The development of object recognition memory in rhesus macaques with neonatal lesions of the perirhinal cortex.

To investigate the role of the perirhinal cortex on the development of recognition measured by the visual paired-comparison (VPC) task, infant monkeys with neonatal perirhinal lesions and sham-operated controls were tested at 1.5, 6, 18, and 48 months of age on the VPC task with color stimuli and intermixed delays of 10 s, 30 s, 60 s, and 120 s. Monkeys with neonatal perirhinal lesions showed an increase in novelty preference between 1.5 and 6 months of age similar to controls, although at these two ages, performance remained significantly poorer than that of control animals. With age, performance in animals with neonatal perirhinal lesions deteriorated as compared to that of controls. In contrast to the lack of novelty preference in monkeys with perirhinal lesions acquired in adulthood, novelty preference in the neonatally operated animals remained above chance at all delays and all ages. The data suggest that, although incidental recognition memory processes can be supported by the perirhinal cortex in early infancy, other temporal cortical areas may support these processes in the absence of a functional perirhinal cortex early in development. The neural substrates mediating incidental recognition memory processes appear to be more widespread in early infancy than in adulthood.

Long-term effects of neonatal hippocampal lesions on novelty preference in monkeys.

In a recent longitudinal study to assess the development of incidental recognition memory processes in monkeys, we showed that the effects of neonatal hippocampal lesions did alter incidental recognition memory only when the animals reached the juvenile period (Zeamer et al., ). The current follow-up study tested whether this incidental memory loss was long-lasting, i.e., present in adulthood, or only transitory, due to functional compensation with further brain maturation. The same animals with neonatal hippocampal lesions and their sham-operated controls were re-tested in the visual paired-comparison task when they reached adulthood (48 months). The results demonstrated that, at least for easily discriminable color pictures of objects, the involvement of the hippocampus was only transitory, given that when re-tested as adults, animals with neonatal hippocampal lesions performed as well as sham-operated controls at all delays. Yet, significant recognition memory impairment was re-instated when the discriminability of the stimuli was made more difficult (black/white pictures of similar objects). The data demonstrate profound functional remodeling within the hippocampus and its interactions with different medial temporal lobe structures from the juvenile period to adulthood, which is substantiated by a parallel morphological maturation of hippocampal intrinsic circuits (Lavenex et al., ; Jabès et al., ).

Impaired spatial working memory learning and performance in normal aged rhesus monkeys.

Aged non-human primates may have deficits in a variety of cognitive functions. However, it is possible that at least some age-related performance deficits relate to a deficit in initial task learning. To assess this, aged rhesus monkeys were trained to perform a Self-Ordered Spatial Search (SOSS) task using the same training and testing parameters used previously with normal young animals. Aged animals failed to reach criterion at the easiest task level. In an attempt to improve learning, a group of aged animals were first trained on SOSS using a standard 5s ITI, followed by trials with low inter-trial interference (e.g., a stimulus used in a trial would not be used again for the next 2 trials) or with trials in which the spatial distance between the stimuli on the screen was maximized. Because performance improved but failed to reach criterion, this was followed by sessions with increasing ITIs (from 5 s to 10 or 15 s). Only increasing the ITI improved the performance of the aged animals enough to allow them to learn the task to criterion. Once the criterion was reached, memory was taxed by increasing the delay between stimulus presentations and increasing the number of spatial positions to be remembered. Performance declined for young animals, but even more so for aged animals. The results of the present study suggests that aged primates have difficulty initially learning a complex working memory task, and that the ITI may be an important parameter to manipulate to improve learning. However, once the task is learned, performance of aged animals is inferior to that of young animals, particularly when memory demands are increased.

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.

The effects of selective hippocampal damage on tests of oddity in rhesus macaques.

The oddity task (e.g., A-, A-, B+) is classified as a conjunctive or relational task in which accurate performance depends upon learning to attend to stimulus relationships, not stimulus identity, and has no retention component as stimuli are presented simultaneously. It has been suggested that the hippocampus may play a particular role in learning this type of task in humans and animals. To test this, we trained adult rhesus macaques with selective neurotoxic damage to the hippocampal formation on their ability to learn and apply an oddity rule. The results suggest that the monkeys were able to adapt simple strategies to solve variations of the oddity task, however as the opportunity for such strategies was reduced, monkeys with hippocampal damage were increasingly impaired.

Attention, executive functioning and memory in normal aged rhesus monkeys.

Understanding how cognition declines in normal aging is vital in order to distinguish between normal cognitive decline due to aging and cognitive decline due to an age-related pathological process such as Parkinson's disease (PD). Several cognitive domains including memory, executive functioning and attention are all adversely affected with age in humans, as well as by PD, yet less is known about how these processes are affected by aging in non-human primates. Thus, in order to characterize baseline performance in aged primates prior to inducing Parkinson-like pathology, male rhesus macaques aged 15-22 years were tested on several tasks analogous to those used in cognitive aging studies in humans. The tasks included simple visual discrimination to assess learning and reference memory, discrimination reversal to assess cognitive flexibility and response inhibition, continuous performance to assess sustained visual attention, and attention set shifting to assess cognitive flexibility and set-shifting ability. Deficits were detected in some aspects of learning, cognitive flexibility, response inhibition and sustained visual attention, whereas reference memory and set-shifting did not appear to be affected. Additionally, there was a greater amount of variability in cognitive abilities across the aged animals than observed previously in young adult animals. These findings will form an important baseline for comparison with cognitive performance after PD-like pathology is superimposed on the normal aging process.

Developmental trajectory of object recognition memory in infant rhesus macaques with and without neonatal hippocampal lesions.

To examine the developmental trajectory of object recognition memory and its neural substrate, 10-12-d-old monkeys (Macaca mulatta) received sham operations or neurotoxic hippocampal lesions and were tested at the ages of 1.5, 6, and 18 months on the visual paired-comparison task using delays of 10, 30, 60, and 120 s. In sham-operated controls, incidental recognition memory was present at 1.5 months, became more robust at 6 months, and was delay-dependent by 18 months of age, suggesting that the brain structures mediating these early developing recognition abilities may undergo significant modifications after 6 months of age in monkeys. A similar developmental progression was also observed in animals with neonatal hippocampal lesions, although the delay-dependent effect at 18 months was significantly more pronounced after the neonatal hippocampal lesions, suggesting that with maturation animals with neonatal hippocampal lesions grow into a recognition-memory deficit. These findings suggest not only that the medial temporal cortical areas, known to mediate incidental recognition memory processes in adulthood, could support these processes in early infancy even when long delays are used, but also that later in development, after reaching functional maturity, the hippocampus begins to interact with the medial temporal cortical areas to mediate this function.