Rosalyn E. Weller

Widespread reward-system activation in obese women in response to pictures of high-calorie foods.

Behavioral studies have suggested that exaggerated reactivity to food cues, especially those associated with high-calorie foods, may be a factor underlying obesity. This increased motivational potency of foods in obese individuals appears to be mediated in part by a hyperactive reward system. We used a Philips 3T magnet and fMRI to investigate activation of reward-system and associated brain structures in response to pictures of high-calorie and low-calorie foods in 12 obese compared to 12 normal-weight women. A regions of interest (ROI) analysis revealed that pictures of high-calorie foods produced significantly greater activation in the obese group compared to controls in medial and lateral orbitofrontal cortex, amygdala, nucleus accumbens/ventral striatum, medial prefrontal cortex, insula, anterior cingulate cortex, ventral pallidum, caudate, putamen, and hippocampus. For the contrast of high-calorie vs. low-calorie foods, the obese group also exhibited a larger difference than the controls did in all of the same regions of interest except for the putamen. Within-group contrasts revealed that pictures of high-calorie foods uniformly stimulated more activation than low-calorie foods did in the obese group. By contrast, in the control group, greater activation by high-calorie foods was seen only in dorsal caudate, whereas low-calorie foods were more effective than high-calorie foods in the lateral orbitofrontal cortex, medial prefrontal cortex, and anterior cingulate cortex. In summary, compared to normal-weight controls, obese women exhibited greater activation in response to pictures of high-calorie foods in a large number of regions hypothesized to mediate motivational effects of food cues.

Obese women show greater delay discounting than healthy-weight women

Delay discounting (DD) is a measure of the degree to which an individual is driven by immediate gratification vs. the prospect of larger, but delayed, rewards. Because of hypothesized parallels between drug addiction and obesity, and reports of increased delay discounting in drug-dependent individuals, we hypothesized that obese individuals would show higher rates of discounting than controls. Obese and healthy-weight age-matched participants of both sexes completed two versions of a DD of money task, allowing us to calculate how subjective value of

Effective connectivity of a reward network in obese women

1000 or

fMRI reactivity on a delay discounting task predicts weight gain in obese women

50,000 declined as delay until hypothetical delivery increased from 2 weeks to 10 years. On both tasks, obese women (N=29) showed greater delay discounting than control women did (N=26; P values <.02). Subsequent analyses showed that these differences were not related to differences in IQ or income. Obese (N=19) and healthy-weight (N=21) men did not differ significantly. Further research is needed to determine why greater delay discounting was not also observed in obese men.

Evidence for the loss of X-cells of the retina after long-term ablation of visual cortex in monkeys

Exaggerated reactivity to food cues in obese women appears to be mediated in part by a hyperactive reward system that includes the nucleus accumbens, amygdala, and orbitofrontal cortex. The present study used functional magnetic resonance imaging (fMRI) to investigate whether differences between 12 obese and 12 normal-weight women in reward-related brain activation in response to food images can be explained by changes in the functional interactions between key reward network regions. A two-step path analysis/General Linear Model approach was used to test whether there were group differences in network connections between nucleus accumbens, amygdala, and orbitofrontal cortex in response to high- and low-calorie food images. There was abnormal connectivity in the obese group in response to both high- and low-calorie food cues compared to normal-weight controls. Compared to controls, the obese group had a relative deficiency in the amygdalas modulation of activation in both orbitofrontal cortex and nucleus accumbens, but excessive influence of orbitofrontal cortexs modulation of activation in nucleus accumbens. The deficient projections from the amygdala might relate to suboptimal modulation of the affective/emotional aspects of a foods reward value or an associated cues motivational salience, whereas increased orbitofrontal cortex to nucleus accumbens connectivity might contribute to a heightened drive to eat in response to a food cue. Thus, it is possible that not only greater activation of the reward system, but also differences in the interaction of regions in this network may contribute to the relatively increased motivational value of foods in obese individuals.

Cortical and Subcortical Connections of Visual Cortex in Primates

Obesity can be accompanied by abnormalities in executive function and related neural circuitry. A useful task for studying executive function is delay discounting (DD), in which an individual chooses between sooner and delayed, but greater, amounts of money or other commodities. We previously found that obese compared to normal-weight women made more immediate choices on a monetary DD task, or had greater delay discounting. In the present study, we performed functional magnetic resonance imaging (fMRI) of obese women during performance of a DD of money task. Confirming the results of previous studies, we found that more difficult compared to easy DD trials resulted in activation in putative executive function areas of the brain, the middle and inferior frontal gyri, and medial prefrontal cortex. Most interestingly, we also found that less activation in executive function areas such as the inferior, middle, and superior frontal gyri on difficult vs. easy DD trials predicted a greater rate of weight gain over the subsequent 1.3-2.9 years. These results suggest that suboptimal functioning of executive function areas such as prefrontal cortex contributes to the progression of obesity.

Motivational state modulates the hedonic value of food images differently in men and women.

We examined the visual system of two macaque monkeys (Macaca mulatta) with large long-standing bilateral lesions of primary visual cortex and found a profound loss of ganglion cells in the retinas and altered projections to the lateral geniculate nucleus. Previously, there have been only two isolated and curiously neglected reports of ganglion cell loss in monkeys after cortical lesions, and neither study investigated the central projections of the remaining ganglion cells4,1L We find that the remaining ganglion cells project almost exclusively to the magnocellular rather than the parvocellular layers of the lateral geniculate nuclei. This observation is important since it is known that the magnocellular and parvocellular layers receive inputs from different classes of ganglion cells of the retina; the magnocellular layers are activated by Y-cells while the parvocellular layers are activated by X-cells 7,17,1s**. The Y-cells of the retina have been characterized by rapidly conducting axons, a relatively even distribution across the retina, phasic responses to visual stimuli, (for review see ref. 15) and, in primates, a generally broad-band responsiveness to colort6,17. The X-cells, in contrast, have been related to slowly conducting axons, a concentration in the central retina, and sustained responses to visual stimuli (for review see ref. 15). X-cells appear to be associated with color-opponent mechanisms in primates16,17. It has been suggested that X-cells subserve form vision, while the properties of Y-cells are compatible with detecting stimulus change so that orientation and fixation can take place (cf. ref. 15). Since our studies indicate that the ganglion cells remaining after cortical lesions project almost exclusively to the magnocellular rather than the parvocellular layers, we conclude that Y-cells of the retina are preserved while X-cells are lost.

Greater Impulsivity is Associated with Decreased Brain Activation in Obese Women during a Delay Discounting Task

Over the last several years, considerable progress has been made in understanding the connections of the visual system in primates. Much of this progress has been the result of applications of the relatively new and powerful autoradiographic and histochemical tracing methods that reveal connections in great detail and clarity. The major limitation on further understanding of visual system connections does not seem to be technical at this time, but rather it is our incomplete knowledge of the functional subdivisions of the primate visual system. It is difficult to study connections of parts of the brain for which the organization and divisions into separate areas or nuclei are still unclear. Quite different schemes of cortical organization have been proposed for visual cortex of New World (5–7) and Old World monkeys (96, 111, 116–118) and neither of these schemes includes all of visually responsive cortex. For example, neither organization deals with subdivisions of inferotemporal cortex, a visually responsive region of cortex that in Old World monkeys has received detailed attention (33, 34, 59), without completely resolving the issue of number and boundaries of subdivisions. Efforts have been made to show similarites in cortical organization between Old and New World primates (1, 95, 99), but how similar or dissimilar the two groups of primates are presently remains uncertain.

Pulvinar and other subcortical connections of dorsolateral visual cortex in monkeys

We investigated visual alimentary alliesthesia in non-fasted (N = 369) and fasted participants (N = 257) viewing photographs of food. Fasted participants were asked to not eat for 12 h before the session. Each participant was shown food and non-food images and rated each image on valence (i.e., pleasantness). The strongest evidence of alliesthesia was found in women. Fasting enhanced the pleasantness of food images for each of the food categories in women, although this alliesthesia effect was smaller in response to dessert foods compared to the less-pleasantly-rated food categories. In addition, non-fasting women exhibited significant positive correlations between hunger ratings and valence ratings of three of the five food categories. There was no significant difference in valence ratings of food between fasting vs. non-fasting men, but non-fasting men showed correlations between hunger and valence that were similar to those observed among the women. No evidence was found of hunger- or fasting-induced enhancement of hedonic ratings of non-foods in women or men, indicating the specificity of the alliesthesia effect for the food images only.

Chapter 27: Two cortical visual systems in Old World and New World primates

Impulsivity and poor inhibitory control are associated with higher rates of delay discounting (DD), or a greater preference for smaller, more immediate rewards at the expense of larger, but delayed rewards. Of the many functional magnetic resonance imaging (fMRI) studies of DD, few have investigated the correlation between individual differences in DD rate and brain activation related to DD trial difficulty, with difficult DD trials expected to activate putative executive function brain areas involved in impulse control. In the current study, we correlated patterns of brain activation as measured by fMRI during difficult vs. easy trials of a DD task with DD rate (k) in obese women. Difficulty was defined by how much a reward choice deviated from an individual’s ‘indifference point’, or the point where the subjective preference for an immediate and a delayed reward was approximately equivalent. We found that greater delay discounting was correlated with less modulation of activation in putative executive function brain areas, such as the middle and superior frontal gyri and inferior parietal lobule, in response to difficult compared to easy DD trials. These results support the suggestion that increased impulsivity is associated with deficient functioning of executive function areas of the brain.