Serotonin affects association of aversive outcomes to past actions

Abstract

Impairment in the serotonergic system has been linked to action choices that are less advantageous in a long run. Such impulsive choices can be caused by a deficit in linking a given reward or punishment with past actions. Here, we tested the effect of manipulation of the serotonergic system by tryptophan depletion and loading on learning the association of current rewards and punishments with past actions. We observed slower associative learning when actions were followed by a delayed punishment in the low serotonergic condition. Furthermore, a model-based analysis revealed a positive correlation between the length of the memory trace for aversive choices and subjects' blood tryptophan concentration. Our results suggest that the serotonergic system regulates the time scale of retrospective association of punishments to past actions.

Figure 1.

A, Experimental task. Two fractal images were displayed on the screen in each trial. When the subject heard a beep, the subject chose one of two fractal images by pressing the corresponding button within 1 s of the beep. The outcome was displayed on the screen. A single trial lasted 2.5 s. At the next trial, a new pair of fractal images was displayed. B, Outcome-delay mapping of fractal images. On each experiment day, we used eight fractal images. Each of the eight images had been assigned a different outcome (40, 10, −10, −40 yen) and delay (0 trial, 3 trials). At each trial, two fractal images were chosen from these eight images in a pseudo-random order. C, If the subject selected a delay 0 image, the outcome was displayed during feedback duration in the present trial (see trials t +1 and t +2). If the subject chose a delay 3 image, the outcome was displayed three trials later (trial t and t +3). If the outcomes from delay 0 and delay 3 images appeared in the same trial, the sum of the immediate and delayed outcomes was displayed (trial t +3). When no outcome was delivered, “0 yen” was displayed (trial t).

Figure 2.

Choice probabilities of the optimal image (in A) for the four pairs with the same delay and different magnitude. B (left top panel), Immediate reward (+10(0) vs +40(0)) (right top panel) delayed reward (+10(3) vs +40(3)) (left bottom panel) immediate punishment (−10(0) vs −40(0)), and (right bottom panel) delayed punishment (−10(3) vs −40(3)). The optimal image was defined as the larger reward or smaller punishment. In each panel, we plotted the averaged choice probabilities of the optimal image in each pair during the early stage (first half of the first session), middle stage (the second session), and late stage (the last session). Each error bar shows the SEM (n = 21). *p < 0.05, multiple comparisons with Bonferroni correction between trp− and other conditions.

Figure 3.

A, Estimated parameters in each tryptophan condition (red triangle, trp− condition; green square, control condition; blue circle, trp+ condition). α, learning rate; β, inverse temperature; λ+, trace decay factor for reward; λ−, trace decay factor for punishment. *p < 0.05 in multiple comparison with Bonferroni correction. B, Simulated choice probabilities for the optimal image in the four pairs with estimated subjects' parameters. Each error bar shows the SEM (n = 21). *p < 0.05, a priori comparisons (uncorrected one-tailed paired t test) between trp− and other conditions.