Prediction error and somatosensory insula activation in women recovered from anorexia nervosa

Prediction error and somatosensory insula activation in women recovered from anorexia nervosa


J Psychiatry Neurosci 2016;41(5):304-11

Guido K.W. Frank, MD; Shaleise Collier, PhD; Megan E. Shott; Randall C. O’Reilly, PhD


Background: Previous research in patients with anorexia nervosa showed heightened brain response during a taste reward conditioning task and heightened sensitivity to rewarding and punishing stimuli. Here we tested the hypothesis that individuals recovered from anorexia nervosa would also experience greater brain activation during this task as well as higher sensitivity to salient stimuli than controls.

Methods: Women recovered from restricting-type anorexia nervosa and healthy control women underwent fMRI during application of a prediction error taste reward learning paradigm.

Results: Twenty-four women recovered from anorexia nervosa (mean age 30.3 ± 8.1 yr) and 24 control women (mean age 27.4 ± 6.3 yr) took part in this study. The recovered anorexia nervosa group showed greater left posterior insula activation for the prediction error model analysis than the control group (family-wise error– and small volume–corrected p < 0.05). A group × condition analysis found greater posterior insula response in women recovered from anorexia nervosa than controls for unexpected stimulus omission, but not for unexpected receipt. Sensitivity to punishment was elevated in women recovered from anorexia nervosa. Limitations: This was a cross-sectional study, and the sample size was modest.

Conclusion: Anorexia nervosa after recovery is associated with heightened prediction error–related brain response in the posterior insula as well as greater response to unexpected reward stimulus omission. This finding, together with behaviourally increased sensitivity to punishment, could indicate that individuals recovered from anorexia nervosa are particularly responsive to punishment. The posterior insula processes somatosensory stimuli, including unexpected bodily states, and greater response could indicate altered perception or integration of unexpected or maybe unwanted bodily feelings. Whether those findings develop during the ill state or whether they are biological traits requires further study.

Submitted Mar. 28, 2015; Revised July 10, 2015; Accepted Sept. 4, 2015; Early-released Feb. 2, 2016

Acknowledgements: This work was supported by NIMH grant K23 MH080135-01A2, NIMH grant R01 MH096777, NIMH grant R01MH103436 and by the Davis Foundation Award of the Klarman Family Foundation Grants Program in Eating Disorders (all GKWF). We would also like to thank all individuals who participated in the study and the staff at the Eating Disorders Center Denver.

Affiliations: From the Department of Psychiatry, University of Colorado, Denver, Aurora, CO, USA (Frank, Collier, Shott); the Department of Neuroscience, University of Colorado Denver; Anschutz Medical Campus, Aurora (Frank); and the Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA (O’Reilly).

Competing interests: R. O’Reilly is the Chief Scientific Officer at eCortex Inc. No other competing interests declared.

Contributors: G. Frank, M. Shott and R. O’Reilly designed the study. G. Frank and M. Shott acquired and analyzed the data, which S. Collier also analyzed. G. Frank, S. Collier and M. Shott wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.150103

Correspondence to: G.K.W. Frank, Department of Psychiatry and Neuroscience, Children’s Hospital Colorado, Gary Pavilion A036/B-130, 13123 East 16th Ave., Aurora CO 80045;