Biomedical subjects

E A Murray

Publications and source records attributed to E A Murray.

At least 37 records · Page 2Linked to original sources

PubMed1998

Object recognition and location memory in monkeys with excitotoxic lesions of the amygdala and hippocampus.

Earlier work indicated that combined but not separate removal of the amygdala and hippocampus, together with the cortex underlying these structures, leads to a severe impairment in visual recognition. More recent work, however, has shown that removal of the rhinal cortex, a region subjacent to the amygdala and rostral hippocampus, yields nearly the same impairment as the original removal. This raises the possibility that the earlier results were attributable to combined damage to the rostral and caudal portions of the rhinal cortex rather than to the combined amygdala and hippocampal removal. To test this possibility, we trained rhesus monkeys on delayed nonmatching-to-sample, a measure of visual recognition, gave them selective lesions of the amygdala and hippocampus made with the excitotoxin ibotenic acid, and then assessed their recognition abilities by using increasingly longer delays and list lengths, including delays as long as 40 min. Postoperatively, monkeys with the combined amygdala and hippocampal lesions performed as well as intact controls at every stage of testing. The same monkeys also were unimpaired relative to controls on an analogous test of spatial memory, delayed nonmatching-to-location. It is unlikely that unintended sparing of target structures can account for the lack of impairment; there was a significant positive correlation between the percentage of damage to the hippocampus and scores on portions of the recognition performance test, suggesting that, paradoxically, the greater the hippocampal damage, the better the recognition. The results show that, within the medial temporal lobe, the rhinal cortex is both necessary and sufficient for visual recognition.

Amygdala↗

PubMed1998

Selective hippocampal lesions yield nonspatial memory impairments in rhesus monkeys.

Monkeys with removals of medial temporal lobe (MTL) structures are widely recognized as valid models of human global anterograde amnesia, a syndrome that arises consequent to damage to a finite set of brain structures situated in the medial temporal lobe and/or medial diencephalon. However, a comparison of memory deficits in human and nonhuman primates with MTL damage has presented a long-standing puzzle. Whereas amnesic patients are impaired in learning object discrimination problems, monkeys with MTL damage are typically not. One possible explanation for this difference is that object discrimination tasks for humans and monkeys differ in that the former but not the latter requires the use of contextual information. If this analysis is correct, monkeys with MTL damage might be disadvantaged in learning to discriminate similar objects presented in different contexts. To test this possibility, we evaluated the effects of excitotoxic lesions of one of the MTL structures, the hippocampus, on the rate of learning of discrimination problems embedded within unique contexts. Monkeys with hippocampal lesions were impaired relative to controls in learning object discrimination problems of this type. These findings strongly support the idea that the difference in the effect on object memory of MTL damage in human and nonhuman primates is due to a difference in the opportunity to employ contextual cues rather than to a difference in the organization of memory.

Animals↗

PubMed1998

Aspiration lesions of the amygdala disrupt the rhinal corticothalamic projection system in rhesus monkeys.

In macaque monkeys, aspiration but not excitotoxic lesions of the medial temporal lobe limbic structures, the amygdala and hippocampus, produce a severe impairment in visual recognition memory. Furthermore, certain ventromedial cortical regions, namely the rhinal (i.e., entorhinal and perirhinal) cortex, are now known to be critical for visual recognition memory. Because the route taken by temporal cortical efferent fibers, especially perirhinal efferents, passes nearby the amygdala, it is possible that inadvertent damage to these fibers is produced by the aspirative but not the excitotoxic process, thereby accounting at least in part for the different behavioral outcomes of the two types of lesion. To test this idea, we assessed the integrity of the rhinal corticothalamic projection system after aspiration lesions of the amygdala. Three rhesus monkeys with unilateral amygdala removals received bilaterally symmetrical injections of a retrograde fluorescent tracer into the medial portion of the mediodorsal nucleus of the thalamus. Retrogradely labeled cells were identified using conventional fluorescence microscopy techniques. In all three cases, the rhinal cortex of the intact hemispheres contained moderate numbers of retrogradely labeled cells. By contrast, the rhinal cortex of the amygdalectomized hemispheres consistently contained few retrogradely labeled cells, and a direct comparison of the two hemispheres showed this difference to be statistically significant. A similar asymmetric pattern was observed for area TE but not for the cortex lining the dorsal bank of the superior temporal sulcus, nor for the rostral cingulate motor area, which was examined as a control. The results indicate that aspiration lesions of the amygdala not only remove the cell bodies of the amygdala, as intended, but also inadvertently disrupt projection fibers arising from cells in the rhinal cortex and area TE that pass nearby or through the amygdala en route to the thalamus. Behavioral studies examining the effects of aspiration lesions of the amygdala in nonhuman primates need to take these findings into consideration.

Amygdala↗

PubMed1998

Rhinal cortex ablations fail to disrupt reinforcer devaluation effects in rhesus monkeys (Macaca mulatta).

Studies have shown that excitotoxic lesions of the amygdala attenuate reinforcer devaluation effects in monkeys and rats. Because the rhinal (i.e., entorhinal and perirhinal) cortex has prominent reciprocal connections with the amygdala and has been suggested to store knowledge about objects, it is possible that it too composes part of the critical circuitry subserving learning about objects and their associated reinforcement value. To test this possibility, rhesus monkeys with rhinal cortex removals as well as unoperated controls were tested using a reinforcer devaluation procedure. Monkeys with rhinal cortex removals and controls, unlike those with amygdala lesions, tended to avoid displacing objects overlying a devalued food. These results indicate that the rhinal cortex is not a critical part of the neural circuitry mediating the effects of reinforcer devaluation.

Analysis of Variance↗

PubMed1998

Monkeys with rhinal cortex damage or neurotoxic hippocampal lesions are impaired on spatial scene learning and object reversals.

Rhesus monkeys (Macaca mulatta) with lesions of the rhinal cortex or parahippocampal gyrus (made by aspiration) or hippocampus (made with ibotenic acid) and unoperated controls were tested on object discrimination and reversal, place discrimination and reversal, and spatial scene learning to determine the contribution of these temporal lobe structures to these forms of learning and memory. Rhinal cortex lesions produced a severe deficit in object reversal learning; hippocampal lesions produced a milder deficit. Monkeys with rhinal cortex removals and those with hippocampal lesions were equally impaired on spatial scene learning. None of the lesions impaired place discrimination or reversal. These results argue against the idea that the mnemonic contributions of the rhinal cortex and hippocampus are limited to object and spatial domains, respectively.

Animals↗

PubMed1997

Rhinal cortex removal produces amnesia for preoperatively learned discrimination problems but fails to disrupt postoperative acquisition and retention in rhesus monkeys.

To test whether the rhinal cortex (i.e., entorhinal and perirhinal cortex) plays a time-limited role in information storage, eight rhesus monkeys were trained to criterion on two sets of 60 object discrimination problems, one set at each of two different time periods separated by 15 weeks. After the monkeys had learned both sets, two groups balanced for preoperative acquisition rates were formed. One group received bilateral ablation of the rhinal cortex (n = 4), and the other was retained as an unoperated control group (n = 4). After a 2 week rest period, monkeys were assessed for retention of the object discrimination problems. Retention was significantly poorer in monkeys with removals of the rhinal cortex relative to the controls (68 vs 91%). Although both groups showed slightly better retention of problems from the more recently learned set, there was no evidence of a differential effect of the cortical removal across sets (i.e., no temporal gradient). In addition, the monkeys with rhinal cortex lesions subsequently learned three new sets of 10 object discrimination problems as quickly as the controls did, thus ruling out the possibility of a gross impairment in visual perception or discrimination abilities. Furthermore, they retained these postoperatively learned object discriminations as well as the controls did. The findings indicate that the rhinal cortex is critical for the storage and/or retrieval of object discrimination problems that were learned up to 16 weeks before rhinal cortex ablation; however, in the absence of the rhinal cortex, efficient learning and retention of new discrimination problems can still occur.

Amnesia, Retrograde↗

PubMed1997

Excitotoxic lesions of the amygdala fail to produce impairment in visual learning for auditory secondary reinforcement but interfere with reinforcer devaluation effects in rhesus monkeys.

Aspiration lesions of the amygdala were found previously to produce a severe impairment in visual discrimination learning for auditory secondary reinforcement in rhesus monkeys (Gaffan and Harrison, 1987). To determine whether excitotoxic amygdala lesions would also produce this effect, we trained four naive rhesus monkeys on the same task. The monkeys were required to learn 40 new visual discrimination problems per session in a situation in which visual choices were guided by an auditory secondary reinforcer that had been previously associated with food reward. Bilateral excitotoxic lesions of the amygdala had no effect on the rate of learning visual discrimination problems for auditory secondary reinforcement. We also tested the amygdalectomized monkeys on a reinforcer devaluation task and compared their performance with a group of three normal monkeys. The monkeys first learned to discriminate 60 pairs of objects, baited with two different food rewards. Each of the food rewards was then devalued by selective satiation in two separate experimental sessions. Normal controls tended to avoid displacing objects that covered the devalued food to a significantly greater degree than did the amygdalectomized monkeys, indicating that the excitotoxic amygdala damage interfered with reinforcer devaluation effects. Our results are consistent with the idea that the amygdala is necessary for learning the association between stimuli and the value of particular food rewards; however, the amygdala is not necessary for maintaining the value of secondary reinforcers, once they have been learned.

Acoustic Stimulation↗

PubMed1997

Functional double dissociation between two inferior temporal cortical areas: perirhinal cortex versus middle temporal gyrus.

There is both anatomic and cytoarchitectural evidence for dorsal-ventral subdivisions of the inferior temporal cortex. Despite this, there has been only limited evidence of corresponding functional subdivisions and no evidence that two adjacent cortical areas within the inferior temporal cortex, namely area TE and the perirhinal cortex, have distinctly different roles in vision and memory. We assessed the color discrimination abilities of cynomolgus monkeys with either bilateral ablation of the perirhinal cortex or bilateral ablation of the middle temporal gyrus. The stimuli were isoluminant colored squares presented on a touch screen. In each trial the subject had to learn to discriminate and select the correct choice (green) from among a maximum of eight other foils, each varying in either hue or saturation. Relative to unoperated controls, monkeys with middle temporal gyrus lesions were severely impaired in the color discrimination task, whereas monkeys with perirhinal lesions were unimpaired on this task. We also assessed the visual recognition abilities, as measured by a basic delayed nonmatching-to-sample task with trial-unique objects presented in a Wisconsin General Test Apparatus, of rhesus monkeys with bilateral middle temporal gyrus lesions. We then tested the monkeys' postoperative performance on a delayed nonmatching-to-sample task with delays and extended list lengths. The results from this experiment were compared with those from two other groups of rhesus monkeys, an unoperated control group and a group with bilateral perirhinal cortex lesions, both of which had performed the identical tasks in a previous experiment. Relative to unoperated controls, monkeys with perirhinal cortex lesions were severely impaired both in relearning the basic delayed nonmatching-to-sample task and on the postoperative performance test. In contrast, monkeys with middle temporal gyrus lesions were only mildly affected in relearning the basic nonmatching task and were unimpaired on the postoperative performance test. Thus our data demonstrate a clear functional double dissociation between the perirhinal cortex and the middle temporal gyrus. This result gives strong support to the hypothesis that the perirhinal cortex and the adjacent area TE have distinctly different roles in visual learning and memory.

Analysis of Variance↗

PubMed1996

The neutron therapy clinical programme at the National Accelerator Centre (NAC).

A total of 721 patients were treated in the neutron therapy programme at NAC from February 1989-March 1995 with a p(66)/Be isocentric unit. The preliminary results showed: 3-year local control and survival probabilities of 57 and 79% respectively for advanced salivary gland tumours; increased local control for twice-daily neutron therapy for advanced head and neck cancer compared with photon therapy; local control rates of 68 and 83% for locally advanced breast cancer treated with 17 and 19 Gy respectively; complete response rates of 67% for macroscopic residual soft tissue sarcomas and those with irresectable disease of less than 10 cm; complete response rate of 56% for macroscopic residual uterine sarcoma with a median follow up of 38 months; 2-year local control rate and survival of 44 and 38% respectively for advanced squamous carcinoma of the maxillary antrum; complete response rate of 38% for advanced osteosarcomas and chondrosarcomas.

Breast Neoplasms↗

PubMed1996

Role of the hippocampus plus subjacent cortex but not amygdala in visuomotor conditional learning in rhesus monkeys.

Rhesus monkeys were trained to learn a large series of visuomotor conditional associations, each involving the arbitrary coupling of a visual stimulus with 1 of 3 potentially correct forelimb movements. The monkeys then received bilateral aspiration lesions of either the amygdala plus subjacent cortex or the hippocampus plus subjacent cortex. Hippocampal but not amygdala removals significantly retarded the learning of new visuomotor associations. Neither lesion affected retention. The findings argue against a general role for the amygdala in associating information across modalities, construed broadly to include motor information. By contrast, the finding that the hippocampal formation and its subjacent cortex play a role in learning new sensorimotor associations supports the view that this region participates in the long-term storage of associative information or in the recall of recently acquired information.

Amygdala↗

PubMed1996

Improved reliability of the Standardized Alzheimer's Disease Assessment Scale (SADAS) compared with the Alzheimer's Disease Assessment Scale (ADAS).

OBJECTIVES: To compare the interrater and intrarater reliability of the Alzheimer's Disease Assessment Scale (ADAS) with the Standardized Alzheimer's Disease Assessment Scale (SADAS). DESIGN: A randomized, double blind trial. Sixteen university students were randomized to administer either version of the instrument. Subjects were randomized to three assessments, at 2-week intervals, using the ADAS or the SADAS. Each subject's first and third tests were administered by the same rater, the second by a different rater. SETTING: A geriatric outpatient clinic in a university teaching hospital. PARTICIPANTS: Fifty-four patients with possible or probable Alzheimer's disease living in the community or in a long-term care facility. MEASUREMENTS: The primary outcome was the interrater reliability of total ADAS and SADAS scores. Secondary outcomes were ADAS and SADAS cognitive scores, noncognitive scores, duration of testing, and sample size estimates. RESULTS: The interrater reliability of the SADAS total score was significantly better than that of the ADAS (interrater ICC 0.93 SADAS vs 0.83 ADAS), and the interrater standard deviation of the total SADAS score was lower than that of the ADAS (38%, P < .05). The SADAS cognitive subscale inter and intrarater reliability, although higher than the ADAS, was not significantly different when used by different raters (interrater ICC 0.91 SADAS vs 0.90 ADAS; intrarater ICC 0.88 SADAS vs 0.86 ADAS). The SADAS noncognitive subscale was significantly more reliable than the ADAS (interrater ICC 0.89 SADAS vs 0.42 ADAS; intrarater ICC 0.87 SADAS vs 0.70 ADAS; P < or = .05) and had a lower standard deviation between raters (59%; P < .01) and within raters (40%; P < .05) compared with the ADAS. CONCLUSION: The improved reliability of the SADAS total score means that investigators can now use this score as a primary outcome measure, and important behavioral symptomatology can be included as a marker for treatment efficacy in AD. The smaller standard deviation of the SADAS means that clinical trials using the SADAS as a primary outcome will demonstrate differences, if present, with smaller sample sizes than with the ADAS.

Aged↗

PubMed1996

Effects of rhinal cortex lesions combined with hippocampectomy on visual recognition memory in rhesus monkeys.

1. We assessed the visual recognition abilities, as measured by delayed nonmatching-to-sample with trial-unique objects, of rhesus monkeys with hippocampectomy (i.e., removal of the hippocampal formation plus parahippocampal gyrus) combined with ablations of the rhinal cortex (i.e., entorhinal cortex plus perirhinal cortex). 2. Relative to unoperated controls, monkeys with combined hippocampectomy and rhinal cortex ablation (H+Rh) were significantly impaired in visual recognition. 3. Comparison of the scores of the monkeys in the present H+Rh group, which sustained near-complete rhinal cortex damage, with the scores of monkeys in an earlier H+Rh group in which the rostral part of the rhinal cortex had been spared indicates that the magnitude of the impairment is greater in the group with the more complete rhinal cortex damage. This finding is consistent with the idea that the rhinal cortex is critical for visual recognition. 4. Comparison of the present results with those from an earlier study on visual recognition that employed lesions limited to the rhinal cortex (Rh group) shows, paradoxically, that adding removal of the hippocampal formation and parahippocampal gyrus to a rhinal cortex lesion significantly reduces the recognition impairment produced by rhinal cortex lesions alone. 5. Our findings do not fit the view that the hippocampal formation, parahippocampal gyrus, and rhinal cortex constitute parts of a single functional system, such that the greater the damage to the entire system, the more severe the impairment. Instead, the results are consistent with the view that there are multiple functional subdivisions within the medial temporal lobe.

Animals↗

PubMed1996

The frontal cortex-basal ganglia system in primates.

The primate basal ganglia receives information from most of the cerebrum, including the frontal cortex, but projects (via the dorsal thalamus) primarily to the frontal lobe, perhaps in its entirety. As such, the frontal cortex and basal ganglia constitute an integrated, distributed neuronal architecture. We review evidence that the frontal lobe and basal ganglia specialize in different, but related, aspects of response learning. Frontal cortex acts when new rules need to be learned and older ones rejected, whereas the basal ganglia potentiate previously learned rules based on environmental context and reinforcement history. Such potentiation increases the probability that the central nervous system will select a particular rule to guide behavior. We outline a possible mechanism for the basal ganglia's proposed role in rule potentiation, one that involves both the direct and indirect striatal output pathways and their dopaminergic input. It has previously been proposed that direct-pathway neurons recognize a pattern of corticostriatal inputs, which promotes activity in recurrent, positive-feedback modules (or loops) of which they are an integral part. We propose that this recurrent activity potentiates a rule associated with those modules. If so, then the dopaminergic system is well situated and organized to modulate rule potentiation in both the short and long term. Dopaminergic neurons of the midbrain increase activity during learning and other periods of relatively unpredictable reinforcement. Dopamine enhances gene expression and other forms of activity in striatal neurons of the direct pathway, while suppressing neurons of the indirect pathway. In the short term, then, dopamine may augment the activity of modules triggered by a recognized context, whereas in the long term it may promote context-dependent activation of the same modules. Together, these modulatory influences could support both rule potentiation and learning the context for potentiating that rule.

Animals↗

PubMed1996

Supervision and consultation services for pediatric occupational therapists.

OBJECTIVE: Occupational therapists with advanced experience or expertise provide supervision and consultation services in a variety of settings. This pilot study examined the use of such supervision and consultation services by pediatric occupational therapists. METHOD: Special education administrators and pediatric occupational therapists from Massachusetts, a state often regarded as a leader in special education, responded to surveys designed especially for this study. These surveys asked about current supervision and consultation use, satisfaction with present services, and the need for additional resources in this area. Opinions regarding practice areas that would best be addressed by supervision and consultation were also obtained. RESULTS: Both administrator and therapist respondents agreed that expert occupational therapy supervision and consultation are needed. Identified areas of interest were classroom supervision and consultation strategies, service delivery decisions, and evaluation methods. CONCLUSION: Pediatric occupational therapists need expert supervision and consultation from occupational therapists with advanced experience or expertise in addition to traditional management, education, and training methods.

Administrative Personnel↗

PubMed1996

Anterior rhinal cortex and amygdala: dissociation of their contributions to memory and food preference in rhesus monkeys.

Rhesus monkeys were trained on 2 versions of delayed nonmatching-to-sample, one with multiple pairs of objects and the other with a single pair, to evaluate their ability to remember objects. They then received either bilateral aspiration lesions of the anterior rhinal cortex or bilateral excitotoxic lesions of the amygdala, or were retained as unoperated controls. On re-presentation of the multiple-pair task, monkeys with anterior rhinal cortex lesions failed to show the improvement observed in both other groups in remembering the objects over delay intervals ranging from 10 to 60 s. Also, monkeys with anterior rhinal cortex lesions were impaired relative to the controls in relearning the single-pair version of the task. Conversely, on a formal test of food preference, monkeys with amygdala lesions showed abnormal patterns of food choice, whereas monkeys with anterior rhinal cortex lesions did not. Visual memory impairments formerly attributed to amygdala damage are probably due to the rhinal cortex damage associated with aspiration lesions of the amygdala.

Amygdala↗

PubMed1995

Zidovudine treatment prolongs survival and decreases virus load in the central nervous system of rhesus macaques infected perinatally with simian immunodeficiency virus.

To assess the potential therapeutic effects of zidovudine, rhesus macaques were inoculated with simian immunodeficiency virus (SIV) strain SMM/B670 at birth and infused either continuously or intermittently with zidovudine for 6-7 months. Zidovudine did not prevent infection but did significantly increase survival time, which was associated with lower serum p26 viral core antigen levels, a lower virus burden in the cerebrospinal fluid (CSF), and lower CSF quinolinic acid levels than in untreated monkeys. Two of 5 infected, untreated monkeys developed motor impairment within 6 months following infection, whereas motor impairments did not occur in infected, zidovudine-treated monkeys until after the drug was discontinued. Zidovudine treatment was well tolerated by rhesus infants with minimal, transient side effects. These results demonstrate that zidovudine treatment significantly decreases virus load within the central nervous system (CNS) and delays the onset of CNS dysfunction and immune disease in rhesus monkeys perinatally infected with SIV.

Animals↗

PubMed1994

Preserved recognition memory for small sets, and impaired stimulus identification for large sets, following rhinal cortex ablations in monkeys.

Seven cynomolgus monkeys (Macaca fascicularis) performed a series of tasks designed to assess their visual memory and their ability to identify visual stimuli. Preoperatively they were trained and tested in delayed and simultaneous matching-to-sample, both with a large stimulus set and with a small stimulus set; there were approximately 500 million possible stimuli in the large set, which effectively means that stimuli were trial-unique with this set, while in the small set there were only four stimuli, which appeared repeatedly in every session of training with the small set. Three of the monkeys then had the cortex within and adjacent to the rhinal sulcus removed bilaterally, while the other four served as an unoperated control group. Postoperatively, the animals with ablation of the rhinal cortex showed severe impairment in delayed matching-to-sample with the large set. With the large set they were also impaired, however, in matching-to-sample with no delay between sample and test (0 s delay) and in simultaneous matching-to-sample, in which the sample and the two choice patterns were simultaneously present for inspection. The impairment in simultaneous matching-to-sample was particularly clear when the task was made more difficult by reducing the physical discriminability of the trial-unique stimuli. With the small set of four stimuli, the animals with rhinal cortex ablation were not significantly impaired in overall performance level in delayed matching-to-sample, though their level was on average below that of the normal control animals. The stimulus set was then further restricted, so that there were now only two stimuli used throughout; in this condition, the animals with rhinal cortex ablation performed delayed matching-to-sample without any suggestion of impairment, showing indistinguishable performance levels from those of the control animals over a range of forgetting intervals. Subsequently, the animals were trained in trial-unique non-matching-to-sample with 0 s delay, which required reversal of the matching-to-sample rule they had previously learned; animals with rhinal cortex ablation showed a clear impairment in this rule-reversal learning. The final experimental task was a concurrent discrimination learning task in which 20 pairs of stimuli were presented once per session; the animals with rhinal cortex ablation learned more slowly than the control animals on average, but the difference between the groups did not attain statistical significance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Stimulus recognition.

This review covers recent research on the neural process through which a novel stimulus becomes familiar. Lesion and recording studies have provided data sufficient to outline a tentative stimulus-recognition circuit and to suggest how the circuit might operate to form the new and relatively lasting stimulus traces that must underlie delayed stimulus recognition. The research has reached a stage where further progress could well be hastened by interaction between experiment and the formal, neurobiologically constrained models that are beginning to appear.

Animals↗