Preclinical laboratory assessments of predictors of social rank in female cynomolgus monkeys.

Physiological and behavioral differences between dominant and subordinate monkeys have been useful in preclinical models investigating numerous disease states. In captivity, it has been inferred that subordinate monkeys live in a context of chronic social stress and may be at risk for a variety of dysfunctions; however, the factors that influence eventual rank are not entirely known. The goal of the present study was to first evaluate several phenotypic characteristics as potential trait markers for eventual social rank and then to determine the consequences of social hierarchy on these measures (i.e., state markers). Baseline estradiol, progesterone, cortisol and testosterone concentrations were obtained from 16 pair-housed female cynomolgus monkeys before and after introduction into new social groups (n = 4/group). Furthermore, effects of the initial week of social rank establishment on outcome measures of cognitive performance and homecage activity were examined. Baseline body weight and mean serum estradiol concentrations were the only statistically significant predictors of eventual rank, with future subordinate monkeys weighing less and having higher estradiol concentrations. During initial hierarchy establishment, future subordinate monkeys had increased morning and afternoon cortisol concentrations, increased locomotor activity and impaired cognitive performance on a working memory task. After 3 months of social housing, subordinate monkeys had blunted circulating estradiol and progesterone concentrations. These findings demonstrate differential effects on gonadal hormones and cortisol as a function of social context in normally cycling female monkeys. Furthermore, disruptions in cognitive performance were associated with subordinate status, suggesting strong face validity of this model to the study of factors related to the etiology and treatment of human diseases associated with chronic stress. Am. J. Primatol. 78:402-417, 2016. © 2015 Wiley Periodicals, Inc.

Relationship between estradiol and progesterone concentrations and cognitive performance in normally cycling female cynomolgus monkeys.

Preclinical research has demonstrated that cognitive function may be influenced by estradiol (E2) and progesterone (P4) concentrations, although few cognition studies involve normally cycling females. The present study examined cognitive performance in normally cycling female cynomolgus macaques (n = 14), a species with similarities to humans in brain organization and a nearly identical menstrual cycle to women. Initial assessments compared cognitive measures to circulating concentrations of E2 and P4 (n = 12). Once a relationship was characterized between hormones and cognitive performance, the menstrual cycle was divided into four distinct phases: early follicular (EF), late follicular (LF), early luteal (EL) and late luteal (LL), verified by the onset of menses and serum concentrations of E2 and P4. Concentrations of E2 were highest during the LF phase and P4 concentrations peaked during the EL phase. All monkeys were trained on two cognitive tasks: reversal learning, involving simple discrimination (SD) and reversal (SDR), which measured associative learning and behavioral flexibility, respectively (n = 3-4 per phase) and a delayed match-to-sample (DMS) task which assessed working memory (n = 11). P4 concentrations were positively correlated with number of trials and errors during acquisition of SD performance, but not during acquisition of the SDR task or maintenance of the reversal-learning task. Across the menstrual cycle, significantly fewer errors were made in the SDR task during the LF phase, when E2 concentrations were high and P4 concentrations low. Working memory, assessed with the DMS task, was not consistently altered based on previously characterized menstrual cycle phases. These findings demonstrate a relationship between P4, E2 and cognitive performance in normally cycling cynomolgus monkeys that is task dependent. Knowledge of these interactions may lead to a better understanding of sex-specific cognitive performance.

Effects of prior cocaine self-administration on cognitive performance in female cynomolgus monkeys.

Cocaine use has been associated with cognitive impairments that may contribute to poor treatment outcomes. However, the degree to which these deficits extend into periods of abstinence has not been completely elucidated. This study tested whether prior experience self-administering cocaine affected acquisition of two cognitive tasks in 16 adult female cynomolgus monkeys. Seven monkeys had previously self-administered cocaine but had not had access to cocaine for 2 months at the start of this study. After monkeys were trained to respond on a touchscreen, associative learning and behavioral flexibility were assessed using a stimulus discrimination (SD) and reversal (SDR) task from the CANTAB battery. Performance on this task was monitored over the subsequent 3 months. Additionally, working memory was assessed with a delayed match-to-sample (DMS) task. Cocaine-naïve monkeys required fewer total trials and made fewer errors and omissions before acquiring the SD and SDR tasks compared with monkeys who had previously self-administered cocaine; two monkeys in the latter group did not acquire the task. However, this cognitive impairment dissipated over several months of exposure to the task. The number of sessions for touch training and delays required to establish a performance-based curve on the DMS task did not differ between groups. Results suggest that cocaine exposure can impair the ability to learn a novel task requiring behavioral inhibition and flexibility, even after an extended period of abstinence. However, this deficit did not extend to maintenance of the task or to acquisition of a working memory task.

What the 'Moonwalk' illusion reveals about the perception of relative depth from motion.

When one visual object moves behind another, the object farther from the viewer is progressively occluded and/or disoccluded by the nearer object. For nearly half a century, this dynamic occlusion cue has been thought to be sufficient by itself for determining the relative depth of the two objects. This view is consistent with the self-evident geometric fact that the surface undergoing dynamic occlusion is always farther from the viewer than the occluding surface. Here we use a contextual manipulation ofa previously known motion illusion, which we refer to as the'Moonwalk' illusion, to demonstrate that the visual system cannot determine relative depth from dynamic occlusion alone. Indeed, in the Moonwalk illusion, human observers perceive a relative depth contrary to the dynamic occlusion cue. However, the perception of the expected relative depth is restored by contextual manipulations unrelated to dynamic occlusion. On the other hand, we show that an Ideal Observer can determine using dynamic occlusion alone in the same Moonwalk stimuli, indicating that the dynamic occlusion cue is, in principle, sufficient for determining relative depth. Our results indicate that in order to correctly perceive relative depth from dynamic occlusion, the human brain, unlike the Ideal Observer, needs additional segmentation information that delineate the occluder from the occluded object. Thus, neural mechanisms of object segmentation must, in addition to motion mechanisms that extract information about relative depth, play a crucial role in the perception of relative depth from motion.

Fragment-based learning of visual object categories in non-human primates.

When we perceive a visual object, we implicitly or explicitly associate it with an object category we know. Recent research has shown that the visual system can use local, informative image fragments of a given object, rather than the whole object, to classify it into a familiar category. We have previously reported, using human psychophysical studies, that when subjects learn new object categories using whole objects, they incidentally learn informative fragments, even when not required to do so. However, the neuronal mechanisms by which we acquire and use informative fragments, as well as category knowledge itself, have remained unclear. Here we describe the methods by which we adapted the relevant human psychophysical methods to awake, behaving monkeys and replicated key previous psychophysical results. This establishes awake, behaving monkeys as a useful system for future neurophysiological studies not only of informative fragments in particular, but also of object categorization and category learning in general.