More Calories when you thnk hard?

[jezzaOZ]

In

Do you burn more calories when you think hard?

Cecil states that Oxygen consumption doesn’t increase when you think hard.

As any athlete knows, Oxygen is not required for any short-term effort - e.g. Sprinting. In fact most short distance races rely on Glycogen for energy. This is called Anaerobic exercise.

The brain may well operate initially anaerobically. I know from personal experience that in orienteering you can outrun your brain easily after a period of time but in the first few minutes there is never an issue with brain related activity - i.e. navigation.

[DSeid]

No, glycogen is later in muscles.

First several seconds is ATP on hand, then some creatine phosphate is used to make more from ADP. It takes a while to get the glycogen system going.

The brain on the other hand does not have much stored glycogen on hand, although there is some in astrocytes (one the types of supporting non-neuronal cells). It runs almost exclusively on glucose that has been delivered to it. But that 1) does not mean that all the brain energy is associated with oxidation, and 2) does not mean that the glucose delivered is not used for other purposes than energy, which still uses up calories.

Details on these bits come from here.

More on 1.

an uncoupling between glucose uptake and oxygen consumption was observed during activation, since the increase in blood flow and in glucose utilization in the activated cortical area was not matched by an equivalent increase in oxygen consumption (13, 14). This observation raises the puzzling possibility that, at least during the early stages of activation, the increased energy demand is met by glycolysis rather than by oxidative phosphorylation. … rises in lactate have been monitored by 1H MRI spectroscopy in the primary visual cortex of humans following appropriate photic stimulation (49, 54). Lactate levels are increased in the rat somatosensory cortex following forepaw stimulation (68). When lactate was measured in vivo by microdialysis in freely moving rats, similar increases in hippocampus and striatum following somatosensory stimulation were demonstrated (11). Interestingly, the rate of lactate clearance from the extracellular space was markedly slowed in the presence of tetrodotoxin, a specific blocker of the neuronal voltage-sensitive sodium channels responsible for the generation of action potentials (11). This latter observation implies that during activation, lactate may normally be taken up by neurons as an energy fuel. It should be remembered that, after conversion to pyruvate, lactate can enter the TCA cycle with the potential to generate a total of 36 mol of ATP/mol of glucose (Fig. 2 ).

These in vivo data reveal a previously unrecognized prevalence of glycolysis over oxidative phosphorylation during activation …

(Boldig mine.)

The authors go on to explain how anaerobic glycolysis and anaerobic glycogenolysis using the small stores of glycogen in astrocytes are used to buffer brain energy demands. They produce lactate which is used by neurons for energy without oxidation involved.

More on 2: Simpler this. From the same article:

Glucose can be incorporated into lipids, proteins, and glycogen, and it is also the precursor of certain neurotransmitters such as g-aminobutyric acid (GABA), glutamate, and acetylcholine (10, 60). …

Glucose used anabolically to replace used up neurotransmitters is still calories required by the body as a result of thinking.

In short Cecil’s assumption that energy use by the brain is equal to oxidation in the brain is faulty. His awe at how efficiently the brain processes information is however well justified!

[njtt]

Well, the fMRI (functional Magnetic Resonance Imaging) technique that lies behind all those pictures of different areas of the brain lighting up when people are thinking of different sorts of things, actually measures the depletion of oxygen in the blood vessels supplying the relevant area of the brain, so yes, thinking does use up oxygen, and it uses it to burn glucose to produce energy. Sure, some of the glucose may turn anaerobically to lactate first, to get fast energy, but that lactate then needs to be oxidized (and quite soon) to produce more energy (and if it built up in the brain, it would soon poison us).

Nevertheless, Cecil is right (of course!). fMRI studies have also taught us that the brain is working all the time, not just when we are consciously thinking. Deliberate “hard” thinking, and other specific cognitive tasks, just shifts around which areas are working hardest a bit.

[Ed_Zotti]

@DSeid

In short Cecil’s assumption that energy use by the brain is equal to oxidation in the brain is faulty. His awe at how efficiently the brain processes information is however well justified!

Cecil made no such assumption. He wrote: “Glucose breakdown increases, but without combustion (oxidation) the energy surge is modest, maybe less than 1 percent.” He wanted to avoid introducing the term glycolysis, which he felt would confuse matters, and is saddened that matters may gotten confused nonetheless. He is gratified, however, that his awe of the brain was adequately conveyed.

[DSeid]

How does he arrive at that 1% figure?

[Ed_Zotti]

It came from Raichle in:

Raichle, Marcus E. and Mintun, Mark A. “Brain Work and Brain Imaging” Annual Review of Neuroscience 29 (2006): 449-476

… who cited himself in:

Raichle, Marcus E. “The Brain’s Dark Energy” Science 314 (2006): 1249-1250

… which was cited in the column. Posting of refs always lags publication by a few days, due to the interference of paying work in Fierra’s life.

[DSeid]

And that citation claims merely:

Depending on the approach used, it is estimated that 60 to 80% of the energy budget of the brain supports communication among neurons and their supporting cells (2). The additional energy burden associated with momentary demands of the environment may be as little as 0.5 to 1.0% of the total energy budget (2)

Nothing that states that oxidation rather than glucose use is a better measure of energy use and citing himself yet again. To here which I do not have behind the wall access to, but which is yet another review!

It would be nice to have some original source at the bottom of this.

[Ed_Zotti]

What is the point at issue?

[RadicalPi]

I actually wrote in to Cecil to ask him this question four years ago. It was good to finally get a response, but I have to admit I’m a bit disappointed that it’s Xandria’s name at the top instead of mine. On the whole though, an interesting column.

[DSeid]

@Ed_Zotti

What is the point at issue?

The bits in this paragraph:

while brain blood flow and glucose went up, oxygen use didn’t, meaning there was no increase in combustion — the brain wasn’t burning appreciably more fuel. Exactly what it is doing neuroscientists are still trying to figure out. Brain blood flow doesn’t increase fast enough to provide an instant energy boost; researchers now guess the blood rate ratchets up to cool the brain or carry away waste products. Glucose breakdown increases, but without combustion (oxidation) the energy surge is modest, maybe less than 1 percent.

Specifically the claim that the brain does not use more energy when it is thinking harder. The conclusion seems to be based on 1) a belief that energy is only supplied by oxidation (while the source I provided suggests that much of immediate brain energy demands are supplied without oxidation being involved) and 2) a reference to a source whose source is review by the same author which references yet another review … no actual explanation of how that conclusion of a “perhaps less than 1 percent” was reached.

Now I am not saying the 1% statement is wrong but given that such was the question of the column I’d like more of a basis for the conclusion than a review citing a review that cites a review …

[C_K_Dexter_Haven]

@RadicalPi

I actually wrote in to Cecil to ask him this question four years ago. It was good to finally get a response, but I have to admit I’m a bit disappointed that it’s Xandria’s name at the top instead of mine. On the whole though, an interesting column.

Yes, RadicalPi, you did indeed ask the question back in 2009. It oftimes happens that several people ask the same (or similar) question, and the rationale by which Cecil picks one over the other is still mysterious to me. And my apologies: I usually send a little note to those who asked a similar question, but I was extremely rushed on Friday (heading for the airport at 5 AM) and consequently failed to send you a note. Sorry.

[DSeid]

The question is a very interesting one Radical Pi. The issue remains how to measure it. Here’s another article explaining the possibility that little of short term energy needs are met by aerobic processes. The supporting cells produce lactate anaerobically from glucose which is then used by the neurons for energy.

Another issue of course is how even to define “at rest” for the brain and that is the better point of Cecil’s answer: short of a coma the brain is never at rest. It is always at work, predicting the future and on guard for novelty. Some of the work is experienced as conscious thought, as the self doing some processing, but that is just the tip of the iceberg.

[Una_Persson]

@DSeid

And that citation claims merely:Nothing that states that oxidation rather than glucose use is a better measure of energy use and citing himself yet again. To here which I do not have behind the wall access to, but which is yet another review!

It would be nice to have some original source at the bottom of this.

I bought the paper. I can’t send you that source via PDF because it has my personal stamp on it (that is, the place I bought it from puts an electronic stamp on the PDF pages), but I can try to quote from it what I think is the pertinent section.

The modest nature of these task-induced
increases in blood flow is further underscored
when one considers the increase in energy
consumption they represent. One should recall,
as discussed in detail above, the average
resting metabolic activity of the brain is supported
by the nearly complete (>90%) oxidation
of glucose to carbon dioxide and water,
producing approximately 32 mol of ATP
per mole of glucose consumed (Siesjo 1978).
Imaging signal activations, conversely, are associated
with increases in glucose utilization
that are not accompanied by a proportionate
increase in oxygen consumption (Blomqvist
et al. 1994, Fox et al. 1988, Madsen et al.
1995), resulting in the production of only 2
mol of ATP per mole of glucose consumed,
typical of glycolysis. Estimates of the actual
increases in oxygen consumption vary somewhat
(Fox & Raichle 1986, Fox et al. 1988,
Fujita et al. 1999, Mintun et al. 2002, Roland
et al. 1989) but are always less than that predicted
by the increase in blood flow. From
knowledge of these relationships, one can estimate
that if blood flow and glucose utilization
increase by 10%, but oxygen consumption
does not, the local energy consumption increase
owing to a typical task-related response
could be as little as 1%. It becomes clear, then,
that the brain continuously expends a considerable
amount of energy even in the absence of
a particular task (i.e., when a subject is awake
and at rest).

It is a review of other studies, you are correct, and bases its conclusions on the citations above, some of which Cecil had reviewed separately in researching the column. I can provide full citations for the links above when I get off my phone and onto a PC, if that would help you out.

[DSeid]

Thank you.

I remain a bit unsure about some of the specifics but the bottom line I cannot dispute: the brain “at rest” is pretty active.

[Una_Persson]

Took me a little longer to get to my PC, but here are the references in the paper.

Siesjo BK. 1978. Brain Energy Metabolism. New York:Wiley & Sons.

Blomqvist G, Seitz RJ, Sjogren I, Halldin C, Stone-Elander S, et al. 1994. Regional cerebral oxidative and total glucose consumption during rest and activation studied with positron emission tomography. Acta Physiol. Scand. 151:29–43

Fox PT, Raichle ME. 1986. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc. Natl. Acad. Sci. USA 83:1140–44

Fox PT, Raichle ME, Mintun MA, Dence C. 1988. Nonoxidative glucose consumption during focal physiologic neural activity. Science 241:462–64

Fujita H, Kuwahara H, Reutens O, Gjedde A. 1999. Oxygen consumption of cerebral cortex fails to increase during continued vibrotactile stimulation. J. Cereb. Blood Flow Metab. 19:266–71

Madsen PL, Hasselbalch SG, Hagemann LP, Olsen KS, Bulow J, et al. 1995. Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation: evidence obtained with the Kety-Schmidt technique. J. Cereb. Blood Flow Metab. 15:485–91

Mintun M, Vlassenko AG, Shulman GI, Snyder AZ. 2002. Time-related increase of oxygen utilization in continuously activated human visual cortex. Neuroimage 16:531–37

Roland PE, Eriksson L, Widen L, Stone-Elander S. 1989. Changes in regional cerebral oxidative metabolism induced by tactile learning and recognition in man. Eur. J. Neurosci. 1:3–17

To be honest though these cites won’t help you out at all unless you get all the papers; it’s just an impressive looking wall of text which doesn’t prove anything by itself. I don’t have them all, I think I only have half of them, but my recollection is that the earlier review did report accurately on the relatively low differential energy use. It might take me more time to re-review them if we need to do that; not to dismiss your concern in the least but I’m really swamped this week (in a good way, though ).

PS I hope you are doing well, DSeid; I haven’t spoken with you in a while. (I don’t know if you’ve posted your real name in public, so I must call you by your screen name).

[Flyer]

This talk about the brain working hard even when we aren’t thinking hard brings up a couple of questions, neither of which may have satisfactory answers.

1–What produces the feeling of thinking/working hard? I imagine that most people are quite familiar with the physical tiredness that mental concentration can produce.

2–Various studies over the years seem to indicate quite strongly that sleep–and more specifically REM sleep–is in some as-yet undetermined way absolutely required for the brain to get adequate rest. If the overall activity level in the brain doesn’t vary much regardless of what we do, then how precisely does the brain rest?

[DSeid]

Thank you again. I’m doing fine, thank you for asking!

I can get to the 1988 Science one. The issue seems to be a divergence of thought from the perspective that believes that oxidative metabolism is where the brain gets it energy (period) and the one that believes in that “lactate shuffle” as posited in that first citation I offered up.

Here is the Science article’s argument:

Local cerebral glucose metabolic rate (CMRglu) and cerebral blood
flow (CBF) are greatly increased by focal
increases in neural activity. The increase in
CMRglu has been thought to indicate a
local increase in glucose oxidation, supporting large energy expenditures required to
maintain membrane ionic gradients. The
increase in local CBF has been considered a
response to’ substrate (02) depletion and
metabolite (CO2) excess.
Challenging the conventional formulation, we reported that a focal, physiological
increase in neural activity induced by peripheral tactile stimulation increased cerebral metabolic rate for 02 (CMRo2) minimally (5%), despite a large increase (29%)
in local CBF (2). … Despite the large increase in glucose uptake observed here, the actual acute energy
yield must be quite small. If one assumes
that the entire increase in 02 uptake was
consumed by glucose oxidation at a 4.1:1
ratio and that all the remaining glucose was
metabolized to lactate, the maximum possible increase in energy (ATP) production is
only 8%. … This result implies that the acute energy expenditures of
neural activity are far less than has been
inferred from the large increases in glucose
uptake and the high (4.1:1) resting-state
02: glucose molar ratio. Finally, blood flow
increases during neural activity are regulated
by a mechanism, and serve a need, other
than oxidative metabolism.

Note that they stop with the lactate as the dead end. What’s emerged over then last decades however is that neurons use the lactate, even preferentially use it, and harvest much energy from it. That maximum is much more than that old quoted 8%. The SD column mentions how interesting this gets and it gets even more interesting than that!

Since neurons account for most of the energy consumption during brain activation, it was first rationally assumed that CMRglc measurements from 18F-fluoro-2-deoxyglucose (FDG)-PET signals directly reflected the neuronal use of glucose (Sokoloff et al., 1977). In addition, neurometabolism was postulated to be a strictly oxidative (i.e., oxygen-depending) process—an assumption based on the higher efficiency to produce ATP from glucose oxidation in the mitochondria (oxidative process) compared to glycolysis (nonoxidative process; i.e., lactate producing) (Figure 1A).

In the mid-1980s, an important series of PET studies conducted by Fox and Raichle challenged this assumption, and led to a major breakthrough in our understanding of the mechanisms underlying task-induced increases in glucose metabolism. In awake adult humans, they observed that the activity-dependent (visual or somatosensory) increases in blood flow and glucose utilization were only marginally matched by parallel increases in oxygen consumption (Fox and Raichle, 1986 and Fox et al., 1988) (Figure 1B). Such uncoupling between CBF and CMRO2 created the rationale for developing blood oxygenation level-dependent (BOLD) fMRI contrast (Ogawa et al., 1992, Magistretti and Pellerin, 1996 and Raichle and Mintun, 2006). These fundamental observations also brought support to the notion that the metabolic needs of active neural tissue are met, at least partially, by nonoxidative glucose metabolism (i.e., glycolysis). This hypothesis was then further supported by various 1H nuclear magnetic resonance studies showing activity-dependent increases in lactate levels in different brain areas (Figley and Stroman, 2011, and references therein), giving empirical demonstration that glycolytic metabolism increases with corresponding elevations in brain activity. It is now generally accepted that following transient changes in neural activity, (1) blood delivery increases with metabolic demand, (2) CBF and CMRglc increase more than oxygen utilization, and (3) both oxidative and nonoxidative processes are involved to meet the increased metabolic requirements (Figley and Stroman, 2011).

These observations raised fundamental questions as to the molecular and cellular mechanisms that could reconcile the coexistence of increases in oxidative and nonoxidative glucose metabolism during synaptic activity. Specifically, the open questions were as follows: are the changes of glucose metabolism (oxidative versus glycolytic) taking place in different cell compartments; and to which precise cellular processes are they linked? The evidence pointing at a major contribution of astrocytes to neuroenergetics (Magistretti et al., 1981 and Pellerin and Magistretti, 1994) has provided a key to the understanding of these questions. …

… Lactate is present in the extracellular space in concentrations similar to those of glucose (between 0.5 and 1.5 mM), and while it has long been considered a metabolic dead end, this view has drastically changed in light of the growing evidence indicating that it represents an important energy source for the brain (Schurr et al., 1999, Gallagher et al., 2009, Smith et al., 2003 and Boumezbeur et al., 2010b). Interestingly, emerging evidence suggests that the end product of glycolysis is lactate (rather than pyruvate) (Schurr and Payne, 2007). In line with this, the existence of a putative mitochondrial lactate oxidation complex has been reported in neurons which would allow lactate entry and oxidation in the mitochondria (Hashimoto et al., 2008).

Importantly, both astrocytes and neurons have the capacity to fully oxidize glucose and/or lactate … a large body of evidence shows that neurons can efficiently use lactate as an energy substrate (Schurr et al., 1997, Bouzier et al., 2000, Qu et al., 2000, Serres et al., 2005 and Boumezbeur et al., 2010b) and even show a preference for lactate over glucose when both substrates are present (Itoh et al., 2003 and Bouzier-Sore et al., 2006). … the astrocyte-neuron lactate shuttle (ANLS) model proposed over a decade ago by Pellerin and Magistretti (Figure 3A) (Pellerin and Magistretti, 1994). The essence of this model is that (1) neuronal activity increases extracellular glutamate (via glutamatergic neurotransmission), which is avidly taken up via a Na±dependent mechanism by specific glial glutamate transporters; (2) the resulting increase in [Na+]i activates the Na+/K+ ATPase (in particular by mobilizing its alpha2 subunit), thereby increasing ATP consumption (Magistretti and Chatton, 2005), glucose uptake, and glycolysis in astrocytes; (3) this in turn leads to a large increase in the production of lactate which is released in the extracellular space; and (4) lactate can be used as an energy substrate for neurons for oxidative-derived ATP production (for review, see Pellerin et al., 2007 and Magistretti, 2009). … By coupling glucose utilization (via astrocyte glycolysis) to neuronal activity and oxidative phosphorylation, the ANLS is consistent with previous studies that have implicated a nonoxidative metabolic component during focal brain activation (see the Introduction and Fox et al., 1988). …

… Overall the observations presented in this review demonstrate that brain energy metabolism involves more complex cellular and molecular mechanisms than previously thought. The field of neuroenergetics has evolved from a neurocentric view into a more integrated one in which complementarities and cooperativities between astrocytes and neurons play a central role. A striking demonstration is the coordination of both the CBF response (neurovascular coupling) and the stimulation of metabolism (neurometabolic coupling), which are necessary to meet the increased energy requirements of active neurons and astrocytes during brain activation. In addition to this, metabolic interactions—in particular in the form of lactate shuttling from astrocytes to neurons—appear to play an important role in the control of neuronal activity and excitability.

(Bolding mine.)

I do not mean to distract from the main point of the column: the brain is always thinking hard and what we perceive as thinking hard hardly reflects the actual work always going on even “at rest.” Our conscious awareness is a small fraction of the processing constantly going on, reverberating. That said local increases in blood flow are likely doing more than serving to cool the brain down or to just cart away waste; it does seem that local processing demand increases are tightly matched to more significantly increased supply, even if it is nonoxidative to some degree.

Flyer

1. I think that is the physiologic effect of stress on the complete body.
2. It never rests; it works in different ways at different time. There are certain jobs, and what those jobs are is a matter of great discussion and debate but most believe they have much to do with memory consolidation, that are done during sleep and some particularly in REM, that are not done in other brain states. Sort of like how certain ride maintenance cannot be done at DisneyWorld while the park is open to the public but just because the park is closed does not mean that there is not still a bustle of activity, different but requisite activity, going on.

[RadicalPi]

@C_K_Dexter_Haven

Yes, RadicalPi, you did indeed ask the question back in 2009. It oftimes happens that several people ask the same (or similar) question, and the rationale by which Cecil picks one over the other is still mysterious to me. And my apologies: I usually send a little note to those who asked a similar question, but I was extremely rushed on Friday (heading for the airport at 5 AM) and consequently failed to send you a note. Sorry.

Your apology is most graciously accepted. I was mostly happy to see that the question was answered at all. As we have been seeing, it’s very interesting (IMHO.)

[dotchan]

Disclaimer: I am not a doctor; I don’t even play one on TV. This is just from my own (limited) internet research and wild-ass guessing.

@Flyer

1–What produces the feeling of thinking/working hard? I imagine that most people are quite familiar with the physical tiredness that mental concentration can produce.

Mental exertion tends to happen around periods of high stress, in which our body triggers that lovely fight or flight response, which cranks up all of our processes (including how the brain thinks). Once the task is done, the crisis is over, and we “unwind”.

@Flyer

2–Various studies over the years seem to indicate quite strongly that sleep–and more specifically REM sleep–is in some as-yet undetermined way absolutely required for the brain to get adequate rest. If the overall activity level in the brain doesn’t vary much regardless of what we do, then how precisely does the brain rest?

Overall activity might not drop too much, yes, but there’s been specific studies about what areas of the brain are not as active when one is asleep.

And even while awake, there are parts of the brain that seem to go on “autopilot” at times–haven’t you ever done a repetitive task so much that your body seems to move on its own without your active input, or just zoned out in the middle of something really boring?

[mr.jp]

I think that the fact that thinking hard makes us tired, and you have to strain to continue doing it, strongly indicates that energy expenditure in the brain increases significantly.

The evolutionary reason that we have to exert ourself to do physical exercise, is that the body is slightly against us wasting fuel. I think the same must be the case with the brain. What else could it be? If there isn’t a good alternative explanation, I think the evidence that the brain fuel consumption doesn’t increase significantly needs to be rock solid.