Interoceptive mismatch is a perceptual discrepancy between ascending bodily signals and higher-order representation of anticipated physiological state. This mismatch is implicated in emotion inference within predictive coding models. We present autonomic perceptual mismatch as a novel in vivo measure of the discrepancy between actual and perceived autonomic signals, for clinical application to brain-body interactions, specifically in the expression of anxiety. Joint hypermobility is disproportionately found in individuals with anxiety disorders, revealing an underexplored link between the mind and body. Atypical autonomic reactivity represents a likely mediating mechanism consequent of altered connective tissue within the vasculature and nervous system. The present fMRI study determined 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.

The authors have declared no competing interest.

Funding for this project came via a fellowship to JAE (MRC MR/K002643/1). JAE was also supported by MQ Transforming Mental Health and Versus Arthritis (MQF 17/19).

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Brighton and Hove National Research Ethics Service (NREC) committee gave ethical approval for this work (ref 12/LO/1942).

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