An active inference theory of allostasis and interoception in depression

Abstract

In this paper, we integrate recent theoretical and empirical developments in predictive coding and active inference accounts of interoception (including the Embodied Predictive Interoception Coding model) with working hypotheses from the theory of constructed emotion to propose a biologically plausible unified theory of the mind that places metabolism and energy regulation (i.e. allostasis), as well as the sensory consequences of that regulation (i.e. interoception), at its core. We then consider the implications of this approach for understanding depression. We speculate that depression is a disorder of allostasis, whose myriad symptoms result from a 'locked in' brain that is relatively insensitive to its sensory context. We conclude with a brief discussion of the ways our approach might reveal new insights for the treatment of depression.This article is part of the themed issue 'Interoception beyond homeostasis: affect, cognition and mental health'.

Keywords: fMRI; interoception; major depressive disorder; prediction; visceromotor.

Figure 1.

A large-scale system for allostasis in the human brain. We consulted anterograde and retrograde tract-tracing studies in macaque monkeys to select eight seed regions in limbic cortices with monosynaptic connections to midbrain and brainstem regions that are known to control the immune, endocrine and autonomic nervous systems in the service of allostasis (for details and coordinates, see [52]). For each seed region, we computed a ‘discovery map’ of voxels whose timecourse correlated with the seed region. (a) A conjunction of all eight maps presented in the volume to display subcortical regions. (b) A conjunction of maps depicted on the cortical surface. (c) Cluster analysis of the eight discovery maps revealed the system for allostasis was composed of two large-scale intrinsic networks (shown in red and blue) that share several hubs (shown in purple). Hubs belonging to the brain's ‘rich club’ are labelled in yellow. Rich club hubs figure adapted with permission from [54]. Maps were constructed with resting state BOLD data from 280 participants binarized at p < 10⁻⁵, and then replicated on a second sample of 270 participants. aMCC, anterior midcingulate cortex; dpIns, dorsal posterior insula; IFG, inferior frontal gyrus; ITG, inferior temporal gyrus; vaIns, ventral anterior insula; MCC, midcingulate cortex; PHG, parahippocampal gyrus; pMCC, posterior midcingulate cortex; PostCG, postcentral gyrus; STS, superior temporal sulcus. (d) Reliable subcortical connections, thresholded p < 0.05 uncorrected. PAG, periaqueductal grey; hypothal, hypothalamus; PBN, parabrachial nucleus; vStriat, ventral striatum; NTS, nucleus of the solitary tract.

Figure 1.

A large-scale system for allostasis in the human brain. We consulted anterograde and retrograde tract-tracing studies in macaque monkeys to select eight seed regions in limbic cortices with monosynaptic connections to midbrain and brainstem regions that are known to control the immune, endocrine and autonomic nervous systems in the service of allostasis (for details and coordinates, see [52]). For each seed region, we computed a ‘discovery map’ of voxels whose timecourse correlated with the seed region. (a) A conjunction of all eight maps presented in the volume to display subcortical regions. (b) A conjunction of maps depicted on the cortical surface. (c) Cluster analysis of the eight discovery maps revealed the system for allostasis was composed of two large-scale intrinsic networks (shown in red and blue) that share several hubs (shown in purple). Hubs belonging to the brain's ‘rich club’ are labelled in yellow. Rich club hubs figure adapted with permission from [54]. Maps were constructed with resting state BOLD data from 280 participants binarized at p < 10⁻⁵, and then replicated on a second sample of 270 participants. aMCC, anterior midcingulate cortex; dpIns, dorsal posterior insula; IFG, inferior frontal gyrus; ITG, inferior temporal gyrus; vaIns, ventral anterior insula; MCC, midcingulate cortex; PHG, parahippocampal gyrus; pMCC, posterior midcingulate cortex; PostCG, postcentral gyrus; STS, superior temporal sulcus. (d) Reliable subcortical connections, thresholded p < 0.05 uncorrected. PAG, periaqueductal grey; hypothal, hypothalamus; PBN, parabrachial nucleus; vStriat, ventral striatum; NTS, nucleus of the solitary tract.

Figure 2.

A depiction of predictive coding in the human brain. (a) We identified key limbic cortices (in blue) that provide cortical control of the body's internal milieu. Primary motor cortex is depicted in red, and primary sensory regions are in yellow. For simplicity, only primary visual, interoceptive and somatosensory cortices are shown; subcortical regions are not shown. (b) Limbic cortices initiate allostatic predictions to the hypothalamus and brainstem nuclei (e.g. periaqueductal grey, parabrachial nucleus, nucleus of the solitary tract) to regulate the autonomic, neuroendocrine and immune systems (solid lines). The incoming sensory inputs from the internal milieu of the body are carried along the vagus nerve and small diameter C and Aδ fibres to limbic regions (dotted lines). Comparisons between prediction signals and ascending sensory input results in prediction error that is available to update the brain's internal model. In this way, prediction errors are learning signals and can adjust subsequent predictions. (c) Efferent copies of allostatic predictions are sent to motor cortex as motor predictions (solid lines) and prediction errors are sent from motor cortex to limbic cortices (dotted lines). (d) Sensory cortices receive sensory predictions from several sources. They receive efferent copies of allostatic predictions (black lines) and efferent copies of motor predictions (red lines). Sensory cortices with less well-developed lamination (e.g. primary interoceptive cortex) also send sensory predictions to sensory cortices that are more well developed (e.g. in this figures, somatosensory and primary visual cortices) (orange lines). For simplicity's sake, prediction errors are not depicted in panel (d). sgACC, subgenual anterior cingulate cortex; vmPFC, ventromedial prefrontal cortex; pgACC, pregenual anterior cingulate cortex; dmPFC, dorsomedial prefrontal cortex; MCC, midcingulate cortex, is ventral to dmPFC and SMA; vaIns, ventral anterior insula; daIns, dorsal anterior insula; vlPFC, ventrolateral prefrontal cortex; SMA, supplementary motor area; PMC, premotor cortex; m/pIns, mid/ posterior insula (primary interoceptive cortex); SSC, somatosensory cortex; V1, primary visual cortex; and MC, motor cortex (for relevant neuroanatomy references, see [52]).