Extended Data Fig. 4: Gender differences in human subjects performing the self-initiated probabilistic reversal learning task.
From: A neural substrate of sex-dependent modulation of motivation
a. Schematic of the online task. After an intertrial interval (ITI), trial start was cued with the appearance of a plus sign (‘+’) on the screen. Subjects initiated a trial by pressing the spacebar which led to the presentation of 2 colored circles on either side of the screen. Subjects indicated their choice by pressing the ‘a’ key for a left choice and the ‘l’ key for a right choice. The outcome was then presented, indicating the number of points received for that choice (rewarded: +10, unrewarded +0) accompanied by auditory cues indicating reward (bell-like sound) or no reward (buzzer). High probability choices were rewarded 60% of the time and low probability choices 10% of the time and the identity of the high and low choice alternated as in the mouse task (see Methods for details). b. Box-plots of the estimates of Q-learning parameters fit with the same hierarchical model used for the mice. The centers are median, the bottom and top of the boxes indicate 25th and 75th percentiles, respectively. Whiskers are the minimum and maximum values that are not outliers (outliers defined as greater (or less) than the 75th percentile (or 25th percentile) plus (or minus) 1.5x the interquartile range. c-d) Choice was similar between men and women. There was a significant main effect of relative side value, but no effect of gender on how relative side value modulated the probability of choosing the right option (mixed-effects, logistic regression: choice ~ relative_side_value_quantile + gender + age + sex:relative_side_value_quantile + sex:age + relative_side_value_quantile:age + sex*relative_side_value_quantile:age + (1 + relative_side_value_quantile|subject). relative side value: F(1,142180) = 100.5, p = 8.58 × 10−209; gender: F(1,142180) = 1.20, p = 0.27; age: F(1,142180) = 0.98, p = 0.32; relative_side_value:gender: F(1,142180) = 0.72, p = 0.71; gender:age: F(1,142180) = 1.26, p = 0.26; relative_side_value:age: F(10,142180) = 0.73, p = 0.70; relative_side_value:gender:age: F(1,142180) = 0.62, p = 0.80, gender was a categorical variable and age was z-scored. Significance was assessed with 2-sided F tests). c. Trials were divided into 11 quantile bins of relative side value and the probability of making a right choice was averaged by bin for each subject younger than or equal to the median age (between 19 and 39 years old). Error bars are standard error of the mean. d. Same as c, except for subjects 40–70 years old. e. Trial initiation latencies were significantly affected by age in men, but not women (linear correlation, males: r = 0.16, p = 0.02, females: r = −0.006, p = 0.95). f-g) The modulation of trial initiation latency by value differed in males and females, and this effect was modulated by age (mixed-effects regression with relative chosen value quantile, gender, age and their interactions as fixed effects and random effects of subject. relative_chosen_value: F(4,1754) = 3.46, p = 0.008: gender: F(1,1754) = 1.68 × 10−4, p = 0.99; age: F(1,1754) = 1.62 × 10−4, p = 0.99; relative_chosen_value:gender: F(4,1754) = 2.49, p = 0.04; relative_chosen_value:age: F(4,1754) = 6.71, p = 2.36 × 10−5; gender:age: F(1,1754) = 1.16 × 10−4, p = 0.99; relative_chosen_value:gender:age: F(4,1754) = 2.46, p = 0.04; n = 141 women, 209 men). f. Trials were divided into 5 quantile bins of relative chosen value for males and females 19–39 years old and trial initiation latencies were averaged by bin. Error bars are standard error of the mean. Two-sided Wilcoxon rank sum tests showed that women were significantly slower than men to initiate trials in the lowest quantile bin of relative chosen value (bin 1: Z = −2.01, p = 0.04, bin 2: Z = –0.10, p = 0.92, bin 3: Z = 0.79, p = 0.43, bin 4: Z = 1.35, p = 0.18, bin 5: Z = 0.54, p = 0.59) g. Same as f except for subjects aged between 40 and 70. There were no significant differences in trial initiation latencies between males and females older than 39 (2-sided Wilcoxon rank sum tests, p > 0.07). QCh: action value for the chosen lever; QU: action value for the unchosen lever; QR: action value for the right lever; QL: action value for the left lever; * p < 0.05.
