Subjective feeling of appetite modulates brain activity: An fMRI study Katarı ´na Porubska ´, a,b, * Ralf Veit, a,b Hubert Preissl, a,b,c Andreas Fritsche, d and Niels Birbaumer a,b,e a MEG-Center, University of Tu ¨bingen, Tu ¨ bingen, Germany b Institute of Medical Psychology and Behavioral Neurobiology, University of Tu ¨bingen, Tu ¨ bingen, Germany c Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA d Medical Clinic, Department of Endocrinology and Metabolism, University Hospital Tu ¨bingen, Tu ¨ bingen, Germany e Center for Cognitive Neuroscience, University of Trento, Trento, Italy Received 14 December 2005; revised 19 April 2006; accepted 27 April 2006 Available online 11 July 2006 Obesity and overweight are important risk factors for the development of diabetes mellitus type 2 and associated chronic diseases, and therefore, they have become serious global problems in the western and developed countries. But little is known about the neuroanatomical correlates of eating behavior and its influences on the central nervous processing in humans. We used functional magnetic resonance imaging (fMRI) to measure the cortical activation in 12 lean healthy humans during visual stimulation with food-related and nonfood pictures after a fasting period of at least 5 h. Compared to the nonfood pictures, the food stimuli elicited a significantly greater activity in the left orbitofrontal cortex and the insular/opercular cortex bilaterally with a stronger focus on the left side. Subjective ratings of appetite during the presentation of food-related stimuli modulated the activity in the insula bilaterally, the left operculum and the right putamen. These results provide further insights in the central nervous processing of food relevant stimuli in humans, specifically with respect to the subjective experience of appetite. D 2006 Elsevier Inc. All rights reserved. Keywords: Eating behavior; Food; Hunger; Motivation; Neuroimaging Introduction Obesity and diabetes mellitus type 2 along with the metabolic syndrome and its cardiovascular complications have become serious health problems worldwide and the leading mortality factor in the developed countries. Easy access to food and increased food consumption especially of high-caloric nutrition are major factors in the development of obesity-related diseases. The eating behavior currently prevalent (consumption of convenience/junk food and changing diets) has an important impact in this context. Our present knowledge about the neuronal processes which determine and control human eating behavior is rather limited. It is well established that the hypothalamus is the major homeostatic control center, which in turn is influenced by peripheral peptides like leptin, insulin, ghrelin or cholecystokinin (Plata-Salaman, 1991; Woods et al., 1998; Schwartz et al., 2000; Leibowitz and Wortley, 2004). Early approaches regarded this energy balance as a simple and stable feedback control loop, in which specialized hypothalamic nuclei play a crucial role. It is well known that some areas in the hypothalamus are responsible for hunger (lateral hypothalamus, perifornical nucleus), others for satiety (ventrome- dial nucleus, paraventricular nucleus). Again, these nuclei are controlled and influenced by the nutritionally relevant hormones mentioned above, as well as the blood sugar level, thus control food intake. But besides this rather basic control circuit, additional factors like emotional and cognitive aspects of food regulation have to be taken in account. This becomes essential especially with regard to the increasing prevalence of obesity and resulting diseases in a nutritionally rich environment. An important psy- chological factor of a rather subjective character is the feeling of appetite. In contrast to hunger, appetite is a psychological desire to eat food without any metabolic needs. The feeling of appetite is thus a strong index for the motivation to food intake. Our food preferences and eating behavior are also influenced by our pre- vious learning experiences. In addition, food stimuli are charac- terized by their multimodal characteristics. Basically there are three sensory modalities which influence our behavior in respect to food: gustatory, olfactory and visual. Recent brain imaging studies addressed the way these sensory inputs determine our eating behavior as well as the different aspects of food-related cortical processes. 1053-8119/$ - see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2006.04.216 * Corresponding author. MEG Center, Otfried-Mu ¨ller-Str. 47, 72076 Tu ¨bingen, Germany. Fax: +49 7071 295706. E-mail address: katarina.porubska@med.uni-tuebingen.de (K. Porubska ´). Available online on ScienceDirect (www.sciencedirect.com). www.elsevier.com/locate/ynimg NeuroImage 32 (2006) 1273 – 1280