Participants

Conclusions• Viewing high-calorie food stimuli resulted in significantly less brain activation in the HWS group than in all other groups in the mid-insula

(where taste, hunger and other interoceptive inputs act to promote eating) and in the lingual gyrus (linked to reward value for food).

• These neural pathways guiding reward-related food behaviour may be more important in controlling food intake in patients with HO than in those who are HWS and may be crucial areas for further investigation into the underlying pathophysiology of obesity in the general population.

• 13 significant brain regions of interest (ROIs) were identified during 2nd level analysis.

• Pictures of high calorie foods produced significantly greater brain activation in HO and OC subjects compared to NOC in the caudate head (P=0.008), middle frontal gyrus (P=0.021), insula (P=0.032), cingulate gyrus (P=0.03) and anterior cingulate gyrus (P<0.001) – areas associated with reward, behaviour, learning and memory.

• Activation in the mid-insula in HWS patients was lower than in the other 3 groups (HWS -0.042, HO 0.237, NOC 0.186, OC 0.175; P=0.02) (Figure 2) whilst viewing high-calorie foods.

• Activation of the lingual gyrus in HWS was also lower than all other 3 groups (HWS 1.309, HO 1.633, NOC 1.698 and OC 1.609;

P=0.025) with high-calorie food photographs.

Results

Abstract

Importance of Brain Reward Regions in Adults with Acquired Structural Hypothalamic Damage:

A Functional Neuroimaging StudyCA Steele1, J Powell2, IA Macfarlane1, JCG Halford3, JPH Wilding1, JA Harrold3, DJ Cuthbertson1, K Das4, M Javadpour4, GJ Kemp2, AStancak3 & C Daousi1

1Department of Obesity & Endocrinology, University Hospital Aintree, Liverpool, 2Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of Liverpool, 3Department of Experimental Psychology, University of Liverpool, 4Departments of Neuroradiology and Neurosurgery, The Walton Centre for Neurology & Neurosurgery, Liverpool.

Background Weight gain and obesity are common, distressing

long-term sequelae of hypothalamic damage secondary to tumours

affecting this brain region.

The hypothalamus is the critical centre regulating internal (homeostatic)

factors affecting appetite and eating. Other areas (e.g./ cortical brain regions) process

non-homeostatic environmental, rewarding effects of food. The interactions between

them remain poorly understood.

fMRI (functional MRI) has been used to explore brain regions involved in regulating

appetite and eating in other groups (e.g./ obese, anorexia).

By studying patients with damage to the hypothalamus (homeostatic regulator), we

could explore the influence of reward-related non-homeostatic areas working in it’s absence.

We hypothesised that reward-related brain regions may assume a more dominant role

in appetite control in hypothalamic obesity (HO) than in those

with hypothalamic damage remaining

weight-stable (HWS).

Design• fMRI scans were performed after a 10 hours fast and 1 and 3 hours

after breakfast, whilst viewing high-calorie, low-calorie and non-food photographs in blocks (Figure 1) via a computer screen.

• Pre-processing and statistical analyses of these scans were conducted using Statistical Parametric Mapping software (SPM8), the MarsBaR toolbox (to identify brain regions of interest) and SPSS 17.

• The contrast between “all foods” (high and low calorie) and objects was selected in the 1st level analysis to remove brain activation caused by any visual stimuli, to leave only activation due to viewing food stimuli.

Figure 2. Neuronal activation for the contrast food images vs. objects across all subjects and all conditions in left insula cortex.

Hypothalamus

Figure 1. fMRI photo protocol.