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. 2022 Jan 26;11:e71877. doi: 10.7554/eLife.71877

Figure 3. Main effect of task and temperature in Brainstem and Cerebrum.

(A) Main effect of temperature and task in the brainstem after permutation testing with a whole brainstem mask showing clusters of activation in PAG, bilateral LC and RVM. Activity reported with corrected p< 0.05 (TFCE). (B) Main effects of temperature and task in brain. In the main effect of temperature contrast there were clusters of activation in a number of pain related sites including in the contralateral primary somatosensory cortex, the dorsal posterior insula and the PAG (red-yellow). The frontal medial cortex de-activated (blue-light blue). In the main effect of task contrast there were clusters of activation in the visual and attention networks including superior parietal cortex, the frontal pole, and the anterior cingulate cortex (red-yellow). The posterior cingulate cortex and lateral occipital cortex showed de-activation (blue-light blue). Activity was estimated with a cluster forming threshold of Z > 3.1 and FWE corrected p < 0.05. (PAG – Periaqueductal grey, LC – Locus coeruleus, RVM – Rostral ventromedial medulla, FMC – Frontomedial cortex, dpIns – dorsal posterior insula, SI – primary somatosensory cortex, LOC – Lateral ocipital cortex (sup and inf), SPL Superior parietal lobule.).

Figure 3—source data 1. Cluster sizes, peak Z-scores, locations and anatomical locations for each experimental contrast.

Figure 3.

Figure 3—figure supplement 1. Whole brain mixed effects analysis of pooled data (inputs are the average of each subject’s three sessions) for the three contrasts (main effects of temperature, task and their interaction).

Figure 3—figure supplement 1.

Slices shown (left to right) (i) midline sagittal, (ii) coronal through the PAG, bilateral LC and RVM masks, and (iii) axial at the level of the midline RVM mask. To allow visualisation of underlying anatomy, data were thresholded at an uncorrected p-value of 0.05 (i.e. Z > 1.65). The location of relevant masks are outlined in white, with labels shown. Also included is the brainstem mask derived from the Harvard-Oxford sub-cortical probabilistic atlas, which was thresholded at 50% and used for estimating brainstem activity reported in the manuscript (rather than the whole brain analysis shown here). Assignment of activity to specific nuclei was based on overlap with probabilistic brainstem nuclei masks (Brooks et al., 2017). Positive Z-scores are shown in Red-Yellow colours, whilst negative ones are in Blue-Light blue. Activity was rarely observed in the 4th ventricle, nor in the aqueduct, indicating that physiological noise was adequately corrected for with the chosen scheme (see Brooks et al., 2008; Kong et al., 2012 for more details).
Figure 3—figure supplement 2. Anterior Insula and medulla response after Naltrexone administration.

Figure 3—figure supplement 2.

(A) The anterior insula responded more strongly in the naltrexone than in the placebo in the main effect of task (obtained with permutation testing with a main effect of task mask, obtained from the pooled analysis). (B) A cluster in the lower medulla responded more strongly in the naltrexone than in the placebo main effect of temperature. Result obtained with permutation testing (using a main effect of temperature brainstem mask, obtained from the pooled analysis). TFCE corrected p < 0.05.