Altered interoceptive activation before, during, and after aversive breathing load in women remitted from anorexia nervosa

Abstract

Background: The neural mechanisms of anorexia nervosa (AN), a severe and chronic psychiatric illness, are still poorly understood. Altered body state processing, or interoception, has been documented in AN, and disturbances in aversive interoception may contribute to distorted body perception, extreme dietary restriction, and anxiety. As prior data implicate a potential mismatch between interoceptive expectation and experience in AN, we examined whether AN is associated with altered brain activation before, during, and after an unpleasant interoceptive state change.

Methods: Adult women remitted from AN (RAN; n = 17) and healthy control women (CW; n = 25) underwent functional magnetic resonance imaging during an inspiratory breathing load paradigm.

Results: During stimulus anticipation, the RAN group, relative to CW, showed reduced activation in right mid-insula. In contrast, during the aversive breathing load, the RAN group showed increased activation compared with CW in striatum and cingulate and prefrontal cortices (PFC). The RAN group also showed increased activation in PFC, bilateral insula, striatum, and amygdala after stimulus offset. Time course analyses indicated that RAN responses in interoceptive processing regions during breathing load increased more steeply than those of CW. Exploratory analyses revealed that hyperactivation after breathing load was associated with markers of past AN severity.

Conclusions: Anticipatory deactivation with a subsequent exaggerated brain response during and after an aversive body state may contribute to difficulty predicting and adapting to internal state fluctuation. Because eating changes our interoceptive state, restriction may be one method of avoiding aversive, unpredictable internal change in AN.

Keywords: Anorexia nervosa; aversive; breathing load; functional magnetic resonance imaging (fMRI); interoception.

Figure 1. Breathing Load Task Design

Participants wore a nose clip and breathed through a hose that intermittently restricted their breathing via 40 cm H20/L/sec loads. During scanning, participants completed a continuous performance task. Participants were instructed to press a left or right button in response to left or right pointing arrows, respectively. During “anticipation” conditions, colored rectangles behind these arrows (mean duration 6 s) signaled the likelihood of an upcoming breathing load period (duration 40 s). A blue rectangle signaled no subsequent breathing load, and a yellow rectangle signaled a 25% chance of subsequent breathing load. A post-load period (mean duration 2 s) followed all breathing load conditions. The task was presented in an event-related design in two runs (total time =17 min and 4 s; TR = 2s). Across both runs, 34 baseline conditions and 32 anticipation conditions were jittered. Eight anticipation conditions were followed by breathing load. All conditions were jittered to optimize resolution of the hemodynamic response function.

Figure 2. Within-condition Group Differences in Peak Activation

A) During breathing load anticipation, the RAN group showed reduced activation in the right mid-insula compared with controls. RAN participants deactivated right mid-insula during aversive interoceptive stimulus anticipation, whereas healthy controls activated this region. B) During breathing load, the RAN group showed increased activation compared with controls in bilateral PCC, right dACC, bilateral IFG and left MFG, left putamen, and right caudate. C) After breathing load, the RAN group showed increased activation compared with controls in bilateral anterior insula, mid-insula, and posterior insula, (graph shown for right mid-insula), bilateral caudate and putamen (graph shown for right putamen), left amygdala, bilateral PCC, bilateral ACC, bilateral IFG and left MFG, bilateral putamen and caudate, and bilateral amygdala. Error bars represent standard error of the mean. When multiple clusters are shown, the graphs correspond to circled clusters. RAN, women remitted from anorexia nervosa; CW, healthy control women; PCC, posterior cingulate cortex; IFG, inferior frontal gyrus; MFG, middle frontal gyrus; dACC, dorsal anterior cingulate cortex; amy, amygdala.

Figure 3. Group Differences in Activation Time Course

Group x Time interaction results suggested that the time course of activation in RAN participants statistically significantly differed from those of controls in left mid-insula and left IFG. Additional clusters in which time course differed between groups are shown in Figure S3. Time course graphs for anticipation, breathing load, and post-breathing load conditions are shown in in light gray and with gray shading the background. Error bars represent standard error of the mean. RAN, women remitted from anorexia nervosa; CW, healthy control women; IFG, inferior frontal gyrus.