Cortical and subcortical mapping of the allostatic-interoceptive system in the human brain using 7 Tesla fMRI

Abstract

The brain continuously anticipates the energetic needs of the body and prepares to meet those needs before they arise, called allostasis. In support of allostasis, the brain continually models the sensory state of the body, called interoception. We replicated and extended a large-scale system supporting allostasis and interoception in the human brain using ultra-high precision 7 Tesla functional magnetic resonance imaging (fMRI) (N = 90), improving the precision of subgenual and pregenual anterior cingulate topography combined with extensive brainstem nuclei mapping. We observed over 90% of the anatomical connections published in tract-tracing studies in non-human animals. The system also included regions of dense intrinsic connectivity broadly throughout the system, some of which were identified previously as part of the backbone of neural communication across the brain. These results strengthen previous evidence for a whole-brain system supporting the modeling and regulation of the internal milieu of the body.

Keywords: Biological Sciences/Neuroscience; allostasis; default mode network; interoception; salience network; visceromotor; viscerosensory.

Figure 1.

Key cortical and subcortical regions involved in interoception and allostasis. (A) Using 3 Tesla fMRI resting state connectivity, we showed a unified system consisting of the default mode network (in red) and salience network (in blue), which overlapped in many key cortical visceromotor allostatic regions (in purple) that also serve as ‘rich club’ hubs, in addition to a portion of primary interoceptive cortex (dpIns) (left panel) (19). We reported the system’s connectivity to some subcortical regions known to play a role in control of the autonomic nervous system, the immune system, and the endocrine system such as the thalamus, hypothalamus, hippocampus, ventral striatum, PAG, PBN and NTS (e.g., –26) (right panel) (19). Figures are reproduced with permission from (19). (B) Expanded set of seed regions used in the present analysis. Abbreviations: aMCC: anterior midcingulate cortex; Amy: amygdala; dmIns: dorsal mid insula; dpIns: dorsal posterior insula; DR: dorsal raphe; Hippo: hippocampus; Hypothal: hypothalamus; LC: locus coeruleus; LGN: lateral geniculate nucleus; NAcc: nucleus accumbens; NTS: nucleus of the solitary tract; pACC: pregenual anterior cingulate cortex; PAG: periaqueductal gray; PBN: parabrachial nucleus; SC: superior colliculus; sgACC: subgenual anterior cingulate cortex; SN: substantia nigra; Thal: thalamus; vaIns: ventral anterior insula; VTA: ventral tegmental area.

Figure 2.

Cortico-cortical functional connectivity within the allostatic-interoceptive system. (A) Left column shows cortical seed locations and right column shows bootstrapped functional connectivity maps depicting all voxels whose time course was correlated (p < .05) with that of the seed in more than 950 iterations (out of 1000) by resampling 80% of the sample in each iteration (N = 72). (B) Seed-to-seed functional connectivity matrix shows connectivity strength between each pair of the cortical seeds (p < .05, uncorrected; white color indicates correlation =1; N = 90). (C) The allostatic-interoceptive system showed connecting regions in all the a priori interoceptive and visceromotor control regions. Connecting regions belonging to the ‘rich club’ are labeled in yellow. ‘Rich club’ hubs figure adapted with permission from (105). To avoid Type II errors, which are enhanced with the use of stringent statistical thresholds (175), we opted to separate signal from random noise using replication, according to the mathematics of classical measurement theory (176). Abbreviations: aMCC: anterior mid cingulate cortex; dpIns: dorsal posterior insula; IFG: inferior frontal gyrus; MFG: middle frontal gyrus; mIns: mid insula; pACC: pregenual anterior cingulate cortex; PHG: parahippocampal gyrus; pMCC: posterior mid cingulate cortex; PCC: posterior cingulate cortex; sgACC: subgenual anterior cingulate cortex; STS: superior temporal sulcus; vaIns: ventral anterior insula.

Figure 3.

Subcortico-cortical intrinsic connectivity within the allostatic-interoceptive system. (A) Left column shows subcortical seed locations and right column shows bootstrapped functional connectivity discovery maps depicting all cortical voxels whose time course was correlated (p < .05) with that of the seed in more than 950 iterations (out of 1000) by resampling 80% of the sample in each iteration (N = 72). (B) Seed-to-seed functional connectivity matrix shows connectivity strength between pairs of subcortical and cortical seeds (p < .05, uncorrected; gray color indicates subthreshold correlations; N = 90). (C) Conjunction map shows the number of binarized maps (p < .05) with shared connecting regions (ranging from 9 to 14). Abbreviations: dAmy: dorsal amygdala; mdThal: mediodorsal thalamus; LGN: lateral geniculate nucleus; Hypothal: hypothalamus; Hippo: hippocampus; NAcc: nucleus accumbens; PAG: periaqueductal gray; DR: dorsal raphe; SC: superior colliculus; SN: substantia nigra; VTA: ventral tegmental area; PBN: parabrachial nucleus; LC: locus coeruleus; VSM: medullary viscero-sensory-motor nuclei complex corresponding to the nucleus tractus solitarius.

Figure 4.

Subcortico-subcortical intrinsic connectivity within the allostatic-interoceptive system. (A) Left column shows subcortical seed locations and right column shows bootstrapped functional connectivity discovery maps depicting all subcortical voxels whose time course was correlated (p < .05) with that of the seed in more than 950 iterations (out of 1000) by resampling 80% of the sample in each iteration (N = 72). (B) Seed-to-seed functional connectivity matrix showed connectivity strength between each pair of the subcortical seeds (p < .05, uncorrected; white color indicates correlation =1 and gray color indicates subthreshold correlations; N = 90). Several seeds had functional connectivity with a subset of voxels within target ROIs, as shown by binarized maps at p < .05 (target ROI outline is shown in blue).

Figure 5.

Summary of the allostatic-interoceptive system based on 7 Tesla fMRI functional connectivity. (A) Circuit diagram indicates dense within-system connectivity between the 21 cortical and subcortical seeds. All seeds are shown as spherical nodes located at their respective centers of gravity. Pairwise connectivity strengths between ROIs are shown as edges between nodes (ranging from p < .05 in red to p < 10⁻¹⁰ in yellow, uncorrected; N = 90). Nodes and edges in the glass brain were visualized using BrainNet Viewer (177) (B) Conjunction map shows the number of binarized maps (p < .05) that shared overlapping regions (ranging from 15 to 21, total number of cortical and subcortical seeds = 21).