Does altitude-like cognition training strengthen brain function?

Many people with psychiatric disorders such as depression and bipolar disorder (mania and depression) struggle with cognitive challenges including memory and concentration difficulties. But treatment options are scarce.

The hypothesis is that simulated altitude cognition training, which involves reducing ambient oxygen levels, can strengthen brain plasticity and regenerative processes.

Now, a new research project – supported with a 2 million euro grant from the European Research Council (ERC) – will investigate whether simulated altitude cognition training has the potential to strengthen brain function and cognitive skills among these patients groups.

Professor Kamilla Woznica Miskowiak, who is leading the project, believes the results could have wide-reaching implications:

“The hypothesis is that simulated altitude cognition training, which involves reducing ambient oxygen levels, can strengthen brain plasticity and regenerative processes. This is especially important for people with psychiatric disorders and associated cognitive impairment for whom effective treatment options are bleak,” explains Kamilla Woznica Miskowiak, who is affiliated with the Department of Psychology at the UCPH and the Mental Health Services, Capital Region of Denmark.

“But in the end, the results may have implications for all of us. We have an ageing population, and there is a strong desire to stay mentally and intellectually active when we grow old.”

New knowledge about EPO is the key behind the study

The scientific basis of the project is the recent evidence that the protein erythropoietin, EPO, is important for more than blood oxygen uptake – which has been illustrated by doping cases in the world of sports.

At higher altitudes in particular, where the oxygen level is low, increased secretion of EPO in the brain seems to contribute to improved brain function by, for instance, maturing the so-called neural progenitor cells and strengthening the neural connections. These are effects that Kamilla Woznica Miskowiak and her collaborators have documented in studies of rats and mice.

However, it remains unclear, which effect altitude simulation and cognitive training has on brain function in humans and on the treatment of cognitive impairments.

The new project aims to answer this question through controlled studies of mice and of human participants with and without psychiatric diagnoses. For a period of three weeks, the participants will spend a few hours each day in an altitude training room, simulating an altitude of 4,400 metres.

At the same time, some of the participants will be given cognitive training tasks. This will allow the researchers to investigate the effect of low oxygen levels, cognitive training and the combination of the two factors. The effects are measured with a series of advanced cognitive tests and brain imaging techniques, while parallel mouse studies will reveal changes in the brain at cellular and molecular levels.

Out of the snowdrift and back on the road

According to Kamilla Woznica Miskowiak, this research aims to map the effect of altitude-like cognition training on cognitive functions, but also to generate greater knowledge of underlying brain processes.

From a treatment perspective, the advantage of altitude cognitive training is that this intervention would be more assessable, less invasive, and safer than traditional EPO treatment. In fact, the majority of patients with psychiatric disorders cannot receive EPO treatment for safety reasons because of their increased risk of side-effects such as blood clotting due to cardiovascular disease, diabetes or smoking. The natural stimulation of brain EPO through the simulated altitude training procedure, on the other hand, has no known side effects.

Kamilla Woznica Miskowiak hopes that the beneficial effect of simulated altitude in combination with cognitive training on brain function will be long-lasting. Other studies have shown that EPO injections may indeed have long-lasting effect on the brain for up to six months and, in her opinion, it is possible that altitude training will provide similar results. However, this will need to be further investigated in future studies.

We have placed psychiatric sanctuaries in the mountains where the air is clean, and the nature is beautiful. But could it be that the lower ambient oxygen levels also contribute to patients’ mental health improvement through stimulating brain EPO?

“Moreover, it is our hypothesis that we will see a positive effect of cognitive training in patients when, in parallel, we upregulate brain plasticity through altitude simulation. That is, the combined intervention may improve brain plasticity sufficiently to raise the patients’ level of cognitive function. It can be compared to your car being stuck in a snowdrift during a snowstorm: Getting it out takes more than just stepping on the accelerator. You will need a helpful push as well – but after getting back on the road, your chances of continuing on your own are better.”

Finally – if the results turn out to be positive – the altitude cognition training could have broader benefits for anyone who simply wants to improve their brain function. As Kamilla Woznica Miskowiak notes, it is even possible that we have long suspected the effect of thin air on mental health.

“We have placed psychiatric sanctuaries in the mountains where the air is clean, and the nature is beautiful. But could it be that the lower ambient oxygen levels also contribute to patients’ mental health improvement through stimulating brain EPO? Our study will elucidate this intriguing question.”