Fluoxetine degrades luminance perceptual thresholds while enhancing motivation and reward sensitivity

Abstract

Selective serotonin reuptake inhibitors (SSRIs) increase serotonin activity in the brain. While they are mostly known for their antidepressant properties, they have been shown to improve visual functions in amblyopia and impact cognitive functions ranging from attention to motivation and sensitivity to reward. Yet, a clear understanding of the specific action of serotonin to each of bottom-up sensory and top-down cognitive control components and their interaction is still missing. To address this question, we characterize, in two adult male macaques, the behavioral effects of fluoxetine, a specific SSRI, on visual perception under varying bottom-up (luminosity, distractors) and top-down (uncertainty, reward biases) constraints while they are performing three different visual tasks. We first manipulate target luminosity in a visual detection task, and we show that fluoxetine degrades luminance perceptual thresholds. We then use a target detection task in the presence of spatial distractors, and we show that under fluoxetine, monkeys display both more liberal responses as well as a degraded perceptual spatial resolution. In a last target selection task, involving free choice in the presence of reward biases, we show that monkeys display an increased sensitivity to reward outcome under fluoxetine. In addition, we report that monkeys produce, under fluoxetine, more trials and less aborts, increased pupil size, shorter blink durations, as well as task-dependent changes in reaction times. Overall, while low level vision appears to be degraded by fluoxetine, performances in the visual tasks are maintained under fluoxetine due to enhanced top-down control based on task outcome and reward maximization.

Keywords: fluoxetine; luminosity thresholds; macaque; response criterion; reward sensitivity; serotonin; visual perception.

FIGURE 1

Effect of fluoxetine on perceptual thresholds in a luminance detection task. (A) Monkeys had to detect a target presented in one of four quadrants. Target luminosity ranged from high to low luminosity in 7 steps. Monkeys were rewarded for a speeded detection of target presentation. Targets were presented at four different locations, in the upper left (UL), upper right (UR), lower right (LR) and lower left (LL) quadrants, at 8° of eccentricity from the center of the screen, for 200 ms. (B) For both monkeys, % of hits were computed independently for each target luminosity. Dots represent individual sessions, continuous lines represent average % hits across all sessions (+/-median absolute error) and dashed lines represent sigmoid fit of the data. Placebo data are represented in light gray and fluoxetine data are represented in dark gray. Behavioral data are represented independently for each target position. Statistical significance is represented as follows: ***, p < 0.001; **, p < 0.01; *, p < 0.05; n. s., p > 0.05. See also companion Supplementary Table S2 for detailed statistics.

FIGURE 2

Effect of fluoxetine on spatial sensitivity d-prime and response criterion in a target detection task in the presence of spatial distractors. (A) Monkeys had to detect a target presented in one of two quadrants (lower left or lower right). Target luminosity was kept high and presented at a fixed location, at 8° of eccentricity from the center of the screen, for 200 ms. Monkeys were rewarded for a speeded detection of target presentation. On 75% of the trials, targets were preceded by a distractor, undistinguishable from the target except for its spatial location. These distractors were located within a circle of 2° of eccentricity around the target. Responses to these distractors interrupted the trial and monkeys were not rewarded. (B) For both monkeys, d’ and criterion were computed independently for each target (left, light gray; right, dark gray). Median+/-median absolute error are presented for placebo and fluoxetine conditions. Statistical significance is represented as follows: ***, p < 0.001; **, p < 0.01; *, p < 0.05; °, p < 0.07. See also companion Supplementary Table S3 for detailed statistics.

FIGURE 3

Effect of fluoxetine on saccadic choices towards targets of different reward contingencies. (A) Monkeys had to fixate a central cross on a screen 60 cm away from their eyes. After an interval of 1–2 s, two stimuli appeared simultaneously at two different locations out of eight. All of the 8 possible target locations were organized along a virtual circle of 8° of eccentricity from the fixation cross, equidistant one from the other. Monkeys were rewarded to make a saccadic eye movement to any of the two targets. (B) Each target was associated with two possible reward quantities, but with a different probability. High expected reward targets were associated with 80% of high reward probability and 20% of low reward probability. Low expected reward targets were associated with 20% of high reward probability and 80% of low reward probability. Intermediate expected reward targets were associated with 50% of high reward probability and 50% of low reward probability. Reward contingencies between neighbors were kept constant as follows: 80% high reward (HR)—50% HR—80% HR—50% HR—20% HR—50% HR—20% HR—50% HR. However, the actual location of high and low rewarding targets changed pseudo-randomly from 1 day to the next. Thus, monkeys had to learn the new reward contingencies every day. We did not evaluate how much monkeys built a representation of the reference contingency map. (C) Polar plots represent the probability that monkeys choose any given target either as a function of the reward contingency map (i.e., irrespective of actual spatial position, left) or as a function of the spatial map (i.e., irrespective of actual reward contingency maps, right). Median are presented for placebo (dashed lines) and fluoxetine (continuous lines) conditions. Statistical significance is represented as follows: ***, p < 0.001; **, p < 0.01; *, p < 0.05. See also companion Supplementary Tables S4, S5 for detailed statistics.

FIGURE 4

Effect of fluoxetine on controlled reaction times. Median+/-median absolute error of reaction times, for monkeys M1 (top) and M2 (bottom), in the placebo and fluoxetine conditions in the luminance task (A), all positions collapsed, high luminance targets only), in the detection tasks with distractors, on target only trials (B), and in trials with distractors (C). Statistical significance is represented as follows: ***, p < 0.001; **, p < 0.01; *, p < 0.05. See also companion Supplementary Table S7 for detailed statistics.

FIGURE 5

Effect of fluoxetine on pupil size and eye blink duration. (A) Median+/-median absolute error of %pupil size changes relative to the entire task, for monkeys M1 (top) and M2 (bottom), during rest (baseline, continuous line) and after target presentation (task, dashed lines), in the placebo and fluoxetine conditions. (B) Median+/-median absolute error of blink duration, for monkeys M1 (top) and M2 (bottom), in the placebo and fluoxetine conditions. Statistical significance is represented as follows: ***, p < 0.001; **, p < 0.01; *, p < 0.05. See also companion Supplementary Table S6 for detailed statistics.

FIGURE 6

Effect of fluoxetine on on-task motivation (# of trials) and on-task compliance (% aborts), on the Luminance detection task (A), the detection task with distractors (B) and the saccadic reward competition task (C). For all plots, median+/-median absolute error. of the median are represented. Placebo data are represented in light gray and fluoxetine data are represented in dark gray. Statistical significance is represented as follows: ***, p < 0.001; **, p < 0.01; *, p < 0.05; n. s., p > 0.05. See also companion Supplementary Table S1 for detailed statistics.