The Von Restorff effect in visual object recognition memory in humans and monkeys. The role of frontal/perirhinal interaction

This study reports the development of a new, modified delayed matching to sample (DMS) visual recognition memory task that controls the relative novelty of test stimuli and can be used in human and nonhuman primates. We report findings from normal humans and unoperated monkeys, as well as three groups of operated monkeys. In the study phase of this modified paradigm, subjects studied lists of two-dimensional visual object stimuli. In the test phase each studied object was presented again, now paired with a new stimulus (a foil), and the subject had to choose the studied item. In some lists one study item (the novel or isolate item) and its associated foil differed from the others (the homogenous items) along one stimulus dimension (color). The critical experimental measure was the comparison of the visual object recognition error rates for isolate and homogenous test items. This task was initially administered to human subjects and unoperated monkeys. Error rates for both groups were reliably lower for isolate than for homogenous stimuli in the same list position (the von Restorff effect). The task was then administered to three groups of monkeys who had selective brain lesions. Monkeys with bilateral lesions of the amygdata and fornix, two structures that have been proposed to play a role in novelty and memory encoding, were similar to normal monkeys in their performance on this task. Two further groups--with disconnection lesions of the perirhinal cortex and either the prefrontal cortex or the magnocellular mediodorsal thalamus--showed no evidence of a von Restorff effect. These findings are not consistent with previous proposals that the hippocampus and amygdala constitute a general novelty processing network. Instead, the results support an interaction between the perirhinal and frontal cortices in the processing of certain kinds of novel information that support visual object recognition memory.     

Perirhinal cortex ablation impairs visual object identification

Impairments in both recognition memory and concurrent discrimination learning have been shown to follow perirhinal cortex ablation in the monkey. The pattern of these impairments is consistent with the hypothesis that the perirhinal cortex has a role in the visual identification of objects. In this study we compared the performance of a group of three cynomolgus monkeys with bilateral perirhinal cortex ablation with that of a group of three normal controls in two tasks designed to test this hypothesis more directly. In experiment 1 the subjects relearned a set of 40 familiar concurrent discrimination problems; the stimuli in each trial were digitized images of real objects presented in one of three different views. After attaining criterion they were tested on the same problems using similar, but previously unseen, views of the objects. In experiment 2 the subjects were tested on their ability to perform 10 of these familiar discriminations with each problem presented in the unfamiliar context of a digitized image of a unique complex scene. The subjects with ablations were significantly impaired on both tasks. These results demonstrate that the role of the perirhinal cortex is not restricted to memory, and they support the hypothesis that the perirhinal cortex is involved in visual object identification. We suggest that the perirhinal cortex is crucially involved in processing coherent concepts of individual objects. A deficit of this nature could underlie the pattern of impairments that follow perirhinal cortex damage in both visual object recognition memory and visual associative memory.     

The role of prefrontal cortex in working memory: examining the contents of consciousness

Working memory enables us to hold in our 'mind's eye' the contents of our conscious awareness, even in the absence of sensory input, by maintaining an active representation of information for a brief period of time. In this review we consider the functional organization of the prefrontal cortex and its role in this cognitive process. First, we present evidence from brain-imaging studies that prefrontal cortex shows sustained activity during the delay period of visual working memory tasks, indicating that this cortex maintains on-line representations of stimuli after they are removed from view. We then present evidence for domain specificity within frontal cortex based on the type of information, with object working memory mediated by more ventral frontal regions and spatial working memory mediated by more dorsal frontal regions. We also propose that a second dimension for domain specificity within prefrontal cortex might exist for object working memory on the basis of the type of representation, with analytic representations maintained preferentially in the left hemisphere and image-based representations maintained preferentially in the right hemisphere. Furthermore, we discuss the possibility that there are prefrontal areas brought into play during the monitoring and manipulation of information in working memory in addition to those engaged during the maintenance of this information. Finally, we consider the relationship of prefrontal areas important for working memory, both to posterior visual processing areas and to prefrontal areas associated with long-term memory.     

Magnitude of the object recognition deficit associated with perirhinal cortex damage in rats: Effects of varying the lesion extent and the duration of the sample period.

The present study examines 2 factors that might moderate the object-recognition deficit seen after perirhinal cortex damage. Object recognition by normal rats was improved by extending (from 4 to 8 min) the sample period during which an object was first explored. Furthermore, there was a significant positive correlation between time spent in close exploration of the sample object and degree of successful novelty discrimination. In contrast, rats with perirhinal cortex lesions failed to benefit from increased close exploration and did not discriminate the novel object after even the longest sample period. Nevertheless, the lesions did not disrupt habituation across repeated exposure to the same object. The second factor was extent of perirhinal cortex damage. A significant correlation was found between total perirhinal cortex loss and degree of recognition impairment. Within the perirhinal cortex, only damage to the caudal perirhinal cortex correlated significantly with recognition memory deficits. This study highlights the critical importance of the perirhinal cortex within the temporal lobe for recognition memory and shows that the lesion-induced deficit occurs despite seemingly normal levels of close object exploration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of the novelty or familiarity of visual stimuli on the expression of the immediate early gene c-fos in rat brain

To investigate substrates of recognition memory, the cellular expression of Fos protein in rat brain has been studied after groups of rats were either shown sets of novel or highly familiar objects, or were exposed to the same pattern of illumination without objects being shown. Counts of stained nuclei were made in eight brain regions, where information about novel or familiar visual stimuli is likely to be processed or stored. The counts were relatively high in occipital visual association cortex and area TE of temporal cortex, intermediate in perirhinal cortex, entorhinal cortex, anterior cingulate cortex and the diagonal band of Broca, and low in the hippocampal formation and mediodorsal nucleus of the thalamus. The number of Fos-stained cells was significantly higher for the rats shown novel objects than for those shown familiar objects in perirhinal cortex, area TE, occipital cortex and anterior cingulate cortex. Arguments are advanced that these differences in counts indicate areas involved in the processing and/or storage of information about the novelty or familiarity of visual stimuli, information important to recognition memory.     

Memory impairment on a delayed non-matching-to-position task after lesions of the perirhinal cortex in the rat.

Previous research conducted in monkeys and rats has established that the perirhinal cortex is critically involved in object- or stimulus-recognition memory, whereas other research suggests this region may contribute to memory for object discriminations. These findings do not rule out the possibility that the perirhinal cortex plays a more general role in memory. The present experiment addressed whether selective lesions of the perirhinal cortex would result in a delay-dependent deficit on a test of memory that did not involve stimulus recognition or object memory. Rats with bilateral perirhinal lesions were tested on a delayed non-matching-to-position task. Lesions of the perirhinal cortex did not interfere with acquisition or performance at short (0–4 s)-delay intervals, but lesions did impair performance at longer delays. It is suggested that the perirhinal cortex is involved in maintaining representations of trial-specific information over time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the rat perirhinal cortex spare the acquisition of a complex configural visual discrimination yet impair object recognition.

Rats with perirhinal cortex lesions were sequentially trained in a rectangular water tank on a series of 3 visual discriminations, each between mirror-imaged stimuli. When these same discriminations were tested concurrently, the rats were forced to use a configural strategy to solve the problems effectively. There was no evidence that lesions of the perirhinal cortex disrupted the ability to learn the concurrent configural discrimination task, which required the rats to learn the precise combination of stimulus identity with stimulus placement (“structural” learning). The same rats with perirhinal cortex lesions were also unimpaired on a test of spatial working memory (reinforced T maze alternation), although they were markedly impaired on a new test of spontaneous object recognition. For the recognition test, rats received multiple trials within a single session in which on every trial, they were allowed to explore 2 objects, 1 familiar, the other novel. On the basis of their differential exploration times, rats with perirhinal cortex lesions showed very poor discrimination of the novel objects, thereby confirming the effectiveness of the surgery. The discovery that bilateral lesions of the perirhinal cortex can leave configural (structural) learning seemingly unaffected points to a need to refine those models of perirhinal cortex function that emphasize its role in representing conjunctions of stimulus features. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the dorsal prestriate cortex in visuospatial configural discrimination by monkeys

Cynomolgus monkeys (Macaca fascicularis) learned a series of visuospatial configural discriminations in which particular discriminative stimulus objects were rewarded only in particular spatial locations. For example, object X was rewarded if it was on the left but not if it was on the right. After ablation of part of the dorsal prestriate cortex they were impaired in learning discriminations of this kind. The same animals were not impaired in learning visual object discriminations in which spatial position was irrelevant, nor in learning spatial discriminations in which object identity was irrelevant. The results were compared with previously reported results from fornix transection in the same tasks; the deficit following dorsal prestriate ablation in visuospatial configural discrimination learning was similar in severity to that which followed fornix transection. The results show that the dorsal prestriate area has a more general role in visuospatial processing than was known hitherto, and they suggest that it interacts with the hippocampal formation and fornix in visuospatial memory tasks.     

Contributions of the entorhinal cortex, amygdala and hippocampus to human memory

Recent studies have indicated that, in the monkey, the rhinal cortex (consisting of the entorhinal and perirhinal cortices) is more important to visual recognition memory than the hippocampus or amygdala. The present study investigated the role of the entorhinal cortex in humans using memory scores from surgical epilepsy patients classified according to their mesial temporal lobe pathology. The temporal lobe removals included 4-5 cm of neocortex, amygdala, rhinal cortex and 2-3 cm of the hippocampus and parahippocampal gyrus. Compared to autopsied control subjects, all of the patients showed significant gliosis in the amygdala, but they differed as to whether or not there were entorhinal and/or hippocampal abnormalities. Both preoperatively and one or more years postoperatively, the patients performed tests of verbal recall (Wechsler Memory Scale Logical Memory), visual recall (Rey Figure), verbal recognition and visual recognition (Warrington Recognition Memory Test: Words and Faces, respectively). Preoperatively, patients with hippocampal pathology showed deficits in visual recall. Postoperatively, a significant drop in verbal and visual recall was seen only for patients who lost intact hippocampal tissue, irrespective of the condition of the excised entorhinal cortex. Together, the results argue that the hippocampus is more important than the entorhinal cortex for the recall of newly learned information.     

Suppression to visual, auditory, and gustatory stimuli habituates normally in rats with excitotoxic lesions of the perirhinal cortex.

In 3 habituation experiments, rats with excitotoxic lesions of the perirhinal cortex were found to be indistinguishable from control rats. Two of the habituation experiments examined the habituation of suppression of responding on an appetitive, instrumental baseline. One of those experiments used stimuli selected from the visual modality (lights), the other used auditory stimuli. The third experiment examined habituation of suppression of novel-flavored water consumption. In contrast to the null results on the habituation experiments, the perirhinal lesions disrupted transfer performance on a configural, visual discrimination, indicating the behavioral effectiveness of the lesions. Implications for comparator theories of habituation are considered, and it is concluded that others’ demonstrations of the sensitivity of object recognition to perirhinal cortex damage is not the result of standard habituation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rhinal cortex lesions produce mild deficits in visual discrimination learning for an auditory secondary reinforcer in rhesus monkeys.

Aspiration, but not neurotoxic, lesions of the amygdala impair performance on a visual discrimination learning task in which an auditory secondary reinforcer signals which of 2 stimuli will be reinforced with food. Because aspiration lesions of the amygdala interrupt projections of the rhinal cortex traveling close to the amygdala, it was hypothesized that damage to the rhinal cortex would severely impair learning in this task. Rhesus monkeys (Macaca mulatta) were trained to solve visual discrimination problems based on an auditory secondary reinforcer, were given lesions of the rhinal cortex or the perirhinal cortex alone, and were then retested. The monkeys displayed a reliable, albeit mild, deficit in postoperative performance. It is concluded that the aspiration lesions of the amygdala that produced a severe impairment did so because they interrupted connections of temporal cortical fields beyond the rhinal cortex that are also involved in learning in this task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction of the amygdala with the frontal lobe in reward memory

Five cynomolgus monkeys (Macaca fascicularis) were assessed for their ability to associate visual stimuli with food reward. They learned a series of new two-choice visual discriminations between coloured patterns displayed on a touch-sensitive monitor screen; the feedback for correct choice was delivery of food. Normal learning in this task is known to be dependent on the amygdala. The monkeys received brain lesions which were designed to disconnect the amygdala from interaction with other brain structures thought to be involved in this memory task. All the monkeys received an amygdalectomy in one hemisphere and lesions in the other hemisphere of some of the projection targets of the amygdala, namely the ventral striatum, the mediodorsal thalamus and the ventromedial prefrontal cortex. The rate of learning new problems was assessed before and after each operation. Disconnection of the amygdala from the ventral striatum was without effect on learning rate. An earlier study had shown that disconnection of the amygdala from either the mediodorsal thalamus or the ventromedial prefrontal cortex produced only a mild impairment, significantly less severe than that produced by bilateral lesions of any of these three structures. The present results show, however, that disconnection of the amygdala from both the mediodorsal thalamus and the ventromedial prefrontal cortex in the same animal, by crossed unilateral lesions of the amygdala in one hemisphere and of both the mediodorsal thalamus and the ventromedial prefrontal cortex in the other hemisphere, produces an impairment as severe as that which follows bilateral lesions of any of these three structures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential neuronal encoding of novelty, familiarity and recency in regions of the anterior temporal lobe

Activity of 2072 neurones was recorded in the anterior temporal lobe--in area TE, perirhinal cortex, entorhinal cortex and hippocampus--during performance of a visual recognition task by monkeys. In area TE, perirhinal cortex and entorhinal cortex, 454 neurones (38% of the 1162 visually responsive neurones) responded differentially on the basis of the relative familiarity or recency of presentation of the stimuli; in the hippocampus only one (3%) of its 40 visually responsive neurones) did so. The differentially responsive neurones were classified into those signalling information concerning the recency (19%), familiarity (37%) or novelty (38%) of stimuli. For 98% of these neurones a decreased response signalled that stimuli had occurred previously: no large response increments were observed. The mean differential latency of each of these types of neurone was shorter (approximately 75 ms) in area TE than in the other areas. Examples of each of these types of neurone with memory spans of approximately 24 h were found in each region. The mean memory span of recency neurones was significantly longer in perirhinal cortex than area TE. For familiarity neurones a significant mean response decrement took 4-8 min to develop, indicating a slow underlying plastic change, in contrast to the rapid change seen for recency and novelty neurones. The implications of these results are discussed in relation to the neuronal basis of recognition memory.     

The effects of neurotoxic lesions of the perirhinal cortex combined to fornix transection on object recognition memory in the rat

The effects of lesions centred in the perirhinal cortex region (Prh) or in both the perirhinal cortex region and the fornix (Prh + Fx) were assessed in two different working memory tasks, one spatial the other nonspatial. For the spatial task the rats were tested in an eight arm radial maze, using a standard procedure in which they were rewarded for avoiding previously visited arms. The Prh + Fx, but not the Prh, rats produced significantly more errors (re-entries) and these started significantly earlier in each session when compared with a surgical control group. The nonspatial task was a test of spontaneous object recognition in which rats were tested on their ability to discriminate between a familiar and a novel object. For the initial tests the Prh group failed to discriminate between the objects, but the Prh + Fx group showed a clear preference for the novel object. Observation of the test showed, however, that the Prh + Fx group were spending a greater length of time initially exploring the sample (familiar) object. When the amount of exposure to the sample object was limited to either 20 or 40 s (i.e. was the same for all three groups), the Prh + Fx group now failed to discriminate between the two objects. This change was especially evident for shorter sample duration (20 s). The Prh group did, however, show an amelioration of their deficit with this further testing. The present results support previous dissociation between spatial and nonspatial working memory, and indicate that there may be some recovery of function following perirhinal cortical damage.     

Material-specific memory in the intracarotid amobarbital procedure

We examined material-specific memory in 45 left hemisphere language dominant patients with temporal complex partial seizures (24 right, 21 left) during the intracarotid amobarbital procedure (IAP) by showing eight cards displaying two line drawings of common objects, two printed words, one colored shape, one math expression, one face, and one abstract shape following amobarbital injection (mean = 109.9 mg). We assessed delayed recall and recognition following clearing. Patients with right foci recognized significantly fewer verbally mediated stimuli (words, object drawings, colored shape) with left than with right injection. Patients with left foci recognized a nonverbal stimulus (abstract shape) more poorly following right versus left injection. Discriminant function analysis lateralized 85% of the sample from memory predictors, upheld to 81% on crossvalidation. Material-specific memory remains intact in the hemisphere contralateral to a seizure focus, but wider representation may occur for stimuli normally dominant for the hemisphere with the seizure focus. The IAP significantly lateralizes a seizure focus with use of both types of stimuli.     

Hemifield-specific visual recognition memory impairments in patients with unilateral temporal lobe removals

Recent evidence on visual neglect suggests that each hemisphere maintains a retinotopically organized representation of the visual world contralateral to the current fixation point and that this representation is based not only on analysis of the current retinal input but, equally importantly, on information retrieved from memory. This idea predicts that unilateral damage to memory systems should produce a lateralized impairment of memory for the retinotopically contralateral visual world. To test this prediction we examined visual recognition memory performance in the left and right visual hemifields of patients who had undergone partial unilateral temporal lobe removals for the relief of epilepsy, either in the left hemisphere (n = 5) or the right (n = 5). The patients were given complex artificial scenes to remember, constructed of independent left and right halves, and were then tested for recognition of the left and the right halves separately. Stimuli were exposed tachistoscopically throughout and fixation was maintained on a central position. Patients made significantly more errors with half-scenes in the hemifield contralateral to their removal than in the ipsilateral hemifield, an increase of 50% in the error rate on average. The effect was seen equally in patients with left and right removals. This finding supports the idea that visual memory retrieval is retinotopically organized.     

Amnesia and neglect: beyond the Delay-Brion system and the Hebb synapse

Hippocampal damage in people causes impairments of episodic memory, but in rats it causes impairments of spatial learning. Experiments in macaque monkeys show that these two kinds of impairment are functionally similar to each other. After any lesion that interrupts the Delay-Brion system (hippocampus, fornix, mamillary bodies and anterior thalamus) monkeys are impaired in scene-specific memory, where an event takes place against a background that is specific to that event. Scene-specific memory in the monkey corresponds to human episodic memory, which is the memory of a unique event set in a particular scene, as opposed to scene-independent human knowledge, which is abstracted from many different scenes. However, interruption of the Delay-Brion system is not sufficient to explain all of the memory impairments that are seen in amnesic patients. To explain amnesia the specialized function of the hippocampus in scene memory needs to be considered alongside the other, qualitatively different functional specializations of other memory systems of the temporal lobe, including the perirhinal cortex and the amygdala. In all these specialized areas, however, including the hippocampus, there is no fundamental distinction between memory systems and perceptual systems. In explaining memory disorders in amnesia it is also important to consider them alongside the memory disorders of neglect patients. Neglect patients fail to represent in memory the side of the world that is contralateral to the current fixation point, in both short- and long-term memory retrieval. Neglect was produced experimentally by unilateral visual disconnection in the monkey, confirming the idea that visual memory retrieval is retinotopically organized; patients with unilateral medial temporal-lobe removals showed lateralized memory impairments for half-scenes in the visual hemifield contralateral to the removal. Thus, in scene-memory retrieval the Delay-Brion system contributes to the retrieval of visual memories into the retinotopically organized visual cortex. This scene memory interpretation of hippocampal function needs to be contrasted with the cognitive-map hypothesis. The cognitive-map model of hippocampal function shares some common assumptions with the Hebb-synapse model of association formation, and the Hebb-synapse model can be rejected on the basis of recent evidence that monkeys can form direct associations in memory between temporally discontiguous events. Our general conclusion is that the primate brain encompasses widespread and powerful memory mechanisms which will continue to be poorly understood if theory and experimentation continue to concentrate too much, as they have in the past, on the hippocampus and the Hebb synapse.     

Dissociable Effects of Lesions to the Perirhinal Cortex and the Postrhinal Cortex on Memory for Context and Objects in Rats.

Memory for the context in which an object appeared was investigated with a version of the spontaneous object recognition paradigm. Sham-operated rats explore familiar objects appearing in incongruent but familiar contexts more than those appearing in congruent contexts, revealing memory for the context in which an object previously appeared. At short delays, perirhinal cortex-lesioned rats were unimpaired on memory for object in context, whereas fornix-lesioned rats showed only a mild impairment. In contrast, postrhinal lesions resulted in severe deficits. However, in a comparable noncontextual object task, postrhinal and fornix lesions had no effect, whereas perirhinal-lesioned rats were severely impaired. Comparison of these tasks and other published data may shed light on the nature of the contextual processing involved. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning of discriminations is impaired, but generalization to altered views is intact, in monkeys (Macaca mulatta) with perirhinal cortex removal.

Rhesus monkeys (Macaca mulatta) were taught a large number of visual discriminations and then either received bilateral removal of the perirhinal cortex or were retained as unoperated controls. Operated monkeys were impaired in retention of the preoperatively learned problems. To test for generalization to novel views, the monkeys were required to discriminate, in probe trials, familiar pairs of images that were rotated, enlarged, shrunken, presented with color deleted, or degraded by masks. Although these manipulations reduced accuracy in both groups, the operated group was not differentially affected. In contrast, the same operated monkeys were impaired in reversal of familiar discriminations and in acquisition of new single-pair discriminations. These results indicate an important role for perirhinal cortex in visual learning, memory, or both, and show that under a variety of conditions, perirhinal cortex is not critical for the identification of stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)