Monkey perirhinal cortex is critical for visual memory, but not for visual perception: reexamination of the behavioural evidence from monkeys.

Overdependence on discrimination learning paradigms to assess the function of perirhinal cortex has complicated understanding of the cognitive role of this structure. Impairments in discrimination learning can result from at least two distinct causes: (a) failure to accurately apprehend and represent the relevant stimuli, or (b) failure to form and remember associations between stimulus representations and reward. Thus, the results of discrimination learning experiments do not readily differentiate deficits in perception from deficits in learning and memory. Here I describe studies that do dissociate learning and memory from perception and show that perirhinal cortex damage impairs learning and/or memory, but not perception. Reanalysis and reconsideration of other published data call into further question the hypothesis that the monkey perirhinal cortex plays a critical role in visual perception.     

Intact visual perceptual discrimination in humans in the absence of perirhinal cortex

While the role of the perirhinal cortex in declarative memory has been well established, it has been unclear whether the perirhinal cortex might serve an additional nonmnemonic role in visual perception. Evidence that the perirhinal cortex might be important for visual perception comes from a recent report that monkeys with perirhinal cortical lesions are impaired on difficult (but not on simple) visual discrimination tasks. We administered these same tasks to nine amnesic patients, including three severely impaired patients with complete damage to perirhinal cortex bilaterally (E.P., G.P., and G.T.). The patients performed all tasks as well as controls. We suggest that the function of perirhinal cortex as well as antero-lateral temporal cortex may differ between humans and monkeys.     

The perceptual-mnemonic/feature conjunction model of perirhinal cortex function.

The perirhinal cortex was once thought to be "silent cortex", virtually ignored by researchers interested in the neurobiology of learning and memory. Following studies of brain damage associated with cases of amnesia, perirhinal cortex is now widely regarded as part of a "medial temporal lobe (MTL) memory system". This system is thought to be more or less functionally homogeneous, having a special role in declarative memory, and making little or no contribution to other functions such as perception. In the present article, we summarize an alternative view. First, we propose that components of the putative MTL system such as the hippocampus and perirhinal cortex have distinct and dissociable functions. Second, we provide evidence that the perirhinal cortex has a role in visual discrimination. In addition, we propose a specific role for perirhinal cortex in visual discrimination: the contribution of complex conjunctive representations to the solution of visual discrimination problems with a high degree of "feature ambiguity". These proposals constitute a new view of perirhinal cortex function, one that does not assume strict modularity of function in the occipito-temporal visual stream, but replaces this idea with the notion of a hierarchical representational continuum.     

The perceptual-mnemonic/feature conjunction model of perirhinal cortex function

The perirhinal cortex was once thought to be “silent cortex”, virtually ignored by researchers interested in the neurobiology of learning and memory. Following studies of brain damage associated with cases of amnesia, perirhinal cortex is now widely regarded as part of a “medial temporal lobe (MTL) memory system”. This system is thought to be more or less functionally homogeneous, having a special role in declarative memory, and making little or no contribution to other functions such as perception. In the present article, we summarize an alternative view. First, we propose that components of the putative MTL system such as the hippocampus and perirhinal cortex have distinct and dissociable functions. Second, we provide evidence that the perirhinal cortex has a role in visual discrimination. In addition, we propose a specific role for perirhinal cortex in visual discrimination: the contribution of complex conjunctive representations to the solution of visual discrimination problems with a high degree of “feature ambiguity”. These proposals constitute a new view of perirhinal cortex function, one that does not assume strict modularity of function in the occipito-temporal visual stream, but replaces this idea with the notion of a hierarchical representational continuum.     

Intact visual discrimination of complex and feature-ambiguous stimuli in the absence of perirhinal cortex

The perirhinal cortex is known to be important for memory, but there has recently been interest in the possibility that it might also be involved in visual perceptual functions. In four experiments, we assessed visual discrimination ability and visual discrimination learning in severely amnesic patients with large medial temporal lobe lesions that included complete lesions of perirhinal cortex. Experiment 1 tested complex visual object perception. Experiments 2a and 2b tested in two different ways the ability to discriminate between feature-ambiguous images, which was reported to be impaired in monkeys with perirhinal lesions. Experiment 3 involved images that were successfully discriminated in Experiment 2a and asked patients to learn across 20 trials which of the images had been designated as "correct." Patients performed as well as controls in Experiments 1, 2a, and 2b, but one of the patients had difficulty in Experiment 3 when the task required remembering from trial to trial which image was "correct." These findings indicate that perirhinal cortex is not needed for visual perception across a wide range of visual perceptual tasks.     

Dissociation between the effects of damage to perirhinal cortex and area TE

Perirhinal cortex and area TE are immediately adjacent to each other in the temporal lobe and reciprocally interconnected. These areas are thought to lie at the interface between visual perception and visual memory, but it has been unclear what their separate contributions might be. In three experiments, monkeys with bilateral lesions of the perirhinal cortex exhibited a different pattern of impairment than monkeys with bilateral lesions of area TE. In experiment 1, lesions of the perirhinal cortex produced a multimodal deficit in recognition memory (delayed nonmatching to sample), whereas lesions of area TE impaired performance only in the visual modality. In experiment 2, on a test of visual recognition memory (the visual paired comparison task) lesions of the perirhinal cortex impaired performance at long delays but spared performance at a very short delay. In contrast, lesions of area TE impaired performance even at the short delay. In experiment 3, lesions of the perirhinal cortex and lesions of area TE produced an opposite pattern of impairment on two visual discrimination tasks, simple object discrimination learning (impaired only by perirhinal lesions), and concurrent discrimination learning (impaired only by TE lesions). Taken together, the findings suggest that the perirhinal cortex, like other medial temporal lobe structures, is important for the formation of memory, whereas area TE is important for visual perceptual processing.     

Effects of selective perirhinal and postrhinal lesions on acquisition and retention of a visual discrimination task in rats

The hippocampal region along with rhinal structures seems to support learning and memory in an important manner. Structures adjacent to the rhinal fissure in the rat have recently been suggested to be divided into the perirhinal and postrhinal cortices. Some effects of perirhinal lesions on cognitive processing are known, whereas effects of postrhinal lesions appear to be unknown. The purpose of the present study was to examine the relative effects of perirhinal and postrhinal lesions in a three-choice visual discrimination test. The results show that both types of lesions impaired acquisition of the task, but only perirhinal lesions impeded subsequent retention. Because the initial phase of acquisition was unaffected by both lesions, it is suggested that the deficits observed may be of mnemonic nature. The apparent differential involvement of the perirhinal cortex and postrhinal cortex in cognition may be associated with differences in anatomical connectivity among these structures.     

Perirhinal cortex resolves feature ambiguity in configural object recognition and perceptual oddity tasks

The perirhinal cortex (PRh) has a well-established role in object recognition memory. More recent studies suggest that PRh is also important for two-choice visual discrimination tasks. Specifically, it has been suggested that PRh contains conjunctive representations that help resolve feature ambiguity, which occurs when a task cannot easily be solved on the basis of features alone. However, no study has examined whether the ability of PRh to resolve configural feature ambiguity is related to its role in object recognition. Therefore, we examined whether bilateral excitotoxic lesions of PRh or PPRh (perirhinal plus post-rhinal cortices) in the rat would cause deficits in a configural spontaneous object recognition task, and a configural simultaneous oddity discrimination task, in which the task could not be solved on the basis of features, but could only be solved using conjunctive representations. As predicted by simulations using a computational model, rats with PPRh lesions were impaired during a minimal-delay configural object recognition task. These same rats were impaired during a zero-delay configural object recognition task. Furthermore, rats with localized PRh lesions were impaired in a configural simultaneous oddity discrimination task. These findings support the idea that PRh contains conjunctive representations for the resolution of feature ambiguity and that these representations underlie a dual role for PRh in memory and perception.     

Differential effects of m1 and m2 receptor antagonists in perirhinal cortex on visual recognition memory in monkeys

Microinfusions of the nonselective muscarinic antagonist scopolamine into perirhinal cortex impairs performance on visual recognition tasks, indicating that muscarinic receptors in this region play a pivotal role in recognition memory. To assess the mnemonic effects of selective blockade in perirhinal cortex of muscarinic receptor subtypes, we locally infused either the m1-selective antagonist pirenzepine or the m2-selective antagonist methoctramine in animals performing one-trial visual recognition, and compared these scores with those following infusions of equivalent volumes of saline. Compared to these control infusions, injections of pirenzepine, but not of methoctramine, significantly impaired recognition accuracy. Further, similar doses of scopolamine and pirenzepine yielded similar deficits, suggesting that the deficits obtained earlier with scopolamine were due mainly, if not exclusively, to blockade of m1 receptors. The present findings indicate that m1 and m2 receptors have functionally dissociable roles, and that the formation of new visual memories is critically dependent on the cholinergic activation of m1 receptors located on perirhinal cells.     

Perirhinal cortex lesions impair feature-negative discrimination

The role of the perirhinal cortex in inhibitory eyeblink conditioning was examined. In Experiment 1, rats were given lesions of the perirhinal cortex or control surgery and subsequently trained with a feature-negative discrimination procedure followed by summation and retardation tests for conditioned inhibition. Perirhinal cortex lesions impaired, but did not prevent acquisition of feature-negative discrimination. Results from the summation test showed that rats with perirhinal cortex lesions could not generalize feature-negative discrimination to a new stimulus. There were no group differences during the retardation test. Experiment 2 showed that lesions of the perirhinal cortex did not impair simple excitatory conditioning. Experiment 3 showed that perirhinal cortex lesions had no effect on acquisition of a simple tone-light discrimination. The results suggest that the perirhinal cortex plays a role in eyeblink conditioning when using discrimination procedures involving overlapping stimuli.     

A neural circuit analysis of visual recognition memory: role of perirhinal, medial, and lateral entorhinal cortex

Using a continuous recognition memory procedure for visual object information, we sequentially presented rats with eight novel objects and four repeated objects (chosen from the 8). These were selected from 120 different three-dimensional objects of varying sizes, shapes, textures, and degree of brightness. Repeated objects had lags ranging from 0 to 4 (from 0 to 4 different objects between the first and repeated presentation). An object was presented on one side of a long table divided in half by an opaque Plexiglas guillotine door, and the latency between opening the door and the rat moving the object was measured. The first presentation of an object resulted in reinforcement, but repeated presentations did not result in a reinforcement. After completion of acquisition training (significantly longer latencies for repeated presentation compared with the first presentation of an object), rats received lesions of the perirhinal, medial, or lateral entorhinal cortex or served as sham operated controls. On the basis of postsurgery testing and additional tests, the results indicated that rats with perirhinal cortex lesions had a sustained impairment in performing the task. There were no sustained deficits with medial or lateral entorhinal cortex lesions. The data suggest that recognition memory for visual object information is mediated primarily by the perirhinal cortex but not by the medial or lateral entorhinal cortex.     

Muscimol,AP5, or scopolamine infused into perirhinal cortex impairs two-choice visual discrimination learning in rats

The perirhinal cortex (PRh) has been strongly implicated in object recognition memory and visual stimulus representation. Studies of object recognition have revealed evidence for the involvement of several neurotransmitter subsystems, including those involving NMDA (N-methyl-d-aspartic acid) and muscarinic cholinergic receptors. In the present study, we assessed the possible involvement of PRh and related receptor subsystems in two-choice visual discrimination learning by Lister Hooded rats tested in touchscreen-equipped operant boxes. In Experiment 1, daily pre-training inactivation of PRh with the GABA_A receptor agonist muscimol (0.5 μg/hemisphere) significantly impaired acquisition of the two-choice visual discrimination. In Experiment 2, daily pre-training blockade of either NMDA or muscarinic receptors in PRh with AP5 (5.9 μg/hemisphere) or scopolamine (10 μg/hemisphere), respectively, impaired task acquisition. These results parallel the findings from object recognition studies and suggest a generality of neurotransmitter receptor involvement underlying the role of PRh in both object recognition memory and visual discrimination learning. The involvement of PRh in both types of tasks may be related to its role in complex visual stimulus representation.     

Perceptual–mnemonic functions of the perirhinal cortex

It is widely acknowledged that the perirhinal cortex, located in the ventromedial aspect of the temporal lobe, is essential for certain types of memory in macaque monkeys. For example, removal of the perirhinal cortex yields severe impairments on tests of stimulus recognition and stimulus–stimulus association. There is considerable disagreement, however, about the most accurate way to characterize the function of the perirhinal cortex; some views emphasize a role in perception whereas others posit a role exclusively in declarative memory. In this article, we review recent findings from anatomical, physiological and ablation studies in monkeys, and discuss related findings obtained in humans, in an attempt to identify not only the cognitive functions of the perirhinal cortex, but also the implications of these findings for theoretical views concerning the organization of memory.     

Differing time dependencies of object recognition memory impairments produced by nicotinic and muscarinic cholinergic antagonism in perirhinal cortex

The roles of muscarinic and nicotinic cholinergic receptors in perirhinal cortex in object recognition memory were compared. Rats' discrimination of a novel object preference test (NOP) test was measured after either systemic or local infusion into the perirhinal cortex of the nicotinic receptor antagonist methyllycaconitine (MLA), which targets alpha-7 (α7) amongst other nicotinic receptors or the muscarinic receptor antagonists scopolamine, AFDX-384, and pirenzepine. Methyllycaconitine administered systemically or intraperirhinally before acquisition impaired recognition memory tested after a 24-h, but not a 20-min delay. In contrast, all three muscarinic antagonists produced a similar, unusual pattern of impairment with amnesia after a 20-min delay, but remembrance after a 24-h delay. Thus, the amnesic effects of nicotinic and muscarinic antagonism were doubly dissociated across the 20-min and 24-h delays. The same pattern of shorter-term but not longer-term memory impairment was found for scopolamine whether the object preference test was carried out in a square arena or a Y-maze and whether rats of the Dark Agouti or Lister-hooded strains were used. Coinfusion of MLA and either scopolamine or AFDX-384 produced an impairment profile matching that for MLA. Hence, the antagonists did not act additively when coadministered. These findings establish an important role in recognition memory for both nicotinic and muscarinic cholinergic receptors in perirhinal cortex, and provide a challenge to simple ideas about the role of cholinergic processes in recognition memory: The effects of muscarinic and nicotinic antagonism are neither independent nor additive.     

Incidental visual memory for objects in scenes

Three experiments were conducted to investigate the existence of incidentally acquired, long-term, detailed visual memory for objects embedded in previously viewed scenes. Participants performed intentional memorization and incidental visual search learning tasks while viewing photographs of real-world scenes. A visual memory test for previously viewed objects from these scenes then followed. Participants were not aware that they would be tested on the scenes following incidental learning in the visual search task. In two types of memory tests for visually specific object information (token discrimination and mirror-image discrimination), performance following both the memorization and visual search conditions was reliably above chance. These results indicate that recent demonstrations of good visual memory during scene viewing are not due to intentional scene memorization. Instead, long-term visual representations are incidentally generated as a natural product of scene perception.     

Distinct roles for medial temporal lobe structures in memory for objects and their locations

The ability to learn and retain novel information depends on a system of structures in the medial temporal lobe (MTL) including the hippocampus and the surrounding entorhinal, perirhinal, and parahippocampal cortices. Damage to these structures produces profound memory deficits; however, the unique contribution to memory of each of these structures remains unclear. Here we have used functional magnetic resonance imaging (fMRI) to determine whether the perirhinal and parahippocampal cortices show differential memory-related activity. Based on the distinct patterns of cortical input to these two areas, we reasoned that these structures might show differential activity for spatial and object recognition memory. In each of 11 subjects, we found that the perirhinal cortex was active during both spatial and object memory encoding, while the anterior parahippocampal cortex was active only during spatial encoding. These data support the idea that MTL structures make distinct contributions to recognition memory performance.     

Recognition memory for complex visual discriminations is influenced by stimulus interference in rodents with perirhinal cortex damage

Rats with perirhinal cortex (PRC), hippocampal, or sham lesions were trained on a successive discrimination go/no-go task to examine recognition memory for an array of visual objects with varying interference among the objects in the array. Rats were trained to recognize a target array consisting of four particular objects that could be presented in any one of four possible configurations to cover baited food wells. If the four target objects were presented, the rat should displace each object to receive food. However, if a novel object replaced any one or more of the target objects, then the rat should withhold its response. The number of novel objects presented on nonrewarded trials varied from one to four. The fewer the number of novel objects in the array, the more interference the array shared with the target array, therefore increasing task difficulty. An increased number of novel objects should result in less interference with the target array and decreased task difficulty. Although accuracy was slightly lower in rats with hippocampal lesions compared with controls, the learning of the groups was not statistically different. In contrast, rats with PRC lesions were significantly impaired in learning compared with both control and hippocampal-lesioned rats. The results suggest that recognition memory for complex visual discriminations is affected by stimulus interference in rodents with PRC damage.     

Muscarinic receptors activity in the perirhinal cortex and hippocampus has differential involvement in the formation of recognition memory

In this work we probed the effects of post-trial infusions of the muscarinic receptor antagonist scopolamine on object recognition memory formation. Scopolamine was infused bilaterally immediately after the sample phase in the perirhinal cortex or dorsal hippocampus and animals were tested for short-term (90 min) or long-term (24 h) memory. Results showed that scopolamine impaired short-term memory when injected in either the perirhinal cortex or hippocampus. Nevertheless, scopolamine disrupted long-term memory when administrated in the perirhinal cortex but not when applied in the hippocampus. Long-term memory was unaffected when scopolamine was infused 160 min after the sample phase or 90 min before test phase. Our data indicate that short-term recognition memory requires muscarinic receptors signaling in both the perirhinal cortex and hippocampus, whereas long-term recognition memory depends on muscarinic receptors in the perirhinal cortex but not hippocampus. These results support a differential involvement of muscarinic activity in these two medial temporal lobe structures in the formation of recognition memory.     

The consolidation of object and context recognition memory involve different regions of the temporal lobe

These experiments investigated the involvement of several temporal lobe regions in consolidation of recognition memory. Anisomycin, a protein synthesis inhibitor, was infused into the hippocampus, perirhinal cortex, insular cortex, or basolateral amygdala of rats immediately after the sample phase of object or object-in-context recognition memory training. Anisomycin infused into perirhinal or insular cortices blocked long-term (24 h), but not short-term (90 min) object recognition memory. Infusions into the hippocampus or amygdala did not impair object recognition memory. Anisomycin infused into the hippocampus blocked long-term, but not short-term object-in-context recognition memory, whereas infusions administered into the perirhinal cortex, insular cortex, or amygdala did not affect object-in-context recognition memory. These results clearly indicate that distinct regions of the temporal lobe are differentially involved in long-term object and object-in-context recognition memory. Whereas perirhinal and insular cortices are required for consolidation of familiar objects, the hippocampus is necessary for consolidation of contextual information of recognition memory. Altogether, these results suggest that temporal lobe structures are differentially involved in recognition memory consolidation.     

Perirhinal cortex lesions produce retrograde amnesia for spatial information in rats: consolidation or retrieval?

Several lines of evidence in humans and experimental animals suggest that the hippocampus is critical for the formation and retrieval of spatial memory. However, although the hippocampus is reciprocally connected to adjacent cortices within the medial temporal lobe and they, in turn, are connected to the neocortex, little is known regarding the function of these cortices in memory. Here, using a reference spatial memory task in the radial maze, we show that neurotoxic perirhinal cortex lesions produce a profound retrograde amnesia when learning-surgery intervals of 1 or 50 d are used (Experiment 1). With the aim of dissociating between consolidation and retrieval processes, we injected lidocaine either daily after training (Experiment 2) or before a retention test once the learning had been completed (Experiment 3). Results show that reversible perirhinal inactivation impairs retrieval but not consolidation. However, the same procedure followed in Experiment 2 disrupted consolidation when the lidocaine was injected into the dorsal hippocampus. The results of Experiment 4 rule out the possibility that the deficit in retrieval is due to a state-dependent effect. These findings demonstrate the differential contribution of various regions of the medial temporal lobe to memory, suggesting that the perirhinal cortex plays a key role in the retrieval of spatial information for a long period of time.