Greater striatopallidal adaptive coding during cue-reward learning and food reward habituation predict future weight gain

Abstract

Animal experiments indicate that after repeated pairings of palatable food receipt and cues that predict palatable food receipt, dopamine signaling increases in response to predictive cues, but decreases in response to food receipt. Using functional MRI and mixed effects growth curve models with 35 females (M age=15.5±0.9; M BMI=24.5±5.4) we documented an increase in BOLD response in the caudate (r=.42) during exposure to cues predicting impending milkshake receipt over repeated exposures, demonstrating a direct measure of in vivo cue-reward learning in humans. Further, we observed a simultaneous decrease in putamen (r=-.33) and ventral pallidum (r=-.45) response during milkshake receipt that occurred over repeated exposures, putatively reflecting food reward habitation. We then tested whether cue-reward learning and habituation slopes predicted future weight over 2-year follow-up. Those who exhibited the greatest escalation in ventral pallidum responsivity to cues and the greatest decrease in caudate response to milkshake receipt showed significantly larger increases in BMI (r=.39 and -.69 respectively). Interestingly, cue-reward learning propensity and food reward habituation were not correlated, implying that these factors may constitute qualitatively distinct vulnerability pathways to excess weight gain. These two individual difference factors may provide insight as to why certain people have shown obesity onset in response to the current obesogenic environment in western cultures, whereas others have not.

Keywords: Cue–reward learning; Food reward habituation; Incentive salience; Obesity risk factors; Pavlovian conditioning; fMRI.

Figure 1

Sample timeline of presentation of geometric shapes (cues) and delivery of milkshake and tasteless solution. Cues followed a similar time course (presented for 5-12 s) with no taste delivery. Presentation of stimuli and assignment of geometric cue were randomized.

Figure 2

Changes in responsivity to cues that signal impending palatable food receipt and palatable food receipt over repeated exposure in one fMRI session. A) Positive relation between number of exposures and caudate response to the cue predicting milkshake receipt > cue predicting tasteless solution receipt (grey curve, solid line; P = 0.014). B) Inverse relation between number of exposures and putamen response to milkshake receipt > tasteless solution receipt (black curve, dashed line; P = 0.04) and C) Inverse relation between number of exposures and ventral pallidum response to milkshake receipt > tasteless solution receipt (black curve, dashed line; P = 0.009).

Figure 3

Mean BOLD response to A) cues that signal impending palatable food receipt and B) palatable food receipt over repeated exposures in one fMRI session. As shown with changes in BOLD response over 4 learning periods (16 total events) in specified region of interest. The color bar represents the T-value of activity over the scan showing: A) increases in caudate responsivity to cue predicting milkshake receipt > cue predicting tasteless solution receipt, and B) decreases in putamen (middle row) and ventral pallidum (bottom row) responsivity to milkshake receipt > tasteless solution receipt.

Figure 4

(A) Greater cue-reward learning in the ventral pallidum predicted increases in BMI over 2-year follow-up (P = 0.02). (B) Greater food reward habituation in the caudate predicted increases in BMI over 2-year follow-up (P < 0.001).