Reduced salience and default mode network activity in women with anorexia nervosa

Reduced salience and default mode network activity in women with anorexia nervosa

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J Psychiatry Neurosci 2014; 39(3): 178-188

Kristina L. McFadden, PhD; Jason R. Tregellas, PhD; Megan E. Shott, BS; Guido K.W. Frank, MD

Department of Psychiatry, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colo., USA


Background: The neurobiology of anorexia nervosa is poorly understood. Neuronal networks contributing to action selection, self-regulation and interoception could contribute to pathologic eating and body perception in people with anorexia nervosa. We tested the hypothesis that the salience network (SN) and default mode network (DMN) would show decreased intrinsic activity in women with anorexia nervosa and those who had recovered from the disease compared to controls. The basal ganglia (BGN) and sensorimotor networks (SMN) were also investigated.

Methods: Between January 2008 and January 2012, women with restricting-type anorexia nervosa, women who recovered from the disease and healthy control women completed functional magnetic resonance imaging during a conditioned stimulus task. Network activity was studied using independent component analysis.

Results: We studied 20 women with anorexia nervosa, 24 recovered women and 24 controls. Salience network activity in the anterior cingulate cortex was reduced in women with anorexia nervosa (p = 0.030; all results false-discovery rate– corrected) and recovered women (p = 0.039) compared to controls. Default mode network activity in the precuneus was reduced in women with anorexia compared to controls (p = 0.023). Sensorimotor network activity in the supplementary motor area (SMA; p = 0.008), and the left (p = 0.028) and right (p = 0.002) postcentral gyrus was reduced in women with anorexia compared to controls; SMN activity in the SMA (p = 0.019) and the right postcentral gyrus (p = 0.008) was reduced in women with anorexia compared to recovered women. There were no group differences in the BGN.

Limitations: Differences between patient and control populations (e.g., depression, anxiety, medication) are potential confounds, but were included as covariates.

Conclusions: Reduced SN activity in women with anorexia nervosa and recovered women could be a trait-related biomarker or illness remnant, altering the drive to approach food. The alterations in the DMN and SMN observed only in women with anorexia nervosa suggest state-dependent abnormalities that could be related to altered interoception and body image in these women when they are underweight but that remit following recovery.

Submitted Mar. 12, 2013; Revised June 9, July 16, 2013; Accepted July 19, 2013.

Acknowledgements: A Davis Foundation Award of the Klarman Family Foundation Grants Program in Eating Disorders, NIMH grant K23 MH080135, and NIMH grant R01 MH096777 provided funding for all aspects of the study to Dr. Frank. We are grateful to the Eating Disorders Center Denver and Children’s Hospital Colorado staff and all the individuals who participated in this study.

Competing interests: K. McFadden and J. Tregellas are supported by a National Institutes of Health (NIH) grant (#R01DK089095, awarded to J. Tregellas) and M. Shott and G. Frank are also supported by an NIH grant (# R01MH096777, awarded to G. Frank).

Contributors: M. Shott and G. Frank designed the study and acquired the data, which all authors analyzed. K. McFadden, J. Tregellas and G. Frank wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.130046

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