The dorsal anterior cingulate cortex is selective for pain: Results from large-scale reverse inference

Abstract

Dorsal anterior cingulate cortex (dACC) activation is commonly observed in studies of pain, executive control, conflict monitoring, and salience processing, making it difficult to interpret the dACC's specific psychological function. Using Neurosynth, an automated brainmapping database [of over 10,000 functional MRI (fMRI) studies], we performed quantitative reverse inference analyses to explore the best general psychological account of the dACC function P(Ψ process|dACC activity). Results clearly indicated that the best psychological description of dACC function was related to pain processing--not executive, conflict, or salience processing. We conclude by considering that physical pain may be an instance of a broader class of survival-relevant goals monitored by the dACC, in contrast to more arbitrary temporary goals, which may be monitored by the supplementary motor area.

Keywords: Neurosynth; dACC; pain; reverse inference.

Fig. 1.

The dorsal anterior cingulate cortex (dACC). (A) The anatomical outlines of the dorsal anterior cingulate cortex (dACC), rostral anterior cingulate cortex (rACC), supplementary motor area (SMA), and presupplementary motor area (pre-SMA). (B) The Neurosynth forward inference map for the term “dACC” showing its peak effect (noted by the brightest part of the activation cluster) in the SMA/pre-SMA (not in the dACC). (C) The Neurosynth forward inference map for the term “anterior cingulate” also showing its peak effect in the SMA/pre-SMA. Maps use Neurosynth’s standard false discovery rate (FDR) criterion of P < 0.01.

Fig. 2.

Neurosynth forward inference maps link several processes to the dACC. Forward inference maps reflect the probability of a region being present when a particular psychological process or task is invoked [P(dACC activity|Ψ process)]. Shown here are forward inference maps for several terms in the categories of pain, executive, conflict, and salience processes that have all been linked to the dACC in prior work. Outlines show the anatomical boundaries for the dACC (bottom) and the SMA/pre-SMA (top). Maps use Neurosynth’s standard FDR criterion of P < 0.01.

Fig. 3.

Neurosynth reverse inference maps indicate that the dACC is selective for pain. Reverse inference maps reflect the probability that a particular psychological process or task was invoked given the presence of activity in a particular region [P(Ψ process|dACC activity)]. Reverse inference maps for executive, conflict, and salience processes show almost no evidence that dACC activity can be explained in terms of those processes. In contrast, these maps show clear evidence that the dACC can be reliably linked to pain processes. Maps use Neurosynth’s standard FDR criterion of P < 0.01.

Fig. 4.

Neurosynth reverse inference maps indicate the anterior insula (AI) is selective for pain. Reverse inference maps covering bilateral AI are shown for the terms “pain,” “somatosensory,” “emotion,” “conflict,” “salience,” and “executive.” Only the terms “pain” and “somatosensory” show substantial coverage of the AI. However, in both hemispheres, most of the AI shows exclusive effects for pain. Outlines show the anatomical boundaries for the AI. Maps use Neurosynth’s standard FDR criterion of P < 0.01.

Fig. 5.

Comparison of reverse inference effects throughout the dACC. (A) Plotted posterior probabilities from Neurosynth reverse inference maps for pain, executive, conflict, and salience processes at eight foci on the midline of dACC. MNI coordinates are listed on the bar graphs. The dashed lines at 0.50 indicate the null hypothesis (i.e., no reverse inference evidence). All starred bars (*) had Z-scores of ≥3.1, P < 0.001, and “ns” indicates not significant at this threshold. For each location where “pain” was a reliable reverse inference term, “pain” was also a significantly stronger reverse inference term than all other terms (P < 0.001). (B) The average posterior probabilities across the eight foci for pain, executive, conflict, and salience.

Fig. S1.

Neurosynth reverse inference maps for emotion-related terms. Distress-related terms, including “negative affect,” “distress,” and “fear” yield reliable reverse inference effects in the dACC (but not terms such as “emotion,” “negative,” “anger,” “anxiety,” or “depression”). Maps use Neurosynth’s standard FDR criterion of P < 0.01.

Fig. 6.

Survival-relevant goal conflicts in the dACC. Several survival goal conflicts produce activations in the dACC. Pain foci were derived from the two strongest reverse inference effects from Neurosynth. Social rejection activation comes from a meta-analysis (34). Hunger (35), breathlessness (–38), and thirst (–41) foci all come from individual studies.