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

Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 10/2006; 103(42):15641-5. DOI: 10.1073/pnas.0601977103
Source: PubMed


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[18F]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 drug-addicted subjects, respectively.

Download full-text


Available from: Panayotis Thanos
  • Source
    • "The vMPFC is composed of the infralimbic (IL), prelimbic (PL), and dorsal peduncular (DP) cortices (Paxinos and Watson, 1997; Zilles et al., 1985) and is particularly related to the limbic system, emotional, cognitive and learning processes for repetition (Vertes, 2004). Studies using functional imaging methods have suggested that the prefrontal cortex is one of the most activated areas after gastric distension (ingestion of a large amount of food) in obese subjects (Wang et al., 2006). Moreover, the prefrontal cortex is strongly connected with the hypothalamus (Vertes, 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The regulation of food intake involves a complex interplay between the central nervous system and the activity of organs involved in energy homeostasis. Besides the hypothalamus, recognized as the center of this regulation, other structures are involved, especially limbic regions such as the ventral medial prefrontal cortex (vMPFC). Monoamines, such as serotonin (5-HT), play an important role in appetite regulation. However, the effect in the vMPFC of the selective serotonin reuptake inhibitor (SSRI), fluoxetine, on food intake has not been studied. The aim of the present study was to study the effects on food intake of fed and fasted rats evoked by fluoxetine injection into the prelimbic cortex (PL), a sub-region of the vMPFC, or given systemically, and which 5-HT receptors in the PL are involved in fluoxetine responses. Fluoxetine was injected into the PL or given systemically in male Wistar rats. Independent groups of rats were pretreated with intra-PL antagonists of 5-HT receptors: 5-HT1A (WAY100635), 5-HT2C (SB242084) or 5-HT1B (SB216641). Fluoxetine (0,1; 1; 3; 10nmol/200nL) injected into the PL induced a dose-dependent hypophagic effect in fasted rats. This effect was reversed by prior local treatment with WAY100635 (1;10nmol) or SB242084 (1;10nmol), but not with SB216641 (0.2; 2.5; 10nmol). Systemic fluoxetine induced a hypophagic effect, which was blocked by intra-PL 5-HT2C antagonist (10nmol) administration. Our findings suggest that PL 5-HT neurotransmission modulates the central control of food intake and 5-HT1A and 5-HT2C receptors in the PL could be potential targets for the action of fluoxetine. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jul 2015 · Pharmacology Biochemistry and Behavior
  • Source
    • "These studies confirm that gastric distension alters brain response [48] [49] and that these responses may be associated with eating behavior. For example, Wang and colleagues used the Transcent Implantable Gastric Stimulator, which generates electrical signals to induce the expansion of the fundus while brain metabolism was assessed with 2-deoy-d[ 18 ]fluoro-D-glucose with PET [50]. They found that gastric stimulation was associated with elevated response in the hippocampus, striatum, orbitofrontal cortex, cerebellum and striatum, with response in the hippocampus correlating with a self-report measure of a tendency for emotional eating. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hormonal and metabolic signals interact with neural circuits orchestrating behavior to guide food intake. Neuroimaging techniques such as functional magnetic resonance imaging (fMRI) enable the identification of where in the brain particular mental processes like desire, satiety and pleasure occur. Once these neural circuits are described it then becomes possible to determine how metabolic and hormonal signals can alter brain response to influence psychological states and decision-making processes to guide intake. Here, we provide an overview of the contributions of functional neuroimaging to the understanding of how subjective and neural responses to food and food cues interact with metabolic/hormonal factors.
    Full-text · Article · Dec 2012 · Molecular Metabolism
  • Source
    • "In this context it also seems noteworthy that reduced GMV of the left dlPFC, a region that is believed to provide top-down control for IFG and vmPFC guided behavior, has been linked to future BMI increases in young females (Yokum et al., 2012). Further functional neuroimaging studies also have demonstrated activation of the caudolateral OFC in response to gastrointestinal stimuli, emphasizing its role in processing visceral information (Stephan et al., 2003; Vandenbergh et al., 2005; Wang et al., 2006). Associations of FFMI with less GMV of the left clOFC did involve a large part of the anterior insula. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity has been associated with alterations of both functional and structural aspects of the human central nervous system. In obese individuals both fat mass (FM; primarily consisting of adipose tissue) and fat-free mass (FFM; all non-adipose tissues) are increased and it remains unknown whether these compartments have separate effects on human brain morphology. We used voxel-based morphometry to investigate the relationships between measures of body composition and regional gray matter volume (GMV) in 76 healthy adults with a wide range of adiposity (24 F/52 M; age 32.1±8.8 years; percentage of body fat [PFAT%] 25.5±10.9%; BMI 29.8±8.9). Fat-free mass index (FFMI kg×m(-2)) showed negative associations in bilateral temporal regions, the bilateral medial and caudolateral OFC, and the left insula. Fat mass index (FMI kg ×m(-2)) showed similar, but less extensive negative associations within temporal cortical regions and the left caudolateral orbitofrontal cortex (OFC). In addition, negative associations were seen for FMI with GMV of the cerebellum. Associations of FFMI with temporal and medial orbitofrontal GMV appeared to be independent of adiposity. No associations were seen between measures of adiposity (i.e. FM and PFAT) and GMV when adjusted for FFM. The majority of regions that we find associated with FFM have been implicated in the regulation of eating behavior and show extensive projections to central autonomic and homeostatic core structures. These data indicate that not adipose tissue or relative adiposity itself, but obesity related increases in absolute tissue mass and particularly FFM may have a more predominant effect on the human brain. This might be explained by the high metabolic demand of FFM and related increases in total energy needs.
    Full-text · Article · Sep 2012 · NeuroImage
Show more