Deficits in visual learning produced by posterior temporal lesions in cats

Eight cats with lesions in the posterior temporal (PT) cortex, seven cats with lesions in the basolateral amygdala (BLA), and eight intact controls were observed on eight tests of visual discrimination learning and of spontaneous responses to salient visual stimuli. The effects of the two lesions were somewhat dissociable. The PT lesions were accompanied by a severe deficit in pattern discrimination learning but no loss in visual tracking or orientation to the silhouette of a threatening cat. The BLA lesions produced a milder and less consistent loss in pattern discrimination but serious defects in tracking and reponse to the cat silhouette. Both operated groups performed well on the visual cliff. The deficit from PT lesions appeared independent of damage to the geniculocortical system. The parallel of symptoms from PT lesions in cats and inferotemporal lesions in monkeys is discussed.     

Cognitive style: problem solving by rhesus macaques (Macaca mulatta) reared with living or inanimate substitute mothers

Cognitive style, reflected in the generation of novel solutions and the use of identifiable response strategies in problem-solving situations, was contrasted in rhesus monkeys (Macaca mulatta) reared individually with either canine companions or inanimate surrogate mothers. Four experiments were conducted over a 5-year period, examining problem solving in relatively unstructured as well as more formal situations. Results indicated that whereas the 2 rearing groups did not differ on most measures of performance, consistent response strategies were identified for the dog-raised monkeys. The results were compared with previously published data from the same monkeys demonstrating rearing group differences in abilities to engage in complex social interaction. The animate nature of the early rearing environment may facilitate-the development of a cognitive style that influences problem-solving abilities in both the social and nonsocial realms.     

Electrolytic,but not neurotoxic,lesions to the lateral tegmental tract increase acoustic startle amplitude and reduce startle stimulus-induced freezing

Startle amplitude and startle stimulus-induced freezing (an index of fear) were measured in a standard acoustic startle response (ASR) paradigm in male Sprague-Dawley rats. Groups with electrolytic lesions to the lateral tegmental tract (LTG) or with axon-sparing lesions to the area around LTG made with the neurotoxin NMDA were compared with vehicle-injected or sham operated control groups on these response measures. Replicating previous results (Leaton & Brucato, 2001), electrolytic lesions to LTG significantly reduced freezing and produced a persistent 300% increase in ASR amplitude compared with all other groups. The NMDA lesions had no effect on freezing or on ASR amplitude compared with the controls. In additional testing the rats with electrolytic lesions to LTG did not differ from controls in the acquisition or retention of context freezing using a footshock unconditioned stimulus. The data made a small, but necessary, step in further clarifying two pathways that modify ASR. The source of the descending pathway that provides tonic inhibition of the sensory input to the ASR circuitry is not within the LTG. The ascending pathway that carries the fear-inducing dimensions of the acoustic stimulus to the amygdala by way of the medial geniculate nucleus does not have an intermediate synapse in the area within LTG.     

Comparison of emotional responses in monkeys with rhinal cortex or amygdala lesions

Four emotionally arousing stimuli were used to probe the behavior of monkeys with bilateral ablations of the entorhinal and perirhinal cortex. The monkeys' behavioral changes were then contrasted with those observed earlier (M. Meunier, J. Bachevalier, E. A. Murray, L. Málková, & M. Mishkin, 1999) in monkeys with either neurotoxic or aspiration lesions of the neighboring amygdala. Rhinal cortex ablations yielded several subtle behavioral changes but none of them resembled any of the disorders typically seen after amygdalectomies. The changes produced by rhinal damage took mainly the form of heightened defensiveness and attenuated submission and approach responses; that is, just the opposite of some of the most distinctive symptoms following amygdala damage. These findings raise the possibility that the rhinal cortex and amygdala have distinct, interactive functions in normal behavioral adaptation to affective stimuli.     

Social and nonsocial behaviors of adult rhesus monkeys after amygdalectomy in infancy or adulthood.

At 6 yr of age six female rhesus monkeys that had sustained bilateral amygdalectomy in infancy, and five intact controls, were transferred to an observation cage where behaviors were recorded while the monkeys were (a) alone, (b) paired with unfamiliar stimulus animals, and (c) paired with familiar monkeys from the opposite experimental group. The five adult controls then underwent amygdalectomy, and all tests were repeated with the infant- and adult-operated animals. Infant-operated monkeys changed behaviors more rapidly than did intact controls in social and nonsocial situations, and their activity levels were less modified after a 24-hr period in the observation cage. They were subordinate to intact controls but expressed less fear than did controls when briefly placed with an unfamiliar aggressive animal. Adult amygdalectomy produced many changes in behavior, but these aberrations were identical to those observed in like-age monkeys that had been amygdalectomized in infancy. Infant-operated monkeys demonstrated more behavioral deficits at 6 yr than they had earlier in life.     

Looming Threats and Animacy: Reduced Responsiveness in Youth with Disrupted Behavior Disorders

Theoretical models have implicated amygdala dysfunction in the development of Disruptive Behavior Disorders (DBDs; Conduct Disorder/Oppositional Defiant Disorder). Amygdala dysfunction impacts valence evaluation/response selection and emotion attention in youth with DBDs, particularly in those with elevated callous-unemotional (CU) traits. However, amygdala responsiveness during social cognition and the responsiveness of the acute threat circuitry (amygdala/periaqueductal gray) in youth with DBDs have been less well-examined, particularly with reference to CU traits. 31 youth with DBDs and 27 typically developing youth (IQ, age and gender-matched) completed a threat paradigm during fMRI where animate and inanimate, threatening and neutral stimuli appeared to loom towards or recede from participants. Reduced responsiveness to threat variables, including visual threats and encroaching stimuli, was observed within acute threat circuitry and temporal, lateral frontal and parietal cortices in youth with DBDs. This reduced responsiveness, at least with respect to the looming variable, was modulated by CU traits. Reduced responsiveness to animacy information was also observed within temporal, lateral frontal and parietal cortices, but not within amygdala. Reduced responsiveness to animacy information as a function of CU traits was observed in PCC, though not within the amygdala. Reduced threat responsiveness may contribute to risk taking and impulsivity in youth with DBDs, particularly those with high levels of CU traits. Future work will need to examine the degree to which this reduced response to animacy is independent of amygdala dysfunction in youth with DBDs and what role PCC might play in the dysfunctional social cognition observed in youth with high levels of CU traits.     

Incidental learning,attention, and curiosity in squirrel monkeys calorie deprived as infants

The long-term effects of infantile malnutrition on information processing were studied in squirrel monkeys. From 2 through 8 weeks of age, four low-calorie infants were fed reduced amounts of a high protein diet, limiting their mean body weight gain to 23% of that of four well-fed controls, with all of this gain occurring during the first 2 weeks on the low-calorie diet. Thereafter, both groups received the standard diet ad libitum. At 68 weeks of age, incidental learning was tested by introducing shape cues that were redundant to the solution of a previously learned, two-choice, color discrimination. Removal of the color cues showed that the low-calorie monkeys had learned significantly less about the shape cues than had the controls. The basis for this incidental learning failure was then examined with an embedded-figures dicrimination, to measure attentional ability, and a novel stimulus substitution task, to measure curiosity. The groups did not differ in detecting embedded figures, but the low-calorie monkeys were significantly less likely than controls to select or handle novel stimuli that had been substituted for previously learned discriminative cues. It was concluded that undernutrition in infancy may induce a long-term strategy of only learning information which leads to an immediate reward, while suppressing the acquisition of information due to intrinsic curiosity.     

Stimulus similarity and encoding time influence incidental recognition memory in adult monkeys with selective hippocampal lesions

Recognition memory impairment after selective hippocampal lesions in monkeys is more profound when measured with visual paired-comparison (VPC) than with delayed nonmatching-to-sample (DNMS). To clarify this issue, we assessed the impact of stimuli similarity and encoding duration on the VPC performance in monkeys with hippocampal lesions and sham-operated controls. The novelty preference was compared for pictures of dissimilar vs. similar objects and for encoding duration of 30, 10, 5, and 1 sec. The novelty preference was spared after hippocampal lesions with dissimilar (colored or black and white [BW]) stimuli and an encoding time ≥10 sec, but declined with similar stimuli or a short encoding time of 1 or 5 sec. Therefore, the severe VPC impairment reported earlier after hippocampal damage cannot be attributed to the long encoding time used (30 sec) relative to DNMS (1-5 sec). However, it may result, at least in part, from the poorer distinctiveness of the stimuli typically used for VPC (BW slides of pictures of equal size and brightness of objects differing in shape) relative to the actual objects used for DNMS, differing in shape, color, size, brightness, and texture. This conclusion fits well with current models that view the hippocampus as a comparator capable of individualizing the representations of highly overlapping inputs.     

Contrasts in visual responsiveness and emotional arousal between rhesus monkeys raised with living and those raised with inanimate substitute mothers.

Rhesus monkeys were raised with dogs or inanimate surrogates in outdoor cages which provided them with complex, highly varied visual surroundings. Visual responsiveness to a variety of colored transparencies was investigated in three experiments, completed when the monkeys were between 18 and 30 mo old. Results indicated that the frequency and duration of looking at slides was significantly higher for dog-raised than for inanimate-surrogate-raised monkeys and that dog-raised monkeys were much more responsive to the novelty, complexity, ansal were obtained during the final experiment. Heart rate, vocalization, and changes in plasma cortisol were higher for monkeys raised with dogs. The frequency of most self-directed behaviors, however, was higher for monkeys raised with inanimate surrogates. Differences between rearing groups can only be the result of contrasts in attributes of the substitute mothers.     

Maternal behavior of mice with cingulate cortical, amygdala, or septal lesions.

Nest building, pup retrieving, and pup survival and growth were evaluated in primiparous control mice and those with cingulate cortical, neocortical, amygdala, or septal lesions. Mice with neocortical or amygdala lesions showed little or no deficits in maternal behavior. Mice with septal lesions were severely impaired in all aspects of maternal care. These mice did not build nests, showed a variety of aberrant behaviors during pup retrieving, and their pups died or gained significantly less weight than those of controls. Mice with cingulate cortical lesions retrieved pups more slowly than controls, and retrieving deficits were correlated with the extent of retrograde degeneration found in the anterior thalamic nuclei.     

Contrasting effects of lateral striate and superior colliculus lesions on visual discrimination performance in rhesus monkeys.

Rhesus monkeys with lesions of lateral striate cortex, monkeys with superior colliculus lesions, and unoperated monkeys were tested for retention of a preoperatively acquired pattern discrimination. The three groups of monkeys were then tested in two-choice, color, color discrimination tests, one involving varying degrees of stimulus-response (S-R) separation and the other, administered several months later, involving various directions of S-R separations. The monkeys were also tested in a series of two-choice pattern discriminations, following each of which they were tested for relearning when the patterns were masked with bars or circles. The monkeys with lateral striate lesions were moderately retarded in retention of the pattern discrimination, whereas those with superior colliculus lesions were not. The monkeys with colliculus lesions, but not those with lateral striate lesions, were impaired in both S-R separation tests, which demonstrates that their deficit was not transient or solely due to a difficulty in shifting the gaze in one direction. The lateral striate monkeys, unlike those with colliculus lesions, were dificient in relearning discriminations between masked patterns. These findings suggest that superior colliculus and striate cortex may be involved in two different aspects of attention: respectively, shifting attention (and orientation) from one spatial locus to another and maintaining attention on fixated stimuli. Alternative interpretations of the effects of the lesions, based on their retinotopic loci, are discussed.     

Functional organization of the rat amygdala with respect to avoidance behavior.

Bilateral electrolytic lesions in the periamygdaloid piriform cortex of female albino rats produced marked disruptive effects on the acquisition of active avoidance responses in a 1-way as well as a 2-way test situation, significantly impaired passive avoidance behavior, and inhibited feeding in a novel environment. Lesions in each of the 6 major subdivisions of the amygdala (cortical, medial, central, intercalated, lateral, and basolateral nuclei) consistently produced facilitatory effects on active avoidance behavior in 1-way as 2-way situations. Passive avoidance behavior was impaired in animals with lesions in the central, intercalated, and basolateral nuclei. Damage to the anterior amygdaloid area or the the nuclei of the lateral olfactory tract did not reliably affect active or passive avoidance behavior.     

Functional connectivity abnormalities vary by amygdala subdivision and are associated with psychiatric symptoms in unilateral temporal epilepsy

The amygdala has been described as a structure affected by mesial temporal lobe epilepsy (MTLE). Indeed, it is suggested that amygdala abnormalities are related to the co-morbid depression and anxiety reported in MTLE. In this context, we investigated the relation between functional connectivity (FC) emerging from this structure in fMRI and depression and anxiety levels reported in MTLE patients. We focused on resting-state BOLD activity and evaluated whether FC differences emerge from each of three amygdala subdivisions (laterobasal, centromedial and superficial) in left and right MTLE groups, compared with healthy controls. Results revealed significant differences between patient groups and controls. Specifically, the left MTLE group showed abnormal FC for the left-sided seeds only. Furthermore, regardless of the seed, we observed more reliable differences between the right MTLE group and controls. Further analysis of these results revealed correlations between these impaired connectivities and psychiatric symptoms in both MTLE groups. Opposite relations, however, were highlighted: the more depressed or anxious the right MTLE patients, the closer their FC values approached controls; whereas the less anxious the left MTLE patients, the closer their FC values were normative. These results highlight how MTLE alter FC emerging from the limbic system. Overall, our data demonstrate that right TLE has a more maladaptive impact on emotion-related networks, in ways specific to the amygdala region, and the emotion symptom involved, than left TLE.     

Social competence is reduced in socially deprived rhesus monkeys (Macaca mulatta)

Rhesus monkeys deprived for some period from their mother have often served as a model for the effect of adverse rearing conditions on social competence in humans. Social competence is the capacity to react in a species-specific way to social interactions. The current study assesses whether early deprivation from peers also affects the rates of behavior and social competence in rhesus monkeys. This was studied in groups of rhesus monkeys with different rearing conditions: subadult females that were mother-only reared during their first year of life and subsequently housed with peers were compared with subadult females from five naturalistic social groups. Socially deprived monkeys showed higher rates of submission and stereotypic behaviors than socially reared individuals. In addition, they show socially incompetent behavior, since they react with agonistic behavior to nonthreatening social situations. The results suggest that this socially incompetent behavior is rooted in a general feeling of anxiety toward group companions. The authors hypothesize that anxiety negatively affects social information processing, which results in socially incompetent behavior.     

Differential fear conditioning induces reciprocal changes in the sensory responses of lateral amygdala neurons to the CS(+) and CS(-)

In classical fear conditioning, a neutral sensory stimulus (CS) acquires the ability to elicit fear responses after pairing to a noxious unconditioned stimulus (US). As amygdala lesions prevent the acquisition of fear responses and the lateral amygdaloid (LA) nucleus is the main input station of the amygdala for auditory afferents, the effect of auditory fear conditioning on the sensory responsiveness of LA neurons has been examined. Although conditioning was shown to increase CS-evoked LA responses, the specificity of the changes in responsiveness was not tested. Because conditioning might induce nonspecific increases in LA responses to auditory afferents, we re-examined this issue in conscious, head-restrained cats using a differential conditioning paradigm where only one of two tones (CS(+) but not CS(-)) was paired to the US. Differential conditioning increased unit and field responses to the CS(+), whereas responses to the CS(-) decreased. Such changes have never been observed in the amygdala except in cases where the CS(-) had been paired to the US before and fear responses not extinguished. This suggests that fear conditioning is not only accompanied by potentiation of amygdalopetal pathways conveying the CS(+) but also by the depression of sensory inputs unpaired to noxious stimuli.     

Differences between Saimiri sciureus and Callicebus moloch in physiological responsiveness: implications for behavior

The New World primates Callicebus moloch and Saimiri sciureus differ markedly in life modes. Physiological responsiveness (heart rate, cortisol) of these related taxa was compared in two situations that differed in the presumed degree of stress imposed, exposure to a novel environment and physical restraint. In both situations, Saimiri exhibited higher initial levels of heart rate and corticosteroids. In addition, the species differed in their patterns of response to both situations. Saimiri maintained initial heart rate levels across a 1-hour exposure period, whereas Callicebus showed a marked and continuous decline in heart rate. Adrenocortical activity increased in both species in response to test situations, but the elevations in plasma corticosteroids were substantially greater for Saimiri than for Callicebus. The results indicate that the species differ with respect to organization of physiological regulatory systems in a manner consistent with behavioral contrasts between them.     

Damage to the lateral and central, but not other, amygdaloid nuclei prevents the acquisition of auditory fear conditioning

It is well established that the amygdala plays an essential role in Pavlovian fear conditioning, with the lateral nucleus serving as the interface with sensory systems that transmit the conditioned stimulus and the central nucleus as the link with motor regions that control conditioned fear responses. The lateral nucleus connects with the central nucleus directly and by way of several other amygdala regions, including the basal, accessory basal, and medial nuclei. To determine which of these regions is necessary, and thus whether conditioning requires the direct or one of the indirect intra-amygdala pathways, we made lesions in rats of the lateral, central, basal, accessory basal, and medial nuclei, as well as combined lesions of the basal and accessory basal nuclei and of the entire amygdala. Animals subsequently underwent fear conditioning trials in which an auditory conditioned stimulus was paired with a footshock unconditioned stimulus. Animals that received lesions of the lateral or central nucleus, or of the entire amygdala, were dramatically impaired, whereas the other lesions had little effect. These findings show that only the lateral and central nuclei are necessary for the acquisition of conditioned fear response to an auditory conditioned stimulus.     

Verbal and Nonverbal Emotional Memory Following Unilateral Amygdala Damage

The amygdala is involved in the normal facilitation of memory by emotion, but the separate contributions of the left and right amygdala to memory for verbal or nonverbal emotional material have not been investigated. Fourteen patients with damage to the medial temporal lobe including the amygdala (seven left, seven right), 18 brain-damaged, and 36 normal controls were exposed to emotional and neutral pictures accompanied by verbal narratives. Memory for both narratives and pictures was assessed with a free recall test 24 h later. Subjects with left amygdala damage failed to show the normally robust enhancement of memory for verbal and nonverbal emotional stimuli. The group with right amygdala damage showed the normal pattern of facilitation of memory by emotion for both verbal and nonverbal stimuli despite an overall reduction in memory performance. Furthermore, subjects with left amygdala damage were disproportionately impaired on memory for emotional narratives as compared with memory for emotional pictures. The latter finding offers partial support for a lateralized and material-specific pattern of the amygdala's contribution to emotional memory.     

Exploration and avoidance learning after ibotenic acid and radio frequency lesions in the rat amygdala

Open-field activity, avoidance behavior, and plasma corticosterone levels were studied after intraamygdala injections of 3.0 micrograms ibotenic acid (IBO) and radio-frequency (RF) lesions in the amygdala complex of male Wistar rats. The experiments were undertaken to evaluate the importance of amygdala neurons versus axons of passage in fear-motivated behavior. The IBO lesions led to increased open-field activity, but no impairments in active avoidance learning, nor changes in basal or experimental levels of plasma corticosterone. The RF lesions, on the other hand, led to an increase in experimental plasma corticosterone levels. In the one-way avoidance task the RF lesions, in contrast to the IBO lesions, led to significant impairments in the acquisition of the avoidance response. Although the long-term axon-sparing effect of IBO is questioned since cavities were detected in the affected areas 8 weeks after the injections, the differences in avoidance learning and in corticosterone levels between the RF and the IBO lesions indicate that the axons were functionally active at the time of testing (14-26 days postoperatively). The increase in open-field activity is attributed to the destruction of amygdala neurons and neurons in the overlying cortex, while an avoidance deficit seem to depend on the destruction of axons. On the basis of the behavioral results and the corticosterone data in these experiments, it is suggested that the behavioral changes are not attributable to a general reduction in the arousal of fear. However, since the IBO lesions did not affect the most medial parts of the amygdala complex including the central amygdala nucleus, the role of this nucleus in fear arousal has to be investigated further.     

Intact visual perceptual discrimination in humans in the absence of perirhinal cortex

While the role of the perirhinal cortex in declarative memory has been well established, it has been unclear whether the perirhinal cortex might serve an additional nonmnemonic role in visual perception. Evidence that the perirhinal cortex might be important for visual perception comes from a recent report that monkeys with perirhinal cortical lesions are impaired on difficult (but not on simple) visual discrimination tasks. We administered these same tasks to nine amnesic patients, including three severely impaired patients with complete damage to perirhinal cortex bilaterally (E.P., G.P., and G.T.). The patients performed all tasks as well as controls. We suggest that the function of perirhinal cortex as well as antero-lateral temporal cortex may differ between humans and monkeys.