Figure 1.

Experimental design and task performance. (a) In each trial, a painful or nonpainful thermal stimulus was applied to the dorsum of the hand for 4 s. During stimulation a task cue (dot) appeared, and participants responded by speeded button press, depending on instructions indicating whether the stimulus was to be considered “signal” or “noise.” In signal trials a button press was required by the task, while in noise trials task instructions required participants to refrain from pressing the button. (b) Heterozygous R221W carriers made more total button-press errors than controls in distinguishing signal from noise during painful stimulation (P < 0.001). (c) Signal and noise distributions for heterozygous R221W carriers and controls exhibited wider separation between signal and noise (task sensitivity, d′) for controls than carriers. (d) d′ covaried with R221W carriers’ C-afferent nerve fiber density (C-NFD), indicating a relationship between behavioral and C-afferent phenotype. To illustrate the full range of task performance variance in the R221W mutation phenotype, additional data from a separate dataset of three homozygous R221W carriers were included.