Is inflammation responsible for the mental sluggishness that often accompanies illness?

Scientists at the University of Birmingham in collaboration with the University of Amsterdam have uncovered a possible explanation for the mental sluggishness that often accompanies illness.

An estimated 12M UK citizens have a chronic medical condition, and many of them report severe mental fatigue that they characterize as ‘sluggishness’ or ‘brain fog’. This condition is often as debilitating as the disease itself.

A team in the University’s Centre for Human Brain Health investigated the link between this mental fog and inflammation – the body’s response to illness. In a study published in Neuroimage, they show that inflammation appears to have a particular negative impact on the brain’s readiness to reach and maintain an alert state.

Dr Ali Mazaheri and Professor Jane Raymond of the University’s Centre for Human Brain Health, are the senior authors of the study. Dr Mazaheri says: “Scientists have long suspected a link between inflammation and cognition, but it is very difficult to be clear about the cause and effect. For example, people living with a medical condition or being very overweight might complain of cognitive impairment, but it’s hard to tell if that’s due to the inflammation associated with these conditions or if there are other reasons.”

“Our research has identified a specific critical process within the brain that is clearly affected when inflammation is present.”

The study focussed specifically on an area of the brain which is responsible for visual attention. A group of 20 young male volunteers took part and received a salmonella typhoid vaccine that causes temporary inflammation but has few other side effects. They were tested for cognitive responses to simple images on a computer screen a few hours after the injection so that their ability to control attention could be measured. Brain activity was measured while they performed the attention tests.

On a different day, either before or after, they received an injection with water (a placebo) and did the same attention tests. On each test day they were unaware of which injection they had received. Their inflammation state was measured by analysing blood taken on each day.

The tests used in the study assessed three separate attention processes, each involving distinct parts of the brain. These processes are: “alerting”  which involves reaching and maintaining an alert state; “orienting”  which involves selecting and prioritising useful sensory information; and “executive control” used to resolving what to pay attention to when available information is conflicting.

The results showed that inflammation specifically affected brain activity related to staying alert, while the other attention processes appeared unaffected by inflammation.

“These results show quite clearly that there’s a very specific part of the brain network that’s affected by inflammation,” says Dr Mazaheri. “This could explain ‘brain fog’.”

Professor Raymond says, “This research finding is major step forward in understanding the links between physical, cognitive, and mental health and tells us that even the mildest of illnesses may reduce alertness.”

Dr Leonie Balter the first author of the study which was completed as part of her PhD, concluded : “Getting a better understanding of the relationships between inflammation and brain function will help us investigate other ways to treat some of these conditions. For example, further research might show that patients with conditions associated with chronic inflammation, such as obesity, kidney disease or Alzheimer’s, could benefit from taking anti-inflammatory drugs to help preserve or improve cognitive function.”

“Furthermore, subtle changes in brain function may be used as an early marker cognitive deterioration in patients with inflammatory diseases.”

The next step for the team will be to test the effects of inflammation on other areas of brain function such as memory.

Learn more: Link between inflammation and mental sluggishness shown in new study