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Biomedical subjects

J Bachevalier

Publications and source records attributed to J Bachevalier.

At least 19 recordsLinked to original sources
PubMed2006

Corpus callosum diffusion anisotropy correlates with neuropsychological outcomes in twins disconcordant for traumatic brain injury.

Conventional and diffusion tensor MR imaging studies in twins sustaining severe pediatric traumatic brain injury identified reduction in fractional anisotropy (FA) in all regions of the corpus callosum, particularly the posterior body, rostral body, and genu, relative to healthy cotwins. FA from the rostrum, genu, anterior body, posterior body, and isthmus were correlated with measures of reading speed and comprehension; verbal working memory and math fact retrieval scores were correlated only with the rostral body FA.

Adolescent↗
PubMed2003

An fMRI study of executive functioning after severe diffuse TBI.

PRIMARY OBJECTIVE: Preliminary study of whether severe diffuse traumatic brain injury (TBI) increases extent of frontal tissue recruited by cognitive control tasks. RESEARCH DESIGN: Functional magnetic resonance imaging (fMRI) on N-back working memory (WM)and arrows inhibition tasks in a 46 year old man who had severe diffuse TBI 1 year earlier, a 44 year old man (inhibition task) and three women (working memory task), age 20-26 years. Images were acquired by 1.5 T magnet with BOLD method and PRESTO pulse sequence and analysed using SPM. MAIN OUTCOMES AND RESULTS: Frontal activation increased under 2-back relative to 1-back condition of working memory in all participants with more extensive activation in the TBI patient relative to controls. Frontal activation increased with inhibition on the arrows task, but was greater in the TBI patient. CONCLUSION: Severe diffuse TBI results in recruitment of additional neural resources for cognitive control.

Adult↗
PubMed2001

Neurotoxic lesions of perirhinal cortex impair visual recognition memory in rhesus monkeys.

Recent excitotoxic lesion studies in monkeys have shown that the recognition memory deficits originally attributed to amygdalo-hippocampal damage were due in whole or in part to the accompanying damage to surrounding tissue, including fibers of passage. Here we show that the same conclusion does not apply to the visual recognition impairment produced by aspiration lesions of perirhinal cortex inasmuch as equally severe impairment was found after excitotoxic lesions of this cortex. The finding demonstrates that damage limited to perirhinal neurons is sufficient to impair visual memory and that damage to fibers of passage neither caused nor exacerbated the effect described initially.

Animals↗
PubMed2001

Effects of selective neonatal temporal lobe lesions on socioemotional behavior in infant rhesus monkeys (Macaca mulatta).

Normal infant monkeys and infant monkeys with neonatal damage to either the medial temporal lobe or the inferior temporal visual area were assessed in dyadic social interactions at 2 and 6 months of age. Unlike the normal infant monkeys, which developed strong affiliative bonds and little or no behavioral disturbances, the lesioned monkeys (each of which was observed with an unoperated control) exhibited socioemotional abnormalities and aberrant behaviors. The socioemotional changes predominated at 6 months of age and were particularly severe in monkeys with medial temporal lesions. In both the pattern and time course, the socioemotional deficits produced by the neonatal medial temporal lesions bear a striking resemblance to the behavioral syndrome in children with autism. Further analysis of these lesion-induced abnormalities in nonhuman primates may therefore provide insight into this debilitating human developmental disorder.

Aging↗
PubMed2000

Volume of focal brain lesions and hippocampal formation in relation to memory function after closed head injury in children.

OBJECTIVES: (1) A study of verbal learning and memory in children who had sustained a closed head injury (CHI) at least 3 months earlier. (2) To relate memory function to focal brain lesion and hippocampal formation volumes using morphometric analysis of MRI. METHODS: A group of 245 children who had been admitted to hospital for CHI graded by the Glasgow coma scale (GCS), including 161 patients with severe and 84 with mild CHI completed the California verbal learning test (CVLT) and underwent MRI which was analysed for focal brain lesion volume independently of memory test data. Brain MRI with 1.5 mm coronal slices obtained in subsets of 25 patients with severe and 25 patients with mild CHI were analysed for hippocampal formation volume. Interoperator reliability in morphometry was satisfactory. RESULTS: Severity of CHI and age at study significantly affected memory performance. Regression analysis showed that bifrontal, left frontal, and right frontal lesion volumes incremented prediction of various learning and memory indices after entering the GCS score and age into the model. Extrafrontal lesion volume did not contribute to predicting memory performance. CONCLUSIONS: Prefrontal lesions contribute to residual impairment of learning and memory after severe CHI in children. Although effects of CHI on hippocampal formation volume might be difficult to demonstrate in non-fatal paediatric CHI, further investigation using functional brain imaging could potentially demonstrate hippocampal dysfunction.

Adolescent↗
PubMed2000

Effects of neonatal inferior prefrontal and medial temporal lesions on learning the rule for delayed nonmatching-to-sample.

The ability of rhesus monkeys to master the rule for delayed nonmatching-to-sample (DNMS) has a protracted ontogenetic development, reaching adult levels of proficiency around 4 to 5 years of age (Bachevalier, 1990). To test the possibility that this slow development could be due, at least in part, to immaturity of the prefrontal component of a temporo-prefrontal circuit important for DNMS rule learning (Kowalska, Bachevalier, & Mishkin, 1991; Weinstein, Saunders, & Mishkin, 1988), monkeys with neonatal lesions of the inferior prefrontal convexity were compared on DNMS with both normal controls and animals given neonatal lesions of the medial temporal lobe. Consistent with our previous results (Bachevalier & Mishkin, 1994; Málková, Mishkin, & Bachevalier, 1995), the neonatal medial temporal lesions led to marked impairment in rule learning (as well as in recognition memory with long delays and list lengths) at both 3 months and 2 years of age. By contrast, the neonatal inferior convexity lesions yielded no impairment in rule-learning at 3 months and only a mild impairment at 2 years, a finding that also contrasts sharply with the marked effects of the same lesion made in adulthood. This pattern of sparing closely resembles the one found earlier after neonatal lesions to the cortical visual area TE (Bachevalier & Mishkin, 1994; Málková et al., 1995). The functional sparing at 3 months probably reflects the fact that the temporo-prefrontal circuit is nonfunctional at this early age, resulting in a total dependency on medial temporal contributions to rule learning. With further development, however, this circuit begins to provide a supplementary route for learning.

Animals↗
PubMed1999

Memory and socioemotional behavior in monkeys after hippocampal damage incurred in infancy or in adulthood.

The present study reviews the long-term effects of neonatal hippocampal damage in monkeys on the development of memory functions and socioemotional behavior. The results showed that neonatal damage to the hippocampal formation impairs specific memory processes, such as those subserving automatic (as opposed to effortful) recognition memory and relational learning, while sparing the abilities to acquire skills, such as object discriminations. Furthermore, the neonatal hippocampectomy led to a progressive loss of social affiliation and a protracted emergence of locomotor stereotypies. While the memory losses following neonatal hippocampal lesions resemble those found after similar lesions acquired in adulthood, only the neonatal lesions resulted in a protracted emergence of abnormal behaviors. These later findings suggested that, presumably, the neonatal lesions impacted on neural systems remote from the site of damage. This was confirmed by our more recent neurobiological studies, demonstrating that neonatal, but not late, lesions of the medial temporal lobe region, disrupt the normal behavioral and cognitive processes subserved by the prefrontal cortex and the caudate nucleus. All together the data support the neurodevelopmental hypothesis viewing early insult to the medial temporal region as the origin of developmental psychosis in humans, such as schizophrenia.

Age Factors↗
PubMed1999

The relationship between dorsolateral prefrontal N-acetylaspartate measures and striatal dopamine activity in schizophrenia.

BACKGROUND: Pathology of dorsolateral prefrontal cortex and dysregulation of dopaminergic neurons have been associated with the pathophysiology of schizophrenia, but how these phenomena relate to each other in patients has not been known. It has been hypothesized that prefrontal cortical pathology might induce both diminished steady-state and exaggerated responses of dopaminergic neurons to certain stimuli (e.g., stress). We examined the relationship between a measure of prefrontal neuronal pathology and striatal dopamine activity in patients with schizophrenia and in a nonhuman primate model of abnormal prefrontal cortical development. METHODS: In the patients, we studied in vivo markers of cortical neuronal pathology with NMR spectroscopic imaging and of steady-state striatal dopamine activity with radioreceptor imaging. In the monkeys, we used the same NMR technique and in vivo microdialysis. RESULTS: Measures of N-acetyl-aspartate concentrations (NAA) in dorsolateral prefrontal cortex strongly and selectively predicted D2 receptor availability in the striatum (n = 14, rho = -.64, p < .01), suggesting that the greater the apparent dorsolateral prefrontal cortex pathology, the less the steady-state dopamine activity in these patients. A similar relationship between NAA measures in dorsolateral prefrontal cortex and steady-state dopamine concentrations in the striatum was found in the monkeys (n = 5, rho = .70, p < .05). We then tested in the same monkeys the relationship of prefrontal NAA and striatal dopamine overflow following amphetamine infusion into dorsolateral prefrontal cortex. Under these conditions, the relationship was inverted, i.e., the greater the apparent dorsolateral prefrontal cortex pathology, the greater the dopamine release. CONCLUSIONS: These data demonstrate direct relationships between putative neuronal pathology in dorsolateral prefrontal cortex and striatal dopamine activity in human and nonhuman primates and implicate a mechanism for dopamine dysregulation in schizophrenia.

Adult↗
PubMed1999

Neonatal aspiration lesions of the hippocampal formation impair visual recognition memory when assessed by paired-comparison task but not by delayed nonmatching-to-sample task.

Previous experiments showed that neonatal aspiration lesions of the hippocampal formation in monkeys yield no visual recognition loss at delays up to 10 min, when recognition memory was assessed by a trial-unique delayed nonmatching-to-sample (DNMS) task. The present study examined whether neonatal hippocampal lesions also have no effect on visual recognition when assessed by a visual paired-comparison (VPC) task. In the VPC task, animals are looking at visual stimuli and their preference for viewing new stimuli is measured. Normal adult monkeys showed strong preference for looking at the novel stimuli at all delays tested. By contrast, adult monkeys with neonatal hippocampal lesions, which included the dentate gyrus, cornus ammon (CA) fields, subicular complex, and portions of parahippocampal areas TH/TF, showed preference for novelty at short delays of 10 s but not at longer delays of 30 s to 24 h. This visual recognition loss contrasts with the normal performance of the same operated animals when tested in the DNMS task. The discrepancy between the results obtained in the two recognition tasks suggests that, to perform normally on the DNMS task, the operated monkeys may have used behavioral strategies that do not depend on the integrity of the hippocampal formation. In this respect, VPC appears to be a more sensitive task than DNMS to detect damage to the hippocampal region in primates.

Animals↗
PubMed1999

Striatal dopamine receptors and transporters in monkeys with neonatal temporal limbic damage.

Developmental cortical damage has been implicated in the basic neurobiology of schizophrenia. Adult rhesus monkeys with neonatal temporal limbic damage show a stimulus-dependent disinhibition of subcortical dopamine (DA) release. We measured dopamine D2 receptors and transporters in vivo in rhesus monkeys with neonatal and adult mesial temporal limbic lesions and control monkeys to explore further the effects of this developmental lesion on striatal DA function. All monkeys were studied with [I-123]IBZM SPECT to assess the availability of striatal dopamine D2 receptors and with [I-123]beta-CIT SPECT to measure the availability of dopamine transporters in the striatum. IBZM binding was significantly reduced in monkeys with neonatal limbic lesions. No group difference in beta-CIT binding was found. The reduction in IBZM binding was significantly correlated with subcortical dopamine release after monoaminergic prefrontal stimulation as determined with in vivo microdialysis. Our findings imply specific interactions between age at lesion and the availability of DA transporter and receptors in non-human primates, and suggest that stimulus-dependent DA activity affects the expression of DA receptors.

Age Factors↗
PubMed1999

Long-term effects of neonatal damage to the hippocampal formation and amygdaloid complex on object discrimination and object recognition in rhesus monkeys (Macaca mulatta).

Rhesus monkeys with neonatal aspiration lesions of the hippocampal formation or the amygdaloid complex were tested on concurrent discrimination learning (24-hr intertrial interval [ITI]) at 3 months, on object recognition memory (delayed nonmatching-to-sample [DNMS]) at 10 months, and retested on both tasks at 6-7 years of age. Neonatal amygdaloid damage mildly impaired acquisition at the 24-hr ITI and the performance test of DNMS at both ages. In contrast, early hippocampal lesions impaired performance only on the longest lists of 10 items in DNMS in adult monkeys. Thus, early amygdala lesions appeared to have resulted in a greater object memory loss than early hippocampal lesions. However, in light of recent findings from lesion studies in adult monkeys, the object memory impairment after early amygdaloid lesions is better accounted for by damage to the entorhinal and perirhinal cortex than by damage to the amygdaloid nuclei.

Amygdala↗
PubMed1999

Effects of aspiration versus neurotoxic lesions of the amygdala on emotional responses in monkeys.

All previous reports describing alterations in emotional reactivity after amygdala damage in monkeys were based on aspiration or radiofrequency lesions which likely disrupted fibres of passage coursing to and from adjacent ventral and medial temporal cortical areas. To determine whether this associated indirect damage was responsible for some or all of the changes described earlier, we compared the changes induced by aspiration of the amygdala with those induced by fibre-sparing neurotoxic lesions. Four different stimuli, two with and two without a social component, were used to evaluate the expression of defence, aggression, submission and approach responses. In unoperated controls, defence and approach behaviours were elicited by all four stimuli, 'social' and inanimate alike, whereas aggression and submission responses occurred only in the presence of the two 'social' stimuli. Furthermore, all defence reactions were reduced with an attractive inanimate item, while freezing was selectively increased with an aversive one. Relative to controls, monkeys with neurotoxic amygdala lesions showed the same array of behavioural changes as those with aspiration lesions, i.e. reduced fear and aggression, increased submission, and excessive manual and oral exploration. Even partial neurotoxic lesions involving less than two-thirds of the amygdala significantly altered fear and manual exploration. These findings convincingly demonstrate that the amygdala is crucial for the normal regulation of emotions in monkeys. Nevertheless, because some of the symptoms observed after neurotoxic lesions were less marked than those seen after aspiration lesions, the emotional disorders described earlier after amygdalectomy in monkeys were likely exacerbated by the attendant fibre damage.

Affective Symptoms↗
PubMed1998

Neonatal lesions of the medial temporal lobe disrupt prefrontal cortical regulation of striatal dopamine.

The effects of early brain damage are often, but not always, milder than the effects of comparable damage in adults, depending on the age at which injury occurred, the region of the brain damaged, and the brain functions involved. Studies of the impact of early brain damage have generally focused on functions primarily associated with the neural structures injured, even though the development and function of distant but interconnected neural systems might also show effects. Here we examine the regulation of striatal dopamine by the dorsolateral prefrontal cortex, in adult monkeys that had had either neonatal or adult lesions of the medial-temporal lobe and in normal animals. We use microdialysis to measure the dopamine response in the caudate nucleus after the infusion of amphetamine into the dorsolateral prefrontal cortex. Normal animals and those with adult lesions showed a reduction in dopamine overflow; in contrast, monkeys with neonatal lesions showed increased dopamine release. Thus, early injury to the primate medial-temporal lobe disrupts the normal regulation of striatal dopamine activity by the dorsolateral prefrontal cortex during adulthood. Early focal lesions may have substantial and long-lasting impacts on the function of a distant neural system.

Animals↗
PubMed1997

Neonatal ablations of the amygdala and inferior temporal cortex alter the vocal response to social separation in rhesus macaques.

Rhesus macaques that had received bilateral ablations to either the amygdala or area TE in inferior temporal cortex in the 1st week of life were briefly separated from familiar conspecifics at 10-14.5 months of age in order to assess the vocal response to this mild challenge. Sound spectrograms were subjected to quantitative analysis and compared with calls from normal, age-matched controls subjected to the same testing conditions. Animals with TE damage called at a higher rate than animals in the other two groups. TE subjects also produced more coos than controls. Males with TE lesions produced noisy calls at a higher rate than males of the other two groups. Females did not differ between groups in this measure. Analysis of the detailed acoustic structure of the 'coo' indicated significant differences in a measure of slope of the fundamental frequency (rate of frequency change over time) between amygdalectomized animals and those of the other 2 groups. The amygdalectomized monkeys produced calls with lower slope values, giving the calls a less inflected quality both in sonagrams and to the listener. These findings suggest an important role for the amygdala and inferior temporal cortex in regulating the vocal response to social separation during development.

Amygdala↗
PubMed1997

Thalamic and temporal cortex input to medial prefrontal cortex in rhesus monkeys.

To determine the source of thalamic input to the medial aspect of the prefrontal cortex, we injected retrograde tracers (wheat germ agglutinin conjugated to horseradish peroxidase, nuclear yellow, and/or bisbenzimide) into seven medial prefrontal sites and anterograde tracers (tritiated amino acids) into six thalamic sites, in a total of nine rhesus monkeys. The results indicated that ventral precallosal and subcallosal areas 14 and 25, and the ventral, subcallosal part of area 32, all receive projections from the mediodorsal portion of the magnocellular division of the medial dorsal nucleus (MDmc). The dorsal, precallosal part of area 32 receives projections mainly from the dorsal portion of the parvocellular division of the medial dorsal nucleus (MDpc), which also provides some input to area 14. Polar area 10 receives input from both MDpc and the densocellular division of the medial dorsal nucleus (MDdc), as does supracallosal area 24. Area 24 receives additional input from the anterior medial nucleus and midline nuclei. All medial prefrontal cortical areas were also found to receive projections from a number of cortical regions within the temporal lobe, such as the temporal pole, superior temporal gyrus, and parahippocampal gyrus. Areas 24, 25, and 32 receive, in addition, input from the entorhinal cortex. Combining these results with prior anatomical and behavioral data, we conclude that medial temporal areas that are important for object recognition memory send information directly both to dorsal medial prefrontal areas 24 and 32 and to ventral medial prefrontal areas 14 and 25. Only the latter two areas have additional access to this information via projections from the mediodorsal part of MDmc.

Animals↗
PubMed1997

Effects of orbital frontal and anterior cingulate lesions on object and spatial memory in rhesus monkeys.

Object memory processes, evaluated in rhesus monkeys by delayed nonmatching-to-sample with trial-unique stimuli and object reversal learning, were more severely impaired by orbital frontal than by anterior cingulate lesions. Spatial memory processes, assessed by spatial delayed response and spatial reversal learning, showed a weak trend in the opposite direction, though on these tasks neither lesion produced a serious loss. Comparison of the present results with those of earlier studies on the effects of various limbic system lesions suggests that object memory processes, including object recognition and object-reward association, are served by a circuit consisting mainly of the rhinal cortex, orbitofrontal cortex, and the magnocellular division of the medial dorsal thalamic nucleus. Although both the rhinal and orbitofrontal components of this circuit appear to participate in both functions, evidence from the present and earlier studies suggests that the orbitofrontal component is the more important one for associative memory, i.e. the formation across trials of associations between particular objects or classes of objects and reward, whereas the rhinal component is the more critical one for recognition memory, i.e. the storage and retrieval within trials of the representations of particular objects.

Animals↗
PubMed1997

Altered development of prefrontal neurons in rhesus monkeys with neonatal mesial temporo-limbic lesions: a proton magnetic resonance spectroscopic imaging study.

Focal brain damage occurring early in development can have widespread repercussions throughout the developing brain. In living adult rhesus monkeys, we studied the long-term effects of early mesial temporo-limbic (MTL) lesions on prefrontal cortex (PFC) neurons using proton magnetic resonance spectroscopic imaging (1H-MRSI), an in vivo neurochemical assay technique for measuring signals from metabolites such as N-acetyl-aspartate (NAA, a neuronal marker), choline-containing compounds (CHO) and creatine + phosphocreatine (CRE). Six monkeys (NL) had undergone surgical ablation of MTL structures within 3 weeks of birth, six monkeys received the same lesion at approximately 5 years of age and six monkeys were normal controls. We found significant bilateral reductions of NAA relative signals exclusively in the PFC of the NL group in comparison with either of the other groups. Our results indicate that neonatal MTL damage specifically affects PFC neurons of adult monkeys as indicated by a reduction of NAA. The basis of this effect involves developmental processes as implicated by two arguments: analogous damage during adulthood does not have the same effect; NAA in the healthy brain increases during development. This finding may have implications for understanding developmental aspects of prefrontal-temporolimbic connectivity, and the reduction of NAA levels observed in prefrontal cortex of patients with schizophrenia.

Aging↗