Figure 2.

Cortical responses depending on signal-to-noise separation during painful stimulation and connectivity as a function of subjective escape urge. Heterozygous R221W carriers’ broad variance on task performance (b) uncovers AI activation in signal-to-noise discrimination as a function of d′ (a). The closer the task-dependent signal-to-noise discrimination (as indexed by d′) to the healthy control range, the greater the activation in AI. To illustrate the full range of task performance variance in the R221W mutation phenotype, (b) also plots d′ data from a separate dataset of three homozygotes. The carriers’ signal-sensitive AI activation cluster was used as a seed in a PPI analysis with “urge to move” slopes as covariates (d), revealing functional connectivity between AI and MCC during pain in controls (c), increasing as a function of the subjective urge to move away from the stimulus. No such interaction was seen in the carrier group, which reported a significantly lower and later urge to move during pain (d), VAS = visual analog scale rating of urge (adapted with permission from Testa et al. 2019). These results indicate that adaptive voluntary responses to pain rely on task-dependent signal-to-noise discrimination processes in AI, in conjunction with functional communication with MCC; impairment of this signal-to-action pathway may underlie the R221W carrier group’s pain underreaction bias. Z statistic images were thresholded using clusters determined by Z > 3.4 and a (corrected) cluster significance threshold of P = 0.05, using the GRF theory (Worsley 2011).