Biomedical subjects

J Bachevalier

Publications and source records attributed to J Bachevalier.

At least 55 records · Page 3Linked to original sources

PubMed1992

Object recognition versus object discrimination: comparison between human infants and infant monkeys.

Human infants (12-32 months old) and adults learned a delayed nonmatching-to-sample (DNMS) task and single- and multiple-pair discrimination tasks using nonverbal procedures previously used with monkeys. Infants learned discriminations rapidly and at a young age (12 months), but they required prolonged training and maturation before learning the DNMS task. Adults learned all tasks rapidly. After learning the DNMS task to criterion, memory performance declined systematically in an inverse relation to age. The dissociation in ability of infants on the DNMS versus discrimination tasks closely resembles the dissociation previously reported with infant monkeys (Bachevalier & Mishkin, 1984). Results from both infant humans and monkeys support a neurocognitive maturational model.

Adolescent↗

PubMed1991

Visual habit formation in 3-month-old monkeys (Macaca mulatta): reversal of sex difference following neonatal manipulations of androgens.

The ability to perform on a concurrent visual discrimination task with 24-h intertrial intervals (24-h ITI task) develops a few weeks earlier in female than in male infant monkeys. To test whether this sex difference was related to the presence of perinatal androgens, plasma testosterone levels were reduced in male infant monkeys by neonatal orchiectomy and increased in neonatally ovariectomized female infant monkeys by treatment with either testosterone propionate (TP) or its reduced metabolite, dihydrotestosterone (DHT). At 3 months of age, the animals were tested on the 24-h ITI task and their performance compared with that of age-matched intact male and female monkeys. Orchiectomy which was followed by a slight but visible atrophy of the external genitalia, hastened performance of male infant monkeys to the level of intact infant females. Conversely, androgenization of ovariectomized female infant monkeys given DHT, which had only a slight virilizing effect on the external genitalia, showed the learning of these female infants to the rate of intact male infant monkeys. Curiously, although TP treatment in ovariectomized female infant monkeys was more effective than DHT in virilizing the external genitalia, it failed to slow the rate of learning. This dissociation between the effects of TP and DHT on external genital organs and learning abilities is discussed in terms of possible differences in dose-dependent, time-dependent, and receptor-binding mechanisms of the two androgens. The present study provides further evidence that early androgen secretions affect the organization not only of brain structures related to primary sexual characteristics but also of those related to learning abilities.

Androgens↗

PubMed1991

The role of the inferior prefrontal convexity in performance of delayed nonmatching-to-sample.

Findings in an earlier study (Bachevalier, J. and Mishkin, M. Behav. Brain Res. 20, 249-261, 1986) indicated that ventromedial prefrontal cortex, which receives thalamic projections from the limbo-diencephalic system, is critical for visual recognition; whereas the dorsolateral prefrontal cortex, which receives no such thalamic projections, makes little or no contribution to this type of memory. In the present study, we examined the role in recognition of another prefrontal area outside the thalamic projection zone of the limbo-diencephalic system, namely, the inferior prefrontal convexity. In the first experiment, monkeys with lesions of this cortex (Group IC) were found to be impaired in relearning delayed nonmatching-to-sample (DNMS), but not on the subsequent DNMS performance test in which memory demands were greatly increased. In a second experiment, monkeys with combined lesions of the inferior and dorsolateral prefrontal cortex (Group LAT) were also found to be impaired in relearning DNMS, but in this case they were impaired, in addition, on the subsequent performance test. Neither group (IC or LAT) showed retardation in acquiring visual discrimination habits. Analysis of the DNMS behavior of both groups suggested that their deficits on this task were due not to a loss in recognition memory, but to various forms of perseverative interference. The results support the view that the inferior prefrontal convexity, like the dorsolateral prefrontal cortex, lies outside the limbo-diencephalic memory system not only anatomically but also functionally.

Animals↗

PubMed1991

Sex differences in the development of learning abilities in primates.

The role of steroid gonadal hormones in promoting sex differences in reproductive behaviors has been thoroughly studied in numerous mammalian species. More recent experiments have indicated that the presence or absence of steroid hormones during the critical period of brain differentiation likewise might promote the development of sex differences in cognitive abilities. Studies in infant rhesus monkeys have demonstrated that there exist sex differences in learning abilities that can be altered by perinatal hormonal manipulations, suggesting that testosterone might be a crucial factor responsible for the development of sex differences in cognitive styles. In addition, neonatal lesion studies have shown that the cortical areas mediating specific learning abilities mature at different rates in male and female infant monkeys. These findings support the view that the perinatal hormonal environment can affect the rate of brain maturation by influencing neuronal connectivity at the cortical level. The combined data from sex differences in learning abilities in human infants and their reversibility in endocrinological syndromes suggest that testosterone may affect the maturation of the human brain in a manner similar to that demonstrated in nonhuman primates.

Animals↗

PubMed1991

Lesions of inferior temporal area TE in infant monkeys alter cortico-amygdalar projections.

When inferior temporal area TE is removed bilaterally in infant monkeys, the normally transient projection from area TEO to the lateral basal nucleus of the amygdala is maintained, and the normally limited projection from area TEO to the dorsal part of the lateral nucleus of the amygdala expands to invade the terminal space in the lateral nucleus that is normally occupied by terminals from area TE. The maintenance and sprouting of these projections from area TEO could play a role in the permanent preservation of visual memory ability in monkeys that have received bilateral removal of area TE in infancy.

Aging↗

PubMed1991

Connections of inferior temporal areas TE and TEO with medial temporal-lobe structures in infant and adult 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 connections between inferior temporal cortex and medial temporal-lobe structures in infant and adult monkeys. Inferior temporal cortical areas TEO and TE were injected with WGA conjugated to HRP and tritiated amino acids, respectively, or vice versa, in 1-week-old and 3-4-yr-old Macaca mulatta, and the distributions of labeled cells and terminals were examined in both limbic structures and temporal-lobe cortical areas. In adult monkeys, inferior temporal-limbic connections included projections from area TEO to the dorsal portion of the lateral nucleus of the amygdala and from area TE to the lateral and lateral basal nuclei; inputs to both areas TEO and TE included those from the lateral, lateral basal, and medial basal nuclei of the amygdala and to area TE from the accessory basal nucleus. Additional limbic inputs to both areas TEO and TE arose from the posterior portion of the presubiculum. In infant monkeys, we found, in addition to these adultlike connections, a projection from area TEO to the lateral basal nucleus of the amygdala. Inferior temporal cortical connections in adult monkeys included projections from area TEO to area TE and, in turn, from area TE to area TG and perirhinal area 36, as well as from area TE back to area TEO; inputs to both areas TEO and TE included those from area TG, perirhinal areas 35 and 36, and parahippocampal areas TF and TH. All of these adultlike connections were also observed in infant monkeys, but, in addition, the infants showed projections from area TE to perirhinal area 35 as well as to parahippocampal areas TF and TH, and from area TEO to area TF. Moreover, in infants, the projection from area TE to perirhinal area 36 was considerably more widespread than in adults, both in areal extent and in laminar distribution. The results therefore indicate the existence of projections in infant monkeys from inferior temporal areas to the amygdala, perirhinal cortex, and parahippocampal cortex that are either totally eliminated in adults or more refined in their distribution. Both elimination and refinement of projections thus appear to characterize the maturation of axonal pathways between the inferior temporal cortex and medial temporal-lobe structures in monkeys.

Aging↗

PubMed1990

Age and sex differences in the effects of selective temporal lobe lesion on the formation of visual discrimination habits in rhesus monkeys (Macaca mulatta).

Three-month-old infant monkeys with neonatal ablations of either cortical area TE or the amygdala and hippocampus and age-matched normal infants were trained in a concurrent object discrimination task with 24-hr intertrial intervals. Neonatal area TE lesions yielded a transient deficit in visual habit formation, present in the female monkeys only, whereas the same lesions in adult monkeys yielded a severe and long-lasting deficit in both males and females. Although pointing to a greater neural compensation for the early loss as compared with the later loss of cortical area TE, the results also corroborate a recent suggestion (Bachevalier, Hagger, & Bercu, 1989) that, at 3 months of age, area TE is more fully functional in females than in males. Neither early nor late amygdalohippocampal lesions impaired the ability to form visual discrimination habits, strengthening the proposal that the habit system uses a corticononlimbic circuit.

Aging↗

PubMed1990

Ontogenetic development of habit and memory formation in primates.

Lesion studies in adult monkeys have suggested that an experience can enter into memory in two ways: as cognitive information stored in a cortico-limbo-thalamocortical system (involving the higher order sensory areas of cortex, the amygdala, hippocampus, and entorhinal cortex, the medial thalamic nuclei, or ventromedial prefrontal cortex, and the basal forebrain) and as a habit stored perhaps in a cortico-striatal system (involving the sensory cortical areas and the caudate and putamen). Our studies of behavioral development in infant monkeys as well as those in human infants provide complementary evidence by suggesting that these two systems are developmentally dissociable, in that the cognitive memory system, assessed by the delayed non-matching to sample task, appears to mature considerably more slowly than the habit system, assessed by the concurrent visual discrimination task, a notion that has also been discussed recently by others (Nadel & Zola-Morgan, 1984; Rose, 1980). Furthermore, despite the late development of the cortico-limbo-diencephalic memory system, this chapter has presented evidence that some limbic-dependent memory processes, such as those required for success on the visual paired comparison task, develop extremely early. The notion that at least one type of recognition process mediated by the limbic system is present neonatally provides new insight into the normal development of memory processes and indicates the need to identify further the memory processes and substrates that become available to an infant at different time points during maturation. Such studies will help one day to determine the immaturity of structure or function that is responsible for the intriguing phenomenon of infantile amnesia, that is, the inability to recall the stimuli or events experienced in the first few years of life.

Animals↗

PubMed1989

Gender differences in visual habit formation in 3-month-old rhesus monkeys.

The rate of learning concurrent visual discriminations with 24-hr intertrial intervals, a measure of habit formation, was assessed in infant monkeys of both sexes and compared with the rate of learning in adults. In two separate series of animals, 3-month-old male monkeys learned an initial set of discriminations (but not later sets) more slowly than 3-month-old females. This gender difference was absent in 6-month-old monkeys and in adults, both of which learned the initial set at the same rate. Determination of plasma gonadal hormone levels at the time of testing revealed a significant correlation (rs = 0.95) between testosterone levels and learning scores on the initial set in the 3-month-old male monkeys (i.e., the higher the level the poorer the score). No such correlation was found in the 3-month-old female monkeys or in the 6-month-olds of either sex. These results suggest that high testosterone levels found perinatally in male monkeys temporarily slows maturation of the neural system underlying visual habit formation.

Animals↗

PubMed1989

Mnemonic and neuropathological effects of occluding the posterior cerebral artery in Macaca mulatta.

To investigate experimentally the mnemonic and neuropathological effects of blockage of the posterior cerebral arteries (PCA), a cerebrovascular accident that can lead to global anterograde amnesia in humans, we permanently occluded these arteries bilaterally in six monkeys and then evaluated their performance on a visual recognition task, after which we assessed the extent of their ischemic infarcts. The latter showed substantial individual variation, ranging from almost no damage in one case to massive unilateral injury of both the ventromedial o occipitotemporal cortex and hippocampal formation in another. In the four remaining cases, however, the infarcts fell within a narrow range, being confined almost entirely to the hippocampal formation and parahippocampal gyrus, and then only to restricted portions of these structures, unilaterally in one case, and bilaterally in the three others. Performance on the recognition task was related to the presence and bilaterality of the hippocampal injury. Thus, the case without any hippocampal damage performed at a rate equal to that of normal controls; the case with unilateral hippocampal damage was mildly impaired; and the three cases with bilateral infarctions, involving between 20 and 55% of the hippocampal formation, showed substantial impairment, with scores averaging 20% below those of normal controls. The only subfields of the hippocampus damaged in common in these cases were CA1 and CA2. Paradoxically, the memory loss found in these three animals with only partial bilateral hippocampal damage was significantly greater than that found in animals with total bilateral ablation of the hippocampal formation, whose scores averaged only 10% below those of normal controls. Possible explanations for this extremely puzzling outcome are proposed.

Amnesia↗

PubMed1988

Dissociation of the effects of inferior temporal and limbic lesions on object discrimination learning with 24-h intertrial intervals.

Monkeys with bilateral ablations of the inferior temporal cortical area TE were trained on a visual discrimination task thought to measure non-cognitive habit formation. The task consisted of 20 object discriminations presented concurrently, but at the rate of only one trial on each per day; successive trials on a given discrimination were thus separated by 24-h intertrial intervals. Performance on this task by the animals with TE lesions was compared to that of both normal control monkeys and monkeys that had sustained bilateral removals of the amygdala and hippocampus. In contrast to the latter animals, which learned the 24-h intertrial interval task about as quickly as the normal controls, monkeys with area TE removals were markedly impaired. Taken together with earlier findings demonstrating that ablation of area TE impairs visual recognition memory, the present results suggest that area TE contributes not only, like limbic structures, to a cognitive memory system, but also, unlike limbic structures, to a non-cognitive habit system. Evidence is reviewed suggesting that this latter system may involve a corticostriatal circuit.

Animals↗

PubMed1986

Visual recognition impairment follows ventromedial but not dorsolateral prefrontal lesions in monkeys.

Visual recognition in monkeys appears to involve the participation of two limbothalamic pathways, one including the amygdala and the magnocellular portion of the medial dorsal nucleus (MDmc) and the other, the hippocampus and the anterior nuclei of the thalamus (Ant N). Both MDmc and Ant N project, in turn, to the prefrontal cortex, mainly to its ventral and medial portions. To test whether the prefrontal projection targets of the two limbothalamic pathways also participate in memory functions, performance on a variety of learning and memory tasks was assessed in monkeys with lesions of the ventromedial prefrontal cortex (Group VM). Normal monkeys and monkeys with lesions of dorsolateral prefrontal cortex (Group DL) served as controls. Group VM was severely impaired on a test of object recognition, whereas Group DL did not differ appreciably from normal animals. Conversely, the animals in Group VM were able to learn a spatial delayed response task, whereas 2 of the 3 animals in Group DL could not. Neither group was impaired in the acquisition of visual discrimination habits, even though the successive trials on a given discrimination were separated by 24-h intervals. The patterns of deficit suggest that ventromedial prefrontal cortex constitutes another station in the limbothalamic system underlying cognitive memory processes, whereas the dorsolateral prefrontal cortex lies outside this system. The results support the view that the classical delayed-response deficit observed after dorsolateral prefrontal lesions represents a perceptuo-mnemonic impairment in spatial functions selectively rather than a memory loss of a more general nature.

Amygdala↗

PubMed1986

Regional distribution of [3H]naloxone binding in the brain of a newborn rhesus monkey.

The distribution of opiate receptors in the brain of a newborn monkey (Macaca mulatta) was mapped by in vitro autoradiographic localization of [3H]naloxone binding to tissue sections. The autoradiographs of the newborn brain were compared to those from two adult brains. The distribution of opiate receptors appeared to be adult-like in subcortical structures (both limbic and nonlimbic) and allocortical areas. By contrast, all neocortical areas, except the primary visual cortex, lacked at birth the laminar specific patterns that characterize the adult. The results therefore suggest that, like many other aspects of neocortical maturation, such as dendritic growth, synaptogenesis, myelination and neurotransmitter concentrations, the distribution of opiate receptors continues to develop postnatally.

Animals↗

PubMed1985

Visual recognition in monkeys: effects of transection of fornix.

An earlier finding from this laboratory of only a mild recognition impairment after hippocampal removal in mature monkeys (Mishkin 1978) contrasts with the severe deficit originally reported by Gaffan (1974) following transection of the fornix in immature monkeys. Investigation of some of the methodological differences between the two studies (lesion site, age of monkeys, and behavioral paradigm) failed to resolve the discrepancy in results, only a small impairment resulting under all conditions examined. While some still unexplored differences must underlie the divergent findings, it appears that only a comparatively mild impairment in recognition memory results from damage to the hippocampal system under a wide variety of conditions.

Age Factors↗

PubMed1985

Visual recognition in monkeys: effects of separate vs. combined transection of fornix and amygdalofugal pathways.

Performance on an object recognition test was assessed in monkeys with transections of either the fornix, the amygdalofugal pathways, or both. Whereas separate transection of the two pathways produced only small and unreliable effects, their combined transection produced a severe deficit. Comparison with the results of a previous study (Mishkin 1978) indicates that combined disconnection of the amygdala and hippocampus from the diencephalon yields a memory impairment similar to that following combined damage to the two limbic structures themselves. The findings suggest that recognition memory in monkeys depends on two parallel limbo-diencephalic pathways.

Amygdala↗

PubMed1984

An early and a late developing system for learning and retention in infant monkeys.

On the evidence that memory formation and habit formation represent two qualitatively different learning processes based on separate neural mechanisms, the functional development of these two processes was followed ontogenetically. Separate groups of rhesus monkeys of different ages were tested in delayed nonmatching-to-sample and 24-hr concurrent discrimination learning, considered to be measures of recognition memory and discrimination habit formation, respectively. The youngest group of infant monkeys failed to learn the nonmatching task until they were approximately 4 months old. With further maturation, learning ability on this task gradually improved, yet it did not reach adult levels of proficiency even at 1 year of age. Postlearning evaluation with long delays and lists confirmed this slow ontogenetic development of recognition memory to adult levels of function. By contrast, infant monkeys 3-4 months old learned to discriminate long lists of object-pairs about as quickly as adult monkeys despite the use of 24-hr intertrial intervals. This striking dissociation in the ability of infants on the two tasks closely resembles the dissociation first found in adult monkeys rendered amnesic by limbic lesions. The results suggest that whereas the nonlimbic habit system matures early in infancy, the limbic-dependent memory system develops only slowly.

Age Factors↗

PubMed1982

Effect of folic acid and vitamin B12 deficiencies on 5-hydroxyindoleacetic acid in human cerebrospinal fluid.

Indoles were measured in cerebrospinal fluid (CSF) from control patients, from patients suffering from folate deficiency, and from patients with vitamin B12 deficiency. The folate-deficient patients were classified according to whether they exhibited a neuropsychiatric syndrome, consisting of organic mental changes, polyneuropathy, and depression, which responded to folate administration. CSF 5-hydroxyindoleacetic acid was low in the vitamin B12-deficient patients and in those folate-deficient patients whose symptoms were not related to folate deficiency. CSF 5-hydroxyindoleacetic acid returned to normal with folate treatment in the patients exhibiting folate-responsive neuropsychiatric signs. The data indicate a close association between folate-responsive neuropsychiatric symptoms and changes in 5-hydroxytryptamine metabolism in the central nervous system.

Adolescent↗

PubMed1982

Cerebrospinal fluid and blood thiamine concentrations in phenytoin-treated epileptics.

Thiamine and folate levels in blood and cerebrospinal fluid (CSF) were determined by microbiological assays in 23 control subjects and 11 phenytoin-treated epileptics. There was no significant difference between the two groups for serum and CSF folate levels. There was, however, a statistically significant difference between the groups for both whole blood thiamine and CSF thiamine levels. Epileptic patients being treated with phenytoin had lower values than control subjects.

Epilepsy↗