Morphine exposure modulates dimensional bias and set formation in anthropoids.

Humans demonstrate significant behavioural advantages with particular perceptual dimensions (such as colour or shape) and when the relevant dimension is repeated in consecutive trials. These dimension-related behavioural modulations are significantly altered in neuropsychological and addiction disorders; however, their underlying mechanisms remain unclear. Here, we studied whether these behavioural modulations exist in other trichromatic primate species and whether repeated exposure to opioids influences them. In a target detection task where the target-defining dimension (colour or shape) changed trial by trial, humans exhibited shorter response time (RT) and smaller event-related electrodermal activity with colour dimension; however, macaque monkeys had shorter RT with shape dimension. Although the dimensional biases were in the opposite directions, both species were faster when the relevant dimension was repeated, compared with conditions when it changed, across consecutive trials. These indicate that both species formed dimensional sets and that resulted in a significant 'switch cost'. Scheduled and repeated exposures to morphine, which is analogous to its clinical and recreational use, significantly augmented the dimensional bias in monkeys and also changed the switch cost depending on the relevant dimension. These cognitive effects occurred when monkeys were in abstinence periods (not under acute morphine effects) but expressing significant morphine-induced conditioned place preference. These findings indicate that significant dimensional biases and set formation are evolutionarily preserved in humans' and monkeys' cognition and that repeated exposure to morphine interacts with their manifestation. Shared neural mechanisms might be involved in the long-lasting effects of morphine and expression of dimensional biases and set formation in anthropoids.

Dynamic modulation of inhibition ability following repeated exposures to morphine in macaque monkey.

BACKGROUND: Deficits in cognitive control, particularly inhibition ability, play crucial roles in susceptibility, progress, and relapse to opioid addiction. However, it is unclear when and how such deficits develop and interact with repeated exposures to prescribed opioids. AIM: Using macaque monkey (Macaca mulatta), as an animal model with high translational merits in cognitive neuroscience, we tried to delineate alterations of inhibition ability in the course of repeated exposures to morphine. METHODS: Monkeys were trained to perform stop-signal task and then we closely monitored their inhibition ability before exposure, after initial exposure, and following repeated exposures to morphine when they experienced abstinent periods. We also assessed morphine-induced conditioned place preference (CPP) in these monkeys to monitor the long-lasting effects of morphine on other behaviors. RESULTS: Compared to the baseline level, monkeys' inhibition ability was significantly enhanced after initial exposure to morphine (early phase); however, it became significantly attenuated after repeated exposures (late phase). These alterations occurred while monkeys consistently expressed the morphine-induced CPP over the course of morphine exposure. CONCLUSIONS: Our findings indicate that repeated and scheduled exposures to morphine, which is akin to its clinical and recreational use, lead to dynamic alterations in primates' cognitive control depending on the extent of exposure. Enhancement of inhibition after limited exposure might provide opportunities to intervene and prevent the progress and culmination of opioid addiction, which is characterized by disinhibited drug-seeking and consumption.

Dimensional bias and adaptive adjustments in inhibitory control of monkeys.

Humans and macaque monkeys, performing a Wisconsin Card Sorting Test (WCST), show a significant behavioral bias to a particular sensory dimension (e.g. color or shape); however, lesions in prefrontal cortical regions do not abolish the dimensional biases in monkeys and, therefore, it has been proposed that these biases emerge in earlier stages of visual information processing. It remains unclear whether such dimensional biases are unique to the WCST, in which attention-shifting between dimensions are required, or affect other aspects of executive functions such as 'response inhibition' and 'error-induced behavioral adjustments'. To address this question, we trained six monkeys (Macaca mulatta) to perform a stop-signal task in which they had to inhibit their response when an instruction for inhibition was given by changing the color or shape of a visual stimulus. Stop Signal Reaction Time (SSRT) is an index of inhibitory processes. In all monkeys, SSRT was significantly shorter, and the probability of a successful inhibition was significantly higher, when a change in the shape dimension acted as the stop-cue. Humans show a response slowing following a failure in response inhibition and also adapt a proactive slowing after facing demands for response inhibition. We found such adaptive behavioral adjustments, with the same pattern, in monkeys' behavior; however, the dimensional bias did not modulate them. Our findings, showing dimensional bias in monkey, with the same pattern, in two different executive control tasks support the hypothesis that the bias to shape dimension emerges in early stages of visual information processing.

Color-hierarchies in executive control of monkeys' behavior.

Processing advantages for particular colors (color-hierarchies) influence emotional regulation and cognitive functions in humans and manifest as an advantage of the red color, compared with the green color, in triggering response inhibition but not in response execution. It remains unknown how such color-hierarchies emerge in human cognition and whether they are the unique properties of human brain with advanced trichromatic vision. Dominant models propose that color-hierarchies are formed as experience-dependent learning that associates various colors with different human-made conventions and concepts (e.g., traffic lights). We hypothesized that if color-hierarchies modulate cognitive functions in trichromatic nonhuman primates, it would indicate a preserved neurobiological basis for such color-hierarchies. We trained six macaque monkeys to perform cognitive tasks that required behavioral control based on colored cues. Color-hierarchies significantly influenced monkeys' behavior and appeared as an advantage of the red color, compared to the green, in triggering response inhibition but not response execution. For all monkeys, the order of color-hierarchies, in response inhibition and also execution, was similar to that in humans. In addition, the cognitive effects of color-hierarchies were not limited to the trial in which the colored cues were encountered but also persisted in the following trials in which there was no colored cue on the visual scene. These findings suggest that color-hierarchies are not resulting from association of colors with human-made conventions and that simple processing advantage in retina or early visual pathways does not explain the cognitive effects of color-hierarchies. The discovery of color-hierarchies in cognitive repertoire of monkeys indicates that although the evolution of humans and monkeys diverged in about 25 million years ago, the color-hierarchies are evolutionary preserved, with the same order, in trichromatic primates and exert overarching effects on the executive control of behavior.