UC Davis

As humans, our daily lives—including the emotions we feel, relationships we form, and decisions we make—play out amongst a complex landscape of sensory experiences. Although there has historically been considerable effort made to characterize the sensations originating in response to stimuli in the external environment (e.g., visual, auditory, gustatory, somatosensory), including extensive interrogation of these sensory systems in non-human animal models, comparatively less attention has been directed toward the sensations originating from the internal milieu—interoceptive signals. As interest in interoception rises, and disordered interoception is increasingly implicated in a variety of human diseases and disorders, there is a growing need for model systems in which we can causally manipulate neurobiology and social environment to gain insights into the mechanisms through which interoceptive signals influence a variety of psychological and physiological processes in health and disease. Existing neuroanatomical evidence suggests that nonhuman primates—and, in particular, macaque monkeys—may offer a critical opportunity for modeling human interoceptive biology. This dissertation aims to determine whether rhesus macaques (Macaca mulatta) exhibit homologous behavioral and neural signatures of interoceptive processing, with a focus on the structure and functions of the insular cortex—the primary sensory cortex for interoceptive signals.

First, I assess the literature on the comparative anatomy of the insula, turning a critical gaze towards homological assumptions being made in animal models of insula structure and function. Through a quantitative synthesis of the extent literature interrogating insula function in rodent models, I provide a previously inaccessible substrate for comparing rodent insular functional organization to that of humans. The results of this synthesis suggest that such rodent models of the insula share few features in common with the human insula, rendering them a potentially poor avenue for further characterization of the insula and its role in interoception. On the other hand, I find that macaques exhibit many key homologies with human insula, including conserved structural and functional organization.

Next, I detail a multimodal investigation of the insula in macaques, utilizing in vivo functional magnetic resonance imaging (MRI), diffusion MRI, and structural MRI to assess whether such methods, which are easily deployed in human populations, provide evidence for conserved structure and function of the insula in macaques. This work provides strong evidence for highly similar patterns of organization in the macaque and human insula, with convergent results across modalities. Further, it suggests that in vivo imaging in macaques has the potential to bridge invasive macaque tract-tracing and non-invasive human imaging work.

Given apparent similarities in interoceptive neurobiology, I then sought to determine whether macaques exhibit behavioral signatures of interoceptive processing consistent with those seen in humans. Using a highly translational eye tracking paradigm adapted from the human infant literature, I present evidence that monkeys spend significantly longer fixating on visual stimuli presented asynchronously vs. synchronously with their cardiac rhythm. Such visual attention patterns mirror the effects shown in human infants and are consistent with the idea that monkeys have similar access to interoceptive sensations like their heartbeats as humans do.

Finally, I bring together the anatomical and behavioral elements of this work in an interoceptive neuroimaging study. I evaluated neural responses to affective touch—a putatively interoceptive signal—in anesthetized monkeys undergoing fMRI scanning. In this work, I found that monkeys exhibit significantly greater activation of the interoceptive-allostatic network—including insula, anterior cingulate cortex, and amygdala—during affective vs. discriminative touch. This pattern of activation parallels that which has been shown in humans, further suggesting evolutionarily conserved interoceptive processing in the bodies and brains of macaques.