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Laboratory of Neuropsychology, National Institute of Mental Health, Bethesda, Maryland 20892
Submitted 26 March 2003; accepted in final form 17 June 2003
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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By the mid-1980s, several studies had found that combined aspiration removals of the amygdala and hippocampus [A+H(ASP)] yield severe impairments in visual recognition memory in macaque monkeys as measured by visual delayed nonmatching-to-sample (DNMS) (Mishkin 1978
; Murray and Mishkin 1984; Saunders et al. 1984; Zola-Morgan et al. 1982). A series of subsequent studies have now established that these severe impairments are a result of damage to the rhinal (i.e., entorhinal and perirhinal) cortex rather than the amygdala or hippocampus (Baxter and Murray 2001a; Buffalo et al. 1999; Meunier et al. 1993, 1996; Murray and Mishkin 1998; Suzuki et al. 1993; Zola et al. 2000; Zola-Morgan et al. 1989a,b). Although a hippocampal contribution to DNMS remains controversial (Baxter and Murray 2001a,b; Zola and Squire 2001), it is widely accepted that the deficits in DNMS that follow rhinal cortex damage are much greater than those that follow hippocampal damage (Meunier et al. 1993; Zola-Morgan et al. 1993). In addition, the perirhinal cortex seems to be more critical for recognition memory than the entorhinal cortex with deficits after perirhinal cortex lesions being more severe and longer-lasting relative to those after entorhinal cortex lesions (Buffalo et al. 1999; Leonard et al. 1995; Meunier et al. 1993).
The earlier-held, incorrect conclusion regarding the neural substrates supporting DNMS can be explained by the fact that A+H(ASP) lesions not only include some direct damage to rhinal cortex, but, perhaps more importantly, these lesions also sever connections of the rhinal cortex and adjacent area TE with cortical and subcortical targets (Baxter et al. 1998; Gaffan et al. 2001; Goulet et al. 1998; Munoz et al. 2001). Hence, A+H(ASP) lesions, by means both direct and indirect, produce a functional disconnection of much of the inferior temporal cortex, including rhinal cortex.
Although rhinal cortex removals that do not directly damage amygdala or hippocampus are sufficient to yield a severe impairment in visual recognition memory, the magnitude of impairment after such lesions (Meunier et al. 1993) is not quite as great as that after either A+H(ASP) lesions (Mishkin 1978) or combined aspiration of the amygdala and rhinal cortex (group A+Rh) (Murray and Mishkin 1986). Specifically, whereas monkeys with rhinal cortex lesions scored a mean of 67% correct responses on the DNMS performance test, monkeys with A+Rh and A+H(ASP) removals scored 60.5 and 59.5, respectively. Indeed, groups A+Rh and A+H(ASP) are each significantly more impaired on DNMS than monkeys with rhinal cortex lesions alone [group Rh (Meunier et al. 1993), t(8) = 3.46 and 2.59, respectively; P < 0.032]. This difference in magnitude of the behavioral effects across lesion groups suggests that some structures included in the larger, combined removals, but not in the rhinal cortex removal alone, are involved in visual recognition. The straightforward conclusion—that the additional removal of the amygdala in the combined lesions [A+Rh and A+H(ASP)] is responsible for the additional impairment— has been rejected based on the results of several studies. Damage to the amygdala that does not involve overlying cortex (for example, by electrolytic or neurotoxic lesions) is without effect on visual recognition memory in monkeys (Murray and Mishkin 1998; Murray et al. 1996; Stefanacci et al. 2001; Zola-Morgan et al. 1989a) and does not exacerbate the effect of damage to the hippocampal formation (Murray and Mishkin 1998; Zola-Morgan et al. 1989a). Likewise, the greater deficit cannot simply be due to combined damage to rhinal cortex and hippocampus: adding a hippocampal aspiration lesion to a rhinal cortex removal yields no greater impairment on DNMS than do rhinal cortex lesions alone (Meunier et al. 1996). Furthermore because the combined amygdalohippocampal removals [A+H(ASP)] were not intended to include perirhinal cortex and damage to perirhinal cortex was minor and inconsistent in these cases (e.g., Murray and Mishkin 1984), greater direct damage to the rhinal cortex itself in group A+H(ASP) at least cannot explain the greater deficit in this group relative to monkeys with rhinal cortex ablation alone.
Because aspiration removals of the amygdala disconnect other cortical areas in the temporal lobe besides the rhinal cortex (Baxter et al. 1998; Goulet et al. 1998; Munoz et al. 2001), it is possible that the difference in behavioral effect between rhinal cortex removal versus A+Rh or A+H(ASP) removals is due to disconnection of one of these other cortical fields. One structure that may potentially contribute to the differential outcome is the cortex lining the rostral portion of the dorsal bank of the superior temporal sulcus (STSd). This cortical region contains neurons that respond to visual sensory inputs as well as inputs from other sensory modalities (Bruce et al. 1981). In addition, STSd exhibits strong interconnections with both the perirhinal and entorhinal cortex, both direct and indirect via parahippocampal cortical areas TF/TH (Amaral et al. 1983; Suzuki 1996; Suzuki and Amaral 1994). Moreover, neurons in rostral STSd bear connections that are remarkably similar to those of neurons in perirhinal and entorhinal cortex. Like rhinal cortex, STSd exhibits reciprocal connections with the orbitofrontal cortex and at least efferent, if not reciprocal, projections to the mediodorsal thalamus (Carmichael and Price 1995; Goulet et al. 1998; Seltzer and Pandya 1978, 1991), regions that are themselves involved in visual recognition memory (Aggleton and Mishkin 1983a,b 1984; Bachevalier and Mishkin 1986; Meunier et al. 1997; Parker et al. 1997; Zola-Morgan and Squire 1985). If STSd has connections with brain regions thought to mediate visual recognition, perhaps it too serves as part of the circuitry subserving visual recognition memory. Importantly, there is direct evidence that efferent fibers of rostral STSd may be disrupted by aspiration lesions of the amygdala, just as are fibers from the rhinal cortex (Baxter et al. 1998; Goulet et al. 1998; Munoz et al. 2001). Thus although this region sustains no direct damage in the course of A+Rh or A+H(ASP) lesions, it may nevertheless have been functionally compromised by the removals, contributing to the recognition memory impairment.
To test this possibility experimentally, we examined the performance of monkeys with bilateral lesions of STSd alone, or combined bilateral removals of STSd and perirhinal cortex, on visual recognition memory as assessed by DNMS. We compared scores of monkeys in these new groups with those of monkeys with perirhinal cortex damage alone (Meunier et al. 1993). We speculated that removals of STSd alone might have an effect on visual recognition memory. Such removals are known to affect visual discrimination performance; for example, lesions of the STSd disrupt discrimination of shape and orientation of simple visual stimuli (Eacott et al. 1993). Even if STSd lesions were without effect on their own, however, they could exacerbate the effect of perirhinal cortex damage on recognition memory; lesions of STSd have been reported to exacerbate the effects of area TE lesions on visual discrimination learning (Aggleton and Mishkin 1990). We chose to study the effects of combined lesions of STSd and perirhinal cortex, rather than STSd and rhinal cortex, to avoid potential floor effects consequent to the severe impairment in recognition memory caused by rhinal cortex damage.
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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This paper reports new data from nine behaviorally naive rhesus monkeys (Macaca mulatta) of both sexes, weighing from 3.5 to 6.5 kg at the beginning of the study. They were housed individually in rooms with automatically regulated lighting (12:12-h light:dark). Monkeys were fed a diet of Purina Primate Chow supplemented with fruit; water was always available. During behavioral training, individual food rations were manipulated to ensure maximum feeding consistent with prompt responding in the testing apparatus. After preoperative training on DNMS, three of these monkeys received bilateral removals of STSd, five received bilateral removals of perirhinal cortex and STSd combined (group PRh+STSd), and one received a bilateral removal limited to perirhinal cortex alone (group PRh). This last case served as a check and control for the use of historical cases [the 4 monkeys in group PRh of Meunier et al. (1993); see next paragraph]. All procedures used in this study were approved by the National Institute of Mental Health Animal Care and Use Committee.
Data from eight additional rhesus monkeys, housed and tested in the same manner, served as a basis for comparison with the present results. These included four unoperated rhesus monkeys and four rhesus monkeys with bilateral perirhinal cortex ablations (groups N and PRh of Meunier et al. 1993). As in the present study, all the monkeys in the earlier studies were behaviorally naive before the initiation of DNMS training. Further, the DNMS task was administered in the same way for all groups under consideration; specifically, the rate and sequence of training, the delay intervals, and the intertrial intervals were in all cases the same as those used here.
Apparatus and materials
Training was conducted in a Wisconsin General Testing Apparatus (WGTA) inside a darkened, sound-shielded room. Additional sound masking was provided by a white-noise generator. The test tray contained a row of three food wells spaced 180 mm apart (center to center) and aligned 160 mm in front of the animal's cage. A single banana-flavored pellet (300 mg; P.J. Noyes) or a half peanut, concealed in one of the wells, served as the reward. Several gray cardboard plaques measuring 76 mm on each side and three three-dimensional objects, reserved for this purpose, were used in preliminary training. Over 1,120 three-dimensional objects that differed widely in size, shape, texture, and color were used in administering DNMS (see next section). The objects were used in order, and only after all the objects had been used did they reappear. On average, objects recurred about once per month.
Preoperative testing
PRELIMINARY TRAINING. On the first day of adaptation, the monkeys were allowed to take food from the test tray in the WGTA. During subsequent days, they were trained by successive approximation to displace a plaque covering a food well to obtain the food reward hidden underneath. Then a plaque or object was presented over a single baited well following a random order. The monkeys were then given 20 pseudotrials to familiarize them with the structure of the task. For this purpose, one of the three pretraining objects was presented as the "sample" over the baited central well, and, 10 s later, the two others were presented over the lateral wells, both or neither of which were baited, in pseudorandom order. The monkey was allowed to displace only one of them. The pseudotrials were separated by 30-s intervals. During the 10-s delay intervals and the 30-s intertrial intervals, an opaque screen separated the monkey from the test tray. During stimulus presentations, when the opaque screen was raised, a one-way vision screen blocked the monkey's view of the experimenter. The preliminary training, which was continued until the monkeys readily displaced the baited plaque or object, was completed in 3–9 days.
DNMS. The monkeys were trained on DNMS with trial-unique objects (Mishkin and Delacour 1975). Each trial was composed of two parts: sample presentation followed by choice test. For the sample presentation, the monkey was presented with the sample object overlying the baited central well of the test tray; the monkey displaced the sample to obtain the food reward hidden underneath. After a 10-s delay, the sample object, now unbaited, and the baited novel object were presented for choice over the lateral wells of the test tray, and the monkey could obtain an additional reward by displacing the novel object. A 30-s intertrial interval ensued, after which the procedure was repeated with a novel pair of objects, and so on, until the 20 trials comprising a test session were completed. During the intertrial and delay intervals, an opaque screen separated the monkey from the test tray. When the opaque screen was raised to permit responses, a one-way vision screen blocked the monkey's view of the experimenter. The left-right position of the novel object on the choice test followed a balanced pseudorandom order, and there was no correction for errors. Monkeys were trained at the rate of 20 trials/day, 5 days/week, to a criterion of 90 correct responses in 100 consecutive trials.
After learning the basic recognition task, the monkeys were assigned to three groups matched on the basis of their preoperative learning score. The three operated groups received either bilateral ablations of perirhinal cortex (group PRh; n = 1), bilateral ablation of the rostral STSd (group STSd; n = 3), or the combination of these two removals (group PRh + STSd; n = 5).
Surgery
Monkeys were anesthetized with ketamine hydrochloride (10 mg/kg im) followed by isoflurane (1–3%, to effect). After induction of anesthesia, the animal was treated with atropine sulfate (0.04 mg/kg im) to reduce secretions. Surgery was carried out using aseptic techniques, and heart rate, respiration rate, and body temperature were monitored throughout the procedure. Isotonic fluids were administered through an intravenous catheter. The ablations were made by direct aspiration of tissue under visual control with the aid of an operating microscope. When the ablation was completed, the wound was closed in anatomical layers with silk or Vicryl sutures. All monkeys received dexamethasone phosphate (0.4 mg/kg) and antibiotics (trimethoprim sulfa, 25 mg/kg, or cefazolin, 15 mg/kg) for 1 day before surgery, and daily for 1 wk after surgery to reduce swelling and prevent infection, respectively. Monkeys also received analgesics for 4–7 days after surgery (selected from 80 mg acetaminophen, 5 mg Banamine (flunixin meglumine), 1.25 grain aspirin, 10 mg ketoprofen, or 50 mg/dose ibuprofen).
The perirhinal cortex removals in the present study were intended to match those described in detail in Meunier et al. (1993). After removal of the zygoma, a craniotomy was performed to expose the ventrolateral surface of the frontal and temporal lobes. The bone removal extended rostrally to the orbit, ventrally to the base of the temporal fossa, and caudally just beyond the external auditory meatus. Two approaches were necessary for the perirhinal cortex ablation. First, a supraorbital approach was used; this procedure involved gently elevating the frontal lobe with a brain spoon and ablating the rostral half of the perirhinal cortex by direct subpial aspiration with a small-gauge sucker. This portion of the lesion extended along the rostral face of the temporal pole from the lateral fissure to the floor of the temporal fossa, and included the cortex lining the lateral bank of the rhinal sulcus as well as 2–3 mm of cortex lateral to the sulcus. Second, a subtemporal approach was used for the subsequent ablation of the caudal half of the perirhnal cortex. For this part of the surgery, the monkey's head was tilted at an angle of 120° from the upright position, and the monkeys usually received mannitol (30%; 30 ml iv over 30 min) to reduce brain volume and increase accessibility of the ventromedial cortex, which was gently pushed away from the temporal fossa. When the caudal end of the removal resulting from the first approach was visualized, the lesion was extended further caudally along the lateral bank of the rhinal sulcus. At this caudal level, the lesion again included 2–3 mm of cortex lateral to the sulcus.
The STSd removal used the same craniotomy as for the perirhinal cortex removal. The intended STSd lesion extended from the rostral tip of the superior temporal sulcus caudally for a distance of 15 mm and included both the dorsal bank of the sulcus as well as 
2 mm of cortex lateral to the sulcus. The dorsal and posterior boundaries of the lesion were first marked by a continuous line of cautery, and the tissue was removed by direct subpial aspiration with a small-gauge sucker. The medial boundary of the removal was the fundus of the superior temporal sulcus. This lesion targeted the part of STSd occupying the same anterior-posterior extent of the temporal lobe as the amygdala and rhinal cortex tissue removed in the A+H(ASP) and A+Rh lesions, as this would be the part of STS potentially disconnected by those ablations (Baxter et al. 1998; Goulet et al. 1998; Munoz et al. 2001).
Postoperative testing
Approximately 2 wk after surgery, the monkeys were retrained on the basic DNMS task to the same criterion as before. All the monkeys were then given a performance test adapted from Gaffan (1974) in which the delay between sample presentation and choice test was lengthened in stages from the initial delay of 10 to 30, 60, and, finally, 120 s, and then the list of sample objects to be remembered was increased in steps from the original single object to 3, 5, and, finally, 10 objects. In the list length tests, the sample objects were presented one at a time at 20-s intervals. Consequently the minimum retention interval for each trial was 20 s multiplied by the length of the list. For each delay condition, the monkeys received five consecutive daily sessions of 20 trials each, and, for each list length condition, they received five consecutive daily sessions of 30 trials each.
Histology
At the conclusion of behavioral testing, the monkeys were given a lethal dose of pentobarbitol sodium (100 mg/kg ip) and were perfused intracardially with normal saline followed by aldehyde fixatives. The brains were removed, photographed, frozen, and cut at 50 µm in the coronal plane. Every fifth section was stained with thionin, mounted, and coverslipped.
For each case in the present study, the volume of the removal was estimated by plotting the lesion onto drawings of coronal sections, at 1-mm intervals, of a standard rhesus monkey brain. The boundaries of the entorhinal cortex, perirhinal cortex, and STSd were delineated on the standard sections. The volume of each structure in the normal brain was determined using a digitizing tablet (Wacom, Vancouver, WA) linked to a computer with software for determining the surface area of the region outlined on each section. Because we used sections at 1-mm intervals, the volume was the sum of the surface areas for the sections comprising that region. The extent of the lesion in each experimental subject was determined in the same manner, and the volume of the lesion in each monkey is expressed as a percentage of normal. The extent of the lesions in the monkeys studied in Meunier et al. (1993) had been assessed in the same manner and the histological findings from that study can therefore be directly compared with the findings from the present study.
The percent damage in each case to entorhinal cortex (ERh), perirhinal cortex (PRh), and to the rostral portion of the dorsal bank of the STS (STSd) is presented in Table 1. The lesions in two representative cases each from groups PRh+STSd and STSd are shown in Figs. 1 and 2, respectively. Cases PRh-1 through PRh-4 are from Meunier et al. (1993); case PRh-5 is the new case prepared for the present study. Photomicrographs and detailed histological evaluation of perirhinal cortex lesions in cases PRh-1 through PRh-4 are presented in Meunier et al. (1993).
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Damage to PRh and STSd was generally as intended. The extent of damage to perirhinal cortex in the PRh+STSd group was on average slightly smaller than that in the PRh alone group. The extent of damage to STSd in group PRh+STSd was generally greater than that in group STSd. Comparison of the amounts of damage to these structures between these pairs of groups, however, did not reveal statistically significant differences between them (Mann-Whitney U = 21 and 15, respectively; P > 0.12). As for inadvertent damage, case PRh+STSd-5 sustained slight damage to dorsal TE, in the ventral bank of the superior temporal sulcus, for 4 mm on the left and 6 mm on the right, with damage extending more ventrally on the right. In addition, case PRh+STSd-1 sustained damage to the rostral half of the middle temporal gyrus in the left hemisphere. Finally, negligible damage to the entorhinal cortex was evident in all cases in groups PRh and PRh+STSd.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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), attained criterion on DNMS in an average of 135 trials (range, 0–260) and 41 errors (range, 0–102). Parametric oneway ANOVA confirmed that the four groups that were formed (N, PRh, STSd, and PRh+STSd) did not differ from each other in their initial learning scores; F(3,13) < 1, P > 0.64. Postoperative relearning scores (Table 2) differed signifi-cantly between the groups; trials to criterion, F(3,13) = 7.36, P = 0.004; errors to criterion, F(3,13) = 6.79, P = 0.005. Fisher's LSD post hoc tests revealed significant differences in trials to criterion between monkeys in groups N and PRh (P = 0.001) and between groups PRh and STSd (P = 0.002). Group PRh+STSd did not differ significantly from group N (P = 0.21), but did differ from group PRh (P = 0.012). The latter findings likely reflect the smaller amount of perirhinal cortex damage sustained by monkeys in group PRh+STSd relative to monkeys in group PRh, a point taken up in the DISCUSSION. The pattern of results for errors to criterion was identical.
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The groups differed markedly in the postoperative performance test (Table 2 and Fig. 3). Monkeys in groups PRh and PRh+STSd performed most poorly, averaging 77 and 81% correct across the six conditions, respectively, compared with 93% for the controls. Monkeys in group STSd performed comparably to controls, averaging 91% correct. Thus the STSd lesion did not impair recognition memory on its own, nor did the addition of an STSd lesion to a perirhinal cortex lesion exacerbate the recognition memory impairment associated with perirhinal cortex damage. These observations were supported by the results of a groups x condition ANOVA (scores at the 10-s delay were excluded from all analyses because monkeys were trained to criterion performance at this delay): main effect of group, F(3,13) = 19.22, P < 0.0005, and condition, F(5,65) = 20.67, P < 0.0005, but no group x condition interaction, F(5,65) = 0.93, P = 0.54. Pairwise comparisons of groups with subsequent repeated-measures ANOVA confirmed that monkeys in groups PRh and PRh+STSd were impaired relative to group N, F(1,7) = 114.5, P < 0.0005, and F(1,7) = 17.72, P = 0.004, respectively; monkeys in group STSd were not impaired relative to group N, F(1,5) = 1.07, P = 0.35. Furthermore, group PRh+STSd was significantly impaired relative to group STSd, F(1,6) = 8.64, P = 0.026, but groups PRh and PRh+STSd did not significantly differ from each other, F(1,8) = 2.07, P = 0.19. The results of these pairwise analyses with repeated-measures factors were confirmed with a one-way ANOVA on average scores across the six performance test conditions (excluding the training delay) followed by Fisher's LSD post hoc tests, to control for familywise differences in type I error rate.
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It was also of interest to determine whether there was any relationship between the size of either lesion and the magnitude of impairment on DNMS. For this analysis, the average score across the six test conditions (excluding the training delay) was used. Considering only monkeys with damage to perirhinal cortex (groups PRh and PRh+STSd), there was a significant negative correlation between the extent of the damage to perirhinal cortex and the DNMS performance test scores, indicating that larger perirhinal cortex lesions are associated with poorer recognition memory, r = –0.640, P = 0.046. Surprisingly, however, there was a correlation of similar magnitude between STSd damage and DNMS performance test scores when only monkeys with STSd damage (groups STSd and PRh+STSd) were considered, r = –0.478, although it did not reach significance, P = 0.23. However, there was also a relationship between the volume of perirhinal cortex and STSd damage in these monkeys, r = 0.569, which calls into question the apparent relationship of STSd damage to DNMS impairment. To test whether the extent of damage to STSd or to perirhinal cortex was more closely associated with DNMS performance test scores, a hierarchical regression analysis was performed, in which the extents of damage to STSd and perirhinal cortex were used to predict DNMS impairment. In the eight monkeys in groups PRh+STSd and STSd, adding STSd damage to the model failed to predict any additional variance beyond that already predicted by perirhinal cortex damage (
R2 = 0), suggesting that damage to perirhinal cortex, not to the dorsal bank of the superior temporal sulcus, is associated with impairment in recognition memory. Other, similar analyses have likewise revealed a correlation between magnitude of perirhinal cortex damage and magnitude of recognition loss (Baxter and Murray 2001a; Meunier et al. 1993).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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Some comment on the extent of the perirhinal cortex damage in the PRh+STSd group is in order. It is worth noting that the lesions in this group are, on average, slightly less complete than those in the PRh group, although these differences were not statistically significant. This might account for the nonsignificant difference in postoperative reacquisition of DNMS between groups PRh+STSd and N as well as the numerically better performance of group PRh+STSd relative to group PRh (although this difference did not even approach statistical significance). As noted in RESULTS, there was a strong positive relationship between extent of perirhinal cortex damage and magnitude of DNMS impairment when the operated monkeys with perirhinal cortex damage (groups PRh and PRh+STSd) were considered together. Thus we think it unlikely that addition of the STSd removal to perirhinal cortex removal produced any facilitation of DNMS performance postoperatively. Similarly, the STSd lesions were not always complete, particularly in the group STSd. Again, however, there is no evidence for a contribution of STSd to visual recognition memory; the case in group STSd with the most complete lesion (STSd-2) scored higher on DNMS than the case with the least extensive lesion (STSd-1). Furthermore, the STSd lesions in group PRh+STSd were more extensive, and this group was no more impaired than group PRh. Finally, there was no evidence for an independent relationship between STSd damage and recognition memory impairment, when the mediating effect of perirhinal cortex damage was taken into account.
We initiated the present study in an attempt to elucidate the neural bases underlying the different DNMS performance test scores of groups Rh and A+H(ASP). Aspiration lesions of the amygdala disconnect rostral temporal cortical areas, including entorhinal cortex, perirhinal cortex, area TE and the dorsal bank of the superior temporal sulcus, from medial thalamic and prefrontal targets (Baxter et al. 1998; Goulet et al. 1998; Munoz et al. 2001) known to be important in visual recognition memory (Aggleton and Mishkin 1983a,b, 1984; Bachevalier and Mishkin 1986; Meunier et al. 1997; Parker et al. 1997; Zola-Morgan and Squire 1985) as well as from subcortical inputs (Gaffan et al. 2001, 2002). Presumably the combination of this disconnection with the disconnection of temporal cortical structures caused by hippocampal aspiration (Aggleton and Saunders 1997), or the rhinal cortex damage that accompanies hippocampal aspiration lesions, produces the more severe impairment following A+H(ASP) lesions relative to Rh lesions (for related discussion, see Murray and Mishkin 1998). Although the negative finding from the present study has failed to resolve the discrepancy, it nevertheless narrows the search somewhat; a neural structure(s) that both contributes to DNMS performance and is indirectly affected by the A+H(ASP) removals, one outside the rhinal cortex and STSd, remains to be identified.
The present study excludes the cortex of STSd as a component of the temporal cortical system contributing to DNMS performance. A previous experiment using behavioral methods identical to those in the present study showed that bilateral removal of the cortex of the middle temporal gyrus (constituting dorsal TE, or TEd, and including the ventral bank of the STS) was without effect on DNMS (Buckley et al. 1997). This finding is consistent with the results of an earlier study that examined effects of cooling or ablation of the middle temporal gyrus on delayed matching-to-sample (Horel et al. 1987). However, Buffalo et al. (1999) reported impairment on DNMS in monkeys with ablation of the cortex on the surface of the middle temporal gyrus, so the question of dorsal area TE's contribution to visual recognition memory remains unresolved. A logical remaining candidate for the missing component of the system for visual recognition memory is the cortex of the inferior temporal gyrus, lateral to the border of perirhinal cortex and medial to the anterior middle temporal sulcus, namely, the ventral portion of area TE, or TEv (Horel 1996; Saleem and Tanaka 1996). To date, the functional contribution of TEv to DNMS performance has not been studied directly, in comparison to the other lesions that have been studied using this test procedure in our laboratory.
Despite its anatomical connectivity with perirhinal cortex and its similar afferent and efferent projection patterns, STSd does not appear to contribute to visual learning and cognition in the same way as perirhinal cortex. Findings from the present study indicate that STSd does not interact with perirhinal cortex in supporting visual recognition memory. Additionally, damage to STSd did not exacerbate the impairment caused by rhinal cortex lesions in visual discrimination learning for auditory secondary reinforcement (Baxter et al. 1999; M. G. Baxter, W. S. Hadfield, and E. A. Murray, unpublished observations). As described in the INTRODUCTION, damage to the cortex lining the banks of the superior temporal sulcus impairs some aspects of visual discrimination learning, including discrimination of color and orientation (Aggleton and Mishkin 1990; Eacott et al. 1993), although this may require damage caudal to the region of STS that was ablated in the present study or combined damage to cortex in the dorsal bank of STS and area TE (Aggleton and Mishkin 1990; Eacott et al. 1993). Alternatively, any obligatory interaction of STSd with perirhinal cortex may relate specifically to specialized functional properties of STSd. Neurons in STS are particularly responsive to visual inputs signaling "biological motion" stimuli (e.g., Oram and Perrett 1994). Current theories about perirhinal cortex involvement in cognitive function emphasize a role in "object identification" functions, representing perceptual qualities of objects in addition to maintaining memory for object representations (Buckley and Gaffan 1998; Buckley et al. 2001; Bussey and Saksida 2002; Bussey et al. 2002, 2003; Hampton and Murray 2002; Murray and Bussey 1999; Murray et al. 1998). Although STSd does not appear to contribute to these functions of perirhinal cortex as assessed in the DNMS task, it remains an open possibility that STSd would make an important contribution to visual recognition memory, or object identification, when "biological motion" characteristics of the objects (for example) were particularly relevant to the behavioral task at hand. The projections from STSd to perirhinal cortex provide a route by which this type of information could become integrated with sensory information about objects from other visual processing streams, as well as other sensory modalities. This possibility invites future empirical study.
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DISCLOSURES |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONDISCLOSURESACKNOWLEDGMENTSREFERENCES |
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FOOTNOTES |
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Address for reprint requests and other correspondence: E. A. Murray, Laboratory of Neuropsychology, National Institute of Mental Health, Bldg. 49, Room 1B80, 49 Convent Dr., Bethesda, MD 20892-4415 (E-mail: eam{at}ln.nimh.nih.gov).
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REFERENCES |
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, the locus and extent of the intended lesion (middle) and lesions in 2 monkeys with removals of the perirhinal cortex and dorsal superior temporal sulcus cortex in group PRh+STSd (left and right) shown reconstructed onto ventral surface views (top) and coronal sections (below) from a standard rhesus monkey brain. The ventral views are reversed to aid in matching to the individual sections (i.e., the left hemisphere is on the left); lines indicate the positions of the stereotaxic levels illustrated in the coronal sections. The numerals to the left of the coronal sections indicate the distance in millimeters from the interaural plane.
