Effects of Processed Foods on Brain Reward Circuitry and Food Cue Learning

Study Overview
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Brief Summary
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Examine if ultra-processed (UP) foods are more effective in activating reward, attention, and memory brain regions and in promoting food cue learning than minimally-processed foods. Assess individual differences in neurobehavioral responses to UP foods.

Detailed Description
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Obesity is the second leading cause of premature death. Consumption of ultra-processed foods is theorized to be a key cause of obesity. Ultra-processed foods are formulations of cheap industrial sources of dietary energy and nutrients plus additives such as fat, sugar, and flavors that enhance acceptability of the foods. A cross-over experiment with overweight adults found that ad lib access to an ultra-processed diet for 2-weeks resulted in increased caloric intake (508 kcal/day) and more weight gain versus ad lib access to a minimally-processed diet matched for presented calories, energy density, macronutrients, sugar, sodium, and fiber. The fact that ad lib access to ultra-processed foods resulted in a large increase in caloric intake and weight gain implies that ultra-processed foods may more effectively activate brain regions implicated in reward processing, attention/salience, and memory that influence eating behavior. However, no brain imaging study has experimentally tested whether ultra-processed foods are more effective in activating brain regions implicated in reward, attention, and memory than minimally-processed foods or experimentally investigated the relative role of the elevated caloric density versus the flavor enhancers of ultra-processed foods in driving greater activation of these brain regions. Preliminary data showed that tastes of ultra-processed high-calorie chocolate milkshake produced greater activation in regions implicated in reward valuation (caudate, nucleus accumbens), attention/salience (precuneus), and memory retrieval (medial temporal gyrus, dorsomedial prefrontal cortex) than tastes of ultra-processed low-calorie chocolate milkshake. The investigators propose to evaluate the efficacy of ultra-processed foods to activate reward, attention, and memory regions compared to minimally-processed foods, investigate the relative role of the higher caloric content versus the flavor additives/enhancers of ultra-processed foods to engage this circuitry using a 2 x 2 experimental design, test whether ultra-processed foods are more effective in increasing the incentive salience of food cues than minimally-processed foods, which is important because elevated reward region response to food cues/images increases risk for excess weight gain, and test whether individuals who show the greatest responsivity of reward, attention, and memory regions to ultra-processed foods and stronger food reward cue learning are at risk for greater ad lib intake of ultra-processed foods and future body fat gain. Aim 1: Test the hypothesis that tastes, anticipated tastes, and images of ultra-processed foods activate reward, attention, and memory brain regions more than tastes, anticipated tastes, and images of minimally-processed foods, and evaluate the relative role of the higher caloric content versus flavor additives/enhancers in activating these regions using a 2 x 2 experimental design. Aim 2: Test the hypothesis that ultra-processed foods foster stronger learning of cues that predict impending tastes of ultra-processed foods than minimally-processed foods, reflected by greater increases in striatal response over the course of cue exposure and quicker responses to cues for tastes of ultra-processed foods. Aim 3: Test the hypothesis that participants who show greater activation in reward/attention/memory regions in response to tastes, anticipated tastes, and images of ultra-processed foods will consume more ultra-processed foods ad libitum (Aim 3a) and show greater future body fat gain (Aim 3b). Exploratory analyses will establish neural fingerprints that predict ad lib intake of ultra-processed foods and body fat gain (Aim 3c). Aim 4: Test the hypothesis that participants who show the most pronounced reward cue learning in response to ultra-processed foods will consume more ultra-processed foods ad libitum (Aim 4a) and show greater future body fat gain (Aim 4b).

Official Title
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Effects of Processed Foods on Brain Reward Circuitry and Food Cue Learning

Conditions
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Ultra-processed Foods (UP)

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: female and male adolescents 13-15 years of age age- and sex- adjusted zBMI scores between the 25th and 75th percentile participant and their guardian must be able to read and speak English to gather valid consent Exclusion Criteria: current eating disorders or other major psychiatric disorders (e.g., depression, bipolar, schizophrenia, substance use disorder) fMRI contra-indicators (e.g., metal implants, braces, claustrophobia, pregnancy) serious medical problems (e.g., Type 2 diabetes, cancer) history of food allergies or restrictive dietary requirements (e.g., lactose intolerance, vegan) use of psychoactive drugs more than once weekly medications that impact appetite or reward functioning (e.g., metformin, anti-psychotic medication, insulin)

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adolescent youth age 13-15<br>age- and sex- adjusted body mass index (zBMI) scores between the 25th and 75th percentile | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Fat | Investigators will use air displacement plethysmography (ADP) via the Bod Pod to assess % body fat. Body density is calculated as body mass divided by body volume; body density is used to calculate % body fat. ADP % body fat shows high test-retest reliability (r = .92-.99) and correlates with dual energy x-ray absorptiometry (DEXA) and hydrostatic weighing estimates (r = .98-.99), with ADP estimate of % body fat falling an average of only 1.7% different relative to DEXA estimates . ADP is as accurate as DEXA for assessing change in % body fat in trials. Height will be measured using a direct reading stadiometer. Weight will be assessed using digital scales with participants wearing light clothing without shoes or coats. Body mass index (BMI)(Kg/M2) will be used to confirm participants are initially at a healthy weight (BMI scores between 25th to 75th age- and sex-adjusted BMI percentile). | Baseline, 1-year, 2-year, 3-year, 4-year follow-up | 
| Dietary Intake of Ultra-Processed and Minimally-Processed Foods | Participants will self-report intake via multiple-pass 24-hr recalls as implemented by the Nutrition Data System for Research (NDS-R). Participants will complete 3 separate 24hr recalls (2 week days and 1 weekend day) within a 1-week period. | Baseline, 1-year, 2-year, 3-year, 4-year follow-up | 
| Baseline Ultra-Processed Food Cue Learning | Participants will complete an ultra-processed food cue learning computer task with solid ultra-processed (e.g., Lay's potato chips, M&Ms) and minimally-processed (e.g., berries, carrots) foods that vary in caloric content and flavor additives. Participants will choose 1 ultra-processed food and 1 minimally-processed food out of 5 options each. There will be three arbitrary fractal cues that signal the dispense of either an ultra-processed food, a minimally-processed food or no food from an apparatus containing a small metal tray. The computer task will include both paired cue trials in which the food is delivered as cued and unpaired cue trials in which the food is not delivered (80:20 ratio) and a fractal cue that is not consistently paired with a food. During the food dispense trials, the presentation of the fractal cues is followed 5 secs later by the delivery of 1 small food portion. | Baseline | 
| Baseline functional magnetic resonance imaging (fMRI) Ultra-Processed Foods Taste, Anticipated Taste, and Picture Paradigm | Participants will complete four rounds of an adapted version of a milkshake paradigm to assess activation in response to receipt (taste) and anticipated receipt of 1) high-calorie, ultra-processed food taste, 2) low-calorie, ultra-processed food taste, 3) high-calorie minimally-processed food taste, 4) low-calorie, minimally-processed food taste, and 5) a tasteless odorless solution containing the main ionic components of saliva. Participants will be cued with a picture of the specific food and label (high-calorie milkshake, low-calorie milkshake, high-calorie smoothie, low-calorie smoothie) before receipt of the tastes. | Baseline | 
| Baseline fMRI Ultra-Processed Food Picture Paradigm | Participants will complete two rounds of a block version of the food picture paradigm to examine activation in response to 40 high-calorie ultra-processed food pictures, 40 low-calorie ultra-processed food pictures, 40 high-calorie minimally-processed food pictures, 40 low-calorie minimally-processed food pictures, and 40 bottles of water. Fifty percent of each category will be branded foods/bottles to increase ecological validity. Pictures will be matched for complexity, valence and intensity across categories. After the scan, participants will be shown 40 food pictures, including pictures that were and were not used in the paradigm, and will be asked whether they had seen the foods to assess aided recall. Participants will also be asked to rate palatability of 20 food pictures per food category. | Baseline | 
| Baseline fMRI Ultra-Processed Food Cue Learning Paradigm | Participants will complete two rounds of an adapted version of the food reward learning paradigm wherein four arbitrary fractal cues will signal the delivery of either 0.7 ml of an ultra-processed milkshake, a minimally-processed smoothie, a tasteless solution, and no taste. To make learning more challenging, the paradigm includes both paired cue trials in which the taste is delivered as cued and unpaired cue trials in which the taste is not delivered at an 80:20 ratio. There will be one fractal cue that is not consistently paired with a taste. Participants will be asked to respond with a button press as soon as possible to indicate on which side of the fixation cross the stimuli appeared (providing a behavioral measure of reaction time to each cue). | Baseline | 
| Baseline Post-fMRI Ad Lib Food Intake | Participants will be presented with a 20-item buffet spread that includes ultra-processed foods (high- and low-calorie), and minimally processed foods (high- and low-calorie). Participants first perform a taste test of 1g of each of the foods. They will then complete perceptual hedonic ratings of the pleasantness, sweetness, savoriness, and desire to consume on generalized labeled magnitude scales. After the taste test, participants will be told that they are free to eat as much as they like because we have to discard the food after each participant. Participants will be alone during the 15-min tasting to minimize demand characteristics. Food will be pre- and post-weighed to determine ad lib intake. Total caloric intake will be calculated and translated to % of calorie needs. | Baseline |