Neural Vulnerability Factors that Increase Risk for Weight Gain: Prevention and Treatment Implications

Abstract

Obese versus lean humans show greater activation of reward valuation regions (caudate, amygdala, orbitofrontal cortex [OFC], insula) in response to palatable food images and to cues that signal impending palatable food receipt. Although this elevated responsivity theoretically results from conditioned associations between reward from palatable food and cues that signal impending palatable food receipt (the incentive sensitization theory), elevated amygdala response to palatable food images, nucleus accumbens response to palatable food images, OFC response to cues that predict palatable food image presentation, and striatal response to palatable food commercials predict future weight gain. These data suggest that elevated reward region responsivity to food cues trigger cravings that drive overeating. One prevention implication is that reducing intake of energy dense food should attenuate the conditioning process that gives rise to the hyper-responsivity of reward regions to food cues. Emerging evidence also suggests that thinking of the long-term health costs of eating unhealthy foods reduces reward region response to food cues, increases activation of inhibitory regions to food cues, and attenuates cravings, implying that prevention and treatment interventions should include cognitive reappraisal training. A pilot trial revealed that an intervention that trained young adults to apply cognitive reappraisals when confronted with unhealthy foods resulted in increased responsivity of a region implicated in inhibitory control and decreased responsivity of a region implicated in attention and expectation in response to palatable food images, but produced only pre-post reductions in body fat relative to participants in an obesity education control condition that did not persist over follow-up. It may be possible to use real time fMRI biofeedback to increase the effects of the cognitive reappraisal obesity prevention program. Yet obese versus lean adults also show less striatal D2 receptor availability, lower capacity of nigrostriatal neurons to synthesize dopamine, and weaker striatal activation (caudate, putamen) in response to high-fat/high-sugar food intake. Although animal experiments indicate that overfeeding results in reduced sensitivity of reward regions to food intake and pharmacologic stimulation, echoing effects from prospective weight gain studies with humans, individuals may overeat to compensate for an inborn or acquired reward deficit. Our pilot obesity prevention trial also encouraged participant-driven reductions dietary fat and sugar intake, but we did not find evidence of pre-post increases in reward region response to palatable beverages. Continued effort to translate neuroscience findings into obesity prevention and treatment interventions may yield more effective interventions for this pernicious public health problem.