Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry

Abstract

The neurobiological mechanisms underlying overeating in obesity are not understood. Here, we assessed the neurobiological responses to an Implantable Gastric Stimulator (IGS), which induces stomach expansion via electrical stimulation of the vagus nerve to identify the brain circuits responsible for its effects in decreasing food intake. Brain metabolism was measured with positron emission tomography and 2-deoxy-2[ 18 F]fluoro-D-glucose in seven obese subjects who had the IGS implanted for 1-2 years. Brain metabolism was evaluated twice during activation (on) and during deactivation (off) of the IGS. The Three-Factor Eating Questionnaire was obtained to measure the behavioral components of eating (cognitive restraint, uncontrolled eating, and emotional eating). The largest difference was in the right hippocampus, where metabolism was 18% higher (P < 0.01) during the ''on'' than ''off'' condition, and these changes were associated with scores on ''emotional eating,'' which was lower during the on than off condition and with ''uncontrolled eating,'' which did not differ between conditions. Metabolism also was significantly higher in right anterior cerebellum, orbitofrontal cortex, and striatum during the on condition. These findings corroborate the role of the vagus nerve in regulating hippocampal activity and the importance of the hippocampus in modulating eating behaviors linked to emotional eating and lack of control. IGS-induced activation of regions previously shown to be involved in drug craving in addicted subjects (orbitofrontal cortex, hippocampus, cerebellum, and striatum) suggests that similar brain circuits underlie the enhanced motivational drive for food and drugs seen in obese and drugaddicted subjects, respectively. brain activation ͉ obesity T he cerebral mechanisms underlying the behaviors that result in pathological overeating and obesity are poorly understood. The regulation of food intake is a complex balance between excitatory and inhibitory processes. The excitatory processes arise from the body's needs for nutrients and calories. The inhibitory processes arise from satiety signals (i.e., electrical and chemical) after food consumption (1). The vagus nerve is one of the ways by which satiety signals are conveyed to the brainstem (2). Gastric and duodenal vagal afferents increase their firing in response to the mechanical pressure from the ingested nutrients and in response to food-induced release of a variety of brain gut peptides (i.e., cholecystokinin and ghrelin). In addition, several neurotransmitters (e.g., serotonin, dopamine, norepinephrine, and opiates) and peptides (i.e., cholecystokinin and corticotrophin releasing factor) are also involved in feeding behaviors (1). It is also recognized that in addition to food's role in fulfilling nutrient requirements, eating also may serve to mitigate stress (comfort food) (3). Disruption in the sensitivity of the brain to these signals could lead to obesity.Recently, the Transcend Implantable Gastric Stimulator (IGS) system, which generates el...

The anterior medial temporal lobes: Their role in food intake and body weight regulation

“…Impaired inhibition in overweight and obese individuals is hypothesized to affect food intake (e.g., [49]). In line with this point of view, gastric stimulation in obese individuals activates primarily the right hippocampus, which correlates with a decrease in emotional and uncontrolled eating [172]. In other words, activation of the hippocampus in obese individuals is linked to inhibitory processes related to food intake.…”

Differences in response to food stimuli in a rat model of obesity: in-vivo assessment of brain glucose metabolism

“…27 The hippocampus in addition to leptin receptors also expresses receptors for other neuropeptides involved in regulating food intake such as insulin and cholecystokinin, 28 and finally, two recent clinical studies showed that gastric stimulation and distention activated the hippocampus. 29,30 This suggests the possibility of functionally relevant connections between peripheral organs that is important in food-intake regulation such as the stomach and the hippocampus.…”

Transcranial direct current stimulation of the prefrontal cortex modulates the desire for specific foods

“…Whereas the right hemisphere might suppress desire to eat in general (or hunger), the left hemisphere might have a selective effect on food craving-decreasing the craving for particular foods. A previous study showed that implantable gastric stimulator (IGS) -which induces stomach expansion via electrical stimulation of the vagus nerve -induces a larger change in the activity of the right hemisphere as compared to the left (Wang et al, 2006). IGS is used to suppress appetite in obese patients.…”