Hemispheric divergence of interoceptive processing across psychiatric disorders

Interactions between top-down attention and bottom-up visceral inputs are
assumed to produce conscious perceptions of interoceptive states, and
while each process has been independently associated with aberrant
interoceptive symptomatology in psychiatric disorders, the neural
substrates of this interface are unknown. We conducted a preregistered
functional neuroimaging study of 46 individuals with anxiety, depression,
and/or eating disorders (ADE) and 46 propensity-matched healthy
comparisons (HC), comparing their neural activity across two interoceptive
tasks differentially recruiting top-down or bottom-up processing within
the same scan session. During an interoceptive attention task, top-down
attention was voluntarily directed towards cardiorespiratory or visual
signals, whereas during an interoceptive perturbation task, intravenous
infusions of isoproterenol (a peripherally-acting beta-adrenergic receptor
agonist) were administered in a double-blinded and placebo-controlled
fashion to drive bottom-up cardiorespiratory sensations. Across both
tasks, neural activation converged upon the insular cortex, localizing
within the granular and ventral dysgranular subregions bilaterally.
However, contrasting hemispheric differences emerged, with the ADE group
exhibiting (relative to HCs) an asymmetric pattern of overlap in the left
insula, with increased or decreased proportions of co-activated voxels
within the left or right dysgranular insula, respectively. The ADE group
also showed less agranular anterior insula activation during periods of
bodily uncertainty (i.e., when anticipating possible isoproterenol-induced
changes that never arrived). Finally, post-task changes in insula
functional connectivity were associated with anxiety and depression
severity. These findings confirm the dysgranular mid-insula as a key
cortical interface where attention and prediction meet real-time bodily
inputs, especially during heightened awareness of interoceptive states.
Further, the dysgranular mid-insula may indeed be a “locus of disruption”
for psychiatric disorders.