Disrupted Dorsal Mid-Insula Activation During Interoception Across Psychiatric Disorders

Abstract

Objective: Maintenance of bodily homeostasis relies on interoceptive mechanisms in the brain to predict and regulate bodily state. While altered neural activation during interoception in specific psychiatric disorders has been reported in many studies, it is unclear whether a common neural locus underpins transdiagnostic interoceptive differences.

Methods: The authors conducted a meta-analysis of neuroimaging studies comparing patients with psychiatric disorders with healthy control subjects to identify brain regions exhibiting convergent disrupted activation during interoception. Bibliographic, neuroimaging, and preprint databases through May 2020 were searched. A total of 306 foci from 33 studies were extracted, which included 610 control subjects and 626 patients with schizophrenia, bipolar or unipolar depression, posttraumatic stress disorder, anxiety, eating disorders, or substance use disorders. Data were pooled using a random-effects model implemented by the activation likelihood estimation algorithm. The preregistered primary outcome was the neuroanatomical location of the convergence of peak voxel coordinates.

Results: Convergent disrupted activation specific to the left dorsal mid-insula was found (Z=4.47, peak coordinates: -36, -2, 14; volume: 928 mm³). Studies directly contributing to the cluster included patients with bipolar disorder, anxiety, major depression, anorexia, and schizophrenia, assessed with task probes including pain, hunger, and interoceptive attention. A series of conjunction analyses against extant meta-analytic data sets 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: These results reveal transdiagnostic, domain-general differences 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.

Keywords: Affect; Cognitive Neuroscience; Emotion; Homeostasis; Insula; Interoception; Neuroimaging; Transdiagnostic.

Figure 1. Flow diagram of study selection.

Figure 2. Transdiagnostic disrupted activation between psychiatric and control participants during interoceptive processing derived from ALE meta-analysis (k=33).

A single significant cluster was found (p<0.05 FWE-corrected; cluster-forming threshold p<0.001; 1000 threshold permutations) in the left dorsal mid-insula (Z=4.47, p=0.0000038; peak: -36, -2, 14; volume: 928mm³) viewed in sagittal (A), axial (B), and coronal (C) sections.

Figure 3. Conjunction analyses indicating significant differences in convergence between disrupted transdiagnostic interoceptive activation and general affect circuitry.

Disrupted interoceptive activation differed significantly from general affect circuitry in the left dorsal mid-insula (visible in A and B) (Z=3.29, p<0.001; peak: -34, -4, 16; volume: 872mm³) and the left entorhinal/perirhinal cortex (visible in C) (Z=2.75, p=0.003, peak: -20, -18, -20; volume: 272mm³) (shown in orange). General affect circuitry preferentially activated a large cluster including the left anterior insula (visible in A) and bilateral inferior frontal gyri, occipito-temporal regions (visible in B) and thalamus (visible in C). There were no regions of significant overlap (see Table S5 for full list of regions).

Figure 4. Conjunction analysis revealing significant differences in convergence between disrupted interoceptive activation and regions of neural change following treatment with antidepressant medication.

Disrupted interoceptive activation differed significantly from the neural changes associated with antidepressant medication treatment in the left dorsal mid-insula (orange cluster, visible in A) (Z=2.33, p=0.01; peak: -42, 2, 10; volume: 408mm³). Changes following antidepressant treatment preferentially converged on clusters in the bilateral amygdala (right: Z=1.87, p=0.031; peak: 34, -6, -22; volume: 256mm³; left: Z=2.23, p=0.013; peak: -22, 2, -22; volume: 256mm³) (blue cluster, visible in A) and the medial globus pallidus (Z=2.23, p=0.013; peak: -15, -6, -10.5; volume: 408mm³) (blue cluster, visible in B). There were no significantly overlapping regions.