Limbic Lesions Research Articles

Emotional response and corticoadrenal function in anterodorsal thalami nuclei lesioned rats.

In male and female rats, the effect of limbic anterodorsal thalami nuclei lesions (ADTN) on the emotional reactivity and their relationship with corticoadrenal function were studied. The emotional reactivity was evaluated by means of the open-field test and the corticoadrenal function by means of plasma anol adrenal corticosterone concentration. The results demonstrate that, on the 8th or 9th day after the lesion, the male rats show lack of habituation and the female ones, an increase in emotional reactivity. They also indicate that the lesion of ADTN does not affect the corticoadrenal response to exposure to novel situations.

ORG 2766 fails to improve visual functions in rats with occipital lesions.

Adult rats were trained on a white versus black card discrimination in a circular water tank. Three independent variables were manipulated: lesion (sham, lateral occipital, medial occipital), dose of ORG 2766 administered (0 or 25 micrograms in saline on alternate days for 18 days), and time of administration (during the post-surgical recovery interval or during post-operative testing). Both visual cortical lesions produced a prominent retention deficit and defective pattern vision. Neither post-surgical nor concurrent administration of ORG 2766 improved visual functions. These results, along with a growing body of evidence, challenge the generality of the positive influences of ORG 2766 upon behavioral recovery observed in animals with limbic lesions.

Functional recovery after limbic lesions in monkeys

Ten monkeys received lesions of either the hippocampus, or the amygdala and hippocampus, or the anterior and medial thalamus (each group with two monkeys), or of all these structures together with additional septal lesions (four monkeys). Postoperatively, the monkeys were trained in tasks of visual and spatial reversal, several concurrent object discriminations, delayed nonmatch-to-sample, and in an angle threshold discrimination task. Their performance was compared to that of five healthy or sham-operated control monkeys. The single- or double-lesioned monkeys were impaired in the delayed nonmatch-to-sample task and the angle threshold discrimination, whereas monkeys with five-fold lesions were unimpaired in these tasks. Correlations between brain volume loss and behavioral performance indicated negative coefficients for the delayed nonmatch-to-sample task (“delays”: rs = −.59; “lists”: rs = −.20) and the angle threshold discrimination (rs = −.60). It is concluded that monkeys with massive limbic lesions display a more effective postlesion reorganization than monkeys with smaller limbic lesions; however, reliability of this effect must be proved by future work with a larger sample. Furthermore, the missing impairments of massively lesioned monkeys especially in the delayed nonmatch-to-sample task also indicate that the limbic targets lesioned here may not be as exclusively involved in mnemonic information processing as suggested earlier.

Limbic lesions in a patient with recurrent mania

Limbic lesions in a patient with recurrent mania

Delta-9-tetrahydrocannabinol impairs visual recognition memory but not discrimination learning in rhesus monkeys.

The effects of orally administered delta-9-tetrahydrocannabinol (THC) were evaluated on two different learning abilities in monkeys. Visual recognition memory, known to depend on limbic system integrity, was tested by means of delayed nonmatching-to-sample and found to be significantly impaired by acute administration of 2 and 4 mg/kg THC given 1 or 2 h prior to testing. Performance was significantly impaired throughout a 21-day period of repeated administration of 4 mg/kg THC and also during a 3-5 day period that began 7-10 days after the last dose of THC. By contrast, 24-h concurrent discrimination learning, a task that monkeys with limbic lesions can perform normally, was not impaired by THC, even following doses as high as 16 mg/kg. These results suggest that THC interferes with recognition memory more than discrimination learning, possibly reflecting a selective action of THC on limbic mechanisms.

Spontaneous alternation and exploration in staggerer mutant mice

Staggerer mutant mice were found to be less active in terms of motor activity in a maze, hole poking and rearing. Staggerer mutant mice also showed a lack of spontaneous alternation in both 2-trial and 4-trial tests. A lack of spontaneous alternation in this mutant may be due to a deficit in response inhibition or in spatial orientation, similar to that of animals with limbic lesions.

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.

The Hebb-Williams test to assess recovery of learning after limbic lesions in mice

A scaled-down Hebb-Williams closed-field maze was constructed and adapted for use with mice. In a first experiment, the acquisition performance of the original 12 Hebb-Williams mazes by BALB/c mice was studied in order to re-group the mazes into 3 main groups of difficulty (low, moderate and high). In a second experiment different problems from each class of difficulty were presented at 3 times intervals (between 3 and 7 weeks after surgery) to mice with lesions of the cingulate cortex. The rate of acquisition in lesioned mice was observed to be facilitated between 3 and 5 weeks after surgery for the most difficult mazes. This effect was reversed (impairment) at 7 weeks post-lesion. The observed biphasic behavioral modifications constitute evidence that our present protocol provides a useful tool to evaluate the time-course of changes in learning performance following brain injury.

The Hebb-Williams test to assess recovery of learning after limbic lesions in mice

The Hebb-Williams test to assess recovery of learning after limbic lesions in mice

Combined lesions of septum, amygdala, hippocampus, anterior thalamus, mamillary bodies and cingulate and subicular cortex fail to impair the acquisition of complex learning tasks

Previous investigations (Irle and Markowitsch 1982a, 1983, 1984) demonstrated that triple or fourfold lesions within the cat's limbic system fail to produce learning impairments, as opposed to lesions of single or double loci, when tasks of visual reversal, delayed alternation, and active two-way avoidance were used. On the basis of these results, limbic regions of the cat's brain might be considered unessential for intact learning and mnemonic functions. Therefore, in order to obtain indisputable information on the importance of the limbic system for learning and memory, lesions of nearly all limbic core regions of the cat were performed. Ten cats received lesions of seven limbic core regions: the septum, amygdala, anterior thalamus, mamillary bodies, cingulate cortex, subicular cortex, and the hippocampus proper. Nine of these animals were tested postoperatively in the acquisition of a visual reversal task, a spatial alternation and delayed alternation task, and an active two-way avoidance task, and were then compared to the performance levels of ten control animals. The experimental animals turned out to be unimpaired in all tasks tested; the performance scores in the visual reversal and delayed alternation task and - for some experimental animals - in the active two-way avoidance task even indicate a slight, though statistically insignificant, facilitation in the learning behavior of these animals. It is assumed that the learning functions underlying the tasks used were taken over by other brain regions, which, prior to massive limbic lesions, may be suppressed or otherwise inhibited. Alternatively, utilization of spared tissue in the damaged limbic regions must be considered as the possible explanation.

Differential effects of prefrontal lesions and combined prefrontal and limbic lesions on subsequent learning performance in the cat.

On the basis of a previous experiment (Irle & Markowitsch, 1983) in which triple limbic lesions as opposed to double limbic lesions in the cat failed to impair the learning behavior of these animals, the effects of a lesion in a fourth brain structure, in addition to the original ones, were examined. Two groups of cats were given lesions in either the prefrontal cortex alone or in the prefrontal cortex, the anterior thalamus, the mamillary bodies, and the subiculum and subsequently tested in the acquisition of a visual reversal, a delayed alternation, and an active two-way avoidance task. Compared with control cats, cats with prefrontal lesions were strongly impaired in the acquisition of the visual reversal task and the delayed alternation task but only slightly impaired in the acquisition of the active two-way avoidance task. In contrast, animals with combined prefrontal cortical, anterior thalamic, mamillary, and subicular lesions were unimpaired in the acquisition of the visual reversal task, slightly facilitated in the acquisition of the active two-way avoidance task, but impaired in the acquisition of the delayed alternation task similarly to the animals with prefrontal lesions. The superior performance rates of the animals with fourfold lesions are considered to be due to a lesion-induced functional shift acting on intact brain structures which, prior to massive limbic lesions, remain inhibited or otherwise suppressed. The failure of the animals with fourfold lesions in the delayed alternation task indicates that the functions underlying this type of behavior cannot be compensated for or, alternatively, that a prefrontal lesion is not sufficient to disinhibit other structures involved in the same behavior.

Differential effects of prefrontal lesions and combined prefrontal and limbic lesions on subsequent learning performance in the cat.

Differential effects of prefrontal lesions and combined prefrontal and limbic lesions on subsequent learning performance in the cat.

Monkeys with combined amygdalo-hippocampal lesions succeed in object discrimination learning despite 24-hour intertrial intervals.

Monkeys with combined amygdalo-hippocampal removal show severe impairments on visual memory tasks after delays of only a minute or two, yet they learn visual discrimination habits about as quickly as normal animals with intertrial intervals of the same duration. In an attempt to resolve this discrepancy between abnormally rapid forgetting and successful retention, tests were conducted to determine whether discrimination learning would be prevented in animals with limbic lesions if intertrial intervals lasted 24 hr. The results showed that as long as the lesion did not encroach on inferior temporal cortex, the operated animals could acquire concurrent sets of 20 object discrimination habits at the same rate as normal animals, in an average of about 10 trials per set. The findings suggest that learning and retention processes are divisible into a mechanism for memory formation that is dependent on the limbic system and a mechanism for habit formation that is not.

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.

Differential effects of double and triple lesions of the cat's limbic system on subsequent learning behavior.

On the basis of recent anatomical experiments in which it was found that the anterior thalamus, the subicular cortex, and the mamillary bodies are directly and strongly interconnected, lesions were made in different combinations of two or all three of these regions in four groups of cats. These found groups and a control group were then subjected to two learning tasks: a visual reversal and an active two-way avoidance task. Compared with cats of the control group, cats with lesions of the anterior thalamus and the mamillary bodies (Group AT/MM), of the anterior thalamus and the subiculum (Group AT/SUB), or of the mamillary bodies and the subiculum (Group MM/SUB) were strongly impaired in acquiring the reversal task, whereas cats with lesions of all three structures together (Group AT/MM/SUB) were unimpaired. Similarly, in the active avoidance task, two of the three groups with double lesions (MM/SUB; AT/SUB) were imparied, but cats of Groups AT/MM and AT/MM/SUB were not, compared with the control group. Consideration is made that lesion-induced shifts possibly act upon intact cortical and/or thalamic structures that, prior to massive limbic lesions, remained inhibited or otherwise suppressed. It is assumed the influence of one of the three core regions of the modified Papez-circuit to be sufficient for inhibiting the action of such structures which following a complete lesion of the system may control essential parts of the behaviors tested.

Hypothalamic-immune interactions: Effect of hypophysectomy on neuroimmunomodulation

Electrolyte destruction of certain nuclei of the brain cause specific structural and functional changes in the immune system. Lesions in the preoptic-anterior hypothalamic area result in thymic involution and a decrease in the number and blastogenic reactivity of splenocytes. In contrast, lesions in the hippocampus increase thymic and splenic mitogenic responsiveness and cellularity. Hypophysectomy abrogates all changes in splenocyte number and function induced by hypothalamic and limbic lesions. The effects of ablating the hippocampus and amygdaloid complex on thymocyte number and function also are abolished. Hypothalamic lesions in hypophysectomized animals result in an increase in the number of thymocytes but suppressed mitogenic activity. These data indicate that neuroimmunomodulation is mediated predominantly but not exclusively by the pituitary gland.

Effect of septal lesions on conditioned defensive burying

Every control rat shocked by a wire-wrapped prod mounted on the wall of a test chamber buried the prod with bedding material from the floor of the chamber. Although this conditioned defensive burying was also observed in every rat with a lesion of the anterior septum (Experiment 2), no rat with a lesion of the entire septum (Experiment 1) or a lesion limited to the posterior septum (Experiment 2) was observed to engage in this behavior. These results confirm previous reports of the involvement of the septal area in defensive behavior and provide the first demonstration of the utility of the conditioned defensive burying paradigm in assessing the behavioral effects of limbic lesions.

Limbic lesions and the blocking effect

Rats with bilateral lesions to either the mamillary bodies, dorsomedial nucleus of the thalamus, dorsal hippocampus, or ventral hippocampus and sham-operated controls were tested on Kamin's 2-stage blocking paradigm. When dorsal hippocampal, thalamic, and sham rats trained to a single auditory or visual cue prior to conditioning to a compound stimulus composed of the initial training cue and a novel, but redundant stimulus were later tested to the redundant element, they did not evidence learning to the redundant cue. Conditioning was blocked to the redundant cue. In contrast, blocking was attenuated in rats lesioned in either the ventral hippocampus or the mamillary bodies. The results suggest that different regions of the hippocampus and related structures comprise distinct systems, which mediate dissociably different behaviors. Moreover, it appears that the ventral hippocampus and mamillary bodies may be involved in “time-tagging” motivationally significant events.

Reductions in aggression and dominance status in guinea pigs following bilateral lesions in the basolateral amygdala or lateral septum

Two studies assessing the effects of limbic lesions on aggression and dominance status in the guinea pig were performed. In Experiment 1 the dominant animal in each of 13 groups (dyads or triads) was selected to receive a bilateral lesion in the basolateral nuclei of the amygdala, while its sham or unoperated peers served as controls. In 6 animals the lesions were in the target area and all of these animals fell in their dominance hierarchies, most to the bottom. The other 7 animals suffered damage to areas proximal to, but not in, the amygdala, and they maintained their dominance status throughout the post-operative observation period. In Experiment 2 the dominant animal in each of 9 triads was selected to receive a bilateral lesion in the lateral septum, while its sham or unoperated peers served as controls. In 5 animals the lesions were in the lateral septum and all of these animals lost their alpha dominance status. One animal died post-operatively; in the remaining 3 animals the lesions were dorsal to the target area and these 3 animals maintained their dominance status throughout. Both types of lesions led to reductions of aggression and dominance status, for apparently different reasons. The reduction following the amygdaloid lesions appears to be a result of the animals' inability to adequately defend themselves, while the reduction following the septal lesions appears to stem from an increase in hyperreactivity. No recovery of function was observed in the amygdaloid animals; however, the septal animals displayed evidence of recovery from the effects of their lesions.

Amphetamine disrupts successive but not simultaneous visual discrimination in the monkey.

Three adolescent marmosets were trained on simultaneous and successive versions of a red-white visual discrimination task. The effects of doses of 0.2-1.2 mg/kg D-amphetamine on the performance of these tasks were assessed using a balanced design. It was found that while there was no drug effect on performance of the simultaneous task, amphetamine exerted a dose dependent disruptive effect on the successive version of the task. It is argued that amphetamine disrupts response control rather than discriminative ability and, in this respect, resembles the effect of orbitofrontal and limbic lesions in contrast to other neocortical lesions.