Disrupted dorsal mid-insula activation during interoception across psychiatric disorders

OBJECTIVE: Maintenance of bodily homeostasis relies on interoceptive mechanisms in the brain to predict and regulate bodily state. While many experiments report altered neural activation during interoception in specific psychiatric disorders, it is unclear whether a common neural locus underpins transdiagnostic interoceptive differences. METHODS: We conducted a meta-analysis of neuroimaging studies comparing psychiatric groups against healthy controls to identify brain regions exhibiting convergent ‘disrupted activation’ during interoception. We searched bibliographic, neuroimaging, and preprint databases through to May 2020. We extracted 306 foci from 33 studies, including 610 controls and 626 patients with schizophrenia, bipolar or unipolar depression, post-traumatic stress disorder, anxiety, eating disorders, and substance use disorders. Data were pooled using a random-effects model implemented by the activation likelihood estimation algorithm. Our pre-registered primary outcome was the neuroanatomical location of the convergence of peak voxel coordinates. RESULTS: We found convergent ‘disrupted activation’ specific to the left dorsal mid-insula (Z=4.47, p=0.0000038; peak: -36, -2, 14; volume: 928mm(3)). Studies directly contributing to the cluster included patients with bipolar, anxiety, major depression, anorexia, and schizophrenia, and task probes assessing pain, hunger, and interoceptive attention. A series of conjunction analyses against extant meta-analytic datasets revealed that this mid-insula cluster was anatomically distinct from brain regions involved in affective processing and from regions altered by psychological or pharmacological interventions for affective disorders. CONCLUSIONS: We report a transdiagnostic, domain-general difference in interoceptive processing in the left dorsal mid-insula. Disrupted mid-insular activation may represent a neural marker of psychopathology and a putative target for novel interventions.