Neuroimaging and obesity: current knowledge and future directions

Abstract

Neuroimaging is becoming increasingly common in obesity research as investigators try to understand the neurological underpinnings of appetite and body weight in humans. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and magnetic resonance imaging (MRI) studies examining responses to food intake and food cues, dopamine function and brain volume in lean vs. obese individuals are now beginning to coalesce in identifying irregularities in a range of regions implicated in reward (e.g. striatum, orbitofrontal cortex, insula), emotion and memory (e.g. amygdala, hippocampus), homeostatic regulation of intake (e.g. hypothalamus), sensory and motor processing (e.g. insula, precentral gyrus), and cognitive control and attention (e.g. prefrontal cortex, cingulate). Studies of weight change in children and adolescents, and those at high genetic risk for obesity, promise to illuminate causal processes. Studies examining specific eating behaviours (e.g. external eating, emotional eating, dietary restraint) are teaching us about the distinct neural networks that drive components of appetite, and contribute to the phenotype of body weight. Finally, innovative investigations of appetite-related hormones, including studies of abnormalities (e.g. leptin deficiency) and interventions (e.g. leptin replacement, bariatric surgery), are shedding light on the interactive relationship between gut and brain. The dynamic distributed vulnerability model of eating behaviour in obesity that we propose has scientific and practical implications.

Figure 1

Dynamic distributed neurobehavioural vulnerability model of eating behaviour in obesity. Bold lines represent exaggerated appetite-related signals, broken lines represent impaired appetite-related signals, and grey dotted lines represent functional interactions between brain areas. For example, satiety signalling from homeostatic areas seems to be impaired (e.g. delayed fMRI inhibition response in hypothalamus) while hunger signals from emotion/memory areas and sensory/motor areas seem to be heightened (e.g. greater activation in amygdala, hippocampus, insula and precentral gyrus in response to food cues), in obese individuals. The functioning of the neurobehavioural system depends on genetic, biological and environmental influences, as well as cognitions, emotions and persistent patterns of behaviour (as well as interactions between these factors). To take a specific example, the role of reward areas may depend on dietary behaviour and genetic factors. For example, long-term exposure to highly palatable high-calorie foods may lead to decreased reward activation following food intake, but increased reward activation following food cues, in obese individuals. Alternatively, individuals with a genetic reward deficit may show decreased reward activation to both intake and cues. Both routes may cause individuals to compensate by over-eating. There is also evidence that the recruitment of cognitive control areas varies between obese individuals, depending on their habitual level of cognitive and/or behavioural dietary restraint. The areas included in this diagram are distributed all over the brain and interact with each other (i.e. functional connectivity), producing the complex and variegated phenotypes associated with common, multifactorial forms of obesity.