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Biomedical subjects

E A Murray

Publications and source records attributed to E A Murray.

At least 55 records · Page 3Linked to original sources

Removal of the amygdala plus subjacent cortex disrupts the retention of both intramodal and crossmodal associative memories in monkeys.

Naive rhesus monkeys (Macaca mulatta) were trained preoperatively in an automated test apparatus on an auditory-visual (crossmodal) conditional task or on a visual-visual (intramodal) conditional task that involved learning a fixed set of stimulus-stimulus associations or paired associates. After having learned their respective tasks, each monkey received bilateral removal of the amygdala plus subjacent cortex. The 2 experimental groups showed equally poor retention of the stimulus-stimulus associations and subsequently relearned their respective crossmodal and intramodal associations at the same rate. These data argue against the idea that the amygdala is specialized for crossmodal associations. Instead, the data indicate that the amygdala or its underlying cortex, or both, play a more generalized role in stimulus-stimulus associative memory.

Amygdala↗

Cytopathologic and neurochemical correlates of progression to motor/cognitive impairment in SIV-infected rhesus monkeys.

Neurochemical, pathologic, virologic, and histochemical correlates of simian immunodeficiency virus (SIV)-associated central nervous system (CNS) dysfunction were assessed serially or at necropsy in rhesus monkeys that exhibited motor and cognitive deficits after SIV infection. Some infected monkeys presented with signs of acquired immunodeficiency disease (AIDS) at the time of sacrifice. Seven of eight animals exhibited motor skill impairment which was associated with elevated quinolinic acid in cerebrospinal fluid (CSF). Examination of the brains revealed diffuse increases in glial fibrillary acidic protein immunoreactivity in cerebral cortex in all animals, regardless of evidence of immunodeficiency disease. Reactive astrogliosis preceded or was coincident with the onset of neuropsychological impairments. Virus rescue from CSF of six of eight infected animals showed that one of three animals with AIDS and none of three animals without AIDS at necropsy had virus rescue-positive CSF. Multinucleated giant cells were seen in the brain of only one animal with end-stage AIDS and high systemic virus burden at death. Neither systemic nor CNS virus burden was associated with the onset of CNS dysfunction. SIV-associated motor/cognitive impairment is associated with subtle, widespread changes in CNS cytology and neurochemistry, rather than with large increases in brain virus burden or widespread virus-associated brain lesions.

Animals↗

A primacy effect in monkeys when list position is relevant.

In Experiment 1 (1a and 1b), Rhesus monkeys (Macaca mulatta) learned lists of two-choice visual discriminations in which list position was relevant to discrimination performance. For example, Stimulus A was the rewarded stimulus if it was presented at List Position 1, but was not rewarded if it was presented at any other position in the list; similarly, Stimulus B was rewarded only at List Position 2, and so on. In learning these lists, all animals showed a marked primacy effect. In Experiment 2 (2a and 2b), Rhesus monkeys and Cynomolgus monkeys (M. fascicularis) learned lists of visual discriminations in which each visual stimulus occupied a fixed position in a list, but list position was not relevant to discrimination performance. For example, Stimulus E was always rewarded, and was always presented at List Position 1. To increase the salience of list beginning as a distinctive event, successive presentations of the list were separated by 24-hr intervals. In Experiment 2 there was no primacy effect, however. These results show for the first time that a primacy effect can be obtained in visual discrimination learning by monkeys. Furthermore, they suggest that it is obtained only when list position is relevant to the discrimination learning task.

Animals↗

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)

Amygdala↗

Hippocampectomized monkeys can remember one place but not two.

In an earlier study by Parkinson et al. (J. Neurosci. 8, 4159-4167, 1988), hippocampectomized monkeys were found to be impaired on a task in which they were required to remember the spatial positions of trial-unique objects overlying two of the wells in a three-well test tray. There were two types of trial in the task. One type (object-place) required memory for the conjunction of object quality and object location, whereas the other (place only) required memory only for the location of the objects, i.e. independent of object quality. The hippocampectomized monkeys performed at near chance levels on both types of trials. The present study sought to determine whether the poor performance of the hippocampectomized monkeys on the place-only trials, which closely resembled spatial delayed response (an ability that is unaffected by hippocampectomy when similarly short delays are used), could have been due to interference from the simultaneous training they had received on the object-place trials. To this end, we examined the effect of hippocampal removals on performance of the "place-only" trial type when that was the only training given. The hippocampectomized monkeys in the present study were found to be just as severely impaired as those in the earlier study, thus ruling out the possible explanation outlined above. Since performance on this modified version of spatial delayed response, unlike performance on the classical version with the same delay, is critically dependent on the hippocampus, it appears that monkeys with hippocampectomy can remember one place after a short delay but not two.

Animals↗

Effects on visual recognition of combined and separate ablations of the entorhinal and perirhinal cortex in rhesus monkeys.

Performance on visual delayed nonmatching-to-sample was assessed in rhesus monkeys with combined and separate ablations of the perirhinal and entorhinal cortex, as well as in unoperated controls. Combined (i.e., rhinal cortex) lesions yielded a striking impairment on this task, one almost as severe as that seen after combined amygdalohippocampal removals that included some of this subjacent cortex (Mishkin, 1978; Murray and Mishkin, 1984). Ablations of the perirhinal cortex alone produced a deficit nearly as severe as that found after rhinal cortex lesions, whereas ablations of the entorhinal cortex alone produced only a mild deficit. Contrary to the conclusion from an earlier study (Murray and Mishkin, 1986), the present results demonstrate not only that damage limited to the rhinal cortex is sufficient to produce a severe loss in visual recognition, but also that such damage leads to a far greater loss than damage to any other single structure in the medial part of the temporal lobe.

Animals↗

Neural substrates of visual stimulus-stimulus association in rhesus monkeys.

Rhesus monkeys learned 10 visual stimulus-stimulus association, or paired associates. They then received bilateral removals of either the amygdaloid complex and underlying cortex, the hippocampal formation and underlying cortex, or both combined, or they were retained as unoperated controls. After surgery or rest, the monkeys were tested for their retention of the preoperatively learned set of paired associates, as well as for their ability to learn new associations of the same type. Both unoperated controls and hippocampectomized monkeys relearned the preoperatively trained set of paired associates almost immediately. By contrast, monkeys with amygdala removals were moderately retarded in relearning, and monkeys with combined amygdala and hippocampal ablations were severely retarded. When confronted with new sets of visual stimuli, monkeys with amygdala removals or hippocampal removals learned new sets of paired associates at the same rate as the controls, whereas monkeys with the combined ablation were again profoundly retarded. Only one monkey with the combined lesion was able to learn new stimulus-stimulus associations to criterion, and then only after extensive training, despite the ability of all three animals in this group to perform delayed matching-to-sample with the same stimuli and the same intraatrial delays as those used in the paired associate task. At the end of the main experiment, two of the unoperated controls received bilateral ablations of the rhinal cortex. These monkeys showed the same level of difficulty in learning new paired associates as the animals in the main experiment that had received the combined amygdala plus hippocampal ablations. The results implicate the medial temporal lobe, and particularly the rhinal cortex, in the formation of stimulus-stimulus associative memories.

Amygdala↗

Cognitive and motor impairments associated with SIV infection in rhesus monkeys.

Cognitive and motor deficits are now recognized as significant clinical features of infection with the human immunodeficiency virus (HIV). Juvenile rhesus macaques infected with simian immunodeficiency virus (SIV) were found to exhibit cognitive and motor deficits characteristic of HIV infection. Impairment on a motor skill task was the most reliable indicator of infection. Various cognitive impairments were also evident. These deficits were related to SIV infection of the brain but not to inflammatory lesions at a particular locus. The results suggest that the SIV-infected rhesus macaque is a valuable model for understanding the cause of HIV-associated central nervous system dysfunction and for developing a treatment.

Animals↗

Monkeys (Macaca fascicularis) with rhinal cortex ablations succeed in object discrimination learning despite 24-hr intertrial intervals and fail at matching to sample despite double sample presentations.

Six cynomolgus monkeys (Macaca fascicularis) learned preoperatively a set of 10 concurrent object discriminations with 24-hr intertrial intervals. Three then had the rhinal cortex removed bilaterally, whereas the other 3 remained as unoperated controls. The animals with ablations were impaired in reacquiring the preoperatively acquired set but subsequently learned without any impairment a new set of 10 discriminations that was presented in the same way. The monkeys with rhinal cortex ablations then failed to learn delayed matching to sample, with double sample presentations, in 510 trials, whereas the control animals learned this task in 270 trials on average. The results add to existing evidence that rhinal cortex ablation produces a severe impairment in visual short-term recognition memory and show for the first time that this impairment is accompanied by normal long-term discrimination learning ability.

Animals↗

The technique of laparoscopic cholecystectomy in children.

Twelve children underwent elective laparoscopic cholecystectomy for symptomatic cholelithiasis during a 10-month period in one institution. The operative technique that has been described for adults was modified because of the smaller dimensions of pediatric patients. These modifications are discussed in this report, as are new alternatives for evaluating the common duct. No operative complications or conversions to open cholecystectomy occurred, and no complications after surgery were seen during an average follow-up period of 4.5 months. The benefits of laparoscopic cholecystectomy include decreased pain and ileus after surgery, shortened hospitalization, and improved cosmesis. Laparoscopic cholecystectomy is safe and efficacious in children, and it compares favorably with traditional cholecystectomy in the pediatric age group.

Adolescent↗

Mechanisms of major biliary injury during laparoscopic cholecystectomy.

Laparoscopic cholecystectomy has become the procedure of choice for surgical removal of the gallbladder. The most significant complication of this new technique is injury to the bile duct. Twelve cases of bile duct injury during laparoscopic cholecystectomy were reviewed. Eight injuries were of a classic type: misidentification of the common duct for the cystic duct, resection of part of the common and hepatic ducts, and associated right hepatic arterial injury. Another injury was similar: clip ligation of the distal common duct with proximal ligation and division of the cystic duct, resulting in biliary obstruction and leakage. Three complications arose from excessive use of cautery or laser in the region of the common duct, resulting in biliary strictures. Evaluation of persistent diffuse abdominal pain led to the recognition of ductal injury in most patients. Ultimately, 10 patients required a Roux-en-Y hepaticojejunostomy to provide adequate biliary drainage. One patient had a successful direct common duct repair, and the remaining patient underwent endoscopic dilatation.

Adult↗

The validity of the Constructional subtests of the Sensory Integration and Praxis Tests.

This study was designed to examine the validity of the Design Copying and Constructional Praxis subtests of the Sensory Integration and Praxis Tests (SIPT) (Ayres, 1989) through an examination of convergent validity and the use of contrast groups. The subjects were 39 children aged 5 to 8 years. Of these children, 21 had learning disabilities and 18, who served as the control group, had no learning disabilities. The subjects were administered the SIPT as well as four other standardized measures of constructional abilities: the Developmental Test of Visual-Motor Integration (Beery, 1980), the Block Design subtest of the Wechsler Intelligence Scale for Children-Revised (Wechsler, 1974), the Primary Visual Motor Test (Haworth, 1970), and the Rey-Osterrieth Complex Figure Test (Waber & Holmes, 1985). The results indicated that the children with learning disabilities performed significantly more poorly than did the control subjects on both the Design Copying and Constructional Praxis subtests. These two subtests showed moderately high correlations (.46 to .71) with the other tests of constructional abilities when both groups were combined. Correlations were mostly in the moderate range for the children with learning disabilities but were generally not significant for the control sample. The results are discussed in terms of task demands and subject variability.

Child↗

The relationship between form and space perception, constructional abilities, and clumsiness in children.

The Sensory Integration and Praxis Tests (SIPT) (Ayres, 1989) were administered to 21 children with learning disabilities and 18 children without learning disabilities, aged 5 to 8 years. The children with learning disabilities were divided into two groups, clumsy and nonclumsy, on the basis of their scores on the Test of Motor Impairment (Stott, Moyes, & Henderson, 1984). It was hypothesized that the learning-disabled children in the clumsy group would score significantly lower than the learning-disabled children in the nonclumsy group on the six SIPT subtests that measure form and space perception and visual construction and that the nonclumsy learning-disabled children, in turn, would score significantly lower than the non-learning-disabled children. It was further hypothesized that there would be a significant correlation between the degree of clumsiness and the degree of visual-perceptual and constructional deficits. An analysis of the data indicated that both groups of learning-disabled children scored lower than the non-learning-disabled children on four of the six SIPT subtests. The clumsy and nonclumsy children with learning disabilities, however, differed from each other on only two subtests. The degree of clumsiness correlated significantly with three of the six subtests. The results are discussed in terms of variations in perceptual and motor skills related to subtypes of learning disabilities.

Child↗

Amygdalar interaction with the mediodorsal nucleus of the thalamus and the ventromedial prefrontal cortex in stimulus-reward associative learning in the monkey.

Cynomolgus monkeys (Macaca fascicularis) were assessed for their ability to associate visual stimuli with food reward. They learned a series of new 2-choice visual discriminations between colored patterns displayed on a monitor screen. The feedback for correct choice was the delivery of food. In order to promote associative learning between the visual stimuli and the incentive value of the food reward, reward delivery was not accompanied by any distinctive visual feedback on the display screen. The rate of learning new problems was assessed before and after surgery in a total of 16 monkeys. Three groups of 3 monkeys received bilaterally symmetrical ablations in either the amygdala, the mediodorsal nucleus of the thalamus, or the ventromedial prefrontal cortex. All these groups showed a severe postoperative learning impairment. Seven other animals were given a unilateral ablation in 1 of those 3 structures and a second unilateral ablation, in each case contralateral to and different from the first, in order to produce 2 groups in which a putative amygdalo-thalamo-prefrontal pathway had been disconnected by crossed unilateral lesions. One disconnection group had lesions in the amygdala and ventromedial prefrontal cortex; the other had lesions in the amygdala and the mediodorsal nucleus of the thalamus. The disconnection groups showed a significant impairment, but the effect of the disconnection surgeries was significantly milder than the effect of any of the 3 bilaterally symmetrical lesions. Therefore, symmetrical bilateral lesions in either the amygdala, the mediodorsal nucleus, or the ventromedial prefrontal cortex produce similar impairments in the present task, implying that these structures are functionally related to each other; but the relatively mild effect of disconnecting these structures from each other argues against the hypothesis that they are serial stages in a single, tightly linked functional pathway.

Amygdala↗

Effects of fornix transection and cingulate cortical ablation on spatial memory in rhesus monkeys.

This study, together with a parallel study in rats (Markowska et al. 1988), attempted to relate the effects of hippocampal-system damage on similar tasks in both rats and monkeys. Not only were monkeys given a task (Experiment 1) which was of the sort usually used with rats, but in the companion study rats were given tasks (Experiment 2) like those usually used with monkeys. Experiment 1 examined the performance of rhesus monkeys with hippocampal-system damage on a spatial working memory task. Monkeys were trained preoperatively on delayed nonmatching-to-sample in a T-maze, placed into groups matched for their preoperative learning scores, and then received one of three treatments: 1) transection of the fornix; 2) ablation of the cingulate cortex; or 3) a sham operation. Monkeys with fornix transection were severely and significantly impaired, but monkeys with cingulate cortical ablations were not significantly impaired, relative to the controls. The results demonstrate that monkeys with fornix transection are severely impaired on a spatial working memory task requiring locomotion and, taken together with earlier work, suggest that the effect of fornix transection in both rodents and nonhuman primates is at least qualitatively similar (see Markowska et al. 1988). Experiment 2 assessed the role of the fornix and cingulate cortex in three conditional tasks in which the monkeys were provided with various spatial cues to indicate which one of two objects was rewarded. Both experimental groups were unimpaired, relative to the control group, on all three tasks, indicating that fornix transection does not produce a general impairment in place learning.

Animals↗

A comparative analysis of the role of fornix and cingulate cortex in memory: rats.

In order to compare the role of the fornix (FX) and cingulate cortex (CC) in memory, rats were trained in a series of discriminations using procedures that were the same as those used for monkeys (Murray et al. 1986, 1988). A spatial delayed nonmatching-to-sample (DNMS) discrimination tested recent memory for spatial location in a T maze using interrun intervals (IRI) that varied from 5 s to 15 min. FX and CC lesions produced a substantial impairment in the performance of this task during postoperative testing. Three conditional discriminations (CD) followed. In each one, the rat was presented with two objects, only one of which was correct. The nature of the conditional stimuli changed in each discrimination: the place of the maze in the room; the direction that the rat moved to approach the objects; the side (left or right) to which the rat turned. Control rats learned all three types of conditional discriminations. FX and CC lesions did not impair choice accuracy. In a subsequent repetition of the spatial DNMS procedure, FX and CC lesions again produced a substantial impairment, indicating that the lack of an impairment in the three CDs was not due to recovery of function. These data indicate that the hippocampal system and its connections through the fornix are importantly involved in spatial working memory in both rats and monkeys, and that the CDs do not require this type of memory. The results are discussed in the context of different theories of the brain mechanisms involved in memory.

Animals↗