheric supratentorial cerebral tumours of neoplastic nature, patients with non-neoplastic intracranial space-occupying lesions being excluded. Grouping of patients according to the characteristics of cerebral tumours as well as to the seizure features is illustrated in tables 1 and 2, respectively. The patients’ age and sex distribution is presented in table 3. Control group II included patients with NCT selected upon the same criteria as those with ECT. In this group, sex and age distribution was similar to that in the ECT patients (table 3). Control group III comprised epileptics in whom the clinical and paraclinical examination failed to evidence the causative factor of the partial or/and generalized seizures. Seizure electro-clinical form and frequency (table 2) as well as age and sex distribution (table 3) in these patients were similar to those in ECT group.

67

R. Rogozea et al. / Habituation in epileptogenic cerebral turnours Table 1 Distribution of patients their characteristics Characteristics

with epileptogenic

of cerebral

and non-epileptogenic

cerebral

Patients with epileptogenic

tumours

%

according

Abs. no.

Frontal or predominantly frontal Central or predominantly central Parietal or predominantly parietal Temporal or predominantly temporal Occipital or predominantly occipital Total

14 5 7 10 5 41

34.1 12.2 17.1 24.4 12.2 100

36

100

Histologicalaspect

Astrocytomas Glioblastomas Meningiomas Oligodendrogliomas Total

7 18 11 5 41

17 43.9 26.9 12.2 100

5 15 9 I 36

13.9 41.7 25 19.4 100

Size

< 3 cm 3-6 cm >6cm Total

9 22 10 41

21.9 53.1 24.4 100

6 18 12 36

16.7 50 33.3 100

= absolute

number

of patients;

% = same numbers

converted

12 5 6 13 _

%

Site

Abs.no.

to

Patients with nonepileptogenic cerebral tumours

tumours Abs. no.

tumours

33.3 13.9 16.7 36.1

into percentages

Control group I included normal volunteers selected from the hospital staff and their families, in whom age range and sex distribution were similar to those in the group of patients (table 3). Both ECT patients and SUE controls were treated with phenobarbital and/or diphenylhydantoin in efficient serum level concentrations. 2.2. Electrographic

procedure

and apparatus

2.2.1. General procedure After routine EEG recordings to evidence the spontaneous bioelectrical activity and after previous testing of responsiveness to a threshold acoustic stimulus (1000 Hz, 20 dB) aimed at eliminating the cases with perceptual disturbances, all our subjects were submitted to an electrographic investigation of the orienting reaction elicited by a repetitive auditory stimulus. The study

R. Rogozea

68

et al. / Habituatron m epileptogenic

cerebral turnours

Table 2 Distribution of patients with epileptogenic according to seizure features

cerebral

Seizure features

Electra-clinical form of seizures

Seizure frequency

Abs.no.

= absolute

Generalized seizures (convulsive, non-convulsive or convulsive + nonconvulsive) Partial seizures (elementary,

ECT group Control group I Control group II Control group III

and seizures

of unknown

etiology

Patients with epileptogenic cerebral tumours

Patients with seizures of unknown etiology

Absno.

Abs.no.

‘%

%

12

29.3

17

34.7

complex or compound) Generalized + partial seizures Total

21 8 41

51.2 19.5 100

20 12 49

40.8 24.5 100

Daily Weekly Monthly Total

8 22 11 41

19.5 53.7 26.8 100

14 18 17 49

28.5 36.8 34.7 100

number

Table 3 Age and sex distribution Group

tumours

or more rarely

of patients;

of patients

% = same numbers

with epileptogenic

Absolute number of subjects

Age range

N=41 N = 43 N = 36 N = 49

11-71 14-70 9-68 13-76

Mean

converted

cerebral

into percentages

tumours

and of control

subjects

Sex distribution

age

41.5 42 38.5 44.5

Males

%

Females

B

24 21 21 27

58.5 62.8 58.3 55.1

17 16 15 22

41.5 37.2 41.7 44.9

consisted in a simultaneous polygraphic analysis of resistance to habituation of the somatic (EMG), autonomic (finger vasoconstriction, galvanic skin reaction, respiration, pulse I) and EEG (acoustic-evoked potential, EEG-blocking reac’ In the autonomic component of the orienting reaction we included, as shown by Gastaut et al. (1957) all the responsive phenomena that are elicited by the repetitive sensory stimulus as a consequence of the activation produced by it at the level of the mesencephalic reticular formation and from that level, through the reticula-bulbo-spinal pathways, at the level of the pre-ganglionic autonomic centers. This activation is expressed by peripheral vasomotor (finger vasoconstriction, pulse), electrodermal (galvanic skin), and respiratory alterations.

R. Rogozea et al. / Habituation

NC I

= 63

-P-

005

Nc2

‘P-

005

Nc3

:36 :b9

NECT

z

S-P-

25t

‘1

69

in epileptogenrc cerebral turnours

---

001

P-

0001

+ + ++ +

+

c

+

cl c2 c3 ECT

cl c2 c3

s 1. Resistance repetitive

r

cl c2 c3 EC,

Cl c2 c3

I c,

c2

r2';l L c3 *. . EC, . . . . xi& c3 EC, cl c2 c3

A to habituation

of the three components

EEG orienting

reaction

elicited

by a

subjects); c2 = control group II (NCT patients); patients); ECT = group of ECT S= somatic (EMG), A = (finger vasoconstriction, reaction, respiration, pulse) and EEG electroencephalographic (acoustic-evoked of trials of the in this In upper of the = number of in control I, of ECT in whom of the is analysed to the of each to the in the of the

tion) components of the orienting reaction during repetitive auditory stimulation (fig. 1). The above electrographic examinations were performed in SUE patients (control group III) and in ECT patients only when they had been free from seizures for the last 12- 14 hours. The orienting reaction was elicited in all the subjects under standard conditions by a repetitive tone which was kept constant throughout the recording session. Up to 50 stimuli were used during a recording session. The orienting reaction components were considered habituated if absent during three successive applications of the stimulus. As the autonomic component of the orienting reaction consisted of several responsive elements (peripheral vasoconstriction, galvanic skin and respiratory responses), this component was considered habituated when none of the above-mentioned elements was present during three successive applications of the stimulus. The number of tone applications required for habituation of the orienting reaction was taken as

=U NC2 = 36 Ncl

He3 I 19 NECT.Ll

10 15 5 20 25 Mean no. of trlals to habituation

Mean no

of trisls to tatiWion

Fig. 2. Relation between the habituation rate and the magnitude of the initial orienting reaction in the four investigated groups of subjects (mean values). - - - - - - = control group I;. . . . = control group II; . - - I -. _ control group III; = ECT patients. EMG = EMG dicharges; PL = plethysmograp~~ (finger vasoconstriction) reactions; GSR = galvanic skin reactions; EP = evoked potentials; EEG-BR = EEG-blocking reactions. In the upper right side of the figure: Ncl, Nc2, Kc3 and NECT = number of subjects in control groups I, II and III and of ECT patients in whom the mean values were calculated. The lower amplitude of PL responses in ECT and SUE patients expresses stronger vasoconstr~ction reactions than in control groups I and II.

R, Rogozea et ai. / ~ubllual~on in epilepiogenic cerebral t~ours

_

71

ft__________-________--_-___w-.-_a ,

c

C Ncl:l,3 NC 3:49

Nc2a12 NECl= y1

Nc2=5 NECTE 5

P Nc2xb NUT-

7

c

Nc2:13 NECTs 10

dc ; NeZ=NECT. 5

Nclri.3 NC 32 69

Fig. 3. Relation between the tumour site and the changes in resistance to habituation of the orienting reaction components in ECT patients (mean values). Abscissa: frontal or predominantly frontal (Ff, centralor pr~ominantly central (C), parietaf and predo~nantly parietal (P), temporal or predo~nan~y temporal (T) or occipital or predominantly occipital (0~) hemispheric tumours; c = control values obtained in the two groups of subjects without tumours (normal and SUE subjects) for comparison with the values noted in the two groups with tumours (ECT and NCT patients). - - - - - - = control group I; * . . . . . = control group II: ’ - *- *- 1= controi group III; = ECT patients; 0, l and X = habituation of the somatic, autonomic and EEG components.

quantitative index of the resistance to habituation (fig. I>. Besides investigation of resistance to habituation of the orienting reaction, we also followed the somatic, automo~ic and EEG spontaneous activity for 5 min before and after the habituation session to establish correlations between spontaneous activity and the habituation process rate. The data obtained were analysed both between the four investigated groups (fig. I> and within the ECT group, in the latter the cerebral tumour peculiarities and the seizure features being taken into consideration (figs. 3,4, 5 and 5).

R. Rogoren et al. / Habituation

cm.--

-

in epileptogenic cerebral turnours

.---.-.--._./7

* _ _ -.-.f_._._+_,_.-.-._.x

fLJ / ----_-_-_-_-_* *-----~--_.~_~~~~~~~~~~~~‘n )”

_..y

.,/

,”

m

._--,,L_.-.-_.a ,./ ...’

r).-.-_-_-.j’

_,,;; ......“’ ..d.” ,,,’

*_--a-l-____-_--____~ l-J_---------_-__

-4

_____--

C

_ :/ -3cm

Nc1=43 Nc3.49

Nc2 ~6 NECT. 9

3-6cm Nc2zlB NECT. 22

-6cm Nc2 ~12 NECT. 10

c N,::::;

Fig. 4. Relation between the tumour size and the changes in resistance to habituation of the orienting reaction components in ECT patients (mean values). Abscissa: tumour size in cm; c = control values obtained in the two groups of subjects without tumours (normal and SUE subjects) for comparison with the values noted in the two groups with tumours (ECT and NCT patients). Legend as in fig. 3.

The data were also analysed in their relation to the magnitude of the initial orienting reaction (fig. 2) and to the somatic, autonomic and EEG spontaneous activity before and after the habituation session (table 4). 2.2.2. Recording The orienting reaction was elicited in all the subjects by a repetitive auditory stimulus of 5 set duration, presented at a constant interstimulus interval of 30 set (offset to onset). Tone frequency was 3000 Hz, and the intensity 75 dB. The acoustic stimuli were produced by a Soneclat-Alvar Electronic phonophotostimulator (type A) and delivered through two loudspeakers 40 cm directly behind the subjects. The orienting reaction components evoked by the above-mentioned repeti-

R. Rogozea et ai. / ~ab~i~aii~n in epile~~#gen~~cerebra) turnours

c3___-_-_-------_-_

73

m.-_-_-_---Q

Fig. 5. Relation between the electro-clinical form of seizures and the changes in resistance to habituation of the orienting reaction components in ECT patients (mean values). Abscissa: patients with generalized (g), partial (p), or generalized + partial (g + p) seizures; c = control values obtained in the two groups of subjects without seizures (norm4 and NCT subjects) for comparison with the values noted in the two groups with seizures (ECT and SUE patients). Legend as in fig. 1.

tive auditory stimulus were simuItaneous registered on a 20-channel Reega-XX Bureau Alvar Electronic polyphysiograph. Separate channels of the polyphysiograph were used for the recording of both the stimulus and each component of the evoked orienting reaction. The technical conditions to record the orienting reaction components were adapted to the specific peculiarities of each component. Thus, the somatic component (EMG discharges) was bipolarly recorded using domed Ag surface electrodes filled with 0.05 M NaCl electrolyte and fastened with a strip on the dorsal surface of the nape muscles approximately at the level of the fourth cervical vertebra. EMG discharges were recorded via a channel of the polyphysiograph, with amplification 2, time constant 3 and filter 0; The autonomic component was recorded in a number of ways:

R. Rogorea

et al. / Habituation

..~

:b;;.;_:., j

fg

k

m epileptogenic

cerebral tumours

,..,*

_,.,, Q

c---____-----_-_----___-

L)---___---__-----__a

C Nc1.43 NC2.M

D-ly ;;g';

WlY NC 3 ~1.3 NUT:22

My Nc3 :17 NKT=ll

c Ncl=L3 NCZ.35

Fig. 6. Relation between seizure frequency and the changes in resistance to habituation of the orienting reaction components in ECT patients (mean values). Abscissa: seizure frequency = daily (D-ly), weekly (W-ly) or monthly or more rarely (M-ly); c = control values obtained in the two groups of subjects without seizures (normal and NCT subjects) for comparison with the values noted in the two groups with seizures (ECT and SUE patients). Legend as in fig. 3.

(1) Finger vasoconstriction was registered using a photoelectric transducer type Pletismovar-Alvar Electronic attached to the distal phalanx of the index finger of the subject’s right hand. It was recorded by means of another channel of the polyphysiograph using amplification 3, time constant 3 and filter 2. (2) Galvanic skin reaction was recorded by means of an Alvar miniature type electrode attached to the medial phalanx of the index finger on the left hand and by a comparable reference electrode placed on a drilled site on the corresponding forearm. For this measure an isotonic electrolyte was employed. The galvanic skin activity was amplified with direct coupling by a preamplifier type PDR of the Alvar polyphysiograph (amplification 4, time constant 1 and filter 1). (3) Respiration was monitored via an Alvar parabuccal thermocouple to

R. Rogozea et al. / Habituation Table 4 Relation between habituation changes of somatic, autonomic No. of

Group

subjects

75

in epileptogenic cerebral turnours

rate of orienting reaction and EEG activity during

components and level of spontaneous a pre- and post-habituation rest period

Analysed component

Mean no. of spontaneous changes/ 5 min in pre-habituation rest period

Mean no. of trials to habituation

Mean no. of spontaneous changes/ 5 min in posthabituation rest period

Control

group

I

43

s A EEG

5.1 1.2 12.8

3.1 5.2 6.3

4 6 12

Control

group

II

36

s A EEG

10 13.8 20.9

6.5 9.3 11

9.3 12 21

Control

group

III

49

S A EEG

18.2 22 33

10.7 19 17.1

14.7 20.9 21.1

41

s A EEG

17.6 24.1 29.8

11.9 22 17.3

15.6 25.4 27.1

ECT group

S = somatic component EEG = EEG component

(EMG discharges); A = autonomic (EEG-blocking reactions)

component

(galvanic

skin changes);

detect the respiratory rate changes induced by the repetitive stimulus (amplification 4, time constant 3, filter 3). (4) Temporal pulse was registered by means of an Alvar transducer of capsular type fastened with rubber strip on the suprazygomatic area to evidence pulse rate changes induced by the repetitive acoustic stimulus (amplification 3, time constant 3 and filter 2). For the EEG component, both acoustic-evoked potentials and EEG-blocking reactions were recorded by 13 Alvar-type silver surface electrodes filled with NaCl electrolyte. Twelve of these electrodes were placed on the scalp of F3, F4, T3, T4, C,, C,, T,, T6, 5, P4, 0, and 0, in the ‘10-20’ international system, and the thirteenth over the vertex and fastened by means of a headgear fashioned from strips of bandage. The EEG recordings were made in monopolar leads. The indifferent electrode for these recordings was attached to the ear. The EEG signals were then amplified with coupling by the Alvar polyphysiograph. The above polygraphic recordings were performed in a sound-proof room.

16

R. Rogorea et al. / Habituatron

in epileptogemc cerebral turnours

The subjects were informed that after a rest period, some tones would be heard from time to time followed by another rest period. They were asked to relax but not go to sleep. After a 5 min rest period when somatic, autonomic and EEG spontaneous activity was recorded, the habituation session commenced being followed by other 5 min of spontaneous activity control after development of habituation process. Throughout the recording session the subjects were lying with their eyes closed. Mean ambient room temperature was 215°C and mean humidity was 50.2%. 2.2.3. Scoring 2.2.3.1. EMG discharges. EMG discharges greater than 40 pV, occurring up to 1 set after stimulus onset were considered stimulus-evoked EMG response. EMG response amplitude was measured in FV (1 mm of pen deflection equal to 10 pV). The level of spontaneous EMG activity was assessed during the two 5 min rest periods before and after the habituation session and was measured by counting the number of spontaneous EMG discharges greater than 30 pV. 2.2.3.2. Finger vasoconstriction. A decrease in pulse amplitude occurring within the interval beginning 1 set after stimulus onset and persisting for at least three consecutive beats was considered a digital vasoconstriction response evoked by the acoustic stimulus. The amplitude of finger vasoconstriction was measured in E.IV(1 mm of pen deflection equal to 50 pV> and response duration in set (1 set equal to 1.5 cm chart speed). 2.2.3.3. Galvanic skin activity. Galvanic skin reactions occurring from 1 to 3 set after stimulus onset with a higher amplitude than 300 PV (scored from peak to isoelectric line) were considered repetitive stimulus-evoked responses. Mono-, di- and triphasic responses were taken into consideration. Spontaneous activity was assessed during the two 5 min rest periods before and after the habituation session and was measured by calculating the number of spontaneous galvanic skin changes greater than 200 pV. Galvanic skin response amplitude was measured in PV (1 mm of pen deflection equal to 50 pV) and response duration in set (1 set equal to 1.5 cm chart speed). 2.2.3.4. Respiratory response. An increase or a decrease in the respiratory rate with minimum 3 breaths/min vs. the respiratory rate of the rest period before the habituation session (inclusive apnea) occurring in the first set after stimulus onset were considered a stimulus-evoked respiratory response. 2.2.3.5. Temporal pulse response. An increase in the temporal pulse rate with minimum 7 beats/min as against the pulse rate of the rest period before the habituation session occurring in the first set after stimulus onset were considered a stimulus-evoked pulse response.

R. Rogorea et al. / Habituation

in epileptogenic cerebral tumours

II

2.2.3.6. Acoustic-evoked potential. As acoustic potential was considered the early negative component of the stimulus-evoked response recorded from the vertex with a minimum amplitude of 25 pV, the evoked potential amplitude was measured in PV (1 mm of pen deflection equal to 10 pV>. 2.2.3.7. EEG-blocking reaction. The reduction by at least 50% occurring in the amplitude of bioelectrical waves following stimulus application was taken as stimulus-evoked EEG-blocking reaction. The duration of this response was measured in set (1 set equal to 1.5 cm chart speed). The spontaneous EEG-blocking reactions were assessed during the two 5 min rest periods before and after the habituation session. As shown in section 2.2.1, all the above-mentioned components of the orienting reaction were considered habituated if absent (i.e., if their magnitude decreased under the minimum size established for each component separately) during three successive applications of the stimulus.

3. Results Significant differences in the resistance to habituation of the orienting reaction were found between the ECT patients, on the one hand, and the control groups I (normal subjects) and II (NCT patients) on the other (fig. 1). The orienting reaction in ECT patients was, as a rule, more resistant to habituation than in control groups I and II (fig. 1). Thus, in these patients, the somatic (EMG discharges), autonomic (peripheral vasoconstriction reactions, galvanic skin responses and respiratory alterations) and EEG (tone-evoked potentials and EEG-blocking reactions) components, necessitated a significantly larger number of repetitive applications of auditory stimulus to become habituated (fig. 1). A compared analysis of the data obtained in the four investigated groups of subjects showed that, besides the significant habituation differences between the ECT patients and the subjects of the control groups I and II, there were also some differences vs. the control group III (SUE patients); however, these differences were inconstant and statistically non-significant (fig. 1). Habituation differences were observed also between the control groups (fig. 1). Thus, we noted that in the patients of both control group II and, especially, control group III, there was an increased resistance to habituation of the orienting reaction as against the normal subjects of control group I. Though not so marked as in ECT patients, it was however, statistically significant (fig. 1). Likewise, in control group III there was a significantly increased resistance to habituation vs. control group II (fig. 1). The investigations showed that, in ECT patients, apart from the modified resistance to habituation there was also an alteration of the sequence in which

78

R. Rogorea et al. / Habituation

in epileptogenx

cerebral turnours

the three components of the orienting reaction became habituated: while in normal subjects of control group I the first to habituate was the somatic component followed by the autonomic and then by the EEG one, in ECT patients the EEG component became habituated prior to the autonomic one which was the most persistent (fig. 1). The tendency to modify the habituation sequence of the orienting reaction components mentioned above was noted also in the SUE patients of control group III (fig. l), the data obtained suggesting that modification of the habituation sequence of the three orienting reaction components observed in the investigated subjects is the more evident as the resistance to habituation is more marked compared to the values noted in the normal subjects of control group I, the most important changes being found in the ECT patients. The data showed that the previously mentioned differences in the habituation rate of the orienting reaction observed in the investigated groups of subjects are determined, on the one hand, by the initial orienting reaction magnitude and, on the other, by the level of the spontaneous changes in the somatic, autonomic and EEG activity. Thus, in the studied subjects, the resistance to habituation was the more increased as the amplitude and/or duration of the initial reaction components (EMG discharges, finger vasoconstriction response, galvanic skin reaction and EEG-blocking response) evoked by the first trial were more marked (fig. 2). The data analysis showed that the probability of this correlation was over 99%: for the amplitude of the initial reaction components [r = 0.94, t = 8.71, p < O.Ol], and for their duration [r = 0.98, t = 15.57, p < 0.011. In this respect, fig. 2 shows that in ECT patients, very much like in SUE ones (control group III), in whom the initial reaction components had the greatest magnitude vs. the corresponding values observed in the normal subjects of control g:xp I, there was also the most increased resistance to habituation (fig. 2). As a matter of fact, in these two groups, the habituation curve also showed that the negatively accelerated decrement in the magnitude of the orienting reaction components during repetitive trials is slower than in the normal control subjects (fig. 2). In NCT patients (control group II) in whom the initial reaction components were less ample than in ECT and SUE patients, resistance to habituation was also less changed than that found in ECT and SUE groups remaining, however, greater than that observed in the normal subjects of control group I (fig. 2). On the other hand, we noted that resistance to habituation was the more increased as the level of the spontaneous changes in the somatic (EMG discharges), autonomic (galvanic skin reactions) and EEG (EEG-blocking reactions) activity of the pre- and post-stimulus rest periods was higher (table 4). In this situation the correlation probability was over 99% [r = 0.89, t = 6.32, p < 0.011. From table 4 it can be seen that in ECT and SUE patients, in whom the highest levels of spontaneous changes in the somatic, autonomic and EEG activity of the rest periods before and after the habituation session

R. Rogozea

et al. / Habituation

in eprleptogenic cerebral turnours

79

were noted as against the corresponding levels observed in the normal subjects of control group I, there was also the most increased resistance to habituation which required application of the greatest number of trials vs. the rest of the subjects investigated to attain the habituation criterion (table 4); in the NCT patients of control group II, in whom the levels of the changes in the somatic, autonomic and EEG activity of the rest periods before and after the habituation session were lower than in ECT and SUE patients, there was a less increased resistance to habituation than in these two groups of patients, but more increased compared with that in the normal subjects of control group I (table 4). While no statistically significant changes in resistance to habituation of the orienting reaction were found in ECT patients in relation to their age and sex, histologic aspect of the tumour or the hemisphere in which it developed, significant changes were recorded in relation to the tumour site and size as well as to the electro-clinical form and frequency of seizures. 3.1. Changes related to tumour site The most significant increases in resistance to habituation of the orienting reaction were noted in patients with temporal or predominantly temporal epileptogenic hemispheric tumours [t = 2.69, p < 0.011 followed, in decreasing order of severity, by habituation changes induced by central or predominantly central [t = 2.4, p < 0.021 and parietal or predominantly parietal tumours [t = 2.12, 0.02 -cp < 0.051 (fig. 3). Frontal or predominantly frontal and occipital tumours induced less important changes [t = 1.6, p > 0.051 (fig. 3). The relation between habituation changes and site of hemispheric tumours was noted also in NCT patients (control group II) (fig. 3) even if the severity of habituation disturbances was, in these patients, signficantly lower than in ECT ones, in temporal tumours [t = 2.3 1, 0.02 < p < 0.051, in central tumours [t = 2.23, p < 0.051, in parietal tumours [t = 1.94, p > 0.051 and in fronto-occipital tumours [t = 1.2, p > 0.11. 3.2. Changes related to tumour size The data pointed out that in ECT patients there was a correlation between the increase in habituation resistance and the tumour size, the most important changes being noted in the patients with large hemispheric epileptogenic tumours (over 6 cm) (fig. 4). The data analysis showed in these patients a correlation probability of 98-99% [r = 0.99, t = 9.2, 0.01 < p < 0.021. The above-mentioned correlation between habituation changes and tumour size was also found in NCT patients of control group II (fig. 4), the severity of these changes being significantly lower than in ECT patients [r = 0.98, t = 4.92, 0.02 < p < 0.051.

80

3.3. Changes

R. Rogorea et al. / Habituation

in epilepiogenlc cerebral turnours

related to electro-clinical form of seizures

The most marked increase in resistance to habituation of the orienting reaction was found in ECT patients with generalized (convulsive, non-convulsive or convulsive + non-convulsive) [t = 2.88, 0.01 < p < 0.021 or generalized + partial seizures [t = 3.05, 0.01

4. Discussion The alterations in resistance to habituation of the orienting reaction found in ECT patients point to the existence of important psychophysiological disorders in these patients. A habituation resistance disturbance of the vegetative component of the orienting reaction was also noted by Homskaya (1960, 1961), Homskaya, Konovalov and Luria (1961), Klimkowsky (1961) and Luria and Homskaya (1964), who found that frontal or parieto-occipital tumours induce psychophysiological disorders expressed, besides changes in the intensity of the vegetative component, also by increase of its resistance to habituation. Unlike the data reported by the above-mentioned authors, inferable from our data is that the most severe habituation disturbances of the orienting reaction components were noted in the temporo-central tumours followed, in terms of severity, by the disturbances induced by parieto-fronto-occipital tumours. These alterations found both in ECT patients and SUE controls cannot be attributed to the antiepileptic treatment applied to them, because, on the one hand, the disturbances were also noted in NCT patients of control group II

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who were not applied such a treatment and, on the other hand, as shown by our previous observations (Rogozea, Florea-Ciocoiu and Pintilie, 1973) epileptics display an incrased resistance to habituation of the orienting reaction before initiation of treatment, its administration determining an improvement to a certain extent of the pre-existing habituation disturbances. The disorders may be ascribed to the effects induced by the pathologic impulses arising from the nervous tissue surrounding the hemispheric tumour on the neural structures and pathways involved in the regulation of nervous excitability and, implicitly, in the control and integration of psychophysiological reactions to repetitive sensory messages. This hypothesis on the mechanism of habituation disturbances in ECT patients seems quite plausible if we bear in mind that, as shown by Penfield and Jasper (1954) in the areas of brain parenchyma adjacent to the tumour, a local aberrant activity (a ‘hyperirritability’) develops consequently both to the long-continued mechanical stress determined by tumour and to the secondary alterations in the blood flow and the biochemical processes. In these conditions, the pathologic impulses from these areas may induce changes in the excitability of neurons at distance and over wide territories, changes that may affect primarily the neural structures involved in the control of excitability and integration of psychophysiological responses to repetitive sensory messages, having repercussions on the habituation process as well. The part excitability changes play in the development of habituation disturbances is demonstrated in our study both by the relation found between the magnitude of the initial orienting reaction and the habituation rate and by the relation between the spontaneous changes in the somatic, autonomic and EEG activity and the development of the habituation process. In this respect, the most important habituation disturbances were noted in ECT and SUE patients who displayed the signs of a marked hyperexcitability (increased magnitude of the initial reaction, slow curve of negatively accelerated decrement in the magnitude of the orienting reaction components during repetitive trials, high levels of spontaneous changes in the somatic, autonomic and EEG activity of the pre- and post-stimulus rest period), the disturbances being less important in NCT patients (control group II) in whom hyperexcitability proved to be less marked. The involvement of excitability changes in the occurrence of habituation disturbances is supported in study also by the fact that the severity of the habituation disorders is related to the size of tumours. Thus, the most increased resistance to habituation was noted in patients wi!h large tumours, in whom the surrounding nervous parenchyma was more affected and, implicitly, the excitability disturbances induced at distance were more severe, while less marked in patients with medium-sized or small tumours in whom the parenchyma adjacent to the tumour was less affected and the consequent excitability disturbances were less important. Among the components of the orienting reaction, the autonomic one was

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the most resistant to habituation in ECT patients. This might be attributed either to some functional disturbances of various severity degrees in the cerebral structures, namely to a more important hyperexcitability at the level of the hypothalamic autonomic centers, or to a deficit in the nervous mechanisms controlling the autonomic hyperexcitability, the result being in either case a modified sequence in the habituation of the orienting reaction components. In this connection, disturbances in the autonomic activity in some diseases of the central nervous system have been reported by many authors (Goldstein, 1965; Hare, 1968; Blankstein, 1969). The possibility for the hemispheric tumours to induce changes in the activity of the structures and pathways involved in the control of excitability and, implicitly, of psychophysiological habituation is underlain by our observation that the habituation disturbances were present in both ECT patients and control NCT ones. Since the habituation disorders found in the latter group were significantly less important than those in ECT or SUE patients, it appears that functional alterations in the activity of the neural pathways and structures involved in the control and integration of repetitive sensory messages are significantly more important when the cerebral pathologic process affects more severely the surrounding parenchyma, which is expressed by the appearance of the epileptic seizures. In their turn, by ictal bombardment with pathologic impulses and by residual interictal functional disturbances, these seizures affect still more the activity of the structures controlling psychophysiological habituation. The seizures additional effect on augmenting the alterations of excitability and, implicitly, of habituation, may therefore explain the differences noted in the ECT and SUE patients contingent upon the seizure electro-clinical form and frequency, the disorders being more marked in patients with generalized or generalized + partial seizures and in those with frequent (daily) seizures. The different severity of habituation disturbances depending on the site of tumour suggests that the habituation changes in ECT patients, the same as in NCT ones, are related by the morpho-functional peculiarities of the hemispheric areas in which they develop. Thus, the fact that the most severe habituation disturbances were noted in patients with tumour in, or predominantly in the temporo-central region may be explained by the particular functional importance of this area for the psychophysiological processes and the richness of its connections with the structures involved in the control of general excitability (Adey, Merrilees and Sunderland, 1956; Kltiver and Bucy, 1939; Lorente de No, 1933; MacLean, 1952; Papez, 1937). References Adey, W.R., Merrilees, N.C.R. and Sunderland, S. (1956). The entorhinal area: behavioural, evoked potential and histological studies of its interrelationship with brain stem regions. Brain, 79, 414-440.

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