Figure 6. Original cue effects on medium heat pain.

We conducted a second mediation analysis to isolate effects of original contingencies, controlling for current contingencies. (A) Effects of original contingencies. The goal of our second mediation analysis was to specifically identify regions that continued to respond to the original contingencies across the entire task, regardless of reversals. (B) Path a: Regions that show greater activation to original high pain contingencies despite reversals. Path a identified regions that showed greater activation to the Original High Cue (dark gray) relative to the Original Low Cue (light gray) across the entire task, while controlling for current contingencies. No voxels survived correction within pain modulatory regions. However, whole brain correction revealed that a number of regions including the brainstem’s rostroventral medulla (RVM), right DLPFC, left medial OFC (mOFC), and other regions (see Figure 6—figure supplement 2 and Figure 6—source data 1) continued to show higher activation when medium heat was paired with the original high pain cue regardless of Phase. Extracting trial-by-trial responses from the RVM (top) confirmed that this region showed greater heat-evoked activation with the Original High Cue during both original and reversed contingencies and that effects were present in both the Instructed Group and the Uninstructed Group. In the mOFC, however, responses did reverse within the Instructed Group (bottom), suggesting that failure to reverse was driven by Uninstructed Group participants. Similar effects were observed in the VMPFC region of interest (See Figure 5—figure supplement 5). See Figure 6—figure supplements 2 and 3 for means within other Path a regions. (B) Associations between original contingencies and pain were statistically mediated by a cluster in the right superior frontal gyrus, in which individuals who had larger effects of original cues on brain responses (controlling for current contingencies; i.e. Path a, x-axis) also had stronger negative associations between brain activation and subjective pain (Path b, y-axis). There were no additional mediators of original cue effects on pain based on whole brain correction identified additional effects in the right DLPFC, precuneus, and cerebellum (see Figure 6—figure supplement 1 and Figure 6—source data 1). Whole brain uncorrected results are presented in Figure 6—figure supplements 4 and 5 and Figure 6—source data 2.

Figure 6—figure supplement 1. Original contingency mediation: Whole-brain FDR correction.

Results are reported in Figure 6—source data 1.

Figure 6—figure supplement 2. Original contingency mediation: Effects of cue and phase.

This figure depicts extracted responses in clusters identified in analyses of Path a of the mediation based on original contingencies, i.e. regions identified as showing higher activation in response to original high pain cues relative to original low pain cues, regardless of phase. We extracted responses and averaged as a function of Group (Instructed vs Uninstructed), Cue (Original low = ‘Orig LM’; Original high = ‘Orig HM’), Phase (Left two lighter bars = Original contingencies; Right two darker bars = reversed contingencies). This confirms that these regions maintain initial responses despite contingency reversals and that responses are similar across both groups.

Figure 6—figure supplement 3. Raw timecourses in Path A regions.

Images depict average baseline-corrected trial timecourse for regions identified in FDR-Corrected Path A analyses (see Figure 6—figure supplement 1) as a function of Group and temperature. Average responses to low heat trials (green) and high heat trials (red) are depicted in the left column, and responses to medium heat trials are depicted in the center column (original contingencies) and right column (reversed contingencies) as a function of original cue type.

Figure 6—figure supplement 4. Original contingency mediation: Whole-brain uncorrected results.

Results are reported in Figure 6—source data 2.

Figure 6—figure supplement 5. Original contingency mediation, including Group as a moderator: Whole-brain uncorrected results.

Results are reported in Figure 6—source data 2.