Lactate supply overtakes glucose when neural computational and cognitive loads scale up 2022 Dembitskaya et al

Significance
Brain activity and performance are constrained by energy metabolism. Glucose and lactate have been proposed as energy substrates for neurons allocated to various forms of memory. We demonstrate that glucose and lactate metabolism are differentially engaged in neuronal fueling depending on the activity-dependent plasticity and behavioral complexity. These results reconcile a decades-long debate regarding the nature of the neuroenergetic sources used by synaptic activity with the potential of inspiring future lines of research regarding neuroenergetic rules. The brain has high energy demands, and alterations in neuroenergetics are hallmarks of several neuropathologies. A better knowledge of the cellular and molecular mechanisms of neuroenergetics, as reported here, may be instructive in targeting energy metabolism deficits as a therapeutic approach for neurodegenerative diseases.

Abstract
Neural computational power is determined by neuroenergetics, but how and which energy substrates are allocated to various forms of memory engram is unclear. To solve this question, we asked whether neuronal fueling by glucose or lactate scales differently upon increasing neural computation and cognitive loads.

Here, using electrophysiology, two-photon imaging, cognitive tasks, and mathematical modeling, we show that both glucose and lactate are involved in engram formation, with lactate supporting long-term synaptic plasticity evoked by high-stimulation load activity patterns and high attentional load in cognitive tasks and glucose being sufficient for less demanding neural computation and learning tasks. Indeed, we show that lactate is mandatory for demanding neural computation, such as theta-burst stimulation, while glucose is sufficient for lighter forms of activity-dependent long-term potentiation (LTP), such as spike timing–dependent plasticity (STDP).

We find that subtle variations of spike number or frequency in STDP are sufficient to shift the on-demand fueling from glucose to lactate. Finally, we demonstrate that lactate is necessary for a cognitive task requiring high attentional load, such as the object-in-place task, and for the corresponding in vivo hippocampal LTP expression but is not needed for a less demanding task, such as a simple novel object recognition. Overall, these results demonstrate that glucose and lactate metabolism are differentially engaged in neuronal fueling depending on the complexity of the activity-dependent plasticity and behavior.

Open access, https://www.pnas.org/doi/10.1073/pnas.2212004119

 

If energy metabolism in the brain is disrupted in ME, the brain's need for different fuels depending on task might explain some of our symptoms.

 

And why cognitive exertion can cause PEM just the same as physical exertion.

Which was always a case of duh, but when the premise of what's happening is not accepted, that the issue is fundamentally about exertion, of any kind, nothing good can flow from there. Because of this, cognitive exertion is basically treated as fully separate, as issues of mind that don't involve the body, as if thinking is free. But all the damn language, still to this day, around post-exercise fatigue or exercise intolerance completely obscures what's actually happening so it can't even be discussed rationally because even the words used commonly are misleading. Because of this almost no one even makes the connection between exertion and PEM. What an incredible uniquely bad mess.

Because really this is the excuse, the weird belief that thinking, or emotional processing or whatever, is basically free, does not amount to exertion. It's all coaxed in wishy-washing stuff about emotions and feelings, entirely separate from the rest of biology, where there is no such thing as a free lunch. The entire computer analogy dies on the hill that computers rely on an external power source and do not consume anything else or change in any way, they are fixed, rigid circuits and nothing else.

Gonna quote Homer Simpson but: in this house we obey the laws of thermodynamics. Because it's not enough to disrespect the linear passage of time, psychosomatic ideology doesn't even care about energy, thinks it gets created psychogenically, or whatever.

 

I agree. It's very strange that BPS people don't recognize the existence of cognitive PEM. In fact, my cognitive PEM is far more disabling than physical PEM. If PEM was only physical, I'd be in poor health but still be able to live a normal-ish lifestyle, as I can do my job at home at my desk. At my physical functioning level I can sit up as much as I want, stand for at least 1-2 hours a day, and go on 20-30 minute walks.

 

For reference, selected quotes from the discussion (my emphasis) —

 

Understanding energy envelopes for cognition, and how they vary for pwME across various types of mental activity, may be the one area where psychologists have a valuable role to play in ME research.

 

This