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Visual localization and discrimination after ibotenic lesion of the cat orbito-insular cortex
Behavioural Brain Research, 22 (1986) 53-62
53
Elsevier BBR 00605
VISUAL LOCALIZATION AND DISCRIMINATION AFTER IBOTENIC LESION OF T H E CAT ORBITO-INSULAR CORTEX
E. MAIRE-LEPOIVRE ~, M. K R U P A 2, J. PRZYBYSLAWSKI 1 and M. I M B E R T 1 ILaboratoire des Neurosciences de la Vision, UniversitO Pierre et Marie Curie, Paris and 2Laboratoire de Neurobiologie du Developpement, Universit~ Paris Sud, Orsay (France) (Received 27 November 1985) (Revised version received 20 June 1986) (Accepted 26 June 1986)
Key words: Orbito-insular cortex - Ibotenic lesion - Visual localization - Cat
Behavioral tasks were used to investigate how the orbito-insular cortex (OIC) of the cat is involved in complex operations such as the orienting reaction towards a novel stimulus. Six cats were trained preoperatively on a perimetry test to assess their ability to orient the head and eyes to objects presented in restricted regions of the visual field, and on brightness, pattern and form discrimination tasks for food reward in a two-choice discrimination apparatus. Two animals then underwent unilateral chemical lesion of the OIC using injections of ibotenic acid, two others received bilateral lesions of this same area, and the remaining two cats were used as normal controls. Postoperative performance of brightness, pattern and form discrimination was normal following OIC lesions, and no lack of retention was observed. In contrast, the cats with OIC lesions had significant deficits in their visually guided behavior. The cats ignored objects presented in the monocular segment of both sides of the visual field, even after unilateral lesion, and there was an effect on the ability to attend and fixate the central preconditioned stimulus.
INTRODUCTION
Anatomical and physiological studies strongly suggest that the cat orbito-insular cortex (OIC) is involved in complex perceptual operations underlying multimodal sensory integration as well as viseral and somatic motoricity. It has been suggested that it could play a role in orienting attention to a novel stimulus 2°. Previous anatomical studies using the retrograde H R P technique showed strong thalamic as well as corticocortical afferents to this area. The most prominant loci of thalamic labeling were the suprageniculate nucleus and parts of the posterol a t e r a l n u c l e u s 2°,29,34 and the majority of the corticocortical connections originated from associative cortices 2°.
This variety of inputs fits with the various functions that have been attributed to this area. Indeed the OIC has been implicated in such various functions as somatic 27 auditory T M and visual processing 3,6,12, as well as vascular and respiratory regulation 23, vagal activities 26, and taste and olfaction sensationZL In addition, the results established with electrophysiological techniques agree with these observations, as was shown by Fallon and Benevento 13. Single units recorded from the OIC are reactive to both visual and auditory stimuli, as are the units recorded from other associative areas of the cat's cortex 3°. The role played by the OIC has been the subject of a series of ablation experiments. Thus, Colavita et al. 7 propose that it is a multimodal area concerned with the perception of temporal sequences
Correspondence: E. Maire-Lepoivre, Laboratoire des Neurosciences de la Vision, Universit6 Pierre et Marie Curie, 4 Place Jussien, 75230 Paris 05, France. 0166-4328/86/$03.50 © 1986 Elsevier Science Publishers B.V. (Biomedical Division)
54 of stimuli such as different auditory frequencies and different light or vibrotactile intensities. Schalg-Rey and Lindsley 35 suggest that this frontal area may play a critical role in tasks requiring flexibility in visual orienting, selective attention, anticipation of events and use of visual responseproduced cues. Consequently, a question of major interest is the behavioral function of the OIC. One approach to answering this question is to determine the behavioral capacities that are disrupted as well as those that remain after selective lesion of the OIC. In the present experiment, chemical lesions with the neurotoxin ibotenic acid were carried out. The great advantage of ibotenate lies in its lack of epileptogenic properties and its ability to produce restricted specific lesions without damaging fibers of passage ~°. Behavioral tasks were chosen to gain an insight into the nature of neural processes disrupted by OIC damage. The first of these was the ability of pre- and postoperative cats to orient the head and eyes to a stimulus presented in particular locations in the visual field, tested with the use of the perimetry method of Sherman 36. In a second study, we tested the possibility that OIC is involved in discrimination performance. Sprague et al. 4~ showed that there are cortical areas involved in simple pattern form discrimination which lie outside areas 17 and 18. It appears likely that many areas of the cortex lying in the suprasylvian sulci (LSA), posterior suprasylvian cortex (area 21 and part of area 19), the lateral gyrus and perhaps other, as yet undefined cortical regions, participate in some integrated fashion in form perception and discrimination in the cat. These methods were used to determine whether or not the ability to discriminate and to orient is differentially disturbed by a lesion of the OIC.
a day (4 h after the daily testing session) and maintained at approximately 90 04 of their normal body weight. All cats were initially trained and test on each visual task described below. They were divided into experimental and control groups. In the experimental group, 2 animals received a unilateral lesion of the orbito-insular cortex (OIU) and 2 animals a bilateral lesion of the same region (OIB). The 2 control animals were shamoperated. For all cats, after a 3-week break, the tasks were presented in the same order as during the original testing.
Surgery Surgery was performed under aseptic conditions. Cats were anesthetized with Alfatesine (0.3 ml/kg/h, i~v.) and positioned in a Narishige stereotaxic instrument. The approach to the orbito-insular cortex was accomplished stereotaxically through the frontal cortex with a 30 ° angle of penetration, thus avoiding enucleation (see Fig. 2B). The microinjections of ibotenic acid (Sigma) were made using a 10-#1 Hamilton syringe fitted to a stereotaxic holder. The outer diameter of the needle was approximately 250 ~m. A volume of 1-2.2 #1 (10 #g//A) of ibotenic acid, dissolved in phosphate buffer (0.1 M pH 7.4), was infused during 15-20 min at 3-5 different depths. After each injection, the needle was left in situ for an additional 10 min to check for backfiow along the needle tract. The control and experimental cats were identically treated, in that the dura was broken and the needle was lowered into the white matter just beneath the OIC in order to avoid a mechanical lesion of the cortex. In the control animals, no injection was made.
MATERIALS AND METHODS
Subjects Six experimentally naive young adult cats were used as subjects. At the beginning of the experiment, they were 7 months old. They were housed together in a special room with a 12 h light-dark cycle. Throughout testing, the cats were fed once
Apparatus and testing methods For all cats, the tests were presented in the order in which they are described. Localization and orientation. Ability to localize and orient to a stimulus in the visual field was tested using perimetry methods described in detail by Sherman 36. A table-top was divided by radial
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Fig. 1. Apparatus and testing method for the localization and orientation test.
lines into twelve 15 ° sectors, extending 75 ° to either side of a 0 ° central guideline. The table-top was delimited by a cylindrical screen of 70 cm diameter with holes corresponding to each guideline (Fig. 1). The cat was placed in the center of the table-top and his head and body were restrained by an experimenter so that the nose was directed along the 0 ° central guideline and the lateral canthi of the eyes were aligned with the 90 ° left and right guidelines. The cat was trained to attend to the central preconditioning stimulus (an empty spoon). While the cat was fixating, a second stimulus (spoon with cat food) was introduced in front of the cat along one of the guidelines through a window 3 cm wide. This stimulus entered the visual field at 35 cm from the cat's nose (at the level of the cylindrical screen). The cat was then freed and its responses noted. A positive respons was scored if the cat immediately oriented the head and eyes toward the second stimulus. Any other behavior was scored as a negative response. Only positive responses were rewarded with a piece of cat food. All testing was first binocular and then monocular, in which case one eye was occluded with a large opaque mask. Each eye was tested separately on the same day, and each daily session usually consisted of 4 trials along each guideline. The order of presentation for each guideline was varied according to a pseudo-quasi random series. Testing was continued for 30 trials along each guideline in binocular and monocular viewing.
One cat (OIU2) was tested to assess the performance and the recovery 3, 6 and 9 weeks after the lesion. Two-choice pattern discrimination. A two-choice discrimination apparatus, similar to that described by Spear and Braun 38, was used for visual discrimination training and testing. It consisted of a rectangular box (150cm long x 56cm wide × 50 cm high), with a start panel at one end and two choice panels at the other end and with a vertical separation along the centre of the box. Each choice-panel contained a 16.5 cm high × 11 cm wide stimulus screen onto which stimuli were rear-projected by two slide-projectors. The choice-panels were hinged at the top and the cat was required to push them open to gain access to the 'food-plate' placed outside the box just beneath each choice-panel. A reward of cat food was delivered if the cat made the correct choice. Three discrimination tasks were employed. The first was a brightness discrimination between a light and a dark stimulus screen. The second was a discrimination between an array of horizontal stripes and a array of vertical stripes projected on each stimulus screen. The third discrimination was between an upright isoceles triangle projected on one stimulus screen, and an inverted isoceles triangle projected on the other. All cats were trained on the 3 tasks in the order of description. Retention testing followed the same order of task presentation. Trial-to-trial position of the positive stimulus was varied from the right and left choice door according to a quasi random series. Usually, 40 trials were given each day, 5 days a week. Training on each task was continued until a criterion of 36/40 correct choices in two consecutive daily blocks of 40 trials was reached.
Histological procedures At the end of the experiment, the animals were deeply anesthetized with pentobarbital sodium (40 mg/kg, i.p.) and perfused intracardially with 0 . 9 ~ saline followed by 10~o formol-saline. The brain was removed from the skull and placed in 10~o formol-20Yo sucrose-saline for a week. It then was cut serially at 50 #m thickness in the
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Fig. 2. A: localization of the orbito-insular cortex (OIC) in the cat. B: frontal section of the cat brain showing the penetration of the microsyringe needle through the frontal cortex to the OIC. C, D, D', E: photomicrographs illustrating the damage to the OIC caused by an injection ofibotenate. Frontal section stained for cell bodies with Cresyl violet. C: contralateral O1C at the level of the lesion. D: photomicrograph centered on the lesion showing needle track and reduction of the cortex width (Bar = 1 mm in C and D). D': schematic representation of the lesion's extent (surrounded by dotted lines). E: high power micrograph of the lesion in D; the lesion affects the deep layers of the cortex Bar = 100/~m).
57 frontal plane on a freezing microtome. Sections were processed histochemically to localize the lesion sites using either P A G E or Nissl-staining. Lesion reconstitutions were plotted through the brain with the aid of the atlas of ReinosoSuarez 33.
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Histology Fig. 2 shows an example o f the lesion made with ibotenic acid in one cat (OIB1). There is a considerable loss o f neuronal cell bodies in the damaged area c o m p a r e d with the normal one. Light microscopic analysis revealed that ibotenic acid p r o d u c e d a marked disappearance o f nerve cells over a restricted range. Axons o f passage did not seem to be damaged. A small number of apparently healthy neurons can be seen, but most o f the cells in the damaged area are glia. Nevertheless, it is very difficult to etablish the real extent o f the lesion after long survival times 9'1°. H o w ever, in all cases, the needle tract could be localized and the tip o f the needle was in the OIC or in the b o t t o m o f the anterior ectosylvian gyrus (see Fig. 3 for summary): the lesion site could be estimated to be in the dorsal bank of the OIC. In the two control cats (sham-operated), the needle tract was also localized. In their case, there was just a mechanical lesion, due to the passage o f the needle through the underlying white matter, with no damage in the cortex.
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Fig. 4. A: percentage correct responses as a function of training sessions before and after surgery for one cat. Forty trials per day were given. B: number of trials required to reach criterion performance on the 3 two-choice discriminations for the 3 experimental groups of cats. Scores for individual cats are shown by the dots. Filled dots: preoperative scores, empty dots: postoperative scores.
Two-choice pattern discrimination The brightness discrimination data, as well a the pattern discrimination results, are quite consistent for the 6 subjects. F r o m 400 to 600 trials were required for the cats to reach criterion preoperatively. The numbers of training trial blocks required for the cat O I U 2 to reach criterion performance successively on brightness, horizontal-vertical grating and upright-inverted triangles discrimination before and after the lesion, are shown in Fig. 4A. Following the retention period the normal cats continued to show the same performance; no relearning was necessary to reach criterion. The results for cats with unilateral or bilateral OIC lesions were very similar to those for normal cats. Following the lesion, no lack of retention was observed. Fig. 4B shows results before and after the operation for the 3 experimental groups.
58 Localization and orientation In agreement with Sherman 37, preoperative cats responded binocularly to objects presented anywhere in the region bounded approximately from 75 ° right lateral to 75 ° left lateral, the most peripheral guideline tested. The monocular visual fields were found to measure approximately from 75 c ipsilateral to the open eye to 45 ° contralateral. Thus the binocular segment of the visual field includes the region bounded bilaterally by about 45 °, and the monocular segment of each side begins approximately at the 45 ° contralateral guideline. This agrees well with previous studies using similar methods (e.g. refs. 36,39). Normal cats. The binocular performance of the two sham-operated cats was practically identical following surgery. With monocular viewing, preand postoperative data are also approximately the same (Fig. 5).
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Unilateral lesions. After a unilateral lesion of the OIC, in binocular viewing, we observed deficits only for the most peripheral guidelines: the unilateral lesion of the OIC has no detectable effect on the ability of the cats to orient rapidly to a stimulus presented in the binocular segment of the visual field. However, we observed a deficit in both monocular segments which was larger in the segment ipsilateral to the lesion. In monocular viewing, as in binocular viewing, the binocular segment of the visual field was not affected. In the monocular segment ipsilateral to the lesion, there was a total lack of response to stimuli presented along the 75 ° guideline and a large deficit along the 60 ° one. In the contralateral monocular segment, we observed a large deficit along the 75 ° guideline and a fall in the performance along the 60 ° guideline
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Fig. 5. Visual field perimetry. Each graph in polar coordinates shows the proportion of correct responses for stimuli presented at each of the guidelines. Open bars indicate the level in preoperative tests (original), filled bars indicate the level in postoperative test (retest). The external semicircle represents the 100% positive response level, and the dotted line semicircle a level of 50%. First, second and third rows: response levels in binocular viewing, in right monocular viewing, and in left monocular viewing. Left column: mean results for the 2 normal cats. Middle column: mean results for the 2 cats with unilateral lesion of the left OIC. Right column: mean results for the 2 cats with bilateral lesion of the OIC.
59 increased considerably (1-3 s). The ability to shift attention to a test stimulus seems to be diminished. This effect is only observed when the stimulus is presented in both monocular segments, even with the unilateral lesion. The ability to orient to a test stimulus presented in the binocular segment is not affected by unilateral or bilateral lesions. Case of the cat OIU2. This cat, with a unilateral lesion of the OIC, was retrained on the perimetry task 3, 6 and 9 weeks after the operation. Fig. 6 shows the performances during those tests. In the binocular segment, the 3 sets of perimetry data were similar to those observed before the lesion. The decrease of the performance in the monocular segment disappeared completely after 9 weeks. This recovery was different depending on the guidelines: the slowest recovery being for the most peripheral stimulus. In monocular viewing, the recovery of preoperative performance along the far nasal guide-
In both monocular segments, we noted a decrease in performance along the far nasal guideline (45 °). Bilateral lesions. During the binocular viewing tests, the performances observed in the binocular segment of the visual field were the same before and after the lesion. The bilateral lesion of the OIC affect only the performance along the 60 ° and 75 ° guidelines. With monocular viewing, performance decreased in both monocular segments, with a total loss of responses at the 75 ° guideline and a large deficit along the 60 ° one. The decrease in performance observed along the far nasal guideline (45 °) was similar to those observed after a unilateral lesion of the OIC. In cats with OIC lesion, the fixation time to the central stimulus was longer after the lesion than before. Before the lesion, the cat showed an immediated motor response (orientation to the second stimulus); after the lesion, the latency
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60 line (45 °) was observed after 6 weeks, but 9 weeks were required before the performance on the 75 ° and 60 ° guidelines recovered to preoperative levels. DISCUSSION
The results of this study provide clear evidence that lesions of the OIC do not affect performance of either form or brightness discrimination tasks. On the other hand, the same lesions have a marked effect on the performance of a perimetry task. Histology One interesting property of ibotenate is its ability to produce specific spherically circumscribed neuronal lesions: the toxin kills the neuronal cells bodies, but does not damage axons of passage and no neuronal degeneration distant from the site of application has been observed ~°'25. This fact is very important in areas such as the O1C where many fibers of passage could be distroyed during mechanic, electrolytic or radio-frequency lesions. Another advantage of ibotenate is its low tendency to generate epileptogenic loci. Ibotenate does not cause electroencephalographic seizures at intracerebral doses < 3/~g, i.e. it is at least 1000 times weaker as a convulsant than kainate ~. Discrimination Campbell 4 has discribed deficits in pattern discrimination after lesions in areas 20 and 21 in the cat and has compared this part of the cat brain with the inferotemporal cortex of the rhesus monkey. Furthermore, his finding of a deficit following a lesion placed in a cortical target area of the pulvinar nucleus, without involvement of any part of the geniculocortical system, area 19 or LSA, is in agreement with the results of Sprague et al. 4~ and Bauman and Spear 2. In other studies, removal of the superior coUiculi has resulted in deficits of pattern discrimination in the cat 4°. OIC receives a collicular projection via the posterior group of the th alamu s ~5.16,17,24,29. These considerations would suggest that the OIC, which is a target of the tectothalamocortical
pathways, might provide a first stage in simple form discrimination. However, after OIC lesions, no lack of retention of visual form discrimination was observed in our experiments. The seeming discrepancy between these results and our hypothesis can be resolved by the fact that such tests are not appropriate because the OIC could only be implicated in more complex discrimination tasks ~. Localization and orientation The perimetry method was chosen to test the ability of the animal to attend to a fixation stimulus and orient the head and eyes to a new stimulus presented anywhere within a wide area of the visual field. The extent of the visual fields, in monocular or binocular viewing, observed during our experiments with sham-operated or preoperated animals are in agreement with those found by Sherman 37 and Spear et al.39 under similar testing conditions. Following OIC lesions, we observed a neglect of the most peripheral part of the visual field. This bilateral neglect was present after both uni- and bi-lateral lesion. Moreover, in both experimental groups of animals, the same deficits appear for stimuli presented in the two monocular segments of the visual field with no effect on performance in the binocular segment (Fig. 5). In our experiments, the cats recovered from all of the behavioral deficits induced by the ibotenate injection. This recovery was delayed in the monocular segment for the more peripheral guidelines (Fig. 6). These deficits disappear within 6 - 9 weeks according to data of Steele Russel and Pereira 42. The complete recovery shown by our results may have had contributions from several sources. (1) Neural mechanisms within the damaged area: it is possible that neurons were temporarily inactived by the ibotenic acid, but recovered since their exposure to the toxin was sublethaP 2, especially in the superficial layers of the cortex which showed no visible damage in histological control (Fig. 1). (2) Behavioural compensation: it is possible that compensatory readjustment occurs rather then functional recovery 42. (3) Alternatively, behavioral recovery may be mediated
61 by other tectocortical pathways such as those involving cruciate and presylvian sulci 18't9. In our experiments, after unilateral lesion of OIC, we observed a bilateral neglect in both monocular segments of the visual field. This result may be related to those obtained in the monkey. For Latto and Cowey 28, unilateral frontal eye field (FEF) lesions induced a neglect limited to the contralateral visual hemifield. More recently, Crowne etal. ~2 showed that unilateral F E F lesions produced not only a neglect of stimulus lights contralateral to the side of the lesions, but also responses to the most peripheral of the ipsilateral stimulus lights were affected as shown in increased errors and response latencies. In the present experiment we observed this increase in latencies, but in both monocular segments. This result may be related to the anatomical finding 5"29 of heavy reciprocal transcallosal connections between the two OIC. Indeed, Crowne et al. 12 showed that a callosal section aggravates the deficits caused by unilateral F E F lesion, or reinstates them after spontaneous recovery. It seems clear that even if the OIC could be considered as a part of the oculomotor areas in the cat 18'19"31, it is not involved in the same operations as the frontal eye field of monkeys 28. The behavioral patterns observed during our experiments were more similar to those observed by Jeannerod et al.2~, for whom bilateral frontal lesions in cat induced an increase in fxation to a central stimulus and also a perseveration in pursuit eye movements in response to a moving target. For these authors, the frontal regions play a role in 'defixation'. This hypothesis is in agreement with Velasco and Lindsley's suggestion 44 that the OIC is involved in inhibitory activity. Deficits observed during the presentation of a stimulus in the monocular segments of the visual field could result from a failure to detect the target or from a problem in shifting attention to a novel stimulus. Similar patterns of neglect have been observed after bilateral lesions of the superior colliculus. Thinus-Blanc 43 has suggested that the superior colliculus could be an element of a system which modulates attentional changes. This interpretation is consistent with our previous anatomical
s t u d y 29 which showed that OIC receives inputs from the suprageniculate nucleus, a part of the posterior group of the thalamus which receives strong collicular projections from the most lateral part of the n u c l e u s 15"16"17"24. Furthermore, Guitton and Mandl ~s'19 showed the existence in the OIC of cells discharging only when the untrained animal attended to, and tracked, an object of interest. These data are also in agreement with the hypothesis of Latto and Cowey 28 who proposed that this oculomotor area plays a role in the purposeful scanning of the environment. Thus, our results give support to the idea that the OIC is involved in the shift of attention which occurs particularly in the early stage of the orienting reaction. ACKNOWLEDGEMENTS
This work was supported by grants from the Centre National de la Recherche Scientifique (CNRS) and the Singer Polignac Foundation. We are grateful to Simon Thorpe for help with the English language. REFERENCES 1 Aldinio, C., French, E.D. and Schwarcz, R., Seizures and neuronal degeneration: relationships investigated by intrahippocampal kainic and ibotenic acid, Soc. Neurosci. Abstr., 7 (1981) 589. 2 Baumann, T.P. and Spear, P.D., Role of the lateral suprasylvian visual area in behavioral recovery from effects of visual cortex damage in cats, Brain Res., 138 (1977) 445-468. 3 Biguall, K.E., lmbert, M. and Buser, P., Optic projections to non-visual cortex of the cat, J. Neurophysiol., 29 (1966) 396-409. 4 Campbell, A. Jr., Deficits in visual learning produced by temporal lesions in cats, J. Comp. Physiol. Psychol., 92 (1976) 45-57. 5 Cavada, C. and Reinoso-Suarez, F., lnterhemispheric corticocortical connections to the prefrontal cortex in the cat, Neurosci. Lett., 24 (1981) 211-214. 6 Colavita, F.B., Auditory cortical lesions and visual pattern discrimination in cat, Brain Res, 39 (1972) 437-447. 7 Colavita, F.B., Szeligo, F.V. and Zimmer, S.D., Temporal pattern discrimination in cats with insular temporal lesions, Brain Res., 79 (1974) 153-156. 8 Colavita, F.B. and Weisberg, D.H., Spatiotemporal pattern discrimination in cats with insular-temporal lesions, Brain Res. Bull., 3 (1978) 7-9.
62 9 Coyle, J.T., Molliver, M.E. and Kuhar, M.J., In situ injection of kainic acid: a new method for selectively lesioning neuronal cell bodies while sparing axons of passage, J. Comp. Neurol., 180 (1978)301-324. 10 Coyle, J.T. and Schwarcz, R., The use of excitatory amino acids as selective neurotoxins. In A. Bjoklend and T. Hokfelt (Eds.), Handbook of Chemical Neuroanatomy. Methods in Chemical Neuroanatomy, Vol. 1, Elsevier, Amsterdam, 1983, pp. 508-525. 11 Cranford, J.L., Ladnre, S.J., Campbell, C.B.G. and Neff, W.D., Efferent projections of insular and temporal neocortex of the cat, Brain Res., 117 (1976) 195-210. 12 Crowne, D.P., Yeo, C.H. and Steele Russel, I., The affects of unilateral frontal eye field lesions in monkey: visualmotor guidance and avoidance behaviour, Behav. Brain Res., 2 (1981) 165-187. 13 Fallon, J.H. and Benevento, L.A., Auditory-visual interaction in cat orbitoinsular cortex, Neurosci. Lett., 6 (1977) t 43-150.
14 Fallon, J.H., Benevento, L.A. and Loe, P.R., Frequencydependent inhibition to tones in neurons of cat insular cortex (AIV), Brain Res., 145 (1978) 161-167. 15 Graybiel, A.M., Some extrageniculate visual pathways in the cat, Invest. Ophthalmol., 11 (1972) 322-332. 16 Graybiel, A.M., The thalamocortical projection of the so-called posterior nuclear group: a study with anterograde degeneration methods in the cat, Brain Res., 49 (1973) 229-244. 17 Graybiel, A.M. and Berson, D.M., Histochemical identification and afferent connections of subdivisions in LP Pulvinar complex and related nuclei in the cat, Neurosc#nce, 5 (1980) 1175-1238. 18 Guitton, D. and Mandl, G., Frontal oculomotor area in alert cat. I. Eye movements and neck activity evoked by stimulation, Brain Res., 149 (1978) 295-312. 19 Guitton, D. and Mandl, G., Frontal oculomotor area in alert cat. 11. Unit discharges associated with movements and neck muscle activity, Brain Res., 149 (1978) 313-327. 20 Guldin, W.O. and Markowitsch, H.J., Cortical and thalamic afferent connections of the insular and adjacent cortex of the cat, J. Comp. Neurol., 229 (1984) 393-418. 21 Jeannerod, M., Kiyono, S. and Mouret, J., Effets des lesions frontales bilat6rales sur le comportment oculomoteur chez le chat, Vision Res., 8 (1968) 575-583. 22 Kaada, B.R., Somatomotor, autonomic and electrocotigraphic responses to electrical stimulation of rhinencephalic and other structures in primates, cat and dog, Acta Physiol. Stand. Suppl., 83 (1951) 285 pp. 23 Kaada, B.R., Pribram, K.H. and Epstein, J.A., Respiratory and vascular responses in monkeys from temporal pole, insula, orbital surface and cingulate gyrus, J. Neurophysiol., 12 (1949) 347-355. 24 Kawamura, S., Topical organization of extrageniculate visual system in the cat, Exp. Neurol., 45 (1974) 451-461. 25 Kohler, C. and Schwarcz, R., Comparison of ibotenate and kainate neurotoxicity in rat brain: a histological study, Neuroscience, 8 (1983) 819-835. 26 Korn, H., Organisation des Projections Somatiques et vOgOtatives sur le Cortex Orbitaire et Controle Cortical des Reflexes Visc&o-Moteurs Chez le Chat, These de doctorat
27 Korn, H., Wendt, R. and Albe-Fessard, D., Somatic projections to the orbital cortex of the cat, Electroencephalogr. Clin. Neurophysiol., 21 (1966) 209-226. 28 Latto, R. and Cowey, A., Frontal eye field lesions in monkeys, Bibl. Ophthalmol., 82 (1972) 159-168. 29 Maire, E., Krupa, M., Przybyslawski, J. and Imbert, M., An anatomical investigation of visual inputs to the cat orbital cortex, Neurosci. Lett., 43 (1983) 25-29. 30 Markowitsch, H.J. and Pritzel, M., Single unit activity in cat prefrontal and posterior association cortex during performance of spatial reversal tasks, Brain Res., 149 (1978) 53-76. 31 Markowitsch, H.J. and Pritzel, M., The insular region; part of the prefrontal cortex? Neurosci. Biobehav. Rev., 2 (1978) 271-276. 32 Newsome, W.T., Wurtz, R.H., Dursteler, M.R. and Mikami, A., Deficits in visual motion processing following ibotenic acid lesions of middle temporal visual area of the macaque monkey, J. Neuroscience, 5 (1985) 825-840. 33 Reinoso-Suarez, F. Topographischer Hirnatlas der Katze fur Experimental-Physiologische Untersuchungen, Merck, Darmstadt, 1961. 34 Roda, J.M. and Reinoso-Suarez, F., Topographical organization of thalamic projections to the cortex of anterior ectosylvian sulcus in the cat, Exp. Brain Res., 49 (1983) 131-139. 35 Schalg-Rey, M. and Lindsley, D.B., Effects of prefrontal lesions on trained anticipatory visual attending in cat, Physiol. Behav., 5 (1970) 1033-1041. 36 Sherman, S.M., Visual field defects in monocularly and binocularly deprived cats, Brain Res., 49 (1973) 25-45. 37 Sherman, S.M., Permanence of visual perimetry deficits in monocularly and binocularly deprived cats, Brain Res., 73 (1974) 491-501. 38 Spear, P.D. and Braun, J.J., Pattern discrimination following removal of visual neocortex in the cat, Exp. Neurol., 25 (1969) 331-348. 39 Spear, P.S., Miller, S. and Ohman, L., Effects of lateral suprasylvian visual cortex lesions on visual localization, discrimination and attention in cats, Behav. Brain Res., 10 (1983) 339-359. 40 Sprague, J.M., Berluccbi, G. and Diberardino, A., The superior colliculus and pretectum in visually guided behavior and visual discrimination in cat, Brain Behav. Evol., 3 (1970) 285-294. 41 Sprague, J.M., Levy, J., Diberardino, A. and Berlucchi, G., Visual cortical areas mediating form discrimination in the cat, J. Comp. Neurol., 172 (1977) 441-488. 42 Steele Russel, I and Pereira, S.L, Visual neglect in rat and monkey: an experimental model for the study of recovery of function following brain damage. In M.W. van Hof and G. Mohm (Eds.), FunctionalRecoveryfrom Brain Damage, Elsevier, Amsterdam, 1981 pp. 209-238. 43 Thinus-Blanc, C., De l'Espaee Perfu h l'Espace Repr~sentO. Etude des M~chanismes d'Orientatation Spaciale Chez les Mammif&es, These de doctorat d'etat, 1983. 44 Velasco, M. and Lindsley, D.B., Role of orbital cortex in regulation of thalamocortical electrical activity, Science, 149 (1965) t375-1377.
53
Elsevier BBR 00605
VISUAL LOCALIZATION AND DISCRIMINATION AFTER IBOTENIC LESION OF T H E CAT ORBITO-INSULAR CORTEX
E. MAIRE-LEPOIVRE ~, M. K R U P A 2, J. PRZYBYSLAWSKI 1 and M. I M B E R T 1 ILaboratoire des Neurosciences de la Vision, UniversitO Pierre et Marie Curie, Paris and 2Laboratoire de Neurobiologie du Developpement, Universit~ Paris Sud, Orsay (France) (Received 27 November 1985) (Revised version received 20 June 1986) (Accepted 26 June 1986)
Key words: Orbito-insular cortex - Ibotenic lesion - Visual localization - Cat
Behavioral tasks were used to investigate how the orbito-insular cortex (OIC) of the cat is involved in complex operations such as the orienting reaction towards a novel stimulus. Six cats were trained preoperatively on a perimetry test to assess their ability to orient the head and eyes to objects presented in restricted regions of the visual field, and on brightness, pattern and form discrimination tasks for food reward in a two-choice discrimination apparatus. Two animals then underwent unilateral chemical lesion of the OIC using injections of ibotenic acid, two others received bilateral lesions of this same area, and the remaining two cats were used as normal controls. Postoperative performance of brightness, pattern and form discrimination was normal following OIC lesions, and no lack of retention was observed. In contrast, the cats with OIC lesions had significant deficits in their visually guided behavior. The cats ignored objects presented in the monocular segment of both sides of the visual field, even after unilateral lesion, and there was an effect on the ability to attend and fixate the central preconditioned stimulus.
INTRODUCTION
Anatomical and physiological studies strongly suggest that the cat orbito-insular cortex (OIC) is involved in complex perceptual operations underlying multimodal sensory integration as well as viseral and somatic motoricity. It has been suggested that it could play a role in orienting attention to a novel stimulus 2°. Previous anatomical studies using the retrograde H R P technique showed strong thalamic as well as corticocortical afferents to this area. The most prominant loci of thalamic labeling were the suprageniculate nucleus and parts of the posterol a t e r a l n u c l e u s 2°,29,34 and the majority of the corticocortical connections originated from associative cortices 2°.
This variety of inputs fits with the various functions that have been attributed to this area. Indeed the OIC has been implicated in such various functions as somatic 27 auditory T M and visual processing 3,6,12, as well as vascular and respiratory regulation 23, vagal activities 26, and taste and olfaction sensationZL In addition, the results established with electrophysiological techniques agree with these observations, as was shown by Fallon and Benevento 13. Single units recorded from the OIC are reactive to both visual and auditory stimuli, as are the units recorded from other associative areas of the cat's cortex 3°. The role played by the OIC has been the subject of a series of ablation experiments. Thus, Colavita et al. 7 propose that it is a multimodal area concerned with the perception of temporal sequences
Correspondence: E. Maire-Lepoivre, Laboratoire des Neurosciences de la Vision, Universit6 Pierre et Marie Curie, 4 Place Jussien, 75230 Paris 05, France. 0166-4328/86/$03.50 © 1986 Elsevier Science Publishers B.V. (Biomedical Division)
54 of stimuli such as different auditory frequencies and different light or vibrotactile intensities. Schalg-Rey and Lindsley 35 suggest that this frontal area may play a critical role in tasks requiring flexibility in visual orienting, selective attention, anticipation of events and use of visual responseproduced cues. Consequently, a question of major interest is the behavioral function of the OIC. One approach to answering this question is to determine the behavioral capacities that are disrupted as well as those that remain after selective lesion of the OIC. In the present experiment, chemical lesions with the neurotoxin ibotenic acid were carried out. The great advantage of ibotenate lies in its lack of epileptogenic properties and its ability to produce restricted specific lesions without damaging fibers of passage ~°. Behavioral tasks were chosen to gain an insight into the nature of neural processes disrupted by OIC damage. The first of these was the ability of pre- and postoperative cats to orient the head and eyes to a stimulus presented in particular locations in the visual field, tested with the use of the perimetry method of Sherman 36. In a second study, we tested the possibility that OIC is involved in discrimination performance. Sprague et al. 4~ showed that there are cortical areas involved in simple pattern form discrimination which lie outside areas 17 and 18. It appears likely that many areas of the cortex lying in the suprasylvian sulci (LSA), posterior suprasylvian cortex (area 21 and part of area 19), the lateral gyrus and perhaps other, as yet undefined cortical regions, participate in some integrated fashion in form perception and discrimination in the cat. These methods were used to determine whether or not the ability to discriminate and to orient is differentially disturbed by a lesion of the OIC.
a day (4 h after the daily testing session) and maintained at approximately 90 04 of their normal body weight. All cats were initially trained and test on each visual task described below. They were divided into experimental and control groups. In the experimental group, 2 animals received a unilateral lesion of the orbito-insular cortex (OIU) and 2 animals a bilateral lesion of the same region (OIB). The 2 control animals were shamoperated. For all cats, after a 3-week break, the tasks were presented in the same order as during the original testing.
Surgery Surgery was performed under aseptic conditions. Cats were anesthetized with Alfatesine (0.3 ml/kg/h, i~v.) and positioned in a Narishige stereotaxic instrument. The approach to the orbito-insular cortex was accomplished stereotaxically through the frontal cortex with a 30 ° angle of penetration, thus avoiding enucleation (see Fig. 2B). The microinjections of ibotenic acid (Sigma) were made using a 10-#1 Hamilton syringe fitted to a stereotaxic holder. The outer diameter of the needle was approximately 250 ~m. A volume of 1-2.2 #1 (10 #g//A) of ibotenic acid, dissolved in phosphate buffer (0.1 M pH 7.4), was infused during 15-20 min at 3-5 different depths. After each injection, the needle was left in situ for an additional 10 min to check for backfiow along the needle tract. The control and experimental cats were identically treated, in that the dura was broken and the needle was lowered into the white matter just beneath the OIC in order to avoid a mechanical lesion of the cortex. In the control animals, no injection was made.
MATERIALS AND METHODS
Subjects Six experimentally naive young adult cats were used as subjects. At the beginning of the experiment, they were 7 months old. They were housed together in a special room with a 12 h light-dark cycle. Throughout testing, the cats were fed once
Apparatus and testing methods For all cats, the tests were presented in the order in which they are described. Localization and orientation. Ability to localize and orient to a stimulus in the visual field was tested using perimetry methods described in detail by Sherman 36. A table-top was divided by radial
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Fig. 1. Apparatus and testing method for the localization and orientation test.
lines into twelve 15 ° sectors, extending 75 ° to either side of a 0 ° central guideline. The table-top was delimited by a cylindrical screen of 70 cm diameter with holes corresponding to each guideline (Fig. 1). The cat was placed in the center of the table-top and his head and body were restrained by an experimenter so that the nose was directed along the 0 ° central guideline and the lateral canthi of the eyes were aligned with the 90 ° left and right guidelines. The cat was trained to attend to the central preconditioning stimulus (an empty spoon). While the cat was fixating, a second stimulus (spoon with cat food) was introduced in front of the cat along one of the guidelines through a window 3 cm wide. This stimulus entered the visual field at 35 cm from the cat's nose (at the level of the cylindrical screen). The cat was then freed and its responses noted. A positive respons was scored if the cat immediately oriented the head and eyes toward the second stimulus. Any other behavior was scored as a negative response. Only positive responses were rewarded with a piece of cat food. All testing was first binocular and then monocular, in which case one eye was occluded with a large opaque mask. Each eye was tested separately on the same day, and each daily session usually consisted of 4 trials along each guideline. The order of presentation for each guideline was varied according to a pseudo-quasi random series. Testing was continued for 30 trials along each guideline in binocular and monocular viewing.
One cat (OIU2) was tested to assess the performance and the recovery 3, 6 and 9 weeks after the lesion. Two-choice pattern discrimination. A two-choice discrimination apparatus, similar to that described by Spear and Braun 38, was used for visual discrimination training and testing. It consisted of a rectangular box (150cm long x 56cm wide × 50 cm high), with a start panel at one end and two choice panels at the other end and with a vertical separation along the centre of the box. Each choice-panel contained a 16.5 cm high × 11 cm wide stimulus screen onto which stimuli were rear-projected by two slide-projectors. The choice-panels were hinged at the top and the cat was required to push them open to gain access to the 'food-plate' placed outside the box just beneath each choice-panel. A reward of cat food was delivered if the cat made the correct choice. Three discrimination tasks were employed. The first was a brightness discrimination between a light and a dark stimulus screen. The second was a discrimination between an array of horizontal stripes and a array of vertical stripes projected on each stimulus screen. The third discrimination was between an upright isoceles triangle projected on one stimulus screen, and an inverted isoceles triangle projected on the other. All cats were trained on the 3 tasks in the order of description. Retention testing followed the same order of task presentation. Trial-to-trial position of the positive stimulus was varied from the right and left choice door according to a quasi random series. Usually, 40 trials were given each day, 5 days a week. Training on each task was continued until a criterion of 36/40 correct choices in two consecutive daily blocks of 40 trials was reached.
Histological procedures At the end of the experiment, the animals were deeply anesthetized with pentobarbital sodium (40 mg/kg, i.p.) and perfused intracardially with 0 . 9 ~ saline followed by 10~o formol-saline. The brain was removed from the skull and placed in 10~o formol-20Yo sucrose-saline for a week. It then was cut serially at 50 #m thickness in the
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Fig. 2. A: localization of the orbito-insular cortex (OIC) in the cat. B: frontal section of the cat brain showing the penetration of the microsyringe needle through the frontal cortex to the OIC. C, D, D', E: photomicrographs illustrating the damage to the OIC caused by an injection ofibotenate. Frontal section stained for cell bodies with Cresyl violet. C: contralateral O1C at the level of the lesion. D: photomicrograph centered on the lesion showing needle track and reduction of the cortex width (Bar = 1 mm in C and D). D': schematic representation of the lesion's extent (surrounded by dotted lines). E: high power micrograph of the lesion in D; the lesion affects the deep layers of the cortex Bar = 100/~m).
57 frontal plane on a freezing microtome. Sections were processed histochemically to localize the lesion sites using either P A G E or Nissl-staining. Lesion reconstitutions were plotted through the brain with the aid of the atlas of ReinosoSuarez 33.
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Histology Fig. 2 shows an example o f the lesion made with ibotenic acid in one cat (OIB1). There is a considerable loss o f neuronal cell bodies in the damaged area c o m p a r e d with the normal one. Light microscopic analysis revealed that ibotenic acid p r o d u c e d a marked disappearance o f nerve cells over a restricted range. Axons o f passage did not seem to be damaged. A small number of apparently healthy neurons can be seen, but most o f the cells in the damaged area are glia. Nevertheless, it is very difficult to etablish the real extent o f the lesion after long survival times 9'1°. H o w ever, in all cases, the needle tract could be localized and the tip o f the needle was in the OIC or in the b o t t o m o f the anterior ectosylvian gyrus (see Fig. 3 for summary): the lesion site could be estimated to be in the dorsal bank of the OIC. In the two control cats (sham-operated), the needle tract was also localized. In their case, there was just a mechanical lesion, due to the passage o f the needle through the underlying white matter, with no damage in the cortex.
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Fig. 4. A: percentage correct responses as a function of training sessions before and after surgery for one cat. Forty trials per day were given. B: number of trials required to reach criterion performance on the 3 two-choice discriminations for the 3 experimental groups of cats. Scores for individual cats are shown by the dots. Filled dots: preoperative scores, empty dots: postoperative scores.
Two-choice pattern discrimination The brightness discrimination data, as well a the pattern discrimination results, are quite consistent for the 6 subjects. F r o m 400 to 600 trials were required for the cats to reach criterion preoperatively. The numbers of training trial blocks required for the cat O I U 2 to reach criterion performance successively on brightness, horizontal-vertical grating and upright-inverted triangles discrimination before and after the lesion, are shown in Fig. 4A. Following the retention period the normal cats continued to show the same performance; no relearning was necessary to reach criterion. The results for cats with unilateral or bilateral OIC lesions were very similar to those for normal cats. Following the lesion, no lack of retention was observed. Fig. 4B shows results before and after the operation for the 3 experimental groups.
58 Localization and orientation In agreement with Sherman 37, preoperative cats responded binocularly to objects presented anywhere in the region bounded approximately from 75 ° right lateral to 75 ° left lateral, the most peripheral guideline tested. The monocular visual fields were found to measure approximately from 75 c ipsilateral to the open eye to 45 ° contralateral. Thus the binocular segment of the visual field includes the region bounded bilaterally by about 45 °, and the monocular segment of each side begins approximately at the 45 ° contralateral guideline. This agrees well with previous studies using similar methods (e.g. refs. 36,39). Normal cats. The binocular performance of the two sham-operated cats was practically identical following surgery. With monocular viewing, preand postoperative data are also approximately the same (Fig. 5).
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Unilateral lesions. After a unilateral lesion of the OIC, in binocular viewing, we observed deficits only for the most peripheral guidelines: the unilateral lesion of the OIC has no detectable effect on the ability of the cats to orient rapidly to a stimulus presented in the binocular segment of the visual field. However, we observed a deficit in both monocular segments which was larger in the segment ipsilateral to the lesion. In monocular viewing, as in binocular viewing, the binocular segment of the visual field was not affected. In the monocular segment ipsilateral to the lesion, there was a total lack of response to stimuli presented along the 75 ° guideline and a large deficit along the 60 ° one. In the contralateral monocular segment, we observed a large deficit along the 75 ° guideline and a fall in the performance along the 60 ° guideline
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59 increased considerably (1-3 s). The ability to shift attention to a test stimulus seems to be diminished. This effect is only observed when the stimulus is presented in both monocular segments, even with the unilateral lesion. The ability to orient to a test stimulus presented in the binocular segment is not affected by unilateral or bilateral lesions. Case of the cat OIU2. This cat, with a unilateral lesion of the OIC, was retrained on the perimetry task 3, 6 and 9 weeks after the operation. Fig. 6 shows the performances during those tests. In the binocular segment, the 3 sets of perimetry data were similar to those observed before the lesion. The decrease of the performance in the monocular segment disappeared completely after 9 weeks. This recovery was different depending on the guidelines: the slowest recovery being for the most peripheral stimulus. In monocular viewing, the recovery of preoperative performance along the far nasal guide-
In both monocular segments, we noted a decrease in performance along the far nasal guideline (45 °). Bilateral lesions. During the binocular viewing tests, the performances observed in the binocular segment of the visual field were the same before and after the lesion. The bilateral lesion of the OIC affect only the performance along the 60 ° and 75 ° guidelines. With monocular viewing, performance decreased in both monocular segments, with a total loss of responses at the 75 ° guideline and a large deficit along the 60 ° one. The decrease in performance observed along the far nasal guideline (45 °) was similar to those observed after a unilateral lesion of the OIC. In cats with OIC lesion, the fixation time to the central stimulus was longer after the lesion than before. Before the lesion, the cat showed an immediated motor response (orientation to the second stimulus); after the lesion, the latency
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60 line (45 °) was observed after 6 weeks, but 9 weeks were required before the performance on the 75 ° and 60 ° guidelines recovered to preoperative levels. DISCUSSION
The results of this study provide clear evidence that lesions of the OIC do not affect performance of either form or brightness discrimination tasks. On the other hand, the same lesions have a marked effect on the performance of a perimetry task. Histology One interesting property of ibotenate is its ability to produce specific spherically circumscribed neuronal lesions: the toxin kills the neuronal cells bodies, but does not damage axons of passage and no neuronal degeneration distant from the site of application has been observed ~°'25. This fact is very important in areas such as the O1C where many fibers of passage could be distroyed during mechanic, electrolytic or radio-frequency lesions. Another advantage of ibotenate is its low tendency to generate epileptogenic loci. Ibotenate does not cause electroencephalographic seizures at intracerebral doses < 3/~g, i.e. it is at least 1000 times weaker as a convulsant than kainate ~. Discrimination Campbell 4 has discribed deficits in pattern discrimination after lesions in areas 20 and 21 in the cat and has compared this part of the cat brain with the inferotemporal cortex of the rhesus monkey. Furthermore, his finding of a deficit following a lesion placed in a cortical target area of the pulvinar nucleus, without involvement of any part of the geniculocortical system, area 19 or LSA, is in agreement with the results of Sprague et al. 4~ and Bauman and Spear 2. In other studies, removal of the superior coUiculi has resulted in deficits of pattern discrimination in the cat 4°. OIC receives a collicular projection via the posterior group of the th alamu s ~5.16,17,24,29. These considerations would suggest that the OIC, which is a target of the tectothalamocortical
pathways, might provide a first stage in simple form discrimination. However, after OIC lesions, no lack of retention of visual form discrimination was observed in our experiments. The seeming discrepancy between these results and our hypothesis can be resolved by the fact that such tests are not appropriate because the OIC could only be implicated in more complex discrimination tasks ~. Localization and orientation The perimetry method was chosen to test the ability of the animal to attend to a fixation stimulus and orient the head and eyes to a new stimulus presented anywhere within a wide area of the visual field. The extent of the visual fields, in monocular or binocular viewing, observed during our experiments with sham-operated or preoperated animals are in agreement with those found by Sherman 37 and Spear et al.39 under similar testing conditions. Following OIC lesions, we observed a neglect of the most peripheral part of the visual field. This bilateral neglect was present after both uni- and bi-lateral lesion. Moreover, in both experimental groups of animals, the same deficits appear for stimuli presented in the two monocular segments of the visual field with no effect on performance in the binocular segment (Fig. 5). In our experiments, the cats recovered from all of the behavioral deficits induced by the ibotenate injection. This recovery was delayed in the monocular segment for the more peripheral guidelines (Fig. 6). These deficits disappear within 6 - 9 weeks according to data of Steele Russel and Pereira 42. The complete recovery shown by our results may have had contributions from several sources. (1) Neural mechanisms within the damaged area: it is possible that neurons were temporarily inactived by the ibotenic acid, but recovered since their exposure to the toxin was sublethaP 2, especially in the superficial layers of the cortex which showed no visible damage in histological control (Fig. 1). (2) Behavioural compensation: it is possible that compensatory readjustment occurs rather then functional recovery 42. (3) Alternatively, behavioral recovery may be mediated
61 by other tectocortical pathways such as those involving cruciate and presylvian sulci 18't9. In our experiments, after unilateral lesion of OIC, we observed a bilateral neglect in both monocular segments of the visual field. This result may be related to those obtained in the monkey. For Latto and Cowey 28, unilateral frontal eye field (FEF) lesions induced a neglect limited to the contralateral visual hemifield. More recently, Crowne etal. ~2 showed that unilateral F E F lesions produced not only a neglect of stimulus lights contralateral to the side of the lesions, but also responses to the most peripheral of the ipsilateral stimulus lights were affected as shown in increased errors and response latencies. In the present experiment we observed this increase in latencies, but in both monocular segments. This result may be related to the anatomical finding 5"29 of heavy reciprocal transcallosal connections between the two OIC. Indeed, Crowne et al. 12 showed that a callosal section aggravates the deficits caused by unilateral F E F lesion, or reinstates them after spontaneous recovery. It seems clear that even if the OIC could be considered as a part of the oculomotor areas in the cat 18'19"31, it is not involved in the same operations as the frontal eye field of monkeys 28. The behavioral patterns observed during our experiments were more similar to those observed by Jeannerod et al.2~, for whom bilateral frontal lesions in cat induced an increase in fxation to a central stimulus and also a perseveration in pursuit eye movements in response to a moving target. For these authors, the frontal regions play a role in 'defixation'. This hypothesis is in agreement with Velasco and Lindsley's suggestion 44 that the OIC is involved in inhibitory activity. Deficits observed during the presentation of a stimulus in the monocular segments of the visual field could result from a failure to detect the target or from a problem in shifting attention to a novel stimulus. Similar patterns of neglect have been observed after bilateral lesions of the superior colliculus. Thinus-Blanc 43 has suggested that the superior colliculus could be an element of a system which modulates attentional changes. This interpretation is consistent with our previous anatomical
s t u d y 29 which showed that OIC receives inputs from the suprageniculate nucleus, a part of the posterior group of the thalamus which receives strong collicular projections from the most lateral part of the n u c l e u s 15"16"17"24. Furthermore, Guitton and Mandl ~s'19 showed the existence in the OIC of cells discharging only when the untrained animal attended to, and tracked, an object of interest. These data are also in agreement with the hypothesis of Latto and Cowey 28 who proposed that this oculomotor area plays a role in the purposeful scanning of the environment. Thus, our results give support to the idea that the OIC is involved in the shift of attention which occurs particularly in the early stage of the orienting reaction. ACKNOWLEDGEMENTS
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