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Biomedical subjects

J Bachevalier

Publications and source records attributed to J Bachevalier.

At least 37 records · Page 2Linked to original sources

Cerebral ischemia: are the memory deficits associated with hippocampal cell loss?

The long-standing notion that damage restricted to the hippocampal formation is sufficient to produce a significant global memory deficit derives from clinical data. Specifically, it is based on the observation that transient global ischemia, which leads to partial cell loss within the hippocampal formation but not in other brain areas important for memory, can produce global amnesia in humans. This view is, however, challenged by a number of experimental findings. First, in both monkeys and rats, there is evidence that ischemia disrupts delayed object recognition, a memory process found to be largely intact following selective hippocampal lesions. These findings indicate that damage confined to the hippocampal formation cannot account for all aspects of the ischemia-induced memory impairments. Second, although some groups of hippocampal neurons are the most prone to degeneration following ischemia, a wide array of extra-hippocampal damage has been observed in all species, for which the precise extent and distribution may well be underestimated by conventional histological evaluations of ischemic brains. Partial neuronal degeneration reported in regions such as the rhinal areas, medial dorsal thalamic nucleus, or cingulate cortex may contribute to varying degrees to ischemia-induced memory deficits. Third, experimental studies have failed to generate a general consensus on the correlation between extent of hippocampal cell loss and memory performance. In sum, the experimental studies do not, as yet, support the view that hippocampal damage is solely responsible for ischemia-induced memory deficits. Rather, they suggest that both the intra- and extra-hippocampal damage contribute to the pattern of memory impairments observed following ischemia. Consequently, although animals with global and focal ischemia represent valuable models for neuropathological and therapeutic studies, they may not be so useful in assessing the role of the hippocampal formation and its sub-components in memory processes.

Animals↗

Children's performance on "animal tests" of oddity: implications for cognitive processes required for tests of oddity and delayed nonmatch to sample.

To investigate the ontogenesis of oddity learning, children (16 to 102 months of age) and adults were tested on two versions of the oddity task using non-verbal procedures originally developed for monkeys. On the standard, "one-part" or "simultaneous" oddity task (Experiment 1), young children (16 to 74 months of age) performed more poorly than older children (81-102 months of age) who were as proficient as adults. The delayed mastery of one-part oddity contrasts to mastery, at much younger ages (3 to 4 years of age) of a similar, but two-part task, delayed non-match to sample (DNMS) (Overman, 1990). In Experiment 2, those children from the first experiment who had difficulty in learning the one-part oddity task were tested on a two-part oddity task, and a subset of the subjects was retested on the one-part oddity task, and, finally, given verbal instructions for the one-part oddity task. The two-part oddity task was mastered significantly more rapidly than the previous one-part task; however, children's performance dropped significantly when tested on the one-part oddity task, and finally, children rapidly mastered the one-part oddity task when given verbal instructions. The data suggested that (a) children used different strategies to solve the different versions of the oddity task, (b) the solution for the two-part-task appeared earlier in life than the solution for the one-part task and did not involve the use of the concept of "oddity relations", and (c) in tasks in which stimuli are shown twice, behavior may come under control of the absolute properties of the exemplar stimulus via a simple "win-shift" pattern of behavior. In contrast, in tasks in which all stimuli are presented simultaneously, behavior may be controlled by stimulus relations, the analysis of which has a protracted ontogenetic development.

Adult↗

Cognitive gender differences in very young children parallel biologically based cognitive gender differences in monkeys.

Infant humans were trained on 2 cognitive tests that have previously revealed, in infant monkeys, a double dissociation that was reversible by perinatal manipulations of androgens and ablations of specific brain sites. Children showed the same sex-linked behavior found with infant monkeys: young boys were superior on the object reversal task and young girls were superior on the concurrent discrimination task. As happened previously with infant monkeys, the gender difference was not apparent in older human subjects. Thus, early in ontogeny, cognitive gender differences have now been discovered in both humans and monkeys, probably a result of gender differences in androgens that influence the maturation rate of specific brain systems.

Adolescent↗

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↗

Neonatal insult to the hippocampal region and schizophrenia: a review and a putative animal model.

OBJECTIVE: To review the mounting evidence implicating early hippocampal dysfunction in the pathogenesis and the pathophysiology of schizophrenia. An account is made of recent neurodevelopmental hypotheses indicating how an early dysfunction of the hippocampal region disrupts maturational events in brain systems connected to that structure, thus inducing dysfunctional connectional development. Finally, an animal model is presented. METHOD: Socioemotional behaviour of monkeys (Macaca mulatta) with selective neonatal hippocampal lesions was assessed by analyzing their interactions with their age-matched controls at 2 months, 6 months, and 5 to 8 years of age and by comparing the social interactions at each age with those of normal controls paired together. RESULTS: At 2 months of age, monkeys with neonatal hippocampal lesions presented minor disturbances in initiation of social interactions. These subtle changes of behaviour were less evident at 6 months, although by that age, the operated monkeys displayed more withdrawals in response to an increase in aggressive responses from their unoperated peers. In adulthood, the amount of time spent by the hippocampectomized monkeys in social contacts with their normal peers decreased markedly. In addition, operated monkeys exhibited more locomotor stereotypies than normal controls. CONCLUSION: These experimental findings indicate that the time-course and nature of the behavioural disturbances resulting from early trauma to the hippocampal region have some similarities with the clinical symptoms of schizophrenic patients and the typical time-course of the disease.

Animals↗

Stereotypies and loss of social affiliation after early hippocampectomy in primates.

The present study was aimed at determining whether early hippocampal damage alters the development of normal social interactions. Results showed that, at 2 months of age, animals with neonatal hippocampal lesions presented minor disturbances in initiation of social interactions. These subtle changes in behavior were less evident at 6 months, although at this age, the operated animals displayed more withdrawals in response to an increase in aggressive responses from their unoperated peers. Finally, in adulthood, the amount of time spent by the operated monkeys in social contacts with their normal peers was markedly less than that in normal dyads. Only in adulthood did the operated animals exhibit more locomotor stereotypies than normal controls. This finding suggest that the hippocampal formation may directly or indirectly affect the maintenance of social bounds in primates.

Animals↗

Transient subcortical connections of inferior temporal areas TE and TEO in infant macaque monkeys.

As part of a long-term study designed to examine the ontogeny of visual memory in monkeys and its underlying neural circuitry, we have examined the subcortical connections of the inferior temporal cortex in infant monkeys and compared them to those previously described in adult monkeys (Webster et al. [1993] J. Comp. Neurol. 335:73-91). Inferior temporal areas TEO and TE were injected with wheat germ agglutinin conjugated to horseradish peroxidase and tritiated amino acids, respectively, or vice versa, in 1-week-old (N = 6) and 3-4-year-old (N = 6) Macaca mulatta, and the distributions of labeled cells and terminals were examined in subcortical structures. Although the connections of inferior temporal cortex with subcortical structures were found to be similar in infant and adult monkeys, several projections appear to undergo refinement during development. Quantitative analysis showed that 1) whereas the projection from TE to the superior colliculus is consistent (5 of 5 cases) and widespread in infants, it is less reliable (2 of 7 cases) and limited in areal extent in adults; 2) although the projections from TE to nucleus medialis dorsalis and the tail of the caudate are present in infants and adults, they are reduced in adults; and 3) TEO receives input from the dorsal lateral geniculate nucleus in both infants and adults, but the number of cells giving rise to this projection is lower in adults. There was also a suggestion that TE projects to nucleus paracentralis in infants (2 of 5 cases) but not in adults (0 of 7 cases). No differences between infants and adults were apparent in other subcortical connections, including those with the pulvinar, reticular nucleus, claustrum, and putamen.

Animals↗

Long-term effects of selective neonatal temporal lobe lesions on learning and memory in monkeys.

Rhesus monkeys with neonatal damage to either the medial temporal lobe or the inferior temporal cortical area TE, and their normal controls, were reassessed in visual habit formation (24-hour intertrial interval task) and visual recognition (delayed nonmatching to sample; DNMS) at 4-5 years of age and then tested on tactile and spatial DNMS. Results on the two visual tasks were the same as those obtained when the monkeys were under 1 year of age. Specifically, early medial temporal lesions, like late lesions, left habit formation intact but severely impaired recognition memory. Furthermore, the memory deficit extended to the tactile and spatial modalities. By contrast, early damage to TE, unlike late damage to it, yielded only mild deficits on both visual tasks and had no effect on tactile or spatial DNMS. Compensatory mechanisms that promote substantial and permanent recovery thus appear to be available after neonatal TE lesions but not after neonatal medial temporal lesions.

Animals↗

Development and plasticity of the neural circuitry underlying visual recognition memory.

In adult monkeys, visual recognition memory, as measured by the delayed nonmatching to sample (DNMS) task, requires the interaction between inferior temporal cortical area TE and medial temporal lobe structures (mainly the entorhinal and perirhinal cortical areas). Ontogenetically, monkeys do not perform at adult levels of proficiency on the DNMS task until 2 years of age. Recent studies have demonstrated that this protracted development of visual recognition memory is due to an immaturity of the association areas of the neocortex rather than the medial temporal lobe. For example, lesions of the medial temporal lobe structures in infancy or in adulthood yield profound and permanent visual recognition loss, indicating that the medial temporal lobe structures operate early in life to sustain visual memory. In contrast, early lesions of area TE, unlike late lesions, result in a significant and long-lasting sparing of visual memory ability. Further evidence for neocortical immaturity is provided by studies of the development of opiatergic and cholinergic receptors, of the maturation of metabolic activity, and of the connectivity between inferior temporal areas TE and TEO and cortical and subcortical structures. Together these results indicate greater compensatory potential after neonatal cortical than after neonatal medial temporal removals. In support of this view, early damage to area TE leads to the maintenance of normally transient projections as well as to reorganization in cortical areas outside the temporal lobe. In addition, lesion studies indicate that, during infancy, visual recognition functions are widely distributed throughout many visual association areas but, with maturation, these functions become localized to area TE. Thus, the maintenance of exuberant projections together with reorganization in other cortical areas of the brain could account for the preservation of visual memories in monkeys that have had area TE removed in infancy.

Animals↗

Medial temporal lobe structures and autism: a review of clinical and experimental findings.

Although substantive understanding of brain dysfunction in autism remains meager, clinical evidence as well as animal brain research on the effects of early damage to selective brain system have now yielded enough knowledge that some provisional hypotheses concerning the etiology of autism can be generated. Basically, the underlying premise of this review is that a major dysfunction of the autistic brain resides in neural mechanisms of the structures in the medial temporal lobe, and, perhaps, more specifically the amygdaloid complex. This review begins with a summary of clinical evidence of the involvement of the medial temporal lobe structures in autism. The major behavioral disturbances seen in monkeys that had received neonatal lesions of the medial temporal lobe structures are then described. From this survey it can be seen that distinct patterns of memory losses and socioemotional abnormalities emerge as a result of extent of damage to the medial temporal lobe structures. The potential value of the experimental findings for an understanding of neural dysfunction in autism as well as directions of future research are discussed in the final section of the review.

Animals↗

Effects of selective neonatal temporal lobe lesions on visual recognition memory in rhesus monkeys.

Ten-month-old infant monkeys that had received neonatal ablations of either inferior temporal cortex (area TE) or the medial temporal region were compared with age-matched normal infant monkeys in visual delayed nonmatching-to-sample with trial-unique objects. Both types of early damage caused impairment in visual recognition, but the degree of deficit after early area TE lesions differed sharply from that after early medial temporal removals. Thus, whereas early medial temporal damage yielded a marked decline in visual recognition when the delays and lists were gradually increased, early area TE damage yielded normal recognition up to a delay of 60 sec and only mild impairment at longer delays and lists. The data indicate that, unlike adult monkeys, which suffer severe and nearly equivalent losses in visual object recognition after both types of ablation, the infant monkeys' recognition ability is largely spared after early damage to area TE but not after early damage to the medial temporal lobe. Together with recent clinical reports of profound memory loss in children with early dysfunction of the medial temporal region, the present findings demonstrate that medial temporal lobe structures operate early to sustain visual recognition memory, and recovery from early damage is limited at best. Early damage to higher-order visual cortex, however, can be largely compensated, presumably by one or more of the visual cortical areas that were left intact.

Animals↗

Subcortical connections of inferior temporal areas TE and TEO in macaque monkeys.

To investigate the subcortical connections of inferior temporal cortex, we injected its anterior and posterior portions (Bonin and Bailey's cytoarchitectonic areas TE and TEO, respectively) in 6 rhesus monkeys with retrograde and anterograde tracers. The results indicate that both areas TE and TEO receive nonreciprocal inputs from several thalamic nuclei, including paracentralis, ventralis anterior, centralis, and limitans, and that TE also receives input from reuniens. Additional nonreciprocal inputs to both areas arise from the hypothalamus, basal nucleus of Meynert, dorsal and median raphe, locus coeruleus, and reticular formation. TE and TEO are reciprocally connected with the lateral, medial, and inferior nuclei of the pulvinar and with the ventral portion of the claustrum. The main subcortical nonreciprocal output from TE and TEO is to the striatum and from TEO to the superior colliculus. TE also sends a very limited projection to nucleus medialis dorsalis magnocellularis of the thalamus. Although the connections of areas TE and TEO are overlapping in most subcortical structures, they are partially segregated in the pulvinar, the reticular nucleus of the thalamus, and the striatum. Specifically, relative to those of TE, the projections of TEO are located more laterally in the medial, lateral, and inferior nuclei of the pulvinar, more ventrally in the reticular nucleus, and more caudally in both the ventral putamen and tail and head of the caudate nucleus.

Animals↗

A comparison of children's performance on two recognition memory tasks: delayed nonmatch-to-sample versus visual paired-comparison.

Although 4- to 6-month-old children have a significant tendency to look at new stimuli in a visual paired-comparison task (VPC), they have difficulty in consistently choosing novel objects in a delayed nonmatch-to-sample task (DNMS). To evaluate which factors could account for this difficulty, we tested human infants (10-107 months) and adults (17-25 years) in a DNMS task while monitoring eye fixations. The results indicated that children at all ages reliably looked at (VPC scores) or chose (DNMS scores) the new stimuli about 60% of the time, indicating that both tasks measure visual recognition memory. A videotape analysis of visual attention revealed that children younger than 22 months, but not older children, spent significantly more time visually exploring the objects rather than looking at the food reward under it. Although this visual attraction to objects in children younger than 22 months of age may have impaired the formation of stimulus-reinforcer association needed to solve the DNMS task, this was not the case for older children, since beyond 22 months of age children consistently looked at the reward while displacing the objects. These results suggest that other cognitive abilities required by the DNMS task may not be fully functional even in children 22 months and older.

Adolescent↗

Limbic-dependent recognition memory in monkeys develops early in infancy.

Infantile amnesia, the absence of memories from infancy and early childhood, has been attributed to an immaturity of the limbic system in infancy. Contrary to this view, we now report that limbic-dependent recognition memory is present as early as one month of age in monkeys. Memory measured by the paired-comparison preferential looking task, normally present in infant monkeys within the first month of life, is absent after damage to the amygdaloid complex and hippocampal formation, suggesting that limbic structures make a critical contribution to visual recognition memory even at this early age. The findings reopen the question of the locus of the neural immaturity that underlies infantile amnesia.

Amygdala↗

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↗