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Interactions between brain and spinal cord mediate value effects in nocebo hyperalgesia

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Science  06 Oct 2017:
Vol. 358, Issue 6359, pp. 105-108
DOI: 10.1126/science.aan1221
  • Fig. 1 Study design and behavioral results.

    (A) Experimental design of the nocebo and value manipulation with photos of the designed medical-cream boxes. During the experience induction on day 2, participants were lying in the scanner, but no images were acquired (scanner off). During the test phase, BOLD responses were recorded (scanner on). (B) The blue cream box was estimated as being significantly more expensive than the orange box (t65 = 5.58, P < 0.001, Cohen’s d = 0.69). (C) The behavioral nocebo effect was significantly larger in the expensive group than in the cheap group (t47 = 2.54, P = 0.014, Cohen’s d = 0.74). (D) Time courses of the nocebo effect expressed as slope in a linear regression model (b) differed significantly between groups (t47 = 2.03, P = 0.048, Cohen’s d = 0.58). *P < 0.05; ***P < 0.005; VAS, visual analog scale; bars represent means and error bars represent SEM.

  • Fig. 2 BOLD responses during nocebo hyperalgesia along the descending pain system.

    (A) Left: Main effect of nocebo pooled across groups (nocebo > control) in the spinal cord at spinal segment C6 (t45 = 4.53, P = 0.001, corrected). Right: Respective fMRI signal changes are shown. The statistical t map is overlaid on an average functional image at a visualization threshold of P < 0.01 (uncorrected). au, arbitrary units. (B) Left: Interaction effect between groups [(expensive > control) > (cheap > control)] in the PAG (xyz: 5,–30,–11; t45 = 3.93, P = 0.038, corrected). Right: Respective fMRI signal changes are shown. xyz values are MNI coordinates of the template brain in three-dimensional space. (C) Left: Correlation between nocebo effects and activation strength in the rACC (xyz: 8,38,–5; t45 = 4.74, P = 0.008, corrected). Middle: Both groups show a negative correlation. Right: Respective fMRI signal changes are shown. In (B) and (C), statistical t maps are overlaid on an average structural image, and the significance threshold is set to P < 0.005 (uncorrected) for visualization purposes only. Bars represent means and error bars represent SEM.

  • Fig. 3 Mediation analysis in the rACC.

    The bootstrapped mediation analysis testing the indirect path a*b was significant (ab = 7.45, SEM = 2.92, P = 0.006), indicating that activity in the rACC mediated the treatment effect on behavioral nocebo effects. Numbers indicate path coefficients; numbers in parentheses indicate SEM. *P < 0.05; **P < 0.01; ***P < 0.005.

  • Fig. 4 Connectivity along the descending pain pathway.

    (A) Key candidates for showing expectation-induced modulation in connectivity displayed on a single-subject anatomical image. (B) Coupling strength between rACC and ventral PAG (red) and between spinal cord and right lateral PAG (blue) correlated with behavioral nocebo effects (for statistical results, see fig. S7). (C) Schematic segregation of anatomical PAG subregions (27, 31) overlaid on an average structural image for illustration purposes: the lateral PAG (blue), the ventral PAG (red), and the dorsal PAG (green).

Supplementary Materials

  • Interactions between brain and spinal cord mediate value effects in nocebo hyperalgesia

    A. Tinnermann,* S. Geuter, C. Sprenger, J. Finsterbusch, C. Büchel

    Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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    • Materials and Methods 
    • Figs. S1 to S8 
    • Tables S1 and S2 
    • References 

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