Pairing Neutral Cues with Alcohol Intoxication: New Findings in Executive and Attention Networks

Rationale: Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication. Objectives: Extending our prior work to examine the influence of alcoholism risk factors, we paired abstract visual stimuli with intravenous alcohol delivered covertly and examined brain responses to these Pavlovian conditioned stimuli in fMRI when subjects were not intoxicated. Methods: Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli. Shapes were paired with a rapidly rising alcohol limb (CS+) using intravenous alcohol infusion targeting a final peak breath alcohol concentration of 0.045 g/dL or saline (CS−) infusion at matched rates. On day two, subjects performed monetary delay discounting outside the scanner to assess delay tolerance and then underwent event-related fMRI while performing the same task with CS+, CS−, and an irrelevant symbol. Results: CS+ elicited stronger activation than CS− in frontoparietal executive/attention and orbitofrontal reward-associated networks. Risk factors including family history, recent drinking, sex, and age of drinking onset did not relate to the [CS+ > CS−] activation. Delay-tolerant choice and [CS+ > CS−] activation in right inferior parietal cortex were positively related. Conclusions: Networks governing executive attention and reward showed enhanced responses to stimuli experimentally paired with intoxication, with the right parietal cortex implicated in both alcohol cue pairing and intertemporal choice. While different from our previous study results in 14 men, we believe this paradigm in a large sample of male and female drinkers offers novel insights into Pavlovian processes less affected by idiosyncratic drug associations

Corticostriatal and dopaminergic response to beer flavor with both fMRI and [11C]raclopride Positron Emission Tomography

Background Cue-evoked drug seeking behavior likely depends on interactions between frontal activity and ventral striatal (VST) dopamine transmission. Using [11C]raclopride (RAC) positron emission tomography (PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST dopamine (DA) release in beer drinkers, inferred by RAC displacement. Here, a subset of subjects from this previous RAC-PET study underwent a similar paradigm during functional magnetic resonance imaging (fMRI) to test how orbitofrontal cortex (OFC) and VST BOLD responses to beer flavor are related to VST DA release and motivation to drink. Methods Male beer drinkers (n=28, age=24±2, drinks/week=16±10) from our previous PET study participated in a similar fMRI paradigm wherein subjects tasted their most frequently consumed brand of beer and Gatorade® (appetitive control). We tested for correlations between blood oxygenation level dependent (BOLD) activation in fMRI and VST DA responses in PET, and drinking-related variables. Results Compared to Gatorade, beer flavor increased wanting and desire to drink, and induced BOLD responses in bilateral OFC and right VST. Wanting and desire to drink correlated with both right VST and medial OFC BOLD activation to beer flavor. Like the BOLD findings, beer flavor (relative to Gatorade) again induced right VST DA release in this fMRI subject subset, but there was no correlation between DA release and the magnitude of BOLD responses in frontal regions of interest. Conclusions Both imaging modalities showed a right lateralized VST response (BOLD and DA release) to a drug-paired conditioned stimulus, whereas fMRI BOLD responses in the VST and medial OFC also reflected wanting and desire to drink. The data suggest the possibility that responses to drug-paired cues may be rightward biased in the VST (at least in right-handed males), and that VST and OFC responses in this gustatory paradigm reflect stimulus wanting

Ghrelin is not Related to Hunger or Calories Consumed at Breakfast in Lean and Obese Women

poster abstractBackground: The mechanisms that result in greater caloric intake in obese individuals are incompletely understood. Ghrelin administration increases ad lib food intake in humans. We investigated the relationship of ghrelin to calorie consumption and hunger at breakfast on two separate occasions in lean and obese women. Methods: 23 lean (BMI 22.3±0.5 kg/m2, 26.5±1.0 yr) and 25 obese (BMI 36.9±0.7 kg/m2, 27.8±1.1 yr) women participated in a noncontiguous 2 day study. The minimum and maximum days between visits were 6 and 43 days. Participants were given the same breakfast on both days (turkey sausage, French toast with margarine/syrup, fruit cup, coffee, tea, diet soda, or water) with portions adjusted to provide 20% of the daily energy requirement for weight maintenance. Subjects were instructed to eat until full. Hunger was evaluated on a Satiety Labeled Intensity Magnitude Scale (SLIM) before and after the meal. Anchors were “greatest imaginable fullness” at 0 and “greatest imaginable hunger” at 100. Blood samples were collected over 120 minutes for measurement of active ghrelin. Results: Lean subjects consumed an equivalent number of calories on both days (380.0±14.6 vs 378.2±14.9 kcal), as did the obese (419.4±16.2 vs 428.8±15.4 kcal). On average for both days, obese consumed significantly more breakfast calories than lean (424.1±11.1 vs 379.1±10.3 kcal; P<0.01), but the same percentage of calories provided (85.7±1.8 vs 86.1±1.7 %kcal). Lean subjects rated hunger before breakfast the same on both days (69.2±1.6 vs 71.7±1.4), as did the obese (69.8±1.6 vs 69.6±1.8), and there was no difference between the groups. Lean subjects rated hunger after breakfast the same on both days (27.8±1.9 vs 30.3±2.4), as did the obese (25.0±1.7 vs 24.3±1.8). The reduction in hunger score following breakfast was significant for both groups (P<0.0001), with the obese reporting significantly less hunger/more fullness after breakfast than the lean (P=0.02). Fasting ghrelin was significantly greater in the lean than obese women (549.9±58.9 vs 231.0±29.1 pg/ml; P<0.0001). Ghrelin was significantly reduced at 60 min following breakfast in the lean (375.8±49.2 pg/ml; P=0.028) but not the obese (212.2±26.4 pg/ml). Ghrelin was not related to hunger score prior to breakfast, and there was no relationship between reduction in ghrelin and hunger score in the lean or obese. Conclusion: Caloric intake (as a percentage provided) and hunger scores before breakfast on two occasions were the same for both lean and obese women. Fasting ghrelin was significantly different between lean and obese women but did not predict hunger score or calories consumed. Our findings do not support a role for ghrelin in driving food intake at breakfast

Family history of alcoholism and the human brain response to oral sucrose

A heightened hedonic response to sweet tastes has been associated with increased alcohol preference and alcohol consumption in both humans and animals. The principal goal of this study was to examine blood oxygenation level dependent (BOLD) activation to high- and low-concentration sweet solutions in subjects who are either positive (FHP) or negative (FHN) for a family history of alcoholism. Seventy-four non-treatment seeking, community-recruited, healthy volunteers (22.8 ± 1.6 SD years; 43% men) rated a range of sucrose concentrations in a taste test and underwent functional magnetic resonance imaging (fMRI) during oral delivery of water, 0.83 M, and 0.10 M sucrose. Sucrose compared to water produced robust activation in primary gustatory cortex, ventral insula, amygdala, and ventral striatum. FHP subjects displayed greater bilateral amygdala activation than FHN subjects in the low sucrose concentration (0.10 M). In secondary analyses, the right amygdala response to the 0.10 M sucrose was greatest in FHP women. When accounting for group differences in drinks per week, the family history groups remained significantly different in their right amygdala response to 0.10 M sucrose. Our findings suggest that the brain response to oral sucrose differs with a family history of alcoholism, and that this response to a mildly reinforcing primary reward might be an endophenotypic marker of alcoholism risk

The apéritif effect: Alcohol's effects on the brain's response to food aromas in women

OBJECTIVE: Consuming alcohol prior to a meal (an apéritif) increases food consumption. This greater food consumption may result from increased activity in brain regions that mediate reward and regulate feeding behavior. Using functional magnetic resonance imaging, we evaluated the blood oxygenation level dependent (BOLD) response to the food aromas of either roast beef or Italian meat sauce following pharmacokinetically controlled intravenous infusion of alcohol. METHODS: BOLD activation to food aromas in non-obese women (n = 35) was evaluated once during intravenous infusion of 6% v/v EtOH, clamped at a steady-state breath alcohol concentration of 50 mg%, and once during infusion of saline using matching pump rates. Ad libitum intake of roast beef with noodles or Italian meat sauce with pasta following imaging was recorded. RESULTS: BOLD activation to food relative to non-food odors in the hypothalamic area was increased during alcohol pre-load when compared to saline. Food consumption was significantly greater, and levels of ghrelin were reduced, following alcohol. CONCLUSIONS: An alcohol pre-load increased food consumption and potentiated differences between food and non-food BOLD responses in the region of the hypothalamus. The hypothalamus may mediate the interplay of alcohol and responses to food cues, thus playing a role in the apéritif phenomenon

Family history of alcoholism and the human brain response to oral sucrose

A heightened hedonic response to sweet tastes has been associated with increased alcohol preference and alcohol consumption in both humans and animals. The principal goal of this study was to examine blood oxygenation level dependent (BOLD) activation to high- and low-concentration sweet solutions in subjects who are either positive (FHP) or negative (FHN) for a family history of alcoholism. Seventy-four non-treatment seeking, community-recruited, healthy volunteers (22.8 ± 1.6 SD years; 43% men) rated a range of sucrose concentrations in a taste test and underwent functional magnetic resonance imaging (fMRI) during oral delivery of water, 0.83 M, and 0.10 M sucrose. Sucrose compared to water produced robust activation in primary gustatory cortex, ventral insula, amygdala, and ventral striatum. FHP subjects displayed greater bilateral amygdala activation than FHN subjects in the low sucrose concentration (0.10 M). In secondary analyses, the right amygdala response to the 0.10 M sucrose was greatest in FHP women. When accounting for group differences in drinks per week, the family history groups remained significantly different in their right amygdala response to 0.10 M sucrose. Our findings suggest that the brain response to oral sucrose differs with a family history of alcoholism, and that this response to a mildly reinforcing primary reward might be an endophenotypic marker of alcoholism risk

Ghrelin is not Related to Hunger or Calories Consumed at Breakfast in Lean and Obese Women

poster abstractBackground: The mechanisms that result in greater caloric intake in obese individuals are incompletely understood. Ghrelin administration increases ad lib food intake in humans. We investigated the relationship of ghrelin to calorie consumption and hunger at breakfast on two separate occasions in lean and obese women. Methods: 23 lean (BMI 22.3±0.5 kg/m2, 26.5±1.0 yr) and 25 obese (BMI 36.9±0.7 kg/m2, 27.8±1.1 yr) women participated in a noncontiguous 2 day study. The minimum and maximum days between visits were 6 and 43 days. Participants were given the same breakfast on both days (turkey sausage, French toast with margarine/syrup, fruit cup, coffee, tea, diet soda, or water) with portions adjusted to provide 20% of the daily energy requirement for weight maintenance. Subjects were instructed to eat until full. Hunger was evaluated on a Satiety Labeled Intensity Magnitude Scale (SLIM) before and after the meal. Anchors were “greatest imaginable fullness” at 0 and “greatest imaginable hunger” at 100. Blood samples were collected over 120 minutes for measurement of active ghrelin. Results: Lean subjects consumed an equivalent number of calories on both days (380.0±14.6 vs 378.2±14.9 kcal), as did the obese (419.4±16.2 vs 428.8±15.4 kcal). On average for both days, obese consumed significantly more breakfast calories than lean (424.1±11.1 vs 379.1±10.3 kcal; P<0.01), but the same percentage of calories provided (85.7±1.8 vs 86.1±1.7 %kcal). Lean subjects rated hunger before breakfast the same on both days (69.2±1.6 vs 71.7±1.4), as did the obese (69.8±1.6 vs 69.6±1.8), and there was no difference between the groups. Lean subjects rated hunger after breakfast the same on both days (27.8±1.9 vs 30.3±2.4), as did the obese (25.0±1.7 vs 24.3±1.8). The reduction in hunger score following breakfast was significant for both groups (P<0.0001), with the obese reporting significantly less hunger/more fullness after breakfast than the lean (P=0.02). Fasting ghrelin was significantly greater in the lean than obese women (549.9±58.9 vs 231.0±29.1 pg/ml; P<0.0001). Ghrelin was significantly reduced at 60 min following breakfast in the lean (375.8±49.2 pg/ml; P=0.028) but not the obese (212.2±26.4 pg/ml). Ghrelin was not related to hunger score prior to breakfast, and there was no relationship between reduction in ghrelin and hunger score in the lean or obese. Conclusion: Caloric intake (as a percentage provided) and hunger scores before breakfast on two occasions were the same for both lean and obese women. Fasting ghrelin was significantly different between lean and obese women but did not predict hunger score or calories consumed. Our findings do not support a role for ghrelin in driving food intake at breakfast