DOI: 10.5061/dryad.xgxd254rc
title: Hemispheric divergence of interoceptive processing across psychiatric disorders

description: 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.
description: Please refer to the "Materials and Methods" section of
 the manuscript for full description of data collection, processing, and
 analysis. 
description: # Hemispheric divergence of interoceptive processing across psychiatric
 disorders
 [https://doi.org/10.5061/dryad.xgxd254rc](https://doi.org/10.5061/dryad.xgxd254rc) ## Description of the data and file structure This dataset accompanies the following publication: Adamic et al. (2024) ([https://doi.org/10.7554/eLife.92820.2)](https://doi.org/10.7554/eLife.92820.2). Here we examined interoceptive neural processing using two different functional magnetic resonance imaging (fMRI) probes: bottom-up manipulation of cardiorespiratory signals, and top-down attention towards cardiac and respiratory sensations. Participants performed two tasks preferentially manipulating either bottom-up or top-down streams, respectively: 1) bottom-up cardiorespiratory stimulation via 2mcg infusion of isoproterenol, or a saline placebo in a double-blinded manner, or 2) top-down attention towards cardiorespiratory sensations during physiological rest (Visceral Interoceptive Attention task). Based on established models of insular processing, we examined fMRI co-activation (i.e., "convergence") within the insular cortex across these two tasks, thus identifying potential regions of intersection between ascending and descending streams of interoceptive processing. We examined this convergence in both healthy comparisons and those with anxiety, depression, and/or eating disorders, and how the neural correlates of interoceptive processing may differ in patients with these disorders. In addition to convergence, we also examined the periods of increased bodily expectancy, where participants anticipate possible changes in body state while the body remains at rest: namely, the Anticipation window immediately following the infusion but before any change in heart rate, and the saline placebo dose. During these periods, we examined neural correlates of anticipatory processing within the agranular insular cortex.  Although we do not include full fMRI data, we have CSV files indicating group- and individual-level data (number of convergent voxels and percent signal change, respectively). This fMRI data is accompanied by subjective response data during and following the isoproterenol infusions, and during the VIA task. Please refer to the publication for full details regarding the collection, processing, and analysis of these data. ### Files and variables #### File: Adamicetal2024\_Figure3b\_data.csv ##### Description This file contains the number of voxels within the insular cortex that were co-activated (i.e, "convergent") during BOTH bottom-up cardiorespiratory stimulation (via 2.0mcg isoproterenol) AND top-down attention towards cardiorespiratory sensations (Heart+Lung condition of the Visceral Interoceptive Attention task). We used the Brainnetome atlas to subdivide the insula into three cytoarchitectonic subregions, and report the number of convergent voxels per each subregion bilaterally.  ##### Variables * **group:** ADE (Anxiety, Depression, and/or Eating Disorder patients) or HC (Healthy Comparisons).  * **number_convergent_voxels:** number of voxels co-activated during both bottom-up cardiorespiratory stimulation and top-dow attention towards cardiorespiratory sensations * **hemisphere:** left or right hemispheres of the brain * **insular_brainnetome_subregion:** the Brainnetome subregion, based on the dominant cytoarchitecture (tripartite divsion into granular, dysgranular, and agranular) * **subregion_voxel_count:** total number of voxels in the subregion, as per the Brainnetome atlas  * **proportion_subregion_activated:** proportion of the subregion that was convergent (number_convergent_voxels/subregion_voxel_count) #### File: Adamicetal2024\_Figure4a\_data.csv ##### Description This file contains neural activation (i.e., fMRI percent signal change) within a functionally-defined subregion of the dysgranular mid-insula, that was activated above baseline during two neuroimaging tasks: 1) bottom-up cardiorespiratory stimulation (the peak period of 2.0mcg isoproterenol infusion), and 2) top-down attention towards cardiorespiratory sensations (Heart & Lung attention condition of the Visceral Interoceptive Attention, or VIA task). We used the Brainnetome Atlas to define the dysgranular mid-insula.  ##### Variables * **group**: ADE (Anxiety, Depression, and/or Eating Disorder patients) or HC (Healthy Comparisons)  * **task**: the ISO (Isoproterenol Infusion Task) or VIA (Visceral Interoceptive Attention) tasks, which the neural activation is from * **hemisphere**: left or right hemispheres of the brain * **percent_signal_change**: fMRI neural activation, in units of percent signal change above baseline #### File: Adamicetal2024\_Figure4b\_data.csv  ##### Description This file contains subjective ratings for the intensity of cardiorespiratory sensations, as well as brain activation within a functionally-defined subregion of the mid-insula, during the peak period of cardiorespiratory stimulation via 2.0mcg of isoproterenol. This brain region was activated at the group-level during this task. Each participant did two trials, and all reported values are averaged across both trials.  ##### Variables * **group**: ADE (Anxiety, Depression, and/or Eating Disorder patients) or HC (Healthy Comparisons) * **mean_dial_rating_iso_two_peak**: subjective rating of cardiorespiratory intensity  * **hemisphere**: left or right hemispheres of the brain * **percent_signal_change**: neural activation (fMRI percent signal change above baseline) within the dysgranular mid-insula during the peak period of the isoproterenol infusion #### File: Adamicetal2024\_Figure6b\_data.csv  ##### Description This file contains the number of voxels in the anterior agranular insula (as defined by the Brainnetome atlas) that were activated during two different windows of the isoproterenol infusion task: the Anticipation window and the peak window of the saline dose. These two windows both involve increased expectancies about the body while the body remains at rest: the Anticipation window represents the 45 seconds after the infusion but before the rise in heart rate that occurs during the 2mcg dose. The peak period of the saline placebo dose represents the time window where the rise in cardiorespiratory activity would occur during the 2mcg dose, but does not occur during saline. Because the task is double-blinded, participants are anticipating a possible change in bodily sensations during this time.  ##### Variables * **group:** ADE (Anxiety, Depression, and/or Eating Disorder patients) or HC (Healthy Comparisons) * **epoch:** Anticipation or Saline Peak (two different periods of the isoproterenol infusion task) * **hemisphere:** left or right hemisphere of the brain * **active_voxels:** number of voxels that were activated during the task  * **agranular_brainnetome_voxcount:** number of voxels in the whole agranular insular subregion, as per the Brainnetome atlas  #### File: Adamicetal2024\_Figure6c\_data.csv ##### Description This file contains brain activation (fMRI percent signal change) within the agranular anterior insula during two different windows of the isporterenol infusion task: the Anticipation window and the peak period of the saline placebo dose. These two windows both involve increased expectancies about the body while the body remains at rest: the Anticipation window represents the 45 seconds after the infusion but before the rise in heart rate that occurs during the 2mcg dose. The peak period of the saline placebo dose represents the time window where the rise in cardiorespiratory activity would occur during the 2mcg dose, but does not occur during saline. Because the task is double-blinded, participants are anticipating a possible change in bodily sensations during this time. The agranular insula was defined using the Brainnetome atlas; fMRI activation was extracted from the group-level activation cluster within the agranular insula during the aforementioned windows of this task.  ##### Variables * **group:** ADE (Anxiety, Depression, and/or Eating Disorder patients) or HC (Healthy Comparisons) * **epoch: **Anticipation or Saline Peak (two different periods of interest in the isoproterenol infusion task) * **percent_signal_change:** brain activation compared to baseline  * **hemisphere**: left or right hemisphere of the brain #### File: Adamicetal2024\_Figure7a-b\_data.csv ##### Description This file contains real-time objective heart rate and subjective intensity ratings for the isoproterenol infusion task, during both the 2.0mcg and saline infusions. Subjective intensity ratings were collected via an fMRI-compatible dial.  ##### Variables * **group:** ADE (Anxiety, Depression, and/or Eating Disorder patients) or HC (Healthy Comparisons). * **time_sec:** elapsed time during the task (in seconds) * **dose_mcg**: infusion dose, either 2mcg or Saline  * **HR_bpm_minusbaseline:** second-by-second heart rate relative to baseline, in beats per minute (baseline is the average of the first 45 seconds of the task) * **Dial_AU_minusbaseline: **second-by-second dial rating, relative to baseline, in arbitrary units on a scale of 0-100 (baseline is the average of the first 45 seconds of the task) #### File: Adamicetal2024\_Figure7c\_data.csv ##### Description This file contains subjective ratings on four different scales: 1) Intensity of Cardiac Sensations, 2) Intensity of Respiratory Sensations, 3) State Anxiety, and 4) Excitement, following double-blinded infusions of either saline or 2.0mcg isoproterenol (a beta-adrenergic receptor agonist, causing temporary increases in cardiorespiratory stimulation). Each participant did two trials of each type of infusion, so the final ratings are averaged across both trials.  ##### Variables * **group**: ADE (Anxiety, Depression, and/or Eating Disorder patients) or HC (Healthy Comparisons) * **dose**: 0mcg (Saline) or 2.0mcg (isoproterenol) * **rating_type**: Cardiac (Intensity of Cardiac Sensations), Respiratory (Intensity of Respiratory Sensations), Anxiety, Excitement * **post_iso_rating**: value of the subjective rating following saline or isoproterenol infusions, averaged across 2 trials at each dose #### File: Adamicetal2024\_Figure7d\_data.csv  ##### Description This file contains post-trial ratings for the Visceral Interoceptive Attention (VIA) task. These ratings were collected following trials of directed attention towards three interoceptive sensations (Cardiac, Respiratory, or Gastric) and one exteroceptive control (visual stimulus). All ratings are reported as the average across all trials for that condition, for each participant.  ##### Variables * **group:** ADE (Anxiety, Depression, and/or Eating Disorder patients) or HC (Healthy Comparisons) * **condition:** Cardiac, Respiratory, Gastric, or Exteroceptive condition of the VIA task  * **via_post_trial_intensity_rating:** intensity of sensation rating  ## Code/software No special software is needed, outside of viewing the CSV files. Analysis scripts (written in R) for these data are posted under the OSF preregistration for this project ([https://osf.io/6nxa3/](https://osf.io/6nxa3/)). Full methods and results are reported in the manuscript.