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Biomedical subjects

L Málková

Publications and source records attributed to L Málková.

12 recordsLinked to original sources
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

MRI-Based evaluation of locus and extent of neurotoxic lesions in monkeys.

To minimize the variability in the extent of lesions made by injections of the excitotoxin ibotenic acid in rhesus monkeys, we developed and validated an MRI-based method to determine the efficacy of the injections soon after surgery. T2-weighted MR images were obtained 6-11 days after surgery from 17 brain hemispheres of monkeys that had received bilateral lesions of either the hippocampal formation (HF), perirhinal cortex, or parahippocampal cortex. The extent of lesion estimated from the hypersignal that appeared in and outside of the targeted area on these MR images was compared with the extent of damage assessed histologically after survival periods ranging from 120-370 days. Highly significant correlations (r values between 0.85-0.99) were found between these two measures for several regions in the medial temporal lobe. Based on this finding, lack of hypersignal in the targeted area of some Ss was followed by successful reinjection of the neurotoxin to create more complete cell loss prior to the postoperative phase of the study. We also assessed the relationship between a postoperative reduction in HF volume, measured from T1-weighted MR images, and the extent of damage determined histologically in 14 hemispheres of monkeys with bilateral excitotoxic HF lesions. The HF volume decreases sharply after surgery until 40-50 days postoperatively, after which there is only a minor further decrease. Based on this finding, we obtained T1-weighted MR images at least 44 days but in most cases close to 1 year after surgery. A highly significant positive correlation (r = 0.95, P < 0.001) was found between neuronal damage and volume reduction, with nearly complete neuronal damage (96-99%) corresponding to a volume reduction of 68-79%. These MRI-based methods thus provide an accurate in vivo evaluation of the locus and extent of neurotoxic lesions. Application of these methods can ensure that each animal in the experiment is used effectively.

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

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

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↗
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↗
PubMed1995

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↗
PubMed1989

Strictly simultaneous classical eyelid conditioning in man.

Strictly simultaneous eyelid conditioning in human Ss on the one hand and forward (ISI: 0.45 s), backward (ISI: -0.45 s), and pseudoconditioning on the other hand were compared in two different experimental situations: one-session experiment (100 reinforcements, 20 isolated CS randomly interspersed), and ten-sessions experiment (20 reinforcements, 4 isolated CS in each session), UCS was a light flash (0.5 J, 20 microseconds duration), CS a tone (1000 Hz, 50 ms, 73 dB). In both the experiments, strictly simultaneous conditioning was significantly different from pseudoconditioning, but significantly less effective than forward conditioning. In the ten-sessions experiment, it was also less effective than backward conditioning, while in the one-session experiment, it did not differ from backward conditioning. Statistical mixture decomposition method applied to the one-session- and the ten-sessions- experimental samples of individual acquisition curves resulted into the division of both samples into 4 subgroups according to the trend of acquisition curves. A significant positive association between the conditioning procedure and the distribution of individual curves into the four subgroups was found.

Adolescent↗
PubMed1986

Statistical mixture decomposition as a method for type analysis of learning curves.

A method for type analysis of learning curves, based on the statistical mixture decomposition, is described. Some critical points in current data-analytic techniques are discussed. The mathematical rationale of the new method is outlined in a brief sketch. The possibilities of the method are documented by two examples. In the first study, done on simulated lata of a known structure (N = 200, 2 classes), it was possible to distinguish, with an average performance of 82%, between two types, and to reproduce their original curves. In the second study data from experiments in classical eye-lid conditioning in man were analysed (N = 80). The decomposition procedure resulted into the classification into four groups, with pronounced inter-class differences in the course of respective learning curves. The variety of class curves ranges from a group with only few CRs (C1, N = 26), through a group with an initial increase and final decrease in CR frequency (C2, N = 16), a group with an apparently biphasic course of CR frequency (C3, N = 20), to a group with a rapid increase of CR and then stable course of CR frequency (C4, N = 18). The results are consistent with earlier findings concerning the existence of distinct types of learning curves. The problem of interpretation is briefly discussed. The method can be applied principally to any problems, where different types of time development trends of an alternative response are to be distinguished.

Conditioning, Classical↗