Sci is still tracking her caloric intake every day for the goddess (well, mostly for herself, but also for the goddess). It’s very long, slow haul. Sci still considers days when she eats no more than 2000 calories (preferably a little less) as good days. That may not seem like much of a diet, but compared to my previous intake, it’s quite a big cut. And many days I just don’t make it.
But obviously, this has stayed on my mind. I can’t help thinking about how we register food in the brain, how we tell when we are full, and if there’s a difference between when we know we are full vs when we KNOW we are full. Sci will admit there’s often a big difference between when I feel myself getting full and when I stop eating.
But then I found something that made the issue even more near and dear to my heart. It could have something to do with dopamine!
Tomasi et al. “Association of body mass and brain activation during gastric distention: implications for obesity” PLoS ONE, 2009
So as I’m sure you all know, when you eat, food goes into your stomach and stretches it. This is called gastric distention (GD) and is totally normal. Your stomach isn’t that big normally. When empty, it’s only got 50mL of volume, but it will easily expand to hold as much as 1- 1.5L.
You may think the way to someone’s heart it through their stomach. This isn’t true, and is in fact a very circuitous route. But you can’t get to someone’s BRAIN through their stomach (sort of). The stomach has a lot of innervation that goes directly to the brain (via the vagus nerve, which is one SERIOUSLY important cranial nerve that Sci will have to blog about someday), detecting when its empty, when its full, and even the caloric and chemical content of what the stomach is full of. There are various hormones (ghrelin and leptin are two) which help control how hungry you are and how much food you consume, but the role of the stomach itself in feelings of satiety is not very well understood. It’s known that if you distend the stomach, it sends signals to the brain, and that stomach distention will stop food intake and is associated with a feeling of fullness. We even know several brain regions (like the amygdala) which are activated when the stomach is distended.
But what we don’t know is how GD relates to brain activation in various areas in obese and non-obese subjects. This is a big issue. One of the issues that obese people often face is that they are not able to stop eating when they are full, even though they DETECT that they are full just fine. It’s very possible that this is a brain and neurochemical issue. So for this study, the scientists took people who were both of healthy and obese BMIs, and distended their stomachs, while imaging their brains for activation, and looking to see what was different.
Now HOW did they go about distending their stomachs? After all, you have to lie pretty still in an MRI. Well they used something called a gastric balloon, which is the main reason I have decided never to volunteer for this study. Observe:
At the bottom of this picture you can see the stomach, and inside the stomach, a little balloon. The patient SWALLOWED the balloon, which was connected to a line, and it dropped into their stomach. And another tip. This “balloon” was really a non-lubricated condom. Yikes. Really. Ick. I couldn’t do that. I wonder what they did about the gag reflex…anyway. So the patients then had this balloon in their stomachs. They they slowly filled the balloon up to 500mL or 700mL maximum volume, causing stomach distention. They also had the subjects rate how full they were and their desire for food during the study (patients did not differ in being full or in desire for food).
So while they were filling this balloon with water to cause stomach distention, they took some MRI pictures. Here they are:
This picture is straight up activation or deactivation of brain regions, without regard for BMI.
Lessee…what we got here… I see some deactivation in the caudate, cerebellum, inferior frontal gyrus…some activation in the insula, inferior parietal lobe…
But the real question is not what’s activated, it’s how that activation relates to BMI. See here:
These are pictures where BMI is correlated with the activation in the brain during GD. They found LESS activation of areas like the midbrain (containing the ventral tegmental area, a source for dopamine neurons), the pons (a source of serotonin neurons), and the hypothalamus (which is known to control food intake. These areas were activated MORE in subjects with normal BMI, and less (or not at all) in obese subjects.
The scientists took these negative correlations (less activation with higher body weight) to means a decreased sensitivity to GD in these regions, possibly correlated with changes in dopamine and serotonin, which are molecules known to be associated with rewarding properties and food intake. They also noticed the negative association between GD and activation in the hypothalamus, which is known to regulate food intake, and a negative association here could indicate some major differences in hypothalamic regulation.
So it appears that obese patients in this study had reduced activation in several brain areas to GD. This could mean they feel it less, causing them to eat more (until they are painfully full), or that they have become desensitized to the effects of GD, and simply don’t feel full at all.
But they found one more thing. They found positive correlations between BMI and activity in areas like the cerebellum and the insula. The insula is becoming a big brain player these days, known to have roles in drug reward, food intake, taste perception, and other types of somatic processing (there was a BIG paper on smokers with strokes affecting their insula a while back…Sci really needs to blog that!). The cerebellum, which used to be associated only with things like balance and motor control, is now known to be far more than that. It has direct connections to the hypothalamus, and reacts in response to taste and smell cues, indicating that it may have a role in feeding.
The authors of this study interpreted this positive correlation as something that might encourage further food intake in obese subjects. This, combined with the decreased sensitivity in other regions, could mean that the brakes are off, and the gas is on. The brakes are off, you no longer stop eating when you are full or feel as rewarded by a meal, and the gas is on, you have increased incentive to keep eating, despite your stomach distention. This could mean that, in looking for therapies for people who overeat chronically, we may have to attack two sides of the issue, the lack of feeling full, and the urge to chronically overeat.
There are several questions that I have about this particular study. First, when you’re dealing with obese patients, is there any statistical difference in the size their stomachs can distend TO? Perhaps the distention provided by the balloon just wasn’t enough to cause equivalent activation, but this was a result of stomach size rather than brain sensitivity.
Also, this isn’t food. It’s a balloon. Well, it’s a condom. Other studies have shown that the brain also reacts to the caloric and chemical makeup of the stuff that is in your stomach (there are chemoreceptors in there as well as mechanoreceptors, though of course most of the nutrient absorption is done in the small intestine). So maybe people who are obese have reduced response to mechanical stretch, but increased response to caloric value, or perhaps the response to caloric value does not differ. It’d be interesting to see what different kinds of food in the stomach produced.
And this is an fMRI study. They got activation in brain regions “associated” with high levels of dopaminergic and serotonergic innervation, but of course you’re not seeing dopamine and serotonin here. It would be really neat to see a PET study done in humans where you could look at dopaminergic changes (or maybe studies done in animals) to look at actual dopamine and serotonin responses to changes in gastric distention, as well as changes that result from different caloric values in the stomach.
I also notice that, while they noticed differences in the midbrain area (where the ventral tegmental area is, with dopamine neurons), they didn’t find any differences in dopaminergic projection areas like the nucleus accumbens, an area known to react to rewarding stimuli, and therefore pretty well expected to react to food. I have to wonder why they didn’t see anything there, though they didn’t offer an explanation. It’s possible that there just weren’t differences correlated with BMI, though you would think it would show up on the original scan. I’m also interested that they saw a DECREASE in activation in the caudate, which is not really what I would expect to see (the caudate is known to be involved in some rewarding processes and also in habit formation).
And while they rated desire for food, hunger, etc, with a balloon in the stomach they couldn’t very well rate things like satisfaction. How does the food make you FEEL? It would be interesting to correlate brain activation studies like this with studies of food consumption and food liking (not to mention food craving) in normal vs obese subjects. Do people who are obese like their food less or more? Some studies suggest they are tolerant to the rewarding effects, but it’d be interesting to correlate that with brain activation.
And of course, the final thing we don’t know. Are these changes the result of having a high BMI? Or are they there before these people ever started gaining weight? That, of course, is a very complicated question to answer. But the more studies we do, the closer we get.
Tomasi D, Wang GJ, Wang R, Backus W, Geliebter A, Telang F, Jayne MC, Wong C, Fowler JS, & Volkow ND (2009). Association of body mass and brain activation during gastric distention: implications for obesity. PloS one, 4 (8) PMID: 19718256
