The Theory

We know that injury or disease of the nervous system causes a neuroinflammation. Microglia cells and astrocytes form inflammatory substances, which are intended to protect the nerve cells from damage, but which can also damage them. Some of these inflammatory substances, e.g. the cytokines TNF-alpha (Tumor Necrosis Factor-alpha) and IL1-beta (Interleukin 1-beta) attenuate the signalling between the brain cells, which can be positive in the case of disease or trauma in the acute phase when the available energy is needed to repair damage to the nervous system. If such substances remain after the injury, they may instead lead to reduced efficiency in nerve cell traffic. To take one example, these cytokines have been shown to reduce the ability of astrocytes to deal with glutamate when released from nerve cells.

Our research group works with the theory that the combination of reduced glutamate handling by astrocytes, more unspecific signalling of larger cell networks, reduced energy supply, less quantity of newly made glutamate, and swelling of astrocytes leads to a “locked” state at the cellular level. This cell-locked situation can serve as a mechanism or at least explanatory model for the complete fatigue experienced by a person with brain fatigue if he or she overworks. It takes a long time to recover the chemical imbalance, which explains the long recovery time for the affected person.

According to our hypothesis, this imbalance occurs in systems that have to do with attention and concentration ability as well as systems that have to do with emotions and physical effects. One of the major signalling agents of importance here is dopamine. Even emotional instability is seen; probably due to decreased and more unspecific signalling in systems dealing with emotions such as serotonin signalling. Thus, there is more noise in the signalling between the nerve cells. 

In the case of neuroinflammation, the astrocytes’ fiber networks inside the cells are affected, which causes the signalling between the astrocytes to be disturbed. As a result, communication between the neural cell networks and the astrocyte networks is affected.

Can our hypothesis also explain the sound and light sensitivity of brain fatigue?

The brain has limitations in how much can be processed and reach conscious areas at a time. Therefore, proper sorting or filtering systems are needed. When repeating information, nerve cells in the healthy brain will reduce their intensity in signalling after a while and, for example, the sound is no longer recognised. We talk about adaptation of the signalling. This does not work for persons suffering from brain fatigue. They describe that everything is recognised, important as well as unimportant information, and that it becomes very tiring and difficult to handle all the impressions. The signalling does not adapt which explains why the affected are very easily disturbed and they cannot maintain focus. If the astrocytes’ handling of glutamate is impaired, it means that incoming information becomes more nonspecific and is perceived as new. It is then not filtered out but reaches up to higher brain centres for processing. In this context, it is important that we are aware that today we know very little about the way the brain works.

How could brain fatigue become long-lasting?

Being brain fatigued immediately after a head injury, stroke or other nervous system disease is understandable to most people, but how could it be that the fatigue persists and lasts for a long time for some people, especially after the injury or illness is visibly healed? Today there is no explanation for this. 

Since the extent or location of the brain injury, or the age or sex of the person does not appear to be significant for the risk of long-term brain fatigue, one may wonder if there are risk factors even before the onset of the disease or injury of the people where the brain fatigue becomes long-lasting. Several studies suggest that people suffering from depression and anxious states before the injury are more likely to suffer from long-term problems after the injury. Hereditary factors have also been shown to be important. People with a special gene set of the apolipoprotein epsilon 4 allele have been shown to be at greater risk of developing long-term problems with neuropsychological impairment following brain injury. There may also be many other factors that are important for the long-term brain fatigue. It also seems that people who have been involved in multiple head injuries are at greater risk of developing brain fatigue.