fMRI reactivity to high-calorie food pictures predicts short- and long-term outcome in a weight-loss program.

Behavioral studies have suggested that food cues have stronger motivating effects in obese than in normal-weight individuals, which may be a risk factor underlying obesity. Previous cross-sectional neuroimaging studies have suggested that this difference is mediated by increased reactivity to food cues in parts of the reward system in obese individuals. To date, however, only a few prospective neuroimaging studies have been conducted to examine whether individual differences in brain activation elicited by food cues can predict differences in weight change. We used functional magnetic resonance imaging (fMRI) to investigate activation in reward-system as well as other brain regions in response to viewing high-calorie food vs. control pictures in 25 obese individuals before and after a 12-week psychosocial weight-loss treatment and at 9-mo follow-up. In those obese individuals who were least successful in losing weight during the treatment, we found greater pre-treatment activation to high-calorie food vs. control pictures in brain regions implicated in reward-system processes, such as the nucleus accumbens, anterior cingulate, and insula. We found similar correlations with weight loss in brain regions implicated by other studies in vision and attention, such as superior occipital cortex, inferior and superior parietal lobule, and prefrontal cortex. Furthermore, less successful weight maintenance at 9-mo follow-up was predicted by greater post-treatment activation in such brain regions as insula, ventral tegmental area, putamen, and fusiform gyrus. In summary, we found that greater activation in brain regions mediating motivational and attentional salience of food cues in obese individuals at the start of a weight-loss program was predictive of less success in the program and that such activation following the program predicted poorer weight control over a 9-mo follow-up period.

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

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.

Peptide YY levels are associated with appetite suppression in response to long-chain fatty acids.

Release of peptide YY(3-36) (PYY(3-36)) has been proposed to contribute to postprandial satiety. Using a randomized, double-blind design, we examined the effects of a 417 kcal beverage with 95% of the calories from long-chain fatty acids compared to a 21 kcal lipid-free control beverage on the temporal profiles of total plasma PYY levels and appetite ratings in 12 normal-weight human subjects. Ratings were taken before ingestion of the beverage and 15, 30, 60, 120, and 180 min later. Blood samples were taken from the subjects when ratings were made. The lipid beverage increased plasma PYY relative to the control beverage at 60-180 min after ingestion. Subjects were divided into High and Low PYY groups (N=6 in each group) on the basis of a median split. In the High PYY group, the lipid beverage was more effective in suppressing hunger and enhancing satiety than in the Low PYY group, in which the lipid beverage had no effects on appetite. Within the High PYY group, changes in mean relative hunger suppression (changes in hunger specifically attributable to the lipid load) across the 3-h test closely paralleled changes in plasma PYY after ingestion of the lipid beverage relative to the control beverage. The close temporal correspondence between these variables supports the proposed role of this peptide in the intermediate-term control of intake, possibly acting to regulate appetite during the intermeal interval.

Subdivisions of inferior temporal cortex in squirrel monkeys make dissociable contributions to visual learning and memory.

Inferior temporal cortex of squirrel monkeys consists of caudal (ITC), intermediate (ITI), and rostral (ITR) subdivisions, possibly homologous to TEO, posterior TE, and anterior TE of macaque monkeys. The present study compared visual learning in squirrel monkeys with ablations of ITC; ITI and ITR (group ITRd); or ITI, ITR, and more ventral cortex, including perirhinal cortex (group ITR+), with visual learning in unoperated controls. The ITC monkeys had significant impairments on pattern discriminations and milder deficits on delayed non-matching to sample (DNMS) of objects. The ITRd monkeys had deficits on some pattern discriminations but not on DNMS. The ITRd monkeys were significantly impaired on DNMS and some pattern discriminations. These results are similar to those found in macaques and support the proposed homologies.

Pulvinar and other subcortical connections of dorsolateral visual cortex in monkeys.

The present study used injections of neuroanatomical tracers to determine the subcortical connections of the caudal and rostral subdivisions of the dorsolateral area (DL) and the middle temporal crescent area (MT(C)) in owl monkeys (Aotus trivirgatus), squirrel monkeys (Saimiri sciureus), and macaque monkeys (Macaca fascicularis and M. radiata). Emphasis was on connections with the pulvinar. Patterns of corticopulvinar connections were related to subdivisions of the inferior pulvinar (PI) defined by histochemical or immunocytochemical architecture. Connections of DL/MT(C) were with the PI subdivisions, PICM, PICL, and PIp; the lateral pulvinar (PL); and, more sparsely, the lateral portion of the medial pulvinar (PM). In squirrel monkeys, there was a tendency for caudal DL to have stronger connections with PICL than PICM and for rostral DL/MT(C) to have stronger connections with PICM than PICL. In all three primates, DL/MT(C) had reciprocal connections with the pulvinar and claustrum; received afferents from the locus coeruleus, dorsal raphe, nucleus annularis, central superior nucleus, pontine reticular formation, lateral geniculate nucleus, paracentral nucleus, central medial nucleus, lateral hypothalamus, basal nucleus of the amygdala, and basal nucleus of Meynert/substantia innominata; and sent efferents to the pons, superior colliculus, reticular nucleus, caudate, and putamen. Projections from DL/MT(C) to the nucleus of the optic tract were also observed in squirrel and owl monkeys. Similarities in the subcortical connections of the dorsolateral region, especially those with the pulvinar, provide further support for the conclusion that the DL regions are homologous in the three primate groups.

Greater impulsivity is associated with decreased brain activation in obese women during a delay discounting task.

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.

Smaller regional gray matter volume in homeless african american cocaine-dependent men: a preliminary report.

Models of addiction include abnormalities in parts of the brain involving executive function/inhibitory control. Although previous studies have reported evidence of structural abnormalities in cocaine-dependent individuals, none have specifically targeted the homeless. The present preliminary study investigated brain structure in such an understudied group, homeless, crack-cocaine-dependent African American men (n = 9), comparing it to that in healthy controls (n = 8). Structural data were analyzed using voxel based morphometry (VBM) and a regions of interest (ROI) analysis. Homeless cocaine-dependent individuals had smaller gray matter volume in dorsolateral prefrontal cortex, anterior cingulate, the cerebellum, insula, and superior temporal gyrus. Most of these areas subserve executive function or inhibitory control. These results are similar to those found in most previous studies of non-homeless cocaine-dependent individuals. Reduced gray matter in executive function/inhibitory control regions of the brain in cocaine-dependent individuals may be a preexisting risk factor for the development of addiction and/or a consequence of drug abuse.

Effective connectivity of a reward network in obese women.

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 amygdala's modulation of activation in both orbitofrontal cortex and nucleus accumbens, but excessive influence of orbitofrontal cortex's modulation of activation in nucleus accumbens. The deficient projections from the amygdala might relate to suboptimal modulation of the affective/emotional aspects of a food's reward value or an associated cue's 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.

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 $1000 or $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.

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

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.