Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards

Prior studies suggest that fructose compared with glucose may be a weaker suppressor of appetite, and neuroimaging research shows that food cues trigger greater brain reward responses in a fasted relative to a fed state. We sought to determine the effects of ingesting fructose versus glucose on brain, hormone, and appetitive responses to food cues and food-approach behavior. Twenty-four healthy volunteers underwent two functional magnetic resonance imaging (fMRI) sessions with ingestion of either fructose or glucose in a double-blinded, random-order cross-over design. fMRI was performed while participants viewed images of high-calorie foods and nonfood items using a block design. After each block, participants rated hunger and desire for food. Participants also performed a decision task in which they chose between immediate food rewards and delayed monetary bonuses. Hormones were measured at baseline and 30 and 60 min after drink ingestion. Ingestion of fructose relative to glucose resulted in smaller increases in plasma insulin levels and greater brain reactivity to food cues in the visual cortex (in whole-brain analysis) and left orbital frontal cortex (in region-of-interest analysis). Parallel to the neuroimaging findings, fructose versus glucose led to greater hunger and desire for food and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods. These findings suggest that ingestion of fructose relative to glucose results in greater activation of brain regions involved in attention and reward processing and may promote feeding behavior.

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Abstract 19: Stimulatory Effects of Fructose vs. Glucose on Brain Reward Activation and Hunger are Heightened in Obese Young Adults

Circulation ◽

10.1161/circ.129.suppl_1.19 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Kathleen Page ◽

Shan Luo ◽

Sandra Huang ◽

Ana Romero ◽

John Monterosso

Keyword(s):

Block Design ◽

Random Order ◽

Brain Regions ◽

Normal Weight ◽

Food Cues ◽

Male Age ◽

Glucose Ingestion ◽

Brain Reward ◽

Lean Group ◽

High Calorie

Increases in consumption of sugar-sweeteners are linked to obesity, diabetes and cardiovascular disease. Studies by our group and others suggest that the fructose component of sugar-sweeteners may act centrally to promote overeating behavior. Using functional magnetic resonance imaging (fMRI), we previously demonstrated that, unlike glucose, fructose ingestion failed to reduce neuronal activity in brain appetite and reward regions and failed to increase satiety in normal-weight adults. The objective of this study was to test the hypothesis that fructose compared to glucose ingestion would cause greater food-cue reactivity in brain reward areas and greater hunger, and that these differential effects would be heightened in obese compared to lean individuals. This study is part of a larger ongoing double-blinded, random-order crossover study on brain, hormone and appetitive responses to acute consumption of drinks containing 75 grams (300kcal) fructose or an equivalent dose of glucose. fMRI scans were performed using a 3-Tesla scanner on 13 participants, 5 obese (3 female,2 male; age 22±2, BMI 37±3.8) and 8 lean (3 female,5 male; age 21±2, BMI 22.8±1.7). Scanning was performed while participants viewed images of high-calorie food pictures and non-food items using a block design. Appetite scales were obtained before and 60 min after drink ingestion. Blood-oxygen level dependent (BOLD) sequences were used to measure brain responses to food and non-food cues after drink ingestion. Paired-t tests were performed to examine drink effects on BOLD responses to high-calorie food vs. non-food cues and hunger responses. Obese vs. lean comparison of drink effects were analyzed using independent samples T-tests. In the total group, fructose vs. glucose ingestion resulted in greater activation of the amygdala (9.1±4, p=.045) and the nucleus accumbens (11.4±6, p=.07), brain regions that mediate reward and pleasure. There were no significant differences in baseline hunger ratings between sessions. However, hunger ratings were significantly greater after consumption of fructose compared to glucose (1.9±0.6, p=.011). Body mass index (BMI) group interactions were seen with drink condition. Amygdala activation was significantly greater after fructose vs. glucose ingestion in the obese group (t(1,4)=4.406, p=0.01), but not the lean group (t(1,7)=0.754, p=0.48). Ratings of hunger tended to be higher after fructose vs. glucose ingestion in the obese compared to the lean group but the differences were not statistically significant with this sample size (p=0.15). In conclusion, these results demonstrate that acute consumption of fructose compared to glucose results in greater brain reward activation to high-calorie food cues and increased hunger. These disparate responses to fructose vs. glucose ingestion were heightened in obese individuals and may play a role in promoting overeating behavior.

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The effects of the form of sugar (solid vs. beverage) on body weight and fMRI activation: A randomized controlled pilot study

PLoS ONE ◽

10.1371/journal.pone.0251700 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0251700

Author(s):

John W. Apolzan ◽

Owen T. Carmichael ◽

Krystal M. Kirby ◽

Sreekrishna R. Ramakrishnapillai ◽

Robbie A. Beyl ◽

...

Keyword(s):

Body Weight ◽

Energy Homeostasis ◽

Pilot Trial ◽

Brain Regions ◽

Reward Processing ◽

Daily Consumption ◽

Fed State ◽

Randomized Controlled ◽

The Right ◽

The Brain

Objective To test if sugar sweetened beverages (SSBs) and sugar sweetened solids (SSSs) have differential effects on body weight and reward processing in the brain. Methods In a single blind randomized controlled pilot trial (RCT), twenty participants with BMI between 20 and 40 kg/m2 were randomized to consume a 20 fluid ounce soda (SSB, 248 kcal) or the equivalent in solid form (SSS; similar to thick gelatin or gummy candy) daily. At baseline and day 28, fasting body weight and fed-state BOLD fMRI of the brain were assessed. Differences in fMRI signals between views of low-fat (LF (<30%)) high sugar (HS (>30%)) food, and non-food images were calculated in brain regions implicated in energy homeostasis, taste, and reward. Results All participants in the SSB (6F 4M; 8 Caucasian; 36±14 y, 28.2±5.5 kg/m2; Mean±SD) and SSS (3F 7M; 6 Caucasian; 39±12; 26.3±4.4) groups completed the study. Weight change was 0.27±0.78 kg between SSB and SSS participants. Changes in the fMRI response to LF/HS foods in reward, homeostatic and taste regions tended to not be different between the groups over the four weeks. However, activation of the right substantia nigra increased following the SSB but decreased activation following the SSS in response to LF/HS foods over 28 days (-0.32±0.12). Ratings of wanting for LF/HS foods were correlated with activation in several brain regions, including the OFC. Conclusions Change in weight was modest between the groups in this study. Daily consumption of a SSB over 28 days led to mixed responses to LF/HS foods in areas of the brain associated with reward. Ratings of wanting are correlated with fMRI activation inside an MRI scanner.

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The Effects of the Form of Sugar (Solid vs. Beverage) on Body Weight and Neuronal Activity: A 28 Day Randomized Pilot Study (P08-001-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.p08-001-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

John Apolzan ◽

Owen Carmichael ◽

S Nicole Fearnbach ◽

Krystal Kirby ◽

Sreekrishna Ramakrishnapillai ◽

...

Keyword(s):

Body Weight ◽

Pilot Study ◽

Energy Homeostasis ◽

Brain Activity ◽

A Priori ◽

Brain Regions ◽

Reward Processing ◽

Group Differences ◽

Fed State ◽

Funding Sources

Abstract Objectives To test if sugar sweetened beverages (SSBs) and sugar sweetened solids (SSSs) have differential effects on body weight and food reward processing. Methods In a single blind RCT, twenty participants with a BMI between 20–40 kg/m2 were randomized to consume a 20 fl oz soda/d (SSB, 248 kcal) vs. the equivalent energy and nutrients in solid form (SSS; similar to a thick jello and/or gummy candy). At baseline and day 28, fasting body weight and fed state brain activation responses to low fat high sugar foods (LF < 30%, HS > 30%) and non-food objects were assessed. The fMRI scan began 30 min after initiation of consumption of the 248 kcal dose of their randomized treatment. Summary measures of differences in fMRI BOLD signals between LFHS vs non-food images were calculated in a set of a priori defined brain regions implicated in energy homeostasis, taste, reward, and motivation to eat. Results Ten participants in the SSB (6F 4 M; 80% White; 39 ±4 y, Mean ± SEM) and ten in the SSS (3F 7 M; 60% White; 36 ± 5) completed the study. Baseline BMI was 28.2 ± 1.7 kg/m2 and 26.3 ± 1.4 in the SSB and SSS groups, respectively. No difference in change in body weight for SSB vs. SSS (0.56 ± 0.43 kg; P = 0.22) was seen. Changes in fMRI activation in homeostatic and taste regions were not different. Among reward and motivation related regions, fMRI activation within the caudate nucleus, cingulate gyrus, and medial orbitofrontal cortex were not different at baseline, but increased in SSS and decreased in SSB group (mean group differences in activation change: –0.30 ± 0.15, –0.36 ± 0.11, and –0.60 ± 0.25, P ˂ 0.05; respectively). fMRI activation in the insula was greater at baseline in SSS compared to SSB but the two groups converged to similar values at day 28 (mean group differences in activation change: 0.19 ± 0.08, P ˂ 0.05). Conclusions Consumption of SSB vs. SSS products produced distinct changes to brain activity within specific brain regions that control eating behavior despite no change in body weight between groups. Understanding the neural and physiological consequences of consuming added sugar in different forms will better inform current efforts to reduce its consumption and help regulate policy. This pilot study provides promising data for a longer duration, well-powered follow-up study. Funding Sources NIH U54GM104940, P30DK072476, Pennington Biomedical Research Foundation.

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Obesity and Dietary Added Sugar Interact to Affect Postprandial GLP-1 and Its Relationship to Striatal Responses to Food Cues and Feeding Behavior

Frontiers in Endocrinology ◽

10.3389/fendo.2021.638504 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sabrina Jones ◽

Shan Luo ◽

Hilary M. Dorton ◽

Alexandra G. Yunker ◽

Brendan Angelo ◽

...

Keyword(s):

Feeding Behavior ◽

Cue Reactivity ◽

Brain Regions ◽

Plain Water ◽

Food Cues ◽

Brain Response ◽

Added Sugar ◽

Low Calorie ◽

Sugar Intake ◽

High Calorie

It has been hypothesized that the incretin hormone, glucagon-like peptide-1 (GLP-1), decreases overeating by influencing mesolimbic brain regions that process food-cues, including the dorsal striatum. We previously showed that habitual added sugar intake was associated with lower glucose-induced circulating GLP-1 and a greater striatal response to high calorie food cues in lean individuals. Less is known about how dietary added sugar and obesity may interact to affect postprandial GLP-1 and its relationship to striatal responses to food cues and feeding behavior. The current study aimed to expand upon previous research by assessing how circulating GLP-1 and striatal food cue reactivity are affected by acute glucose consumption in participants with varied BMIs and amounts of habitual consumption of added sugar. This analysis included 72 participants from the Brain Response to Sugar Study who completed two study visits where they consumed either plain water or 75g glucose dissolved in water (order randomized; both drinks were flavored with non-caloric cherry flavoring) and underwent repeated blood sampling, a functional magnetic resonance imaging (fMRI) based food-cue task, and an ad-libitum buffet meal. Correlations between circulating GLP-1 levels, striatal food-cue reactivity, and food intake were assessed, and interactions between obesity and added sugar on GLP-1 and striatal responses were examined. An interaction between BMI and dietary added sugar was associated with reduced post-glucose GLP-1 secretion. Participants who were obese and consumed high levels of added sugar had the smallest increase in plasma GLP-1 levels. Glucose-induced GLP-1 secretion was correlated with lower dorsal striatal reactivity to high-calorie versus low-calorie food-cues, driven by an increase in reactivity to low calorie food-cues. The increase in dorsal striatal reactivity to low calorie food-cues was negatively correlated with sugar consumed at the buffet. These findings suggest that an interaction between obesity and dietary added sugar intake is associated with additive reductions in postprandial GLP-1 secretion. Additionally, the results suggest that changes to dorsal striatal food cue reactivity through a combination of dietary added sugar and obesity may affect food consumption.

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No effect of a dopaminergic modulation fMRI task by amisulpride and L-DOPA on reward anticipation in healthy volunteers

Psychopharmacology ◽

10.1007/s00213-020-05693-8 ◽

2020 ◽

Author(s):

Oliver Grimm ◽

Magdalena Nägele ◽

Lea Küpper-Tetzel ◽

Moritz de Greck ◽

Michael Plichta ◽

...

Keyword(s):

Healthy Volunteers ◽

Region Of Interest ◽

Reward System ◽

Blood Oxygen Level Dependent ◽

Brain Regions ◽

Reward Processing ◽

Activity Level ◽

Placebo Condition ◽

Reward Anticipation ◽

Monetary Incentive Delay

Abstract Rationale Dysregulation of dopaminergic neurotransmission, specifically altered reward processing assessed via the reward anticipation in the MID task, plays a central role in the etiopathogenesis of neuropsychiatric disorders. Objectives We hypothesized to find a difference in the activity level of the reward system (measured by the proxy reward anticipation) under drug administration versus placebo, in that amisulpride reduces, and L-DOPA enhances, its activity. Methods We studied the influence of dopamine agonist L-DOPA and the antagonist amisulpride on the reward system using functional magnetic resonance imaging (fMRI) during a monetary incentive delay (MID) task in n = 45 healthy volunteers in a randomized, blinded, cross-over study. Results The MID paradigm elicits strong activation in reward-dependent structures (such as ventral striatum, putamen, caudate, anterior insula) during reward anticipation. The placebo effect demonstrated the expected significant blood oxygen level–dependent activity in reward-dependent brain regions. Neither amisulpride nor L-DOPA led to significant changes in comparison with the placebo condition. This was true for whole-brain analysis as well as analysis of a pre-defined nucleus accumbens region-of-interest mask. Conclusion The present results cast doubt on the sensitivity of reward anticipation contrast in the MID task for assessing dopamine-specific changes in healthy volunteers by pharmaco-fMRI. While our task was not well-suited for detailed analysis of the outcome phase, we provide reasonable arguments that the lack of effect in the anticipation phase is not due to an inefficient task but points to unexpected behavior of the reward system during pharmacological challenge. Group differences of reward anticipation should therefore not be seen as simple representatives of dopaminergic states.

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Brain Responses to High-Calorie Visual Food Cues in Individuals with Normal-Weight or Obesity: An Activation Likelihood Estimation Meta-Analysis

Brain Sciences ◽

10.3390/brainsci11121587 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1587

Author(s):

Yingkai Yang ◽

Qian Wu ◽

Filip Morys

Keyword(s):

Weight Gain ◽

Meta Analysis ◽

Likelihood Estimation ◽

Neural Mechanism ◽

Normal Weight ◽

Reward Processing ◽

Activation Likelihood Estimation ◽

Food Cues ◽

Middle Occipital Gyrus ◽

High Calorie

Overconsumption of high-calorie or unhealthy foods commonly leads to weight gain. Understanding people’s neural responses to high-calorie food cues might help to develop better interventions for preventing or reducing overeating and weight gain. In this review, we conducted a coordinate-based meta-analysis of functional magnetic resonance imaging studies of viewing high-calorie food cues in both normal-weight people and people with obesity. Electronic databases were searched for relevant articles, retrieving 59 eligible studies containing 2410 unique participants. The results of an activation likelihood estimation indicate large clusters in a range of structures, including the orbitofrontal cortex (OFC), amygdala, insula/frontal operculum, culmen, as well as the middle occipital gyrus, lingual gyrus, and fusiform gyrus. Conjunction analysis suggested that both normal-weight people and people with obesity activated OFC, supporting that the two groups share common neural substrates of reward processing when viewing high-calorie food cues. The contrast analyses did not show significant activations when comparing obesity with normal-weight. Together, these results provide new important evidence for the neural mechanism underlying high-calorie food cues processing, and new insights into common and distinct brain activations of viewing high-calorie food cues between people with obesity and normal-weight people.

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Neural substrates of propranolol-induced impairments in the reconsolidation of nicotine-associated memories in smokers

Translational Psychiatry ◽

10.1038/s41398-021-01566-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xiao Lin ◽

Jiahui Deng ◽

Kai Yuan ◽

Qiandong Wang ◽

Lin Liu ◽

...

Keyword(s):

Neural Activity ◽

Neural Substrates ◽

Brain Regions ◽

Reward Processing ◽

Memory Reconsolidation ◽

Functional Magnetic Resonance ◽

Resonance Imaging ◽

Postcentral Gyrus ◽

Propranolol Group ◽

Propranolol Administration

AbstractThe majority of smokers relapse even after successfully quitting because of the craving to smoking after unexpectedly re-exposed to smoking-related cues. This conditioned craving is mediated by reward memories that are frequently experienced and stubbornly resistant to treatment. Reconsolidation theory posits that well-consolidated memories are destabilized after retrieval, and this process renders memories labile and vulnerable to amnestic intervention. This study tests the retrieval reconsolidation procedure to decrease nicotine craving among people who smoke. In this study, 52 male smokers received a single dose of propranolol (n = 27) or placebo (n = 25) before the reactivation of nicotine-associated memories to impair the reconsolidation process. Craving for smoking and neural activity in response to smoking-related cues served as primary outcomes. Functional magnetic resonance imaging was performed during the memory reconsolidation process. The disruption of reconsolidation by propranolol decreased craving for smoking. Reactivity of the postcentral gyrus in response to smoking-related cues also decreased in the propranolol group after the reconsolidation manipulation. Functional connectivity between the hippocampus and striatum was higher during memory reconsolidation in the propranolol group. Furthermore, the increase in coupling between the hippocampus and striatum positively correlated with the decrease in craving after the reconsolidation manipulation in the propranolol group. Propranolol administration before memory reactivation disrupted the reconsolidation of smoking-related memories in smokers by mediating brain regions that are involved in memory and reward processing. These findings demonstrate the noradrenergic regulation of memory reconsolidation in humans and suggest that adjunct propranolol administration can facilitate the treatment of nicotine dependence. The present study was pre-registered at ClinicalTrials.gov (registration no. ChiCTR1900024412).

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A probabilistic atlas of the human ventral tegmental area (VTA) based on 7 Tesla MRI data

Brain Structure and Function ◽

10.1007/s00429-021-02231-w ◽

2021 ◽

Vol 226 (4) ◽

pp. 1155-1167 ◽

Cited By ~ 1

Author(s):

Anne C. Trutti ◽

Laura Fontanesi ◽

Martijn J. Mulder ◽

Pierre-Louis Bazin ◽

Bernhard Hommel ◽

...

Keyword(s):

Ventral Tegmental Area ◽

Region Of Interest ◽

Reward Processing ◽

7 Tesla ◽

Subcortical Structures ◽

7 Tesla Mri ◽

Subcortical Nuclei ◽

Ventral Tegmental ◽

The Brain

AbstractFunctional magnetic resonance imaging (fMRI) BOLD signal is commonly localized by using neuroanatomical atlases, which can also serve for region of interest analyses. Yet, the available MRI atlases have serious limitations when it comes to imaging subcortical structures: only 7% of the 455 subcortical nuclei are captured by current atlases. This highlights the general difficulty in mapping smaller nuclei deep in the brain, which can be addressed using ultra-high field 7 Tesla (T) MRI. The ventral tegmental area (VTA) is a subcortical structure that plays a pivotal role in reward processing, learning and memory. Despite the significant interest in this nucleus in cognitive neuroscience, there are currently no available, anatomically precise VTA atlases derived from 7 T MRI data that cover the full region of the VTA. Here, we first provide a protocol for multimodal VTA imaging and delineation. We then provide a data description of a probabilistic VTA atlas based on in vivo 7 T MRI data.

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Cannabinoids, reward processing, and psychosis

Psychopharmacology ◽

10.1007/s00213-021-05801-2 ◽

2021 ◽

Author(s):

Brandon Gunasekera ◽

Kelly Diederen ◽

Sagnik Bhattacharyya

Keyword(s):

Psychotic Disorders ◽

Neural Substrates ◽

Brain Regions ◽

Reward Processing ◽

Anterior Cingulate ◽

Psychotic Symptoms ◽

Dopamine Synthesis ◽

Future Research ◽

Drug Challenge ◽

Psychotomimetic Effects

Abstract Background Evidence suggests that an overlap exists between the neurobiology of psychotic disorders and the effects of cannabinoids on neurocognitive and neurochemical substrates involved in reward processing. Aims We investigate whether the psychotomimetic effects of delta-9-tetrahydrocannabinol (THC) and the antipsychotic potential of cannabidiol (CBD) are underpinned by their effects on the reward system and dopamine. Methods This narrative review focuses on the overlap between altered dopamine signalling and reward processing induced by cannabinoids, pre-clinically and in humans. A systematic search was conducted of acute cannabinoid drug-challenge studies using neuroimaging in healthy subjects and those with psychosis Results There is evidence of increased striatal presynaptic dopamine synthesis and release in psychosis, as well as abnormal engagement of the striatum during reward processing. Although, acute THC challenges have elicited a modest effect on striatal dopamine, cannabis users generally indicate impaired presynaptic dopaminergic function. Functional MRI studies have identified that a single dose of THC may modulate regions involved in reward and salience processing such as the striatum, midbrain, insular, and anterior cingulate, with some effects correlating with the severity of THC-induced psychotic symptoms. CBD may modulate brain regions involved in reward/salience processing in an opposite direction to that of THC. Conclusions There is evidence to suggest modulation of reward processing and its neural substrates by THC and CBD. Whether such effects underlie the psychotomimetic/antipsychotic effects of these cannabinoids remains unclear. Future research should address these unanswered questions to understand the relationship between endocannabinoid dysfunction, reward processing abnormalities, and psychosis.

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Mapping the common and distinct neural correlates of visual, rule and motor conflict

10.1101/2020.11.19.388231 ◽

2020 ◽

Author(s):

Bryony Goulding Mew ◽

Darije Custovic ◽

Eyal Soreq ◽

Romy Lorenz ◽

Ines Violante ◽

...

Keyword(s):

Region Of Interest ◽

Neural Correlates ◽

Brain Regions ◽

Control Mechanisms ◽

Activation Patterns ◽

The Common ◽

Full Factorial ◽

The Brain ◽

Categorical Scale ◽

Conflict Types

AbstractFlexible behaviour requires cognitive-control mechanisms to efficiently resolve conflict between competing information and alternative actions. Whether a global neural resource mediates all forms of conflict or this is achieved within domainspecific systems remains debated. We use a novel fMRI paradigm to orthogonally manipulate rule, response and stimulus-based conflict within a full-factorial design. Whole-brain voxelwise analyses show that activation patterns associated with these conflict types are distinct but partially overlapping within Multiple Demand Cortex (MDC), the brain regions that are most commonly active during cognitive tasks. Region of interest analysis shows that most MDC sub-regions are activated for all conflict types, but to significantly varying levels. We propose that conflict resolution is an emergent property of distributed brain networks, the functional-anatomical components of which place on a continuous, not categorical, scale from domain-specialised to domain general. MDC brain regions place towards one end of that scale but display considerable functional heterogeneity.

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