Schematics of the Stimulus Sequences

<p>Schematics of the stimulus sequences in the three main conditions (veridical-rabbit, illusory-rabbit, and control). The cartoon of the forearm schematically indicates the three different electrode positions (P1, P2, and P3). For the veridical-rabbit condition, three pulses at P1 were followed by three at P2 and then three at P3. The illusory-rabbit condition used a P1-P1-P3 sequence instead, but phenomenally, this was equivalent to the veridical-rabbit condition, with stimulation being felt around P2 for later repetitions at P1, despite no actual stimulation at P2. The control condition was a P1-P3-P1 sequence, thus stimulating the same two actual sites as for the illusory-rabbit condition, but now in a different sub-second order, which did not induce any illusion of stimulation around P2. The nine pulses in each condition were given in 400 ms.</p

Common Activation for the Illusory-Rabbit and the Veridical-Rabbit versus Control Conditions beyond Somatosensory Cortex in the Whole-Brain Analysis

<p>Regions beyond the somatosensory cortex that displayed activity increases during both illusory- and veridical-rabbit, relative to control conditions (whole-brain, random-effects, group analysis). The graph shows the statistical T-map of the conjunction contrast of illusory-rabbit versus control data, and veridical-rabbit versus the other (equivalent but independent) control dataset (<i>p</i> < 0.001 for display). This revealed activation of the left inferior frontal gyrus (peak at X = −48, Y = 38, Z = 2). The format for the plot in (D) is as for the analogous plot in<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040069#pbio-0040069-g002" target="_blank">Figure 2</a>D. Note that the veridical-rabbit and the illusory-rabbit conditions showed significantly higher activation than the two control datasets, which were equivalent, whereas the two rabbit conditions did not differ from each other.</p

Activations for the Illusory-Rabbit versus the Veridical-Rabbit Conditions

<p>Regions beyond the somatosensory cortex that were more active for the illusory- than veridical-rabbit sequences (whole-brain, random-effects, group analysis). The graph shows the statistical T-map for the contrast illusory-rabbit minus veridical-rabbit, projected onto: (A) sagittal and (B) transversal slices of the Montreal Neurological Institute standard brain (<i>p</i> <0.001 for display purposes). This contrast revealed activation of the right dorsal prefrontal cortex (middle frontal gyrus, peak at X = 50, Y = 28, Z = 30) and of the right premotor cortex (precentral/inferior frontal gyrus, peak at X = 48, Y = 0, Z = 34).</p

Common Activation for the Illusory-Rabbit and the Veridical-Rabbit versus Control Conditions Embedded in the Localizer Results for Skin-Sites P1, P2, and P3

<p>The brain images (A, B, C) again show the common activation (random-effects group analysis) for the veridical-rabbit and illusory-rabbit conditions in orange (peak at X = 36, Y = −32, Z = 66), now projected onto the differential contrasts for the localizer conditions (P1 versus P2 and P3 in bright gray, P2 versus P1 and P3 in intermediate gray, P3 versus P1 and P2 in dark gray) within BAs 3a, 3b, 1, and 2, as defined by the cytoarchitectonic atlas [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040069#pbio-0040069-b011" target="_blank">11</a>]. The differential activations for P1, P2, and P3 show the expected medial-to-lateral ordering for the different forearm positions (B and C). Although there is some spread in these localizer activations (as expected for smoothed fMRI data across a group, but see also<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040069#pbio-0040069-g004" target="_blank">Figure 4</a>), note that the critical experimental activation for the two rabbit conditions (shown in orange here) clearly falls quite centrally within the localizer activation that corresponds to P2 (see B and C). Moreover, (D) plots the parameter estimates (SPM beta-values and standard errors in red) extracted from the region that was experimentally activated by the rabbit (orange), showing these for each of the separate group-localizer conditions. Note the stronger response to P2 than P3 or P1 here, as shown by the vast majority of individuals (9/10 and 8/10 respectively, see main text).</p

Common Activation for the Illusory-Rabbit and the Veridical-Rabbit versus Control Conditions with Less Spatial Smoothing

<p>The brain images (A, B) show the common activation for the veridical-rabbit and illusory-rabbit in yellow (<i>p</i> < 0.001, uncorrected), from a group analysis using a considerably reduced smoothing kernel (4-mm FWHM). Note that the activation elicited by both the illusory- and veridical-rabbit (relative to the control) conditions is in virtually the identical location within SI (peak at X = 38, Y = −32, Z = 68) as before (see<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040069#pbio-0040069-g003" target="_blank">Figure 3</a>), and at the same threshold. Panel C shows the outcome of single-participant ROI analysis of the mean parameter estimates (SPM beta-values, from the analysis with 4-mm FWHM smoothing), extracted separately for each individual from the participant-specific locations within SI responding maximally to stimulation at P1, P2, or P3 (relative to the other two skin sites from these three) during the individual localizer sessions. The bars show the signal change during illusory- (left bar in each pair) and veridical- (right bar in each pair) rabbit, relative to the control conditions (standard errors indicated in red), for the individually defined cortical ROIs activated by P1, P2, or P3 stimulation (see above). This individual analysis thus confirms that both rabbit conditions led to significant activity increases (relative to control) only within the individual participant-specific cortical representations of P2, but not of P1 or P3. Thus, the rabbit-related activations corresponded to the skin location where stimulation was illusorily felt in the critical rabbit condition.</p

Values and hemispheric ratios of T2’ and rCBV for different degrees of perfusion delay in perfusion-disturbed and corresponding normoperfused tissue.

<p>Values and hemispheric ratios of T2’ and rCBV for different degrees of perfusion delay in perfusion-disturbed and corresponding normoperfused tissue.</p

Values and hemispheric ratios of R2’ und rCBV for different degrees of perfusion delay in perfusion-disturbed and corresponding normoperfused tissue.

<p>Values and hemispheric ratios of R2’ und rCBV for different degrees of perfusion delay in perfusion-disturbed and corresponding normoperfused tissue.</p

Estimates of the CO₂, H₂S and vanillin stimuli with respect to pain, smell or pleasantness, rated by means of a visual analog scale displayed at 3.4–6.6 s after stimulus presentation and ranging from “no pain” to “pain experienced at maximum” or “no odour” to “intensive odour” or “unpleasant” to “very pleasant”.

<p>CO₂ was always painful and never smelled. H₂S or vanillin stimuli were never painful but smelled.</p

Brain activations observed following the intranasal administration of 500 ms pulses of gaseous CO₂ at 75% v/V, which was clearly above pain threshold.

<p><b>Left column:</b> Pain-stimulus associated activations. <b>Middle and right column:</b> Pain-stimulus associated brain activations where the contrast pain > smell was significant (conjunction of second-level t-contrasts 1 −1 0 and 1 0 −1 denoting CO₂, H₂S and vanillin stimuli associated responses respectively). The left Rolandic operculum and insular cortex contralateral to the stimulation displayed these pain predominant activations although activations were observed bilaterally. Statistically significantly activated voxels (p<0.05 FWE-corrected; t>5.14) are presented overlaid (red) on 3D surface renderings of a standard MNI brain (Panel A) and as coloured overlay on the horizontal and sagittal plane of a structural standard T1-weighted MRI template (left). In the right parts of the figure, the colour depth of the displayed voxels reflects the respective t value of the voxel. Furthermore, stimulus related brain activations corresponding to the different stimuli are reported as mean percent signal change in a 5 mm spherical search volume around a selected FWE-corrected peak coordinate (MNI 42 −10 22; bottom). Single subject activations are depicted as dots and the 95% confidence interval as white bars. Results reflect a 12-subject group analysis.</p

Clusters of brain regions, which were activated more following pain than following non-nociceptive stimuli (Conjunction of CO₂>H₂S and CO₂>Vanillin).

<p>The table contains the anatomic location of the voxels with highest voxel level t in the respective region of a 12-subject group analysis. Voxels are given at a threshold of p<0.05 family wise error (FWE) corrected. Coordinates are reported in the MNI space [mm].</p>*<p>contralateral to the stimulus application side.</p