Identifying a network of brain regions involved in aversion-related processing: a cross-species translational investigation

Abstract

The ability to detect and respond appropriately to aversive stimuli is essential for all organisms, from fruit flies to humans. This suggests the existence of a core neural network which mediates aversion-related processing. Human imaging studies on aversion have highlighted the involvement of various cortical regions, such as the prefrontal cortex, while animal studies have focused largely on subcortical regions like the periaqueductal gray and hypothalamus. However, whether and how these regions form a core neural network of aversion remains unclear. To help determine this, a translational cross-species investigation in humans (i.e., meta-analysis) and other animals (i.e., systematic review of functional neuroanatomy) was performed. Our results highlighted the recruitment of the anterior cingulate cortex, the anterior insula, and the amygdala as well as other subcortical (e.g., thalamus, midbrain) and cortical (e.g., orbitofrontal) regions in both animals and humans. Importantly, involvement of these regions remained independent of sensory modality. This study provides evidence for a core neural network mediating aversion in both animals and humans. This not only contributes to our understanding of the trans-species neural correlates of aversion but may also carry important implications for psychiatric disorders where abnormal aversive behavior can often be observed.

Keywords: animal models; aversion; imaging; meta-analysis; translational.

Figure 1

Aversion network in humans. Results of meta-analysis for human aversion-related studies. Yellow represents peak voxels in a local neighborhood, blue represents significant extended clusters. All results are family wise error rate whole-brain corrected at p < 0.05. The numbers below each axial section represent the Z coordinate. Note that each area is noted only once unilaterally for clarity. See Tables 1 and 2 for related coordinates and Figure 2 for an illustrated summary. Abbreviation: ACC, anterior cingulate cortex; AI, anterior insula; Amyg, amygdala; DMPFC, dorsomedial prefrontal cortex; DS, dorsal striatum; Parahipp/Hipp, parahippocampus/hippocampus; RTG, rostral temporal gyri; SMA, secondary motor cortex; Thal, thalamus; VLOFC, ventrolateral orbitofrontal cortex.

Figure 2

Core aversion-related circuitry. Sagittal section of a human brain illustrating core areas consistent with all data (dark blue; for abbreviations see Figure 1 or abbreviations list) as well as those implicated mainly in non-human animal studies (light beige) but which may be core areas across mammals. Abbreviation: BNST, bed nucleus of the stria terminalis; Hab, habenula; Hyp, hypothalamus; NAc, nucleus accumbens; NTS, nucleus of the tractus solitarius; PAG, periaqueductal gray; PBN, parabrachial nucleus.