Experimental Design and Behavioral Results.

A. All trials started with instructions on the probability (ranging from 0% to 100%) and intensity (weak, moderate, strong) of a potentially painful electrical stimulation (1 second), followed by the addition of a countdown bar that indicated the exact moment of stimulation or omission. The duration of the countdown clock was jittered between 3-7 seconds. Then, the screen cleared and the electrical stimulation was either delivered or omitted. Most of the trials (48 trials) did not contain the anticipated electrical stimulation (omission trials). Following a delay of 4 to 8 seconds, a rating scale appeared, probing stimulation-unpleasantness on stimulation trials, and relief-pleasantness on omission trials. After 8 seconds, an ITI between 4 and 7 seconds started, during which a fixation cross was presented on the screen. The task consisted in total of 72 trials, divided equally over 4 runs (18 trials/run). Each run contained all probability (25, 50, 75) x intensity (weak, moderate, strong) combinations exactly once not followed by the stimulation (9 omission trials), three 0%-omission trials (without any intensity information), three 100%-stimulation trials (followed by the stimulation of the given intensity, one per intensity level per run), and three additional trials from the probability (25,50,75) x Intensity (weak, moderate, strong) matrix that were followed by the stimulation (per run each level of intensity and probability was once paired with the stimulation). For a detailed overview of the trials see Supplementary Figure 1. B. SCR were scored as the time integral of the deconvoluted phasic activity (using CDA in Ledalab) within a response window of 1-4s post omission. Responses were square root transformed. SCR were larger following omissions of more probable and more intense US omissions. C. The pleasantness of the relief elicited by US omissions was rated on a VAS-scale ranging from 0 (neutral) to 100 (very pleasant). Omission-relief was rated as being more pleasant following omissions of more intense and more probable US. In both graphs, individual data points are presented, with the group averages plotted on top. The error bars represent standard error of the mean.

Omission-related activations in the a priori ROIs.

Unexpected omissions of stimulation (non0% > 0%) triggered significant fMRI responses in (A) the VTA/SN, and (B) left ventral putamen, but deactivations in (C) the vmPFC and no change in activation in (D) the NAc. Only for the VTA/SN did the activations increase with increasing Probability and Intensity of omitted stimulation. vmPFC responses decreased with increasing intensity of the omitted stimulation. Fully predicted stimulations (100%) elicited stronger activations than fully predicted omission (0%) in (E) the VTA/SN, no difference in activation for (F) the left Putamen and (G) the NAc, and stronger deactivations for fully predicted stimulation versus omission in (H) the vmPFC. In all figures, the unexpected omission maps were overlayed with the a priori ROI masks (in teal) and were displayed at threshold p < .001 (unc) for visualization purposes. The crosshairs represent the peak activation within each a priori ROI. The extracted beta-estimates in figures A-D represent the ROI averages from each non-0% > 0% contrast (i.e., 25%>0%; 50%>0%; and 75%>0% for the weak, moderate and strong intensity levels). Any positive beta therefore indicates a stronger activation in the given region compared to a fully predicted omission. Any negative beta indicates a weaker activation. The dots and error bars represent the mean and standard error of the mean.

Omission-related activations in the secondary mask.

We extracted unexpected omission (non0% > 0%) processing clusters within our secondary mask, using a voxel threshold, p < .001, followed by a cluster-threshold (FWE-corrected) of p < .05. We found significant positive omission processing clusters in (A) the bilateral putamen, (B) bilateral aINS, (C) dmPFC/aMCC, and a trend-level negative omission processing cluster in (D) the right amygdala. Omission related activations in the bilateral aINS and dmPFC/aMCC increased with increasing probability and intensity of omitted threat, whereas amygdala activations decreased with omissions of increasingly intense threat. Nevertheless, fully predicted stimulations (100%) elicited stronger activations than fully predicted omission (0%) in (F) the bilateral aIns, and (G) the dmPFC/aMCC, and stronger deactivations in the (H) right amygdala, but no difference in activation in the (E) bilateral putamen. In all figures, the unexpected omission maps are displayed at threshold p < .001 (unc) for visualization purposes. The extracted beta-estimates in figures A-D represent the ROI averages from each non-0% > 0% contrast (i.e., 25%>0%; 50%>0%; and 75%>0% for the weak, moderate and strong intensity levels). Any positive beta therefore indicates a stronger activation in the given region compared to a fully predicted omission. Any negative beta indicates a weaker activation. The dots and error bars represent the mean and standard error of the mean.

Relief modulation in the a priori and secondary ROIs.

Omission-related activations were modulated by trial-by-trial levels of relief-pleasantness in (A) the VTA/SN, (B) left ventral Putamen, and (D) vmPFC, but not in (C) the NAc. Omission-related activations in the secondary ROIs were modulated by trial-by-trial levels of relief-pleasantness in (A) the right putamen, (B) bilateral aINS, (C) dmPFC/aMCC, and the (D) right amygdala. In all figures, the relief modulation maps are displayed at threshold p < .001 (unc) for visualization purposes.

LASSO-PCR based neural signature of relief-pleasantness.

A. Relief predictive signature map consisting of all voxels within a grey matter mask. All weights were used for prediction. B. Thresholded signature map (p < .001), consisting of clusters that contribute significantly to the relief prediction (all clusters < 65 voxels). C. Predicted and reported relief-pleasantness correlated significantly, r = 0.28, p < .001. Each line/color represents data of a single participant. D. Correlations between reported and predicted relief in all lesion models (in each model one of the ROIs was removed from the grey matter mask). The stable correlation across models confirmed that none of our ROIs contributed significantly to the relief-predictive signature model.

Main clusters contributing to the relief signature identified via bootstrapping