Two systems are commonly referred to in the neurobiology of eating and obesity: the “homeostatic” and “hedonic” systems.
Homeostatic systems regulate eating relative to energy balance, e.g., increasing motivation to eat when energy stores are depleted.
Conversely, hedonic systems are reward-based and may promote eating in the absence of energetic need [i.e., overconsumption].
Our understanding of the neurobiology of eating accelerated over the past two decades, however, with the advent of functional magnetic resonance imaging [fMRI] to investigate brain responses to food and food cues.
What does this research paradigm tell us about the relationship between central regulation of appetite and food intake, and associations with obesity in the field of weight loss research?
Functional MRI Research
fMRI scans provide an indirect measure of activity of neurons in particular brain regions, by measuring changes in blood flow in areas of the brain that are activated by different stimuli.
This allows researchers to examine responses to a variety of dietary exposures: visual images, taste, smell, palatability, energy density, and in different contexts of fed or fasted.
fMRI research paradigms used in weight loss research may often use visual stimuli, either visible food presentations or image-based food cues, to analyse the responsiveness of brain regions associated with eating regulation.
Another common method is to provide a milkshake and its effects to water, but this does not necessarily test the influence of specific nutrients, e.g., glucose or saturated fat, on food cravings and reward pathways.
Finally, note that the actual method of consumption may trigger cognitive and related neural responses, i.e., whether food is in liquid form and drunk, or requires chewing, or is administered as an infusion or nasogastric feeding.
The potential advantage of nasogastric feeding is to isolate specific effects of a nutrient, as this method of administration would bypass the act of ingestion [i.e., drinking, chewing, etc.].
Does BMI Moderate Brain Responses?
An interesting 2021 paper by Stopyra et al. compared the effects of a nasogastric glucose infusion to water in women with a mean BMI of 35.5 and women with a BMI of 21.1.
Following the administration of either the glucose or water infusion, participants underwent two image-based exposure conditions, an attention viewing condition and a distracted viewing condition.
In the attention viewing condition, participants were asked to look attentively at high-calorie food images and non-food images, respectively. Participants then rated their craving for the food displayed in the image.
In the distracted viewing condition, participants were asked to complete a maths equation while the food images were being displayed. Participants then rated their craving for the food displayed in the image.
The findings were interesting in suggesting a moderating effect of BMI on brain region activations and the effects of distraction.
In normal weight participants, activation of brain regions associated with reward anticipation increased following the glucose infusion and during the distracted viewing condition.
However, in participants with obesity, there were no differences in brain region activations between either glucose or water infusions during either attentive or distracted viewing.
In participants with obesity, there were significant increases in the activity of brain regions associated with self-regulation and appetite regulation during the distracted viewing condition compared to the attentive viewing condition.
Conversely, in normal weight participants there was significant activation in a brain region associated with evaluating rewarding stimuli during the attentive viewing condition compared to the distracted viewing condition.
Let’s make sense of these outcomes. In this experimental design, the maths equation was presented as an overlay on the high-calorie food image to distract the participant.
And in participants with obesity, the distracted condition led to significant increases in brain activation in specific regions associated with executive function and self-regulation.
These regions are activated during conscious effort to suppress a desire to consume palatable, unhealthy foods.
The researchers basically put a pink elephant in the room, and the brain regions that showed increased activation suggest that the participants with obesity had to try very hard not to look at the pink elephant.
All Very Interesting, But Is It Reliable?
What do brain region correlates really tell us?
Two important questions arise when we try to think about this area of research within the context of weight loss research. The first is whether any such brain activations and correlations with cravings or other hedonic responses lead to clinical outcomes such as obesity.
The second is whether fMRI are reliable in the context of repeated measures over time, in order to be confident of any potential cause-and-effect relationship.
Let’s take the first question: Do fMRI studies prospectively demonstrate clinical outcomes related to neural characteristics?
Although limited, the research to date conducted in normal weight BMI participants at baseline suggested that higher reward responsiveness at baseline was associated with greater subsequent weight gain over 3 years.
The second question now becomes important: can we rely on these associations? This is where things get a little more ambiguous.
To be confident that we can relate the results of an fMRI scan to a clinical outcome like weight gain, we need to be confident that an fMRI would generate reproducible results over time.
However, the body of evidence on this question suggests that the reliability of fMRI brain activation patterns to food-related exposures from test to test may be poor.
A 26-week study by Bach et al. in patients preparing for bariatric surgery did, however, demonstrate good reliability in patterns of brain activation of food cravings over three fMRI sessions.
It is possible that differences between the Bach et al. study and previous research could be that previous research analysed selected brain regions, while the Bach et al. study used whole-brain fMRI.
Until this question is more conclusively resolved, however, we are left to conclude that the reliability of fMRI for prospective associations is questionable and, therefore, requires caution against overextrapolation.
The complexity of reward-responsiveness to eating behaviour and future weight gain was underscored by a meta-analysis from Boswell and Kober, highlighting a key challenge in weight loss research: Food cue reactivity explained about 11% of the weight-related outcomes.
This is a low overall proportion of the association, indicating that other factors—likely multiple—mediate the relationship between food cues and weight gain.
Final Thoughts
While the fMRI research provides us with fascinating insights into this complexity, we are left with the most important question: how does this apply in real life?
There is very little to draw on specifically related to diet and lifestyle, as almost all fMRI research investigating associations between brain activations and weight loss is in the context of bariatric surgery.
And the dietary interventions that have utilised fMRI provide insights into brain activations related to weight loss, not strategies that may influence those very regions to aid weight loss, a critical gap in current weight loss research.
There is some evidence that food cue reactivity, measured at baseline by fMRI, may predict successful weight loss in response to a weight loss intervention.
As I’m sure you can imagine, however, popping everyone through an fMRI scan before a weight loss intervention isn’t feasible.
And in any event, the GLP-1 agonist era may make much of this research somewhat redundant.
Yours in Science,
Alan
Learn with Us.
You’ll find our most comprehensive resources in the Alinea Nutrition Education Hub.
Our weekly Deepdive takes a take a forensic look at a recent study: you’ll understand the background, the findings, and the relevance of the study in the context of the wider literature.
Our bi-monthly video Research Lectures condense complex topics into a visual presentation for you to maximise your learning experience.
And Exclusive Articles from researchers and academics in the field of nutrition science provide insights and perspectives from the people producing the research.