Abstract
Elucidation of how neuromodulators influence motivated behaviors is a major challenge of neuroscience research. It has been proposed that the locus-cœruleus-norepinephrine system promotes behavioral flexibility and provides resources required to face challenges in a wide range of cognitive processes. Both theoretical models and computational models suggest that the locus-cœruleus-norepinephrine system tunes neural gain in brain circuits to optimize behavior. However, to the best of our knowledge, empirical proof demonstrating the role of norepinephrine in performance optimization is scarce. Here, we modulated norepinephrine transmission in monkeys performing a Go/No-Go discrimination task using atomoxetine, a norepinephrine-reuptake inhibitor. We tested the optimization hypothesis by assessing perceptual sensitivity, response bias, and their functional relationship within the framework of the signal detection theory. We also manipulated the contingencies of the task (level of stimulus discriminability, target stimulus frequency, and decision outcome values) to modulate the relationship between sensitivity and response bias. We found that atomoxetine increased the subject’s perceptual sensitivity to discriminate target stimuli regardless of the task contingency. Atomoxetine also improved the functional relationship between sensitivity and response bias, leading to a closer fit with the optimal strategy in different contexts. In addition, atomoxetine tended to reduce reaction time variability. Taken together, these findings support a role of norepinephrine transmission in optimizing response strategy.
Highlights
The locus cœruleus-norepinephrine (LC-NE) system is currently viewed as a key component of behavioral flexibility (Aston-Jones et al 1999; Bouret and Sara 2004), energizing behavior during cognitive and/or physical effort (Robbins 1997; Raizada and Poldrack 2007; Bouret and Richmond 2009; Malecek and Poldrack 2013; Kalwani et al 2014; Varazzani et al 2015)
Generalized linear mixed models We examined the effect of the smallest efficient dose of ATX on the different variables computed above (i.e., HIT and correct rejections (CR) responses, sensitivity, response bias, line of optimal response (LOR), median and standard deviation of the reaction times) for each monkey, using generalized linear mixed models (“lmer” R-package)
We tested whether the modulatory effects following ATX injection in monkeys translate into an adjustment of the behavior toward the line of optimal response, reflected in the functional relationship between sensitivity index and response bias (Lynn and Barrett 2014)
Summary
The locus cœruleus-norepinephrine (LC-NE) system is currently viewed as a key component of behavioral flexibility (Aston-Jones et al 1999; Bouret and Sara 2004), energizing behavior during cognitive and/or physical effort (Robbins 1997; Raizada and Poldrack 2007; Bouret and Richmond 2009; Malecek and Poldrack 2013; Kalwani et al 2014; Varazzani et al 2015). The LC activity is positively modulated by the level of difficulty in a context.
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