Omissions of threat trigger subjective relief and prediction error-like signaling in the human reward and salience systems
- Laboratory of Biological Psychology, Department of Brain & Cognition, KU Leuven, Belgium
- Leuven Brain Institute, KU Leuven, Belgium
- Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research in GastroIntestinal Disorders (TARGID), Department of chronic diseases and metabolism, KU Leuven, Belgium
Figures
Figure 1
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 s), followed by the …
Figure 2
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 …
Figure 3
Omission-related activations in the secondary mask.
We extracted unexpected omission (non0%>0%) processing clusters within our secondary mask, using a voxel threshold, p<0.001, followed by a cluster-threshold (FWE-corrected) of p<0.05. We found …
Figure 4
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 …
Figure 5
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<0.001), consisting of clusters that …
Appendix 3—figure 1
Whole-brain (grey-matter masked) omission responses identified via the non0 % > 0% omission contrast, thresholded at p < 0.001 (uncorrected) for display purposes.
Appendix 3—figure 2
Probability- and intensity-related changes in threat omission-related fMRI responses per exploratory cluster.
Significant effects are indicated by the p-value.
Appendix 3—figure 3
Probability- and intensity-related changes in threat omission-related fMRI responses per exploratory cluster.
Significant effects are indicated by the p-value.
Appendix 3—figure 4
Whole-brain (grey-matter masked) relief modulation of omission-related fMRI responses identified via the relief modulation contrast, thresholded at p < 0.001 (uncorrected) for display purposes.
Appendix 4—figure 1
Anticipatory SCR to the instructions were larger for stimulations of a higher instructed probability and intensity.
Individual data points are presented, with the group averages plotted on top. The error bars represent standard error of the mean.
Appendix 4—figure 2
Individual anticipatory SCR followed probability instructions.
Appendix 4—figure 3
Whole-brain (grey-matter masked) anticipatory fMRI responses to the presentation of the instructions identified via the non0 % > 0% anticipation contrast, thresholded at p < 0.001 (uncorrected) for display purposes.
Appendix 4—figure 4
A linear increase in whole-brain (grey-matter masked) anticipatory fMRI activations for increasing probability instructions, identified via the probability contrast, thresholded at p < 0.001 (uncorrected) for display purposes.
Appendix 4—figure 5
Intensity contrast in whole-brain (grey-matter masked) anticipatory fMRI activations, identified via the Intensity contrast, and thresholded at p < 0.001 (uncorrected) for display purposes.
Appendix 4—figure 6
Probability and intensity effects for self-reported unpleasantness (A) and stimulation SCR (B).
Appendix 4—figure 7
Whole-brain (grey-matter masked) stimulation-related fMRI responses based on the stimulation > baseline contrast, thresholded at p < 0.001 (uncorrected) for display purposes.
Appendix 4—figure 8
Whole-brain (grey-matter masked) unexpected stimulation-related fMRI responses based on the non-100% stimulation > 100% stimulation contrast, and thresholded at p < 0.001 (uncorrected) for display purposes.
Appendix 5—figure 1
Post experimental recollections of stimulation and effort to avoid future stimulations.
A. Participants recollected having received more stimulations following instructions of a higher probability. B. Participants were willing to exert more effort to prevent stronger stimulations. In …
Appendix 5—figure 2
Results from an unpublished pilot study where the reinforcement rate matched the instructions.
Main effect of Probability including 0% : F(1.74,31.23) = 53.94, p < 0.001, ηp 2 = 0.75; Main effect of Probability excluding 0%: F(1.50, 28.43) = 21.03, p < 0.001, ηp 2 = 0.53.
Appendix 5—figure 3
Run and US unpleasantness effects for subjective and physiological omission responses.
Reported relief-pleasantness (A) and omission SCR (B) decreased over runs. C. Participants who perceived the stimulation as more unpleasant (on average) reported higher levels of relief (on average).
Appendix 6—figure 1
Whole-brain (grey-matter masked) SCR modulation of omission-related fMRI responses identified via the SCR modulation contrast, thresholded at p < 0.001 (uncorrected) for display purposes.
Appendix 6—figure 2
The signature of omission SCR.
A. Signature weights. Positive weights are presented in orange-yellow; negative weights are presented in blue. B. Regions that contributed most to the signature response based on bootstrap tests …
Tables
Table 1
Main clusters contributing to the relief signature identified via bootstrapping.
| Positive weight clusters | |||||||
|---|---|---|---|---|---|---|---|
| L/R | Region | K | MNI Coordinates (xyz) | Z (peak) | |||
| R | Cerebellum Crus 2 | 17 | 6 | –85 | –30 | 0.006 | |
| L | Cerebellum Crus 1 | 18 | –41 | –75 | –28 | 0.005 | |
| L | Inferior orbitofrontal gyrus | 10 | –21 | 14 | –23 | 0.005 | |
| R | Inferior temporal gyrus | 10 | 56 | –23 | –15 | 0.006 | |
| L | Middle orbitofrontal gyrus | 15 | –25 | 54 | –15 | 0.007 | |
| R | Middle orbitofrontal gyrus | 13 | 38 | 58 | –10 | 0.007 | |
| R | Caudate gyrus | 12 | 4 | 14 | -1 | 0.007 | |
| L | Superior temporal gyrus | 11 | –55 | 2 | 1 | 0.005 | |
| R | Rolandic operculum | 19 | 58 | 10 | 3 | 0.006 | |
| R | Superior occipital gyrus | 13 | 20 | –103 | 7 | 0.006 | |
| L | Middle occipital gyrus | 14 | –23 | –97 | 7 | 0.006 | |
| R | Calcarine gyrus | 18 | 12 | –79 | 10 | 0.007 | |
| L | Middle occipital gyrus | 12 | –31 | –95 | 14 | 0.005 | |
| R | Middle temporal gyrus | 19 | 54 | –47 | 14 | 0.005 | |
| R | Cuneus | 12 | 4 | –79 | 25 | 0.006 | |
| R | Supramarginal gyrus | 12 | 52 | –37 | 29 | 0.005 | |
| L | Superior occipital gyrus | 17 | –25 | –71 | 38 | 0.004 | |
| R | Precentral gyrus | 15 | 50 | 6 | 43 | 0.005 | |
| L | Superior occipital gyrus | 14 | –13 | –79 | 43 | 0.004 | |
| L | Mid cingulate gyrus | 27 | -9 | –23 | 45 | 0.005 | |
| R | Mid cingulate gyrus | 12 | 2 | –13 | 45 | 0.005 | |
| Negative weight clusters | |||||||
| R | Cerebellum Crus 1 | 12 | 30 | –69 | –28 | –0.005 | |
| L | Cerebellum Crus 1 | 11 | –17 | –89 | –19 | –0.007 | |
| R | Cerebellum Crus 1 | 41 | 30 | –85 | –19 | –0.014 | |
| R | Fusiform gyrus | 10 | 28 | –49 | -8 | –0.006 | |
| R | Superior temporal gyrus | 10 | 52 | -2 | -6 | –0.004 | |
| R | Inferior occipital gyrus | 11 | 28 | –89 | -4 | –0.006 | |
| R | Superior temporal gyrus | 10 | 66 | –17 | -4 | –0.006 | |
| L | Superior temporal gyrus | 16 | –63 | -5 | -1 | –0.005 | |
| L | Caudate | 10 | –17 | 18 | 1 | –0.006 | |
| L | Middle temporal gyrus | 14 | –57 | –65 | -1 | –0.004 | |
| R | Middle occipital gyrus | 12 | 34 | –93 | 5 | –0.005 | |
| L | Middle occipital gyrus | 11 | –39 | –89 | 3 | –0.004 | |
| R | Middle temporal gyrus | 40 | 58 | –57 | 10 | –0.005 | |
| L | Calcarine gyrus | 18 | –11 | –81 | 12 | –0.007 | |
| L | Cuneus | 20 | -3 | –89 | 21 | –0.006 | |
| L | Angular gyrus | 16 | –45 | –59 | 29 | –0.005 | |
| L | Middle frontal gyrus | 12 | –33 | 46 | 34 | –0.005 | |
| R | Postcentral gyrus | 64 | 46 | –31 | 49 | –0.005 | |
| R | Middle frontal gyrus | 19 | 26 | 32 | 45 | –0.004 | |
| L | Postcentral gyrus | 10 | –49 | –17 | 45 | –0.005 | |
| R | Middle frontal gyrus | 12 | 26 | 10 | 47 | –0.004 | |
-
Note. Contributing clusters are defined based on voxels-wise FDR-correction with q<0.05, k>10; L/R indicates if the cluster (or peak of the cluster) is part of the left or right hemisphere; Region name is identified using the AAL atlas; K is the number of voxels in the cluster; coordinates are the MNI coordinates of cluster peak; Z is the weight of the cluster peak.
Appendix 3—table 1
Whole-brain omission fMRI responses.
| Contrast: non0%>0% | |||||||
|---|---|---|---|---|---|---|---|
| L/R | Region | K | p (cluster) | MNI Coordinates (xyz) | T (peak) | ||
| L | Mid cingulate gyrus, extending to supplementary motor area and anterior cingulate gyrus | 1606 | <0.001 | -3 | 4 | 45 | 8.19 |
| R | Insula | 1287 | <0.001 | 44 | 12 | 1 | 8.05 |
| L | Insula | 1117 | <0.001 | –33 | 24 | 10 | 7.45 |
| L | Putamen | 65 | 0.006 | –25 | 6 | 1 | 6.83 |
| R | Cerebellum | 417 | <0.001 | 10 | –61 | –10 | 6.46 |
| R | Cerebellum | 37 | 0.093 | 38 | –63 | –26 | 5.70 |
| L | Supplementary motor area | 40 | 0.068 | –15 | 2 | 67 | 5.26 |
| L | Superior temporal gyrus | 148 | <0.001 | –59 | –33 | 21 | 5.26 |
| L | Inferior parietal gyrus | 170 | <0.001 | –43 | –53 | 54 | 5.03 |
| L | Cerebellum vermis | 55 | 0.016 | -3 | –75 | –15 | 4.84 |
| R | Inferior parietal gyrus | 37 | 0.093 | 50 | –47 | 54 | 4.74 |
| L | Supplementary motor area | 44 | 0.046 | -7 | -9 | 71 | 4.51 |
| Contrast: non0%<0% | |||||||
| L | Fusiform gyrus, extending to lingual gyrus, occipital gyrus and calcarine gyrus | 2408 | <0.001 | –31 | –59 | –15 | 8.86 |
| L | Posterior cingulate gyrus | 638 | <0.001 | -9 | –49 | 34 | 7.34 |
| L | vmPFC | 665 | <0.001 | -5 | 42 | –17 | 6.91 |
| R | Superior occipital gyrus, extending to calcarine gyrus | 1686 | <0.001 | 26 | –93 | 18 | 6.87 |
| L | Middle temporal gyrus | 176 | <0.001 | –63 | -9 | -8 | 6.73 |
| R | Fusiform gyrus | 294 | <0.001 | 32 | –37 | –15 | 6.73 |
| R | Precentral gyrus | 60 | 0.010 | 44 | –23 | 60 | 6.70 |
| R | Cerebellum | 87 | 0.001 | 16 | –87 | –41 | 6.33 |
| R | Middle temporal gyrus | 81 | 0.002 | 62 | -5 | –15 | 5.74 |
| R | Precuneus | 79 | 0.002 | 12 | –53 | 12 | 5.73 |
| L | Hippocampus | 64 | 0.007 | –25 | –11 | –23 | 5.17 |
| L | Posterior orbitofrontal gyrus | 37 | 0.093 | –43 | 28 | –15 | 5.12 |
| R | Middle frontal gyrus | 91 | 0.001 | 28 | 26 | 45 | 4.98 |
| L | Middle frontal gyrus | 230 | <0.001 | –27 | 22 | 54 | 4.93 |
| L | Middle temporal gyrus | 60 | 0.010 | –57 | –57 | -4 | 4.89 |
| L | Paracentral lobule | 46 | 0.037 | -5 | –31 | 67 | 4.68 |
| R | Paracentral lobule | 39 | 0.076 | 6 | –37 | 62 | 4.59 |
-
Note. Regions are identified at voxel-level p<0.001, and with cluster correction p<0.05 (FWE-corrected); L/R indicates if the cluster (or peak of the cluster) is part of the left or right hemisphere; Region name is identified using the AAL atlas; K is the number of voxels in the cluster; Coordinates are the MNI coordinates of cluster peak; T is the value of the T-statistic of the cluster peak.
Appendix 3—table 2
Whole-brain relief modulation.
| Contrast: Positive modulation | |||||||
|---|---|---|---|---|---|---|---|
| L/R | Region | K | p (cluster) | MNI Coordinates (xyz) | T (peak) | ||
| R | Insula | 1212 | <0.001 | 42 | 16 | -4 | 8.91 |
| L | Insula | 1027 | <0.001 | –35 | 12 | 5 | 8.31 |
| R | Mid cingulate gyrus, extending to supplementary motor area and anterior cingulate gyrus | 1739 | <0.001 | 2 | 10 | 43 | 6.80 |
| R | Cerebellum | 191 | <0.001 | 38 | –51 | –30 | 6.74 |
| R | Superior temporal gyrus, extending to supramarginal gyrus | 174 | <0.001 | 66 | –39 | 23 | 6.71 |
| R | Cerebellum | 114 | <0.001 | 8 | –71 | –12 | 6.60 |
| L | Supramarginal gyrus | 155 | <0.001 | –63 | –47 | 29 | 5.84 |
| L | Cerebellum | 99 | <0.001 | –37 | –51 | –32 | 5.22 |
| R | Medial frontal gyrus | 44 | 0.042 | 6 | 34 | 38 | 5.00 |
| Contrast: Negative modulation | |||||||
| L | vmPFC | 381 | <0.001 | -7 | 32 | –17 | 9.12 |
| R | Angular gyrus, extending to occipital gyri | 523 | <0.001 | 48 | –73 | 32 | 7.59 |
| L | Angular gyrus, extending to occipital gyri | 535 | <0.001 | –45 | –73 | 36 | 6.62 |
| L | Fusiform gyrus | 40 | 0.063 | –27 | –39 | –19 | 5.98 |
| R | Middle frontal gyrus | 107 | <0.001 | 26 | 28 | 45 | 5.70 |
| R | Lingual gyrus | 167 | <0.001 | 14 | –79 | –12 | 5.68 |
| R | Superior occipital gyrus | 39 | 0.070 | 16 | –91 | 18 | 5.40 |
| L | Precuneus | 534 | <0.001 | -1 | –63 | 45 | 5.33 |
| L | Lingual gyrus | 191 | <0.001 | –29 | –81 | –17 | 5.22 |
| L | Middle frontal gyrus | 194 | <0.001 | –29 | 20 | 47 | 5.19 |
| L | Postcentral gyrus | 69 | 0.004 | –63 | -5 | 32 | 4.78 |
| L | Lingual gyrus | 48 | 0.028 | –27 | –53 | -6 | 4.46 |
-
Note. Regions are identified at voxel-level p<0.001, and with cluster correction p<0.05 (FWE-corrected); L/R indicates if the cluster (or peak of the cluster) is part of the left or right hemisphere; Region name is identified using the AAL atlas; K is the number of voxels in the cluster; Coordinates are the MNI coordinates of cluster peak; T is the value of the T-statistic of the cluster peak.
Appendix 4—table 1
Whole-brain anticipatory fMRI responses to the presentation of the instructions.
| Contrast: non0%>0% | |||||||
|---|---|---|---|---|---|---|---|
| L/R | Region | K | p (cluster) | MNI Coordinates (xyz) | T (peak) | ||
| R | Cerebellum, vermis | 149 | <0.001 | 4 | –63 | -8 | 8.80 |
| L | Superior temporal gyrus | 362 | <0.001 | –59 | –33 | 21 | 8.13 |
| L | Mid cingulate gyrus | 2058 | <0.001 | -5 | -1 | 45 | 7.95 |
| L | Rolandic operculum | 919 | <0.001 | –59 | 4 | 5 | 7.49 |
| L | Thalamus | 175 | <0.001 | –5 | –21 | 1 | 7.26 |
| R | Insula | 852 | <0.001 | 42 | 18 | -6 | 7.18 |
| L | Inferior frontal gyrus | 76 | 0.003 | –39 | 38 | 12 | 6.08 |
| R | Brain stem | 128 | <0.001 | 6 | –29 | -8 | 6.03 |
| L | Insula | 50 | 0.033 | –41 | –13 | -4 | 5.66 |
| R | Cerebellum | 220 | <0.001 | 30 | –45 | –30 | 5.56 |
| L | Precuneus | 72 | 0.005 | -7 | –49 | 51 | 5.36 |
| R | Supplementary motor area | 54 | 0.023 | 12 | -9 | 67 | 5.26 |
| L | Inferior parietal gyrus | 78 | 0.003 | –45 | –55 | 49 | 4.94 |
| Contrast: non0%<0% | |||||||
| L | Fusiform gyrus | 369 | <0.001 | –31 | –45 | -6 | 8.08 |
| L | Middle temporal gyrus | 678 | <0.001 | –59 | -9 | -8 | 7.80 |
| R | Angular gyrus | 329 | <0.001 | 50 | –71 | 36 | 7.30 |
| R | Fusiform gyrus | 286 | <0.001 | 32 | –45 | -6 | 7.24 |
| L | Fusiform gyrus | 545 | <0.001 | –23 | –85 | –17 | 6.78 |
| R | Middle temporal gyrus | 109 | <0.001 | 58 | -1 | –21 | 6.66 |
| L | Superior frontal gyrus | 43 | 0.063 | -9 | 48 | 45 | 6.14 |
| L | Angular gyrus | 398 | <0.001 | –41 | –75 | 43 | 5.81 |
| R | Middle frontal gyrus | 118 | <0.001 | 28 | 26 | 45 | 5.60 |
| L | Precuneus | 83 | 0.002 | -5 | –49 | 36 | 5.12 |
| L | Middle frontal gyrus | 154 | <0.001 | –23 | 26 | 45 | 5.10 |
| R | Cerebellum | 62 | 0.011 | 16 | –85 | –41 | 4.35 |
-
Note. Regions are identified at voxel-level p<0.001, and with cluster correction p<0.05 (FWE-corrected); L/R indicates if the cluster (or peak of the cluster) is part of the left or right hemisphere; Region name is identified using the AAL atlas; K is the number of voxels in the cluster; Coordinates are the MNI coordinates of cluster peak; T is the value of the T-statistic of the cluster peak.
Appendix 4—table 2
ity contrast in whole-brain anticipatory fWhole-brain anticipatory fMRI responses to increasing probability.
| Contrast: Increase with increasing probability | |||||||
|---|---|---|---|---|---|---|---|
| L/R | Region | K | p (cluster) | MNI Coordinates (xyz) | T (peak) | ||
| L | Mid cingulate gyrus | 1394 | <0.001 | -3 | 4 | 43 | 7.88 |
| L | Middle temporal gyrus | 63 | 0.004 | –57 | –65 | 7 | 6.74 |
| L | Precentral gyrus | 278 | <0.001 | –59 | 10 | 10 | 6.65 |
| L | Putamen | 125 | <0.001 | –23 | 4 | -4 | 6.30 |
| L | Postcentral gyrus | 98 | <0.001 | –33 | –43 | 62 | 6.07 |
| R | Cerebellum | 64 | 0.004 | 28 | –45 | –50 | 6.03 |
| L | Supramarginal gyrus | 201 | <0.001 | –65 | –33 | 27 | 6.02 |
| L | Middle frontal gyrus | 347 | <0.001 | –41 | 46 | 16 | 5.84 |
| R | Cerebellum | 39 | 0.050 | 52 | –55 | –34 | 5.83 |
| R | Insula | 71 | 0.002 | 40 | 20 | 5 | 5.81 |
| L | Precuneus | 266 | <0.001 | -9 | –55 | 54 | 5.77 |
| R | Cerebellum | 216 | <0.001 | 34 | –51 | –32 | 5.72 |
| R | Middle frontal gyrus | 62 | 0.004 | 32 | 42 | 27 | 5.43 |
| R | Supramarginal gyrus | 277 | <0.001 | 58 | –41 | 32 | 5.37 |
| L | Cerebellum | 122 | <0.001 | –45 | –53 | –37 | 5.17 |
| R | Insula | 37 | 0.063 | 40 | 6 | 5 | 5.06 |
| L | Precuneus | 95 | <0.001 | -7 | –77 | 45 | 5.06 |
| L | Cerebellum | 73 | 0.002 | –13 | –75 | –41 | 4.89 |
| L | Putamen | 35 | 0.079 | –25 | 6 | 7 | 4.65 |
| R | Cerebellum | 34 | 0.089 | 36 | –61 | –39 | 4.44 |
| Contrast: Decrease with increasing probability | |||||||
| No significant clusters of activation | |||||||
-
Note. Regions are identified at voxel-level p<0.001, and with cluster correction p<0.05 (FWE-corrected); L/R indicates if the cluster (or peak of the cluster) is part of the left or right hemisphere; Region name is identified using the AAL atlas; K is the number of voxels in the cluster; Coordinates are the MNI coordinates of cluster peak; T is the value of the T-statistic of the cluster peak.
Appendix 4—table 3
Intensity contrast in whole-brain anticipatory fMRI activations.
| Contrast: Strong >Weak | |||||||
|---|---|---|---|---|---|---|---|
| L/R | Region | K | p (cluster) | MNI Coordinates (xyz) | T (peak) | ||
| R | Supplementary motor area | 2942 | <0.001 | 6 | 6 | 67 | 9.92 |
| R | Insula | 1028 | <0.001 | 30 | 22 | -8 | 8.90 |
| R | Cerebellum | 1194 | <0.001 | 22 | –57 | –21 | 8.37 |
| L | Cerebellum | 478 | <0.001 | –35 | –57 | –26 | 7.71 |
| L | Superior temporal gyrus | 814 | <0.001 | –51 | 2 | 1 | 7.66 |
| R | Supramarginal gyrus | 674 | <0.001 | 64 | –45 | 32 | 6.91 |
| L | Cerebellum | 147 | <0.001 | 36 | –51 | –52 | 6.90 |
| L | Thalamus | 184 | <0.001 | 6 | –17 | 1 | 6.78 |
| L | Supramarginal gyrus | 568 | <0.001 | –59 | –25 | 29 | 6.48 |
| L | Postcentral gyrus | 111 | <0.001 | –35 | –19 | 45 | 6.47 |
| L | Postcentral gyrus | 100 | <0.001 | –31 | –43 | 62 | 6.21 |
| R | Precentral gyrus | 166 | <0.001 | 52 | -7 | 47 | 6.19 |
| L | Postcentral gyrus | 75 | 0.002 | –31 | –31 | 54 | 5.47 |
| R | Cerebellum | 40 | 0.064 | 16 | –67 | –48 | 5.45 |
| L | Insula | 47 | 0.031 | –35 | -9 | 1 | 5.05 |
| R | Amygdala | 63 | 0.007 | 22 | -1 | –12 | 5.04 |
| Contrast: Strong <Weak | |||||||
| R | Superior frontal gyrus | 170 | <0.001 | 24 | 36 | 47 | 6.09 |
| R | Angular gyrus | 115 | <0.001 | 40 | –73 | 45 | 5.24 |
| L | Inferior parietal gyrus | 72 | 0.003 | –33 | –71 | 43 | 4.80 |
| R | Middle frontal gyrus | 63 | 0.007 | 48 | 42 | 14 | 4.71 |
-
Note. Regions are identified at voxel-level p<0.001, and with cluster correction p<0.05 (FWE-corrected); L/R indicates if the cluster (or peak of the cluster) is part of the left or right hemisphere; Region name is identified using the AAL atlas; K is the number of voxels in the cluster; Coordinates are the MNI coordinates of cluster peak; T is the value of the T-statistic of the cluster peak.
Appendix 4—table 4
Whole-brain stimulation-induced activations.
| Contrast: Stimulation >baseline | |||||||
|---|---|---|---|---|---|---|---|
| L/R | Region | K | p (cluster) | MNI Coordinates (xyz) | T (peak) | ||
| L | Insula | 5078 | <0.001 | –39 | -1 | 16 | 15.62 |
| R | Insula | 3774 | <0.001 | 44 | 10 | -4 | 11.71 |
| R | Cerebellum | 2577 | <0.001 | 14 | –55 | –17 | 11.32 |
| L | Cerebellum | 684 | <0.001 | –35 | –63 | –26 | 9.92 |
| L | Mid cingulate gyrus | 2048 | <0.001 | -3 | 8 | 43 | 9.44 |
| L | Middle frontal gyrus | 271 | <0.001 | –41 | 42 | 23 | 7.12 |
| R | Middle temporal gyrus | 119 | <0.001 | 54 | –31 | 1 | 5.11 |
| L | Cerebellum | 78 | 0.007 | –17 | –77 | –37 | 4.85 |
| Contrast: Stimulation <baseline | |||||||
| R | Occipital gyri, extending to fusiform, lingual gyri | 4348 | <0.001 | 32 | –91 | –10 | 14.53 |
| L | Occipital gyri, extending to fusiform, lingual gyri | 4411 | <0.001 | –35 | –91 | –15 | 13.70 |
| L | vmPFC | 1883 | <0.001 | -5 | 42 | –15 | 11.66 |
| R | Precentral gyrus | 271 | <0.001 | 40 | –21 | 51 | 10.21 |
| R | Postcentral gyrus | 85 | 0.004 | 36 | –31 | 56 | 8.25 |
| R | Middle temporal gyrus | 188 | <0.001 | 60 | -3 | –19 | 7.95 |
| L | Middle temporal gyrus | 582 | <0.001 | –61 | –13 | –15 | 6.69 |
| R | Superior frontal gyrus | 136 | <0.001 | 26 | 32 | 49 | 6.22 |
| L | Precentral gyrus | 143 | <0.001 | –57 | -3 | 29 | 6.20 |
| L | Posterior cingulate gyrus | 887 | <0.001 | -3 | –55 | 29 | 6.11 |
| L | Superior frontal gyrus | 136 | <0.001 | –27 | 26 | 56 | 5.94 |
| R | Cerebellum | 46 | 0.083 | 20 | –83 | –41 | 5.31 |
-
Note. Regions are identified at voxel-level p<0.001, and with cluster correction p<0.05 (FWE-corrected); L/R indicates if the cluster (or peak of the cluster) is part of the left or right hemisphere; Region name is identified using the AAL atlas; K is the number of voxels in the cluster; Coordinates are the MNI coordinates of cluster peak; T is the value of the T-statistic of the cluster peak.
Appendix 4—table 5
Whole-brain unexpected stimulation-induced activations.
| Contrast: non100%>100% stimulations | |||||||
|---|---|---|---|---|---|---|---|
| L/R | Region | K | p (cluster) | MNI Coordinates (xyz) | T (peak) | ||
| R | Middle temporal gyrus | 121 | <0.001 | 54 | –21 | -6 | 6.52 |
| R | Rolandic operculum | 50 | 0.014 | 42 | –11 | 18 | 5.57 |
| R | Frontal superior gyrus | 44 | 0.027 | 24 | 20 | 47 | 5.17 |
| L | Middle temporal gyrus | 42 | 0.034 | –59 | –25 | -4 | 5.10 |
| L | Precentral gyrus | 72 | 0.002 | –57 | -7 | 32 | 4.75 |
| R | Middle temporal gyrus | 36 | 0.067 | 50 | –55 | 21 | 4.67 |
| R | Medial superior frontal gyrus | 34 | 0.085 | 8 | 54 | 23 | 4.49 |
| R | Mid cingulate gyrus | 34 | 0.085 | 4 | –47 | 34 | 4.32 |
| L | Middle temporal gyrus | 33 | 0.096 | –53 | –55 | 23 | 4.32 |
| Contrast: non100%<100% stimulations | |||||||
| No significant clusters of activation | |||||||
-
Note. Regions are identified at voxel-level p<0.001, and with cluster correction p<0.05 (FWE-corrected); L/R indicates if the cluster (or peak of the cluster) is part of the left or right hemisphere; Region name is identified using the AAL atlas; K is the number of voxels in the cluster; Coordinates are the MNI coordinates of cluster peak; T is the value of the T-statistic of the cluster peak.
Appendix 5—table 1
F-statistics and corresponding p-values from the overall lag model.
| Relief | SCR | VTA/SN (*) | Left vPut | NAC | vmPFC | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Regressor | F | P | F | P | F | P | F | P | F | P | F | P |
| Probability | 30.04 | <0.001 | 4.90 | <0.01 | 3.59 | <0.05 | 0.18 | n.s. | 0.88 | n.s. | 1.73 | n.s. |
| Intensity | 620.62 | <0.001 | 106.65 | <0.001 | 7.81 | <0.001 | 3.88 | <0.05 | 0.70 | n.s. | 4.90 | <0.01 |
| Run | 9.71 | <0.001 | 15.56 | <0.001 | 1.13 | n.s. | 0.76 | n.s. | 0.62 | n.s. | 0.44 | n.s. |
| Probability x Intensity | 3.69 | <0.01 | 1.54 | n.s. | 1.15 | n.s. | 1.39 | n.s. | 1.76 | n.s. | 0.70 | n.s. |
| Probability x Run | 1.13 | n.s. | 1.24 | n.s. | 1.02 | n.s. | 1.22 | n.s. | 1.74 | n.s. | 1.26 | n.s. |
| Intensity x Run | 1.94 | 0.07 | 1.30 | n.s. | 1.94 | 0.07 | 1.59 | n.s. | 1.01 | n.s. | 2.41 | <0.05 |
| Probability x Intensity x Run | 0.56 | n.s. | 0.87 | n.s. | 0.76 | n.s. | 0.71 | n.s. | 0.76 | n.s. | 0.83 | n.s. |
| Overall-lag | 2.56 | n.s. | 4.68 | <0.05 | 11.30 | <0.001 | <0.01 | n.s. | 0.16 | n.s. | <0.01 | n.s. |
| US-unpleasantness | 29.60 | <0.001 | 3.00 | 0.096 | 1.84 | n.s. | 0.06 | n.s. | 3.44 | 0.07 | 0.26 | n.s. |
-
*
(*) F-test and p-values were based on the model where outliers were rescored to 2SD from the mean. Note that when retaining the influential outliers for this model, the p-value of the probability effect was p=0.06. For all other outcome variables, rescoring the outliers did not change the results. Significant effects are indicated in bold.
Appendix 5—table 2
F-statistics and corresponding p-values from the lag per probability level model.
| Relief | SCR | VTA/SN (*) | Left vPut | NAC | vmPFC | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Regressor | F | P | F | P | F | P | F | P | F | P | F | P |
| Probability | 23.07 | <0.001 | 4.44 | <0.05 | 3.28 | <0.05 | 0.22 | n.s. | 0.18 | n.s. | 0.31 | n.s. |
| Intensity | 625.52 | <0.001 | 107.49 | <0.001 | 7.33 | <0.001 | 3.88 | <0.05 | 0.66 | n.s. | 4.85 | <0.01 |
| Run | 8.63 | <0.001 | 13.91 | <0.001 | 1.09 | n.s. | 0.72 | n.s. | 0.60 | n.s. | 1.09 | n.s. |
| Probability x Intensity | 3.87 | <0.01 | 1.33 | n.s. | 1.01 | n.s. | 1.40 | n.s. | 1.81 | n.s. | 0.63 | n.s. |
| Probability x Run | 1.63 | n.s. | 1.10 | n.s. | 1.25 | n.s. | 1.16 | n.s. | 1.60 | n.s. | 1.17 | n.s. |
| Intensity x Run | 2.08 | 0.053 | 1.25 | n.s. | 1.84 | 0.09 | 1.61 | n.s. | 1.02 | n.s. | 2.55 | <0.05 |
| Probability x Intensity x Run | 0.55 | n.s. | 0.90 | n.s. | 0.72 | n.s. | 0.71 | n.s. | 0.73 | n.s. | 0.84 | n.s. |
| Lag per probability: Probability | 1.51 | n.s. | 1.32 | n.s. | 1.12 | n.s. | 0.10 | n.s. | 0.96 | n.s. | 4.14 | <0.01 |
| US-unpleasantness | 29.69 | <0.001 | 2.99 | 0.097 | 1.63 | n.s. | 0.06 | n.s. | 3.34 | 0.08 | 0.27 | n.s. |
-
*
(*) F-test and p-values were based on the model where outliers were rescored to 2SD from the mean. Note that when retaining the influential outliers for this model, the p-value of the Intensity x Run interaction was p=0.05. For all other outcome variables, rescoring the outliers did not change the results. Significant effects are indicated in bold.
Appendix 6—table 1
Whole-brain SCR modulation.
| Contrast: Positive modulation | ||||||||
|---|---|---|---|---|---|---|---|---|
| L/R | Region | K | p (cluster) | MNI Coordinates (xyz) | T (peak) | |||
| L | Insula | 426 | <0.001 | –35 | 8 | 10 | 6.86 | |
| R | Mid cingulate gyrus | 410 | <0.001 | 2 | 12 | 38 | 6.03 | |
| L | Superior temporal gyrus | 87 | 0.001 | –63 | –33 | 21 | 6.03 | |
| R | Supplementary motor gyrus | 235 | <0.001 | 4 | 4 | 65 | 6.01 | |
| R | Insula | 554 | <0.001 | 46 | 20 | -4 | 5.91 | |
| L | Cerebellum | 163 | <0.001 | –35 | –53 | –30 | 5.76 | |
| L | Thalamus | 45 | 0.029 | -1 | –11 | 12 | 5.70 | |
| R | Cerebellum | 50 | 0.017 | 30 | –49 | –50 | 5.59 | |
| R | Cerebellum | 156 | <0.001 | 24 | –63 | –19 | 5.56 | |
| R | Cerebellum, vermis | 45 | 0.029 | 6 | –61 | -6 | 5.16 | |
| R | Supramarginal gyrus | 35 | 0.087 | 64 | –33 | 29 | 5.07 | |
| L | Cerebellum | 42 | 0.040 | -9 | –81 | –26 | 5.01 | |
| L | Cerebellum | 47 | 0.023 | –45 | –71 | –26 | 4.90 | |
| Contrast: Negative modulation | ||||||||
| L | Hippocampus | 110 | <0.001 | –23 | –11 | –23 | 7.02 | |
| R | Hippocampus | 153 | <0.001 | 26 | –17 | –19 | 7.00 | |
| L | Paracentral lobule | 123 | <0.001 | -3 | –31 | 69 | 6.65 | |
| R | Paracentral lobule | 128 | <0.001 | 4 | –31 | 67 | 6.49 | |
| L | vmPFC | 317 | <0.001 | -3 | 42 | –15 | 6.38 | |
| R | Angular gyrus | 332 | <0.001 | 44 | –59 | 29 | 6.31 | |
| L | Precuneus | 64 | 0.004 | -1 | –61 | 36 | 5.96 | |
| L | Precuneus | 37 | 0.070 | -9 | –63 | 16 | 5.74 | |
| R | Middle frontal gyrus | 50 | 0.017 | 30 | 36 | –12 | 5.67 | |
| R | Posterior cingulate gyrus | 102 | <0.001 | 10 | –57 | 21 | 5.61 | |
| L | Fusiform gyrus | 146 | <0.001 | –29 | –41 | –21 | 5.56 | |
| R | Precentral gyrus | 109 | <0.001 | 46 | –21 | 60 | 5.54 | |
| L | Middle occipital gyrus | 274 | <0.001 | –37 | –75 | 34 | 5.36 | |
| R | Inferior temporal gyrus | 71 | 0.002 | 42 | –67 | -4 | 5.17 | |
| L | Superior temporal gyrus | 52 | 0.014 | –63 | -5 | -6 | 5.11 | |
| L | Middle temporal gyrus | 40 | 0.050 | –59 | –63 | -1 | 5.02 | |
| L | Middle temporal gyrus | 39 | 0.056 | –61 | –41 | 3 | 4.91 | |
| L | Middle cingulate gyrus | 89 | <0.001 | -5 | –41 | 36 | 4.88 | |
| R | Middle frontal gyrus | 58 | 0.008 | 26 | 18 | 47 | 4.79 | |
| L | Inferior temporal gyrus | 56 | 0.009 | –47 | 2 | –41 | 4.54 | |
-
Note. Regions are identified at voxel-level p<0.001, and with cluster correction p<.05 (FWE-corrected); L/R indicates if the cluster (or peak of the cluster) is part of the left or right hemisphere; Region name is identified using the AAL atlas; K is the number of voxels in the cluster; Coordinates are the MNI coordinates of cluster peak; T is the value of the T-statistic of the cluster peak.
Appendix 6—table 2
Main omission SCR signature clusters identified via bootstrapping.
| Positive weight clusters | |||||||
|---|---|---|---|---|---|---|---|
| L/R | Region | K | MNI Coordinates (xyz) | Z (peak) | |||
| R | Cerebellum Crus 2 | 11 | 8 | –87 | –30 | 0.00019 | |
| L | Cerebellum Crus 2 | 12 | –19 | –87 | –28 | 0.00016 | |
| L | Cerebellum Crus 1 | 16 | –41 | –71 | –26 | 0.00015 | |
| R | Calcarine gyrus | 12 | 2 | –91 | –12 | 0.00023 | |
| R | Fusiform gyrus | 10 | 30 | –57 | -8 | 0.00020 | |
| R | Inferior occipital gyrus | 15 | 36 | –89 | -6 | 0.00023 | |
| L | Anterior cingulate cortex | 12 | -1 | 26 | 18 | 0.00026 | |
| L | Supramarginal gyrus | 21 | –55 | –45 | 27 | 0.00020 | |
| L | Cuneus | 12 | -9 | –81 | 29 | 0.00018 | |
| R | Superior occipital gyrus | 70 | 30 | –71 | 43 | 0.00018 | |
| L | Postcentral gyrus | 12 | –61 | –19 | 36 | 0.00013 | |
| L | Precuneus | 21 | -3 | –71 | 51 | 0.00023 | |
| Negative weight clusters | |||||||
| L | Cerebellum | 18 | –33 | –45 | –26 | –0.00025 | |
| L | Cerebellum Crus 1 | 11 | –35 | –83 | –21 | –0.00031 | |
| R | Lingual gyrus | 12 | 30 | –85 | –17 | –0.00026 | |
| L | Fusiform gyrus | 33 | –23 | –69 | –15 | –0.00025 | |
| R | Superior frontal gyrus | 16 | 40 | 42 | –15 | –0.00020 | |
| L | Lingual gyrus | 15 | –39 | –85 | –12 | –0.00014 | |
| R | Inferior occipital gyrus | 29 | 42 | –79 | –12 | –0.00014 | |
| R | Inferior temporal gyrus | 10 | 60 | –41 | –12 | –0.00015 | |
| R | Inferior occipital gyrus | 13 | 30 | –89 | -6 | –0.00015 | |
| R | Middle temporal gyrus | 11 | 52 | –55 | 1 | –0.00017 | |
| L | Middle occipital gyrus | 24 | –39 | –87 | 5 | –0.00016 | |
| R | Middle occipital gyrus | 17 | 40 | –85 | 5 | –0.00019 | |
| R | Middle frontal gyrus | 17 | 42 | 42 | 7 | –0.00014 | |
| L | Middle occipital gyrus | 17 | –51 | –73 | 7 | –0.00020 | |
| L | Caudate | 11 | –17 | 20 | 7 | –0.00019 | |
| L | Thalamus | 16 | –13 | –31 | 10 | –0.00026 | |
| R | Calcarine gyrus | 10 | 4 | –75 | 12 | –0.00019 | |
| R | Caudate | 14 | 14 | 6 | 16 | –0.00016 | |
| R | Postcentral gyrus | 10 | 62 | -3 | 21 | –0.00017 | |
| R | Frontal middle gyrus | 17 | 44 | 40 | 23 | –0.00015 | |
| R | Superior frontal gyrus | 11 | 20 | 62 | 23 | –0.00015 | |
| L | Precentral gyrus | 11 | –55 | 6 | 29 | –0.00013 | |
| R | Precuneus | 10 | 2 | –77 | 45 | –0.00019 | |
| L | Postcentral gyrus | 11 | –51 | –15 | 54 | –0.00016 | |
| R | Precuneus | 11 | 10 | –69 | 60 | –0.00021 | |
| R | Supplementary motor area | 15 | 4 | –25 | 60 | –0.00015 | |
-
Note. Clusters (FDR-corrected, k>10, following bootstrapping). L/R indicates if the cluster (or peak of the cluster) is part of the left or right hemisphere; Region name is identified using the AAL atlas. K is the number of voxels in the cluster; coordinates are the MNI coordinates of cluster peak, Z is the signature weight of the cluster peak.
Author response table 1
| Omission responses | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Regressor | Relief | SCR | VTA/SN (*) | Left vPut | NAC | vmPFC | ||||||
| F | P | P | F | P | ||||||||
| Probability | 30.04 | <.001 | 4.9 | <.01 | 3.59 | <.05 | 0.18 | n.s. | 0.88 | n.s. | 1.73 | n.s. |
| Intensity | 620.62 | <.001 | 106.65 | <.001 | 7.81 | <.001 | 3.88 | <.05 | 0.7 | n.s. | 4.9 | <.01 |
| Run | 9.71 | <.001 | 15.56 | <.001 | 1.13 | n.s. | 0.76 | n.s. | 0.62 | n.s. | 0.44 | n.s. |
| Probability x Intensity | 3.69 | <.01 | 1.54 | n.s. | 1.15 | n.s. | 1.39 | n.s. | 1.76 | n.s. | 0.7 | n.s. |
| Probability x Run | 1.13 | n.s. | 1.24 | n.s. | 1.02 | n.s. | 1.22 | n.s. | 1.74 | n.s. | 1.26 | n.s. |
| Intensity x Run | 1.94 | 0.07 | 1.3 | n.s. | 1.94 | 0.07 | 1.59 | n.s. | 1.01 | n.s. | 2.41 | <.05 |
| Probability x Intensity x Run | 0.56 | n.s. | 0.87 | n.s. | 0.76 | n.s. | 0.71 | n.s. | 0.76 | n.s. | 0.83 | n.s. |
| Overall-lag | 2.56 | n.s. | 4.68 | <.05 | 11.3 | <.001 | <0.01 | n.s. | 0.16 | n.s. | <0.01 | n.s. |
| US-unpleasantness | 29.6 | <.001 | 3 | 0.096 | 1.84 | n.s. | 0.06 | n.s. | 3.44 | 0.07 | 0.26 | n.s. |
Author response table 2
| Omission responses | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Regressor | Relief | SCR | VTA/SN (*) | Left vPut | NAC | vmPFC | ||||||
| FF | P | F | P | F | P | F | P | F | P | F | P | |
| Probability | 23.07 | <.001 | 4.44 | <.05 | 3.28 | <.05 | 0.22 | n.s. | 0.18 | n.s. | 0.31 | n.s. |
| Intensity | 625.52 | <.001 | 107.49 | <0.01 | 7.33 | <0.01 | 3.88 | <.05 | 0.66 | n.s. | 4.85 | <.01 |
| Run | 8.63 | <.001 | 13.91 | <0.01 | 1.09 | n.s. | 0.72 | n.s. | 0.60 | n.s. | 1.09 | n.s. |
| Probability x Intensity | 3.87 | <.01 | 1.33 | n.s. | 1.01 | n.s. | 1.40 | n.s. | 1.81 | n.s. | 0.63 | n.s. |
| Probability x Run | 1.63 | n.s. | 1.10 | n.s. | 1.25 | n.s. | 1.16 | n.s. | 1.60 | n.s. | 1.17 | n.s. |
| Intensity x Run | 2.08 | .053 | 1.25 | n.s. | 1.84 | .09 | 1.61 | n.s. | 1.02 | n.s. | 2.55 | <.05 |
| Probability x Intensity x Run | 0.55 | n.s. | 0.90 | n.s. | 0.72 | n.s. | 0.71 | n.s. | 0.73 | n.s. | 0.84 | n.s. |
| Lag per probability: Probability | 1.51 | n.s. | 1.32 | n.s. | 1.12 | n.s. | 0.10 | n.s. | 0.96 | n.s. | 4.14 | <.01 |
| US- unpleasantness | 26.69 | <.001 | 2.99 | .097 | 1.63 | n.s. | 0.06 | n.s. | 3.34 | .08 | 0.27 | n.s. |
Additional files
-
MDAR checklist
- https://cdn.elifesciences.org/articles/91400/elife-91400-mdarchecklist1-v1.docx
-
Supplementary file 1
Demographics of included participants.
- https://cdn.elifesciences.org/articles/91400/elife-91400-supp1-v1.docx
-
Supplementary file 2
Descriptives of questionnaire scores.
- https://cdn.elifesciences.org/articles/91400/elife-91400-supp2-v1.docx
-
Supplementary file 3
Trial types and numbers.
- https://cdn.elifesciences.org/articles/91400/elife-91400-supp3-v1.docx
