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Articles   |    
Altered Insula Response to Sweet Taste Processing After Recovery From Anorexia and Bulimia Nervosa
Tyson A. Oberndorfer, M.D.; Guido K.W. Frank, M.D.; Alan N. Simmons, Ph.D.; Angela Wagner, M.D., Ph.D.; Danyale McCurdy, Ph.D.; Julie L. Fudge, M.D.; Tony T. Yang, M.D., Ph.D.; Martin P. Paulus, M.D.; Walter H. Kaye, M.D.
Am J Psychiatry 2013;170:1143-1151. doi:10.1176/appi.ajp.2013.11111745
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Supported by NIMH grants MH46001, MH42984, and K05-MD01894; by NIMH training grant T32-MH18399; and by the Price Foundation.

Dr. Frank has received support from NIMH and the Klarman Family Foundation Grants Program in Eating Disorders. Dr. Kaye has received support from NIMH and the Price Foundation. The other authors report no financial relationships with commercial interests.

From the Department of Psychiatry, University of California San Diego, La Jolla, Calif.; Department of Psychiatry, University of Colorado at Denver and Health Sciences Center, Aurora; San Diego Veterans Affairs Health Care System, San Diego; and Departments of Psychiatry and Neurobiology and Anatomy, University of Rochester Medical Center, Rochester, N.Y.

Address correspondence to Dr. Kaye (wkaye@ucsd.edu).

Copyright © 2013 by the American Psychiatric Association

Received November 29, 2011; Revised November 02, 2012; Revised January 18, 2013; Revised March 01, 2013; Accepted March 13, 2013.

Abstract

Objective  Recent studies suggest that altered function of higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa and overeating in bulimia nervosa. This study used sweet tastes to interrogate gustatory neurocircuitry involving the anterior insula and related regions that modulate sensory-interoceptive-reward signals in response to palatable foods.

Method  Participants who had recovered from anorexia nervosa and bulimia nervosa were studied to avoid confounding effects of altered nutritional state. Functional MRI measured brain response to repeated tastes of sucrose and sucralose to disentangle neural processing of caloric and noncaloric sweet tastes. Whole-brain functional analysis was constrained to anatomical regions of interest.

Results  Relative to matched comparison women (N=14), women recovered from anorexia nervosa (N=14) had significantly diminished and women recovered from bulimia nervosa (N=14) had significantly elevated hemodynamic response to tastes of sucrose in the right anterior insula. Anterior insula response to sucrose compared with sucralose was exaggerated in the recovered group (lower in women recovered from anorexia nervosa and higher in women recovered from bulimia nervosa).

Conclusions  The anterior insula integrates sensory reward aspects of taste in the service of nutritional homeostasis. One possibility is that restricted eating and weight loss occur in anorexia nervosa because of a failure to accurately recognize hunger signals, whereas overeating in bulimia nervosa could represent an exaggerated perception of hunger signals. This response may reflect the altered calibration of signals related to sweet taste and the caloric content of food and may offer a pathway to novel and more effective treatments.

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FIGURE 1. Main-Effect Neural Activation During Sucrose Taste Processinga

a Taste pathway: chemoreceptors on the tongue detect the sweet taste. This signal is transmitted through the spinal cord and into the brainstem. The thalamus (purple) relays this information to the primary gustatory cortex, which is interconnected with the anterior insula (green). The anterior insula is a vital component of the ventral neurocircuit, or limbic system, through its connections with the amygdala (blue), the anterior cingulate cortex (ACC; turquoise), and the orbitofrontal cortex (OFC; yellow). Afferents from cortical structures involved in the ventral neurocircuit are directed to the ventral striatum (VS); cortical structures more involved in cognitive strategies, forming a dorsal neurocircuit that includes the dorsolateral prefrontal cortex (DLPFC; pink), send inputs to the dorsal striatum (DS). RAN=women recovered from anorexia nervosa; CW=comparison women; RBN=women recovered from bulimia nervosa.

FIGURE 2. Group-by-Condition Interactions for Response to Sucrose and Sucralose in Women Recovered From Anorexia Nervosa or Bulimia Nervosa and Healthy Comparison Womena

a In panel A, regions of interest were defined by a one-way group-by-condition (p<0.05) analysis of variance. The centers of mass, with Talairach coordinates, were as follows: for region 1, the anterior insula (5,504 mm3, 86 voxels; 39, −2, 8); for region 2, the dorsal caudate (1,984 mm3, 31 voxels; 10, 9, 8); for region 3, the thalamus (1,088 mm3, 17 voxels; 12, −12, 12). In panel B, post hoc t tests in the right anterior and middle insula showed that response to sucrose was significantly less in women recovered from anorexia nervosa (RAN) relative to comparison women (CW) (**p<0.01) but significantly greater in women recovered from bulimia nervosa (RBN) relative to comparison women (*p<0.05). In panel C, post hoc t tests in the right dorsal caudate showed a decreased response to sucrose in women recovered from anorexia nervosa relative to comparison women that approached significance (p=0.079). No significant condition or group activation differences were observed in the right thalamus (region 3, data not shown). Error bars indicate standard deviations.

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TABLE 1.Demographic, Clinical, and Behavioral Data for Women Recovered From Anorexia Nervosa or Bulimia Nervosa and Healthy Comparison Women
Table Footer Note

a Dose of sucralose that matched a 10% sucrose solution. While women recovered from anorexia nervosa (F=7.66, df=1, 27, p=0.010) and from bulimia nervosa (F=8.94, df=1, 27, p=0.006) required more sucralose to taste match with sucrose than comparison women, when asked after the fMRI scan, all participants reported that they were unable to distinguish between the sucrose and sucralose solutions.

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TABLE 2.Main-Effect BOLD Signal Response to Sucrose and Sucralose in Regions of Interesta
Table Footer Note

a BOLD=blood-oxygen-level-dependent. Thresholded at p<0.005 and a minimum cluster size of 8 contiguous voxels (512 mm3). The volume of each voxel is 64 mm3. Coordinates are for center of mass in Talairach space.

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TABLE 3.Summary of ANOVA Comparisons From the Right Anterior Insula and Right Dorsal Caudate in Healthy Comparison Women (CW), Women Recovered From Anorexia Nervosa (RAN), and Women Recovered From Bulimia Nervosa (RBN)a
Table Footer Note

a In the right anterior insula region defined by the group-by-condition contrast, response to sucralose was significantly lower in the recovered anorexia nervosa group relative to the healthy comparison group but was not significantly different between the comparison and recovered bulimia nervosa groups. Sucrose elicited greater blood-oxygen-level-dependent (BOLD) signal than sucralose for women in the recovered bulimia nervosa group in the right anterior insula, while the BOLD response was lower in sucrose compared with sucralose for those in the recovered anorexia nervosa group. The healthy comparison group showed no condition differences in the right anterior insula. In the right caudate region defined by the group-by-condition contrast, decreased sucralose response relative to the healthy comparison group did not reach significance in either the recovered anorexia nervosa group or the recovered bulimia nervosa group. Sucrose elicited greater BOLD signal than sucralose for women in the recovered bulimia nervosa group in the right caudate, while the BOLD response was lower in sucrose versus sucralose for women in both recovered groups.

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