Insula neuroanatomical networks predict interoceptive awareness

Abstract

Interoceptive awareness (IA), the subjective and conscious perception of visceral and physiological signals from the body, has been associated with functions of cortical and subcortical neural systems involved in emotion control, mood and anxiety disorders. We recently hypothesized that IA and its contributions to mental health are realized by a brain interoception network (BIN) linking brain regions that receive ascending interoceptive information from the brainstem, such as the amygdala, insula and anterior cingulate cortex (ACC). However, little evidence exists to support this hypothesis. In order to test this hypothesis, we used a publicly available dataset that contained both anatomical neuroimaging data and an objective measure of IA assessed with a heartbeat detection task. Whole-brain Voxel-Based Morphometry (VBM) was used to investigate the association of IA with gray matter volume (GMV) and the structural covariance network (SCN) of the amygdala, insula and ACC. The relationship between IA and mental health was investigated with questionnaires that assessed depressive symptoms and anxiety. We found a positive correlation between IA and state anxiety, but not with depressive symptoms. In the VBM analysis, only the GMV of the left anterior insula showed a positive association with IA. A similar association was observed between the parcellated GMV of the left dorsal agranular insula, located in the anterior insula, and IA. The SCN linking the right dorsal agranular insula with the left dorsal agranular insula and left hyper-granular insula were positively correlated with IA. No association between GMV or SCN and depressive symptoms or anxiety were observed. These findings revealed a previously unknown association between IA, insula volume and intra-insula SCNs. These results may support development of non-invasive neuroimaging interventions, e.g., neurofeedback, seeking to improve IA and to prevent development of mental health problems, such anxiety disorders.

Keywords: Active inference; Brain interoception network; Insula; Interoception; Interoceptive awareness.

Fig. 1

Insula volume representation of interoceptive awareness. (A) Brain regions of interest with their volumes parcellated based on the Brainnetome Atlas (BNA). hgInsula (hyper-granular insula), dgInsula (dorsal granular insula), vgInsula (ventral granular insula), ddInsula (dorsal dysgranular insula), daInsula (dorsal agranular insula), vaInsula (ventral agranular insula). (B) Right: the left anterior insula was the only region of interest with volume positively associated with IA. Left: For visualization purposes, voxels with T-values >2.5 within the insula were extracted and are displayed overlayed onto a bilateral insula mask image. The shaded gray area surrounding the left anterior insula cluster represents the area 167 (dorsal agranular area) of the Brainnetome Atlas (C) The parcellated volume of the dorsal agranular area is positively correlated with IA, consistent with the result in (B) panel.

Fig. 2

Whole-brain statistical maps of SCNs of each insula sub-region by hemisphere. (A) SCN of the hyper-granular insula (BNA areas 163 and 164). (B) SCN of the dorsal granular insula (BNA areas 171 and 172). (C) SCN of the ventral granular insula (BNA areas 169 and 170). (D) SCN of the dorsal dysgranular insula (BNA areas 173 and 174). (E) SCN of the dorsal agranular insula (BNA areas 165 and 166). (F) SCN of the ventral agranular insula (BNA areas 167 and 168). All images are thresholded at P < 0.001, uncorrected.

Fig. 3

Intra-insula, insula-amygdala, and insula-anterior cingulate SCNs. (A) An SCN of the left and right hyper-granular insula. (B) An SCN of the left and right ventral-agranular insula. (C) An SCN of the left and right dorsal agranular insula. (D) An SCN of the left and right ventral granular insula. (E) An SCN of the left and right dorsal granular insula. (F) An SCN of the left and right dorsal dysgranular insula. Black lines indicate the identified SCN (see Fig. 2) that survived P < 0.001 uncorrected, followed by SVC with P_FWE < 0.05. Large red circles indicate the SCNs positively correlated with interoceptive awareness (Two-tailed Pearson correlations and P < 0.05, uncorrected, controlling for age and TIV). L: left. R: Right. hgINS: hyper-granular insula. vaINS: ventral agranular insula. daINS: dorsal agranular insula. vgINS: ventral granular insula. dgINS: dorsal granular insula. ddINS: dorsal dysgranular insula. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Right dorsal agranular insula SCN linked with interoceptive awareness. (A) Right dorsal agranular insula SCNs (black lines) and SCNs linked with interoceptive awareness (large red circles). Among all SCN linked with interoceptive awareness displayed in Fig. 3, only the SCNs of the right dorsal agranular insula with the left hyper-granular insula (B) and left dorsal agranular insula (C) survived a False Discovery Rate (FDR) test for multiple comparisons (also indicated by red arrows in panel A). L: left. R: Right. hgINS: hyper-granular insula. vaINS: ventral agranular insula. daINS: dorsal agranular insula. vgINS: ventral granular insula. dgINS: dorsal granular insula. ddINS: dorsal dysgranular insula. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)