Figure 1.

Hierarchical organization of homeostatic reflex systems within the brain-gut axis. (a) Homeostatic afferents that report the physiological condition of the GI tract terminate in lamina I of the dorsal horn (corresponding vagal afferent pathways are not shown). The ascending projections of these neurons provide the basis for autonomic reflex arcs at different levels of the brain-gut axis (enteric nervous system reflexes not shown). Limbic, paralimbic, and prefrontal centers provide modulatory influences on the gain of these reflexes. The interoceptive input into these reflexes is generally not consciously perceived except in situations that require an action (e.g., pain) or in pathological conditions. Modified with permission from Reference 82. (b) Cortical modulation of homeostatic afferent input to the central nervous system. Prefrontal regions modulate activity in limbic and paralimbic regions, subregions of the anterior cingulate cortex, and hypothalamus, which in turn regulate activity of descending inhibitory and facilitatory descending pathways through the periaqueductal gray and pontomedullary nuclei. Activity in these corticolimbic pontine networks mediates the effect of cognitions and emotions on the perception of homeostatic feelings, including visceral pain and discomfort. Abbreviations: ANS, autonomic nervous system; dlPFC, dorsolateral PFC; orbFC, orbitofrontal cortex; PAG, periaqueductal gray; RVM, rostroventral medulla; RVLM, rostroventrolateral medulla; VMM, ventromedial medulla; A6, locus coeruleus; Ins, insula; Hypoth, hypothalamus; Amy, amygdala; ACC, anterior cingulate cortex.