- Email: [email protected]
Habituation of orienting and motor responses elicited by stimulation of the cortex in the cat
Physiology & Behavior, Vol. 16, pp. 337-341. Pergamon Press and Brain Research Publ., 1976. Printed in the U.S.A.
Habituation of Orienting and Motor Responses Elicited by Stimulation of the Cortex in the Cat HANS VALE, HAKAN SUNDBERG AND HOLGER URSIN
Institute o f Physiology and Institute o f Psychology, University o f Bergen, Norway (Received 27 March 1975) VALE, H., H. SUNDBERG AND H. URSIN. Habituation of orienting and motor responses elicited by stimulation of the cortex in the cat. PHYSIOL. BEHAV. 16(3) 337-341, 1976. - Orienting and motor responses have been elicited by electrical stimulation of the cortex in the unanesthetized, freely moving cat. A total of 73 electrodes from 29 cats was studied. The orienting response was elicited from 56 sites. The response was undistinguishable from that elicited by ordinary sensory stimulation, and no difference was observed in the responses elicited from different cortical areas. Motor responses were observed less frequently. The orienting response showed habituation and dishabituation in all cases except 4. This finding is in agreement with previous work in this area. However, motor responses, with or without accompanying orienting responses, also showed habituation, dishabituation, and even savings from one day to another. Stimulus recognition models [10] seem inadequate to explain our findings for the motor response, but the data are explained by synaptic models of habituation [3]. Habituation
Orienting response
Motor response
Electrical brain stimulation
E L E C T R I C A L stimulation of cortical areas and subcortical structures in the cat f r e q u e n t l y produces an orienting response. This response is undistinguishable f r o m the orienting response as described by Pavlov [2, 13, 14]. In addition to the behavioral characteristics of arousal, there is also an a c c o m p a n y i n g electroencephalographic arousal [6,151. If such stimulation is repeated, response habituation is observed from most electrode sites [14, 15, 16, 18]. Dishabituation, i.e. arousal p r o d u c e d f r o m a n o t h e r source, re-establishes the orienting response. This p h e n o m e n o n d e m o n s t r a t e s that the disappearance of the response is not due to artifacts such as polarization or damage to the tissue
Cortex
METHOD
Animals and Surgery A total of 73 electrodes in 29 cats were included in the material. During N e m b u t a l (R) anesthesia platinum or stainless steel electrodes were implanted in the lateral and frontal part of the cortex. The platinum electrodes consisted of 0.18 m m thick platinum/iridium wire covered by Teflon except for 1 m m at the tip. Since this wire was too flexible to be implanted unsupported, it was fed through a stainless steel catheter of 0.6 m m bore, the bare platinum tip protruding at the end. The stainless steel wires were 0.5 m m thick and were insulated except for 0 . 5 - 1 m m at the tip. O t h e r details of the implantation and observation procedure have been given previously [ 14,15 ].
[151. F r o m o t h e r points, in the reticular f o r m a t i o n , thalamus, the septal area, and amygdala, h a b i t u a t i o n was not always observed [ 1 5 , 1 6 ] . These n o n h a b i t u a t i n g responses are probably due to electrical stimulation o f areas of primary importance for activation or motivation. Orienting responses and electroencephalographic arousal have been elicited f r o m m a n y cortical areas, although negative areas also exist [2,6]. For cortical areas habituation to electrical stimulation has o n l y been studied for the occipital field [ 15] and for the sylvian and ectosylvian gyri [18]. F r o m m a n y of the o t h e r cortical areas m o t o r responses are elicited as well. The present paper deals with the habituation o f the orienting response and the m o t o r responses elicited by cortical stimulation in the cat.
Procedure The intensity of behavioral arousal was evaluated by a scoring m e t h o d described previously [ 1 5 ] . Briefly it consisted of 4 categories of behavior (see Table 1), and the sum of the scores for these 4 categories served as the arousal score. The level of arousal was evaluated just before stimulus onset and a second score was given for the behavior occurring during and i m m e d i a t e l y after the stimulation. The difference b e t w e e n these 2 scores has been used as an indicator of the arousal effect of stimulation.
This work was supported by the Norwegian Research Council for Science and the Humanities. Authors are grateful to Aase Larsen and Nina Holmelid for their technical assistance. 337
338
VALE, SUNDBERG AND URSIN TABLE 1
)
SCORING S C H E D U L E : O R I E N T I N G RESPONSE
Points
Head
Eye-lids
Ears
Posture
6 5 4 3 2
-Searching Turning Lifted Quiet
---Moving Quiet
Running Walking Standing Sitting Lying on belly
1
Laid down
--Open Half open Membrana nict. contracted Closed
--
Curled u p o r lying on side
T h e b r a i n was s t i m u l a t e d w i t h 5 sec t r a i n s of positive m o n o p h a s i c square waves, each pulse lasting for 1 msec, a n d 100 pulses per sec. O n l y 1 site was t e s t e d each day. H a b i t u a t i o n was said to o c c u r w h e n t h e cat for 3 trials in a row did n o t show m o r e t h a n 0.5 in d i f f e r e n c e b e t w e e n t h e pre- a n d p o s t s t i m u l a t i o n score. T h e n u m b e r o f trials t o h a b i t u a t i o n , including t h e 3 trials in t h e c r i t e r i o n run, was used as t h e h a b i t u a t i o n score. D i s h a b i t u a t i o n was t h e n p r o d u c e d b y i n t r o d u c i n g o t h e r arousal p r o d u c i n g stimuli ( k n o c k i n g o n t h e w i n d o w , t u r n i n g lights o n a n d off, etc.) T h e n u m b e r o f trials necessary to p r o d u c e r e h a b i t u a t i o n was t h e n tested. In a d d i t i o n t o t h e o r i e n t i n g response, o t h e r m o t o r responses were also observed. These r e s p o n s e s varied f r o m o n e e l e c t r o d e site to a n o t h e r , each particular r e s p o n s e was described as carefully as possible d u r i n g t h e screening, a n d an individual profile was o b t a i n e d for each point. During the h a b i t u a t i o n sessions, all b e h a v i o r categories observed to t h e initial s t i m u l a t i o n were observed. F o r t h e final evaluat i o n of t h e h a b i t u a t i o n data, a scoring sheet was designed (Table 2). This m a d e it possible to o b t a i n a n u m e r i c a l score. H a b i t u a t i o n session were r u n for all t h e s e p o i n t s , u n t i l n o r e s p o n s e was o b s e r v e d or to a preset cut o f f at 100 trials. W h e n b o t h o r i e n t i n g r e s p o n s e s a n d m o t o r r e s p o n s e s were elicited, h a b i t u a t i o n was r u n u n t i l b o t h t y p e s of r e s p o n s e s disappeared. F o r 7 p o i n t s savings of t h e h a b i t u a t i o n f r o m o n e d a y t o the o t h e r were testedi 5 p o i n t s yielded o r i e n t i n g r e s p o n s e s
FIG. 1. Electrode placements in the cortex of the cat. Top: Electrode sites yielding orienting responses. The number in each circle indicates number of trials to habituation. Circle filled with horizontal bars: No habituation. Bottom: Triangles: mixed motor and orienting behavior, squares: motor response only. The number in each symbol indicate number of trials to habituation criterion.
TABLE 2 SCORING SCHEDULE: MOTOR AND MIXED RESPONSE Points
Face
3
Neck and back --
Paws
Strong tonic contraction OF
repeated clonic contractions 2
Repeated chewing
Tonic contraction, occasional slow withdrawal of head and/or body
Repeated striking with forepaw
1
Contracting muscles in the face or a chewing motion
Slight tonic contraction, small jerk
Spasm in one or more paws, or striking
0
No response
No response
No response
CORTICAL STIMULATION
339
AND HABITUATION
in combination with motor responses, while 2 yielded only motor responses. At the end of the experiment the animals were killed, the brains perfused and electrode sites identified histologically in Nissl-stained material. RESULTS
There were no differences in the behavioral effects depending on whether the electrode was made from platinum or stainless steel, or between bipolar and monopolar stimulation. In the following, all these results will be grouped together. Behavioral responses Orienting responses. From 56 electrode sites the typical orienting response was obtained [ 2, 13, 14, 1.5, 161. The response was adequately described by the scoring categories in Table 1. Motor responses. From 4 electrode sites a motor response was obtained. The most frequently observed was a slow, tonic contraction of the neck muscles, often combined with clonic movements of the contralateral foreleg. It looked as if the cat struck repeatedly at something in front of it. Other motor responses were tonic/clonic contractions of the contralateral facial muscles. Tonic contractions of the muscles of the back were also observed, sometimes combined with withdrawal of the frontal part of the body and clonic movements of the neck muscles. Each point gave the same response when stimulated on later sessions. Mixed motor and orienting responses. These reactions were obtained from 13 electrode points, and consisted of one or more of the motor responses described above combined with or followed immediately by an orienting response. Other responses. Stimulation of 1 point resulted in no reaction even if the intensity was increased. Stimulation of
26 66
Habituation Orienting responses. Repeated stimulation of 52 points resulted in the gradual reduction of the response described previously for stimulation of the occipital cortex, the caudate nucleus and the amygdala [ 14,151. (Fig. 3A). There was no significant difference in the number of trials to criterion between points stimulated in the frontal and the lateral areas. For 4 electrode sites, the criterion for habituation was not reached after 100 repeated presentations of the stimulus. Three of these points were localized in g.subproreus and g.proreus, and 1 point was localized in the ventral aspect of the occipital field (Figs, 1, 2). These nonhabituating points were not tested further with other stimulus parameters. For the habituated orienting responses, the whole pattern was restored after presentation of other stimuli producing orienting responses (dishabituation). The number of trials necessary to reach criterion again (rehabituation) was less than that needed to reach the initial habituation. Motor responses. Repeated stimulation of 2 of the 4 points that yielded motor responses only, resulted in a gradual disappearance of the particular motor response obtained from that point. The gradual disappearance followed the same waxing and waning pattern described for the orienting response (Fig. 3B). One point required 24 trials, the other point 59 trials to habituation criterion. The
29 33
3066
32 00
7 points resulted in fullfledged tonic/clonic convulsions. Some of these convulsions started with orienting responses, but developed rapidly into a convulsive fit. No further stimulation was given to such points, and all these points have been excluded from the material. Localization. The localization of the points in the cortex on the lateral surface of the brain is evident from Figure 1, the frontal cortex points are evident from Figure 2.
25 33
24 00
FIG. 2. Frontal sections through the frontal area of the cat (modified from [7]). Left side of each section: Orienting responses (circles). Right side: Mixed motor and orienting responses (triangles), and motor responses only (squares). The number in each symbol signifies the number of trial to habituation criterion. Horizontal bars: No habituation.
340
VALE, SUNDBERG AND URSIN
A i I
orienting response (pomtsi
I
i
savings,
15
e/e
.... IIIIIII iI .,IIIIIIiiiI
10
I 5
I 10
100
75
I
t 15
25
20
X
30
sum. no
50
B l
T motor
response (points)
5
Ii ~
X
25
TTTYTYYYYYTYTYY TTTYT IT',' l 5
1 10
• I 15
•VV
I 20
••
25
30
sum. no
C
I i
orienting response (points)
I
I
I
3
4
5
days
i
FIG. 4. Savings from day to day habituation for 6 different points yielding motor responses or mixed motor and orienting responses. The number of trials to criterion the first session was set to 100%.
i I
10
001
I
Ill
,, I I I
1I
motor r e s p o n s e (points)
10
I
2
i i
15
5
I
1
I t I I
15 5tlm
20
25
30
35
no
FIG. 3. Habituation to stimulation of the cortex in the cat. (A) Orienting response. (B) Motor response only. (C) Mixed responses. For each stimulation (abscissa) the intensity of the response is indicated by the height of the bar. Circles indicate level before stimulation (only for orienting response) triangles level during and after stimulation. Black symbols indicate no difference between the prestimulation and the poststimulation values. The arrow indicates dishabituation. The results shown have been picked at random from the total material. same m o t o r r e s p o n s e r e a p p e a r e d after d i s h a b i t u a t i o n and could be r e h a b i t u a t e d . F o r t h e o t h e r 2 points, r e p e a t e d s t i m u l a t i o n did n o t lead to h a b i t u a t i o n . Mixed motor and orienting responses. Mixed m o t o r and orienting r e s p o n s e s also gradually d i s a p p e a r e d as a result o f s t i m u l a t i o n for 12 o f t h e 13 p o i n t s t h a t gave t h e s e reactions. F r e q u e n t l y 1 o f these r e s p o n s e s disappeared
before the other, but there was no significant tendency in which response disappeared first. Criterion was reached between 8 and 57 trials. (Md = 17). After presentation of an external stimulus both responses were restored, and both disappeared gradually during rehabituation (Fig. 3C). Repeated stimulation of 1 point in prefrontal cortex did not produce habituation. Saving was tested for 2 of the motor responses and 5 of the points yielding mixed motor and orienting responses. Saving was tested by running 5 consecutive habituation sessions, 1 session per day. Only 1 electrode placement in each cat was used for this test. The number of trials necessary to reach criterion for each session was gradually lower from one session to another for 6 of these points, thus demonstrating savings (Fig. 4). There was significantly less trials to criterion on the fifth session as compared with the first session (p<0.02, Wilcoxon matched pair signed ranks test, 2-tailed). DISCUSSION
Orienting Responses The present findings comfirm previous observations [2] that electrical stimulation of the lateral surface of the cortex of the cat, frequently results in a behavior response which is indistinguishable from the normal orienting response in the cat [ 2,15 ]. In the present material stimulation of all points except 4 showed habituation, following the same number of stimulus presentations as that found for stimulation of the amygdala
CORTICAL STIMULATION AND HABITUATION
341
[15], the caudate nucleus [14] and the specific nuclei of the thalamus [16]. The nonhabituating points were localised in the frontal pole (n = 3) and on the lateral posterior surface of the cortex (n = 1). These points were not tested for any motivational properties. In the rat, stimulation of ventral frontal areas has produced positive reinforcement [8]. Wester [17] has shown that points yielding negative reinforcement do not show habituation. The possibility exists, therefore, that there are parts of the frontal cortex also in the cat that will yield positive reinforcement upon electrical stimulation. The gradual decrease of the response can not be explained by local changes around the electrode tip, as polarization or tissue damage. In all cases the response was restored after presenting an external stimulus producing arousal. The response attenuation, therefore, seems to be a result of a habituation process as defined by Thompson and Spencer [ 12 ].
Motor responses. It was possible to demonstrate that the m o to r responses also showed the habituation phenomenon, dishabituation and faster rehabituation after dishabituation. We have also observed spontaneous recovery and savings between consecutive habituation sessions also for these motor responses. Five of the 9 criteria for habituation as suggested by Thompson and Spencer [ 12] therefore have been met. The other 4 were not tested. We conclude that the habituation
phenomenon also exist for cortically induced mot or responses. Attenuation of cortically induced motor responses has been observed previously, but, to our knowledge, this attenuation has not been discussed within the habituation conceptual framework. Dusser de Barenne and McCulloch [1] demonstrated that in awake monkeys, the response to the last of two stimuli was smaller or not observed at all if the interval between these stimuli was around 4 sec. They called this phenomenon extinction, and the discussion of this was part of the suppression controversy [5]. It seems evident from our data that the complex networks responsible for the motor responses we elicit is subject to habituation. In the dual process theory of habituation [3] 3 types of synapses are described, habituating, sensitizating and nonhabituating. Repeated tactile stimulation demonstrates that in the unanesthetized cat the pyramidal tract contains units that show habituation as well as sensitization [1 1]. The simplest explanation of our finding, therefore, is that the network we interfere with contain such habituating synapses. This may also be true for the areas from which we elicit orienting behavior. While the Sokolov [10] cognitive stimulus-recognition model gives a satisfactory explanation for the data on habituation of the orienting responses, this same model gives less satisfactory explanations for the habituation of the m o t o r response. Also, the Sokolov model seems unable to account for the finding of the habituation in deeply unconscious human patients [4].
REFERENCES 1. Dusser de Barenne, J. G. and W. S. McCulloch. Local stimulatory inactivation within the cerebral cortex, the factor for extinction. Am. J. Physiol. 118: 510-524, 1937. 2. Fangel, C. and B. R. Kaada. Behavior "attention" and fear induced by cortical stimulation in the cat. Electroenceph. clin. Neurophysiol. 12: 575-588, 1960. 3. Groves, P. M. and R. F. Thompson. Habituation: A dualprocess theory. Psychol. Rev. 77: 419-450, 1970. 4. Gulbrandsen, G. B., K. Kristiansen and H. Ursin. Response habituation in unconscious patients. Neuropsychologia 10: 313-320, 1972. 5. Kaada, B. R. Cingulate, posterior orbital, anterior insular and temporal pole cortex. In: Handbook o f Physiology - Neurophysiology II, edited by J. Field, H. W. Magoun and V. E. Hall. Washington, D.C., 1960. Pp. 1345-1372. 6. Kaada, B. R. and N. B. Johannessen. Generalized electrocortical activation by cortical stimulation in the cat. Electroenceph, clin. Neurophysiol. 12: 567-573, 1960. 7. Kreiner, J. The neocortex of the cat. Acta Neurobiol. exp. 31: 151-201, 1971. 8. Routtenberg, A. Forebrain pathways of reward in Rattus norvegicus. J. comp. physiol. Psychol. 75: 269-276, 1971. 9. Sharpless, S. and H. Jasper. Habituation of the arousal reaction. Brain 79: 665-680.
10. Sokolov, Y. N. Perception and the conditioned reflex. Oxford: Pergamon, 1963, pp. 309. 11. Teyler, T. J., R. A. Roemer and R. F. Thompson. Habituation of the pyramidal response in unanesthetized cat. Physiol. Behav. 8:201-205, 1972. 12. Thompson, R. F. and W. A. Spencer. Habituation: A model phenomenon for the study of neuronal substrates of behavior. Psychol. Rev. 73: 16-43. 13. Ursin, H. and B. R. Kaada. Functional localization within the amygdaloid complex in the cat. Electroenceph. clin. Neurophysiol. 12:1-20, 1960. 14. Ursin, H., H. Sundberg and S. Menaker. Habituation of the orienting response elicited by stimulation of the caudate nucleus in the cat. Neuropsychologia 7:313 -318, 1969. 15. Ursin, H., K. Wester and R. Ursin. Habituation to electrical stimulation of the brain in unanesthetized cats. Electroenceph. clin. Neurophysiol. 23: 41-49, 1967. 16. Wester, K. Habituation to electrical stimulation of the thalamus in unanesthetized cats. Electroenceph. clin. Neurophysiol. 30: 52-61, 1971. 17. Wester, K. Reinforcing effects of thalamic stimulation resistant to habituation. Brain Res. 43: 139-145, 1972. 18. Wilcott, R. C. and C. E. Hoel. Arousal response to electrical stimulation of the cerebral cortex in cats. J. comp. physiol. Psychol. 85: 413-420, 1973.
Habituation of Orienting and Motor Responses Elicited by Stimulation of the Cortex in the Cat HANS VALE, HAKAN SUNDBERG AND HOLGER URSIN
Institute o f Physiology and Institute o f Psychology, University o f Bergen, Norway (Received 27 March 1975) VALE, H., H. SUNDBERG AND H. URSIN. Habituation of orienting and motor responses elicited by stimulation of the cortex in the cat. PHYSIOL. BEHAV. 16(3) 337-341, 1976. - Orienting and motor responses have been elicited by electrical stimulation of the cortex in the unanesthetized, freely moving cat. A total of 73 electrodes from 29 cats was studied. The orienting response was elicited from 56 sites. The response was undistinguishable from that elicited by ordinary sensory stimulation, and no difference was observed in the responses elicited from different cortical areas. Motor responses were observed less frequently. The orienting response showed habituation and dishabituation in all cases except 4. This finding is in agreement with previous work in this area. However, motor responses, with or without accompanying orienting responses, also showed habituation, dishabituation, and even savings from one day to another. Stimulus recognition models [10] seem inadequate to explain our findings for the motor response, but the data are explained by synaptic models of habituation [3]. Habituation
Orienting response
Motor response
Electrical brain stimulation
E L E C T R I C A L stimulation of cortical areas and subcortical structures in the cat f r e q u e n t l y produces an orienting response. This response is undistinguishable f r o m the orienting response as described by Pavlov [2, 13, 14]. In addition to the behavioral characteristics of arousal, there is also an a c c o m p a n y i n g electroencephalographic arousal [6,151. If such stimulation is repeated, response habituation is observed from most electrode sites [14, 15, 16, 18]. Dishabituation, i.e. arousal p r o d u c e d f r o m a n o t h e r source, re-establishes the orienting response. This p h e n o m e n o n d e m o n s t r a t e s that the disappearance of the response is not due to artifacts such as polarization or damage to the tissue
Cortex
METHOD
Animals and Surgery A total of 73 electrodes in 29 cats were included in the material. During N e m b u t a l (R) anesthesia platinum or stainless steel electrodes were implanted in the lateral and frontal part of the cortex. The platinum electrodes consisted of 0.18 m m thick platinum/iridium wire covered by Teflon except for 1 m m at the tip. Since this wire was too flexible to be implanted unsupported, it was fed through a stainless steel catheter of 0.6 m m bore, the bare platinum tip protruding at the end. The stainless steel wires were 0.5 m m thick and were insulated except for 0 . 5 - 1 m m at the tip. O t h e r details of the implantation and observation procedure have been given previously [ 14,15 ].
[151. F r o m o t h e r points, in the reticular f o r m a t i o n , thalamus, the septal area, and amygdala, h a b i t u a t i o n was not always observed [ 1 5 , 1 6 ] . These n o n h a b i t u a t i n g responses are probably due to electrical stimulation o f areas of primary importance for activation or motivation. Orienting responses and electroencephalographic arousal have been elicited f r o m m a n y cortical areas, although negative areas also exist [2,6]. For cortical areas habituation to electrical stimulation has o n l y been studied for the occipital field [ 15] and for the sylvian and ectosylvian gyri [18]. F r o m m a n y of the o t h e r cortical areas m o t o r responses are elicited as well. The present paper deals with the habituation o f the orienting response and the m o t o r responses elicited by cortical stimulation in the cat.
Procedure The intensity of behavioral arousal was evaluated by a scoring m e t h o d described previously [ 1 5 ] . Briefly it consisted of 4 categories of behavior (see Table 1), and the sum of the scores for these 4 categories served as the arousal score. The level of arousal was evaluated just before stimulus onset and a second score was given for the behavior occurring during and i m m e d i a t e l y after the stimulation. The difference b e t w e e n these 2 scores has been used as an indicator of the arousal effect of stimulation.
This work was supported by the Norwegian Research Council for Science and the Humanities. Authors are grateful to Aase Larsen and Nina Holmelid for their technical assistance. 337
338
VALE, SUNDBERG AND URSIN TABLE 1
)
SCORING S C H E D U L E : O R I E N T I N G RESPONSE
Points
Head
Eye-lids
Ears
Posture
6 5 4 3 2
-Searching Turning Lifted Quiet
---Moving Quiet
Running Walking Standing Sitting Lying on belly
1
Laid down
--Open Half open Membrana nict. contracted Closed
--
Curled u p o r lying on side
T h e b r a i n was s t i m u l a t e d w i t h 5 sec t r a i n s of positive m o n o p h a s i c square waves, each pulse lasting for 1 msec, a n d 100 pulses per sec. O n l y 1 site was t e s t e d each day. H a b i t u a t i o n was said to o c c u r w h e n t h e cat for 3 trials in a row did n o t show m o r e t h a n 0.5 in d i f f e r e n c e b e t w e e n t h e pre- a n d p o s t s t i m u l a t i o n score. T h e n u m b e r o f trials t o h a b i t u a t i o n , including t h e 3 trials in t h e c r i t e r i o n run, was used as t h e h a b i t u a t i o n score. D i s h a b i t u a t i o n was t h e n p r o d u c e d b y i n t r o d u c i n g o t h e r arousal p r o d u c i n g stimuli ( k n o c k i n g o n t h e w i n d o w , t u r n i n g lights o n a n d off, etc.) T h e n u m b e r o f trials necessary to p r o d u c e r e h a b i t u a t i o n was t h e n tested. In a d d i t i o n t o t h e o r i e n t i n g response, o t h e r m o t o r responses were also observed. These r e s p o n s e s varied f r o m o n e e l e c t r o d e site to a n o t h e r , each particular r e s p o n s e was described as carefully as possible d u r i n g t h e screening, a n d an individual profile was o b t a i n e d for each point. During the h a b i t u a t i o n sessions, all b e h a v i o r categories observed to t h e initial s t i m u l a t i o n were observed. F o r t h e final evaluat i o n of t h e h a b i t u a t i o n data, a scoring sheet was designed (Table 2). This m a d e it possible to o b t a i n a n u m e r i c a l score. H a b i t u a t i o n session were r u n for all t h e s e p o i n t s , u n t i l n o r e s p o n s e was o b s e r v e d or to a preset cut o f f at 100 trials. W h e n b o t h o r i e n t i n g r e s p o n s e s a n d m o t o r r e s p o n s e s were elicited, h a b i t u a t i o n was r u n u n t i l b o t h t y p e s of r e s p o n s e s disappeared. F o r 7 p o i n t s savings of t h e h a b i t u a t i o n f r o m o n e d a y t o the o t h e r were testedi 5 p o i n t s yielded o r i e n t i n g r e s p o n s e s
FIG. 1. Electrode placements in the cortex of the cat. Top: Electrode sites yielding orienting responses. The number in each circle indicates number of trials to habituation. Circle filled with horizontal bars: No habituation. Bottom: Triangles: mixed motor and orienting behavior, squares: motor response only. The number in each symbol indicate number of trials to habituation criterion.
TABLE 2 SCORING SCHEDULE: MOTOR AND MIXED RESPONSE Points
Face
3
Neck and back --
Paws
Strong tonic contraction OF
repeated clonic contractions 2
Repeated chewing
Tonic contraction, occasional slow withdrawal of head and/or body
Repeated striking with forepaw
1
Contracting muscles in the face or a chewing motion
Slight tonic contraction, small jerk
Spasm in one or more paws, or striking
0
No response
No response
No response
CORTICAL STIMULATION
339
AND HABITUATION
in combination with motor responses, while 2 yielded only motor responses. At the end of the experiment the animals were killed, the brains perfused and electrode sites identified histologically in Nissl-stained material. RESULTS
There were no differences in the behavioral effects depending on whether the electrode was made from platinum or stainless steel, or between bipolar and monopolar stimulation. In the following, all these results will be grouped together. Behavioral responses Orienting responses. From 56 electrode sites the typical orienting response was obtained [ 2, 13, 14, 1.5, 161. The response was adequately described by the scoring categories in Table 1. Motor responses. From 4 electrode sites a motor response was obtained. The most frequently observed was a slow, tonic contraction of the neck muscles, often combined with clonic movements of the contralateral foreleg. It looked as if the cat struck repeatedly at something in front of it. Other motor responses were tonic/clonic contractions of the contralateral facial muscles. Tonic contractions of the muscles of the back were also observed, sometimes combined with withdrawal of the frontal part of the body and clonic movements of the neck muscles. Each point gave the same response when stimulated on later sessions. Mixed motor and orienting responses. These reactions were obtained from 13 electrode points, and consisted of one or more of the motor responses described above combined with or followed immediately by an orienting response. Other responses. Stimulation of 1 point resulted in no reaction even if the intensity was increased. Stimulation of
26 66
Habituation Orienting responses. Repeated stimulation of 52 points resulted in the gradual reduction of the response described previously for stimulation of the occipital cortex, the caudate nucleus and the amygdala [ 14,151. (Fig. 3A). There was no significant difference in the number of trials to criterion between points stimulated in the frontal and the lateral areas. For 4 electrode sites, the criterion for habituation was not reached after 100 repeated presentations of the stimulus. Three of these points were localized in g.subproreus and g.proreus, and 1 point was localized in the ventral aspect of the occipital field (Figs, 1, 2). These nonhabituating points were not tested further with other stimulus parameters. For the habituated orienting responses, the whole pattern was restored after presentation of other stimuli producing orienting responses (dishabituation). The number of trials necessary to reach criterion again (rehabituation) was less than that needed to reach the initial habituation. Motor responses. Repeated stimulation of 2 of the 4 points that yielded motor responses only, resulted in a gradual disappearance of the particular motor response obtained from that point. The gradual disappearance followed the same waxing and waning pattern described for the orienting response (Fig. 3B). One point required 24 trials, the other point 59 trials to habituation criterion. The
29 33
3066
32 00
7 points resulted in fullfledged tonic/clonic convulsions. Some of these convulsions started with orienting responses, but developed rapidly into a convulsive fit. No further stimulation was given to such points, and all these points have been excluded from the material. Localization. The localization of the points in the cortex on the lateral surface of the brain is evident from Figure 1, the frontal cortex points are evident from Figure 2.
25 33
24 00
FIG. 2. Frontal sections through the frontal area of the cat (modified from [7]). Left side of each section: Orienting responses (circles). Right side: Mixed motor and orienting responses (triangles), and motor responses only (squares). The number in each symbol signifies the number of trial to habituation criterion. Horizontal bars: No habituation.
340
VALE, SUNDBERG AND URSIN
A i I
orienting response (pomtsi
I
i
savings,
15
e/e
.... IIIIIII iI .,IIIIIIiiiI
10
I 5
I 10
100
75
I
t 15
25
20
X
30
sum. no
50
B l
T motor
response (points)
5
Ii ~
X
25
TTTYTYYYYYTYTYY TTTYT IT',' l 5
1 10
• I 15
•VV
I 20
••
25
30
sum. no
C
I i
orienting response (points)
I
I
I
3
4
5
days
i
FIG. 4. Savings from day to day habituation for 6 different points yielding motor responses or mixed motor and orienting responses. The number of trials to criterion the first session was set to 100%.
i I
10
001
I
Ill
,, I I I
1I
motor r e s p o n s e (points)
10
I
2
i i
15
5
I
1
I t I I
15 5tlm
20
25
30
35
no
FIG. 3. Habituation to stimulation of the cortex in the cat. (A) Orienting response. (B) Motor response only. (C) Mixed responses. For each stimulation (abscissa) the intensity of the response is indicated by the height of the bar. Circles indicate level before stimulation (only for orienting response) triangles level during and after stimulation. Black symbols indicate no difference between the prestimulation and the poststimulation values. The arrow indicates dishabituation. The results shown have been picked at random from the total material. same m o t o r r e s p o n s e r e a p p e a r e d after d i s h a b i t u a t i o n and could be r e h a b i t u a t e d . F o r t h e o t h e r 2 points, r e p e a t e d s t i m u l a t i o n did n o t lead to h a b i t u a t i o n . Mixed motor and orienting responses. Mixed m o t o r and orienting r e s p o n s e s also gradually d i s a p p e a r e d as a result o f s t i m u l a t i o n for 12 o f t h e 13 p o i n t s t h a t gave t h e s e reactions. F r e q u e n t l y 1 o f these r e s p o n s e s disappeared
before the other, but there was no significant tendency in which response disappeared first. Criterion was reached between 8 and 57 trials. (Md = 17). After presentation of an external stimulus both responses were restored, and both disappeared gradually during rehabituation (Fig. 3C). Repeated stimulation of 1 point in prefrontal cortex did not produce habituation. Saving was tested for 2 of the motor responses and 5 of the points yielding mixed motor and orienting responses. Saving was tested by running 5 consecutive habituation sessions, 1 session per day. Only 1 electrode placement in each cat was used for this test. The number of trials necessary to reach criterion for each session was gradually lower from one session to another for 6 of these points, thus demonstrating savings (Fig. 4). There was significantly less trials to criterion on the fifth session as compared with the first session (p<0.02, Wilcoxon matched pair signed ranks test, 2-tailed). DISCUSSION
Orienting Responses The present findings comfirm previous observations [2] that electrical stimulation of the lateral surface of the cortex of the cat, frequently results in a behavior response which is indistinguishable from the normal orienting response in the cat [ 2,15 ]. In the present material stimulation of all points except 4 showed habituation, following the same number of stimulus presentations as that found for stimulation of the amygdala
CORTICAL STIMULATION AND HABITUATION
341
[15], the caudate nucleus [14] and the specific nuclei of the thalamus [16]. The nonhabituating points were localised in the frontal pole (n = 3) and on the lateral posterior surface of the cortex (n = 1). These points were not tested for any motivational properties. In the rat, stimulation of ventral frontal areas has produced positive reinforcement [8]. Wester [17] has shown that points yielding negative reinforcement do not show habituation. The possibility exists, therefore, that there are parts of the frontal cortex also in the cat that will yield positive reinforcement upon electrical stimulation. The gradual decrease of the response can not be explained by local changes around the electrode tip, as polarization or tissue damage. In all cases the response was restored after presenting an external stimulus producing arousal. The response attenuation, therefore, seems to be a result of a habituation process as defined by Thompson and Spencer [ 12 ].
Motor responses. It was possible to demonstrate that the m o to r responses also showed the habituation phenomenon, dishabituation and faster rehabituation after dishabituation. We have also observed spontaneous recovery and savings between consecutive habituation sessions also for these motor responses. Five of the 9 criteria for habituation as suggested by Thompson and Spencer [ 12] therefore have been met. The other 4 were not tested. We conclude that the habituation
phenomenon also exist for cortically induced mot or responses. Attenuation of cortically induced motor responses has been observed previously, but, to our knowledge, this attenuation has not been discussed within the habituation conceptual framework. Dusser de Barenne and McCulloch [1] demonstrated that in awake monkeys, the response to the last of two stimuli was smaller or not observed at all if the interval between these stimuli was around 4 sec. They called this phenomenon extinction, and the discussion of this was part of the suppression controversy [5]. It seems evident from our data that the complex networks responsible for the motor responses we elicit is subject to habituation. In the dual process theory of habituation [3] 3 types of synapses are described, habituating, sensitizating and nonhabituating. Repeated tactile stimulation demonstrates that in the unanesthetized cat the pyramidal tract contains units that show habituation as well as sensitization [1 1]. The simplest explanation of our finding, therefore, is that the network we interfere with contain such habituating synapses. This may also be true for the areas from which we elicit orienting behavior. While the Sokolov [10] cognitive stimulus-recognition model gives a satisfactory explanation for the data on habituation of the orienting responses, this same model gives less satisfactory explanations for the habituation of the m o t o r response. Also, the Sokolov model seems unable to account for the finding of the habituation in deeply unconscious human patients [4].
REFERENCES 1. Dusser de Barenne, J. G. and W. S. McCulloch. Local stimulatory inactivation within the cerebral cortex, the factor for extinction. Am. J. Physiol. 118: 510-524, 1937. 2. Fangel, C. and B. R. Kaada. Behavior "attention" and fear induced by cortical stimulation in the cat. Electroenceph. clin. Neurophysiol. 12: 575-588, 1960. 3. Groves, P. M. and R. F. Thompson. Habituation: A dualprocess theory. Psychol. Rev. 77: 419-450, 1970. 4. Gulbrandsen, G. B., K. Kristiansen and H. Ursin. Response habituation in unconscious patients. Neuropsychologia 10: 313-320, 1972. 5. Kaada, B. R. Cingulate, posterior orbital, anterior insular and temporal pole cortex. In: Handbook o f Physiology - Neurophysiology II, edited by J. Field, H. W. Magoun and V. E. Hall. Washington, D.C., 1960. Pp. 1345-1372. 6. Kaada, B. R. and N. B. Johannessen. Generalized electrocortical activation by cortical stimulation in the cat. Electroenceph, clin. Neurophysiol. 12: 567-573, 1960. 7. Kreiner, J. The neocortex of the cat. Acta Neurobiol. exp. 31: 151-201, 1971. 8. Routtenberg, A. Forebrain pathways of reward in Rattus norvegicus. J. comp. physiol. Psychol. 75: 269-276, 1971. 9. Sharpless, S. and H. Jasper. Habituation of the arousal reaction. Brain 79: 665-680.
10. Sokolov, Y. N. Perception and the conditioned reflex. Oxford: Pergamon, 1963, pp. 309. 11. Teyler, T. J., R. A. Roemer and R. F. Thompson. Habituation of the pyramidal response in unanesthetized cat. Physiol. Behav. 8:201-205, 1972. 12. Thompson, R. F. and W. A. Spencer. Habituation: A model phenomenon for the study of neuronal substrates of behavior. Psychol. Rev. 73: 16-43. 13. Ursin, H. and B. R. Kaada. Functional localization within the amygdaloid complex in the cat. Electroenceph. clin. Neurophysiol. 12:1-20, 1960. 14. Ursin, H., H. Sundberg and S. Menaker. Habituation of the orienting response elicited by stimulation of the caudate nucleus in the cat. Neuropsychologia 7:313 -318, 1969. 15. Ursin, H., K. Wester and R. Ursin. Habituation to electrical stimulation of the brain in unanesthetized cats. Electroenceph. clin. Neurophysiol. 23: 41-49, 1967. 16. Wester, K. Habituation to electrical stimulation of the thalamus in unanesthetized cats. Electroenceph. clin. Neurophysiol. 30: 52-61, 1971. 17. Wester, K. Reinforcing effects of thalamic stimulation resistant to habituation. Brain Res. 43: 139-145, 1972. 18. Wilcott, R. C. and C. E. Hoel. Arousal response to electrical stimulation of the cerebral cortex in cats. J. comp. physiol. Psychol. 85: 413-420, 1973.