The Neural Correlates of Autonomic Interoception: Perceptual Mismatch and Clinical Implications

Interoceptive mismatch is a perceptual discrepancy between ascending bodily signals and higher-order representation of anticipated physiological state. Inspired by predictive coding models, we present autonomic perceptual mismatch as a measure of this discrepancy for clinical application to brain-body interactions. Joint hypermobility is disproportionately found in individuals with anxiety disorders. Previous work has shown atypical autonomic reactivity represents a likely mediating mechanism consequent of altered connective tissue in the vasculature and nervous system. This fMRI study investigates the neural substrates of autonomic perceptual mismatch on affective processing in the hypermobility-anxiety interaction. We compared regional brain activity during emotional face processing in participants with and without hypermobility and generalized anxiety disorder diagnosis, then tested association with perceptual mismatch. In the brain, autonomic perceptual mismatch correlated with enhanced activation in emotion processing and autonomic control regions, notably anterior cingulate cortex. Anxious individuals exhibited increased mid-insula cortex activity in relation to perceptual mismatch. Activity was decreased within the inferior frontal gyrus, a region implicated in cognitive control. Dysautonomia mediated the link between hypermobility and anxiety. Together, these findings support a neural basis of an autonomic perceptual mismatch model in a clinical sample. This is supported by the engagement of neural systems for emotion-cognition and interoception. This work highlights convergent aspects of neurodiversity, mental health, connective tissue disorders and brain-body interactions relevant to precision healthcare.