Visual stimulation-induced mild stress enhances cognitive behavior in cynomolgus monkey

Abstract

Cortisol is a well-known endogenous glucocorticoid that serves as a stress indicator. It is normally released under stressful condition to warn about imminent danger and thus is critical for survival of the species. However, it is unclear how cortisol relates to cognitive process under physiological condition in high-order primates such as non-human primates (NHP). Here, we report that a slight but significant increase in blood cortisol level by mild stress is positively correlated with the cognitive function in cynomolgus monkey. We stimulated 3 groups of monkeys by viewing consecutive series of pictures of monkeys, pictures of humans, or animation still pictures. We first found that the blood cortisol level was significantly higher during the stimulation session and returned to normal after stimulation session. Among the three types of pictures, the monkeys which were stimulated with monkey pictures showed the most significant increase in cortisol level during stimulation. Furthermore, the monkeys showed significantly enhanced manipulation, suggesting that cortisol affected cognitive processes. Overall, our study demonstrates that visual stimulation both increases blood cortisol and enhances manipulating behavior. Therefore, unlike the common notion that cortisol is a stress indicator, our data supports that a mild increase of cortisol enhances cognition in NHP.

Figure 1

Method of visual stimulation and experimental procedure. (A) Contents of visual stimulation, monkey still picture, human still picture, animation still picture, and blank picture. 57 pictures are prepared for 1 trial. (B) Daily session is for 3hrs per day. Blank images for 1hr, and visual stimulations such as Monkey, human, and animation pictures are for 1hr 2 times. Each trial is for 1 min, 57 seconds for 57 pictures and 3 seconds for blank. The session of visual stimulation composes of 60 trials. (C) Experimental timeline. 4 days of 1 week for 1 pre-stimulation, 4 days of 1 weeks 3 times for visual stimulations, and 4 days of 1 week for 1 post- stimulation. Red arrows indicate collecting time of blood for analyzing cortisol.

Figure 2

Blood cortisol level of cynomolgus monkey with visual stimulation of (A) monkey pictures, (B) human pictures, and (C) animation pictures. (A) Cortisol level is significant in the presence of 2^nd stimulation with monkey pictures (one-way ANOVA, F_4,19 = 2.72, p = 0.07, followed by Dunnett’s posthoc test, *p < 0.05). (D) All data are summed (one-way ANOVA, F_4,59 = 5.43, p = 0.0009, followed by Dunnett’s posthoc test, *p < 0.05, ***p < 0.001). Blood cortisol concentrations with 2^nd and 3^rd visual stimulation are significantly increased.

Figure 3

Behavioral changes. (A) Frequency of behavioral counting before, during, and after visual stimulation. Biting (brown), pacing (pink), masturbation (yellow), foraging (green), manipulation (blue), interaction with neighbor (purple), uncountable actions (gray) are pie chart for showing overall change in behaviors. (B) Foraging, behaviors using hand or mouth to put the food into mouth (one-way ANOVA F_2,35 = 4.91, p = 0.020, followed by Dunnett’s post hoc test **p < 0.01). Manipulation, fingering, grasping of hands (one-way ANOVA F_2,35 = 7.84, p = 0.0016, followed by Dunnett’s post hoc test **p < 0.01). Abnormal behavior, hit and suck by himself (one-way ANOVA F_2,35 = 6.73, p = 0.0035, followed by Dunnett’s post hoc test **p < 0.01). Uncountable (one-way ANOVA F_2,35 = 5.51, p = 0.0086, followed by Dunnett’s post hoc test **p < 0.01).