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.     

The Effects of Muscarinic Cholinergic Receptor Blockade in the Rat Anterior Cingulate and Prelimbic/Infralimbic Cortices on Spatial Working Memory

Previous findings indicate that cholinergic input to the medial prefrontal cortex may modulate mnemonic processes. The present experiment determined whether blockade of muscarinic cholinergic receptors in the rodent anterior cingulate and prelimbic/infralimbic cortices impairs spatial working memory. In a 12-arm radial maze, a working memory for spatial locations task was employed using a continuous recognition go/no-go procedure. Rats were allowed to enter 12 arms for a reinforcement. Of the 12 arm presentations, 3 or 4 arms were presented for a second time in a session that did not contain a reinforcement. The number of trials between the first and second presentations of an arm ranged from 0 to 6 (lags). Infusions of scopolamine (1, 5, and 10 μg), a muscarinic cholinergic antagonist, into the prelimbic/infralimbic cortices, but not the anterior cingulate cortex, significantly impaired spatial working memory in a lag- and dose-dependent manner. The deficit induced by scopolamine (10 μg) was attenuated by concomitant intraprelimbic/infralimbic injections of oxotremorine (2 μg), a muscarinic cholinergic agonist. A separate group of rats was tested on a successive spatial discrimination task. Injections of scopolamine (1, 5, and 10 μg) into the prelimbic/infralimbic cortices did not impair performance on the spatial discrimination task. These findings suggest that muscarinic transmission in the prelimbic/infralimbic cortices, but not the anterior cingulate cortex, is important for spatial working memory.     

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.     

Role of CA3 and CA1 subregions of the dorsal hippocampus on temporal processing of objects

Previous research in the dorsal CA1 and dorsal CA3 subregions of the hippocampus has been shown to play an important role in mediating temporal order memory for spatial location information. What is not known is whether the dorsal CA3 and dorsal CA1 subregions of the hippocampus are also involved in temporal order for visual object information. Rats with dorsal CA1, dorsal CA3 or control lesions were tested in a temporal order task for visual objects using an exploratory paradigm. The results indicated that the controls and the dorsal CA3 lesioned rats preferred the first rather then the last object they had explored previously, indicating good memory for temporal order of object presentation. In contrast, rats with dorsal CA1 lesions displayed a profound deficit in remembering the order of the visual object presentations in that they preferred the last object rather than the first. All three groups of rats preferred a novel object compared to a previously explored object suggesting normal detection of visual object novelty. The results suggest that only the dorsal CA1, but not dorsal CA3, region is critical for processing temporal information for visual objects without affecting the detection of new visual objects.     

Memory for Duration: Role of Hippocampus and Medial Prefrontal Cortex

In this task rats had to learn that a three-dimensional object stimulus (a rectangle) that was visible for 2 s would result in a positive (go) reinforcement for one object (a ball) and no reinforcement (no go) for a different object (a bottle). However, if the rectangle stimulus was visible for 8 s then there would be no reinforcement for the ball (no go), but a reinforcement for the bottle (go). After rats learned this conditional discrimination by responding differentially in terms of latency to approach the object, they received large (dorsal and ventral) lesions of the hippocampus, lesions of the medial prefrontal cortex (anterior cingulate and precentral cortex), lesions of the cortex dorsal to the dorsal hippocampus, or served as sham-operated controls. Following recovery from surgery they were retested. The results indicate that there were major impairments following hippocampal lesions, in contrast to cortical control and medial prefrontal cortex lesions, as indicated by smaller latency differences between positive and negative trials on postsurgery tests. In order to ensure that the deficits observed with hippocampal lesions were not due to a discrimination problem, new rats were trained in an object (gray cylinder) duration discrimination task. In this go/no go procedure, the rats were reinforced for a 2-s exposure (duration) of the gray cylinder, but not a 10-s duration, or vice versa. The results indicate that after hippocampal lesions, there was an initial deficit followed by complete recovery. There were no significant changes for the medial prefrontal, cortical control, or sham-operated animals. It appears that the hippocampus, but not the medial prefrontal cortex, is actively involved in representing in short-term memory temporal attribute information based on the use of markers for the beginning and end of the presence (duration) of a stimulus (object).     

Effects of rodent prefrontal lesions on object-based, visual scene memory

It has been suggested that certain prefrontal areas contribute to a neural circuit that mediates visual object memory. Using a successive go/no-go visual scene discrimination task, object-based long-term memory was assessed in two rodent prefrontal regions. Rewarded trials consisted of a standard scene of four toy objects placed over baited food wells. The objects and their locations composing the standard scene remained constant for the duration of the study. Trials in which one of the standard scene objects was replaced with a novel object were not rewarded. Following the establishment of a significant difference between latency to approach the rewarded standard scene compared to latency to approach non-rewarded scenes, quinolinic acid or control vehicle was infused into either the prelimbic and infralimbic cortices or the anterior cingulate cortex. Following a 1 week recovery period, subjects were retested. Animals with prelimbic/infralimbic cortex lesions displayed a profound and sustained deficit, whereas, animals with anterior cingulate cortex lesions showed a slight initial impairment but eventually recovered. Both lesion groups acquired a simple single object discrimination task as quickly as controls indicating that the deficits on the original scene discrimination task were not due to motivational, response inhibition, or perceptual problems.     

Not all visual memories are created equal

Two experiments examined how well the long-term visual memories of objects that are encountered multiple times during visual search are updated. Participants searched for a target two or four times (e.g., white cat) among distractors that shared the target's colour, category, or were unrelated while their eye movements were recorded. Following the search, a surprise visual memory test was given. With additional object presentations, only target memory reliably improved; distractor memory was unaffected by the number of object presentations. Regression analyses using the eye movement variables as predictors indicated that number of object presentations predicted target memory with no additional impact of other viewing measures. In contrast, distractor memory was best predicted by the viewing pattern on the distractor objects. Finally, Experiment 2 showed that target memory was influenced by number of target object presentations, not number of searches for the target. Each of these experiments demonstrates visual memory differences between target and distractor objects and may provide insight into representational differences in visual memory.     

Role of the dorsal hippocampus in object memory load

The dorsal hippocampus is crucial for mammalian spatial memory, but its exact role in item memory is still hotly debated. Recent evidence in humans suggested that the hippocampus might be selectively involved in item short-term memory to deal with an increasing memory load. In this study, we sought to test this hypothesis. To this aim we developed a novel behavioral procedure to study object memory load in mice by progressively increasing the stimulus set size in the spontaneous object recognition task. Using this procedure, we demonstrated that naive mice have a memory span, which is the number of elements they can remember for a short-time interval, of about six objects. Then, we showed that excitotoxic selective lesions of the dorsal hippocampus did not impair novel object discrimination in the condition of low memory load. In contrast, the same lesion impaired novel object discrimination in the high memory load condition, and reduced the object memory span to four objects. These results have important heuristic and clinical implications because they open new perspective toward the understanding of the role of the hippocampus in item memory and in memory span deficits occurring in human pathologies, such as Alzheimer's disease and schizophrenia.     

Effects of verbal and nonverbal interference on spatial and object visual working memory

We tested the hypothesis that a verbal coding mechanism is necessarily engaged by object, but not spatial, visual working memory tasks. We employed a dual-task procedure that paired n-back working memory tasks with domain-specific distractor trials inserted into each interstimulus interval of the n-back tasks. In two experiments, object n-back performance demonstrated greater sensitivity to verbal distraction, whereas spatial n-back performance demonstrated greater sensitivity to motion distraction. Visual object and spatial working memory may differ fundamentally in that the mnemonic representation of featural characteristics of objects incorporates a verbal (perhaps semantic) code, whereas the mnemonic representation of the location of objects does not. Thus, the processes supporting working memory for these two types of information may differ in more ways than those dictated by the "what/where" organization of the visual system, a fact more easily reconciled with a component process than a memory systems account of working memory function.     

The Effects of Hippocampal and Area Parahippocampalis Lesions in Pigeons: II. Concurrent Discrimination and Spatial Memory

Two experiments were conducted to examine the effects of bilateral hippocampus (Hp) and area parahippocampalis (APH) lesions in pigeons on the acquisition of a visual and spatial task. In Experiment 1, pigeons were trained on three successive six-pair concurrent discrimination tasks, each using a novel set of stimuli. There was no difference between control unoperated pigeons and Hp-APH pigeons in terms of the number of sessions required to learn either the first, second, or third concurrent discrimination task. In Experiment 2, the same pigeons were trained on an open-field spatial task similar in many ways to the radial-arm maze task used with rats. In contrast to the absence of impairments on the visual concurrent discrimination task, pigeons with Hp-APH lesions were severely impaired on the acquisition of the spatial task. These findings support the view that the Hp-APH in pigeons is important for the processing of spatial, rather than visual information.     

Initial storage of unfamiliar objects: examining memory stores with signal detection analyses

The memory source(s) underlying performance of the object decision task were examined. Application of signal detection theory with independent indices of sensitivity and bias indicated that greater object decision sensitivity (possible vs. impossible object discrimination) is observed for primed than for unprimed objects and a greater bias to respond "possible" is observed for primed than for unprimed objects. To test whether a single memory store underlies the two effects, we assessed whether the two effects would be influenced in similar ways by a particular experimental manipulation. Sensitivity did not differ between processing of 180 degrees -rotated primed objects vs. un-rotated primed objects, but bias to respond "possible" differed between those conditions in predictable ways depending on the cerebral hemisphere of direct test presentations. Results support a conciliatory resolution to the debate concerning memory in this task and help to clarify properties of memory stores underlying the initial storage of unfamiliar objects.     

Effects of motor congruence on visual working memory

Grounded-cognition theories suggest that memory shares processing resources with perception and action. The motor system could be used to help memorize visual objects. In two experiments, we tested the hypothesis that people use motor affordances to maintain object representations in working memory. Participants performed a working memory task on photographs of manipulable and nonmanipulable objects. The manipulable objects were objects that required either a precision grip (i.e., small items) or a power grip (i.e., large items) to use. A concurrent motor task that could be congruent or incongruent with the manipulable objects caused no difference in working memory performance relative to nonmanipulable objects. Moreover, the precision- or power-grip motor task did not affect memory performance on small and large items differently. These findings suggest that the motor system plays no part in visual working memory.     

Perceptual organization influences visual working memory

Previous studies have demonstrated that top-down factors can bias the storage of information in visual working memory. However, relatively little is known about the role that bottom-up stimulus characteristics play in visual working memory storage. In the present study, subjects performed a change detection task in which the to-be-remembered objects were organized in accordance with Gestalt grouping principles. When an attention-capturing cue was presented at the location of one object, other objects that were perceptually grouped with the cued object were more likely to be stored in working memory than were objects that were not grouped with the cued object. Thus, objects that are grouped together tend to be stored together, indicating that bottom-up perceptual organization influences the storage of information in visual working memory.     

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.     

Persistence of acquired behavioral control in the context of imprinting

Newly hatched Khaki Campbell ducklings (Anas platyrhynchos domesticus) were exposed to a moving object that immediately suppressed distress vocalizations occurring in a novel environment. The static visual and auditory features of this object acquired the ability to suppress distress vocalizations after eight 20-min sessions of exposure to the object in motion. The acquired suppressive properties of these features were found to persist throughout thirty 20-min sessions given over 10 days. During these sessions, the ducklings were continually exposed to the static features in the absence of visual movement. In a second experiment, the ability of these features in the absence of visual movement. In a second experiment, the ability of these features to serve as reinforcement for a pecking response was shown to persist for up to 56 hr. In one duckling, presentations of the static visual features did not maintain pecking behavior. However, it was shown that pecking responses could be re-instated in this duckling by introducing novel stimuli to the environment.     

Effects of fornix transection upon associative memory in monkeys: Role of the hippocampus in learned action

Thirty-three monkeys took part in seven experiments designed to elucidate further the effect of fornix transection on learning and memory. In the first experiment the monkeys had to remember whether stimulus objects had previously been paired with reward or no reward, and they had to use this memory to guide choice between stimulus objects at retention tests according to an arbitrary rule which they had learned: to choose objects previously paired with no reward in preference to objects previously paired with reward. Fornix transection produced a severe and permanent impairment in this task. In the second experiment the monkeys also had to remember object-reward associations but the performance rule was more natural: to choose objects previously paired with reward. Here fornix transection had no effect. The third experiment required the monkeys to remember, given a stimulus object, which of two events of equal valence had previously been the outcome of displacing that object. The two events were either a peanut and a sultana or a black penny and a white penny of equal secondary reinforcing value. Performance was unimpaired by fornix transection. The fourth experiment also demonstrated, in a different paradigm, unimpaired recall of sensory events. The fifth experiment demonstrated an impairment following fornix transection in acquisition of simultaneous spatial-visual conditional discriminations; the sixth demonstrated normal learning by fornix-transected monkeys of a successive spatial-visual conditional discrimination and the seventh demonstrated unimpaired acquisition of a simultaneous auditory-visual conditional discrimination. These results, when considered in detail and together, are incompatible with existing hypotheses of hippocampal function. A new hypothesis is discussed.     

When do spatial and visual working memory interact?

This study examined how spatial working memory and visual (object) working memory interact, focusing on two related questions: First, can these systems function independently from one another? Second, under what conditions do they operate together? In a dual-task paradigm, participants attempted to remember locations in a spatial working memory task and colored objects in a visual working memory task. Memory for the locations and objects was subject to independent working memory storage limits, which indicates that spatial and visual working memory can function independently from one another. However, additional experiments revealed that spatial working memory and visual working memory interact in three memory contexts: when retaining (1) shapes, (2) integrated color-shape objects, and (3) colored objects at specific locations. These results suggest that spatial working memory is needed to bind colors and shapes into integrated object representations in visual working memory. Further, this study reveals a set of conditions in which spatial and visual working memory can be isolated from one another.     

Toddlers’ cognition of adding and subtracting objects in action and in perception

A first experiment tested infants’ perceptual discrimination between correct and incorrect adding and subtracting objects with a standardized violation-of-expectation procedure. Eleven-, 16- and 21-month-olds did not look longer at incorrect (one object) than at correct (two objects) results of adding one object to another, nor at incorrect (two objects) than at correct (one object) results of subtracting one object from two. A second experiment tested 21-month-olds’ sensorimotor production of addition and subtraction results using a search-for-objects procedure. They already searched correctly for two objects when one object is added to another and for one object when one is subtracted from two objects. These findings support the constructivist hypothesis that infants’ active sensorimotor production may develop before their reactive perceptual discrimination of adding and subtracting objects.     

Evidence for neocortical involvement in reference memory

Rats were trained on an eight-arm radial maze task using a procedure that provides for an assessment of both working and reference memory. Following training, rats received parietal cortex, medial prefrontal cortex, visual cortex, or nucleus basalis magnocellularis lesions. Rats with visual cortex lesions showed no change in performance on either working or reference memory. Rats with parietal cortex lesions displayed a temporary deficit in reference, but no deficit on working memory. Animals with medial prefrontal cortex lesions showed a temporary deficit on both working and reference memory. Rats with extensive lateral frontal and parietal cortex depletion of acetylcholinesterase following nucleus basalis magnocellularis lesions had a marked disruption only of reference but not of working memory. It is concluded that neocortex and possibly the cholinergic projections to neocortex play an important role in mediating reference memory.     

Interactions between visual working memory and selective attention

The relationship between working memory and selective attention has traditionally been discussed as operating in one direction: Attention filters incoming information, allowing only relevant information into short-term processing stores. This study tested the prediction that the contents of visual working memory also influence the guidance of selective attention. Participants held a sample object in working memory on each trial. Two objects, one matching the sample and the other novel, were then presented simultaneously. As measured by a probe task, attention shifted to the object matching the sample. This effect generalized across object type, attentional-probe task, and working memory task. In contrast, a matched task with no memory requirement showed the opposite pattern, demonstrating that this effect is not simply due to exposure to the sample. These results confirm a specific prediction about the influence of working memory contents on the guidance of attention.