Trait#125: BDNF, memory and overeating
Tuesday, June 14, 2022. Author FitnessGenes
Tuesday, June 14, 2022. Author FitnessGenes
Episodic memory refers to our ability to recall personal experiences, events, or “episodes” from our past.
It typically involves consciously remembering the what’s, where’s, and when’s of events that happened to us. For example, being able to recall what you did first thing this morning would employ episodic memory. As we’ll explore in this article, our ability to recall what we recently ate is also a form of episodic memory.
- Different types of memory
We have lots of different types of memory, which are employed over different timescales and in different tasks.
Episodic memory is part of our long-term memory that involves the storage of information for an extended period (ranging anywhere from a minute to a lifetime). Our episodic memory of past events are also explicit or 'declarative' - we consciously remember them. This contrasts with implicit memory, which is unconscious. For example, when we tie our shoelaces, most of us are not consciously remembering the individual steps, but doing so unconsciously - we are employing a form of implicit memory known as ‘procedural memory’.
Source: Queensland Brain Institute - URL: https://qbi.uq.edu.au/brain-basics/memory/types-memory
Episodic memory can also be distinguished from semantic memory, which is our ability to recall facts and knowledge about the world. Being able to recall the fact that the Battle of Hastings happened in 1066AD, for instance, would employ semantic memory. (William the Conqueror, by contrast, would be using his episodic memory when recalling the battle!).
- Brain structures involved in episodic memory
Lots of different brain areas are involved in episodic memory, with the (medial) temporal lobe being an area containing several key structures.
One of the key structures located deep in the temporal lobe and involved in episodic memory is the hippocampus. It plays an important role in the formation, organisation, storage, and retrieval of episodic memories.
Source: Nadel, L., & Hardt, O. (2011). Update on memory systems and processes. Neuropsychopharmacology, 36(1), 251-273.
Highlighting its importance in episodic memory, damage to the hippocampus (acutely, such as from a stroke, or from more low-grade damage, such as from inflammation or prolonged stress) is shown to impair performance on episodic memory tasks.
Studies show that remembering what we’ve recently eaten acts to reduce the amount we subsequently eat later in the day.
For example, in one seminal study, subjects ate a fixed amount of pizza for lunch in a laboratory and then were invited back 3 hours later to participate in a cookie-tasting test. Before tasting the cookies, half the group were asked to recall and write down their thoughts about the pizza they had eaten 3 hours previously. The other half were asked to write down their thoughts on other topics.
When it came to eating cookies as part of the tasting test, researchers covertly monitored how many cookies each subject consumed. Those who were asked to recall their previous lunch were found to eat significantly fewer cookies.
Interestingly, in variations of the above experiment, recalling non-food related information, exercise episodes, or what you’ve eaten for lunch the previous day does not seem to affect subsequent food intake.* This suggests that it is specifically episodic memory of recent meals that seems to inhibit future food intake.
(The graph below shows how subjects asked to recall recent eating (food recall) eat fewer grams of cookies compared to those asked to recall non-food events (non-food recall) and those not asked to recall anything (control). Interestingly, thinking about what food you plan to eat later in the day (EFT - Episodic Future Thinking) is also shown to inhibit subsequent food intake).
Source: Vartanian, L. R., Chen, W. H., Reily, N. M., & Castel, A. D. (2016). The parallel impact of episodic memory and episodic future thinking on food intake. Appetite, 101, 31-36.
So, why is this the case?
The answer is complicated but, in very basic terms, involves how our brain integrates several different signals from our body and environment in order to regulate hunger and appetite.
As we’ve explored in countless previous traits, whether or not we feel hungry is not a simple function of how much food is currently in our stomach. Our body has a complex system of satiety and hunger hormones / signalling molecules (such as leptin and ghrelin) that act on brain circuits (such as the melanocortin system) that regulate food intake and energy balance.
These circuits also interface with outputs from our hippocampus, thereby receiving episodic memory information about our recent meals. It is thought that memory of recent eating serves as a useful signal of the current availability of nutrients in our environment. This allows the brain to plan future energy needs and adapt hunger, satiety (i.e. feelings of fullness) and, more broadly, our motivation to seek out food, accordingly.
In evolutionary terms, it’s easy to see how this mechanism might have been beneficial. An ability to remember recent meals and then limit subsequent food intake might have allowed our ancestors to ration food accordingly. By contrast, an inability to remember recent eating may signal uncertainty about where future food is going to come from, forcing us to seek out further food sources.
* Interested readers are directed to this excellent review paper that looks at the various studies linking memory and eating behaviour.
In the previous section we saw how memory of recent meals acts to inhibit subsequent food intake. But, is the opposite true; that is, does interrupting the memory of recent meals lead to greater subsequent food intake?
The answer seems to be yes.
Several studies have adopted a paradigm whereby subjects are deliberately distracted when eating, for example by getting them to watch TV or play a computer game. By diverting attention away from the meal, these distractions interrupt memory encoding - they prevent us from effectively forming a memory of the meal.
When the snack intake of these distracted subjects is monitored a few hours later, researchers find that they consume significantly more than subjects who were not distracted.
For example, the graph below shows that young women watching television while eating lunch go on to consume significantly more cookies in the afternoon compared to those not watching television.
Source: Higgs, S., & Woodward, M. (2009). Television watching during lunch increases afternoon snack intake of young women. Appetite, 52(1), 39-43.
Another line of evidence comes from studies of neuropsychiatric patients with damage to their hippocampus, resulting in amnesia. One of the most famous patients in the history of neuroscience is patient H.M., who underwent surgery to remove parts of both his medial temporal lobes (including both hippocampi) to treat severe epilepsy.
Clinicians working with H.M noticed that he didn’t report feeling full, even just after a hefty meal. In one experiment, all evidence of a recently eaten meal was removed, and a second meal immediately offered to him. H.M readily ate the meal, reporting no significant increase in appetite. Other studies of amnesic patients with hippocampal damage also demonstrate that they consume multiple meals. This is likely due to an inability to encode memory of recent eating, which would otherwise inhibit future eating.
Of course, most of us are fortunate enough not to have major lesions of our hippocampus. Nevertheless, as we’ll discuss in the following section, being overweight has been associated with smaller hippocampal volume and poorer episodic memory, suggesting that carrying excess fat tissue (particularly visceral fat) can lead to mild memory deficits. This may, in turn, increase the risk of overeating.
Several studies have shown that obesity (defined as having a BMI ≥ 30 kg/m2) and higher amounts of body fat are associated with poorer episodic memory.
For example, one study assessed episodic memory with a ‘What-Where-When’ (WWW) task and looked at its relationship with BMI. Briefly, this task requires subjects to hide various food items somewhere within a computerised image of a scene (e.g. a desert with palm trees) at different times. Participants are then instructed to later recall what items they hid, as well as where and at what time of day they hid them.
As can be shown in the graph below, the higher a subject’s BMI was, the poorer their performance at the WWW task.
Source: Cheke, L. G., Simons, J. S., & Clayton, N. S. (2016). Higher body mass index is associated with episodic memory deficits in young adults. Quarterly Journal of Experimental Psychology, 69(11), 2305-2316.
Another large study, based on the National Survey of Midlife Development in the United States (MIDUS II): Cognitive Project, 2004–2006, found that a higher waist-to-hip ratio (WHR), which is a more accurate measure of how much visceral body fat (the type of fat that surrounds internal organs) one carries, was associated with poorer episodic memory performance.
In addition to psychological tests that assess memory performance, neuroimaging studies have widely demonstrated that people who are overweight and obese have structural changes to brain regions involved in memory.
More specifically, these studies show a reduction in grey matter volume of structures such as the hippocampus. Moreover, such structural brain changes seem to underpin poorer performance on memory tasks.
- Cause or effect?
Despite plentiful evidence showing a relationship between obesity and poorer episodic memory, it is difficult to tease out cause and effect. Does being overweight and obese cause memory deficits? Or, do pre-existing memory deficits drive overeating, giving rise to obesity?
The research suggests that both processes seem to be at play.
In terms of obesity causing memory deficits, we know that visceral body fat can cause insulin resistance and inflammation that damage key brain structures involved in memory, such as the hippocampus. As explained in the Sex hormones and visceral fat article, visceral fat (the kind of fat that sits around our internal organs) is metabolically active and secretes pro-inflammatory signalling molecules (cytokines) that give rise to low-grade inflammation.
Pro-inflammatory cytokines (such as IL-1β and TNF-α) secreted by visceral fat are shown to impair synaptic plasticity in the hippocampus (a process crucial to forming memories), thereby disrupting episodic memory.
Similarly, high-fat diets, excessive sugar intake, and lack of physical activity, all of which can contribute to obesity, are also shown to cause insulin resistance and inflammatory damage to brain structures involved in memory.
By contrast, some longitudinal studies show that deficits in episodic memory seem to pre-exist weight gain.
In reality, there is likely to be a vicious cycle relationship between obesity and episodic memory.
Accumulating body fat and unhealthy lifestyles give rise to insulin resistance and inflammation, which gradually damages key brain areas involved in memory, resulting in poorer episodic memory and ability to remember recent meals. A worse ability to remember recent meals would then lead to a loss of inhibition of future food intake, thereby causing that person to overeat. This would then engender further accumulation of body fat, perpetuating the cycle.
The good news is that, whatever the relationship between obesity and memory deficits, interventional studies show that losing weight through diet and exercise can improve episodic memory.
For example, one small neuroimaging study found that subjects improved episodic memory and increased hippocampal activity after 6 weeks of either a modified Paleolithic diet or diet based on the Nordic Nutrition Recommendations.
BDNF stands for Brain Derived Neurotrophic Factor and is a key molecule secreted by neurons that is involved in memory.
It belongs to a family of proteins known as ‘neurotrophins’. One of the overarching roles of neurotrophins is to allow the brain and nervous system to adapt and reorganize its structure in response to new experiences and stimuli in the environment. You may have come across this concept before under the term “neuroplasticity” and it underlies our ability to learn and remember new things.
BDNF is central to neuroplasticity, with some of its main functions including:
In particular, it is thought that BDNF mediates changes in synaptic plasticity within the hippocampus that support the formation of new episodic memories.
On this note, improvements in memory and other cognitive skills following exercise and social interaction may be partly due to the enhanced secretion of BDNF that such activities bring about.
You can read more about BDNF in the BDNF activity and cognition trait article.
The BDNF protein is coded for by the BDNF gene.
A Single Nucleotide Polymorphism (SNP) within this gene, designated rs6265, causes a G→A change in the DNA code, resulting in an amino acid change from valine (Val) to methionine (Met) in the BDNF protein.
The rs6265 SNP therefore gives rise to two different BDNF gene variants or alleles - the Val (G) allele and the Met (A) allele.
Studies suggest that the Met (A) allele is associated with poorer episodic memory, reduced activation of the hippocampus, and smaller hippocampal volume.
A 2012 meta-analysis of 28 studies, for example, found that Met (A) allele carriers performed significantly worse than those with the Val/Val (GG) genotype on tasks assessing explicit memory (which includes episodic memory). This is illustrated in the Forest plot below.
Source: Kambeitz, J. P., Bhattacharyya, S., Kambeitz-Ilankovic, L. M., Valli, I., Collier, D. A., & McGuire, P. (2012). Effect of BDNF val66met polymorphism on declarative memory and its neural substrate: A meta-analysis. Neuroscience & Biobehavioral Reviews, 36(9), 2165-2177.
So, why is the Met (A) allele of the BDNF gene associated with poorer episodic memory?
The reasons are not entirely clear but may be partly due to lower BDNF levels in the brain in Met (A) allele carriers. BDNF is secreted by neurons in response to stimulation - a process known as activity-dependent secretion. The Met (A) allele codes for an incorrectly folded BDNF protein, resulting in lower activity-dependent secretion of BDNF, which may negatively impact synaptic plasticity and the formation of episodic memories.
Source: de Las Heras, B., Rodrigues, L., Cristini, J., Weiss, M., Prats-Puig, A., & Roig, M. (2022). Does the brain-derived neurotrophic factor Val66Met polymorphism modulate the effects of physical activity and exercise on cognition?. The Neuroscientist, 28(1), 69-86.
Interestingly, some studies also show that those with the Val/Val (GG) genotype, which is linked to relatively higher activity-dependent BDNF secretion, reap greater cognitive benefits from exercise, although the evidence is mixed.
It hasn’t been explicitly tested at the time of writing, but it may be reasonable to hypothesise that Met (A) allele carriers, by virtue of being more likely to have episodic memory deficits, are at greater risk of forgetting recent meals and, as a result, overeating.
Hopefully future studies can address this question specifically. It should be noted however, that studies have not consistently found a relationship between the Met (A) allele and obesity, with several in fact finding the opposite association (i.e. Met (A) carriers having a lower risk of obesity).
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