Functional neuroimaging in craniopharyngioma: a useful tool to better understand hypothalamic obesity?

Abstract

Objective: To use functional magnetic resonance imaging (fMRI) in craniopharyngioma (CP) patients to examine the hypothesis that hypothalamic damage due to CP and its treatment results in enhanced perception of food reward and/or impaired central satiety processing.

Methods: Pre- and post-meal responses to visual food cues in brain regions of interest (ROI; bilateral nucleus accumbens, bilateral insula, and medial orbitofrontal cortex) were assessed in 4 CP patients versus 4 age- and weight-matched controls. Stimuli consisted of images of high- ('fattening') and low-calorie ('non-fattening') foods in blocks, alternating with non-food object blocks. After the first fMRI scan, subjects drank a high-calorie test meal to suppress appetite, then completed a second fMRI scan. Within each ROI, we calculated mean z-scores for activation by fattening as compared to non-fattening food images.

Results: Following the test meal, controls showed suppression of activation by food cues while CP patients showed trends towards higher activation.

Conclusion: These data, albeit in a small group of patients, support our hypothesis that perception of food cues may be altered in hypothalamic obesity (HO), especially after eating, i.e. in the satiated state. The fMRI approach is encouraging for performing future mechanistic studies of the brain response to food cues and satiety in patients with hypothalamic or other forms of childhood obesity.

Fig. 1

Sample photographs. Example of pictures showing low-calorie a ‘non-fattening’ and b high-calorie ‘fattening’ food as well as c non-food items.

Fig. 2

Subjective hunger, fullness and actual caloric intake in CP patients versus controls. Ratings of a hunger and b fullness from VAS before and 30 min after the test meal in the CP (circles) and control (triangles) groups are shown as mean values (± SEM). Possible scores ranged from 0–100 mm. Higher scores indicated more hunger or fullness. Panel c shows group means (± SEM) kilocalories ingested at an ad libitum buffet meal that immediately followed the second fMRI scan, occurring 60 min after the test meal. CP = Craniopharyngioma; Ctr = control.

Fig. 3

Representative images from a control subject and a CP patient showing brain activation by visual food cues before and after a meal in the bilateral nucleus accumbens. Coronal sections through the nucleus accumbens in standard space are shown for 2 individual subjects at 2 time points, selected as representative of the mean z-score for the contrast of high-calorie > low-calorie food for each group. Control subject a before and b after the test meal. CP patient c before and d after the test meal. The decrease in voxel z-scores (change from yellow/orange to red/blue color) indicates suppression of activation by high-calorie food cues after a meal in the control subject but not in the CP patient. R = Right; L = left.

Fig. 4

Activation by food cues in CP patients vs. controls. a Mean activation in selected brain regions of interest (ROIs) from CP patients (black bars) and control subjects (white bars) before the test meal. b Change in activation from pre- to post-meal. Group means (± SEM) were calculated from individual mean z-scores for the contrast of high-calorie > low-calorie food extracted from each ROI. R = Right; L = left; Acc = nucleus accumbens; Ins = insula; MOFC = medial orbitofrontal cortex. *p = 0.05 versus control, #p = 0.04 versus control. P-values determined by one-sided Student's t-tests.