Common brain activations for painful and non-painful aversive stimuli

Abstract

Background: Identification of potentially harmful stimuli is necessary for the well-being and self-preservation of all organisms. However, the neural substrates involved in the processing of aversive stimuli are not well understood. For instance, painful and non-painful aversive stimuli are largely thought to activate different neural networks. However, it is presently unclear whether there is a common aversion-related network of brain regions responsible for the basic processing of aversive stimuli. To help clarify this issue, this report used a cross-species translational approach in humans (i.e. meta-analysis) and rodents (i.e. systematic review of functional neuroanatomy).

Results: Animal and human data combined to show a core aversion-related network, consisting of similar cortical (i.e. MCC, PCC, AI, DMPFC, RTG, SMA, VLOFC; see results section or abbreviation section for full names) and subcortical (i.e. Amyg, BNST, DS, Hab, Hipp/Parahipp, Hyp, NAc, NTS, PAG, PBN, raphe, septal nuclei, Thal, LC, midbrain) regions. In addition, a number of regions appeared to be more involved in pain-related (e.g. sensory cortex) or non-pain-related (e.g. amygdala) aversive processing.

Conclusions: This investigation suggests that aversive processing, at the most basic level, relies on similar neural substrates, and that differential responses may be due, in part, to the recruitment of additional structures as well as the spatio-temporal dynamic activity of the network. This network perspective may provide a clearer understanding of why components of this circuit appear dysfunctional in some psychiatric and pain-related disorders.

Figure 1

Pain and aversion networks in humans. Results of meta-analysis for human pain-related (left) and aversion-related (right) studies. Pain-related (left) activations (see Additional file 1: Table S1A for related coordinates): Red represents peak voxels in a local neighbourhood, blue represents significant extended clusters. Aversion-related (right) activations (see Additional file 1: Table S1B for related coordinates): Red represents peak voxels in a local neighbourhood, yellow represents significant extended clusters. All results are family-wise error rate whole-brain corrected at p < 0.05. Numbers below each axial section represent the Z coordinates. The anatomical reference space is MNI 152 (i.e. the average of 152 healthy MRI brain scans). The aversion network was previously reported by [5] and is reprinted here with permission from Frontiers in Integrative Neuroscience.

Figure 2

Overlap of pain- and aversion-related networks in humans. Results of meta-analyses for human pain- (blue) and aversion- (yellow) related studies (top row), overlapping activations (green; top row and isolated in bottom row), and a corresponding table of associated brain regions. All results are family-wise error rate whole-brain corrected at p < 0.05. See Table 3 for overlap coordinates.

Figure 3

Similarities and differences in pain- and non-pain-related aversive circuitry. Sagittal section of a human brain summarizing the main results across species; illustrating core areas consistent with responses to all pain- and non-pain-related aversive stimuli (green), those responding to painful (blue) or non-painful (yellow) aversive stimuli alone, and regions implicated mainly in non-human animal studies (beige).