Brain Behav. Evol. 12: 57-74 (1975)

Bilateral Sensory Neglect following Midsagittal Reticular Formation Lesions in C ats1 H arold P. G reeley , Susan J. H agamen , W ilbur D. H agamen and A lexander G. R eeves Division of Neurology, Department of Medicine, Dartmouth Medical School, Hanover, N.H.

Key Words. Frontal lobes • Neglect • Striatum • Increased attention • Olfactory tubercle • Midsagittal • Reticular formation Abstract. We have observed that midsagittal reticular formation lesions in cats produce bilateral deficits in attention to and localization of various sensory modali­ ties. To correlate these changes with previously reported changes following lesions in other areas of the brain, we propose the existence of two interdependent inhibito­ ry pathways which originate in the frontal lobes.

Introduction Alterations in attention and responsiveness have been produced by a variety of lesions in cats and monkeys [B ard and R ioch , 1937; H agamen ct al., 1959; W atson et al., 1974; K ennard , 1944; S prague et al., 1961]. Unilateral frontal lobe lesions make cats and monkeys relatively unres­ ponsive to tactile [K ennard , 1944; W elch and Stuteville , 1958; W at­ son et al., 1974], nociceptive [B ard and R ioch , 1937; H agamen et al., 1959; L angworthy and K olb , 1935; R eeves and H agamen , 1971], vis­ ual, and auditory stimuli [H agamen et al., 1959; R eeves and H agamen , 1971], applied to the side of the body contralateral to the lesions. There is increased attention to these same stimuli when applied ipsilaterally [B ard and R io ch , 1937; H agamen et al., 1959; R eeves and H agamen , 1971]. This is manifest as perseverative following the lack of habituation. That these results are not due merely to interruption of main sensory pathways is indicated by the observation that bilateral frontal lobe abiaDownloaded by: Nagoya University 133.6.82.173 - 1/15/2019 6:36:39 AM

1 Supported by grant MH25621 from NIMH.

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tions produce increased attention and following in both directions [H agaet ai, 1959; L angworthy and K olb , 1935; M agoun and R anson , 1938], and with unilateral lesions true allesthesia to tactile stimulation of the body contralateral to lesions has been reported [W atson et al., 1974]. Unilateral, total or deep aspiration of the superior colliculus in cats causes contralateral neglect to visual, auditory, tactile, and nociceptive stimuli [M eikle and Sprague , 1962; Sprague and M eikle , 1965]. Uni­ lateral lesions of the subcollicular tegmentum in cats and monkeys [R eeves and H agamen , 1971; Sprague et al., 1961, 1963; Sprague and M eile , 1965; W atson et a l, 1974] produce contralateral deficits in vis­ ual, auditory, tactile and nociceptive responsiveness and this is present whether the primary sensory pathways are involved or not [R eeves and H agamen , 1971; W atson et al., 1974], Bilateral lesions of the entire su­ perior colliculus [Sprague and M eikle , 1965] and the underlying teg­ mentum [M yers, 1964] produce bilateral deficiencies in responsiveness to visual, tactile, and olfactory stimuli. An hypothesis consistent with the above observations predicts that narrow, midsagittal brain lesions, if sufficiently long and properly posi­ tioned, will result in bilateral deficits in responsiveness to sensory stimuli. To test the hypothesis, cats were subjected to a series of midsagittal brain lesions. men

Method

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25 adult, untrained, male and female cats, randomly chosen for behavioral test­ ing and operation, were used. Each was placed in one of five groups determined by the intended anterior-posterior and dorsal-ventral extent of the stereotaxically placed [ J a s p e r and A j m o n e -M a r s o n , 1960] midsagittal brain lesions. Group Cl le­ sions (3 cats) extended from A7 to P10 and from the dorsal surface of the brain down to the ventricular system (fig. 1). In the remaining four groups the lesions ex­ tended from the dorsal surface to the ventral surface of the brain. Group C2 lesions (4 cats) extended from A20 to A7 (fig. 2). Group LI lesions (7 cats) extended from A7 to APO in six cats and from A14 to APO in one (fig. 3). Group L2 lesions (6 cats) extended from APO to P6 in two cats and from APO to P10 in four (fig. 4). Group L3 lesions (5 cats) extended from A7 to P6 (fig. 5). Groups Cl and C2 were utilized as controls. Behavior was tested with the cat in a 4X 4X 2ft high pen which was placed in a small, well-lighted room. Procedures were designed to evaluate responsiveness to auditory, visual, tactile, nociceptive, and olfactory stimuli in the unrestrained ani­ mal. Auditory evaluation was based on movements of the head and body in orienting

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to and following various noises such as rattle of keys, finger snapping, loud tapping sound, paper crackle, and pencil dropping on the floor. Visual evaluation was based on movements of the head and body in orienting to objects suddenly introduced into the visual field such as empty or full food pans, moving string, moving fingers or hand, falling pencil, and a falling paper ball. Abil­ ity to follow objects rapidly moving from the midline to a lateroposterior position, and to circle in response to more slowly moving stimuli was studied. The use of vi­ sion in aiding specific localization of nociceptive stimuli was observed. Blink re­ sponse to a threatening stimulus and pupillary light reflexes were also tested. Tactile evaluation was based on head, limb, and body movements in response and orientation to stroking the paw lightly, stimulating the perigenital region, strok­ ing the side, stroking the posterior midline, scratching the neck, and supporting a full or empty food pan on the shoulder. Nociceptive evaluation was based on the briskness of affective response, and ori­ entation, both gross and specific, to pinching the thigh, paws or tail. Olfactory evaluation was conducted by observing sniffing, approach and orienta­ tion to a pan of food placed in various areas of the testing pen, and placed on the cat’s shoulder. Following rapidly to the side, with the food-containing pan as the stimulus, and circling were also observed. The cats were fasted 12-24 h prior to such testing. Cats were tested postoperatively and preoperatively. Testing was usually con­ ducted twice preoperatively and three or more times postoperatively. Postoperative testing was conducted in the interval between 6 and 24 months after operation. All animals had stabilized by 3 months after operation but the time period chosen leaves no doubt as to the chronicity of the observed behavior. Cats were scored 0 (no response) to 6 (fully responsive) on each test conducted, and were given separate scores for the right and left sides of the body if any asym­ metry was noted. The results were statistically analyzed for each test. First, each test was studied for its distributive properties by performance of normal equivalent deviate analysis, and when necessary the scores were transformed to logarithms or square roots to establish the property of normal distribution. It is these normally distributed raw scores or transformations upon which all subsequent analyses were performed. Variance analysis was then utilized to determine the statistical signifi­ cance (0.05 level) of differences observed preoperatively to postoperatively and of differences observed between the animal groups. All of the cats were utilized in four different postoperative comparisons. First, the controls (Cl and C2) were com­ pared with each other. Then, the controls (Cl and C2) were compared with the reti­ cular lesion groups (LI, L2, and L3). Finally the rostral reticular lesions group (LI) was compared with the caudal reticular lesion group (L2), and the combined reticu­ lar lesion group (L3) was compared with the two shorter reticular lesion groups (LI and L2). AH operations were performed using intravenous pentobarbital anesthesia and sterile technique. After retraction of the skin and muscles, a symmetrical 1 by 2-3 cm midsagittal opening was made in the skull. The center of the tentorium was removed where necessary. The dura was incised close to the sagittal sinus over the cerebrum and in the midline over the cerebellum. Following retraction of the dura, the stereotaxically oriented lesion was produced with a blunt 1 by 3 mm spatula in-

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troduccd into the brain at 1 mm intervals, or a 1 by 1 mm spatula introduced every 0.5 mm. The dura was not sutured, nor was any bone replaced. Muscles and skin were approximated, and the cat was allowed to recover from the anesthesia. After complete testing, cats were anesthetized with pentobarbital and perfused through the heart with normal saline followed by 10% formalin. The brains were re­ moved, further fixed in 10% formalin, and embedded in celloidin. Brains were serially sectioned at 50 itm. Every fifth section was preserved through the lesion site, and every tenth section anterior and posterior to the lesion. Alternate sections were stained by Weil and NissI techniques.

Results Cats with midsagittal lesions of the rostral (LI), caudal (L2), or total (L3) reticular formation demonstrated statistically significant deficits in attention and responsiveness to unilateral or bilateral sensory stimuli in­ volving audition, vision, olfaction, nociception, and touch. Cats with midsagittal lesions anterior to or above the reticular formation (Cl, C2) did not have such deficits. General Description

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The animals within each group showed a range of activity, and no sin­ gle lesion produced a consistent decrease or increase in spontaneous mo­ tor activity. Groups C l and C2 recovered relatively quickly from the op­ eration. They began to stand and walk in 1-3 days and began to eat spon­ taneously in 2-7 days. Improvement occurred over the next 3-4 weeks, but a mild posterior limb and trunk ataxia persisted in group C l. Groups LI and L2 began to stand and walk in 1-12 days and to eat spontaneous­ ly in 1-13 days. These functions improved slowly over the next 4-6 weeks. Group LI had persistent high-stepping in all limbs, while group L2 had a persistent, moderate posterior limb and trunk ataxia. Group L3 began to stand and walk in 4-20 days and to eat spontanesouly in 10-30 days. Recovery progressed for as long as 3 months. All L3 cats persist­ ently exhibited high-stepping in all limbs and moderate to marked ataxia. In three cats the ataxia was marked, movements were slow and poorly coordinated, and the head was held low, often cocked to one side. They never walked completely upright and often fell. They did not clean them­ selves and their fur became matted over the back. One cat persistently cir­ cled to the right with or without stimulation of any sort. One cat re-

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Table I. Descriptive title of each test conducted 1 Looks at pencil thrown within visual field 2 Looks at paper balls thrown within visual field 3 Watches string waved within visual field 4 Responds to stroking posterior paw 5 Follows rapidly moving full food pan 6 Hears snapping fingers 7 Hears pencils landing on floor 8 Responds to stroking side 9 Specific localization of tail pinch 10 Gross localization of tail pinch 11 Affective response to tail pinch 12 Hears paper balls landing on floor 13 Hears loud tapping sound 14 Hears rattling keys 15 Circles for full food pan 16 Circles for empty food pan 17 Follows rapidly moving empty food pan 18 Circles for moving string 19 Follows rapidly moving waving string 20 Circles for snapping fingers 21 Affective response to anterior paw pinch

22 Affective response to posterior paw pinch 23 Gross localization of anterior paw pinch 24 Gross localization of posterior paw pinch 25 Specific localization of anterior paw pinch 26 Specific localization of posterior paw pinch 27 Gross localization of thigh pinch 28 Affective response to thigh pinch 29 Specific localization of thigh pinch 30 Responds to empty food pan by shoulder 31 Responds to full food pan by shoulder 32 Localizes perigenital stimulation 33 Affective response to perigenital stimulation 34 Responds to stroking anterior paw 35 Localizes empty food pan in pen 36 Localizes full food pan in pen 37 Watches moving hand 38 Responds to stroking over dorsal midline 39 Responds to neck scratching

covered to the same degree as the group LI and L2 animals, but clouding of its right cornea caused at least partial blindness in that eye.

Analysis of Specific Sensory Modalities

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Each sensory modality was evaluated by a number of individual tests. Table I provides descriptive titles for each test. Table II summarizes the statistical analysis of each test. By placing the individual tests in catego­ ries corresponding to the modality being tested, it is possible to ascertain whether the responsiveness in that modality was changed by any of the

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Table II Auditory

Visual

Olfactory

Affective

Nociceptive Tactile

Absolute mine (average) Prcop. Cl C2 LI L2 L3

5.81 4.00 4.51 1.87 0.68 0.01

5.45 4.52 4.32 1.73 2.77 0.76

5.66 4.95 4.89 1.15 2.19 1.18

5.61 5.78 6.00 5.54 5.53 5.74

5.60 5.78 5.31 3.08 4.02

o.so

4.59 3.65 4.35 1.88 2.62 0.95

Decrease, % Cl C2 LI L2 L3

31 22 68 8S 100

17 21 68 49 86

13 14 80 61 79

0 0

0

0 5 45 28 86

20 5 59 43 79

Significance o f Cl C2 LI L2 L3

difference 0 0 -1 _2 -3

0 0 -2

0 0 -2 -1 -2

0 0 0 0 0

0 0 -2 -1 -3

0 0 -1.5

-1 -3

1 1

-1 -3

Variations in the negative values indicate significant differences from preoperative to postoperative levels and between the lesion groups; the more negative the value, the greater the deficit. A zero indicates a nonsignificant difference.

five lesions. In addition, the analysis could indicate the significance of variations in responisveness between the various lesion groups. Several of the individual tests were placed in more than one sensory category. This was considered necessary because some of the tests clearly provided more than one type of sensory stimulus.

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Auditory Tests The lesions of groups LI, L2, and L3 caused a significant decrease in auditory responsiveness. This decrease was manifest when preoperative and postoperative levels were compared, and when groups C l and C2 were compared with groups LI, L2, and L3. In 2 of 6 tests, group C l also demonstrated a significant loss of responsiveness. The deficit was greatest in group L3, less in group L2, and least in group LI.

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Visual Tests The lesions of groups L I, L2 and L3 caused a significant decrease in visual responsiveness. This decrease was manifest when preoperative and postoperative levels were compared with each other, and when groups C l and C2 were compared with groups L I, L2 and L3. In one test, group C l also demonstrated a significant loss of responsiveness. The deficit was greatest in group L3, less in group L I, and least in group L2. Olfactory Tests The lesions of groups L I, L2 and L3 caused a significant decrease in olfactory responsiveness. This decrease was manifest when preoperative and postoperative levels were compared, and when groups C l and C2 were compared with groups L I, L2, and L3. The deficit was greater in group LI than in group L2, and was not consistently greater in group L3 than in group LI. Tactile Tests The lesions of groups L I, L2 and L3 caused a significant decrease in tactile responsiveness. This decrease was manifest when preoperative and postoperative levels were compared, and when groups C l and C2 were compared with groups L I, L2 and L3. Group L3 showed a greater de­ crease than groups L I and L2. There was a suggestion that group L I was less responsive than group L2. Responsiveness to neck scratching (test 39) showed a nonsignificant deficit from preoperative to postoperative levels and groups C l and C2 were not significantly different from groups L I, L2, and L3. Tactile responsiveness to a special stimulus, perigential stimulation (test 33), was not significantly changed when preoperative and postopera­ tive levels were compared. Tactile responsiveness to stroking the spine (test 38) appeared to in­ crease in groups C l, C2, L I, and L3, but actually there was a nonsignifi­ cant difference from preoperative to postoperative levels.

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Nociceptive Test The response to nociceptive stimuli seemed best analyzed by looking first at the animal’s immediate affective response to the stimulus, that is, whether the cat quickly expressed anger or tried to escape. Then we noted the animal’s ability to localize, both grossly and specifically, the site of the painful stimulus.

G reeley/H agamen/H agamen/R eeves

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Nerve VIT Nerve 8 Nuc. Vr

*8rachium Pontis ' Sup.Olivary Nuc.

VIII Rest ¡form Body

F ig.l. Group Cl. Cat No. 50. The stippled area indicates microscopic cell and fiber loss. The black area indicates gross destruction.

Nociceptive (affective) test. No change was detected in immediate affective response to a nociceptive stimulus. Nociceptive (gross and specific localization) test. The lesions of groups LI, L2, and L3 caused a significant decrease in the localization of noci­ ceptive stimuli. The decrease was readily noted when groups C l and C2 were compared with groups LI, L2, and L3, but was slightly less evident when preoperative and postoperative levels were compared. The deficit was greatest in group L3, less in group LI and least in group L2. Summary of all Tests The results described above are summarized in table II, which was composed by taking average values for each modality.

Anatomy and Analysis of Individual Lesion Groups

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Group C l (No. 50, 51, 52). These cats could not be differentiated from normal animals by our sensory testing procedures. Drawings of re­ presentative sections from one of these animals are shown in figure I. In the other two animals, the lesion did not involve the superior colliculus, and there was only slight leftward asymmetry of the lesion track.

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Group C2 (No. 4, 26, 38, 41). These cats could not be differentiated from normal animals by our sensory testing procedures except that they did not blink to threatening stimuli. Drawings of representative sections from one animal are shown in figure 2. These sections are typical of the midsagittal lesion ventral to the corpus callosum and of the fornical de­ generation seen in all four cats; however, in one cat the asymmetry was to the right. Another had more extensive cortical destruction than illustrated and it was on the side opposite the subcallosal lesions. One cat had mini­ mal cortical loss, but had a symmetrical vascular lesion involving the medial and dorsal amygdala, the medial globus pallidus, the interpedun­ cular nucleus, the ansa lenticularis, and the internal capsule. Cat 4 had only minimal destruction of the cortex, including part of the cingulate gy­ rus. Group L I (No. 3, 13, 22, 42, 43, 44, 45). These cats showed deficits in attention and orientation to auditory, visual, olfactory, nociceptive, and tactile stimulation. They could not follow rapidly moving visual stimuli to either side, nor would they circle for more slowly moving stimuli even though the stimulus was food. Pupillary light reflexes were deficient in all cats. Blink response to threat was absent bilaterally in five cats, absent on the right in cat 42, and present bilaterally in cat 44. Drawings of repre­ sentative sections of cat 43 are shown in figure 3. Cat 44 was quite simi­ lar in its lesions, while cats 22, 45, and 13 had slightly less cortical dam­ age and the lesion was not so wide in the area of the red nucleus. Cat 42 had more cortical loss, but a narrower subcallosal lesion. Cat 3 had a le­ sion longer than the others, extending forward to A14. In the reticular formation its lesion was similar to the above cats in its group, and anter­ ior to this was similar to cat 41. However, this cat also had marked lateral ventricular dilatation, greater on the right than on the left. It was one of the two least responsive cats in this group, the other being cat 45 which had the smallest overall lesion and no ventricular dilatation. Group L2 (No. 11, 14, 23, 46, 48, 49). Auditory inattention was more marked here than in group LI. Deficits in visual, olfactory, nociceptive, and tactile responsiveness were readily noted, but were not as marked as in group LI. Pupils were normally responsive to light. Blink response to threat was present. Cat 11 circled to the right spontaneously and cat 49 had the same tendency to a lesser degree. Cat 14 circled to the left spon­ taneously and cat 48 had the same tendency to a lesser degree. The lesion was asymmetric to the left in cats 11, 48 and 49, and asymmetric to the right in cat 14. Drawings of representative sections of cat 49 are shown in

G reeley/H agamen/H agamen/R eeves

Fornix

Fig. 2. Group C2. Cat No. 41.

Fig. 3. Group LI. Cal No. 43.

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Fig. 4. Group L2. Cat No. 49.

Nuc. «I

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Fig. 5. Group L3. Cat No. 30.

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figure 4. They are quite typical of the lesions, the others differing in the side of asymmetry of the lesion, less to no cortical damage, and one cat (45) had more destruction in the superior cerebellum. Group L3 (No. 7, 27, 29, 30, 35). These cats demonstrated the most marked deficits in sensory responsiveness to all stimuli; however, their only 100% deficit was in audition. Blink response to threat was absent. Only cat 29 did not have deficient pupillary responses to light. Cats 7 and 27 circled spontaneously to the right, 7 quite rapidly, 27 slowly and labo­ riously. Drawings of representative sections of cat 30 are presented in fig­ ure 5. The lesion was similar in cats 27 and 35. In cats 29 and 7, there was more cortical destruction, and in 7 there was a wider lesion in the medulla.

The data indicate that a midsagittal lesion of the rostral and/or caudal reticular formation caused cats to be relatively inattentive to auditory, visual, olfactory, nociceptive, and tactile stimuli applied to either side of the body. This was manifest as bilateral deficits in localization and atten­ tion. There was an associated deficit in following stimuli which were rap­ idly moved to the side, and in circling to more slowly moving objects. Rostral reticular midsagittal-lesioned cats had 16-19% greater deficit in vision, olfaction, nociception, and touch, and 20% less deficit in audi­ tion, than did caudal reticular midsagittal lesions. Animals with rostral re­ ticular lesions also demonstrated deficiencies in pupillary light responses, and in blink response to threatening stimuli. The effects of a combined rostral and caudal reticular lesion were greater than those of the smaller rostral or caudal lesion in each modality, with the unexplained exception of olfaction. Thus, the effects of the two smaller lesions are additive to a certain degree, but only auditory responsiveness was completely lost with the larger lesion. Four of the cats of group L3 also had severe motor incapacitation, making testing more difficult and raising the question of motor ability to respond. Despite these difficulties, and after careful evaluation, we felt that these cats were truly less responsive. Support for this statement lies in cat 35, which had no significant motor incapacitation (only a moderate posterior ataxia and high-stepping). It was the most responsive animal in its group, but was less responsive than cats with the shorter lesions.

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Discussion

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Affective response to nociceptive stimulation was not substantially changed. Thus, it would seem that the cats were aware of the stimulus, but failed in gross and, especially, specific orientation to the nociceptive stimulus. Dorsal midline responsiveness to stroking was not decreased, but only a few centimeters from the midline, the tactile deficit was evident. Tactile responsiveness to neck scratching showed no deficit. All cats readily blinked when periorbital hairs were touched; and tactile respon­ siveness on the forepaws, while diminished, showed less deficit than on the hindpaws, where it was markedly impaired. Tactile responsiveness was therefore more deficient caudally and became progressively less defi­ cient toward the neck and head of the cat. The hypothesis tested by these experiments correlates the alterations in behavior resulting from unilateral and bilateral frontal lobe lesions, from unilateral and bilateral superior colliculus and subcollicular tegmen­ tum lesions, and from midsagittal reticular formation lesions and behav­ ioral changes resulting from rewarding site stimulation [O’D onohue and H agamen, 1967]. We believe that there are ipsilateral inhibitory pathways (open and closed circles in figure 6A), which originate in the frontal lobes and prob­ ably other areas of the forebrain. These normally exert a tonic inhibitory influence on the various sensory pathways, probably at or near the end organ, represented in figure 6A as the cochlea. In addition, we postulate crossing pathways (open and closed triangles) originating in the frontal lobes, which tonically inhibit the ipsilateral efferent pathways (circles), and that many of the crossing fibers (triangles) pass through or synapse in the superior colliculus or subcollicular tegmentum. Although the path­ ways are represented as uninterrupted arrows, both ipsilateral and crossed pathways are probably multisynaptic and intermixed with many different types of fibers. Various lesions which may interrupt the proposed pathways are shown in figure 6B-F. The expected alterations in behavior and the mechanism of their production, according to this hypothesis, will be described for each of the lesions. The unilateral frontal lobe lesion (fig. 6B) would interrupt the ipsila­ teral inhibitory pathway (open circle); thus, the tonic inhibition to the sensory receptor is removed, and the cat demonstrates increased attention and fails to habituate to stimuli applied to receptors on that side. It also interrupts the crossing inhibitory' pathway (open triangle), thereby remov-

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mg the tonic inhibition to the contralateral efferent pathway (closed circle). The contralateral efferent is now free to exert a stronger inhibitory effect on the receptors of that side of the body. We have studied cats with this type of lesion and they demonstrate decreased attention to stimuli applied contralateral to the lesion [R eeves and H agamen , 1971]. A bilateral frontal lobe lesion (fig. 6C) interrupts the descending inhi­ bitory pathway (circles) on both sides, thus removing the tonic inhibition to sensory receptors bilaterally. The crossing inhibitory pathways (trian­ gles) are also interrupted, but this has no effect since the descending inhi­ bitory pathways are now interrupted. Such a cat demonstrates increased attentiveness to stimuli applied to either side of the body and fails to habi­ tuate to these same stimuli [H agamen et al., 1959]. A unilateral superior colliculus or subcollicular tegmentum lesion (fig. 6D) interrupts only one crossing inhibitory pathway (open triangle), thereby removing the tonic inhibition to the contralateral efferent pathway (closed circle). The proposed resulting tonic inhibition of sensory' reception on the contralateral side produces an animal with contralateral deficits in attention and orientation to stimuli applied to the receptors of that side [M eikle and Sprague , 1962; R eeves and H agamen , 1971; W atson et al., 1974], If the crossing inhibitory pathway is the only path­ way interrupted, the ipsilateral side is unaffected. Bilateral lesions of the superior colliculus or subcollicular tegmentum (fig. 6E) disrupt both crossing inhibitory pathways (triangles), but not the efferent inhibitory pathways (circles), which are now free to exert tonic inhibition of the sensory receptors on both sides of the body. Such a cat has been shown to demonstrate bilateral deficiencies in sensory respon­ siveness [Sprague and M eikle , 1965; M agoun and R anson , 1938]. Further support for the hypothesis comes from the midsagittal reticu­ lar formation lesion (fig. 6F). This lesion interrupts the proposed crossing inhibitory pathways (triangles), thereby removing the tonic inhibition from the efferent inhibitory pathways (circles), and allows them to exert a stronger inhibitory force on both sides of the body. Such cats become re­ latively inattentive to stimuli applied to the receptors on either side of the body. Cats with each of the above lesions have been prepared in our labora­ tory. In each instance the observed behavior of the cat has supported the results predicted by the hypothesis [H agamen et al., 1971; R eeves and H agamen , unpublished]. Further support comes from the work of V oneida [1970] whose report

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Fig. 6. A Diagrammatically represented are the frontal lobes and the superior colliculi with arrows indicating the proposed inhibitory pathways. B Unilateral fron­ tal lobe lesion causing ipsilateral increased responsiveness and contralateral neglect. C Bilateral frontal lobe lesion causing bilateral increased responsiveness. D Unilat­ eral superior colliculus or midbrain reticular formation lesion causing contralateral neglect. E Bilateral superior colliculus or midbrain reticular formation lesion caus­ ing bilateral hyporesponsiveness. F Midsaggittal reticular formation lesion causing bilateral neglect.

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concerns cats with a midsagittal section extending into the mesencephalic tegmentum along with section of fore- and midbrain commissures. The extension of the lesion into the midline of the tegmentum caused loss of the ability to respond to visual cues, although partial recovery occurred over 8-10 months. Some auditory and tactile deficits occurred but lasted only several days to weeks. No other sensory modality was impaired, and no anatomic basis for the visual deficit was found. More conclusive support for the hypothesis may emerge from a study recently conceived, but not yet undertaken. Cats rendered bilaterally defi­ cient in responsiveness after a midsagittal reticular formation lesion should demonstrate increased attention and fail to habituate on the side of a superimposed unilateral frontal lobe lesion (the result of interrupting the ipsilateral efferent inhibitor pathway). If the superimposed lesion is a bilateral frontal lobe ablation, the cat should demonstrate increased atten­ tion and fail to habituate to stimuli applied to either side of the body. There are several possibilities for the somatotopic organization of the proposed pathways. Greater deficits were seen in vision, olfaction, noci­ ception, and touch after the rostral reticular lesion than after the caudal

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reticular lesion. This suggests that the greater concentration of crossing fi­ bers subserving these modalities is situated in the rostral portion of the re­ ticular formation. Varying lesions of lesser anterior-posterior dimensions will be required to determine the presence of more discrete somatopic organization. The greater auditory deficit resulted from the caudal reticular lesion, rather than from the rostral reticular lesion. It is not now possible to state whether the increased deficit is due to the interruption of a greater num­ ber of crossing auditory inhibitory fibers, or to the interruption of the main auditory pathways located in the trapezoid body. Somatotopic organization in the medial-lateral direction is suggested by the retention of dorsal midline and cephalic tactile responsiveness in the midsagiltally sectioned cat. If the ipsilateral inhibitory fibers for the midline and cephalic regions descend close to the midline in the reticular formation, they would be interrupted by the midsagittal lesion. The cat should demonstrate increased attention to tactile stimulation in these areas; there is the suggestion of increased responsiveness to midline strok­ ing as shown in test 38.

Concluding Statements

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We have observed that midsagittal reticular formation lesions produce bilateral deficits in attention and localization, and propose that this is due to interruption of part of a system of inhibitory pathways. Behavioral testing, designed to measure responsiveness to various sensory modalities, was conducted on 25 cats before and 6-24 months after placement of a midsagittal brain lesion. Cats with midsagittal lesions involving the reticu­ lar formation demonstrated bilateral deficits in responsiveness to audito­ ry, visual, olfactory, nociceptive, and tactile stimuli. This bilateral sensory neglect was manifest as a deficiency in attention and localization. Cats with midsagittal lesions anterior to or above the reticular formation did not have such deficits. Rostral reticular lesions caused greater deficits in responsiveness to visual, olfactory, nociceptive, and tactile stimuli, while caudal reticular lesions caused a greater deficit in responsiveness to audi­ tory stimuli. Except in the case of olfaction, combined rostral and caudal reticular lesions were associated with greater deficits than were the short­ er lesions. To correlate the above behavioral changes with previously re­ ported changes following lesions of the frontal lobes and of the superior

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colliculus or subcollicular tegmentum, we propose the existence of two in­ hibitory pathways which would originate in the frontal lobes. One re­ mains ipsilateral and exerts tonic inhibition at or near the end organ. The second crosses the midline in the reticular formation and ascends to the opposite frontal lobe to exert tonic inhibition on the ipsilateral pathway. Interruption of the ipsilateral inhibitory pathway produces increased at­ tention and failure to habituate to sensory stimuli applied to the receptors of that side. Interruption of the crossing inhibitory pathway produces de­ creased attention to stimuli, or sensory neglect, on the side where the pathway terminates. References Bard, P. and R ioch, D. M.: Study of 4 cats deprived of neocortex and additional portions of the forebrain. Bull. Johns Hopkins Hosp. 60: 73-147 (1937).

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H a g a m e n , W . D .; L a n c e ,

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G reeley/H agamen/H agamen/R eeves

Vo n e id a » T. J.: Visual loss following midline section of the mesencephalic tegmen­ tum in the cat and monkey. Brain Behav. Evol. 3: 241-260 (1970). W a t s o n , R. T.; H e il m a n , K. M.; M i l l e r , B. D., and K in g , F. A.: Neglect after mesencephalic reticular formation lesions. Neurology, Minneap. 24: 294-298 (1974). W e l c h , K. and S t u t e v i l l e , P.: Experimental production of unilateral neglect in monkeys. Brain 81: 341-347 (1958).

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Dr. A l e x a n d e r G. R e e v e s , Division of Neurology, Department of Medicine, Dart­ mouth Medical School, Hanover, N.H. (USA)

Bilateral sensory neglect following midsagittal reticular formation lesions in cats.

We have observed that midsagittal reticular formation lesions in cats produce bilateral deficits in attention to and localization of various sensory m...
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