Neural Insensitivity to the Effects of Hunger in Women Remitted From Anorexia Nervosa

Abstract

Objective: Anorexia nervosa has the highest mortality rate of any psychiatric condition, yet the pathophysiology of this disorder and its primary symptom, extreme dietary restriction, remains poorly understood. In states of hunger relative to satiety, the rewarding value of food stimuli normally increases to promote eating, yet individuals with anorexia nervosa avoid food despite emaciation. This study's aim was to examine potential neural insensitivity to these effects of hunger in anorexia nervosa.

Methods: At two scanning sessions scheduled 24 hours apart, one after a 16-hour fast and one after a standardized meal, 26 women who were in remission from anorexia nervosa (to avoid the confounding effects of malnutrition) and 22 matched control women received tastes of sucrose solution or ionic water while functional MRI data were acquired. Within a network of interest responsible for food valuation and transforming taste signals into motivation to eat, the authors compared groups across conditions on blood-oxygen-level-dependent (BOLD) signal and task-based functional connectivity.

Results: Participants in the two groups had similar BOLD responses to sucrose and water tastants. A group-by-condition interaction in the ventral caudal putamen indicated that hunger had opposite effects on tastant response in the control group and the remitted anorexia nervosa group, with an increase and a decrease, respectively, in BOLD response when hungry. Hunger had a similar opposite effect on insula-to-ventral caudal putamen functional connectivity in the remitted anorexia nervosa group compared with the control group. Exploratory analyses indicated that lower caudate response to tastants when hungry was associated with higher scores on harm avoidance among participants in the remitted anorexia nervosa group.

Conclusions: Reduced recruitment of neural circuitry that translates taste stimulation to motivated eating behavior when hungry may facilitate food avoidance and prolonged periods of extremely restricted food intake in anorexia nervosa.

Keywords: Anorexia Nervosa; Feeding and Eating Disorders; Neuroimaging; Reward Processing; fMRI.

Figure 1.

Line graphs reflecting self-report Likert visual analog scale values for a pre- and post-scan measure of hunger and thirst. A) We compared groups on hunger and thirst ratings across conditions and timepoints using a Group x Condition (hungry, fed) x Interval (pre-scan, post-scan) linear mixed effects model with subject as a random effect. For hunger, there was a main effect of Condition, F(1,134)=181.37, p<0.001, with post-hoc analyses suggesting all participants reported greater hunger during the hungry condition relative to fed condition, t(134)=13.47, p<0.001. There was a main effect of Interval, F(1,134)=17.59, p<0.001, with post-hoc analyses suggesting all participants reported greater hunger post-scan relative to pre-scan, t(134)=4.26, p<0.001. However, there was no main effect of Group, and interactions were not statistically significant. B) For thirst, similar effects were observed: There was a main effect of Condition, F(1,134)=40.55, p<0.001, with all participants reporting greater thirst in the hungry relative to fed condition, t(134)=6.27, p<0.001, and a main effect of Interval, F(1,134)=26.93, p<0.001, with all participants reporting greater thirst post-scan relative to pre-scan, t(134)=5.15, p<0.001. However, there was no main effect of Group, and interactions were not statistically significant.

Figure 2.

A) Linear mixed effect results showing two separate clusters demonstrating an interaction of Group (CW, RAN) by Condition (hungry, fed) in response to tastants (sucrose and water combined) within the left ventral caudal putamen (top peak coordinate: x=−30, y=−15, z=0; bottom peak coordinate: x=−27, y=−9, z=0). CW were significantly more responsive to tastants when hungry versus fed (ps<0.037). In contrast, RAN were significantly less responsive to tastants when hungry versus fed (ps<0.001). When hungry, RAN showed lower response to tastants than CW in both clusters, but this finding was statistically significant within only one cluster (shown in the bottom panel, p=0.035). Intrinsic smoothness was estimated using the spatial autocorrelation function (acf) option in AFNI’s 3dFWHMx. Minimum cluster sizes were calculated with AFNI’s 3dClustSim to guard against false positives (voxel-wise p<0.001, α=0.05). B) Plot demonstrating statistically significant relationships between the BOLD percent signal change response to tastants when hungry and harm avoidance within the bilateral rostral caudate (left peak coordinate: x=−12, y=+18, z=+6; right peak coordinate: x=+18, y=+24, z=+3) for RAN using Huber robust regression (left: t=−3.46, p=0.017; right: t=−3.94, p=0.009). CW: healthy control women; RAN: women remitted from anorexia nervosa; ☨p<0.1; *p<0.05; **p<0.01; ***p<0.001.

Figure 3.

A)Functional connectivity analyses for the right caudal mid insula seed. Linear mixed effect results demonstrated an interaction of Group (CW, RAN) by Condition (hungry, fed) between the right insula seed and clusters within the left ventral caudal putamen (peak coordinate: x=−30, y=−15, z=0) and right dorsal rostral putamen (peak coordinate: x=+27, y=+9, z=+6) in response to tastants (sucrose and water combined). B) Functional connectivity analyses for the right ventral caudal putamen seed. Linear mixed effect results demonstrated an interaction of Group (CW, RAN) by Condition (hungry, fed) between the right putamen seed and clusters within the left ventral caudal putamen (peak coordinate: x=−30, y=−15, z=0) and right dorsal rostral putamen (peak coordinate: x=+27, y=+6, z=+6) in response to tastants (sucrose and water combined). CW: healthy control women; RAN: women remitted from anorexia nervosa; ☨p<0.1; *p<0.05; **p<0.01; ***p<0.001.

Figure 4.

A) Schematic diagram of insula-striatal pathways. The mid insula relays somato- and viscero-sensory signals to the anterior insula and striatum. The anterior insula projects along the ventromedial axis of the striatum, including the rostral ventral striatum and ventral caudal putamen. Through feed-forward connections, DA-mediated information progresses from the limbic to cognitive to sensorimotor areas of the striatum to generate action-selection related to the mediation and regulation of goal-directed behavior, such as the consumption of palatable food. B & C) The top panel within B reflects the rostro-caudal gradient of striatum-to-frontal-cortex structural connectivity as identified in healthy adults . Areas of the striatum are color-coded by their ultimate cortical projection targets, as indicated within the semicircle. The remaining panels depict BOLD activation from the current study in the context of the above identified structural circuits in healthy adults. Reference slices depicting significant clusters identified for each analysis in the current study (from Figure 2) are shown in boxes on the left. Colored areas shown on brain slices on the right reflect the gradients from the top semicircular panel. Overlap between clusters from our main analyses and these structural projection areas is shown in dark purple. Ventral caudal putamen clusters showing Group (AN, CW) x Condition (hungry, fed) interactions overlap primarily with areas of the putamen that have been shown previously in healthy adults to project to limbic (red, orange) and pre-motor (green) associative cortices. Rostral caudate clusters showing associations with harm avoidance in the RAN group overlap with areas of the caudate that have been shown previously to project to limbic (red, orange) and cognitive control-related dorsolateral prefrontal cortices (yellow). Structural connectivity maps adapted with permission from Draganski et al 2008 .