Separate but interacting recognition memory systems for different senses: the role of the rat perirhinal cortex

Two different models (convergent and parallel) potentially describe how recognition memory, the ability to detect the re-occurrence of a stimulus, is organized across different senses. To contrast these two models, rats with or without perirhinal cortex lesions were compared across various conditions that controlled available information from specific sensory modalities. Intact rats not only showed visual, tactile, and olfactory recognition, but also overcame changes in the types of sensory information available between object sampling and subsequent object recognition, e.g., between sampling in the light and recognition in the dark, or vice versa. Perirhinal lesions severely impaired object recognition whenever visual cues were available, but spared olfactory recognition and tactile-based object recognition when tested in the dark. The perirhinal lesions also blocked the ability to recognize an object sampled in the light and then tested for recognition in the dark, or vice versa. The findings reveal parallel recognition systems for different senses reliant on distinct brain areas, e.g., perirhinal cortex for vision, but also show that: (1) recognition memory for multisensory stimuli involves competition between sensory systems and (2) perirhinal cortex lesions produce a bias to rely on vision, despite the presence of intact recognition memory systems serving other senses.     

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.     

The effects of prelimbic and infralimbic lesions on working memory for visual objects in rats.

The present experiment investigated the effects of quinolinic acid (90 mM) lesions of the prelimbic-infralimbic cortices on working memory for visual objects and on acquisition of a visual object discrimination. In both tests a GO/NO-GO procedure was used. In the working memory task, rats were tested before and after surgery. A continuous recognition procedure was used to assess working memory, which involved successive exposure to different three-dimensional objects that could be displaced to receive a cereal reinforcement. Of the 12 object presentations/session, 4 objects were presented for a second time in which displacing the object did not result in a reinforcement. The number of trials between the first and second presentations of an object ranged from 0 to 3 (lags). Memory was assessed by the latency to displace an object during the second presentation. In the visual object discrimination, rats had successive exposure to two different objects. Displacement of one object resulted in a cereal reinforcement, while displacement of the other did not. The findings indicated that prelimbic-infralimbic lesions significantly impaired memory for visual objects across all lags. Prelimbic-infralimbic lesions did not impair acquisition of the visual object discrimination. The results suggest that the prelimbic-infralimbic areas are part of neural system important in the short-term memory for visual objects.     

Lateralized spatial and object memory encoding in entorhinal and perirhinal cortices

The perirhinal and entorhinal cortices are critical components of the medial temporal lobe (MTL) declarative memory system. Study of their specific functions using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI), however, has suffered from severe magnetic susceptibility signal dropout resulting in poor temporal signal-to-noise (tSNR) and thus weak BOLD signal detectability. We have demonstrated that higher spatial resolution in the z-plane leads to improved BOLD fMRI signal quality in the anterior medial temporal lobes when using a 16-element surface coil array at 3 T (Tesla). Using this technique, the present study investigated the roles of the anterior medial temporal lobe, particularly the entorhinal and perirhinal cortices, in both object and spatial memory. Participants viewed a series of fractal images and were instructed to encode either the object's identity or location. Object and spatial recognition memory were tested after 18-sec delays. Both the perirhinal and entorhinal cortices were active during the object and spatial encoding tasks. In both regions, object encoding was biased to the left hemisphere, whereas spatial encoding was biased to the right. A similar hemispheric bias was evident for recognition memory. Recent animal studies suggest functional dissociations among regions of the entorhinal cortex for spatial vs. object processing. Our findings suggest that this process-specific distinction may be expressed in the human brain as a hemispheric division of labor.     

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.     

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.     

The role of the human medial temporal lobe in object recognition and object discrimination.

This paper reviews evidence from neuropsychological patient studies relevant to two questions concerning the functions of the medial temporal lobe in humans. The first is whether the hippocampus and the adjacent perirhinal cortex make different contributions to memory. Data are discussed from two patients with adult-onset bilateral hippocampal damage who show a sparing of item recognition relative to recall and certain types of associative recognition. It is argued that these data are consistent with Aggleton and Brown's (1999) proposal that familiarity-based recognition memory is not dependent on the hippocampus but is mediated by the perirhinal cortex and dorso-medial thalamic nucleus. The second question is whether the recognition memory deficit observed in medial temporal lobe amnesia can be explained by a deficit in perceptual processing and representation of objects rather than a deficit in memory per se. The finding that amnesics were impaired at recognizing, after short delays, patterns that they could successfully discriminate suggests that their memory impairment did not result from an object-processing deficit. The possibility remains, however, that the human perirhinal cortex plays a role in object processing, as well as in recognition memory, and data are presented that support this possibility.     

The role of the human medial temporal lobe in object recognition and object discrimination

This paper reviews evidence from neuropsychological patient studies relevant to two questions concerning the functions of the medial temporal lobe in humans. The first is whether the hippocampus and the adjacent perirhinal cortex make different contributions to memory. Data are discussed from two patients with adult-onset bilateral hippocampal damage who show a sparing of item recognition relative to recall and certain types of associative recognition. It is argued that these data are consistent with Aggleton and Brown's (1999) proposal that familiarity-based recognition memory is not dependent on the hippocampus but is mediated by the perirhinal cortex and dorso-medial thalamic nucleus. The second question is whether the recognition memory deficit observed in medial temporal lobe amnesia can be explained by a deficit in perceptual processing and representation of objects rather than a deficit in memory per se. The finding that amnesics were impaired at recognizing, after short delays, patterns that they could successfully discriminate suggests that their memory impairment did not result from an object-processing deficit. The possibility remains, however, that the human perirhinal cortex plays a role in object processing, as well as in recognition memory, and data are presented that support this possibility.     

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.     

Content-specific source encoding in the human medial temporal lobe

Although the medial temporal lobe (MTL) is known to be essential for episodic encoding, the contributions of individual MTL subregions remain unclear. Data from recognition memory studies have provided evidence that the hippocampus supports relational encoding important for later episodic recollection, whereas the perirhinal cortex has been linked with encoding that supports later item familiarity. However, extant data also strongly implicate the perirhinal cortex in object processing and encoding, suggesting that perirhinal processes may contribute to later episodic recollection of object source details. To investigate this possibility, encoding activation in MTL subregions was analyzed on the basis of subsequent memory outcome while participants processed novel scenes paired with 1 of 6 repeating objects. Specifically, encoding activation correlating with later successful scene recognition memory was evaluated against that of source recollection for the object paired with the scene during encoding. In contrast to studies reporting a link between perirhinal cortex and item familiarity, it was found that encoding activation in the right perirhinal cortex correlates with successful recollection of the paired object. Furthermore, other MTL subregions also exhibited content-specific source encoding patterns of activation, suggesting that MTL subsequent memory effects are sensitive to stimulus category.     

On the neural correlates of object recognition awareness: relationship to computational activities and activities mediating perceptual awareness

Based on theoretical considerations of Aurell (1979) and Block (1995), we argue that object recognition awareness is distinct from purely sensory awareness and that the former is mediated by neuronal activities in areas that are separate and distinct from cortical sensory areas. We propose that two of the principal functions of neuronal activities in sensory cortex, which are to provide sensory awareness and to effect the computations that are necessary for object recognition, are dissociated. We provide examples of how this dissociation might be achieved and argue that the components of the neuronal activities which carry the computations do not directly enter the awareness of the subject. The results of these computations are sparse representations (i.e., vector or distributed codes) which are activated by the presentation of particular sensory objects and are essentially engrams for the recognition of objects. These final representations occur in the highest order areas of sensory cortex; in the visual analyzer, the areas include the anterior part of the inferior temporal cortex and the perirhinal cortex. We propose, based on lesion and connectional data, that the two areas in which activities provide recognition awareness are the temporopolar cortex and the medial orbitofrontal cortex. Activities in the temporopolar cortex provide the recognition awareness of objects learned in the remote past (consolidated object recognition), and those in the medial orbitofrontal cortex provide the recognition awareness of objects learned in the recent past. The activation of the sparse representation for a particular sensory object in turn activates neurons in one or both of these regions of cortex, and it is the activities of these neurons that provide the awareness of recognition of the object in question. The neural circuitry involved in the activation of these representations is discussed.     

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.     

Marked Retrograde and Anterograde Amnesia of a Visual Discrimination Task in Rats with Selective Lesions of the Perirhinal Cortex

Damage to the temporal cortex (TC), the lateral entorhinal cortex (LEC), or their interconnections has disruptive effects on visual memory. The fiber connections between TC and LEC are relayed in the perirhinal cortex (PC) or in the adjacent white matter of PC. PC seems to make up a particularly important structure for mnemonic processing. The purpose of the present study was to examine whether selective PC lesions might affect retroactive or proactive memory, since TC/LEC transections can cause both retrograde and anterograde amnesia. The results show that both PC and TC/LEC lesions impair retroactive memory to similar degrees (Experiment 1). However, PC lesions yielded a slightly stronger impairment of both acquisition and retention in the proactive paradigm than TC/LEC lesions (Experiment 2). These findings give support to the notion that PC plays an important role in formation of memory.     

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.     

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.     

Infusion of protein synthesis inhibitors in the entorhinal cortex blocks consolidation but not reconsolidation of object recognition memory

Memory consolidation and reconsolidation require the induction of protein synthesis in some areas of the brain. Here, we show that infusion of the protein synthesis inhibitors anisomycin, emetine and cycloheximide in the entorhinal cortex immediately but not 180 min or 360 min after training in an object recognition learning task hinders long-term memory retention without affecting short-term memory or behavioral performance. Inhibition of protein synthesis in the entorhinal cortex after memory reactivation involving either a combination of familiar and novel objects or two familiar objects does not affect retention. Our data suggest that protein synthesis in the entorhinal cortex is necessary early after training for consolidation of object recognition memory. However, inhibition of protein synthesis in this cortical region after memory retrieval does not seem to affect the stability of the recognition trace.     

The role of the perirhinal cortex and hippocampus in learning, memory, and perception.

One traditional and long-held view of medial temporal lobe (MTL) function is that it contains a system of structures that are exclusively involved in memory, and that the extent of memory loss following MTL damage is simply related to the amount of MTL damage sustained. Indeed, human patients with extensive MTL damage are typically profoundly amnesic whereas patients with less extensive brain lesions centred upon the hippocampus typically exhibit only moderately severe anterograde amnesia. Accordingly, the latter observations have elevated the hippocampus to a particularly prominent position within the purported MTL memory system. This article reviews recent lesion studies in macaque monkeys in which the behavioural effects of more highly circumscribed lesions (than those observed to occur in human patients with MTL lesions) to different subregions of the MTL have been examined. These studies have reported new findings that contradict this concept of a MTL memory system. First, the MTL is not exclusively involved in mnemonic processes; some MTL structures, most notably the perirhinal cortex, also contribute to perception. Second, there are some forms of memory, including recognition memory, that are not always affected by selective hippocampal lesions. Third, the data support the idea that regional functional specializations exist within the MTL. For example, the macaque perirhinal cortex appears to be specialized for processing object identity whereas the hippocampus may be specialized for processing spatial and temporal relationships.     

The role of the perirhinal cortex and hippocampus in learning, memory, and perception

One traditional and long-held view of medial temporal lobe (MTL) function is that it contains a system of structures that are exclusively involved in memory, and that the extent of memory loss following MTL damage is simply related to the amount of MTL damage sustained. Indeed, human patients with extensive MTL damage are typically profoundly amnesic whereas patients with less extensive brain lesions centred upon the hippocampus typically exhibit only moderately severe anterograde amnesia. Accordingly, the latter observations have elevated the hippocampus to a particularly prominent position within the purported MTL memory system. This article reviews recent lesion studies in macaque monkeys in which the behavioural effects of more highly circumscribed lesions (than those observed to occur in human patients with MTL lesions) to different subregions of the MTL have been examined. These studies have reported new find-ings that contradict this concept of a MTL memory system. First, the MTL is not exclusively involved in mnemonic processes; some MTL structures, most notably the perirhinal cortex, also contribute to perception. Second, there are some forms of memory, including recognition memory, that are not always affected by selective hippocampal lesions. Third, the data support the idea that regional functional specializations exist within the MTL. For example, the macaque perirhinal cortex appears to be specialized for processing object identity whereas the hippocampus may be specialized for processing spatial and temporal relationships.     

The roles of perirhinal cortex, postrhinal cortex, and the fornix in memory for objects, contexts, and events in the rat

Investigation of the anatomical substructure of the medial temporal lobe has revealed a number of highly interconnected areas, which has led some to propose that the region operates as a unitary memory system. However, here we outline the results of a number of studies from our laboratories, which investigate the contributions of the rat's perirhinal cortex and postrhinal cortex to memory, concentrating particularly on their respective roles in memory for objects. By contrasting patterns of impairment and spared abilities on a number of related tasks, we suggest that perirhinal cortex and postrhinal cortex make distinctive contributions to learning and memory: for example, that postrhinal cortex is important in learning about within-scene position and context. We also provide evidence that despite the strong connectivity between these cortical regions and the hippocampus, the hippocampus, as evidenced by lesions of the fornix, has a distinct function of its own—combining information about objects, positions, and contexts.     

Contrasting hippocampal and perirhinal cortex function using immediate early gene imaging.

The perirhinal cortex and hippocampus have close anatomical links, and it might, therefore, be predicted that they have close, interlinked roles in memory. Lesion studies have, however, often failed to support this prediction, providing dissociations and double dissociations between the two regions on tests of object recognition and spatial memory. In a series of rat studies we have compared these two regions using the expression of the immediate early gene c-fos as a marker of neuronal activity. This gene imaging approach makes it possible to assess the relative involvement of different brain regions and avoids many of the limitations of the lesion approach. A very consistent pattern of results was found as the various hippocampal subfields but not the perirhinal cortex show increased c-fos activity following tests of spatial learning. In contrast, the perirhinal cortex but none of the hippocampal subfields show increased c-fos activity when presented with novel rather than familiar visual objects. When novel scenes are created by the spatial rearrangement of familiar objects it is the hippocampus and not the perirhinal cortex that shows c-fos changes. This double dissociation for gene expression accords with that found from lesion studies and highlights the different contributions of the perirhinal cortex and hippocampus to memory.