Biomedical subjects

Elisabeth A Murray

Publications and source records attributed to Elisabeth A Murray.

At least 19 recordsLinked to original sources

PubMed2006

Impairment and facilitation of transverse patterning after lesions of the perirhinal cortex and hippocampus, respectively.

We have recently suggested that certain effects of perirhinal cortex removals in monkeys can be attributed to the lesion compromising complex configural representations of visual stimuli. On this view, monkeys with perirhinal cortex lesions will be impaired on acquisition of discrimination problems that possess high "feature ambiguity," that is, those in which many of the same features belong to both rewarded and unrewarded stimuli. A subclass of feature-ambiguous problems includes "configural" discrimination problems in which all features are ambiguous. In the present study, we tested control monkeys and monkeys with bilateral lesions of perirhinal cortex on a configural discrimination problem, the transverse-patterning task (i.e., A+ vs. B-, B+ vs. C-, C+ vs. A-), using complex 2-dimensional visual stimuli. In addition, we investigated the effects of lesions to another structure that has been implicated in configural learning, the hippocampus. Monkeys with perirhinal cortex lesions were impaired, whereas monkeys with selective hippocampal lesions were facilitated, on acquisition of the transverse-patterning task. These data do not provide support for mass action theories of medial temporal lobe function, which cannot account for the opposing effects of the 2 lesions. These results are, however, compatible with a view that perirhinal cortex, and not the hippocampus, contains complex configural representations of visual stimuli critical to the solution of the transverse-patterning task.

Animals↗

PubMed2006

No effect of hippocampal lesions on perirhinal cortex-dependent feature-ambiguous visual discriminations.

Previous studies have shown that perirhinal cortex lesions in monkeys impair visual discriminations with a high degree of "feature ambiguity," a property of visual discriminations that can emerge when features are a part of both rewarded and unrewarded stimuli. The effects of damage to the hippocampus on these perirhinal-dependent feature-ambiguous tasks are, however, unknown. Prominent theories of medial temporal lobe function predict similar effects of perirhinal cortex and hippocampal lesions on cognitive tasks. In contrast, our hypothesis is that perirhinal cortex, and not the hippocampus, is important for nonspatial complex feature-ambiguous discriminations. We sought to distinguish between these competing theories in a straightforward way, by testing rhesus monkeys with hippocampal lesions on the same feature-ambiguous tasks shown previously to depend on perirhinal cortex. It was found that hippocampal lesions had no effects on any of these tasks. The findings support the perceptual-mnemonic/feature conjunction model of perirhinal cortex function, and provide further evidence for heterogeneity of function within the putative medial temporal lobe memory system.

Agnosia↗

PubMed2006

Prospective memory in the formation of learning sets by rhesus monkeys (Macaca mulatta).

In conventional discrimination learning-set formation, it is possible that rhesus monkeys (Macaca mulatta) learn to lay down prospective memories by anticipating the next trial and deciding in advance what choice will be made. To test this hypothesis, the authors administered discrimination problems with 24-hr intertrial intervals, predicting that these long intervals would disrupt or prevent the putative anticipation of the next trial. Confirming their expectation, the authors found no indication of learning-set formation under these conditions.

Animals↗

PubMed2005

Functional specialization in the human medial temporal lobe.

Investigations of memory in rats and nonhuman primates have demonstrated functional specialization within the medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampal formation and underlying entorhinal, perirhinal, and parahippocampal cortices. Most studies in humans, however, especially in patients with brain damage, suggest that the human MTL is a unitary memory system supporting all types of declarative memory, our conscious memory for facts and events. To resolve this discrepancy, amnesic patients with either selective hippocampal damage or more extensive MTL damage were tested on variations of an object discrimination task adapted from the nonhuman primate literature. Although both groups were equally impaired on standard recall-based memory tasks, they exhibited different profiles of performance on the object discrimination test, arguing against a unitary view of MTL function. Cases with selective hippocampal damage performed normally, whereas individuals with broader MTL lesions were impaired. Furthermore, deficits in this latter group were related not to the number of discriminations to be learned and remembered, but to the degree of "feature ambiguity," a property of visual discriminations that can emerge when features are part of both rewarded and unrewarded stimuli. These findings resolve contradictions between published studies in humans and animals and introduce a new way of characterizing the impairments that arise after damage to the MTL.

Aged↗

PubMed2005

Comparison of the effects of bilateral orbital prefrontal cortex lesions and amygdala lesions on emotional responses in rhesus monkeys.

The present study examines the effects of bilateral orbital prefrontal cortex (PFo) lesions on monkeys' emotional responses in two different contexts: in the presence of a rubber snake and in the presence of a human intruder. For comparison, we also assessed the responses of rhesus monkeys with selective amygdala lesions on these same tasks. Monkeys with PFo lesions, like those with amygdala lesions, displayed blunted emotional responses to the fake snake. Unlike monkeys with amygdala lesions, however, monkeys with PFo lesions displayed more mild aggression than controls in the presence of a human intruder. The findings support the idea that the PFo helps integrate sensory signals in the service of choosing among competing responses. In addition, they point to a divergence of the roles of the PFo and amygdala in responding to a social stimulus, the human intruder.

Amygdala↗

PubMed2005

Perceptual deficits in amnesia: challenging the medial temporal lobe 'mnemonic' view.

Recent animal studies suggest that the medial temporal lobe (MTL), which is thought to subserve memory exclusively, may support non-mnemonic perceptual processes, with the hippocampus and perirhinal cortex contributing to spatial and object perception, respectively. There is, however, no support for this view in humans, with human MTL lesions causing prominent memory deficits in the context of apparently normal perception. We assessed visual discrimination in amnesic cases to reveal that while selective hippocampal damaged patients could discriminate faces, objects, abstract art and colour, they were significantly poorer in discriminating spatial scenes. By contrast, patients with MTL damage, including perirhinal cortex, were significantly impaired in discriminating scenes, faces, and to a lesser extent objects, with relatively intact discrimination of art and colour. These novel observations imply that the human MTL subserves both perceptual and mnemonic functions, with the hippocampus and perirhinal cortex playing distinct roles in spatial and object discrimination, respectively.

Aged↗

PubMed2005

Opposing effects of amygdala and orbital prefrontal cortex lesions on the extinction of instrumental responding in macaque monkeys.

Extinction is a well-known behavioural phenomenon that allows organisms to respond flexibly to a changing environment. Although recent work implicates the amygdala and orbital prefrontal cortex (PFo) in extinction of Pavlovian conditioned fear and aversion, much less is known about the neural bases of instrumental extinction. To explore the contribution of the macaque amygdala to flexible responding in the face of changing reward contingency, we tested the effects of selective, excitotoxic lesions of the amygdala on extinction of an instrumental response. For comparison, we evaluated the effects of ablation of PFo on the same task. Amygdala lesions facilitated the extinction of instrumental responses, whereas lesions of PFo had the opposite effect.

Amygdala↗

PubMed2004

Bilateral orbital prefrontal cortex lesions in rhesus monkeys disrupt choices guided by both reward value and reward contingency.

The orbital prefrontal cortex (PFo) operates as part of a network involved in reward-based learning and goal-directed behavior. To test whether the PFo is necessary for guiding behavior based on the value of expected reward outcomes, we compared four rhesus monkeys with two-stage bilateral PFo removals and six unoperated controls for their responses to reinforcer devaluation, a task that assesses the monkeys' abilities to alter choices of objects when the value of the underlying food has changed. For comparison, the same monkeys were tested on a standard test of flexible stimulus-reward learning, namely object reversal learning. Relative to controls, monkeys with bilateral PFo removals showed a significant attenuation of reinforcer devaluation effects on each of two separate assessments, one performed shortly after surgery and the other approximately 19 months after surgery; the operated monkeys were also impaired on object reversal learning. The same monkeys, however, were unimpaired in acquisition of object discrimination learning problems and responded like controls when allowed to choose foods alone, either on a food preference test among six different foods or after selective satiation. Thus, satiety mechanisms and the ability to assign value to familiar foods appear to be intact in monkeys with PFo lesions. The pattern of results suggests that the PFo is critical for response selection based on predicted reward outcomes, regardless of whether the value of the outcome is predicted by affective signals (reinforcer devaluation) or by visual signals conveying reward contingency (object reversal learning).

Animals↗

PubMed2004

DNA targeting of rhinal cortex D2 receptor protein reversibly blocks learning of cues that predict reward.

When schedules of several operant trials must be successfully completed to obtain a reward, monkeys quickly learn to adjust their behavioral performance by using visual cues that signal how many trials have been completed and how many remain in the current schedule. Bilateral rhinal (perirhinal and entorhinal) cortex ablations irreversibly prevent this learning. Here, we apply a recombinant DNA technique to investigate the role of dopamine D2 receptor in rhinal cortex for this type of learning. Rhinal cortex was injected with a DNA construct that significantly decreased D2 receptor ligand binding and temporarily produced the same profound learning deficit seen after ablation. However, unlike after ablation, the D2 receptor-targeted, DNA-treated monkeys recovered cue-related learning after 11-19 weeks. Injecting a DNA construct that decreased N-methyl-d-aspartate but not D2 receptor ligand binding did not interfere with learning associations between the cues and the schedules. A second D2 receptor-targeted DNA treatment administered after either recovery from a first D2 receptor-targeted DNA treatment (one monkey), after N-methyl-d-aspartate receptor-targeted DNA treatment (two monkeys), or after a vector control treatment (one monkey) also induced a learning deficit of similar duration. These results suggest that the D2 receptor in primate rhinal cortex is essential for learning to relate the visual cues to the schedules. The specificity of the receptor manipulation reported here suggests that this approach could be generalized in this or other brain pathways to relate molecular mechanisms to cognitive functions.

Animals↗

PubMed2004

Rhesus monkeys (Macaca mulatta) discriminate between knowing and not knowing and collect information as needed before acting.

Humans use memory awareness to determine whether relevant knowledge is available before acting, as when we determine whether we know a phone number before dialing. Such metacognition, or thinking about thinking, can improve selection of appropriate behavior. We investigated whether rhesus monkeys ( Macaca mulatta) are capable of a simple form of metacognitive access to the contents of short-term memory. Monkeys chose among four opaque tubes, one of which concealed food. The tube containing the reward varied randomly from trial to trial. On half the trials the monkeys observed the experimenter baiting the tube, whereas on the remaining trials their view of the baiting was blocked. On each trial, monkeys were allowed a single chance to select the tube containing the reward. During the choice period the monkeys had the opportunity to look down the length of each tube, to determine if it contained food. When they knew the location of the reward, most monkeys chose without looking. In contrast, when ignorant, monkeys often made the effort required to look, thereby learning the location of the reward before choosing. Looking improved accuracy on trials on which monkeys had not observed the baiting. The difference in looking behavior between trials on which the monkeys knew, and trials on which they were ignorant, suggests that rhesus monkeys discriminate between knowing and not knowing. This result extends similar observations made of children and apes to a species of Old World monkey, suggesting that the underlying cognitive capacities may be widely distributed among primates.

Animals↗

PubMed2004

Combined unilateral lesions of the amygdala and orbital prefrontal cortex impair affective processing in rhesus monkeys.

The amygdala and orbital prefrontal cortex (PFo) interact as part of a system for affective processing. To assess whether there is a hemispheric functional specialization for the processing of emotion or reward or both in nonhuman primates, rhesus monkeys (Macaca mulatta) with combined lesions of the amygdala and PFo in one hemisphere, either left or right, were compared with unoperated controls on a battery of tasks that tax affective processing, including two tasks that tax reward processing and two that assess emotional reactions. Although the two operated groups did not differ from each other, monkeys with unilateral lesions, left and right, showed altered reward-processing abilities as evidenced by attenuated reinforcer devaluation effects and an impairment in object reversal learning relative to controls. In addition, both operated groups showed blunted emotional reactions to a rubber snake. By contrast, monkeys with unilateral lesions did not differ from controls in their responses to an unfamiliar human (human "intruder"). Although the results provide no support for a hemispheric specialization of function, they yield the novel finding that unilateral lesions of the amygdala-orbitofrontal cortical circuit in monkeys are sufficient to significantly disrupt affective processing.

Affect↗

PubMed2004

Method for making selective lesions of the hippocampus in macaque monkeys using NMDA and a longitudinal surgical approach.

We describe a method for making selective lesions of the hippocampus in macaque monkeys, using a magnetic resonance imaging (MRI)-guided stereotaxic approach in which the excitotoxin N-methyl-D-aspartic acid (NMDA) is injected at intervals along a single needle track that extends longitudinally through the rostrocaudal extent of the hippocampus. Procedures were conducted on six rhesus monkeys (Macaca mulatta) and were assessed with either in vivo MRI (n = 3) or postmortem microscopic examination of the tissue after standard histological processing of the brains (n = 3). Based on our extensive experience with the standard stereotaxic procedure in which ibotenic acid (IBO) is injected via the dorsal approach, we report that the new method provides a viable and potentially advantageous alternative to the standard procedure. First, the longitudinal approach combined with N-methyl-D-aspartic acid (NMDA) injections increases the reliability and efficacy of hippocampal excitotoxic lesions, probably by limiting the leakage of injectant into the ventricles. Second, the present procedure led to more rapid postoperative recovery compared with that after the standard procedure. Third, because the new method requires fewer needle penetrations than the standard method, it most likely reduces the chances of infarction in extrahippocampal tissue. Finally, the new surgical approach may provide a mechanism for infusing agents into the hippocampus from a single cannula.

Animals↗

PubMed2004

Selective hippocampal damage in rhesus monkeys impairs spatial memory in an open-field test.

The hippocampus is critical for remembering locations in a wide variety of species, including humans. However, recent findings from monkeys following selective hippocampal lesions have been equivocal. To approximate more closely the situations in which rodents and birds are tested, we used a spatial memory task in which rhesus monkeys (Macaca mulatta) moved about freely in a large room, on a tether. We used MRI-guided stereotaxic surgery to produce selective hippocampal lesions in five monkeys, and retained five unoperated control monkeys. In the study phase of each trial of the matching-to-location task, monkeys found food in one site in an array of identical foraging sites. During the test, which occurred after a delay, monkeys could return to the site where the food had been found during study to obtain more food. In Experiment 1, normal monkeys showed a small significant tendency to return directly to a site where they had previously found food that day. Operated monkeys showed no such matching tendency. In Experiment 2, further training produced reliable matching-to-location performance in both groups at short delays, but monkeys with selective hippocampal lesions rapidly forgot the location of the food. In Experiment 3, we tested whether monkeys used a "cognitive map" to encode the location of the hidden food, by requiring them to relocate the food from a starting location different from that used during study. As a group, monkeys were more accurate than expected by chance, indicating that they did encode the rewarded location with respect to allocentric landmarks; however, both groups of monkeys were significantly worse at relocating the food when required to approach from a different location. In Experiment 4, probe trials using symmetrical test arrays found no evidence for egocentric coding of the rewarded location.

Animals↗

PubMed2004

What, if anything, is the medial temporal lobe, and how can the amygdala be part of it if there is no such thing?

Should the medial temporal lobe (MTL) of primates--which includes allocortical structures such as the hippocampus, neocortical structures such as the parahippocampal cortex, and nuclear structures such as the basolateral amygdala--be considered a single "thing"? According to the prevailing view, here termed the reification theory, the answer is yes. According to this theory, the MTL functions as an amalgamated entity that provides the neuronal mechanisms for declarative memory; the greater the damage to the MTL or any of its components, the greater the deleterious effects on declarative memory. A countervailing view, here called the balkanization theory, holds that the various components of the MTL process and store different kinds of information. According to this theory, damage to each part of the MTL causes a unique set of behavioral deficits-some involving memory, others involving perception, and yet others involving response selection. The empirical neuropsychological evidence favors the balkanization theory, as do some new concepts in theoretical neuroanatomy.

Amygdala↗

PubMed2003

Effects of combined and separate removals of rostral dorsal superior temporal sulcus cortex and perirhinal cortex on visual recognition memory in rhesus monkeys.

The dorsal bank of the superior temporal sulcus (STSd) bears anatomical relations similar to those of perirhinal cortex, an area critical for visual recognition memory. To examine whether STSd makes a similar contribution to visual recognition memory, performance on visual delayed nonmatching-to-sample (DNMS) was assessed in rhesus monkeys with combined or separate ablations of the perirhinal cortex and STSd as well as in unoperated controls. Consistent with previous findings, ablations of perirhinal cortex produced deficits nearly as severe as that found after rhinal (i.e., entorhinal plus perirhinal) cortex lesions. However, combined lesions of perirhinal cortex and STSd produced a deficit no greater than that produced by perirhinal cortex ablation alone, and lesions of STSd alone were without effect on DNMS. We conclude that STSd is not critically involved in visual recognition memory.

Animals↗

PubMed2003

Impairments in visual discrimination after perirhinal cortex lesions: testing 'declarative' vs. 'perceptual-mnemonic' views of perirhinal cortex function.

Two experiments tested the predictions of 'declarative' vs. 'perceptual-mnemonic' views of perirhinal cortex function. The former view predicts that perirhinal cortex lesions should impair rapidly learned, but not more slowly learned, visual discriminations, whereas the latter view predicts that impairments should be related not to speed of learning but to perceptual factors. It was found that monkeys with perirhinal cortex lesions were impaired in the acquisition and performance of slowly learned, perceptually difficult greyscale picture discriminations, but were not impaired in the acquisition of rapidly learned, perceptually easier discriminations. In addition, these same monkeys were not impaired in the acquisition or performance of difficult colour or size discriminations, indicating that the observed pattern of impairments was not due to ceiling effects or difficulty per se. These findings, taken together, are consistent with the 'perceptual-mnemonic' view that the perirhinal cortex is involved in both perception and memory, but are not consistent with the 'declarative' view that the perirhinal cortex is important exclusively for declarative memory, having little or no role in perception. Moreover, the results are consistent with the more specific proposal that the perirhinal cortex contributes to the solution of complex visual discriminations with a high degree of 'feature ambiguity', a property of visual discrimination problems that can emerge when features of an object are rewarded when part of one object, but not when part of another. These and other recent findings suggest the need for a revision of prevailing views regarding the neural organization of perception and memory.

Animals↗

PubMed2002

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.

Animals↗

PubMed2002

The amygdala and reward.

The amygdala -- an almond-shaped group of nuclei at the heart of the telencephalon -- has been associated with a range of cognitive functions, including emotion, learning, memory, attention and perception. Most current views of amygdala function emphasize its role in negative emotions, such as fear, and in linking negative emotions with other aspects of cognition, such as learning and memory. However, recent evidence supports a role for the amygdala in processing positive emotions as well as negative ones, including learning about the beneficial biological value of stimuli. Indeed, the amygdala's role in stimulus-reward learning might be just as important as its role in processing negative affect and fear conditioning.

Amygdala↗